Antimicrobial-resistant infections

SAN FRANCISCO – A combination of ceftriaxone, a beta-lactamase inhibitor, and disodium ethylenediaminetetraacetic acid (EDTA) is superior to meropenem in the treatment of complicated urinary tract infections caused by extended-spectrum beta-lactamase (ESBL) gram-negative bacteria, according to a new study.

Jim Kling/MDedge News

The post-hoc analysis also found that the three-drug combination – known as CSE – is noninferior to meropenem in multidrug-resistant (MDR) and ceftriaxone-nonsusceptible (C-NS) pathogens.

CSE is aimed at the growing problem of antibiotic resistance, particularly the mechanisms used by bacteria to counter beta-lactamase inhibitors. EDTA chelates zinc and calcium, and many of the resistance mechanisms rely on one or the other of these ions to function. In in vitro models, the combination of sulbactam and EDTA restores activity of ceftriaxone against various beta-lactamases.

Mohd Amin Mir, MD, head of clinical research at the Venus Medicine Research Center, Panchkula, India, and presenter of the study, said that, in the case of efflux pumps, “when there is EDTA present, it chelates the calcium, and that means there is no energy for the efflux pump to throw out the drug.”

The penems, which include meropenem, are a class of synthetic antibiotics with an unsaturated beta-lactam ring. Like other antibiotics, they are under assault from antibiotic resistance, especially beta-lactamase enzymes. “Penems are very precious drugs. The objective of developing [EDTA combinations] is to save the penems,” Dr. Mir said at an annual scientific meeting on infectious diseases.

The PLEA trial randomized 143 patients with complicated urinary tract infections or acute pyelonephritis to CSE (1 g ceftriaxone/500 mg sulbactam/37 mg EDTA) every 12 hours or 1 g meropenem (MR) as a 30-minute intravenous infusion over 30 minutes. Patients received treatment for 5-14 days.

The original study demonstrated that CSE is noninferior to meropenem at a 10% noninferiority margin. The researchers conducted a post-hoc analysis of patients who presented with complicated UTIs or acute pyelonephritis cases that were C-NS, ESBL-positive, or multidrug-resistant (MDR) pathogens. The researchers defined MDR as resistance to three or more categories of antimicrobial agents.

Of patients who received CSE, 97.3% had pathogens that were nonsusceptible to ceftriaxone, as did 98.6% of those who received MR; 85.1% of CSE and 81.2% of MR patients had an ESBL-producing pathogen; and 74.3% of infections in the CSE group were MDR, as were 65.2% of the MR group.

In all three resistant phenotypes, CSE at least trended to more favorable outcomes. In the MDR group, 96.4% of CSE patients achieved a clinical cure, compared with 88.9% in the MR group, and 94.5% achieved microbial eradication, compared with 86.75% in the MR group.

In the ESBL subgroup, 100% of patients in the CSE group achieved a clinical cure, compared with 89.3%, while 98.4% had complete eradication in the CSE group, compared with 87.5%. In the C-NS subgroup, 95.8% in the CSE group achieved a clinical cure, compared with 91.2%, and 94.4% achieved eradication, compared with 89.7% in the MR group.

In the ESBL subgroup, the lower bound of the 95% confidence interval of the between-group difference was greater than 0, indicating superiority of CSE over MR for both clinical cure and eradication. In the MDR and C-NS subgroups, CSE achieved noninferiority at a –10% margin.

CSE is currently commercially available in India, and the manufacturer is now seeking approval in Europe and the United States.

SOURCE: Mir MA et al. IDWeek 2018, Abstract 1959.

SAN FRANCISCO – A combination of ceftriaxone, a beta-lactamase inhibitor, and disodium ethylenediaminetetraacetic acid (EDTA) is superior to meropenem in the treatment of complicated urinary tract infections caused by extended-spectrum beta-lactamase (ESBL) gram-negative bacteria, according to a new study.

Jim Kling/MDedge News

The post-hoc analysis also found that the three-drug combination – known as CSE – is noninferior to meropenem in multidrug-resistant (MDR) and ceftriaxone-nonsusceptible (C-NS) pathogens.

CSE is aimed at the growing problem of antibiotic resistance, particularly the mechanisms used by bacteria to counter beta-lactamase inhibitors. EDTA chelates zinc and calcium, and many of the resistance mechanisms rely on one or the other of these ions to function. In in vitro models, the combination of sulbactam and EDTA restores activity of ceftriaxone against various beta-lactamases.

Mohd Amin Mir, MD, head of clinical research at the Venus Medicine Research Center, Panchkula, India, and presenter of the study, said that, in the case of efflux pumps, “when there is EDTA present, it chelates the calcium, and that means there is no energy for the efflux pump to throw out the drug.”

The penems, which include meropenem, are a class of synthetic antibiotics with an unsaturated beta-lactam ring. Like other antibiotics, they are under assault from antibiotic resistance, especially beta-lactamase enzymes. “Penems are very precious drugs. The objective of developing [EDTA combinations] is to save the penems,” Dr. Mir said at an annual scientific meeting on infectious diseases.

The PLEA trial randomized 143 patients with complicated urinary tract infections or acute pyelonephritis to CSE (1 g ceftriaxone/500 mg sulbactam/37 mg EDTA) every 12 hours or 1 g meropenem (MR) as a 30-minute intravenous infusion over 30 minutes. Patients received treatment for 5-14 days.

The original study demonstrated that CSE is noninferior to meropenem at a 10% noninferiority margin. The researchers conducted a post-hoc analysis of patients who presented with complicated UTIs or acute pyelonephritis cases that were C-NS, ESBL-positive, or multidrug-resistant (MDR) pathogens. The researchers defined MDR as resistance to three or more categories of antimicrobial agents.

Of patients who received CSE, 97.3% had pathogens that were nonsusceptible to ceftriaxone, as did 98.6% of those who received MR; 85.1% of CSE and 81.2% of MR patients had an ESBL-producing pathogen; and 74.3% of infections in the CSE group were MDR, as were 65.2% of the MR group.

In all three resistant phenotypes, CSE at least trended to more favorable outcomes. In the MDR group, 96.4% of CSE patients achieved a clinical cure, compared with 88.9% in the MR group, and 94.5% achieved microbial eradication, compared with 86.75% in the MR group.

In the ESBL subgroup, 100% of patients in the CSE group achieved a clinical cure, compared with 89.3%, while 98.4% had complete eradication in the CSE group, compared with 87.5%. In the C-NS subgroup, 95.8% in the CSE group achieved a clinical cure, compared with 91.2%, and 94.4% achieved eradication, compared with 89.7% in the MR group.

In the ESBL subgroup, the lower bound of the 95% confidence interval of the between-group difference was greater than 0, indicating superiority of CSE over MR for both clinical cure and eradication. In the MDR and C-NS subgroups, CSE achieved noninferiority at a –10% margin.

CSE is currently commercially available in India, and the manufacturer is now seeking approval in Europe and the United States.

SOURCE: Mir MA et al. IDWeek 2018, Abstract 1959.

SAN FRANCISCO – A combination of ceftriaxone, a beta-lactamase inhibitor, and disodium ethylenediaminetetraacetic acid (EDTA) is superior to meropenem in the treatment of complicated urinary tract infections caused by extended-spectrum beta-lactamase (ESBL) gram-negative bacteria, according to a new study.

Jim Kling/MDedge News

The post-hoc analysis also found that the three-drug combination – known as CSE – is noninferior to meropenem in multidrug-resistant (MDR) and ceftriaxone-nonsusceptible (C-NS) pathogens.

CSE is aimed at the growing problem of antibiotic resistance, particularly the mechanisms used by bacteria to counter beta-lactamase inhibitors. EDTA chelates zinc and calcium, and many of the resistance mechanisms rely on one or the other of these ions to function. In in vitro models, the combination of sulbactam and EDTA restores activity of ceftriaxone against various beta-lactamases.

Mohd Amin Mir, MD, head of clinical research at the Venus Medicine Research Center, Panchkula, India, and presenter of the study, said that, in the case of efflux pumps, “when there is EDTA present, it chelates the calcium, and that means there is no energy for the efflux pump to throw out the drug.”

The penems, which include meropenem, are a class of synthetic antibiotics with an unsaturated beta-lactam ring. Like other antibiotics, they are under assault from antibiotic resistance, especially beta-lactamase enzymes. “Penems are very precious drugs. The objective of developing [EDTA combinations] is to save the penems,” Dr. Mir said at an annual scientific meeting on infectious diseases.

The PLEA trial randomized 143 patients with complicated urinary tract infections or acute pyelonephritis to CSE (1 g ceftriaxone/500 mg sulbactam/37 mg EDTA) every 12 hours or 1 g meropenem (MR) as a 30-minute intravenous infusion over 30 minutes. Patients received treatment for 5-14 days.

The original study demonstrated that CSE is noninferior to meropenem at a 10% noninferiority margin. The researchers conducted a post-hoc analysis of patients who presented with complicated UTIs or acute pyelonephritis cases that were C-NS, ESBL-positive, or multidrug-resistant (MDR) pathogens. The researchers defined MDR as resistance to three or more categories of antimicrobial agents.

Of patients who received CSE, 97.3% had pathogens that were nonsusceptible to ceftriaxone, as did 98.6% of those who received MR; 85.1% of CSE and 81.2% of MR patients had an ESBL-producing pathogen; and 74.3% of infections in the CSE group were MDR, as were 65.2% of the MR group.

In all three resistant phenotypes, CSE at least trended to more favorable outcomes. In the MDR group, 96.4% of CSE patients achieved a clinical cure, compared with 88.9% in the MR group, and 94.5% achieved microbial eradication, compared with 86.75% in the MR group.

In the ESBL subgroup, 100% of patients in the CSE group achieved a clinical cure, compared with 89.3%, while 98.4% had complete eradication in the CSE group, compared with 87.5%. In the C-NS subgroup, 95.8% in the CSE group achieved a clinical cure, compared with 91.2%, and 94.4% achieved eradication, compared with 89.7% in the MR group.

In the ESBL subgroup, the lower bound of the 95% confidence interval of the between-group difference was greater than 0, indicating superiority of CSE over MR for both clinical cure and eradication. In the MDR and C-NS subgroups, CSE achieved noninferiority at a –10% margin.

CSE is currently commercially available in India, and the manufacturer is now seeking approval in Europe and the United States.

SOURCE: Mir MA et al. IDWeek 2018, Abstract 1959.

SAN FRANCISCO – Daptomycin plus fosfomycin is more effective than daptomycin alone for methicillin-resistant Staphylococcus aureus bacteremia, according to a multicenter, randomized trial from Spain.

M. Alexander Otto/MDedge News

“I think this is really an important study; I think it will change clinical practice for this infection” once it’s published, said lead investigator Miquel Pujol, MD, PhD, clinical head of infectious diseases at Bellvitge University Hospital in Barcelona.

The current standard for MRSA bacteremia is daptomycin (Cubicin) or vancomycin (Vancocin) monotherapy on both sides of the Atlantic, but mortality rates are way too high, more than 30% in some reviews. Dr. Pujol and his colleagues wanted to find something better.

Their lab work showed that daptomycin and fosfomycin (Monurol) were synergistic and rapidly bactericidal against MRSA, and anecdotal experience in Spain suggested the drugs improved bacteremia outcomes, so they decided to put the combination to the test.

They randomized 74 MRSA bacteremia patients to the combination, daptomycin 10mg/kg IV daily plus fosfomycin 2g IV q 6h. They randomized 81 other subjects to standard of care with daptomycin monotherapy, also at 10mg/kg IV daily. Treatment was 10-14 days for uncomplicated and 28-42 days for complicated bacteremia.

The open-label trial was conducted at 18 medical centers in Spain, where fosfomycin was discovered in dirt samples in the late 1960s and remains a matter of pride.

At day 7, 69 of the 74 combination patients (93.2%) were alive with clinical improvement, clearance of bacteremia, and no subsequent relapse, versus 62 of 81 patients (76.5%) on monotherapy (absolute difference 16.7%; 95% confidence interval, 5.4%-27.7%). Three people in the combination arm (4.1%) had died by day 7, versus six on monotherapy (7.4%).

