Antimicrobial-resistant infections

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Does antibiotic prophylaxis prevent future episodes of urinary tract infections?

Background: Recurrent urinary tract infections (UTI) in children might be associated with renal scarring and subsequent clinical consequences associated with long-term morbidity. Historically, antibiotic prophylaxis has been recommended for children who might have risk factors for recurrent infection, most commonly vesicoureteral reflux. However, scars may be present in the absence of known risk factors and upon first UTI. The efficacy of antibiotic prophylaxis in preventing recurrent UTIs is unclear.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Four centers in Australia.

Synopsis: The study looked at 576 children under the age of 18 with a history of at least one symptomatic UTI. The patients were randomized to receive trimethoprim-sulfamethoxazole (TMP-SMX) or placebo for 12 months. Children with vesicoureteral reflux were included, but those with known neurologic, skeletal, or urologic predispositions were excluded.

Thirteen percent of patients in the antibiotic group developed a UTI compared with 19% of patients in the placebo group (P=0.02). The authors calculate that at 12 months, 14 patients would need to be treated to prevent one UTI.

This study was unable to enroll the planned number of children but remained adequately powered to show a reduction in the primary outcome (rate of symptomatic UTI). However, a significant number of patients (approximately 28%) in each arm stopped taking the medication, the majority for undisclosed reasons. Despite an intention-to-treat analysis, this degree of dropout raises questions about the true effect size. Additionally, this study does not answer the more important clinical question regarding the effect of prophylaxis on potential future renal damage, specifically in children with vesicoureteral reflux.

Bottom line: Antibiotic prophylaxis might be modestly effective in preventing recurrent UTIs.

Citation: Craig JC, Simpson JM, Williams GJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009;361(18):1748-1759.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Does antibiotic prophylaxis prevent future episodes of urinary tract infections?

Background: Recurrent urinary tract infections (UTI) in children might be associated with renal scarring and subsequent clinical consequences associated with long-term morbidity. Historically, antibiotic prophylaxis has been recommended for children who might have risk factors for recurrent infection, most commonly vesicoureteral reflux. However, scars may be present in the absence of known risk factors and upon first UTI. The efficacy of antibiotic prophylaxis in preventing recurrent UTIs is unclear.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Four centers in Australia.

Synopsis: The study looked at 576 children under the age of 18 with a history of at least one symptomatic UTI. The patients were randomized to receive trimethoprim-sulfamethoxazole (TMP-SMX) or placebo for 12 months. Children with vesicoureteral reflux were included, but those with known neurologic, skeletal, or urologic predispositions were excluded.

Thirteen percent of patients in the antibiotic group developed a UTI compared with 19% of patients in the placebo group (P=0.02). The authors calculate that at 12 months, 14 patients would need to be treated to prevent one UTI.

This study was unable to enroll the planned number of children but remained adequately powered to show a reduction in the primary outcome (rate of symptomatic UTI). However, a significant number of patients (approximately 28%) in each arm stopped taking the medication, the majority for undisclosed reasons. Despite an intention-to-treat analysis, this degree of dropout raises questions about the true effect size. Additionally, this study does not answer the more important clinical question regarding the effect of prophylaxis on potential future renal damage, specifically in children with vesicoureteral reflux.

Bottom line: Antibiotic prophylaxis might be modestly effective in preventing recurrent UTIs.

Citation: Craig JC, Simpson JM, Williams GJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009;361(18):1748-1759.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Does antibiotic prophylaxis prevent future episodes of urinary tract infections?

Background: Recurrent urinary tract infections (UTI) in children might be associated with renal scarring and subsequent clinical consequences associated with long-term morbidity. Historically, antibiotic prophylaxis has been recommended for children who might have risk factors for recurrent infection, most commonly vesicoureteral reflux. However, scars may be present in the absence of known risk factors and upon first UTI. The efficacy of antibiotic prophylaxis in preventing recurrent UTIs is unclear.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Four centers in Australia.

Synopsis: The study looked at 576 children under the age of 18 with a history of at least one symptomatic UTI. The patients were randomized to receive trimethoprim-sulfamethoxazole (TMP-SMX) or placebo for 12 months. Children with vesicoureteral reflux were included, but those with known neurologic, skeletal, or urologic predispositions were excluded.

Thirteen percent of patients in the antibiotic group developed a UTI compared with 19% of patients in the placebo group (P=0.02). The authors calculate that at 12 months, 14 patients would need to be treated to prevent one UTI.

This study was unable to enroll the planned number of children but remained adequately powered to show a reduction in the primary outcome (rate of symptomatic UTI). However, a significant number of patients (approximately 28%) in each arm stopped taking the medication, the majority for undisclosed reasons. Despite an intention-to-treat analysis, this degree of dropout raises questions about the true effect size. Additionally, this study does not answer the more important clinical question regarding the effect of prophylaxis on potential future renal damage, specifically in children with vesicoureteral reflux.

Bottom line: Antibiotic prophylaxis might be modestly effective in preventing recurrent UTIs.

Citation: Craig JC, Simpson JM, Williams GJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009;361(18):1748-1759.

Clinical question: What antibiotic-resistant bacteria are the greatest threats for the next 10 years?

Background: Two million people suffer antibiotic-resistant infections yearly, and 23,000 die each year as a result. Most of these infections occur in the community, but deaths usually occur in healthcare settings. Cost estimates vary but may be as high as $20 billion in excess direct healthcare costs.

Study design: The CDC used several different surveys and databanks, including the National Antimicrobial Resistance Monitoring System, to collect data. The threat level for antibiotic-resistant bacteria was determined using several factors: clinical impact, economic impact, incidence, 10-year projection of incidence, transmissibility, availability of effective antibiotics, and barriers to prevention.

Setting: United States.

Synopsis: The CDC has three classifications of antibiotic-resistant bacteria: urgent, serious, and concerning. Urgent threats are high-consequence, antibiotic-resistant threats because of significant risks identified across several criteria. These threats might not currently be widespread but have the potential to become so and require urgent public health attention to identify infections and to limit transmission. They include carbapenem-resistant Enterobacteriaceae, drug-resistant Neisseria gonorrhoeae, and Clostridium difficile (does not have true resistance, but is a consequence of antibiotic overuse).

Serious threats are significant antibiotic-resistant threats. These threats will worsen and might become urgent without ongoing public health monitoring and prevention activities. They include multidrug-resistant Acinetobacter, drug-resistant Campylobacter, fluconazole-resistant Candida (a fungus), extended-spectrum β-lactamase-producing Enterobacteriaceae, vancomycin-resistant Enterococcus, multidrug-resistant Pseudomonas aeruginosa, drug-resistant non-typhoidal Salmonella, drug-resistant Salmonella Typhimurium, drug-resistant Shigella, methicillin-resistant Staphylococcus aureus, drug-resistant Streptococcus pneumonia, and drug-resistant tuberculosis.

