ICAAC 2013

DENVER – Only one-third of a group of patients with hepatitis C achieved a sustained virologic response when a protease inhibitor was added to standard ribavirin and interferon dual therapy, a real-world finding that flies in the face of reported response rates closer to 90%, according to Dr. Arpita Sheth who presented a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Of 42 patients at the Veterans Affairs hospital in East Orange, N.J., who started on triple therapy with the protease inhibitor boceprevir, 9 had to drop out because of previously recognized adverse events, including thrombocytopenia, neutropenia, anemia, and depression. Five other patients did not comply with treatment, and treatment failed in 10. About half of the patients were new to therapy and the rest either non- responders to dual-therapy or triple-therapy relapsers.

Of the 18 who completed treatment, 9 achieved SVR [sustained virological response] at 3 months and 5 at 6 months. The four remaining patients relapsed.

"The incremental gain of adding protease inhibitors to the traditional regimen of ribavirin and interferon has a potential SVR rate of 33% (14/42) among retreaters and naive-to-treatment patients. Treatment should be evaluated at a more realistic number of 33% success [rather] than the 80%-90% SVR rate so frequently quoted from the FDA registration trials," concluded Dr. Sheth, a fellow at Rutgers New Jersey Medical School in Newark, in her presentation.

The real-world rate is lower, at least in Newark’s VA population. To avoid disappointment, "we should always make our patients aware of that; we’ve seen a lot of patients get upset that they didn’t really get cured" with triple therapy, she said at the meeting. The findings from the study conducted by Dr. Sheth and her associates was published earlier (N. Engl. J. Med. 2011;364:1207-17).

The results probably had something to do with "the patient population we had. They do have some underlying history that includes depression, alcohol use, drug use, and a lot of other things. Even though [most] said they were compliant, I don’t think [compliance was] what they reported," Dr. Sheth said.

About a third of patients in the study required erythropoietin to maintain their hemoglobin at 10 g/dL or higher while on triple therapy.

Dr. Sheth and her team reported that they have no disclosures.

[email protected]

DENVER – Only one-third of a group of patients with hepatitis C achieved a sustained virologic response when a protease inhibitor was added to standard ribavirin and interferon dual therapy, a real-world finding that flies in the face of reported response rates closer to 90%, according to Dr. Arpita Sheth who presented a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Of 42 patients at the Veterans Affairs hospital in East Orange, N.J., who started on triple therapy with the protease inhibitor boceprevir, 9 had to drop out because of previously recognized adverse events, including thrombocytopenia, neutropenia, anemia, and depression. Five other patients did not comply with treatment, and treatment failed in 10. About half of the patients were new to therapy and the rest either non- responders to dual-therapy or triple-therapy relapsers.

Of the 18 who completed treatment, 9 achieved SVR [sustained virological response] at 3 months and 5 at 6 months. The four remaining patients relapsed.

"The incremental gain of adding protease inhibitors to the traditional regimen of ribavirin and interferon has a potential SVR rate of 33% (14/42) among retreaters and naive-to-treatment patients. Treatment should be evaluated at a more realistic number of 33% success [rather] than the 80%-90% SVR rate so frequently quoted from the FDA registration trials," concluded Dr. Sheth, a fellow at Rutgers New Jersey Medical School in Newark, in her presentation.

The real-world rate is lower, at least in Newark’s VA population. To avoid disappointment, "we should always make our patients aware of that; we’ve seen a lot of patients get upset that they didn’t really get cured" with triple therapy, she said at the meeting. The findings from the study conducted by Dr. Sheth and her associates was published earlier (N. Engl. J. Med. 2011;364:1207-17).

The results probably had something to do with "the patient population we had. They do have some underlying history that includes depression, alcohol use, drug use, and a lot of other things. Even though [most] said they were compliant, I don’t think [compliance was] what they reported," Dr. Sheth said.

About a third of patients in the study required erythropoietin to maintain their hemoglobin at 10 g/dL or higher while on triple therapy.

Dr. Sheth and her team reported that they have no disclosures.

[email protected]

DENVER – Only one-third of a group of patients with hepatitis C achieved a sustained virologic response when a protease inhibitor was added to standard ribavirin and interferon dual therapy, a real-world finding that flies in the face of reported response rates closer to 90%, according to Dr. Arpita Sheth who presented a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Of 42 patients at the Veterans Affairs hospital in East Orange, N.J., who started on triple therapy with the protease inhibitor boceprevir, 9 had to drop out because of previously recognized adverse events, including thrombocytopenia, neutropenia, anemia, and depression. Five other patients did not comply with treatment, and treatment failed in 10. About half of the patients were new to therapy and the rest either non- responders to dual-therapy or triple-therapy relapsers.

Of the 18 who completed treatment, 9 achieved SVR [sustained virological response] at 3 months and 5 at 6 months. The four remaining patients relapsed.

"The incremental gain of adding protease inhibitors to the traditional regimen of ribavirin and interferon has a potential SVR rate of 33% (14/42) among retreaters and naive-to-treatment patients. Treatment should be evaluated at a more realistic number of 33% success [rather] than the 80%-90% SVR rate so frequently quoted from the FDA registration trials," concluded Dr. Sheth, a fellow at Rutgers New Jersey Medical School in Newark, in her presentation.

The real-world rate is lower, at least in Newark’s VA population. To avoid disappointment, "we should always make our patients aware of that; we’ve seen a lot of patients get upset that they didn’t really get cured" with triple therapy, she said at the meeting. The findings from the study conducted by Dr. Sheth and her associates was published earlier (N. Engl. J. Med. 2011;364:1207-17).

The results probably had something to do with "the patient population we had. They do have some underlying history that includes depression, alcohol use, drug use, and a lot of other things. Even though [most] said they were compliant, I don’t think [compliance was] what they reported," Dr. Sheth said.

About a third of patients in the study required erythropoietin to maintain their hemoglobin at 10 g/dL or higher while on triple therapy.

Dr. Sheth and her team reported that they have no disclosures.

[email protected]

DENVER – Candida africana, a species previously unreported in the United States, has been isolated from three women from North Carolina and one from Virginia.

Identified ultimately by sequencing, the organism was first isolated from the Virginia woman’s urine, and then, over the course of a few months, from endometrial biopsy samples from one of the North Carolina women, and vaginal discharge swabs from the two others. The women were aged 15-35 years; one may have been an immigrant. None tested positive for C. albicans.

Courtesy CDC/Dr. Brinkman

The good news is that the isolates were susceptible to standard azole therapy and other treatments. "It’s a little bit different from C. albicans because it becomes resistant faster, but [intravaginal] fluconazole should work just fine for" yeast infections, said lead investigator Kevin Hazen, Ph.D., director of clinical microbiology at the Duke University Health System in Durham, N.C.

Even so, "you want to tell your laboratory to be on the lookout for this organism. We need to get much better information about how prevalent it is in the United States, because with that information we can investigate why this supposedly low pathogenic organism is out-competing albicans in [some] women and causing disease. We don’t know why these specific women are getting it or how significant it is in terms of causing recurrent yeast infections or subsequent disease," he said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

C. africana may well be endemic in the United States at this point, but it has been unrecognized until now because laboratories have reported it simply as "yeast, not Candida albicans."

