Table 1. Characteristics of the studies included in the meta-analysis.
| Study (yr) | Design | Enrolled patients | Study period | Age (mean or median*), yr / male, % | Disease severity score (mean) | Mechanical ventilation, % | Severe sepsis or septic shock, % | The isolation rate of Streptococcus pneumoniae / MDR bacteria, % | Mortality, % | Primary objective of study | Risk of bias * |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Adrie (2013) | Multicenter, prospective observational cohort study | 394, exclusion of COPD | 1997–2010 | 64*/69.5 | CURB-65 score (3.17); % of CURB-65 score 4–5 (43.4) | Invasive (52.5), noninvasive (14.7) | Severe sepsis (91.4), septic shock (38.6) | 17.5/11.2 | 27.2% (60-day mortality) | To compare the impact on 60-day mortality in patients admitted to the ICU for CAP using one (β-lactam†) or two antibiotics (β-lactam + macrolide, β-lactam + fluoroquinolone) | Low |
| Bratzler (2008) | Multicenter, retrospective observational cohort study | 880 | 1998–1999 and 2000–2001 | NR/NR | NR | NR | NR | NR | 12.8% (30-day mortality) | To evaluate associations between various antimicrobial regimens including 2nd or 3rd β-lactam + macrolide and 2nd or 3rd β-lactam + fluoroquinolone and risk-adjusted mortality in patients admitted with CAP | High |
| Gaillat (1994) | Multicenter, prospective randomized study | 102 | 1990–1991 | 62.7/NR | SAPS score (10.5) | 24.5 | NR | 34.3/1.9 | 11.7% (total hospital mortality) | To compare of the efficacy of penicillin G/ofloxacin vs. erythromycin/amoxicillin-clavulanate in patients with severe CAP. | High |
| Karhu (2013) | Single center, retrospective observational cohort study | 210 | 2000–2010 | 55*/64.7 | % of number of patients with IDSA/ATS severe CAP criteria (76.1) | 52.3 | 47.1 | 23.8/NR | 20.4% (30-day mortality), 24.2 (60-day mortality), 10.9 (ICU mortality) | To compare the outcome of patients with severe CAP treated with the combination of 2nd or 3rd β-lactam + fluoroquinolone vs. 2nd or 3rd β-lactam + macrolide | Low |
| Martin-Loeches (2010) | Multicenter, prospective observational cohort study | 100 | 2007–2008 | 57.6/61 | SAPS II score (46.9); SOFA score (7.68) | 100 | 92 | NR | 37% (ICU mortality) | To access the effect on survival of 3rd or 4th β-lactam + macrolides or 3rd or 4th β-lactam + fluoroquinolones in intubated patients admitted to the ICU with severe CAP | High |
| Mortensen (2006) | Two center, retrospective observational cohort study | 137 | 1999–2002 | 63/88 | % of pneumonia severity index class IV/V (76.7) | NR | NR | 36.5/NR | 21.8% (30-day mortality) | To compare the mortality of patients with severe CAP treated with either 2nd or 3rd β-lactam + fluoroquinolone or other recommended antibiotics | High |
| Waterer (2001) | Single center, retrospective observational cohort study | 61 | 1996–2000 | 61.1/NR | Pneumonia severity index score (101) | NR | NR | NR | 8.1% (total hospital mortality) | To evaluate the outcome of various combination of antibiotics including 3rd β-lactam + macrolide and 3rd β-lactam + fluoroquinolone in patients with severe bacteremic CAP | High |
| Wilson (2012) | Multicenter, retrospective observational cohort study | 1,989 | 2001–2007 | 74/98.5 | NR | 39.3 | 23.6 | NR | 25.6% (30-day mortality) | To compare the outcome of elderly patients (aged > 65 yr) with severe CAP treated with the combination of either 2nd or 3rd β-lactam + fluoroquinolone or 2nd or 3rd β-lactam + macrolide | Low |
NR = not reported, COPD = chronic obstructive pulmonary disease, CURB-65 = confusion, blood urea nitrogen, respiratory rate, blood pressure, age > 65, ICU = intensive care unit, CAP = community-acquired pneumonia, SAPS = simplified acute physiology score, IDSA/ATS = Infectious Diseases Society of America/American Thoracic Society, SOFA = sequential organ failure assessment.
*The risk of bias in observational trials and randomized controlled trials was assessed using the Newcastle-Ottawa quality assessment scale (NOS) and Cochrane risk of bias tool, respectively; †β-lactam included penicillin and cephalosporin. When we could find the generation of cephalosporin from original articles, we added ‘2nd,’ ‘3rd or 4th’ into β-lactam. When original articles did not describe anything about the generation of cephalosporin, we used only ‘β-lactam’ without addition of ‘2nd,’ ‘3rd or 4th.’ 2nd, 3rd, and 4th means second generation, third generation, and fourth generation, respectively.