Concerning threats are bacteria for which the threat of antibiotic resistance is low, and/ or there are multiple therapeutic options for resistant infections. These bacterial pathogens cause severe illness. Threats in this category require monitoring and, in some cases, rapid incident or outbreak response. These include vancomycin-resistant Staphylococcus aureus, erythromycin-resistant Group A Streptococcus, and clindamycin-resistant Group B Streptococcus. Research has shown patients with resistant infections have significantly longer hospital stays, delayed recuperation, long-term disability, and higher mortality. As resistance to current antibiotics occurs, providers are forced to use antibiotics that are more toxic, more expensive, and less effective.

The CDC recommends four core actions to fight antibiotic resistance:

• Preventing infections from occurring and preventing resistant bacteria from spreading (immunization, infection control, screening, treatment, and education);
• Tracking resistant bacteria;
• Improving the use of antibiotics (antibiotic stewardship); and
• Promoting the development of new antibiotics and new diagnostic tests for resistant bacteria.

Bottom line: Antibiotics are a limited resource. The more antibiotics are used today, the less likely they will continue to be effective in the future. The CDC lists 18 antibiotic-resistant organisms as urgent, serious, or concerning and recommends actions to combat the spread of current organisms and emergence of new antibiotic organisms.

Citation: Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. CDC website. September 16, 2013. Available at: www.cdc.gov/drugresistance/threat-report-2013. Accessed Nov. 30, 2013.

Clinical question: What antibiotic-resistant bacteria are the greatest threats for the next 10 years?

Background: Two million people suffer antibiotic-resistant infections yearly, and 23,000 die each year as a result. Most of these infections occur in the community, but deaths usually occur in healthcare settings. Cost estimates vary but may be as high as $20 billion in excess direct healthcare costs.

Study design: The CDC used several different surveys and databanks, including the National Antimicrobial Resistance Monitoring System, to collect data. The threat level for antibiotic-resistant bacteria was determined using several factors: clinical impact, economic impact, incidence, 10-year projection of incidence, transmissibility, availability of effective antibiotics, and barriers to prevention.

Setting: United States.

Synopsis: The CDC has three classifications of antibiotic-resistant bacteria: urgent, serious, and concerning. Urgent threats are high-consequence, antibiotic-resistant threats because of significant risks identified across several criteria. These threats might not currently be widespread but have the potential to become so and require urgent public health attention to identify infections and to limit transmission. They include carbapenem-resistant Enterobacteriaceae, drug-resistant Neisseria gonorrhoeae, and Clostridium difficile (does not have true resistance, but is a consequence of antibiotic overuse).

Serious threats are significant antibiotic-resistant threats. These threats will worsen and might become urgent without ongoing public health monitoring and prevention activities. They include multidrug-resistant Acinetobacter, drug-resistant Campylobacter, fluconazole-resistant Candida (a fungus), extended-spectrum β-lactamase-producing Enterobacteriaceae, vancomycin-resistant Enterococcus, multidrug-resistant Pseudomonas aeruginosa, drug-resistant non-typhoidal Salmonella, drug-resistant Salmonella Typhimurium, drug-resistant Shigella, methicillin-resistant Staphylococcus aureus, drug-resistant Streptococcus pneumonia, and drug-resistant tuberculosis.

Concerning threats are bacteria for which the threat of antibiotic resistance is low, and/ or there are multiple therapeutic options for resistant infections. These bacterial pathogens cause severe illness. Threats in this category require monitoring and, in some cases, rapid incident or outbreak response. These include vancomycin-resistant Staphylococcus aureus, erythromycin-resistant Group A Streptococcus, and clindamycin-resistant Group B Streptococcus. Research has shown patients with resistant infections have significantly longer hospital stays, delayed recuperation, long-term disability, and higher mortality. As resistance to current antibiotics occurs, providers are forced to use antibiotics that are more toxic, more expensive, and less effective.

The CDC recommends four core actions to fight antibiotic resistance:

• Preventing infections from occurring and preventing resistant bacteria from spreading (immunization, infection control, screening, treatment, and education);
• Tracking resistant bacteria;
• Improving the use of antibiotics (antibiotic stewardship); and
• Promoting the development of new antibiotics and new diagnostic tests for resistant bacteria.

Bottom line: Antibiotics are a limited resource. The more antibiotics are used today, the less likely they will continue to be effective in the future. The CDC lists 18 antibiotic-resistant organisms as urgent, serious, or concerning and recommends actions to combat the spread of current organisms and emergence of new antibiotic organisms.

Citation: Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. CDC website. September 16, 2013. Available at: www.cdc.gov/drugresistance/threat-report-2013. Accessed Nov. 30, 2013.

Clinical question: What antibiotic-resistant bacteria are the greatest threats for the next 10 years?

Background: Two million people suffer antibiotic-resistant infections yearly, and 23,000 die each year as a result. Most of these infections occur in the community, but deaths usually occur in healthcare settings. Cost estimates vary but may be as high as $20 billion in excess direct healthcare costs.

Study design: The CDC used several different surveys and databanks, including the National Antimicrobial Resistance Monitoring System, to collect data. The threat level for antibiotic-resistant bacteria was determined using several factors: clinical impact, economic impact, incidence, 10-year projection of incidence, transmissibility, availability of effective antibiotics, and barriers to prevention.

Setting: United States.

Synopsis: The CDC has three classifications of antibiotic-resistant bacteria: urgent, serious, and concerning. Urgent threats are high-consequence, antibiotic-resistant threats because of significant risks identified across several criteria. These threats might not currently be widespread but have the potential to become so and require urgent public health attention to identify infections and to limit transmission. They include carbapenem-resistant Enterobacteriaceae, drug-resistant Neisseria gonorrhoeae, and Clostridium difficile (does not have true resistance, but is a consequence of antibiotic overuse).

Serious threats are significant antibiotic-resistant threats. These threats will worsen and might become urgent without ongoing public health monitoring and prevention activities. They include multidrug-resistant Acinetobacter, drug-resistant Campylobacter, fluconazole-resistant Candida (a fungus), extended-spectrum β-lactamase-producing Enterobacteriaceae, vancomycin-resistant Enterococcus, multidrug-resistant Pseudomonas aeruginosa, drug-resistant non-typhoidal Salmonella, drug-resistant Salmonella Typhimurium, drug-resistant Shigella, methicillin-resistant Staphylococcus aureus, drug-resistant Streptococcus pneumonia, and drug-resistant tuberculosis.

Concerning threats are bacteria for which the threat of antibiotic resistance is low, and/ or there are multiple therapeutic options for resistant infections. These bacterial pathogens cause severe illness. Threats in this category require monitoring and, in some cases, rapid incident or outbreak response. These include vancomycin-resistant Staphylococcus aureus, erythromycin-resistant Group A Streptococcus, and clindamycin-resistant Group B Streptococcus. Research has shown patients with resistant infections have significantly longer hospital stays, delayed recuperation, long-term disability, and higher mortality. As resistance to current antibiotics occurs, providers are forced to use antibiotics that are more toxic, more expensive, and less effective.