Six weeks after the end of treatment at the test-of-cure visit, 40 of 74 combination patients (54.1%) were alive with resolution of all clinical signs and symptoms, negative blood cultures, and no previous or subsequent relapses; just 34 of 81 patients (42%) in the monotherapy arm hit that mark. The 12.1% difference was not statistically significant, nor was the difference in 12-week survival.

However, patients in the combination arm were 70% less likely to have complicated bacteremia at the test-of-cure visit (9.5% vs. 28.4%; relative risk 0.3; 95% CI, 0.2-0.7). There were no cases of persistent or recurrent infection in the combination arm, but nine persistent (11.1%) and five recurrent (6.2%) cases with daptomycin monotherapy. The differences were statistically significant.

The subjects all had at least one positive MRSA blood culture within 72 hours of randomization. Exclusion criteria included MRSA pneumonia, prosthetic valve endocarditis, end-stage liver disease, and moderate to severe heart failure.

There were no significant baseline differences between the groups. About half the subjects were men, and the mean age was about 73 years. The mean Charlson Comorbidity Index score was a bit under 4, and the mean Pitt bacteremia score a bit over 1. The leading source of infection was vascular catheter; acquisition was thought to be nosocomial in more than 40% of patients.

There were no discontinuations from drug side effects in the daptomycin arm, but there were five in the combination arm, including two for heart failure, two for respiratory insufficiency, and one for GI bleeding. Even so, the benefit outweighed the risk, Dr. Pujol said.

Intravenous fosfomycin is available in Europe, but the drug is approved in the United States only as an oral formulation. That could change soon; Nabriva Therapeutics plans to file its IV formulation (Contepo) for Food and Drug Administration approval in late 2018.

Though it is not standard of practice yet, the combination is increasingly being used in Spain for MRSA bacteremia, according to Dr. Pujol. “Patients probably need the combination [at least] initially, especially if they have complicated bacteremia” or fail monotherapy, he said at ID week, an annual scientific meeting on infectious diseases.

The work was funded by the Spanish government. Dr. Pujol said he had no relevant disclosures.
 

[email protected]

SOURCE: Pujol M et al. 2018 ID Week abstract LB3

SAN FRANCISCO – Daptomycin plus fosfomycin is more effective than daptomycin alone for methicillin-resistant Staphylococcus aureus bacteremia, according to a multicenter, randomized trial from Spain.

M. Alexander Otto/MDedge News

“I think this is really an important study; I think it will change clinical practice for this infection” once it’s published, said lead investigator Miquel Pujol, MD, PhD, clinical head of infectious diseases at Bellvitge University Hospital in Barcelona.

The current standard for MRSA bacteremia is daptomycin (Cubicin) or vancomycin (Vancocin) monotherapy on both sides of the Atlantic, but mortality rates are way too high, more than 30% in some reviews. Dr. Pujol and his colleagues wanted to find something better.

Their lab work showed that daptomycin and fosfomycin (Monurol) were synergistic and rapidly bactericidal against MRSA, and anecdotal experience in Spain suggested the drugs improved bacteremia outcomes, so they decided to put the combination to the test.

They randomized 74 MRSA bacteremia patients to the combination, daptomycin 10mg/kg IV daily plus fosfomycin 2g IV q 6h. They randomized 81 other subjects to standard of care with daptomycin monotherapy, also at 10mg/kg IV daily. Treatment was 10-14 days for uncomplicated and 28-42 days for complicated bacteremia.

The open-label trial was conducted at 18 medical centers in Spain, where fosfomycin was discovered in dirt samples in the late 1960s and remains a matter of pride.

At day 7, 69 of the 74 combination patients (93.2%) were alive with clinical improvement, clearance of bacteremia, and no subsequent relapse, versus 62 of 81 patients (76.5%) on monotherapy (absolute difference 16.7%; 95% confidence interval, 5.4%-27.7%). Three people in the combination arm (4.1%) had died by day 7, versus six on monotherapy (7.4%).

Six weeks after the end of treatment at the test-of-cure visit, 40 of 74 combination patients (54.1%) were alive with resolution of all clinical signs and symptoms, negative blood cultures, and no previous or subsequent relapses; just 34 of 81 patients (42%) in the monotherapy arm hit that mark. The 12.1% difference was not statistically significant, nor was the difference in 12-week survival.

However, patients in the combination arm were 70% less likely to have complicated bacteremia at the test-of-cure visit (9.5% vs. 28.4%; relative risk 0.3; 95% CI, 0.2-0.7). There were no cases of persistent or recurrent infection in the combination arm, but nine persistent (11.1%) and five recurrent (6.2%) cases with daptomycin monotherapy. The differences were statistically significant.

The subjects all had at least one positive MRSA blood culture within 72 hours of randomization. Exclusion criteria included MRSA pneumonia, prosthetic valve endocarditis, end-stage liver disease, and moderate to severe heart failure.

There were no significant baseline differences between the groups. About half the subjects were men, and the mean age was about 73 years. The mean Charlson Comorbidity Index score was a bit under 4, and the mean Pitt bacteremia score a bit over 1. The leading source of infection was vascular catheter; acquisition was thought to be nosocomial in more than 40% of patients.

There were no discontinuations from drug side effects in the daptomycin arm, but there were five in the combination arm, including two for heart failure, two for respiratory insufficiency, and one for GI bleeding. Even so, the benefit outweighed the risk, Dr. Pujol said.

Intravenous fosfomycin is available in Europe, but the drug is approved in the United States only as an oral formulation. That could change soon; Nabriva Therapeutics plans to file its IV formulation (Contepo) for Food and Drug Administration approval in late 2018.

Though it is not standard of practice yet, the combination is increasingly being used in Spain for MRSA bacteremia, according to Dr. Pujol. “Patients probably need the combination [at least] initially, especially if they have complicated bacteremia” or fail monotherapy, he said at ID week, an annual scientific meeting on infectious diseases.

The work was funded by the Spanish government. Dr. Pujol said he had no relevant disclosures.
 

[email protected]

SOURCE: Pujol M et al. 2018 ID Week abstract LB3

SAN FRANCISCO – Daptomycin plus fosfomycin is more effective than daptomycin alone for methicillin-resistant Staphylococcus aureus bacteremia, according to a multicenter, randomized trial from Spain.

M. Alexander Otto/MDedge News

“I think this is really an important study; I think it will change clinical practice for this infection” once it’s published, said lead investigator Miquel Pujol, MD, PhD, clinical head of infectious diseases at Bellvitge University Hospital in Barcelona.

The current standard for MRSA bacteremia is daptomycin (Cubicin) or vancomycin (Vancocin) monotherapy on both sides of the Atlantic, but mortality rates are way too high, more than 30% in some reviews. Dr. Pujol and his colleagues wanted to find something better.

Their lab work showed that daptomycin and fosfomycin (Monurol) were synergistic and rapidly bactericidal against MRSA, and anecdotal experience in Spain suggested the drugs improved bacteremia outcomes, so they decided to put the combination to the test.

They randomized 74 MRSA bacteremia patients to the combination, daptomycin 10mg/kg IV daily plus fosfomycin 2g IV q 6h. They randomized 81 other subjects to standard of care with daptomycin monotherapy, also at 10mg/kg IV daily. Treatment was 10-14 days for uncomplicated and 28-42 days for complicated bacteremia.

The open-label trial was conducted at 18 medical centers in Spain, where fosfomycin was discovered in dirt samples in the late 1960s and remains a matter of pride.

At day 7, 69 of the 74 combination patients (93.2%) were alive with clinical improvement, clearance of bacteremia, and no subsequent relapse, versus 62 of 81 patients (76.5%) on monotherapy (absolute difference 16.7%; 95% confidence interval, 5.4%-27.7%). Three people in the combination arm (4.1%) had died by day 7, versus six on monotherapy (7.4%).

Six weeks after the end of treatment at the test-of-cure visit, 40 of 74 combination patients (54.1%) were alive with resolution of all clinical signs and symptoms, negative blood cultures, and no previous or subsequent relapses; just 34 of 81 patients (42%) in the monotherapy arm hit that mark. The 12.1% difference was not statistically significant, nor was the difference in 12-week survival.

However, patients in the combination arm were 70% less likely to have complicated bacteremia at the test-of-cure visit (9.5% vs. 28.4%; relative risk 0.3; 95% CI, 0.2-0.7). There were no cases of persistent or recurrent infection in the combination arm, but nine persistent (11.1%) and five recurrent (6.2%) cases with daptomycin monotherapy. The differences were statistically significant.

The subjects all had at least one positive MRSA blood culture within 72 hours of randomization. Exclusion criteria included MRSA pneumonia, prosthetic valve endocarditis, end-stage liver disease, and moderate to severe heart failure.

There were no significant baseline differences between the groups. About half the subjects were men, and the mean age was about 73 years. The mean Charlson Comorbidity Index score was a bit under 4, and the mean Pitt bacteremia score a bit over 1. The leading source of infection was vascular catheter; acquisition was thought to be nosocomial in more than 40% of patients.

There were no discontinuations from drug side effects in the daptomycin arm, but there were five in the combination arm, including two for heart failure, two for respiratory insufficiency, and one for GI bleeding. Even so, the benefit outweighed the risk, Dr. Pujol said.

Intravenous fosfomycin is available in Europe, but the drug is approved in the United States only as an oral formulation. That could change soon; Nabriva Therapeutics plans to file its IV formulation (Contepo) for Food and Drug Administration approval in late 2018.

Though it is not standard of practice yet, the combination is increasingly being used in Spain for MRSA bacteremia, according to Dr. Pujol. “Patients probably need the combination [at least] initially, especially if they have complicated bacteremia” or fail monotherapy, he said at ID week, an annual scientific meeting on infectious diseases.

The work was funded by the Spanish government. Dr. Pujol said he had no relevant disclosures.
 

[email protected]

SOURCE: Pujol M et al. 2018 ID Week abstract LB3

SAN FRANCISCO – In gram-negative bloodstream infections, in patients who are stable at 48 hours, are no longer feverish, and whose infections aren’t invasive, it may be safe to step down from IV antibiotics to oral ciprofloxacin (PO). That is the tentative conclusion from a new single-center, retrospective chart review.

Jim Kling/MDedge News

The study adds to growing suspicion among practitioners that stepping down may be safe in gram-negative patients, as well as mounting evidence that shorter treatment durations may also be safe, according to Gregory Cook, PharmD, who presented the study at a poster session at an annual scientific meeting on infectious diseases. “We’re getting more aggressive” in backing off IV treatment, he said in an interview.

Oral medications are associated with shorter hospital stays and decreased costs.

Froedtert & the Medical College of Wisconsin, where the study was performed, switched some years ago from levofloxacin to ciprofloxacin for cost reasons. But ciprofloxacin has a lower bioavailability, and a recent study showed levofloxacin had less treatment failure at 90 days than ciprofloxacin. Levofloxacin is restricted at the institution and requires antibiotic stewardship approval for use, whereas ciprofloxacin can be used without approval.

But the researchers were concerned about bioavailability. “We like to think of ciprofloxacin as having excellent bioavailability, and it does, it has 80% bioavailability, but it’s still not exactly the same as levofloxacin. We wanted to look into this and see if we were doing our patients a disservice or not (by stepping down to ciprofloxacin),” said Dr. Cook, who is now the antimicrobial stewardship pharmacist at Children’s Hospital New Orleans. The results were reassuring. “Ultimately we were trying to see how our patients were doing on oral ciprofloxacin, and after 2-3 days of IV therapy, most of them did extremely well,” he said. 

The researchers analyzed the records of 198 patients who presented with a monomicrobial, gram-negative bloodstream infection between January 2015 and January 2018, and who survived at least 5 days past blood culture collection. One hundred and three switched to PO within 5 days, while 95 remained on intravenous antibiotics for longer than 5 days. On average, patients in the PO group received IV antibiotics for 2 days, while the IV group averaged 15 days. Oral ciprofloxacin treatment length averaged 12 days.

