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Antibiotic Therapy for Adults Hospitalized With Community-Acquired Pneumonia A Systematic Review

Jonathan S. Lee, MD1,2; Daniel L. Giesler, MD, PharmD1; Walid F. Gellad, MD, MPH1,3; Michael J. Fine, MD, MSc1,3
[+] Author Affiliations
1Division of General Internal Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
2Now with Division of General Internal Medicine, Department of Medicine, University of California, San Francisco
3Center for Health Equity Research and Promotion, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
JAMA. 2016;315(6):593-602. doi:10.1001/jama.2016.0115.
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Importance  Antibiotic therapy is the cornerstone of medical management for community-acquired pneumonia.

Objective  To assess the associations between 3 key aspects of antibiotic therapy (optimal time to antibiotic initiation, initial antibiotic selection, and criteria for the transition from intravenous to oral therapy) and short-term mortality in adults hospitalized with community-acquired pneumonia.

Evidence Review  Bibliographic databases of MEDLINE, EMBASE, and the Cochrane Collaboration were searched for studies of adults hospitalized with radiographically confirmed community-acquired pneumonia published from January 1, 1995, until November 5, 2015.

Findings  Twenty studies (17 observational and 3 randomized trials) met eligibility criteria. Among 8 observational studies identified, the 4 largest (study populations of 2878 to 1 170 022) found that antibiotic initiation within 4 to 8 hours of hospital arrival was associated with relative reductions of 5% to 43% in mortality; the 4 smallest studies (study populations of 451 to 2076) found no associations between the timing of antibiotic initiation and mortality. One cluster randomized trial (n = 1737) demonstrated noninferiority of β-lactam monotherapy (n = 506) vs β-lactam plus macrolide combination therapy (n = 566), with an absolute adjusted difference of 2.5% (90% CI, −0.6% to 5.2%) in 90-day mortality favoring β-lactam monotherapy. A second randomized trial (n = 580) failed to demonstrate noninferiority of β-lactam monotherapy vs β-lactam plus macrolide combination therapy, with an absolute difference of 7.6% (1-sided 90% CI upper limit, 13.0%) in attainment of clinical stability on hospital day 7 favoring β-lactam plus macrolide combination therapy. Six of 8 observational studies (study populations of 1188 to 24 780) found that β-lactam plus macrolide combination therapy was associated with relative reductions of 26% to 68% in short-term mortality and all 3 observational studies (study populations of 2068 to 24 780) reported that fluoroquinolone monotherapy was associated with relative reductions of 30% to 43% in mortality compared with β-lactam monotherapy. One randomized trial (n = 302) reported significantly reduced hospital length of stay (absolute difference, 1.9 days; 95% CI, 0.6 to 3.2 days), but no differences in treatment failure when objective clinical criteria were used to decide when to transition patients from intravenous to oral therapy.

Conclusions and Relevance  In adults hospitalized with community-acquired pneumonia, antibiotic therapy consisting of β-lactam plus macrolide combination therapy or fluoroquinolone monotherapy initiated within 4 to 8 hours of hospital arrival was associated with lower adjusted short-term mortality, supported predominantly by low-quality observational studies. One randomized trial supports the use of objective clinical criteria to guide the transition from intravenous to oral antibiotic therapy.

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Figure 1.
Studies Assessing Initiation of Antibiotic Therapy Within Various Time Thresholds and Short-term Mortality for Patients Hospitalized With Community-Acquired Pneumonia

Time threshold evaluated <4 h. Some values were estimated based on available data. NR indicates not reported; OR, odds ratio.

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Figure 2.
Studies Assessing Short-term Mortality for β-Lactam Plus Macrolide Combination Therapy or Respiratory Fluoroquinolone Monotherapy vs β-Lactam Monotherapy for Patients Hospitalized With Community-Acquired Pneumonia

Some values were estimated based on available data. NR indicates not reported; OR, odds ratio.

aUnless otherwise indicated.

bHazard ratio not adjusted OR.

cData collected in 1993.

dData collected in 1995.

eData collected in 1997.

fCalculated using available data and is unadjusted.

gData are for subgroup with radiographically confirmed pneumonia.

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