The CDC recommends four core actions to fight antibiotic resistance:

• Preventing infections from occurring and preventing resistant bacteria from spreading (immunization, infection control, screening, treatment, and education);
• Tracking resistant bacteria;
• Improving the use of antibiotics (antibiotic stewardship); and
• Promoting the development of new antibiotics and new diagnostic tests for resistant bacteria.

Bottom line: Antibiotics are a limited resource. The more antibiotics are used today, the less likely they will continue to be effective in the future. The CDC lists 18 antibiotic-resistant organisms as urgent, serious, or concerning and recommends actions to combat the spread of current organisms and emergence of new antibiotic organisms.

Citation: Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. CDC website. September 16, 2013. Available at: www.cdc.gov/drugresistance/threat-report-2013. Accessed Nov. 30, 2013.

Background: Acute bacterial skin infections are common and often require hospitalization for intravenous antibiotic administration. Treatment covering gram-positive bacteria usually is indicated. Dalbavancin is effective against gram-positives, including MRSA. Its long half-life makes it an attractive alternative to other commonly used antibiotics, which require more frequent dosing.

Study design: Phase 3, double-blinded RCT.

Setting: Multiple international centers.

Synopsis: Researchers randomized 1,312 patients with acute bacterial skin and skin-structure infections with signs of systemic infection requiring intravenous antibiotics to receive dalbavancin on days one and eight, with placebo on other days, or several doses of vancomycin with an option to switch to oral linezolid. The primary endpoint was cessation of spread of erythema and temperature of =37.6°C at 48–72 hours. Secondary endpoints included a decrease in lesion area of =20% at 48–72 hours and clinical success at end of therapy (determined by clinical and historical features). Results of the primary endpoint were similar with dalbavancin and vancomycin-linezolid groups (79.7% and 79.8%, respectively) and were within 10 percentage points of noninferiority. The secondary endpoints were similar between both groups. Limitations of the study were the early primary endpoint, lack of noninferiority analysis of the secondary endpoints, and cost-effective analysis.

Bottom line: Once-weekly dalbavancin appears to be similarly efficacious to intravenous vancomycin in the treatment of acute bacterial skin infections in terms of outcomes within 48–72 hours of therapy and might provide an alternative to continued inpatient hospitalization for intravenous antibiotics in stable patients.

Citation: Boucher HW, Wilcox M, Talbot GH, Puttagunta S, Das AF, Dunne MW. Once-weekly dalbavancin versus daily conventional therapy for skin infection. N Engl J Med. 2014;370(23):2169-2179.

Background: Acute bacterial skin infections are common and often require hospitalization for intravenous antibiotic administration. Treatment covering gram-positive bacteria usually is indicated. Dalbavancin is effective against gram-positives, including MRSA. Its long half-life makes it an attractive alternative to other commonly used antibiotics, which require more frequent dosing.

Study design: Phase 3, double-blinded RCT.

Setting: Multiple international centers.

Synopsis: Researchers randomized 1,312 patients with acute bacterial skin and skin-structure infections with signs of systemic infection requiring intravenous antibiotics to receive dalbavancin on days one and eight, with placebo on other days, or several doses of vancomycin with an option to switch to oral linezolid. The primary endpoint was cessation of spread of erythema and temperature of =37.6°C at 48–72 hours. Secondary endpoints included a decrease in lesion area of =20% at 48–72 hours and clinical success at end of therapy (determined by clinical and historical features). Results of the primary endpoint were similar with dalbavancin and vancomycin-linezolid groups (79.7% and 79.8%, respectively) and were within 10 percentage points of noninferiority. The secondary endpoints were similar between both groups. Limitations of the study were the early primary endpoint, lack of noninferiority analysis of the secondary endpoints, and cost-effective analysis.

Bottom line: Once-weekly dalbavancin appears to be similarly efficacious to intravenous vancomycin in the treatment of acute bacterial skin infections in terms of outcomes within 48–72 hours of therapy and might provide an alternative to continued inpatient hospitalization for intravenous antibiotics in stable patients.

Citation: Boucher HW, Wilcox M, Talbot GH, Puttagunta S, Das AF, Dunne MW. Once-weekly dalbavancin versus daily conventional therapy for skin infection. N Engl J Med. 2014;370(23):2169-2179.

Background: Acute bacterial skin infections are common and often require hospitalization for intravenous antibiotic administration. Treatment covering gram-positive bacteria usually is indicated. Dalbavancin is effective against gram-positives, including MRSA. Its long half-life makes it an attractive alternative to other commonly used antibiotics, which require more frequent dosing.

Study design: Phase 3, double-blinded RCT.

Setting: Multiple international centers.

Synopsis: Researchers randomized 1,312 patients with acute bacterial skin and skin-structure infections with signs of systemic infection requiring intravenous antibiotics to receive dalbavancin on days one and eight, with placebo on other days, or several doses of vancomycin with an option to switch to oral linezolid. The primary endpoint was cessation of spread of erythema and temperature of =37.6°C at 48–72 hours. Secondary endpoints included a decrease in lesion area of =20% at 48–72 hours and clinical success at end of therapy (determined by clinical and historical features). Results of the primary endpoint were similar with dalbavancin and vancomycin-linezolid groups (79.7% and 79.8%, respectively) and were within 10 percentage points of noninferiority. The secondary endpoints were similar between both groups. Limitations of the study were the early primary endpoint, lack of noninferiority analysis of the secondary endpoints, and cost-effective analysis.

Bottom line: Once-weekly dalbavancin appears to be similarly efficacious to intravenous vancomycin in the treatment of acute bacterial skin infections in terms of outcomes within 48–72 hours of therapy and might provide an alternative to continued inpatient hospitalization for intravenous antibiotics in stable patients.

Citation: Boucher HW, Wilcox M, Talbot GH, Puttagunta S, Das AF, Dunne MW. Once-weekly dalbavancin versus daily conventional therapy for skin infection. N Engl J Med. 2014;370(23):2169-2179.

Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.

Clinical question: Has the frequency of sepsis rates, along with administration of antibiotics in U.S. emergency departments (EDs), changed over time?

Background: Prior studies reviewing discharge data from hospitals suggest an increase of sepsis over time; however, little epidemiological research has evaluated the diagnosis of sepsis and antibiotic use in ED settings.

Study design: Retrospective, four-stage probability sample.

Setting: National Hospital Ambulatory Medical Care Survey (NHAMCS).

Synopsis: The NHAMCS includes a sample of all U.S. ED visits, except federal, military, and VA hospitals. According to NHAMCS data, an estimated 1.3 billion visits by adults to U.S. EDs occurred from 1994-2009, or approximately 81 million visits per year. Explicit sepsis was defined by the presence of the following, with ICD-9 codes: septicemia (038), sepsis (995.91), severe sepsis (995.92), or septic shock (785.52). Implicit sepsis was defined as a code indicating infection plus a code indicting organ dysfunction.

