Observational studies assessingβ-lactam macrolide combination therapy versus β-lactams alone among adult patients hospitalised with pneumonia
| First author [Ref.] | Study design | Patient characteristics | Baseline differences reported between patient groups | Adjustment variables for the comparison between treatments | Outcomes assessed | Results for the comparison of combination versus monotherapy |
| Aspa 25 | Prospective | 638 patients with CAP due to Streptococcus pneumoniae | Lower PSI class with monotherapy, otherwise not reported | Risk factors for mortality | 30-day survival | No significant difference |
| Baddour 11 | Prospective | 582 adults with pneumococcal bacteremia | Among severely ill patients, HIV and mechanical ventilation associated with monotherapy# | HIV and mechanical ventilation | 14-day mortality | No significant difference overall; significantly higher among severely ill patients |
| Burgess 26 | Retrospective | 213 adults with CAP and no organism specified | Combination patients, younger, less severely ill | Baseline differences between treatment groups | Length of stay mortality | No difference |
| Dudas 9 | Prospective | 2963 adults with an admission diagnosis of physician-presumed CAP | Not reported | Risk factors for mortality identified on univariate analysis | Length of hospital stay; in-hospital mortality | Both significantly lower with combination among non-ICU patients |
| Dwyer 27 | Retrospective analysis of prospectively collected data | 370 adult patients with bacteremic pneumococcal CAP | IVDU, liver disease, higher APACHE score and APS associated with combination; cardiac disease associated with monotherapy | Risk factors for mortality, including the APS score | Mortality | No difference |
| Garcia Vazquez 12 | Retrospective analysis of prospectively collected data | 1188 adults with CAP | PSI class IV associated with monotherapy; older age associated with combination | PSI | In-hospital mortality (after 24 h) | Significantly lower with combination |
| Gleason 6 | Retrospective | 12945 community- or long-term care facility dwelling patients ≥65 yrs old with CAP | Monotherapy more common among patients admitted from long-term care facility; combinations more common in lower PSI risk classes | Previously known risk factors for mortality | 30-day mortality | Significantly lower with combination therapy or fluouroquinolone monotherapy |
| Houck 7 | Retrospective | 10069 patients ≥65 yrs old from the community or nursing facilities with CAP | Combination more common in lower risk classes, other differences not reported | PSI and other risk factors for mortality | 30-day mortality | Significantly lower with combination, or quinolone/macrolide monotherapy; yearly fluctuation |
| Loh 28 | Prospective | 141 adults with CAP | No significant differences in age and comorbidity scores | Unadjusted, stratified by severe pneumonia | In-hospital mortality; length of hospital stay | No difference |
| Martinez 13 | Retrospective analysis of prospectively collected data | 409 adults with bacteremic pneumococcal pneumonia | Monotherapy associated with fatal and nonfatal comorbidities; combination associated with shock and ICU admission | Risk factors for mortality identified on univariate analysis | In-hospital mortality | Lower with combination |
| Metersky 10 | Retrospective | 2349 episodes of bacteremic pneumonia among adults admitted from home or a nursing facility | No atypical coverage associated with older age, admission from nursing home, higher PSI and longer time to antibiotic initiation | Risk factors for mortality | 30-day mortality; in-hospital mortality; hospital readmission | All significantly lower with macrolides, but not with quinolones or teteracyclines |
| Mufson 15, 29 | Retrospective | 328 adults and 45 children with bacteremic pneumococcal pneumonia | No significant differences observed | Unadjusted | In-hospital mortality | Lower with combination |
| Stahl 8 | Prospective | 67 adults with CAP | Monotherapy associated with nursing home residence; no differences in age and PSI score | Adjusted for admission from nursing home | Length of hospital stay | Significantly shorter with combination |
| Waterer 14 | Retrospective | 225 adults with bacteremic pneumococcal CAP | Monotherapy associated with significantly higher APACHE and PSI scores; chronic organ failure not significantly different | Risk factors for mortality | Mortality | Significantly lower with dual effective combination therapy |
| Weiss 16 | Retrospective | 95 adults with bacteremic pneumococcal CAP | Similar PSI score, otherwise not reported | Unadjusted | Mortality | Significantly lower with combination therapy |
CAP: community-acquired pneumonia; PSI: Pneumonia Severity Index; ICU: intensive care unit; IVDU: intravenous drug abuse; APACHE: Acute Physiology and Chronic Health Evaluation; APS: acute physiology score. #: monotherapy in this study was not limited to β-lactam alone.