"This organism kind of looks like albicans "on wet mount and is also germ tube positive. "Most labs will stop testing at that point," Dr. Hazen said.

But unlike C. albicans, C. africana doesn’t produce chlamydospores, doesn’t grow at 42° C, tests negative for L-proline aminopeptidase activity, and grows in rough colonies on bird seed agar, instead of smooth ones.

C. africana was first isolated on vaginal swabs from women in Madagascar and Angola and described in 1995; it’s since been isolated in Europe, Japan, Chile, and Saudi Arabia, almost exclusively from the female genitourinary tract, but on blood culture in at least one case.

Dr. Hazen said he has no disclosures.

[email protected]

DENVER – Candida africana, a species previously unreported in the United States, has been isolated from three women from North Carolina and one from Virginia.

Identified ultimately by sequencing, the organism was first isolated from the Virginia woman’s urine, and then, over the course of a few months, from endometrial biopsy samples from one of the North Carolina women, and vaginal discharge swabs from the two others. The women were aged 15-35 years; one may have been an immigrant. None tested positive for C. albicans.

Courtesy CDC/Dr. Brinkman

The good news is that the isolates were susceptible to standard azole therapy and other treatments. "It’s a little bit different from C. albicans because it becomes resistant faster, but [intravaginal] fluconazole should work just fine for" yeast infections, said lead investigator Kevin Hazen, Ph.D., director of clinical microbiology at the Duke University Health System in Durham, N.C.

Even so, "you want to tell your laboratory to be on the lookout for this organism. We need to get much better information about how prevalent it is in the United States, because with that information we can investigate why this supposedly low pathogenic organism is out-competing albicans in [some] women and causing disease. We don’t know why these specific women are getting it or how significant it is in terms of causing recurrent yeast infections or subsequent disease," he said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

C. africana may well be endemic in the United States at this point, but it has been unrecognized until now because laboratories have reported it simply as "yeast, not Candida albicans."

"This organism kind of looks like albicans "on wet mount and is also germ tube positive. "Most labs will stop testing at that point," Dr. Hazen said.

But unlike C. albicans, C. africana doesn’t produce chlamydospores, doesn’t grow at 42° C, tests negative for L-proline aminopeptidase activity, and grows in rough colonies on bird seed agar, instead of smooth ones.

C. africana was first isolated on vaginal swabs from women in Madagascar and Angola and described in 1995; it’s since been isolated in Europe, Japan, Chile, and Saudi Arabia, almost exclusively from the female genitourinary tract, but on blood culture in at least one case.

Dr. Hazen said he has no disclosures.

[email protected]

DENVER – Candida africana, a species previously unreported in the United States, has been isolated from three women from North Carolina and one from Virginia.

Identified ultimately by sequencing, the organism was first isolated from the Virginia woman’s urine, and then, over the course of a few months, from endometrial biopsy samples from one of the North Carolina women, and vaginal discharge swabs from the two others. The women were aged 15-35 years; one may have been an immigrant. None tested positive for C. albicans.

Courtesy CDC/Dr. Brinkman

The good news is that the isolates were susceptible to standard azole therapy and other treatments. "It’s a little bit different from C. albicans because it becomes resistant faster, but [intravaginal] fluconazole should work just fine for" yeast infections, said lead investigator Kevin Hazen, Ph.D., director of clinical microbiology at the Duke University Health System in Durham, N.C.

Even so, "you want to tell your laboratory to be on the lookout for this organism. We need to get much better information about how prevalent it is in the United States, because with that information we can investigate why this supposedly low pathogenic organism is out-competing albicans in [some] women and causing disease. We don’t know why these specific women are getting it or how significant it is in terms of causing recurrent yeast infections or subsequent disease," he said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

C. africana may well be endemic in the United States at this point, but it has been unrecognized until now because laboratories have reported it simply as "yeast, not Candida albicans."

"This organism kind of looks like albicans "on wet mount and is also germ tube positive. "Most labs will stop testing at that point," Dr. Hazen said.

But unlike C. albicans, C. africana doesn’t produce chlamydospores, doesn’t grow at 42° C, tests negative for L-proline aminopeptidase activity, and grows in rough colonies on bird seed agar, instead of smooth ones.

C. africana was first isolated on vaginal swabs from women in Madagascar and Angola and described in 1995; it’s since been isolated in Europe, Japan, Chile, and Saudi Arabia, almost exclusively from the female genitourinary tract, but on blood culture in at least one case.

Dr. Hazen said he has no disclosures.

[email protected]

DENVER – Once-weekly intravenous dalbavancin was effective against acute bacterial skin and skin structure infections, and not inferior to twice-daily IV vancomycin followed by oral linezolid, results from a randomized, double-blind study showed.

Dalbavancin is an investigational lipoglycopeptide being developed by Branford, Conn.–based Durata Therapeutics for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible gram-positive microorganisms.

ABSSSIs are common and are among the most frequent indications for antibiotic therapy and hospitalization of adults in the United States today, Dr. Helen W. Boucher said in an interview prior to the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented. ABSSSIs are most often caused by Staphylococcus aureus and streptococci.

"Increasing antimicrobial resistance presents a particular treatment challenge and limits options available for the treatment of these infections," said Dr. Boucher of Tufts Medical Center, Boston. "Treatment of ABSSSI can involve substantial costs in terms of direct medical costs and time away from work or school. The pharmacokinetics of dalbavancin allow once weekly dosing, which is more convenient for patients and increases adherence to therapy. It may allow patients to be treated without being admitted to the hospital or allow for shorter hospital stays," she said.

In the study, known as DISCOVER 1, a total of 573 patients with severe ABSSSI were randomized to receive either dalbavancin 1 g IV over 30 minutes on day 1 followed by 500 mg IV on day 8; or vancomycin 1 g or 15 mg/kg IV every 12 hours for at least 3 days, with an option to switch to oral linezolid 600 mg every 12 hours.

The primary endpoint for regulatory review in the United States was combined factors known as the early response endpoint – cessation of the spread of the erythema of the infection, and the absence of fever at 48-72 hours after treatment initiation.

Overall, 83.3% of patients in the dalbavancin group achieved the early response endpoint compared with 81.8% of patients in the vancomycin group, for a difference of 1.5%. The most commonly reported adverse events in the dalbavancin and vancomycin/linezolid groups were nausea (4.2% vs. 4.6%, respectively), diarrhea (1.4% vs. 3.9%), headache (4.9% vs. 4.9%), pruritus (0.4% vs. 3.9%), hypertension (2.5% vs. 2.5%), rash (2.1% vs. 2.1%), and asthenia (0.4% vs. 2.1%).

Dr. Boucher, director of the infectious diseases fellowship program and an associate professor of medicine at Tufts, characterized the findings as especially impressive, considering that patients in DISCOVER 1 had very large skin lesions (a median area of about 333 cm²), and high frequencies of fever (85%) and systemic inflammatory response syndrome (61%), which is a marker of very severe illness. "It means that the drug stood up to very ill patients," she said.

She acknowledged certain limitations of the study, including the fact that adherence to twice-daily therapy with vancomycin/linezolid "may not be as high in a real-world setting as that seen in a closely monitored clinical trial setting."