In U.S. EDs, explicit sepsis did not become more prevalent from 1994-2009; however, implicitly diagnosed sepsis increased by 7% every two years. There were 260,000 explicit sepsis-related ED visits per year, or 1.23 visits per 1,000 U.S. population. In-hospital mortality was 17% and 9% for the explicit and implicit diagnosis groups, respectively. On review of the explicit sepsis group, only 61% of the patients were found to have received antibiotics in the ED. The rate did increase over the time studied, from 52% in 1994-1997 to 69% in 2006-2009.

The study was limited by the retrospective analysis of data not designed to track sepsis or antibiotic use.

Bottom Line: Explicitly recognized sepsis remained stable in the ED setting from 1994-2009, and early antibiotic use has improved during this time, but there is still much opportunity for improvement.

Citation: Filbin MR, Arias SA, Camargo CA Jr, Barche A, Pallin DJ. Sepsis visits and antibiotic utilization in the U.S. emergency departments. Crit Care Med. 2014;42(3):528-535.

Clinical question: Has the frequency of sepsis rates, along with administration of antibiotics in U.S. emergency departments (EDs), changed over time?

Background: Prior studies reviewing discharge data from hospitals suggest an increase of sepsis over time; however, little epidemiological research has evaluated the diagnosis of sepsis and antibiotic use in ED settings.

Study design: Retrospective, four-stage probability sample.

Setting: National Hospital Ambulatory Medical Care Survey (NHAMCS).

Synopsis: The NHAMCS includes a sample of all U.S. ED visits, except federal, military, and VA hospitals. According to NHAMCS data, an estimated 1.3 billion visits by adults to U.S. EDs occurred from 1994-2009, or approximately 81 million visits per year. Explicit sepsis was defined by the presence of the following, with ICD-9 codes: septicemia (038), sepsis (995.91), severe sepsis (995.92), or septic shock (785.52). Implicit sepsis was defined as a code indicating infection plus a code indicting organ dysfunction.

In U.S. EDs, explicit sepsis did not become more prevalent from 1994-2009; however, implicitly diagnosed sepsis increased by 7% every two years. There were 260,000 explicit sepsis-related ED visits per year, or 1.23 visits per 1,000 U.S. population. In-hospital mortality was 17% and 9% for the explicit and implicit diagnosis groups, respectively. On review of the explicit sepsis group, only 61% of the patients were found to have received antibiotics in the ED. The rate did increase over the time studied, from 52% in 1994-1997 to 69% in 2006-2009.

The study was limited by the retrospective analysis of data not designed to track sepsis or antibiotic use.

Bottom Line: Explicitly recognized sepsis remained stable in the ED setting from 1994-2009, and early antibiotic use has improved during this time, but there is still much opportunity for improvement.

Citation: Filbin MR, Arias SA, Camargo CA Jr, Barche A, Pallin DJ. Sepsis visits and antibiotic utilization in the U.S. emergency departments. Crit Care Med. 2014;42(3):528-535.

Clinical question: Has the frequency of sepsis rates, along with administration of antibiotics in U.S. emergency departments (EDs), changed over time?

Background: Prior studies reviewing discharge data from hospitals suggest an increase of sepsis over time; however, little epidemiological research has evaluated the diagnosis of sepsis and antibiotic use in ED settings.

Study design: Retrospective, four-stage probability sample.

Setting: National Hospital Ambulatory Medical Care Survey (NHAMCS).

Synopsis: The NHAMCS includes a sample of all U.S. ED visits, except federal, military, and VA hospitals. According to NHAMCS data, an estimated 1.3 billion visits by adults to U.S. EDs occurred from 1994-2009, or approximately 81 million visits per year. Explicit sepsis was defined by the presence of the following, with ICD-9 codes: septicemia (038), sepsis (995.91), severe sepsis (995.92), or septic shock (785.52). Implicit sepsis was defined as a code indicating infection plus a code indicting organ dysfunction.

In U.S. EDs, explicit sepsis did not become more prevalent from 1994-2009; however, implicitly diagnosed sepsis increased by 7% every two years. There were 260,000 explicit sepsis-related ED visits per year, or 1.23 visits per 1,000 U.S. population. In-hospital mortality was 17% and 9% for the explicit and implicit diagnosis groups, respectively. On review of the explicit sepsis group, only 61% of the patients were found to have received antibiotics in the ED. The rate did increase over the time studied, from 52% in 1994-1997 to 69% in 2006-2009.

The study was limited by the retrospective analysis of data not designed to track sepsis or antibiotic use.

Bottom Line: Explicitly recognized sepsis remained stable in the ED setting from 1994-2009, and early antibiotic use has improved during this time, but there is still much opportunity for improvement.

Citation: Filbin MR, Arias SA, Camargo CA Jr, Barche A, Pallin DJ. Sepsis visits and antibiotic utilization in the U.S. emergency departments. Crit Care Med. 2014;42(3):528-535.

Clinical question: What are the current prescribing practices for antibiotics used to treat skin and soft tissue infections in the outpatient setting?

Background: Uncomplicated skin and soft tissue infections are among the most frequent indications for outpatient antibiotic use. Because antibiotic use is associated with bacterial resistance and adverse events, understanding antibiotic prescribing practices is necessary to minimize these types of complications.

Study design: Retrospective cohort.

Setting: Ambulatory care setting in the Denver Health System.

Synopsis: Data from 364 adults and children who presented to an ambulatory setting with a primary diagnosis of skin and soft tissue infection were analyzed using a stepwise multivariate logistic regression in order to determine factors associated with avoidable antibiotic exposure. Among cellulitis cases, 61% of patients were prescribed antibiotics to treat methicillin-resistant Staphylococcus aureus. Avoidable antibiotic exposure occurred in 46% of cases, including use of antibiotics with broad Gram-negative activity (4%), combination therapy (12%), and treatment for ≥10 days (42%). Use of short-course, single-antibiotic treatment approaches consistent with national guidelines would have reduced prescribed antibiotic days by 19%, to 55%.

Bottom line: Avoidable antibiotic exposure frequently occurs in the treatment of uncomplicated skin infections; using short-course, single-antibiotic treatment strategies could significantly reduce total antibiotic use.

Citation: Hurley HJ, Knepper BC, Price CS, Mehler PS, Burman WJ, Jenkins TC. Avoidable antibiotic exposure for uncomplicated skin and soft tissue infections in the ambulatory care setting. Am J Med. 2013;126(12):1099-1106.

Clinical question: What are the current prescribing practices for antibiotics used to treat skin and soft tissue infections in the outpatient setting?

Background: Uncomplicated skin and soft tissue infections are among the most frequent indications for outpatient antibiotic use. Because antibiotic use is associated with bacterial resistance and adverse events, understanding antibiotic prescribing practices is necessary to minimize these types of complications.

Study design: Retrospective cohort.

Setting: Ambulatory care setting in the Denver Health System.