The primary endpoint of treatment failure at 90 days, defined as recurrent infection or all-cause mortality, favored the PO group (1.9% versus 16.8%, P less than .01). This was likely because of patient selection, as those in the IV group tended to be more ill, according to Dr. Cook. More were immunosuppressed (41% IV versus 22% in PO group, P less than .01). There were more nonurinary sources of infection (41% in IV group, P less than .01; 65% urinary source in PO group). Thirty-four percent of the PO group had an infectious disease consult, compared with 60% of the IV group.

SOURCE: Gregory Cook et al. ID Week 2018. Abstract 39.

SAN FRANCISCO – In gram-negative bloodstream infections, in patients who are stable at 48 hours, are no longer feverish, and whose infections aren’t invasive, it may be safe to step down from IV antibiotics to oral ciprofloxacin (PO). That is the tentative conclusion from a new single-center, retrospective chart review.

Jim Kling/MDedge News

The study adds to growing suspicion among practitioners that stepping down may be safe in gram-negative patients, as well as mounting evidence that shorter treatment durations may also be safe, according to Gregory Cook, PharmD, who presented the study at a poster session at an annual scientific meeting on infectious diseases. “We’re getting more aggressive” in backing off IV treatment, he said in an interview.

Oral medications are associated with shorter hospital stays and decreased costs.

Froedtert & the Medical College of Wisconsin, where the study was performed, switched some years ago from levofloxacin to ciprofloxacin for cost reasons. But ciprofloxacin has a lower bioavailability, and a recent study showed levofloxacin had less treatment failure at 90 days than ciprofloxacin. Levofloxacin is restricted at the institution and requires antibiotic stewardship approval for use, whereas ciprofloxacin can be used without approval.

But the researchers were concerned about bioavailability. “We like to think of ciprofloxacin as having excellent bioavailability, and it does, it has 80% bioavailability, but it’s still not exactly the same as levofloxacin. We wanted to look into this and see if we were doing our patients a disservice or not (by stepping down to ciprofloxacin),” said Dr. Cook, who is now the antimicrobial stewardship pharmacist at Children’s Hospital New Orleans. The results were reassuring. “Ultimately we were trying to see how our patients were doing on oral ciprofloxacin, and after 2-3 days of IV therapy, most of them did extremely well,” he said. 

The researchers analyzed the records of 198 patients who presented with a monomicrobial, gram-negative bloodstream infection between January 2015 and January 2018, and who survived at least 5 days past blood culture collection. One hundred and three switched to PO within 5 days, while 95 remained on intravenous antibiotics for longer than 5 days. On average, patients in the PO group received IV antibiotics for 2 days, while the IV group averaged 15 days. Oral ciprofloxacin treatment length averaged 12 days.

The primary endpoint of treatment failure at 90 days, defined as recurrent infection or all-cause mortality, favored the PO group (1.9% versus 16.8%, P less than .01). This was likely because of patient selection, as those in the IV group tended to be more ill, according to Dr. Cook. More were immunosuppressed (41% IV versus 22% in PO group, P less than .01). There were more nonurinary sources of infection (41% in IV group, P less than .01; 65% urinary source in PO group). Thirty-four percent of the PO group had an infectious disease consult, compared with 60% of the IV group.

SOURCE: Gregory Cook et al. ID Week 2018. Abstract 39.

SAN FRANCISCO – In gram-negative bloodstream infections, in patients who are stable at 48 hours, are no longer feverish, and whose infections aren’t invasive, it may be safe to step down from IV antibiotics to oral ciprofloxacin (PO). That is the tentative conclusion from a new single-center, retrospective chart review.

Jim Kling/MDedge News

The study adds to growing suspicion among practitioners that stepping down may be safe in gram-negative patients, as well as mounting evidence that shorter treatment durations may also be safe, according to Gregory Cook, PharmD, who presented the study at a poster session at an annual scientific meeting on infectious diseases. “We’re getting more aggressive” in backing off IV treatment, he said in an interview.

Oral medications are associated with shorter hospital stays and decreased costs.

Froedtert & the Medical College of Wisconsin, where the study was performed, switched some years ago from levofloxacin to ciprofloxacin for cost reasons. But ciprofloxacin has a lower bioavailability, and a recent study showed levofloxacin had less treatment failure at 90 days than ciprofloxacin. Levofloxacin is restricted at the institution and requires antibiotic stewardship approval for use, whereas ciprofloxacin can be used without approval.

But the researchers were concerned about bioavailability. “We like to think of ciprofloxacin as having excellent bioavailability, and it does, it has 80% bioavailability, but it’s still not exactly the same as levofloxacin. We wanted to look into this and see if we were doing our patients a disservice or not (by stepping down to ciprofloxacin),” said Dr. Cook, who is now the antimicrobial stewardship pharmacist at Children’s Hospital New Orleans. The results were reassuring. “Ultimately we were trying to see how our patients were doing on oral ciprofloxacin, and after 2-3 days of IV therapy, most of them did extremely well,” he said. 

The researchers analyzed the records of 198 patients who presented with a monomicrobial, gram-negative bloodstream infection between January 2015 and January 2018, and who survived at least 5 days past blood culture collection. One hundred and three switched to PO within 5 days, while 95 remained on intravenous antibiotics for longer than 5 days. On average, patients in the PO group received IV antibiotics for 2 days, while the IV group averaged 15 days. Oral ciprofloxacin treatment length averaged 12 days.

The primary endpoint of treatment failure at 90 days, defined as recurrent infection or all-cause mortality, favored the PO group (1.9% versus 16.8%, P less than .01). This was likely because of patient selection, as those in the IV group tended to be more ill, according to Dr. Cook. More were immunosuppressed (41% IV versus 22% in PO group, P less than .01). There were more nonurinary sources of infection (41% in IV group, P less than .01; 65% urinary source in PO group). Thirty-four percent of the PO group had an infectious disease consult, compared with 60% of the IV group.

SOURCE: Gregory Cook et al. ID Week 2018. Abstract 39.

SAN FRANCISCO – Intravenous metronidazole (Flagyl) did not improve 30-day mortality when it was added to oral vancomycin in adult ICU patients with severe Clostridium difficile infections, according to a review of 101 cases at the University of Maryland.

Adding metronidazole is a common move in ICUs when patients start circling the drain with C. difficile, in part because delivery to the gut doesn’t depend on gut motility. “At that point, you are throwing the kitchen sink at them, but it’s” based, like much in C. difficile management, on expert opinion, not evidence, said study lead Ana Vega, PharmD, a former resident at the university’s school of pharmacy in Baltimore, and now an infectious disease pharmacist at Jackson Memorial Hospital, Miami. The investigators wanted to plug the evidence gap. Forty-seven of the 101 patients in their review – all with signs of C. difficile sepsis – had IV metronidazole added to their vancomycin regimens. Thirty-day mortality was 14.9% in the combination group versus 7.4% in the monotherapy arm, and not significantly different (P = .338). There were also no significant differences in resolution rates or normalization of white blood cell counts and temperature.

“Our data question the utility of” of adding IV metronidazole to oral vancomycin in patients with severe disease. “It’s definitely something to think twice about because metronidazole isn’t benign. It makes people feel crummy; you can induce resistance; and it increases the risk of vancomycin-resistant Enterococci colonization,” already a risk with vancomycin, Dr. Vega said at an annual scientific meeting on infectious diseases.

“When you get to the point that you are trying combination therapy based on expert opinion, I think fecal transplants are something to consider” because the success rates are so high. “That would be my suggestion,” she said, even though “it’s much easier to write an order for a drug than to get a fecal transplant.”

The issue is far from resolved, and debate will continue. A similar review of ICU patients at Wake Forest University in Winston-Salem, N.C., did find a significant mortality benefit with combination therapy, regardless of C. difficile severity (Clin Infect Dis. 2015 Sep 15. doi: 10.1093/cid/civ409).

The Maryland investigators excluded patients with toxic megacolon and other life-threatening intra-abdominal complications requiring surgery, because combination therapy is more strongly recommended in fulminant disease. They were interested in people who were not quite ready for the operating room, when what to do is more in doubt.

Subjects were admitted to the ICU from April 2016 to April 2018 with positive C. difficile nucleic acid testing and an order for oral vancomycin. The only statistically significant baseline differences were that patients who got IV metronidazole had higher median white blood cell counts (18,400 versus 13,900 cells/mL; P = .035) and were more likely to receive higher than 500-mg doses of vancomycin (36.2% versus 7.4%; P less than .0001).

The Mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score in the combination group was 23 versus 19 in the monotherapy arm (P = .247). There was no difference in the probability of receiving metronidazole based on the score.

The study again found no significant 30-day mortality differences among 76 patients matched by their APACHE II scores (15.8% in the combination arm versus 9.7%; P = .480).

Severe C. difficile infection was defined as either a white cell count above 15,000 or below 4,000 cells/mL, or a serum creatinine at least 1.5 times above baseline, plus at least one other sign of severe sepsis, such as a mean arterial pressure at or below 60 mm Hg. Metronidazole was started within 72 hours of the first vancomycin dose, and subjects on combination therapy were on both for at least 72 hours.

The mean age in the study was about 60 years old, and just over half of the subjects were men.

Dr. Vega said the investigators hope to expand their sample size and see if patients with more virulent strains of C. difficile do better on combination therapy.

There was no industry funding for the work, and the investigators didn’t have any relevant disclosures.

[email protected]

SOURCE: Vega AD et al. ID Week 2018, Abstract 488.

SAN FRANCISCO – Intravenous metronidazole (Flagyl) did not improve 30-day mortality when it was added to oral vancomycin in adult ICU patients with severe Clostridium difficile infections, according to a review of 101 cases at the University of Maryland.

Adding metronidazole is a common move in ICUs when patients start circling the drain with C. difficile, in part because delivery to the gut doesn’t depend on gut motility. “At that point, you are throwing the kitchen sink at them, but it’s” based, like much in C. difficile management, on expert opinion, not evidence, said study lead Ana Vega, PharmD, a former resident at the university’s school of pharmacy in Baltimore, and now an infectious disease pharmacist at Jackson Memorial Hospital, Miami. The investigators wanted to plug the evidence gap. Forty-seven of the 101 patients in their review – all with signs of C. difficile sepsis – had IV metronidazole added to their vancomycin regimens. Thirty-day mortality was 14.9% in the combination group versus 7.4% in the monotherapy arm, and not significantly different (P = .338). There were also no significant differences in resolution rates or normalization of white blood cell counts and temperature.

“Our data question the utility of” of adding IV metronidazole to oral vancomycin in patients with severe disease. “It’s definitely something to think twice about because metronidazole isn’t benign. It makes people feel crummy; you can induce resistance; and it increases the risk of vancomycin-resistant Enterococci colonization,” already a risk with vancomycin, Dr. Vega said at an annual scientific meeting on infectious diseases.

“When you get to the point that you are trying combination therapy based on expert opinion, I think fecal transplants are something to consider” because the success rates are so high. “That would be my suggestion,” she said, even though “it’s much easier to write an order for a drug than to get a fecal transplant.”

The issue is far from resolved, and debate will continue. A similar review of ICU patients at Wake Forest University in Winston-Salem, N.C., did find a significant mortality benefit with combination therapy, regardless of C. difficile severity (Clin Infect Dis. 2015 Sep 15. doi: 10.1093/cid/civ409).

The Maryland investigators excluded patients with toxic megacolon and other life-threatening intra-abdominal complications requiring surgery, because combination therapy is more strongly recommended in fulminant disease. They were interested in people who were not quite ready for the operating room, when what to do is more in doubt.

Subjects were admitted to the ICU from April 2016 to April 2018 with positive C. difficile nucleic acid testing and an order for oral vancomycin. The only statistically significant baseline differences were that patients who got IV metronidazole had higher median white blood cell counts (18,400 versus 13,900 cells/mL; P = .035) and were more likely to receive higher than 500-mg doses of vancomycin (36.2% versus 7.4%; P less than .0001).

The Mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score in the combination group was 23 versus 19 in the monotherapy arm (P = .247). There was no difference in the probability of receiving metronidazole based on the score.