Dr. Boucher disclosed that she is a scientific adviser for Durata Therapeutics, which sponsored the study, and has ties to numerous other pharmaceutical companies.

[email protected]

DENVER – Once-weekly intravenous dalbavancin was effective against acute bacterial skin and skin structure infections, and not inferior to twice-daily IV vancomycin followed by oral linezolid, results from a randomized, double-blind study showed.

Dalbavancin is an investigational lipoglycopeptide being developed by Branford, Conn.–based Durata Therapeutics for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible gram-positive microorganisms.

ABSSSIs are common and are among the most frequent indications for antibiotic therapy and hospitalization of adults in the United States today, Dr. Helen W. Boucher said in an interview prior to the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented. ABSSSIs are most often caused by Staphylococcus aureus and streptococci.

"Increasing antimicrobial resistance presents a particular treatment challenge and limits options available for the treatment of these infections," said Dr. Boucher of Tufts Medical Center, Boston. "Treatment of ABSSSI can involve substantial costs in terms of direct medical costs and time away from work or school. The pharmacokinetics of dalbavancin allow once weekly dosing, which is more convenient for patients and increases adherence to therapy. It may allow patients to be treated without being admitted to the hospital or allow for shorter hospital stays," she said.

In the study, known as DISCOVER 1, a total of 573 patients with severe ABSSSI were randomized to receive either dalbavancin 1 g IV over 30 minutes on day 1 followed by 500 mg IV on day 8; or vancomycin 1 g or 15 mg/kg IV every 12 hours for at least 3 days, with an option to switch to oral linezolid 600 mg every 12 hours.

The primary endpoint for regulatory review in the United States was combined factors known as the early response endpoint – cessation of the spread of the erythema of the infection, and the absence of fever at 48-72 hours after treatment initiation.

Overall, 83.3% of patients in the dalbavancin group achieved the early response endpoint compared with 81.8% of patients in the vancomycin group, for a difference of 1.5%. The most commonly reported adverse events in the dalbavancin and vancomycin/linezolid groups were nausea (4.2% vs. 4.6%, respectively), diarrhea (1.4% vs. 3.9%), headache (4.9% vs. 4.9%), pruritus (0.4% vs. 3.9%), hypertension (2.5% vs. 2.5%), rash (2.1% vs. 2.1%), and asthenia (0.4% vs. 2.1%).

Dr. Boucher, director of the infectious diseases fellowship program and an associate professor of medicine at Tufts, characterized the findings as especially impressive, considering that patients in DISCOVER 1 had very large skin lesions (a median area of about 333 cm²), and high frequencies of fever (85%) and systemic inflammatory response syndrome (61%), which is a marker of very severe illness. "It means that the drug stood up to very ill patients," she said.

She acknowledged certain limitations of the study, including the fact that adherence to twice-daily therapy with vancomycin/linezolid "may not be as high in a real-world setting as that seen in a closely monitored clinical trial setting."

Dr. Boucher disclosed that she is a scientific adviser for Durata Therapeutics, which sponsored the study, and has ties to numerous other pharmaceutical companies.

[email protected]

DENVER – Once-weekly intravenous dalbavancin was effective against acute bacterial skin and skin structure infections, and not inferior to twice-daily IV vancomycin followed by oral linezolid, results from a randomized, double-blind study showed.

Dalbavancin is an investigational lipoglycopeptide being developed by Branford, Conn.–based Durata Therapeutics for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible gram-positive microorganisms.

ABSSSIs are common and are among the most frequent indications for antibiotic therapy and hospitalization of adults in the United States today, Dr. Helen W. Boucher said in an interview prior to the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented. ABSSSIs are most often caused by Staphylococcus aureus and streptococci.

"Increasing antimicrobial resistance presents a particular treatment challenge and limits options available for the treatment of these infections," said Dr. Boucher of Tufts Medical Center, Boston. "Treatment of ABSSSI can involve substantial costs in terms of direct medical costs and time away from work or school. The pharmacokinetics of dalbavancin allow once weekly dosing, which is more convenient for patients and increases adherence to therapy. It may allow patients to be treated without being admitted to the hospital or allow for shorter hospital stays," she said.

In the study, known as DISCOVER 1, a total of 573 patients with severe ABSSSI were randomized to receive either dalbavancin 1 g IV over 30 minutes on day 1 followed by 500 mg IV on day 8; or vancomycin 1 g or 15 mg/kg IV every 12 hours for at least 3 days, with an option to switch to oral linezolid 600 mg every 12 hours.

The primary endpoint for regulatory review in the United States was combined factors known as the early response endpoint – cessation of the spread of the erythema of the infection, and the absence of fever at 48-72 hours after treatment initiation.

Overall, 83.3% of patients in the dalbavancin group achieved the early response endpoint compared with 81.8% of patients in the vancomycin group, for a difference of 1.5%. The most commonly reported adverse events in the dalbavancin and vancomycin/linezolid groups were nausea (4.2% vs. 4.6%, respectively), diarrhea (1.4% vs. 3.9%), headache (4.9% vs. 4.9%), pruritus (0.4% vs. 3.9%), hypertension (2.5% vs. 2.5%), rash (2.1% vs. 2.1%), and asthenia (0.4% vs. 2.1%).

Dr. Boucher, director of the infectious diseases fellowship program and an associate professor of medicine at Tufts, characterized the findings as especially impressive, considering that patients in DISCOVER 1 had very large skin lesions (a median area of about 333 cm²), and high frequencies of fever (85%) and systemic inflammatory response syndrome (61%), which is a marker of very severe illness. "It means that the drug stood up to very ill patients," she said.

She acknowledged certain limitations of the study, including the fact that adherence to twice-daily therapy with vancomycin/linezolid "may not be as high in a real-world setting as that seen in a closely monitored clinical trial setting."

Dr. Boucher disclosed that she is a scientific adviser for Durata Therapeutics, which sponsored the study, and has ties to numerous other pharmaceutical companies.

[email protected]

DENVER – Oral vancomycin at a dose of 125 mg four times daily is just as effective as is a dose of 250 mg or higher given at the same frequency in the treatment of diarrhea associated with Clostridium difficile infection, judging from the results from a retrospective study.

Use of the lower dosing regimen has the potential to decrease treatment costs without worsening outcomes, Philip Chung, Pharm.D., said in an interview before the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

According to current recommendations, oral vancomycin 125 mg q.i.d. is the treatment of choice for severe uncomplicated C. difficile infection. To date, no studies have shown the use of oral vancomycin doses higher than 125 mg q.i.d. to be more efficacious than the recommended 125 mg q.i.d. in this setting, said Dr. Chung, clinical pharmacy manager of infectious diseases at Montefiore Medical Center, New York.

"Prior to 2008, prescribers at our institution frequently requested vancomycin doses higher than the recommended 125 mg q.i.d. for treatment of [C. difficile infection] despite the absence of data showing added benefits with the higher dosing regimens," he said. "This practice not only increases medication and/or preparation costs, but it may also increase the potential for untoward effects in patients being treated with the higher doses (e.g., increased risks for vancomycin-resistant enterococci colonization or higher likelihood to further alter the GI flora)."

