Therapeutics
Review: Short and long courses of antibiotics do not differ for mortality in ventilator-associated pneumonia
Dimopoulos G, Poulakou G, Pneumatikos IA, et al. Short- vs longduration antibiotic regimens for ventilator-associated pneumonia: a systematic review and meta-analysis. Chest. 2013;144:1759-67.
Clinical impact ratings: c ★★★★★✩✩ p ★★★★★✩✩ Question
Source of funding: No external funding.
In patients with ventilator-associated pneumonia (VAP), what is the relative efficacy of short and long courses of antibiotics?
For correspondence: Dr. D.K. Matthaiou, Attikon University Hospital, Athens, Greece. E-mail [email protected]. ■
Review scope
Commentary
Included studies compared short (≤ 8 d) and long (≥ 10 d) courses of antibiotics in patients with VAP diagnosed by culture, with or without complementary imaging, laboratory, or microbiologic criteria. Trials had to report any of mortality, antibiotic-free days, VAP relapse, mechanical ventilation–free days, duration of mechanical ventilation, or length of intensive care unit (ICU) stay.
Review methods MEDLINE and Cochrane Central Register of Controlled Trials (Nov 2012), and reference lists were searched for randomized controlled trials (RCTs). Conference abstracts were excluded. 4 RCTs (n = 883) met the selection criteria. Trial size ranged from 30 to 401 patients. 2 RCTs included patients with late-onset VAP, 1 included patients with early-onset VAP, and 1 included patients with both types of VAP. All RCTs had Jadad quality scores ≥ 3 out of 5; 2 RCTs were blinded.
Main results The short-course group had more antibiotic-free days than the long-course group, but groups did not differ for mortality, relapse, mechanical ventilation–free days, duration of mechanical ventilation, or length of ICU stay (Table).
Conclusion In patients with ventilator-associated pneumonia, short antibiotic courses reduce the number of days on antibiotics but do not affect mortality or relapses compared with long courses. Short (≤ 8 d) vs long (≥ 10 d) courses of antibiotics in ventilatorassociated pneumonia* Outcomes
Number of trials (n)
Weighted event rates Short Long course course
Mortality
4 (883)
18%
15%
Relapse
3 (656)
13%
8%
At 28 d RRI (95% CI)
NNH (CI)
16% (−14 to 55)
NS
59% (−0.9 to 147)
NS
Weighted mean difference (CI) Antibiotic-free days
2 (431)
3.40 (1.43 to 5.37)
Mechanical ventilation– free days
2 (NA)
0.75 (−0.32 to 1.82)
Duration of mechanical ventilation (d)
2 (NA)
0.15 (−1.12 to 1.42)
Length of ICU stay (d)
3 (NA)
0.16 (−0.99 to 1.31)
*NA = not available; NS = not significant; other abbreviations defined in Glossary. Weighted short-course event rate, RRI, and CI calculated from control event rates and odds ratios in article using a fixed-effect model.
20 May 2014 | ACP Journal Club | Volume 160 • Number 10 Downloaded From: http://annals.org/ by a Univ of Utah User on 12/02/2014
VAP is one of the most common nosocomial infections and is associated with high morbidity, mortality, and health care costs. The ideal duration of antibiotic treatment for VAP remains undefined. Although shorter antibiotic courses may be desirable to minimize the risk for antimicrobial resistance and drug toxicity, it is important also to ensure that clinical outcomes are at least unchanged, if not improved. In their meta-analysis, Dimopoulos and colleagues showed that antibiotic courses ≤ 8 days increased antibiotic-free days without increasing mortality compared with courses ≥ 10 days. However, a trend toward higher relapse rates was observed. This finding was heavily weighted by 1 large RCT (1) in which relapses were more common in patients with VAP due to nonfermenting gramnegative bacteria (largely Pseudomonas species). An important proviso is that, overall, relapses were probably overestimated by inclusion of cases with colonization (rather than true infection) by virtue of the investigators’ definition of relapse. The strengths of this meta-analysis include a clear objective, inclusion of trials with acceptable quality standards, rigorous review methodology, and sensitivity analyses. Weaknesses include the small number of RCTs analyzed, which makes assessing for publication bias difficult; inclusion of early-onset VAP (which could, in fact, represent community-acquired pneumonia); and lack of long-term outcome data. The results suggest that short-course therapy for VAP is a reasonable alternative to longer antibiotic courses, with the caveat that close monitoring is needed as well as a low threshold to reevaluate and restart therapy if clinical deterioration or nonresolving signs and symptoms develop. The findings also underscore the need to further elucidate the “true” noninferiority of short antibiotic courses by measuring the clinical consequences and financial cost of relapse. Larger RCTs with reproducible and reliable definitions for VAP, uniform antibiotic administration, and more stringent criteria for identifying relapses are needed (2). Sameer S. Kadri, MD Naomi P. O’Grady, MD National Institutes of Health Clinical Center Bethesda, Maryland, USA References 1. Chastre J, Wolff M, Fagon JY, et al; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290:2588-98. 2. Magill SS, Klompas M, Balk R, et al. Developing a new, national approach to surveillance for ventilator-associated events: executive summary. Clin Infect Dis. 2013;57:1742-6.