The study again found no significant 30-day mortality differences among 76 patients matched by their APACHE II scores (15.8% in the combination arm versus 9.7%; P = .480).

Severe C. difficile infection was defined as either a white cell count above 15,000 or below 4,000 cells/mL, or a serum creatinine at least 1.5 times above baseline, plus at least one other sign of severe sepsis, such as a mean arterial pressure at or below 60 mm Hg. Metronidazole was started within 72 hours of the first vancomycin dose, and subjects on combination therapy were on both for at least 72 hours.

The mean age in the study was about 60 years old, and just over half of the subjects were men.

Dr. Vega said the investigators hope to expand their sample size and see if patients with more virulent strains of C. difficile do better on combination therapy.

There was no industry funding for the work, and the investigators didn’t have any relevant disclosures.

[email protected]

SOURCE: Vega AD et al. ID Week 2018, Abstract 488.

SAN FRANCISCO – Intravenous metronidazole (Flagyl) did not improve 30-day mortality when it was added to oral vancomycin in adult ICU patients with severe Clostridium difficile infections, according to a review of 101 cases at the University of Maryland.

Adding metronidazole is a common move in ICUs when patients start circling the drain with C. difficile, in part because delivery to the gut doesn’t depend on gut motility. “At that point, you are throwing the kitchen sink at them, but it’s” based, like much in C. difficile management, on expert opinion, not evidence, said study lead Ana Vega, PharmD, a former resident at the university’s school of pharmacy in Baltimore, and now an infectious disease pharmacist at Jackson Memorial Hospital, Miami. The investigators wanted to plug the evidence gap. Forty-seven of the 101 patients in their review – all with signs of C. difficile sepsis – had IV metronidazole added to their vancomycin regimens. Thirty-day mortality was 14.9% in the combination group versus 7.4% in the monotherapy arm, and not significantly different (P = .338). There were also no significant differences in resolution rates or normalization of white blood cell counts and temperature.

“Our data question the utility of” of adding IV metronidazole to oral vancomycin in patients with severe disease. “It’s definitely something to think twice about because metronidazole isn’t benign. It makes people feel crummy; you can induce resistance; and it increases the risk of vancomycin-resistant Enterococci colonization,” already a risk with vancomycin, Dr. Vega said at an annual scientific meeting on infectious diseases.

“When you get to the point that you are trying combination therapy based on expert opinion, I think fecal transplants are something to consider” because the success rates are so high. “That would be my suggestion,” she said, even though “it’s much easier to write an order for a drug than to get a fecal transplant.”

The issue is far from resolved, and debate will continue. A similar review of ICU patients at Wake Forest University in Winston-Salem, N.C., did find a significant mortality benefit with combination therapy, regardless of C. difficile severity (Clin Infect Dis. 2015 Sep 15. doi: 10.1093/cid/civ409).

The Maryland investigators excluded patients with toxic megacolon and other life-threatening intra-abdominal complications requiring surgery, because combination therapy is more strongly recommended in fulminant disease. They were interested in people who were not quite ready for the operating room, when what to do is more in doubt.

Subjects were admitted to the ICU from April 2016 to April 2018 with positive C. difficile nucleic acid testing and an order for oral vancomycin. The only statistically significant baseline differences were that patients who got IV metronidazole had higher median white blood cell counts (18,400 versus 13,900 cells/mL; P = .035) and were more likely to receive higher than 500-mg doses of vancomycin (36.2% versus 7.4%; P less than .0001).

The Mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score in the combination group was 23 versus 19 in the monotherapy arm (P = .247). There was no difference in the probability of receiving metronidazole based on the score.

The study again found no significant 30-day mortality differences among 76 patients matched by their APACHE II scores (15.8% in the combination arm versus 9.7%; P = .480).

Severe C. difficile infection was defined as either a white cell count above 15,000 or below 4,000 cells/mL, or a serum creatinine at least 1.5 times above baseline, plus at least one other sign of severe sepsis, such as a mean arterial pressure at or below 60 mm Hg. Metronidazole was started within 72 hours of the first vancomycin dose, and subjects on combination therapy were on both for at least 72 hours.

The mean age in the study was about 60 years old, and just over half of the subjects were men.

Dr. Vega said the investigators hope to expand their sample size and see if patients with more virulent strains of C. difficile do better on combination therapy.

There was no industry funding for the work, and the investigators didn’t have any relevant disclosures.

[email protected]

SOURCE: Vega AD et al. ID Week 2018, Abstract 488.

SAN FRANCISCO – The University of Kentucky Medical Center, Lexington, halved the rate of MRSA and CRE infections in the ICU by switching from contact precautions to decolonization with nasal povidone iodine swabs and daily chlorhexidine wipes, according to a report presented at ID Week 2018.

M. Alexander Otto/MDedge News

The move prevented an estimated eight methicillin-resistant Staphylococcus aureus (MRSA) and three carbapenem-resistant Enterobacteriaceae (CRE) infections and saved the medical center more than $150,000 in the year following the November 2016 switch.

The goal was to address the rate of MRSA bacteremia, which was higher than national ICU averages. Contact precautions began to make less sense as MRSA became more common in the surrounding community, and “we just wanted to get rid of contact precautions,” said study lead Jason Moss, DO, an infectious disease fellow at the university.

Contact precautions are expensive, make patients feel isolated, and according to some studies, lead to worse outcomes, he said at the annual scientific meeting on infectious diseases.

Decolonization is not routine in most ICUs, but it’s gaining traction. Guidelines recommend chlorhexidine bathing with wipes to stop CRE transmission, and chlorhexidine is used to prevent central line–associated bloodstream infections (CLABSI).

A recent analysis of 17 trials found marked decreases in MRSA and CLABSI with decolonization and concluded that chlorhexidine bathing “appears to be of the most clinical benefit when infection rates are high for a given ICU population,” as was the case in Kentucky (Crit Care. 2016 Nov 23;20[1]:379).

When researchers compared the year before the change to the year after, “we were pretty surprised at how much the rates of infection and colonization decreased. There have been some people that have been doing this in the ICU, but probably not to our extent. If you want to get rid of contact precautions, this is a great process to do it with,” Dr. Moss said.

Rates of colonization with MRSA or CRE fell from about 14 isolates per 10,000 patient-days to fewer than 6 (P = .026). Infection rates fell from 3.9 isolates per 10,000 patient-days to 2 (P = .083). Combined rates of infections and colonizations fell from almost 18 isolates per 10,000 patient-days to fewer than 8 (P = .010).

Decolonization is now standard practice at the university. Every ICU patient gets a one-time povidone iodine nasal swab at admission, then daily baths with 2% chlorhexidine gluconate applied by impregnated wipe. It usually takes four or five wipes to do the entire body.

Spending on gowns fell from about $153,000 per year to just under $60,000, but spending on wipes went up from about $2,700 to $275,000, and spending on povidone iodine nasal swabs went up to more than $100,000.

When balanced against the money not spent on those 11 prevented infections, however, the program saved the medical center about $152,000 in its first year, according to Dr. Moss and his team.

There was no funding for the work, and the investigators had no disclosures.
 

[email protected]

SOURCE: Moss J et al. ID Week 2018, Abstract 32.

SAN FRANCISCO – The University of Kentucky Medical Center, Lexington, halved the rate of MRSA and CRE infections in the ICU by switching from contact precautions to decolonization with nasal povidone iodine swabs and daily chlorhexidine wipes, according to a report presented at ID Week 2018.

M. Alexander Otto/MDedge News

The move prevented an estimated eight methicillin-resistant Staphylococcus aureus (MRSA) and three carbapenem-resistant Enterobacteriaceae (CRE) infections and saved the medical center more than $150,000 in the year following the November 2016 switch.

The goal was to address the rate of MRSA bacteremia, which was higher than national ICU averages. Contact precautions began to make less sense as MRSA became more common in the surrounding community, and “we just wanted to get rid of contact precautions,” said study lead Jason Moss, DO, an infectious disease fellow at the university.

Contact precautions are expensive, make patients feel isolated, and according to some studies, lead to worse outcomes, he said at the annual scientific meeting on infectious diseases.

Decolonization is not routine in most ICUs, but it’s gaining traction. Guidelines recommend chlorhexidine bathing with wipes to stop CRE transmission, and chlorhexidine is used to prevent central line–associated bloodstream infections (CLABSI).

A recent analysis of 17 trials found marked decreases in MRSA and CLABSI with decolonization and concluded that chlorhexidine bathing “appears to be of the most clinical benefit when infection rates are high for a given ICU population,” as was the case in Kentucky (Crit Care. 2016 Nov 23;20[1]:379).

When researchers compared the year before the change to the year after, “we were pretty surprised at how much the rates of infection and colonization decreased. There have been some people that have been doing this in the ICU, but probably not to our extent. If you want to get rid of contact precautions, this is a great process to do it with,” Dr. Moss said.

Rates of colonization with MRSA or CRE fell from about 14 isolates per 10,000 patient-days to fewer than 6 (P = .026). Infection rates fell from 3.9 isolates per 10,000 patient-days to 2 (P = .083). Combined rates of infections and colonizations fell from almost 18 isolates per 10,000 patient-days to fewer than 8 (P = .010).

Decolonization is now standard practice at the university. Every ICU patient gets a one-time povidone iodine nasal swab at admission, then daily baths with 2% chlorhexidine gluconate applied by impregnated wipe. It usually takes four or five wipes to do the entire body.

Spending on gowns fell from about $153,000 per year to just under $60,000, but spending on wipes went up from about $2,700 to $275,000, and spending on povidone iodine nasal swabs went up to more than $100,000.

When balanced against the money not spent on those 11 prevented infections, however, the program saved the medical center about $152,000 in its first year, according to Dr. Moss and his team.

There was no funding for the work, and the investigators had no disclosures.
 

[email protected]

SOURCE: Moss J et al. ID Week 2018, Abstract 32.

SAN FRANCISCO – The University of Kentucky Medical Center, Lexington, halved the rate of MRSA and CRE infections in the ICU by switching from contact precautions to decolonization with nasal povidone iodine swabs and daily chlorhexidine wipes, according to a report presented at ID Week 2018.

M. Alexander Otto/MDedge News

The move prevented an estimated eight methicillin-resistant Staphylococcus aureus (MRSA) and three carbapenem-resistant Enterobacteriaceae (CRE) infections and saved the medical center more than $150,000 in the year following the November 2016 switch.

The goal was to address the rate of MRSA bacteremia, which was higher than national ICU averages. Contact precautions began to make less sense as MRSA became more common in the surrounding community, and “we just wanted to get rid of contact precautions,” said study lead Jason Moss, DO, an infectious disease fellow at the university.

Contact precautions are expensive, make patients feel isolated, and according to some studies, lead to worse outcomes, he said at the annual scientific meeting on infectious diseases.

Decolonization is not routine in most ICUs, but it’s gaining traction. Guidelines recommend chlorhexidine bathing with wipes to stop CRE transmission, and chlorhexidine is used to prevent central line–associated bloodstream infections (CLABSI).

A recent analysis of 17 trials found marked decreases in MRSA and CLABSI with decolonization and concluded that chlorhexidine bathing “appears to be of the most clinical benefit when infection rates are high for a given ICU population,” as was the case in Kentucky (Crit Care. 2016 Nov 23;20[1]:379).

When researchers compared the year before the change to the year after, “we were pretty surprised at how much the rates of infection and colonization decreased. There have been some people that have been doing this in the ICU, but probably not to our extent. If you want to get rid of contact precautions, this is a great process to do it with,” Dr. Moss said.

Rates of colonization with MRSA or CRE fell from about 14 isolates per 10,000 patient-days to fewer than 6 (P = .026). Infection rates fell from 3.9 isolates per 10,000 patient-days to 2 (P = .083). Combined rates of infections and colonizations fell from almost 18 isolates per 10,000 patient-days to fewer than 8 (P = .010).