Synopsis: Data from 364 adults and children who presented to an ambulatory setting with a primary diagnosis of skin and soft tissue infection were analyzed using a stepwise multivariate logistic regression in order to determine factors associated with avoidable antibiotic exposure. Among cellulitis cases, 61% of patients were prescribed antibiotics to treat methicillin-resistant Staphylococcus aureus. Avoidable antibiotic exposure occurred in 46% of cases, including use of antibiotics with broad Gram-negative activity (4%), combination therapy (12%), and treatment for ≥10 days (42%). Use of short-course, single-antibiotic treatment approaches consistent with national guidelines would have reduced prescribed antibiotic days by 19%, to 55%.

Bottom line: Avoidable antibiotic exposure frequently occurs in the treatment of uncomplicated skin infections; using short-course, single-antibiotic treatment strategies could significantly reduce total antibiotic use.

Citation: Hurley HJ, Knepper BC, Price CS, Mehler PS, Burman WJ, Jenkins TC. Avoidable antibiotic exposure for uncomplicated skin and soft tissue infections in the ambulatory care setting. Am J Med. 2013;126(12):1099-1106.

Clinical question: What are the current prescribing practices for antibiotics used to treat skin and soft tissue infections in the outpatient setting?

Background: Uncomplicated skin and soft tissue infections are among the most frequent indications for outpatient antibiotic use. Because antibiotic use is associated with bacterial resistance and adverse events, understanding antibiotic prescribing practices is necessary to minimize these types of complications.

Study design: Retrospective cohort.

Setting: Ambulatory care setting in the Denver Health System.

Synopsis: Data from 364 adults and children who presented to an ambulatory setting with a primary diagnosis of skin and soft tissue infection were analyzed using a stepwise multivariate logistic regression in order to determine factors associated with avoidable antibiotic exposure. Among cellulitis cases, 61% of patients were prescribed antibiotics to treat methicillin-resistant Staphylococcus aureus. Avoidable antibiotic exposure occurred in 46% of cases, including use of antibiotics with broad Gram-negative activity (4%), combination therapy (12%), and treatment for ≥10 days (42%). Use of short-course, single-antibiotic treatment approaches consistent with national guidelines would have reduced prescribed antibiotic days by 19%, to 55%.

Bottom line: Avoidable antibiotic exposure frequently occurs in the treatment of uncomplicated skin infections; using short-course, single-antibiotic treatment strategies could significantly reduce total antibiotic use.

Citation: Hurley HJ, Knepper BC, Price CS, Mehler PS, Burman WJ, Jenkins TC. Avoidable antibiotic exposure for uncomplicated skin and soft tissue infections in the ambulatory care setting. Am J Med. 2013;126(12):1099-1106.

By Mark Shen, MD

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Is a short course (less than four weeks) of antibiotics effective for the treatment of acute osteomyelitis and septic arthritis?

Background: The optimal duration of treatment for acute bone and joint infections in children has not been assessed adequately in prospectively designed trials. Historically, intravenous (IV) antibiotics in four- to six-week durations have been recommended, although the evidence for this practice is limited. There is widespread variation in both the route of administration (oral vs. IV) and duration of this treatment.

Study design: Prospective cohort study.

Setting: Two children’s hospitals in Australia.

Synopsis: Seventy children ages 17 and under who presented to two tertiary-care children’s hospitals with osteomyelitis or septic arthritis were enrolled. Primary surgical drainage was performed for patients with septic arthritis. Intravenous antibiotics were administered for at least three days, and until clinical symptoms improved and the C-reactive protein levels had stabilized. Patients then were transitioned to oral antibiotics and discharged to complete a minimum of three weeks of therapy.

Fifty-nine percent of patients were converted to oral antibiotics by day three, 86% by day five of therapy. Based on clinical and hematologic assessment, 83% of patients had oral antibiotics stopped at the three-week followup and remained well through the 12-month follow-up period.

This study essentially involved prospective data collection for a cohort of children receiving standardized care. Although the results suggest that a majority of children can be treated with a three-week course of oral antibiotics, the results would have been further strengthened by an explicit protocol with well-defined criteria for the oral to IV transition and cessation of antibiotic therapy. Additional limitations include pathogens and antibiotic choices that might not be applicable to North American populations.

Bottom line: After initial intravenous therapy, a three-week course of oral antibiotics can be effective for acute osteomyelitis and septic arthritis in children.

Citation: Jagodzinski NA, Kanwar R, Graham K, Bache CE. Prospective evaluation of a shortened regimen of treatment for acute osteomyelitis and septic arthritis in children. J Pediatr Orthop. 2009;29(5):518-525.

By Mark Shen, MD

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Is a short course (less than four weeks) of antibiotics effective for the treatment of acute osteomyelitis and septic arthritis?

Background: The optimal duration of treatment for acute bone and joint infections in children has not been assessed adequately in prospectively designed trials. Historically, intravenous (IV) antibiotics in four- to six-week durations have been recommended, although the evidence for this practice is limited. There is widespread variation in both the route of administration (oral vs. IV) and duration of this treatment.

Study design: Prospective cohort study.

Setting: Two children’s hospitals in Australia.

Synopsis: Seventy children ages 17 and under who presented to two tertiary-care children’s hospitals with osteomyelitis or septic arthritis were enrolled. Primary surgical drainage was performed for patients with septic arthritis. Intravenous antibiotics were administered for at least three days, and until clinical symptoms improved and the C-reactive protein levels had stabilized. Patients then were transitioned to oral antibiotics and discharged to complete a minimum of three weeks of therapy.

Fifty-nine percent of patients were converted to oral antibiotics by day three, 86% by day five of therapy. Based on clinical and hematologic assessment, 83% of patients had oral antibiotics stopped at the three-week followup and remained well through the 12-month follow-up period.

This study essentially involved prospective data collection for a cohort of children receiving standardized care. Although the results suggest that a majority of children can be treated with a three-week course of oral antibiotics, the results would have been further strengthened by an explicit protocol with well-defined criteria for the oral to IV transition and cessation of antibiotic therapy. Additional limitations include pathogens and antibiotic choices that might not be applicable to North American populations.

Bottom line: After initial intravenous therapy, a three-week course of oral antibiotics can be effective for acute osteomyelitis and septic arthritis in children.

Citation: Jagodzinski NA, Kanwar R, Graham K, Bache CE. Prospective evaluation of a shortened regimen of treatment for acute osteomyelitis and septic arthritis in children. J Pediatr Orthop. 2009;29(5):518-525.

By Mark Shen, MD

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: Is a short course (less than four weeks) of antibiotics effective for the treatment of acute osteomyelitis and septic arthritis?

Background: The optimal duration of treatment for acute bone and joint infections in children has not been assessed adequately in prospectively designed trials. Historically, intravenous (IV) antibiotics in four- to six-week durations have been recommended, although the evidence for this practice is limited. There is widespread variation in both the route of administration (oral vs. IV) and duration of this treatment.