Since the inception of the Antimicrobial Stewardship Program at Montefiore Medical Center in 2008, Dr. Chung and his associates observed a shift in oral vancomycin prescribing practices from a higher dosing regimen to a lower dosing regimen. "Because of this change in practice, we wished to evaluate the efficacy of the different oral vancomycin dosing regimen in order to ensure treatment outcomes remained unchanged at our institution," he said. To do so, the researchers retrospectively reviewed clinical outcomes of 300 adult patients treated with oral vancomycin at the medical center between 2006 and 2010. They looked at clinical parameters, concomitant antibiotics, in-hospital mortality, and 30-day readmission.

The primary endpoint was clinical improvement at 72 hours of oral vancomycin. Secondary endpoints included clinical improvement at end of therapy or discharge, length of stay, in-hospital mortality, and 30-day readmission rate.

Of the 300 patients, 197 were prescribed oral vancomycin 125 mg q.i.d. (low-dose group) and 103 patients were prescribed 250 mg or higher q.i.d. (high-dose group). Dr. Chung and his associates reported that clinical improvement assessed 72 hours after starting oral vancomycin therapy was observed in 85% and 86% of patients in the low- and high-dose groups, respectively (P less than 0.05). Rates of clinical improvement at end of therapy or time of hospital discharge between the two groups were also found to be similar (93% vs. 96%), as were total length of hospital stay (20 days vs. 19 days), in-hospital mortality (15% vs. 23%), and rates of 30-day readmission (34% vs. 24%).

"The finding that oral vancomycin 125 mg q.i.d. works as well as higher doses for severe uncomplicated C. difficile infection for the most part is not a surprise to us, as some evidence already exists in the literature," said Dr. Chung, also of Albert Einstein College of Medicine in New York. "Our finding only confirmed what is already known."

Limitations include the fact that this is a single-center study, and that it is subject to selection bias because of its retrospective design, Dr. Chung said. "However, we took steps to ensure that all patients treated with oral vancomycin who had laboratory-confirmed [C. difficile infection] and symptoms consistent with [C. difficile infection] were included in the study," he said.

Dr. Chung said that he had no relevant financial conflicts to disclose.

[email protected]

DENVER – Oral vancomycin at a dose of 125 mg four times daily is just as effective as is a dose of 250 mg or higher given at the same frequency in the treatment of diarrhea associated with Clostridium difficile infection, judging from the results from a retrospective study.

Use of the lower dosing regimen has the potential to decrease treatment costs without worsening outcomes, Philip Chung, Pharm.D., said in an interview before the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

According to current recommendations, oral vancomycin 125 mg q.i.d. is the treatment of choice for severe uncomplicated C. difficile infection. To date, no studies have shown the use of oral vancomycin doses higher than 125 mg q.i.d. to be more efficacious than the recommended 125 mg q.i.d. in this setting, said Dr. Chung, clinical pharmacy manager of infectious diseases at Montefiore Medical Center, New York.

"Prior to 2008, prescribers at our institution frequently requested vancomycin doses higher than the recommended 125 mg q.i.d. for treatment of [C. difficile infection] despite the absence of data showing added benefits with the higher dosing regimens," he said. "This practice not only increases medication and/or preparation costs, but it may also increase the potential for untoward effects in patients being treated with the higher doses (e.g., increased risks for vancomycin-resistant enterococci colonization or higher likelihood to further alter the GI flora)."

Since the inception of the Antimicrobial Stewardship Program at Montefiore Medical Center in 2008, Dr. Chung and his associates observed a shift in oral vancomycin prescribing practices from a higher dosing regimen to a lower dosing regimen. "Because of this change in practice, we wished to evaluate the efficacy of the different oral vancomycin dosing regimen in order to ensure treatment outcomes remained unchanged at our institution," he said. To do so, the researchers retrospectively reviewed clinical outcomes of 300 adult patients treated with oral vancomycin at the medical center between 2006 and 2010. They looked at clinical parameters, concomitant antibiotics, in-hospital mortality, and 30-day readmission.

The primary endpoint was clinical improvement at 72 hours of oral vancomycin. Secondary endpoints included clinical improvement at end of therapy or discharge, length of stay, in-hospital mortality, and 30-day readmission rate.

Of the 300 patients, 197 were prescribed oral vancomycin 125 mg q.i.d. (low-dose group) and 103 patients were prescribed 250 mg or higher q.i.d. (high-dose group). Dr. Chung and his associates reported that clinical improvement assessed 72 hours after starting oral vancomycin therapy was observed in 85% and 86% of patients in the low- and high-dose groups, respectively (P less than 0.05). Rates of clinical improvement at end of therapy or time of hospital discharge between the two groups were also found to be similar (93% vs. 96%), as were total length of hospital stay (20 days vs. 19 days), in-hospital mortality (15% vs. 23%), and rates of 30-day readmission (34% vs. 24%).

"The finding that oral vancomycin 125 mg q.i.d. works as well as higher doses for severe uncomplicated C. difficile infection for the most part is not a surprise to us, as some evidence already exists in the literature," said Dr. Chung, also of Albert Einstein College of Medicine in New York. "Our finding only confirmed what is already known."

Limitations include the fact that this is a single-center study, and that it is subject to selection bias because of its retrospective design, Dr. Chung said. "However, we took steps to ensure that all patients treated with oral vancomycin who had laboratory-confirmed [C. difficile infection] and symptoms consistent with [C. difficile infection] were included in the study," he said.

Dr. Chung said that he had no relevant financial conflicts to disclose.

[email protected]

DENVER – Oral vancomycin at a dose of 125 mg four times daily is just as effective as is a dose of 250 mg or higher given at the same frequency in the treatment of diarrhea associated with Clostridium difficile infection, judging from the results from a retrospective study.

Use of the lower dosing regimen has the potential to decrease treatment costs without worsening outcomes, Philip Chung, Pharm.D., said in an interview before the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

According to current recommendations, oral vancomycin 125 mg q.i.d. is the treatment of choice for severe uncomplicated C. difficile infection. To date, no studies have shown the use of oral vancomycin doses higher than 125 mg q.i.d. to be more efficacious than the recommended 125 mg q.i.d. in this setting, said Dr. Chung, clinical pharmacy manager of infectious diseases at Montefiore Medical Center, New York.

"Prior to 2008, prescribers at our institution frequently requested vancomycin doses higher than the recommended 125 mg q.i.d. for treatment of [C. difficile infection] despite the absence of data showing added benefits with the higher dosing regimens," he said. "This practice not only increases medication and/or preparation costs, but it may also increase the potential for untoward effects in patients being treated with the higher doses (e.g., increased risks for vancomycin-resistant enterococci colonization or higher likelihood to further alter the GI flora)."

Since the inception of the Antimicrobial Stewardship Program at Montefiore Medical Center in 2008, Dr. Chung and his associates observed a shift in oral vancomycin prescribing practices from a higher dosing regimen to a lower dosing regimen. "Because of this change in practice, we wished to evaluate the efficacy of the different oral vancomycin dosing regimen in order to ensure treatment outcomes remained unchanged at our institution," he said. To do so, the researchers retrospectively reviewed clinical outcomes of 300 adult patients treated with oral vancomycin at the medical center between 2006 and 2010. They looked at clinical parameters, concomitant antibiotics, in-hospital mortality, and 30-day readmission.