Decolonization is now standard practice at the university. Every ICU patient gets a one-time povidone iodine nasal swab at admission, then daily baths with 2% chlorhexidine gluconate applied by impregnated wipe. It usually takes four or five wipes to do the entire body.

Spending on gowns fell from about $153,000 per year to just under $60,000, but spending on wipes went up from about $2,700 to $275,000, and spending on povidone iodine nasal swabs went up to more than $100,000.

When balanced against the money not spent on those 11 prevented infections, however, the program saved the medical center about $152,000 in its first year, according to Dr. Moss and his team.

There was no funding for the work, and the investigators had no disclosures.
 

[email protected]

SOURCE: Moss J et al. ID Week 2018, Abstract 32.

PARIS – Using a point-of-care test for viral pathogens, hospital admissions were avoided in about a third of emergency department patients with suspected respiratory infection when other clinical signs also suggested a low risk of a bacterial pathogen, according to a single-center experience presented at the annual congress of the European Respiratory Society.

Wikimedia Commons

“We found that when patients had point-of-care respiratory viral testing soon after they were admitted to the emergency department, we were able to reduce unnecessary admission and improve bed flow in our center,” reported Kay Roy, MBBS, consultant physician in respiratory medicine, West Hertfordshire (England) Hospital NHS Trust.

In a protocol that was launched at Dr. Kay’s institution in January 2018, the point-of-care viral test was combined with other clinical factors, particularly chest x-rays and elevated C-reactive protein (CRP), to determine whether patients had a viral pathogen and whether they could be discharged without antibiotics.

“Clinical judgment will always be required in individual patient decisions regarding antibiotic avoidance and early discharge,” Dr. Roy maintained. “But the point-of-care viral assay can be integrated into a strategy that permits more informed and rapid decision-making.”

This assertion is supported by the experience using a protocol anchored with the point-of-care viral test over a 4-month period. During this time, 901 patients with respiratory symptoms suspected of having a viral etiology were evaluated with the proprietary point-of-care device called FilmArray (bioMérieux).

From a sample taken with a nasopharyngeal swab, the test can identify a broad array of viruses using polymerase chain reaction technology in less than 45 minutes. However, the ED protocol for considering discharge without antibiotics requires additional evidence that the pathogen is viral, including a normal chest x-ray and a CRP less than 50 mg/L.

Of the 901 patients tested, a substantial proportion of whom had chronic obstructive pulmonary disease (COPD) or asthma, 507 (56%) tested positive for at least one virus, including influenza, rhinoviruses, coronaviruses, and adenovirus. Of these, 239 had normal chest x-rays and CRPs less than 50 mg/L. Because of the severity of symptoms or other clinical considerations, 154 patients were admitted, but 85 (36% of those meeting protocol criteria) were discharged without an antibiotic prescription.

“Antibiotics were continued in 90% of the patients who had an abnormal chest x-ray and abnormal CRP,” Dr. Roy reported. However, an objective strategy that permits clinicians to discharge patients at very low risk of a bacterial infection has many advantages even if it applies to a relatively modest proportion of those tested, according to Dr. Roy.

“Each respiratory admission can cost around [2,000 pounds] at our center,” reported Dr. Kay, referring to a figure equivalent to more than $2,600. In addition, she said that avoiding hospitalization frees up hospital beds and facilitates improved antimicrobial stewardship, which is vital to stem resistance.

Avoiding antibiotic use in patients with viral respiratory infections also is relevant to improved antibiotic stewardship in the community. For this reason, a randomized trial with a similar protocol involving the point-of-care viral test is planned in the outpatient setting. According to Dr. Roy, this will involve a community hub to which patients can be referred for testing and clinical evaluation.

“We hope that the quality of care can be improved with the point-of-care test for respiratory viruses as well as helping to reduce antibiotic resistance,” Dr. Roy said.

This approach is promising, according to Tobias Welte, MD, of the department of respiratory medicine at Hannover (Germany) Medical School, but he cautioned that it is not a standard approach.

“The protocol described by Dr. Roy will have to be compared to guidelines and recommended best clinical practice to confirm its usefulness,” he said, while conceding that any strategy that reduces unnecessary hospitalizations deserves further evaluation.

PARIS – Using a point-of-care test for viral pathogens, hospital admissions were avoided in about a third of emergency department patients with suspected respiratory infection when other clinical signs also suggested a low risk of a bacterial pathogen, according to a single-center experience presented at the annual congress of the European Respiratory Society.

Wikimedia Commons

“We found that when patients had point-of-care respiratory viral testing soon after they were admitted to the emergency department, we were able to reduce unnecessary admission and improve bed flow in our center,” reported Kay Roy, MBBS, consultant physician in respiratory medicine, West Hertfordshire (England) Hospital NHS Trust.

In a protocol that was launched at Dr. Kay’s institution in January 2018, the point-of-care viral test was combined with other clinical factors, particularly chest x-rays and elevated C-reactive protein (CRP), to determine whether patients had a viral pathogen and whether they could be discharged without antibiotics.

“Clinical judgment will always be required in individual patient decisions regarding antibiotic avoidance and early discharge,” Dr. Roy maintained. “But the point-of-care viral assay can be integrated into a strategy that permits more informed and rapid decision-making.”

This assertion is supported by the experience using a protocol anchored with the point-of-care viral test over a 4-month period. During this time, 901 patients with respiratory symptoms suspected of having a viral etiology were evaluated with the proprietary point-of-care device called FilmArray (bioMérieux).

From a sample taken with a nasopharyngeal swab, the test can identify a broad array of viruses using polymerase chain reaction technology in less than 45 minutes. However, the ED protocol for considering discharge without antibiotics requires additional evidence that the pathogen is viral, including a normal chest x-ray and a CRP less than 50 mg/L.

Of the 901 patients tested, a substantial proportion of whom had chronic obstructive pulmonary disease (COPD) or asthma, 507 (56%) tested positive for at least one virus, including influenza, rhinoviruses, coronaviruses, and adenovirus. Of these, 239 had normal chest x-rays and CRPs less than 50 mg/L. Because of the severity of symptoms or other clinical considerations, 154 patients were admitted, but 85 (36% of those meeting protocol criteria) were discharged without an antibiotic prescription.

“Antibiotics were continued in 90% of the patients who had an abnormal chest x-ray and abnormal CRP,” Dr. Roy reported. However, an objective strategy that permits clinicians to discharge patients at very low risk of a bacterial infection has many advantages even if it applies to a relatively modest proportion of those tested, according to Dr. Roy.

“Each respiratory admission can cost around [2,000 pounds] at our center,” reported Dr. Kay, referring to a figure equivalent to more than $2,600. In addition, she said that avoiding hospitalization frees up hospital beds and facilitates improved antimicrobial stewardship, which is vital to stem resistance.

Avoiding antibiotic use in patients with viral respiratory infections also is relevant to improved antibiotic stewardship in the community. For this reason, a randomized trial with a similar protocol involving the point-of-care viral test is planned in the outpatient setting. According to Dr. Roy, this will involve a community hub to which patients can be referred for testing and clinical evaluation.

“We hope that the quality of care can be improved with the point-of-care test for respiratory viruses as well as helping to reduce antibiotic resistance,” Dr. Roy said.

This approach is promising, according to Tobias Welte, MD, of the department of respiratory medicine at Hannover (Germany) Medical School, but he cautioned that it is not a standard approach.

“The protocol described by Dr. Roy will have to be compared to guidelines and recommended best clinical practice to confirm its usefulness,” he said, while conceding that any strategy that reduces unnecessary hospitalizations deserves further evaluation.

PARIS – Using a point-of-care test for viral pathogens, hospital admissions were avoided in about a third of emergency department patients with suspected respiratory infection when other clinical signs also suggested a low risk of a bacterial pathogen, according to a single-center experience presented at the annual congress of the European Respiratory Society.

Wikimedia Commons

“We found that when patients had point-of-care respiratory viral testing soon after they were admitted to the emergency department, we were able to reduce unnecessary admission and improve bed flow in our center,” reported Kay Roy, MBBS, consultant physician in respiratory medicine, West Hertfordshire (England) Hospital NHS Trust.

In a protocol that was launched at Dr. Kay’s institution in January 2018, the point-of-care viral test was combined with other clinical factors, particularly chest x-rays and elevated C-reactive protein (CRP), to determine whether patients had a viral pathogen and whether they could be discharged without antibiotics.

“Clinical judgment will always be required in individual patient decisions regarding antibiotic avoidance and early discharge,” Dr. Roy maintained. “But the point-of-care viral assay can be integrated into a strategy that permits more informed and rapid decision-making.”

This assertion is supported by the experience using a protocol anchored with the point-of-care viral test over a 4-month period. During this time, 901 patients with respiratory symptoms suspected of having a viral etiology were evaluated with the proprietary point-of-care device called FilmArray (bioMérieux).

From a sample taken with a nasopharyngeal swab, the test can identify a broad array of viruses using polymerase chain reaction technology in less than 45 minutes. However, the ED protocol for considering discharge without antibiotics requires additional evidence that the pathogen is viral, including a normal chest x-ray and a CRP less than 50 mg/L.

Of the 901 patients tested, a substantial proportion of whom had chronic obstructive pulmonary disease (COPD) or asthma, 507 (56%) tested positive for at least one virus, including influenza, rhinoviruses, coronaviruses, and adenovirus. Of these, 239 had normal chest x-rays and CRPs less than 50 mg/L. Because of the severity of symptoms or other clinical considerations, 154 patients were admitted, but 85 (36% of those meeting protocol criteria) were discharged without an antibiotic prescription.

“Antibiotics were continued in 90% of the patients who had an abnormal chest x-ray and abnormal CRP,” Dr. Roy reported. However, an objective strategy that permits clinicians to discharge patients at very low risk of a bacterial infection has many advantages even if it applies to a relatively modest proportion of those tested, according to Dr. Roy.

“Each respiratory admission can cost around [2,000 pounds] at our center,” reported Dr. Kay, referring to a figure equivalent to more than $2,600. In addition, she said that avoiding hospitalization frees up hospital beds and facilitates improved antimicrobial stewardship, which is vital to stem resistance.

Avoiding antibiotic use in patients with viral respiratory infections also is relevant to improved antibiotic stewardship in the community. For this reason, a randomized trial with a similar protocol involving the point-of-care viral test is planned in the outpatient setting. According to Dr. Roy, this will involve a community hub to which patients can be referred for testing and clinical evaluation.

“We hope that the quality of care can be improved with the point-of-care test for respiratory viruses as well as helping to reduce antibiotic resistance,” Dr. Roy said.

This approach is promising, according to Tobias Welte, MD, of the department of respiratory medicine at Hannover (Germany) Medical School, but he cautioned that it is not a standard approach.

“The protocol described by Dr. Roy will have to be compared to guidelines and recommended best clinical practice to confirm its usefulness,” he said, while conceding that any strategy that reduces unnecessary hospitalizations deserves further evaluation.

WASHINGTON – A strategy combining stewardship and science is needed to help combat antimicrobial resistance, and updated plans from the U.S. Food and Drug Administration include four key components to address all aspects of product development and use, FDA commissioner Scott Gottlieb, MD, said in a press briefing in Washington on Sept. 14. 

“The FDA plays a unique role in advancing human and animal health” that provides a unique vantage point for coordinating all aspects of product development and application, he said. 

The FDA’s comprehensive approach to the challenge of antimicrobial resistance (AMR) includes:

• Facilitating product development.
• Promoting antimicrobial stewardship.
• Supporting the development of new tools for surveillance.
• Advancing scientific initiatives, including research for the development of alternative treatments.

The FDA’s product development plan to combat AMR includes the creation of incentives for companies to develop new antibiotic products and create a robust pipeline, which is a challenge because of the lack of immediate economic gain, Dr. Gottlieb said.
“It necessary to change the perception that the costs and risks of antibiotic innovation are too high relative to their expected gains,” he emphasized. 

Strategies to incentivize companies include fast track designation, priority review, and breakthrough therapy designation. In addition, the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) is designed to promote development of antimicrobial drugs for limited and underserved populations, Dr. Gottlieb said. The FDA plan also calls for pursuing reimbursement options with the Centers for Medicare & Medicaid Services. 