Study design: Prospective cohort study.

Setting: Two children’s hospitals in Australia.

Synopsis: Seventy children ages 17 and under who presented to two tertiary-care children’s hospitals with osteomyelitis or septic arthritis were enrolled. Primary surgical drainage was performed for patients with septic arthritis. Intravenous antibiotics were administered for at least three days, and until clinical symptoms improved and the C-reactive protein levels had stabilized. Patients then were transitioned to oral antibiotics and discharged to complete a minimum of three weeks of therapy.

Fifty-nine percent of patients were converted to oral antibiotics by day three, 86% by day five of therapy. Based on clinical and hematologic assessment, 83% of patients had oral antibiotics stopped at the three-week followup and remained well through the 12-month follow-up period.

This study essentially involved prospective data collection for a cohort of children receiving standardized care. Although the results suggest that a majority of children can be treated with a three-week course of oral antibiotics, the results would have been further strengthened by an explicit protocol with well-defined criteria for the oral to IV transition and cessation of antibiotic therapy. Additional limitations include pathogens and antibiotic choices that might not be applicable to North American populations.

Bottom line: After initial intravenous therapy, a three-week course of oral antibiotics can be effective for acute osteomyelitis and septic arthritis in children.

Citation: Jagodzinski NA, Kanwar R, Graham K, Bache CE. Prospective evaluation of a shortened regimen of treatment for acute osteomyelitis and septic arthritis in children. J Pediatr Orthop. 2009;29(5):518-525.

Clinical question: Is once-weekly intravenous dalbavancin as effective as conventional therapy for the treatment of acute bacterial skin infections?

Background: Acute bacterial skin infections are common and often require hospitalization for intravenous antibiotic administration. Treatment covering gram-positive bacteria usually is indicated. Dalbavancin is effective against gram-positives, including MRSA. Its long half-life makes it an attractive alternative to other commonly used antibiotics, which require more frequent dosing.

Study design: Phase 3, double-blinded RCT.

Setting: Multiple international centers.

Synopsis: Researchers randomized 1,312 patients with acute bacterial skin and skin-structure infections with signs of systemic infection requiring intravenous antibiotics to receive dalbavancin on days one and eight, with placebo on other days, or several doses of vancomycin with an option to switch to oral linezolid. The primary endpoint was cessation of spread of erythema and temperature of ≤37.6°C at 48-72 hours. Secondary endpoints included a decrease in lesion area of ≥20% at 48-72 hours and clinical success at end of therapy (determined by clinical and historical features).

Results of the primary endpoint were similar with dalbavancin and vancomycin-linezolid groups (79.7% and 79.8%, respectively) and were within 10 percentage points of noninferiority. The secondary endpoints were similar between both groups.

Limitations of the study were the early primary endpoint, lack of noninferiority analysis of the secondary endpoints, and cost-effective analysis.

Bottom line: Once-weekly dalbavancin appears to be similarly efficacious to intravenous vancomycin in the treatment of acute bacterial skin infections in terms of outcomes within 48-72 hours of therapy and might provide an alternative to continued inpatient hospitalization for intravenous antibiotics in stable patients.

Citation: Boucher HW, Wilcox M, Talbot GH, Puttagunta S, Das AF, Dunne MW. Once-weekly dalbavancin versus daily conventional therapy for skin infection. N Engl J Med. 2014;370(23):2169-2179.

Clinical question: Is once-weekly intravenous dalbavancin as effective as conventional therapy for the treatment of acute bacterial skin infections?

Background: Acute bacterial skin infections are common and often require hospitalization for intravenous antibiotic administration. Treatment covering gram-positive bacteria usually is indicated. Dalbavancin is effective against gram-positives, including MRSA. Its long half-life makes it an attractive alternative to other commonly used antibiotics, which require more frequent dosing.

Study design: Phase 3, double-blinded RCT.

Setting: Multiple international centers.

Synopsis: Researchers randomized 1,312 patients with acute bacterial skin and skin-structure infections with signs of systemic infection requiring intravenous antibiotics to receive dalbavancin on days one and eight, with placebo on other days, or several doses of vancomycin with an option to switch to oral linezolid. The primary endpoint was cessation of spread of erythema and temperature of ≤37.6°C at 48-72 hours. Secondary endpoints included a decrease in lesion area of ≥20% at 48-72 hours and clinical success at end of therapy (determined by clinical and historical features).

Results of the primary endpoint were similar with dalbavancin and vancomycin-linezolid groups (79.7% and 79.8%, respectively) and were within 10 percentage points of noninferiority. The secondary endpoints were similar between both groups.

Limitations of the study were the early primary endpoint, lack of noninferiority analysis of the secondary endpoints, and cost-effective analysis.

Bottom line: Once-weekly dalbavancin appears to be similarly efficacious to intravenous vancomycin in the treatment of acute bacterial skin infections in terms of outcomes within 48-72 hours of therapy and might provide an alternative to continued inpatient hospitalization for intravenous antibiotics in stable patients.

Citation: Boucher HW, Wilcox M, Talbot GH, Puttagunta S, Das AF, Dunne MW. Once-weekly dalbavancin versus daily conventional therapy for skin infection. N Engl J Med. 2014;370(23):2169-2179.

Clinical question: Is once-weekly intravenous dalbavancin as effective as conventional therapy for the treatment of acute bacterial skin infections?

Background: Acute bacterial skin infections are common and often require hospitalization for intravenous antibiotic administration. Treatment covering gram-positive bacteria usually is indicated. Dalbavancin is effective against gram-positives, including MRSA. Its long half-life makes it an attractive alternative to other commonly used antibiotics, which require more frequent dosing.

Study design: Phase 3, double-blinded RCT.

Setting: Multiple international centers.

Synopsis: Researchers randomized 1,312 patients with acute bacterial skin and skin-structure infections with signs of systemic infection requiring intravenous antibiotics to receive dalbavancin on days one and eight, with placebo on other days, or several doses of vancomycin with an option to switch to oral linezolid. The primary endpoint was cessation of spread of erythema and temperature of ≤37.6°C at 48-72 hours. Secondary endpoints included a decrease in lesion area of ≥20% at 48-72 hours and clinical success at end of therapy (determined by clinical and historical features).

Results of the primary endpoint were similar with dalbavancin and vancomycin-linezolid groups (79.7% and 79.8%, respectively) and were within 10 percentage points of noninferiority. The secondary endpoints were similar between both groups.

Limitations of the study were the early primary endpoint, lack of noninferiority analysis of the secondary endpoints, and cost-effective analysis.

Bottom line: Once-weekly dalbavancin appears to be similarly efficacious to intravenous vancomycin in the treatment of acute bacterial skin infections in terms of outcomes within 48-72 hours of therapy and might provide an alternative to continued inpatient hospitalization for intravenous antibiotics in stable patients.