The primary endpoint was clinical improvement at 72 hours of oral vancomycin. Secondary endpoints included clinical improvement at end of therapy or discharge, length of stay, in-hospital mortality, and 30-day readmission rate.

Of the 300 patients, 197 were prescribed oral vancomycin 125 mg q.i.d. (low-dose group) and 103 patients were prescribed 250 mg or higher q.i.d. (high-dose group). Dr. Chung and his associates reported that clinical improvement assessed 72 hours after starting oral vancomycin therapy was observed in 85% and 86% of patients in the low- and high-dose groups, respectively (P less than 0.05). Rates of clinical improvement at end of therapy or time of hospital discharge between the two groups were also found to be similar (93% vs. 96%), as were total length of hospital stay (20 days vs. 19 days), in-hospital mortality (15% vs. 23%), and rates of 30-day readmission (34% vs. 24%).

"The finding that oral vancomycin 125 mg q.i.d. works as well as higher doses for severe uncomplicated C. difficile infection for the most part is not a surprise to us, as some evidence already exists in the literature," said Dr. Chung, also of Albert Einstein College of Medicine in New York. "Our finding only confirmed what is already known."

Limitations include the fact that this is a single-center study, and that it is subject to selection bias because of its retrospective design, Dr. Chung said. "However, we took steps to ensure that all patients treated with oral vancomycin who had laboratory-confirmed [C. difficile infection] and symptoms consistent with [C. difficile infection] were included in the study," he said.

Dr. Chung said that he had no relevant financial conflicts to disclose.

[email protected]

DENVER – The incidence of Clostridium difficile infections in United States hospitals nearly doubled between 2001 and 2010, with little evidence of recent decline. In addition, there does not appear to be a significant decline in mortality or hospital length of stay among patients with the infection, an analysis of national data showed.

"These data underscore the importance of directing resources to the prevention of [C. difficile infection], as well as developing public policy for reducing the incidence of these infections in U.S. hospitals," Kelly R. Daniels, Pharm.D., said in an interview prior to the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"Judicious use of antibiotics is essential to reducing these infections, as antibiotics are the main risk factor for the development of CDI," she noted. "Compliance with other infection control measures, such as hand washing, is also key. Further research is needed to identify effective measures for preventing CDI and improving outcomes in patients with CDI."

Dr. Daniels, a graduate student in the translational science PhD program at the University of Texas, Austin, and her associates retrospectively reviewed U.S. National Hospital Discharge Surveys from 2001 to 2010. They included patients aged 18 years and older who were discharged from the hospital with an ICD-9-CM diagnosis code for CDI (008.45) and used data weights to determine national estimates. They presented incidence rates as CDI cases per 1,000 hospitalizations, and they used multivariable logistic and linear regression models to compare mortality and hospital length of stay between primary and secondary CDI.

Over the 10-year study period, 2.2 million patients were discharged from the hospital with CDI. Their median age was 75 years, most (86%) were white, and more than half (59%) were female. One-third of cases (33%) were primary CDI, while the remainder were secondary CDI. The three most common concomitant infectious diagnoses were urinary tract infection (21%), pneumonia (14%), and sepsis/septicemia (12%).

Dr. Daniels reported that the incidence of CDI increased from 4.5 cases/1,000 hospitalizations in 2001 to 8.2 cases/1,000 hospitalizations in 2010. Similar trends were observed in patients with primary and secondary CDI.

The overall mortality rate was 7.1% for the study period and was significantly higher among patients with secondary CDI, compared with those who had primary CDI (8.8% vs. 3.3%, respectively; relative risk, 1.8). The median hospital length of stay was 8 days and was significantly higher among patients with secondary CDI, compared with those who had primary CDI (9 days vs. 5 days, respectively; RR, 13.3).

"We found that in-hospital mortality among patients with primary CDI is decreasing, while mortality among patients with secondary CDI is increasing," Dr. Daniels said. "This trend is different from prior studies, which demonstrated increases in CDI-related mortality from the 1990s to the early 2000s."

The decline in in-hospital mortality among patients with primary CDI might reflect improvements in care in recent years, she explained. In contrast, the increase in mortality among those with secondary CDI may be caused by changes in the frequency or severity of other comorbid illnesses. However, "this was not specifically examined as part of our study," Dr. Daniels added.

She acknowledged certain limitations of the analysis, including the fact that it relied on administrative codes to identify cases of CDI. "Although CDI codes have high accuracy for identifying CDI, they cannot be considered equivalent to medical chart reviews," Dr. Daniels explained. Also, "the use of administrative codes precludes our ability to confirm the CDI diagnosis using laboratory methods or to identify the causative strain of C. difficile." In addition, the National Hospital Discharge Surveys don’t include federal hospitals and long-term care hospitals. "Therefore, our estimates may not be generalizable to those settings and may underestimate the true burden of CDI in the United States," Dr. Daniels explained.

No outside funding was obtained for the conduct of this study. Dr. Daniels disclosed that she is supported by the National Institutes of Health National Center for Advancing Translational Sciences Loan Repayment Program.

[email protected]

DENVER – The incidence of Clostridium difficile infections in United States hospitals nearly doubled between 2001 and 2010, with little evidence of recent decline. In addition, there does not appear to be a significant decline in mortality or hospital length of stay among patients with the infection, an analysis of national data showed.

"These data underscore the importance of directing resources to the prevention of [C. difficile infection], as well as developing public policy for reducing the incidence of these infections in U.S. hospitals," Kelly R. Daniels, Pharm.D., said in an interview prior to the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"Judicious use of antibiotics is essential to reducing these infections, as antibiotics are the main risk factor for the development of CDI," she noted. "Compliance with other infection control measures, such as hand washing, is also key. Further research is needed to identify effective measures for preventing CDI and improving outcomes in patients with CDI."

Dr. Daniels, a graduate student in the translational science PhD program at the University of Texas, Austin, and her associates retrospectively reviewed U.S. National Hospital Discharge Surveys from 2001 to 2010. They included patients aged 18 years and older who were discharged from the hospital with an ICD-9-CM diagnosis code for CDI (008.45) and used data weights to determine national estimates. They presented incidence rates as CDI cases per 1,000 hospitalizations, and they used multivariable logistic and linear regression models to compare mortality and hospital length of stay between primary and secondary CDI.

Over the 10-year study period, 2.2 million patients were discharged from the hospital with CDI. Their median age was 75 years, most (86%) were white, and more than half (59%) were female. One-third of cases (33%) were primary CDI, while the remainder were secondary CDI. The three most common concomitant infectious diagnoses were urinary tract infection (21%), pneumonia (14%), and sepsis/septicemia (12%).

Dr. Daniels reported that the incidence of CDI increased from 4.5 cases/1,000 hospitalizations in 2001 to 8.2 cases/1,000 hospitalizations in 2010. Similar trends were observed in patients with primary and secondary CDI.

The overall mortality rate was 7.1% for the study period and was significantly higher among patients with secondary CDI, compared with those who had primary CDI (8.8% vs. 3.3%, respectively; relative risk, 1.8). The median hospital length of stay was 8 days and was significantly higher among patients with secondary CDI, compared with those who had primary CDI (9 days vs. 5 days, respectively; RR, 13.3).