© 2014 American College of Physicians
JC3
Review: Short and long courses of antibiotics do not differ for mortality in ventilator-associated pneumonia
Dimopoulos G, Poulakou G, Pneumatikos IA, et al. Short- vs longduration antibiotic regimens for ventilator-associated pneumonia: a systematic review and meta-analysis. Chest. 2013;144:1759-67.
Clinical impact ratings: c ★★★★★✩✩ p ★★★★★✩✩ Question
Source of funding: No external funding.
In patients with ventilator-associated pneumonia (VAP), what is the relative efficacy of short and long courses of antibiotics?
For correspondence: Dr. D.K. Matthaiou, Attikon University Hospital, Athens, Greece. E-mail [email protected]. ■
Review scope
Commentary
Included studies compared short (≤ 8 d) and long (≥ 10 d) courses of antibiotics in patients with VAP diagnosed by culture, with or without complementary imaging, laboratory, or microbiologic criteria. Trials had to report any of mortality, antibiotic-free days, VAP relapse, mechanical ventilation–free days, duration of mechanical ventilation, or length of intensive care unit (ICU) stay.
Review methods MEDLINE and Cochrane Central Register of Controlled Trials (Nov 2012), and reference lists were searched for randomized controlled trials (RCTs). Conference abstracts were excluded. 4 RCTs (n = 883) met the selection criteria. Trial size ranged from 30 to 401 patients. 2 RCTs included patients with late-onset VAP, 1 included patients with early-onset VAP, and 1 included patients with both types of VAP. All RCTs had Jadad quality scores ≥ 3 out of 5; 2 RCTs were blinded.
Main results The short-course group had more antibiotic-free days than the long-course group, but groups did not differ for mortality, relapse, mechanical ventilation–free days, duration of mechanical ventilation, or length of ICU stay (Table).
Conclusion In patients with ventilator-associated pneumonia, short antibiotic courses reduce the number of days on antibiotics but do not affect mortality or relapses compared with long courses. Short (≤ 8 d) vs long (≥ 10 d) courses of antibiotics in ventilatorassociated pneumonia* Outcomes
Number of trials (n)
Weighted event rates Short Long course course
Mortality
4 (883)
18%
15%
Relapse
3 (656)
13%
8%
At 28 d RRI (95% CI)
NNH (CI)
16% (−14 to 55)
NS
59% (−0.9 to 147)
NS
Weighted mean difference (CI) Antibiotic-free days
2 (431)
3.40 (1.43 to 5.37)
Mechanical ventilation– free days
2 (NA)
0.75 (−0.32 to 1.82)
Duration of mechanical ventilation (d)
2 (NA)
0.15 (−1.12 to 1.42)
Length of ICU stay (d)
3 (NA)
0.16 (−0.99 to 1.31)
*NA = not available; NS = not significant; other abbreviations defined in Glossary. Weighted short-course event rate, RRI, and CI calculated from control event rates and odds ratios in article using a fixed-effect model.
20 May 2014 | ACP Journal Club | Volume 160 • Number 10 Downloaded From: http://annals.org/ by a Univ of Utah User on 12/02/2014
VAP is one of the most common nosocomial infections and is associated with high morbidity, mortality, and health care costs. The ideal duration of antibiotic treatment for VAP remains undefined. Although shorter antibiotic courses may be desirable to minimize the risk for antimicrobial resistance and drug toxicity, it is important also to ensure that clinical outcomes are at least unchanged, if not improved. In their meta-analysis, Dimopoulos and colleagues showed that antibiotic courses ≤ 8 days increased antibiotic-free days without increasing mortality compared with courses ≥ 10 days. However, a trend toward higher relapse rates was observed. This finding was heavily weighted by 1 large RCT (1) in which relapses were more common in patients with VAP due to nonfermenting gramnegative bacteria (largely Pseudomonas species). An important proviso is that, overall, relapses were probably overestimated by inclusion of cases with colonization (rather than true infection) by virtue of the investigators’ definition of relapse. The strengths of this meta-analysis include a clear objective, inclusion of trials with acceptable quality standards, rigorous review methodology, and sensitivity analyses. Weaknesses include the small number of RCTs analyzed, which makes assessing for publication bias difficult; inclusion of early-onset VAP (which could, in fact, represent community-acquired pneumonia); and lack of long-term outcome data. The results suggest that short-course therapy for VAP is a reasonable alternative to longer antibiotic courses, with the caveat that close monitoring is needed as well as a low threshold to reevaluate and restart therapy if clinical deterioration or nonresolving signs and symptoms develop. The findings also underscore the need to further elucidate the “true” noninferiority of short antibiotic courses by measuring the clinical consequences and financial cost of relapse. Larger RCTs with reproducible and reliable definitions for VAP, uniform antibiotic administration, and more stringent criteria for identifying relapses are needed (2). Sameer S. Kadri, MD Naomi P. O’Grady, MD National Institutes of Health Clinical Center Bethesda, Maryland, USA References 1. Chastre J, Wolff M, Fagon JY, et al; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290:2588-98. 2. Magill SS, Klompas M, Balk R, et al. Developing a new, national approach to surveillance for ventilator-associated events: executive summary. Clin Infect Dis. 2013;57:1742-6.
© 2014 American College of Physicians
JC3