Citation: Boucher HW, Wilcox M, Talbot GH, Puttagunta S, Das AF, Dunne MW. Once-weekly dalbavancin versus daily conventional therapy for skin infection. N Engl J Med. 2014;370(23):2169-2179.

Overuse of antibiotics is fueling antimicrobial resistance, posing a threat to people around the world and prompting increased attention to antibiotic stewardship practices. Good stewardship requires hospitals and clinicians to adopt coordinated interventions that focus on reducing inappropriate antibiotic prescribing while remaining focused on the health of patients.

Although it can seem overwhelming to physicians with busy workloads and sick patients to engage in these practices, not addressing the issue of responsible antibiotic prescribing is putting patients at risk.

“We know development of resistance is complicated,” says Arjun Srinivasan, MD, FSHEA, associate director for the CDC’s Healthcare Associated Infection Prevention Program and medical director of Get Smart for Healthcare in the CDC’s division of Healthcare Quality Promotion. Dr. Srinivasan is one of the authors of a recent CDC report on antibiotic prescribing practices across the U.S. “Nonetheless, we know that overuse of antibiotics leads to increases in resistance. We also know that if we can improve the way we prescribe them, we can reduce antibiotic resistance.”

The CDC recommends that hospitals adopt, at a minimum, the following antibiotic stewardship checklist:

• Commit leadership: Dedicate necessary human, financial, and information technology resources.
• Create accountability: Appoint a single leader responsible for program outcomes. Physicians have proven successful in this role.
• Provide drug expertise: Appoint a single pharmacist leader to support improved prescribing.
• Act: Take at least one prescribing improvement action, such as requiring reassessment within 48 hours to check drug choice, dose, and duration.
• Track: Monitor prescribing and antibiotic resistance patterns.
• Report: Regularly report to staff on prescribing and resistance patterns, as well as steps to improve.
• Educate: Offer education about antibiotic resistance and improving prescribing practices.
• Work with other healthcare facilities to prevent infections, transmission, and resistance.

These practices are not just the domain of infectious disease clinicians, either, says Neil Fishman, MD, chief patient safety officer and associate chief medical officer at the University of Pennsylvania Health System and past president of the Society for Healthcare Epidemiology of America. In 1992, Dr. Fishman helped establish an antibiotic stewardship program at Penn, working with infectious disease staff to identify and adopt best practices tailored to their needs.

Their efforts have shown promise in improving the health of their patients, he says, and many institutions that adopt stewardship programs typically see cost savings, too.

“These programs do usually end up decreasing drug costs but also increasing the quality of care,”

Dr. Fishman says. “If you can cut out 30% of unnecessary drugs, you cut drug costs. To me, that meets the true definition of value in healthcare.”

In one study that looked at stewardship-related cost reduction, primarily among larger healthcare settings, the average annual savings from reduced inappropriate antibiotic prescribing ranged from $200,000 to $900,000.

The recent CDC report, to which Dr. Srinivasan contributed, was published March 4 in Vital Signs. The study found that as many as a third of antibiotics prescribed are done so inappropriately. According to experts, hospitals and other healthcare institutions need to develop processes and standards to assist physicians in efforts to be responsible antibiotic prescribers.

“Sometimes, when you’re focusing on other issues, antibiotics are a bit of an afterthought,” says Scott Flanders, MD, FACP, MHM, professor of internal medicine and director of hospital medicine at University of Michigan Medical School in Ann Arbor.

“If there is not a checklist of processes [and] things are not accounted for in a systematic way, it doesn’t happen.”

Dr. Flanders and colleague Sanjay Saint, MD, MPH, the University of Michigan George Dock Collegiate professor of internal medicine and associate chief of medicine at the VA Ann Arbor Healthcare System, recently published an article in the Journal of the American Medical Association Internal Medicine in which they recommend the following:

• Antimicrobial stewardship programs, which aim to develop guidelines and implement programs that help optimize antibiotic use among hospitalized patients, should partner with front-line clinicians to tackle the problem.
• Clinicians should better document aspects of antibiotic use that can be shared with other providers caring for the same patient throughout his or her hospital stay and after discharge.
• Clinicians should take an “antibiotic time-out” after 48-72 hours of a patient’s use of antibiotics to reassess the use of these drugs.
• Treatment and its duration should be in line with evidence-based guidelines, and institutions should work to clearly identify appropriate treatment duration.
• Improved diagnostic tests should be available to physicians.
• Target diagnostic error by working to improve how physicians think when considering whether to provide antibiotics.
• Develop performance measures that highlight common conditions in which antibiotics are overprescribed, to shine a brighter light on the problem.

“I think we can make a lot of progress,” Dr. Flanders says. “The problem is complex; it developed over decades, and any solutions are unlikely to solve the problem immediately. But there are several examples of institutions and hospitals making significant inroads in a short period of time.” —KAT

Overuse of antibiotics is fueling antimicrobial resistance, posing a threat to people around the world and prompting increased attention to antibiotic stewardship practices. Good stewardship requires hospitals and clinicians to adopt coordinated interventions that focus on reducing inappropriate antibiotic prescribing while remaining focused on the health of patients.

Although it can seem overwhelming to physicians with busy workloads and sick patients to engage in these practices, not addressing the issue of responsible antibiotic prescribing is putting patients at risk.

“We know development of resistance is complicated,” says Arjun Srinivasan, MD, FSHEA, associate director for the CDC’s Healthcare Associated Infection Prevention Program and medical director of Get Smart for Healthcare in the CDC’s division of Healthcare Quality Promotion. Dr. Srinivasan is one of the authors of a recent CDC report on antibiotic prescribing practices across the U.S. “Nonetheless, we know that overuse of antibiotics leads to increases in resistance. We also know that if we can improve the way we prescribe them, we can reduce antibiotic resistance.”

The CDC recommends that hospitals adopt, at a minimum, the following antibiotic stewardship checklist:

• Commit leadership: Dedicate necessary human, financial, and information technology resources.
• Create accountability: Appoint a single leader responsible for program outcomes. Physicians have proven successful in this role.
• Provide drug expertise: Appoint a single pharmacist leader to support improved prescribing.
• Act: Take at least one prescribing improvement action, such as requiring reassessment within 48 hours to check drug choice, dose, and duration.
• Track: Monitor prescribing and antibiotic resistance patterns.
• Report: Regularly report to staff on prescribing and resistance patterns, as well as steps to improve.
• Educate: Offer education about antibiotic resistance and improving prescribing practices.
• Work with other healthcare facilities to prevent infections, transmission, and resistance.

These practices are not just the domain of infectious disease clinicians, either, says Neil Fishman, MD, chief patient safety officer and associate chief medical officer at the University of Pennsylvania Health System and past president of the Society for Healthcare Epidemiology of America. In 1992, Dr. Fishman helped establish an antibiotic stewardship program at Penn, working with infectious disease staff to identify and adopt best practices tailored to their needs.

Their efforts have shown promise in improving the health of their patients, he says, and many institutions that adopt stewardship programs typically see cost savings, too.