Promoting antimicrobial stewardship remains an ongoing element of the FDA’s plan to reduce AMR. In conjunction with the release of the FDA’s updated approach to AMR, the FDA’s Center for Veterinary Medicine CVM released a 5-year action plan to promote and support antimicrobial stewardship in not only the agricultural arena, but in companion animals as well. 

The FDA plans to bring all antimicrobials of medical importance that are approved for use in animals under the oversight of CVM, which will pursue the improve labeling on antimicrobial drugs used in the feed and water of food-producing animals, including defining durations of use, Dr. Gottlieb noted.

Supporting the development and improvement of surveillance tools is “essential to understanding the drivers of resistance in human and veterinary settings and formulating appropriate responses” to outbreaks, Dr. Gottlieb said.

To help meet this goal, the FDA will expand sampling via the National Antimicrobial Resistance Monitoring System (NARMS) database, he said. Other surveillance goals include supporting genomics research and expanding AMR monitoring to include pathogens associated with animal feed and companion animals, he added. 

As part of the final component of the FDA’s AMR strategy to advance scientific initiatives, the FDA has released a new Request for Information “to obtain additional, external input on how best to develop an annual list of regulatory science initiatives specific for antimicrobial products,” Dr. Gottlieb announced. The FDA intends to use the information gained from clinicians and others in its creation of guidance documents and recommendations to streamline the antibiotic development process. He also cited the FDA’s ongoing support of partnerships with public and private organizations such as the Clinical Trials Transformation Initiative, which focuses on drug development for severe bacterial infections with current unmet medical need.

“We need to harness science and policy to help our public health systems and researchers become nimbler in the battle against drug-resistant pathogens,” Dr. Gottlieb concluded. 

In a panel discussion following the briefing, several experts offered perspective on the FDA’s goals and on the challenges of AMR. 

William Flynn, DVM, deputy director of science policy for the Center of Veterinary Medicine, noted some goals for reducing the use of antibiotics in the veterinary arena. 

“We are trying to focus on the driver: What are the disease conditions that drive use of the product,” he said. Ideally, better management of disease conditions can reduce reliance on antibiotics, he added. 

Also in the panel discussion, Steven Gitterman, MD, deputy director of the division of microbiology devices at the Center for Devices and Radiological Health, emphasized the value of sustainable trial databases so AMR research can continue on an ongoing basis. Finally, Carolyn Wilson, PhD, associate director of research at the Center for Biologics Evaluation and Research, noted that the FDA’s research and development efforts include antibiotic alternatives, including live biotherapeutic products, fecal microbiota transplantation, and bacteriophage therapy.

Visit www.fda.gov for a transcript of Dr. Gottlieb’s talk, and for the updated FDA website page with more details on the agency’s plans to combat antimicrobial resistance. 

Dr. Gottlieb and the panelists had no financial conflicts to disclose.

WASHINGTON – A strategy combining stewardship and science is needed to help combat antimicrobial resistance, and updated plans from the U.S. Food and Drug Administration include four key components to address all aspects of product development and use, FDA commissioner Scott Gottlieb, MD, said in a press briefing in Washington on Sept. 14. 

“The FDA plays a unique role in advancing human and animal health” that provides a unique vantage point for coordinating all aspects of product development and application, he said. 

The FDA’s comprehensive approach to the challenge of antimicrobial resistance (AMR) includes:

• Facilitating product development.
• Promoting antimicrobial stewardship.
• Supporting the development of new tools for surveillance.
• Advancing scientific initiatives, including research for the development of alternative treatments.

The FDA’s product development plan to combat AMR includes the creation of incentives for companies to develop new antibiotic products and create a robust pipeline, which is a challenge because of the lack of immediate economic gain, Dr. Gottlieb said.
“It necessary to change the perception that the costs and risks of antibiotic innovation are too high relative to their expected gains,” he emphasized. 

Strategies to incentivize companies include fast track designation, priority review, and breakthrough therapy designation. In addition, the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) is designed to promote development of antimicrobial drugs for limited and underserved populations, Dr. Gottlieb said. The FDA plan also calls for pursuing reimbursement options with the Centers for Medicare & Medicaid Services. 

Promoting antimicrobial stewardship remains an ongoing element of the FDA’s plan to reduce AMR. In conjunction with the release of the FDA’s updated approach to AMR, the FDA’s Center for Veterinary Medicine CVM released a 5-year action plan to promote and support antimicrobial stewardship in not only the agricultural arena, but in companion animals as well. 

The FDA plans to bring all antimicrobials of medical importance that are approved for use in animals under the oversight of CVM, which will pursue the improve labeling on antimicrobial drugs used in the feed and water of food-producing animals, including defining durations of use, Dr. Gottlieb noted.

Supporting the development and improvement of surveillance tools is “essential to understanding the drivers of resistance in human and veterinary settings and formulating appropriate responses” to outbreaks, Dr. Gottlieb said.

To help meet this goal, the FDA will expand sampling via the National Antimicrobial Resistance Monitoring System (NARMS) database, he said. Other surveillance goals include supporting genomics research and expanding AMR monitoring to include pathogens associated with animal feed and companion animals, he added. 

As part of the final component of the FDA’s AMR strategy to advance scientific initiatives, the FDA has released a new Request for Information “to obtain additional, external input on how best to develop an annual list of regulatory science initiatives specific for antimicrobial products,” Dr. Gottlieb announced. The FDA intends to use the information gained from clinicians and others in its creation of guidance documents and recommendations to streamline the antibiotic development process. He also cited the FDA’s ongoing support of partnerships with public and private organizations such as the Clinical Trials Transformation Initiative, which focuses on drug development for severe bacterial infections with current unmet medical need.

“We need to harness science and policy to help our public health systems and researchers become nimbler in the battle against drug-resistant pathogens,” Dr. Gottlieb concluded. 

In a panel discussion following the briefing, several experts offered perspective on the FDA’s goals and on the challenges of AMR. 

William Flynn, DVM, deputy director of science policy for the Center of Veterinary Medicine, noted some goals for reducing the use of antibiotics in the veterinary arena. 

“We are trying to focus on the driver: What are the disease conditions that drive use of the product,” he said. Ideally, better management of disease conditions can reduce reliance on antibiotics, he added. 

Also in the panel discussion, Steven Gitterman, MD, deputy director of the division of microbiology devices at the Center for Devices and Radiological Health, emphasized the value of sustainable trial databases so AMR research can continue on an ongoing basis. Finally, Carolyn Wilson, PhD, associate director of research at the Center for Biologics Evaluation and Research, noted that the FDA’s research and development efforts include antibiotic alternatives, including live biotherapeutic products, fecal microbiota transplantation, and bacteriophage therapy.

Visit www.fda.gov for a transcript of Dr. Gottlieb’s talk, and for the updated FDA website page with more details on the agency’s plans to combat antimicrobial resistance. 

Dr. Gottlieb and the panelists had no financial conflicts to disclose.

WASHINGTON – A strategy combining stewardship and science is needed to help combat antimicrobial resistance, and updated plans from the U.S. Food and Drug Administration include four key components to address all aspects of product development and use, FDA commissioner Scott Gottlieb, MD, said in a press briefing in Washington on Sept. 14. 

“The FDA plays a unique role in advancing human and animal health” that provides a unique vantage point for coordinating all aspects of product development and application, he said. 

The FDA’s comprehensive approach to the challenge of antimicrobial resistance (AMR) includes:

• Facilitating product development.
• Promoting antimicrobial stewardship.
• Supporting the development of new tools for surveillance.
• Advancing scientific initiatives, including research for the development of alternative treatments.

The FDA’s product development plan to combat AMR includes the creation of incentives for companies to develop new antibiotic products and create a robust pipeline, which is a challenge because of the lack of immediate economic gain, Dr. Gottlieb said.
“It necessary to change the perception that the costs and risks of antibiotic innovation are too high relative to their expected gains,” he emphasized. 

Strategies to incentivize companies include fast track designation, priority review, and breakthrough therapy designation. In addition, the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) is designed to promote development of antimicrobial drugs for limited and underserved populations, Dr. Gottlieb said. The FDA plan also calls for pursuing reimbursement options with the Centers for Medicare & Medicaid Services. 

Promoting antimicrobial stewardship remains an ongoing element of the FDA’s plan to reduce AMR. In conjunction with the release of the FDA’s updated approach to AMR, the FDA’s Center for Veterinary Medicine CVM released a 5-year action plan to promote and support antimicrobial stewardship in not only the agricultural arena, but in companion animals as well. 

The FDA plans to bring all antimicrobials of medical importance that are approved for use in animals under the oversight of CVM, which will pursue the improve labeling on antimicrobial drugs used in the feed and water of food-producing animals, including defining durations of use, Dr. Gottlieb noted.

Supporting the development and improvement of surveillance tools is “essential to understanding the drivers of resistance in human and veterinary settings and formulating appropriate responses” to outbreaks, Dr. Gottlieb said.

To help meet this goal, the FDA will expand sampling via the National Antimicrobial Resistance Monitoring System (NARMS) database, he said. Other surveillance goals include supporting genomics research and expanding AMR monitoring to include pathogens associated with animal feed and companion animals, he added. 

As part of the final component of the FDA’s AMR strategy to advance scientific initiatives, the FDA has released a new Request for Information “to obtain additional, external input on how best to develop an annual list of regulatory science initiatives specific for antimicrobial products,” Dr. Gottlieb announced. The FDA intends to use the information gained from clinicians and others in its creation of guidance documents and recommendations to streamline the antibiotic development process. He also cited the FDA’s ongoing support of partnerships with public and private organizations such as the Clinical Trials Transformation Initiative, which focuses on drug development for severe bacterial infections with current unmet medical need.

“We need to harness science and policy to help our public health systems and researchers become nimbler in the battle against drug-resistant pathogens,” Dr. Gottlieb concluded. 

In a panel discussion following the briefing, several experts offered perspective on the FDA’s goals and on the challenges of AMR. 

William Flynn, DVM, deputy director of science policy for the Center of Veterinary Medicine, noted some goals for reducing the use of antibiotics in the veterinary arena. 

“We are trying to focus on the driver: What are the disease conditions that drive use of the product,” he said. Ideally, better management of disease conditions can reduce reliance on antibiotics, he added. 

Also in the panel discussion, Steven Gitterman, MD, deputy director of the division of microbiology devices at the Center for Devices and Radiological Health, emphasized the value of sustainable trial databases so AMR research can continue on an ongoing basis. Finally, Carolyn Wilson, PhD, associate director of research at the Center for Biologics Evaluation and Research, noted that the FDA’s research and development efforts include antibiotic alternatives, including live biotherapeutic products, fecal microbiota transplantation, and bacteriophage therapy.

Visit www.fda.gov for a transcript of Dr. Gottlieb’s talk, and for the updated FDA website page with more details on the agency’s plans to combat antimicrobial resistance. 

Dr. Gottlieb and the panelists had no financial conflicts to disclose.

Mortality within 90 days of infection was 45% among 51 patients diagnosed with antibiotic-resistant Candida auris infections in a multihospital outbreak in New York City from 2012 to 2017.

Transmission is ongoing in health care facilities, primarily among patients with extensive health care exposures, according to a report published in Emerging Infectious Diseases.

Shawn Lockhart/CDC

In the intensive case-patient analysis conducted by the New York State Health Department, 21 cases were from seven hospitals in Brooklyn, 16 were from three hospitals and one private medical office in Queens, 12 were from five hospitals and one long-term acute care hospital in Manhattan, and 1 was from a hospital in the Bronx. The remaining clinical case was identified in a western New York hospital in a patient who had recently been admitted to an involved Brooklyn hospital.

Among these patients, 31 (61%) had resided in long-term care facilities immediately before being admitted to the hospital in which their infection was diagnosed, and 19 of these 31 resided in skilled nursing facilities with ventilator beds; 1 (2%) resided in a long-term acute care hospital; 5 (10%) had been transferred from another hospital; and 4 (8%) had traveled internationally within 5 years before diagnosis, according to the investigators.