"We found that in-hospital mortality among patients with primary CDI is decreasing, while mortality among patients with secondary CDI is increasing," Dr. Daniels said. "This trend is different from prior studies, which demonstrated increases in CDI-related mortality from the 1990s to the early 2000s."

The decline in in-hospital mortality among patients with primary CDI might reflect improvements in care in recent years, she explained. In contrast, the increase in mortality among those with secondary CDI may be caused by changes in the frequency or severity of other comorbid illnesses. However, "this was not specifically examined as part of our study," Dr. Daniels added.

She acknowledged certain limitations of the analysis, including the fact that it relied on administrative codes to identify cases of CDI. "Although CDI codes have high accuracy for identifying CDI, they cannot be considered equivalent to medical chart reviews," Dr. Daniels explained. Also, "the use of administrative codes precludes our ability to confirm the CDI diagnosis using laboratory methods or to identify the causative strain of C. difficile." In addition, the National Hospital Discharge Surveys don’t include federal hospitals and long-term care hospitals. "Therefore, our estimates may not be generalizable to those settings and may underestimate the true burden of CDI in the United States," Dr. Daniels explained.

No outside funding was obtained for the conduct of this study. Dr. Daniels disclosed that she is supported by the National Institutes of Health National Center for Advancing Translational Sciences Loan Repayment Program.

[email protected]

DENVER – The incidence of Clostridium difficile infections in United States hospitals nearly doubled between 2001 and 2010, with little evidence of recent decline. In addition, there does not appear to be a significant decline in mortality or hospital length of stay among patients with the infection, an analysis of national data showed.

"These data underscore the importance of directing resources to the prevention of [C. difficile infection], as well as developing public policy for reducing the incidence of these infections in U.S. hospitals," Kelly R. Daniels, Pharm.D., said in an interview prior to the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"Judicious use of antibiotics is essential to reducing these infections, as antibiotics are the main risk factor for the development of CDI," she noted. "Compliance with other infection control measures, such as hand washing, is also key. Further research is needed to identify effective measures for preventing CDI and improving outcomes in patients with CDI."

Dr. Daniels, a graduate student in the translational science PhD program at the University of Texas, Austin, and her associates retrospectively reviewed U.S. National Hospital Discharge Surveys from 2001 to 2010. They included patients aged 18 years and older who were discharged from the hospital with an ICD-9-CM diagnosis code for CDI (008.45) and used data weights to determine national estimates. They presented incidence rates as CDI cases per 1,000 hospitalizations, and they used multivariable logistic and linear regression models to compare mortality and hospital length of stay between primary and secondary CDI.

Over the 10-year study period, 2.2 million patients were discharged from the hospital with CDI. Their median age was 75 years, most (86%) were white, and more than half (59%) were female. One-third of cases (33%) were primary CDI, while the remainder were secondary CDI. The three most common concomitant infectious diagnoses were urinary tract infection (21%), pneumonia (14%), and sepsis/septicemia (12%).

Dr. Daniels reported that the incidence of CDI increased from 4.5 cases/1,000 hospitalizations in 2001 to 8.2 cases/1,000 hospitalizations in 2010. Similar trends were observed in patients with primary and secondary CDI.

The overall mortality rate was 7.1% for the study period and was significantly higher among patients with secondary CDI, compared with those who had primary CDI (8.8% vs. 3.3%, respectively; relative risk, 1.8). The median hospital length of stay was 8 days and was significantly higher among patients with secondary CDI, compared with those who had primary CDI (9 days vs. 5 days, respectively; RR, 13.3).

"We found that in-hospital mortality among patients with primary CDI is decreasing, while mortality among patients with secondary CDI is increasing," Dr. Daniels said. "This trend is different from prior studies, which demonstrated increases in CDI-related mortality from the 1990s to the early 2000s."

The decline in in-hospital mortality among patients with primary CDI might reflect improvements in care in recent years, she explained. In contrast, the increase in mortality among those with secondary CDI may be caused by changes in the frequency or severity of other comorbid illnesses. However, "this was not specifically examined as part of our study," Dr. Daniels added.

She acknowledged certain limitations of the analysis, including the fact that it relied on administrative codes to identify cases of CDI. "Although CDI codes have high accuracy for identifying CDI, they cannot be considered equivalent to medical chart reviews," Dr. Daniels explained. Also, "the use of administrative codes precludes our ability to confirm the CDI diagnosis using laboratory methods or to identify the causative strain of C. difficile." In addition, the National Hospital Discharge Surveys don’t include federal hospitals and long-term care hospitals. "Therefore, our estimates may not be generalizable to those settings and may underestimate the true burden of CDI in the United States," Dr. Daniels explained.

No outside funding was obtained for the conduct of this study. Dr. Daniels disclosed that she is supported by the National Institutes of Health National Center for Advancing Translational Sciences Loan Repayment Program.

[email protected]

DENVER – A single intravenous 1,200-mg dose of the investigational agent oritavancin was noninferior to 7-10 days of intravenous vancomycin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, results from a multicenter trial showed.

Oritavancin is a novel lipoglycopeptide being developed by Parsippany, N.J.–based The Medicines Company for the treatment of serious gram-positive infections. If it earns Food and Drug Administration approval, oritavancin "may contribute to improving the efficiency of the pathway of care for how we clinicians treat ABSSSIs," Dr. G. Ralph Corey, lead study investigator, said in an interview before the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"It has the potential to provide a single-dose alternative to multidose therapies for the treatment of ABSSSI. Administering the entire course of therapy upfront ensures 100% compliance," said Dr. Corey of Duke University, Durham, N.C.

In a double-blind, phase III trial known as SOLO-1, sponsored by The Medicines Company and carried out at 46 centers worldwide, Dr. Corey and his associates randomized 475 patients with ABSSSIs to a single 1,200-mg dose of IV oritavancin and 479 patients with ABSSSIs to 7-10 days of twice-daily IV vancomycin.

Three efficacy endpoints were tested for noninferiority: the primary composite endpoint at 48-72 hours, which comprised cessation of spreading or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic; the investigator-assessed clinical cure 7-14 days after end of treatment; and at a reduction of at least 20% in lesion area at 48-72 hours.

The researchers found that more patients in the oritavancin group than in the vancomycin group achieved the primary composite endpoint (82.3% vs. 78.9%, respectively), and at least a 20% reduction in the lesion area (86.9% vs. 82.9%). The percentage of patients who achieved investigator-assessed clinical cure was essentially the same between the two groups (79.6% vs. 80%).

"It was well-tolerated, with a safety profile similar to vancomycin," said Dr. Corey. "The most frequently reported adverse events were nausea, headache, vomiting and diarrhea."

Dr. Corey was impressed by oritavancin’s quick response "and the increase in response rate at the early clinical evaluation endpoint – 48-72 hours after infusion as measured in the primary efficacy endpoint," he said. "The results in MRSA patients were found to be particularly strong in subgroup analyses and warrant additional study."

Dr. Corey acknowledged certain limitations of SOLO-1, including the fact that the double-blind nature of the infusions "created a limitation in measuring the ability to discharge a patient from the hospital earlier with single-dose treatment," he said. "This can be modeled, but warrants additional study in the real-world setting. Moreover, I think this trial has actually inspired additional new research opportunities," he added. "There are other, potentially more severe indications that oritavancin could cover, and I’m excited to explore further studies on this drug."