“These programs do usually end up decreasing drug costs but also increasing the quality of care,”

Dr. Fishman says. “If you can cut out 30% of unnecessary drugs, you cut drug costs. To me, that meets the true definition of value in healthcare.”

In one study that looked at stewardship-related cost reduction, primarily among larger healthcare settings, the average annual savings from reduced inappropriate antibiotic prescribing ranged from $200,000 to $900,000.

The recent CDC report, to which Dr. Srinivasan contributed, was published March 4 in Vital Signs. The study found that as many as a third of antibiotics prescribed are done so inappropriately. According to experts, hospitals and other healthcare institutions need to develop processes and standards to assist physicians in efforts to be responsible antibiotic prescribers.

“Sometimes, when you’re focusing on other issues, antibiotics are a bit of an afterthought,” says Scott Flanders, MD, FACP, MHM, professor of internal medicine and director of hospital medicine at University of Michigan Medical School in Ann Arbor.

“If there is not a checklist of processes [and] things are not accounted for in a systematic way, it doesn’t happen.”

Dr. Flanders and colleague Sanjay Saint, MD, MPH, the University of Michigan George Dock Collegiate professor of internal medicine and associate chief of medicine at the VA Ann Arbor Healthcare System, recently published an article in the Journal of the American Medical Association Internal Medicine in which they recommend the following:

• Antimicrobial stewardship programs, which aim to develop guidelines and implement programs that help optimize antibiotic use among hospitalized patients, should partner with front-line clinicians to tackle the problem.
• Clinicians should better document aspects of antibiotic use that can be shared with other providers caring for the same patient throughout his or her hospital stay and after discharge.
• Clinicians should take an “antibiotic time-out” after 48-72 hours of a patient’s use of antibiotics to reassess the use of these drugs.
• Treatment and its duration should be in line with evidence-based guidelines, and institutions should work to clearly identify appropriate treatment duration.
• Improved diagnostic tests should be available to physicians.
• Target diagnostic error by working to improve how physicians think when considering whether to provide antibiotics.
• Develop performance measures that highlight common conditions in which antibiotics are overprescribed, to shine a brighter light on the problem.

“I think we can make a lot of progress,” Dr. Flanders says. “The problem is complex; it developed over decades, and any solutions are unlikely to solve the problem immediately. But there are several examples of institutions and hospitals making significant inroads in a short period of time.” —KAT

Overuse of antibiotics is fueling antimicrobial resistance, posing a threat to people around the world and prompting increased attention to antibiotic stewardship practices. Good stewardship requires hospitals and clinicians to adopt coordinated interventions that focus on reducing inappropriate antibiotic prescribing while remaining focused on the health of patients.

Although it can seem overwhelming to physicians with busy workloads and sick patients to engage in these practices, not addressing the issue of responsible antibiotic prescribing is putting patients at risk.

“We know development of resistance is complicated,” says Arjun Srinivasan, MD, FSHEA, associate director for the CDC’s Healthcare Associated Infection Prevention Program and medical director of Get Smart for Healthcare in the CDC’s division of Healthcare Quality Promotion. Dr. Srinivasan is one of the authors of a recent CDC report on antibiotic prescribing practices across the U.S. “Nonetheless, we know that overuse of antibiotics leads to increases in resistance. We also know that if we can improve the way we prescribe them, we can reduce antibiotic resistance.”

The CDC recommends that hospitals adopt, at a minimum, the following antibiotic stewardship checklist:

• Commit leadership: Dedicate necessary human, financial, and information technology resources.
• Create accountability: Appoint a single leader responsible for program outcomes. Physicians have proven successful in this role.
• Provide drug expertise: Appoint a single pharmacist leader to support improved prescribing.
• Act: Take at least one prescribing improvement action, such as requiring reassessment within 48 hours to check drug choice, dose, and duration.
• Track: Monitor prescribing and antibiotic resistance patterns.
• Report: Regularly report to staff on prescribing and resistance patterns, as well as steps to improve.
• Educate: Offer education about antibiotic resistance and improving prescribing practices.
• Work with other healthcare facilities to prevent infections, transmission, and resistance.

These practices are not just the domain of infectious disease clinicians, either, says Neil Fishman, MD, chief patient safety officer and associate chief medical officer at the University of Pennsylvania Health System and past president of the Society for Healthcare Epidemiology of America. In 1992, Dr. Fishman helped establish an antibiotic stewardship program at Penn, working with infectious disease staff to identify and adopt best practices tailored to their needs.

Their efforts have shown promise in improving the health of their patients, he says, and many institutions that adopt stewardship programs typically see cost savings, too.

“These programs do usually end up decreasing drug costs but also increasing the quality of care,”

Dr. Fishman says. “If you can cut out 30% of unnecessary drugs, you cut drug costs. To me, that meets the true definition of value in healthcare.”

In one study that looked at stewardship-related cost reduction, primarily among larger healthcare settings, the average annual savings from reduced inappropriate antibiotic prescribing ranged from $200,000 to $900,000.

The recent CDC report, to which Dr. Srinivasan contributed, was published March 4 in Vital Signs. The study found that as many as a third of antibiotics prescribed are done so inappropriately. According to experts, hospitals and other healthcare institutions need to develop processes and standards to assist physicians in efforts to be responsible antibiotic prescribers.

“Sometimes, when you’re focusing on other issues, antibiotics are a bit of an afterthought,” says Scott Flanders, MD, FACP, MHM, professor of internal medicine and director of hospital medicine at University of Michigan Medical School in Ann Arbor.

“If there is not a checklist of processes [and] things are not accounted for in a systematic way, it doesn’t happen.”

Dr. Flanders and colleague Sanjay Saint, MD, MPH, the University of Michigan George Dock Collegiate professor of internal medicine and associate chief of medicine at the VA Ann Arbor Healthcare System, recently published an article in the Journal of the American Medical Association Internal Medicine in which they recommend the following:

• Antimicrobial stewardship programs, which aim to develop guidelines and implement programs that help optimize antibiotic use among hospitalized patients, should partner with front-line clinicians to tackle the problem.
• Clinicians should better document aspects of antibiotic use that can be shared with other providers caring for the same patient throughout his or her hospital stay and after discharge.
• Clinicians should take an “antibiotic time-out” after 48-72 hours of a patient’s use of antibiotics to reassess the use of these drugs.
• Treatment and its duration should be in line with evidence-based guidelines, and institutions should work to clearly identify appropriate treatment duration.
• Improved diagnostic tests should be available to physicians.
• Target diagnostic error by working to improve how physicians think when considering whether to provide antibiotics.
• Develop performance measures that highlight common conditions in which antibiotics are overprescribed, to shine a brighter light on the problem.

“I think we can make a lot of progress,” Dr. Flanders says. “The problem is complex; it developed over decades, and any solutions are unlikely to solve the problem immediately. But there are several examples of institutions and hospitals making significant inroads in a short period of time.” —KAT