Isolates from 50 patients (98%) were resistant to fluconazole and 13 (25%) were resistant to fluconazole and amphotericin B. No initial isolates were resistant to echinocandins, although subsequent isolates obtained from 3 persons who had received an echinocandin acquired resistance to it, according to the researchers. Whole-genome sequencing performed at The Centers for Disease Control and Prevention indicated that 50 of 51 isolates belonged to a South Asia clade; the remaining isolate was the only one susceptible to fluconazole.

The work was supported by the CDC. No disclosures were reported.

[email protected]

SOURCE: Adams E et al. Emerg Infect Dis. 2018 Sep 12; 24(10); ID: 18-0649.

Mortality within 90 days of infection was 45% among 51 patients diagnosed with antibiotic-resistant Candida auris infections in a multihospital outbreak in New York City from 2012 to 2017.

Transmission is ongoing in health care facilities, primarily among patients with extensive health care exposures, according to a report published in Emerging Infectious Diseases.

Shawn Lockhart/CDC

In the intensive case-patient analysis conducted by the New York State Health Department, 21 cases were from seven hospitals in Brooklyn, 16 were from three hospitals and one private medical office in Queens, 12 were from five hospitals and one long-term acute care hospital in Manhattan, and 1 was from a hospital in the Bronx. The remaining clinical case was identified in a western New York hospital in a patient who had recently been admitted to an involved Brooklyn hospital.

Among these patients, 31 (61%) had resided in long-term care facilities immediately before being admitted to the hospital in which their infection was diagnosed, and 19 of these 31 resided in skilled nursing facilities with ventilator beds; 1 (2%) resided in a long-term acute care hospital; 5 (10%) had been transferred from another hospital; and 4 (8%) had traveled internationally within 5 years before diagnosis, according to the investigators.

Isolates from 50 patients (98%) were resistant to fluconazole and 13 (25%) were resistant to fluconazole and amphotericin B. No initial isolates were resistant to echinocandins, although subsequent isolates obtained from 3 persons who had received an echinocandin acquired resistance to it, according to the researchers. Whole-genome sequencing performed at The Centers for Disease Control and Prevention indicated that 50 of 51 isolates belonged to a South Asia clade; the remaining isolate was the only one susceptible to fluconazole.

The work was supported by the CDC. No disclosures were reported.

[email protected]

SOURCE: Adams E et al. Emerg Infect Dis. 2018 Sep 12; 24(10); ID: 18-0649.

Mortality within 90 days of infection was 45% among 51 patients diagnosed with antibiotic-resistant Candida auris infections in a multihospital outbreak in New York City from 2012 to 2017.

Transmission is ongoing in health care facilities, primarily among patients with extensive health care exposures, according to a report published in Emerging Infectious Diseases.

Shawn Lockhart/CDC

In the intensive case-patient analysis conducted by the New York State Health Department, 21 cases were from seven hospitals in Brooklyn, 16 were from three hospitals and one private medical office in Queens, 12 were from five hospitals and one long-term acute care hospital in Manhattan, and 1 was from a hospital in the Bronx. The remaining clinical case was identified in a western New York hospital in a patient who had recently been admitted to an involved Brooklyn hospital.

Among these patients, 31 (61%) had resided in long-term care facilities immediately before being admitted to the hospital in which their infection was diagnosed, and 19 of these 31 resided in skilled nursing facilities with ventilator beds; 1 (2%) resided in a long-term acute care hospital; 5 (10%) had been transferred from another hospital; and 4 (8%) had traveled internationally within 5 years before diagnosis, according to the investigators.

Isolates from 50 patients (98%) were resistant to fluconazole and 13 (25%) were resistant to fluconazole and amphotericin B. No initial isolates were resistant to echinocandins, although subsequent isolates obtained from 3 persons who had received an echinocandin acquired resistance to it, according to the researchers. Whole-genome sequencing performed at The Centers for Disease Control and Prevention indicated that 50 of 51 isolates belonged to a South Asia clade; the remaining isolate was the only one susceptible to fluconazole.

The work was supported by the CDC. No disclosures were reported.

[email protected]

SOURCE: Adams E et al. Emerg Infect Dis. 2018 Sep 12; 24(10); ID: 18-0649.

A new study finds that piperacillin-tazobactam doesn’t improve mortality compared to meropenem in patients with ceftriaxone-resistant blood poisoning caused by E. coli or K. pneumoniae. The findings were so striking that the study was ended early.

Vidyard Video

Courtesy: JAMA

“These findings do not support use of piperacillin-tazobactam in this setting,” wrote the authors. The report was published Sept. 11 in JAMA (2018;320[10]:984-94.)

According to the Centers for Disease Control and Prevention, an estimated 1,700 deaths in the United States in 2011 were caused by gram-negative bacteria that produce extended-spectrum beta-lactamase enzymes.

While carbapenems such as meropenem (Merrem) are “regarded as the treatment of choice for serious infections,” the MERINO trial (NCT02176122) authors wrote, their rising use could lead to drug resistance.

One alternate option is to embrace beta-lactam/beta-lactamase inhibitors such as piperacillin-tazobactam (Zosyn), the researchers noted, but research has produced conflicting results.

Piperacillin-tazobactam is an injected penicillin antibiotic used to treat conditions such as severe pneumonia, complicated urinary tract infections and complicated skin and soft tissue infections.

For the new study, researchers led by Patrick N. A. Harris, MBBS, of the University of Queensland, randomly assigned 188 patients to intravenous piperacillin-tazobactam (4.5 g every 6 hours) and 191 patients to meropenem (1 g every 8 hours) for 4-14 days, depending on clinician’s preference. (12 other patients did not continue with the study after initial randomization due to factors such as errors).

All patients were adults and had at least one blood test showing they were positive for E. coli or K. pneumoniae. They all had to be nonsusceptible to ceftriaxone (Rocephin) but susceptible to piperacillin-tazobactam.

The study was ceased prior to enrollment because of the risk of harm. Interim findings suggested the study was unlikely to show higher effectiveness for piperacillin-tazobactam

The primary analysis included 379 patients (mean age 67 years, 48% were women), and the primary outcome analysis included 378 patients.

A total of 23 (12.3%) of 187 patients in the piperacillin-tazobactam group died by 30 days compared to 7 (3.7%) of 191 in the meropenem group (risk difference: 8.6%, P = .90 for noninferiority).

By day 4, 68% of the piperacillin-tazobactam group and 75% of the meropenem group achieved clinical and microbiological resolution.

Serious adverse effects other than death were rare, occurring in around 3% of the piperacillin-tazobactam group and nearly 2% of the meropenem group.

The researchers note various limitations, including the unblinded nature of the study and the fact that it’s not known if extended or continuous infusions of piperacillin-tazobactam would boost the drug’s effectiveness. They also note that delays resulted in some patients initially receiving treatment with one of the study’s two drugs before being randomized to the other.

The study authors caution that it’s not clear if newer beta-lactam/beta-lactamase inhibitors agents such as ceftolozane-tazobactam or ceftazidime-avibactam may be effective in this population.

The study was funded by the University of Queensland, Australian Society for Antimicrobials, International Society for Chemotherapy, and National University Hospital Singapore. Various organizations funded the researchers and the study’s whole-genome sequencing. The study authors report various disclosures, including funding from drugmakers such as Pfizer, maker of Zosyn (through its subsidiary Wyeth) and Merrem.
 

SOURCE: Harris PNA et al. JAMA 2018 Sep 11;320[10]:984-94. doi: 10.1001/jama.2018.12163.

A new study finds that piperacillin-tazobactam doesn’t improve mortality compared to meropenem in patients with ceftriaxone-resistant blood poisoning caused by E. coli or K. pneumoniae. The findings were so striking that the study was ended early.

Vidyard Video

Courtesy: JAMA

“These findings do not support use of piperacillin-tazobactam in this setting,” wrote the authors. The report was published Sept. 11 in JAMA (2018;320[10]:984-94.)

According to the Centers for Disease Control and Prevention, an estimated 1,700 deaths in the United States in 2011 were caused by gram-negative bacteria that produce extended-spectrum beta-lactamase enzymes.

While carbapenems such as meropenem (Merrem) are “regarded as the treatment of choice for serious infections,” the MERINO trial (NCT02176122) authors wrote, their rising use could lead to drug resistance.

One alternate option is to embrace beta-lactam/beta-lactamase inhibitors such as piperacillin-tazobactam (Zosyn), the researchers noted, but research has produced conflicting results.

Piperacillin-tazobactam is an injected penicillin antibiotic used to treat conditions such as severe pneumonia, complicated urinary tract infections and complicated skin and soft tissue infections.

For the new study, researchers led by Patrick N. A. Harris, MBBS, of the University of Queensland, randomly assigned 188 patients to intravenous piperacillin-tazobactam (4.5 g every 6 hours) and 191 patients to meropenem (1 g every 8 hours) for 4-14 days, depending on clinician’s preference. (12 other patients did not continue with the study after initial randomization due to factors such as errors).

All patients were adults and had at least one blood test showing they were positive for E. coli or K. pneumoniae. They all had to be nonsusceptible to ceftriaxone (Rocephin) but susceptible to piperacillin-tazobactam.

The study was ceased prior to enrollment because of the risk of harm. Interim findings suggested the study was unlikely to show higher effectiveness for piperacillin-tazobactam

The primary analysis included 379 patients (mean age 67 years, 48% were women), and the primary outcome analysis included 378 patients.

A total of 23 (12.3%) of 187 patients in the piperacillin-tazobactam group died by 30 days compared to 7 (3.7%) of 191 in the meropenem group (risk difference: 8.6%, P = .90 for noninferiority).

By day 4, 68% of the piperacillin-tazobactam group and 75% of the meropenem group achieved clinical and microbiological resolution.

Serious adverse effects other than death were rare, occurring in around 3% of the piperacillin-tazobactam group and nearly 2% of the meropenem group.

The researchers note various limitations, including the unblinded nature of the study and the fact that it’s not known if extended or continuous infusions of piperacillin-tazobactam would boost the drug’s effectiveness. They also note that delays resulted in some patients initially receiving treatment with one of the study’s two drugs before being randomized to the other.

The study authors caution that it’s not clear if newer beta-lactam/beta-lactamase inhibitors agents such as ceftolozane-tazobactam or ceftazidime-avibactam may be effective in this population.

The study was funded by the University of Queensland, Australian Society for Antimicrobials, International Society for Chemotherapy, and National University Hospital Singapore. Various organizations funded the researchers and the study’s whole-genome sequencing. The study authors report various disclosures, including funding from drugmakers such as Pfizer, maker of Zosyn (through its subsidiary Wyeth) and Merrem.
 

SOURCE: Harris PNA et al. JAMA 2018 Sep 11;320[10]:984-94. doi: 10.1001/jama.2018.12163.

A new study finds that piperacillin-tazobactam doesn’t improve mortality compared to meropenem in patients with ceftriaxone-resistant blood poisoning caused by E. coli or K. pneumoniae. The findings were so striking that the study was ended early.

Vidyard Video

Courtesy: JAMA

“These findings do not support use of piperacillin-tazobactam in this setting,” wrote the authors. The report was published Sept. 11 in JAMA (2018;320[10]:984-94.)

According to the Centers for Disease Control and Prevention, an estimated 1,700 deaths in the United States in 2011 were caused by gram-negative bacteria that produce extended-spectrum beta-lactamase enzymes.

While carbapenems such as meropenem (Merrem) are “regarded as the treatment of choice for serious infections,” the MERINO trial (NCT02176122) authors wrote, their rising use could lead to drug resistance.

One alternate option is to embrace beta-lactam/beta-lactamase inhibitors such as piperacillin-tazobactam (Zosyn), the researchers noted, but research has produced conflicting results.

Piperacillin-tazobactam is an injected penicillin antibiotic used to treat conditions such as severe pneumonia, complicated urinary tract infections and complicated skin and soft tissue infections.