According to information from The Medicines Company, the purpose of SOLO-1 was to support the filing of a New Drug Application in the United States as well as a Marketing Authorization Application in Europe.

Dr. Corey disclosed that he is a consultant, scientific adviser, and investigator for The Medicines Company. He serves in similar capacities for numerous other pharmaceutical companies, including Pfizer and Merck.

[email protected]

DENVER – A single intravenous 1,200-mg dose of the investigational agent oritavancin was noninferior to 7-10 days of intravenous vancomycin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, results from a multicenter trial showed.

Oritavancin is a novel lipoglycopeptide being developed by Parsippany, N.J.–based The Medicines Company for the treatment of serious gram-positive infections. If it earns Food and Drug Administration approval, oritavancin "may contribute to improving the efficiency of the pathway of care for how we clinicians treat ABSSSIs," Dr. G. Ralph Corey, lead study investigator, said in an interview before the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"It has the potential to provide a single-dose alternative to multidose therapies for the treatment of ABSSSI. Administering the entire course of therapy upfront ensures 100% compliance," said Dr. Corey of Duke University, Durham, N.C.

In a double-blind, phase III trial known as SOLO-1, sponsored by The Medicines Company and carried out at 46 centers worldwide, Dr. Corey and his associates randomized 475 patients with ABSSSIs to a single 1,200-mg dose of IV oritavancin and 479 patients with ABSSSIs to 7-10 days of twice-daily IV vancomycin.

Three efficacy endpoints were tested for noninferiority: the primary composite endpoint at 48-72 hours, which comprised cessation of spreading or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic; the investigator-assessed clinical cure 7-14 days after end of treatment; and at a reduction of at least 20% in lesion area at 48-72 hours.

The researchers found that more patients in the oritavancin group than in the vancomycin group achieved the primary composite endpoint (82.3% vs. 78.9%, respectively), and at least a 20% reduction in the lesion area (86.9% vs. 82.9%). The percentage of patients who achieved investigator-assessed clinical cure was essentially the same between the two groups (79.6% vs. 80%).

"It was well-tolerated, with a safety profile similar to vancomycin," said Dr. Corey. "The most frequently reported adverse events were nausea, headache, vomiting and diarrhea."

Dr. Corey was impressed by oritavancin’s quick response "and the increase in response rate at the early clinical evaluation endpoint – 48-72 hours after infusion as measured in the primary efficacy endpoint," he said. "The results in MRSA patients were found to be particularly strong in subgroup analyses and warrant additional study."

Dr. Corey acknowledged certain limitations of SOLO-1, including the fact that the double-blind nature of the infusions "created a limitation in measuring the ability to discharge a patient from the hospital earlier with single-dose treatment," he said. "This can be modeled, but warrants additional study in the real-world setting. Moreover, I think this trial has actually inspired additional new research opportunities," he added. "There are other, potentially more severe indications that oritavancin could cover, and I’m excited to explore further studies on this drug."

According to information from The Medicines Company, the purpose of SOLO-1 was to support the filing of a New Drug Application in the United States as well as a Marketing Authorization Application in Europe.

Dr. Corey disclosed that he is a consultant, scientific adviser, and investigator for The Medicines Company. He serves in similar capacities for numerous other pharmaceutical companies, including Pfizer and Merck.

[email protected]

DENVER – A single intravenous 1,200-mg dose of the investigational agent oritavancin was noninferior to 7-10 days of intravenous vancomycin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, results from a multicenter trial showed.

Oritavancin is a novel lipoglycopeptide being developed by Parsippany, N.J.–based The Medicines Company for the treatment of serious gram-positive infections. If it earns Food and Drug Administration approval, oritavancin "may contribute to improving the efficiency of the pathway of care for how we clinicians treat ABSSSIs," Dr. G. Ralph Corey, lead study investigator, said in an interview before the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"It has the potential to provide a single-dose alternative to multidose therapies for the treatment of ABSSSI. Administering the entire course of therapy upfront ensures 100% compliance," said Dr. Corey of Duke University, Durham, N.C.

In a double-blind, phase III trial known as SOLO-1, sponsored by The Medicines Company and carried out at 46 centers worldwide, Dr. Corey and his associates randomized 475 patients with ABSSSIs to a single 1,200-mg dose of IV oritavancin and 479 patients with ABSSSIs to 7-10 days of twice-daily IV vancomycin.

Three efficacy endpoints were tested for noninferiority: the primary composite endpoint at 48-72 hours, which comprised cessation of spreading or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic; the investigator-assessed clinical cure 7-14 days after end of treatment; and at a reduction of at least 20% in lesion area at 48-72 hours.

The researchers found that more patients in the oritavancin group than in the vancomycin group achieved the primary composite endpoint (82.3% vs. 78.9%, respectively), and at least a 20% reduction in the lesion area (86.9% vs. 82.9%). The percentage of patients who achieved investigator-assessed clinical cure was essentially the same between the two groups (79.6% vs. 80%).

"It was well-tolerated, with a safety profile similar to vancomycin," said Dr. Corey. "The most frequently reported adverse events were nausea, headache, vomiting and diarrhea."

Dr. Corey was impressed by oritavancin’s quick response "and the increase in response rate at the early clinical evaluation endpoint – 48-72 hours after infusion as measured in the primary efficacy endpoint," he said. "The results in MRSA patients were found to be particularly strong in subgroup analyses and warrant additional study."

Dr. Corey acknowledged certain limitations of SOLO-1, including the fact that the double-blind nature of the infusions "created a limitation in measuring the ability to discharge a patient from the hospital earlier with single-dose treatment," he said. "This can be modeled, but warrants additional study in the real-world setting. Moreover, I think this trial has actually inspired additional new research opportunities," he added. "There are other, potentially more severe indications that oritavancin could cover, and I’m excited to explore further studies on this drug."

According to information from The Medicines Company, the purpose of SOLO-1 was to support the filing of a New Drug Application in the United States as well as a Marketing Authorization Application in Europe.

Dr. Corey disclosed that he is a consultant, scientific adviser, and investigator for The Medicines Company. He serves in similar capacities for numerous other pharmaceutical companies, including Pfizer and Merck.

[email protected]

DENVER – A novel breathalyzerlike test detected fungal gas metabolites in the breath of immunocompromised patients with suspected invasive aspergillosis, with excellent sensitivity and specificity, a single-center study demonstrated.

"We envision this work can be adapted to a rapid, noninvasive point-of-care detection system for real-time surveillance of patient breath for the emergence of aspergillosis and potentially for the diagnosis of lung infections caused by other fungal and bacterial pathogens," Dr. Sophia Koo said in an interview prior to a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"An urgent need" exists for better diagnostic tests for invasive aspergillosis, a life-threatening fungal pneumonia in immunocompromised patients, explained Dr. Koo of Harvard Medical School, Boston. Current diagnostic tests – respiratory tract cultures, serum and bronchoalveolar lavage for fungal antigen testing, and nucleic acid detection assays – "have significant limitations in their sensitivity and specificity, and the turnaround time of these assays in clinical practice is often days," she said.