For the new study, researchers led by Patrick N. A. Harris, MBBS, of the University of Queensland, randomly assigned 188 patients to intravenous piperacillin-tazobactam (4.5 g every 6 hours) and 191 patients to meropenem (1 g every 8 hours) for 4-14 days, depending on clinician’s preference. (12 other patients did not continue with the study after initial randomization due to factors such as errors).

All patients were adults and had at least one blood test showing they were positive for E. coli or K. pneumoniae. They all had to be nonsusceptible to ceftriaxone (Rocephin) but susceptible to piperacillin-tazobactam.

The study was ceased prior to enrollment because of the risk of harm. Interim findings suggested the study was unlikely to show higher effectiveness for piperacillin-tazobactam

The primary analysis included 379 patients (mean age 67 years, 48% were women), and the primary outcome analysis included 378 patients.

A total of 23 (12.3%) of 187 patients in the piperacillin-tazobactam group died by 30 days compared to 7 (3.7%) of 191 in the meropenem group (risk difference: 8.6%, P = .90 for noninferiority).

By day 4, 68% of the piperacillin-tazobactam group and 75% of the meropenem group achieved clinical and microbiological resolution.

Serious adverse effects other than death were rare, occurring in around 3% of the piperacillin-tazobactam group and nearly 2% of the meropenem group.

The researchers note various limitations, including the unblinded nature of the study and the fact that it’s not known if extended or continuous infusions of piperacillin-tazobactam would boost the drug’s effectiveness. They also note that delays resulted in some patients initially receiving treatment with one of the study’s two drugs before being randomized to the other.

The study authors caution that it’s not clear if newer beta-lactam/beta-lactamase inhibitors agents such as ceftolozane-tazobactam or ceftazidime-avibactam may be effective in this population.

The study was funded by the University of Queensland, Australian Society for Antimicrobials, International Society for Chemotherapy, and National University Hospital Singapore. Various organizations funded the researchers and the study’s whole-genome sequencing. The study authors report various disclosures, including funding from drugmakers such as Pfizer, maker of Zosyn (through its subsidiary Wyeth) and Merrem.
 

SOURCE: Harris PNA et al. JAMA 2018 Sep 11;320[10]:984-94. doi: 10.1001/jama.2018.12163.

The Society of Hospital Medicine is pleased to share successes and resources from a 3-year national quality improvement program called STRIVE (States Targeting Reduction in Infections Via Engagement). This program targeted opportunities to streamline and enhance infection prevention and control efforts in participating hospitals.

SHM was a key partner in the STRIVE program, which was managed by the Health Research & Educational Trust, the not-for-profit research and education affiliate of the American Hospital Association. Other partners included the American Society for Healthcare Engineering, Association for Professionals in Infection Control and Epidemiology, University of Michigan, Ann Arbor, and experts from academic institutions and professional societies such as Cornell University, Ithaca, N.Y.; Rush University, Chicago; and the Association for the Healthcare Environment. SHM provided specific knowledge and experience on HAI prevention and helped develop the STRIVE curriculum and resources. Faculty coaches from SHM also supported STRIVE hospitals by presenting on webinars, attending in-person meetings, and consulting on calls.

Following the U.S. experience with Ebola, the Centers for Disease Control and Infection identified the critical importance of enhancing infection control for all infectious threats to protect both patients and health care personnel. The CDC also recognized that many state and regional organizations and agencies work with the same health care facilities in order to coordinate efforts to address infectious threats. The STRIVE program provided tools and resources to help communities strengthen the relationships among diverse organizations to maximize improvement and coordination.

Closely aligned with SHM’s mission to promote exceptional care for hospitalized patients, the CDC’s STRIVE program goals were as follows:

• To expand the CDC’s Targeting Assessment for Prevention (TAP) strategy of using surveillance data to identify hospitals with a disproportionately high burden of health care–associated infections (HAIs),
• To build and strengthen relationships between state and regional organizations that help hospitals with infection control and prevention, and
• To provide technical assistance to hospitals to improve implementation of infection control practices in existing and newly constructed health care facilities.

The participants in this program included 449 hospitals from 28 states and the District of Columbia. Short-stay and long-term acute care hospitals that had a high burden of Clostridium difficile infection, and a high burden of one or more of the following HAIs – central line–associated bloodstream infection, catheter associated urinary tract infection, and health care–associated methicillin-resistant Staphylococcus aureus (MRSA) bacteremia – were targeted. Each participant had access to specific education modules, webinars, and learning networks designed to enhance collaboration, performance improvement, and understanding of the successes and barriers to coordinating hospital- and community-based services. Hospitals joined the program in cohorts and engaged in a year-long effort to reduce infection burden. During the program implementation period, many hospitals showed measurable improvement by achieving an HAI-specific relative rate reduction or maintenance of a rate of zero between baseline and intervention periods.

Key successes of the program centered around development of multidisciplinary teams that engaged not only the infection preventionists but also such areas as environmental services and other departments that may not have traditionally been included in infection prevention efforts. These teams focused on establishing competency-based trainings and processes for auditing competencies. One series of STRIVE resources helped hospitals learn new ways to implement best practices and communicate with diverse departments so every team member could participate in removing barriers to infection prevention in the hospital.

SHM was especially pleased to be a part of a program that brought together state health departments, state hospital associations, quality innovation network–quality improvement organizations, and other agencies and health systems committed to infection prevention. The collaboration and partnerships among the STRIVE program participants helped minimize duplication of work and improve efficiency and effectiveness of infection prevention efforts lead by hospitals.

To learn more about the STRIVE resources, visit www.hret.org/quality/projects/strive.shtml.


 

The Society of Hospital Medicine is pleased to share successes and resources from a 3-year national quality improvement program called STRIVE (States Targeting Reduction in Infections Via Engagement). This program targeted opportunities to streamline and enhance infection prevention and control efforts in participating hospitals.

SHM was a key partner in the STRIVE program, which was managed by the Health Research & Educational Trust, the not-for-profit research and education affiliate of the American Hospital Association. Other partners included the American Society for Healthcare Engineering, Association for Professionals in Infection Control and Epidemiology, University of Michigan, Ann Arbor, and experts from academic institutions and professional societies such as Cornell University, Ithaca, N.Y.; Rush University, Chicago; and the Association for the Healthcare Environment. SHM provided specific knowledge and experience on HAI prevention and helped develop the STRIVE curriculum and resources. Faculty coaches from SHM also supported STRIVE hospitals by presenting on webinars, attending in-person meetings, and consulting on calls.

Following the U.S. experience with Ebola, the Centers for Disease Control and Infection identified the critical importance of enhancing infection control for all infectious threats to protect both patients and health care personnel. The CDC also recognized that many state and regional organizations and agencies work with the same health care facilities in order to coordinate efforts to address infectious threats. The STRIVE program provided tools and resources to help communities strengthen the relationships among diverse organizations to maximize improvement and coordination.

Closely aligned with SHM’s mission to promote exceptional care for hospitalized patients, the CDC’s STRIVE program goals were as follows:

• To expand the CDC’s Targeting Assessment for Prevention (TAP) strategy of using surveillance data to identify hospitals with a disproportionately high burden of health care–associated infections (HAIs),
• To build and strengthen relationships between state and regional organizations that help hospitals with infection control and prevention, and
• To provide technical assistance to hospitals to improve implementation of infection control practices in existing and newly constructed health care facilities.

The participants in this program included 449 hospitals from 28 states and the District of Columbia. Short-stay and long-term acute care hospitals that had a high burden of Clostridium difficile infection, and a high burden of one or more of the following HAIs – central line–associated bloodstream infection, catheter associated urinary tract infection, and health care–associated methicillin-resistant Staphylococcus aureus (MRSA) bacteremia – were targeted. Each participant had access to specific education modules, webinars, and learning networks designed to enhance collaboration, performance improvement, and understanding of the successes and barriers to coordinating hospital- and community-based services. Hospitals joined the program in cohorts and engaged in a year-long effort to reduce infection burden. During the program implementation period, many hospitals showed measurable improvement by achieving an HAI-specific relative rate reduction or maintenance of a rate of zero between baseline and intervention periods.

Key successes of the program centered around development of multidisciplinary teams that engaged not only the infection preventionists but also such areas as environmental services and other departments that may not have traditionally been included in infection prevention efforts. These teams focused on establishing competency-based trainings and processes for auditing competencies. One series of STRIVE resources helped hospitals learn new ways to implement best practices and communicate with diverse departments so every team member could participate in removing barriers to infection prevention in the hospital.

SHM was especially pleased to be a part of a program that brought together state health departments, state hospital associations, quality innovation network–quality improvement organizations, and other agencies and health systems committed to infection prevention. The collaboration and partnerships among the STRIVE program participants helped minimize duplication of work and improve efficiency and effectiveness of infection prevention efforts lead by hospitals.

To learn more about the STRIVE resources, visit www.hret.org/quality/projects/strive.shtml.


 

The Society of Hospital Medicine is pleased to share successes and resources from a 3-year national quality improvement program called STRIVE (States Targeting Reduction in Infections Via Engagement). This program targeted opportunities to streamline and enhance infection prevention and control efforts in participating hospitals.

SHM was a key partner in the STRIVE program, which was managed by the Health Research & Educational Trust, the not-for-profit research and education affiliate of the American Hospital Association. Other partners included the American Society for Healthcare Engineering, Association for Professionals in Infection Control and Epidemiology, University of Michigan, Ann Arbor, and experts from academic institutions and professional societies such as Cornell University, Ithaca, N.Y.; Rush University, Chicago; and the Association for the Healthcare Environment. SHM provided specific knowledge and experience on HAI prevention and helped develop the STRIVE curriculum and resources. Faculty coaches from SHM also supported STRIVE hospitals by presenting on webinars, attending in-person meetings, and consulting on calls.

Following the U.S. experience with Ebola, the Centers for Disease Control and Infection identified the critical importance of enhancing infection control for all infectious threats to protect both patients and health care personnel. The CDC also recognized that many state and regional organizations and agencies work with the same health care facilities in order to coordinate efforts to address infectious threats. The STRIVE program provided tools and resources to help communities strengthen the relationships among diverse organizations to maximize improvement and coordination.

Closely aligned with SHM’s mission to promote exceptional care for hospitalized patients, the CDC’s STRIVE program goals were as follows:

• To expand the CDC’s Targeting Assessment for Prevention (TAP) strategy of using surveillance data to identify hospitals with a disproportionately high burden of health care–associated infections (HAIs),
• To build and strengthen relationships between state and regional organizations that help hospitals with infection control and prevention, and
• To provide technical assistance to hospitals to improve implementation of infection control practices in existing and newly constructed health care facilities.

The participants in this program included 449 hospitals from 28 states and the District of Columbia. Short-stay and long-term acute care hospitals that had a high burden of Clostridium difficile infection, and a high burden of one or more of the following HAIs – central line–associated bloodstream infection, catheter associated urinary tract infection, and health care–associated methicillin-resistant Staphylococcus aureus (MRSA) bacteremia – were targeted. Each participant had access to specific education modules, webinars, and learning networks designed to enhance collaboration, performance improvement, and understanding of the successes and barriers to coordinating hospital- and community-based services. Hospitals joined the program in cohorts and engaged in a year-long effort to reduce infection burden. During the program implementation period, many hospitals showed measurable improvement by achieving an HAI-specific relative rate reduction or maintenance of a rate of zero between baseline and intervention periods.

Key successes of the program centered around development of multidisciplinary teams that engaged not only the infection preventionists but also such areas as environmental services and other departments that may not have traditionally been included in infection prevention efforts. These teams focused on establishing competency-based trainings and processes for auditing competencies. One series of STRIVE resources helped hospitals learn new ways to implement best practices and communicate with diverse departments so every team member could participate in removing barriers to infection prevention in the hospital.

SHM was especially pleased to be a part of a program that brought together state health departments, state hospital associations, quality innovation network–quality improvement organizations, and other agencies and health systems committed to infection prevention. The collaboration and partnerships among the STRIVE program participants helped minimize duplication of work and improve efficiency and effectiveness of infection prevention efforts lead by hospitals.

To learn more about the STRIVE resources, visit www.hret.org/quality/projects/strive.shtml.