Dr. Koo and her colleagues developed a new method to detect volatile fungal metabolites directly in patient breath. First, they defined the fungal volatile metabolite profile of Aspergillus fumigatus, the most common cause of invasive aspergillosis, in in vitro culture. Next, they used gas chromatography–mass spectrometry to detect those metabolites in the breath of 54 immunocompromised patients with suspected invasive aspergillosis pneumonia. Of those 54 patients, 29 ultimately had invasive aspergillosis, and 25 had other causes of pneumonia.

The breathalyzerlike test correctly identified 27 of 29 patients with invasive aspergillosis and 24 of 25 patients without invasive aspergillosis, for an overall diagnostic sensitivity of 93% and a diagnostic specificity of 96%.

"We were a bit surprised by how clearly we were able to discriminate patients with invasive aspergillosis from patients with other pneumonias using this approach," Dr. Koo noted. "When we made our initial plot of breath fungal volatile metabolites, clustered by patients with and without invasive aspergillosis, there was a clear line demarcating the two groups. We expected some differences in the fungal volatile metabolite profile in vitro and in vivo, with the overlay of the host-pathogen interaction, and we did indeed see some fungal metabolites in vivo that we did not see in any of our in vitro experiments."

While Dr. Koo described gas chromatography–mass spectrometry as "labor intensive," she characterized the findings of the current study as "easily translatable to a point of care platform for the detection of these fungal breath metabolites and potentially the diagnosis of other bacterial and fungal pneumonias at the bedside."

Dr. Koo acknowledged certain limitations of the study, including its single-center design and the fact that it will require validation in a larger cohort of patients.

The National Institutes of Health and the Harvard Catalyst/the Harvard Clinical and Translational Science Center Pilot Grant Program supported the study. The authors stated that they have no relevant financial conflicts.

[email protected]

DENVER – A novel breathalyzerlike test detected fungal gas metabolites in the breath of immunocompromised patients with suspected invasive aspergillosis, with excellent sensitivity and specificity, a single-center study demonstrated.

"We envision this work can be adapted to a rapid, noninvasive point-of-care detection system for real-time surveillance of patient breath for the emergence of aspergillosis and potentially for the diagnosis of lung infections caused by other fungal and bacterial pathogens," Dr. Sophia Koo said in an interview prior to a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"An urgent need" exists for better diagnostic tests for invasive aspergillosis, a life-threatening fungal pneumonia in immunocompromised patients, explained Dr. Koo of Harvard Medical School, Boston. Current diagnostic tests – respiratory tract cultures, serum and bronchoalveolar lavage for fungal antigen testing, and nucleic acid detection assays – "have significant limitations in their sensitivity and specificity, and the turnaround time of these assays in clinical practice is often days," she said.

Dr. Koo and her colleagues developed a new method to detect volatile fungal metabolites directly in patient breath. First, they defined the fungal volatile metabolite profile of Aspergillus fumigatus, the most common cause of invasive aspergillosis, in in vitro culture. Next, they used gas chromatography–mass spectrometry to detect those metabolites in the breath of 54 immunocompromised patients with suspected invasive aspergillosis pneumonia. Of those 54 patients, 29 ultimately had invasive aspergillosis, and 25 had other causes of pneumonia.

The breathalyzerlike test correctly identified 27 of 29 patients with invasive aspergillosis and 24 of 25 patients without invasive aspergillosis, for an overall diagnostic sensitivity of 93% and a diagnostic specificity of 96%.

"We were a bit surprised by how clearly we were able to discriminate patients with invasive aspergillosis from patients with other pneumonias using this approach," Dr. Koo noted. "When we made our initial plot of breath fungal volatile metabolites, clustered by patients with and without invasive aspergillosis, there was a clear line demarcating the two groups. We expected some differences in the fungal volatile metabolite profile in vitro and in vivo, with the overlay of the host-pathogen interaction, and we did indeed see some fungal metabolites in vivo that we did not see in any of our in vitro experiments."

While Dr. Koo described gas chromatography–mass spectrometry as "labor intensive," she characterized the findings of the current study as "easily translatable to a point of care platform for the detection of these fungal breath metabolites and potentially the diagnosis of other bacterial and fungal pneumonias at the bedside."

Dr. Koo acknowledged certain limitations of the study, including its single-center design and the fact that it will require validation in a larger cohort of patients.

The National Institutes of Health and the Harvard Catalyst/the Harvard Clinical and Translational Science Center Pilot Grant Program supported the study. The authors stated that they have no relevant financial conflicts.

[email protected]

DENVER – A novel breathalyzerlike test detected fungal gas metabolites in the breath of immunocompromised patients with suspected invasive aspergillosis, with excellent sensitivity and specificity, a single-center study demonstrated.

"We envision this work can be adapted to a rapid, noninvasive point-of-care detection system for real-time surveillance of patient breath for the emergence of aspergillosis and potentially for the diagnosis of lung infections caused by other fungal and bacterial pathogens," Dr. Sophia Koo said in an interview prior to a poster session at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy, where the study was presented.

"An urgent need" exists for better diagnostic tests for invasive aspergillosis, a life-threatening fungal pneumonia in immunocompromised patients, explained Dr. Koo of Harvard Medical School, Boston. Current diagnostic tests – respiratory tract cultures, serum and bronchoalveolar lavage for fungal antigen testing, and nucleic acid detection assays – "have significant limitations in their sensitivity and specificity, and the turnaround time of these assays in clinical practice is often days," she said.

Dr. Koo and her colleagues developed a new method to detect volatile fungal metabolites directly in patient breath. First, they defined the fungal volatile metabolite profile of Aspergillus fumigatus, the most common cause of invasive aspergillosis, in in vitro culture. Next, they used gas chromatography–mass spectrometry to detect those metabolites in the breath of 54 immunocompromised patients with suspected invasive aspergillosis pneumonia. Of those 54 patients, 29 ultimately had invasive aspergillosis, and 25 had other causes of pneumonia.

The breathalyzerlike test correctly identified 27 of 29 patients with invasive aspergillosis and 24 of 25 patients without invasive aspergillosis, for an overall diagnostic sensitivity of 93% and a diagnostic specificity of 96%.

"We were a bit surprised by how clearly we were able to discriminate patients with invasive aspergillosis from patients with other pneumonias using this approach," Dr. Koo noted. "When we made our initial plot of breath fungal volatile metabolites, clustered by patients with and without invasive aspergillosis, there was a clear line demarcating the two groups. We expected some differences in the fungal volatile metabolite profile in vitro and in vivo, with the overlay of the host-pathogen interaction, and we did indeed see some fungal metabolites in vivo that we did not see in any of our in vitro experiments."

While Dr. Koo described gas chromatography–mass spectrometry as "labor intensive," she characterized the findings of the current study as "easily translatable to a point of care platform for the detection of these fungal breath metabolites and potentially the diagnosis of other bacterial and fungal pneumonias at the bedside."

Dr. Koo acknowledged certain limitations of the study, including its single-center design and the fact that it will require validation in a larger cohort of patients.

The National Institutes of Health and the Harvard Catalyst/the Harvard Clinical and Translational Science Center Pilot Grant Program supported the study. The authors stated that they have no relevant financial conflicts.

[email protected]