Table 3.
More recent studies on benefits of beta-lactam macrolide combination antibiotic therapy in terms of outcome in adults hospitalized for CAP.
| Study, Year | Country | Patient Number | Type of Study | Site of Care | Comparison | Measure of Severity of Illness | Outcomes |
|---|---|---|---|---|---|---|---|
| Ito et al. 2019 [97] | Japan | 1131 | Prospective cohort study. Hospitalized cases. |
Non-ICU | BL versus BLM | PSI, CURB-65, IDSA/ATS criteria were measured. Patients were classified as mild, moderate, or severe. |
Based on PSI and CURB-65 severity scores, combination therapy did not reduce 30-day mortality, in either treatment group. Based on IDSA/ATS criteria for severity, combination therapy significantly reduced 30-day mortality in severe, but not non-severe pneumonia (OR 0.12; 95%CI 0.007–0.57). |
| Ceccato et al. 2019 [95] | Spain | 1715 | Prospective observational cohort study. Hospitalized cases of known microbial etiology. |
ICU and non-ICU cases | BL plus FQ or FQ alone versus BLM | High inflammatory response (CRP > 15 mg/dL) | BLM had a protective effect on mortality only in cases with a high inflammatory response and pneumococcal CAP (adjusted OR 0.28; 95% CI 0.09–0.93), but not in those without a high inflammatory response and pneumococcal CAP or with other etiologies. |
| Shorr et al. 2021 [107] | USA | 140 | Retrospective cohort study of hospitalized patients with pneumococcal pneumonia, including cases with M-resistant pathogens | ICU | Comparison of outcomes in patients treated with antibiotic therapy with or without a M | Markers of acute and chronic disease (e.g., Charlson score, need for mechanical ventilation, and/or vasopressors and APACHE II) | The addition of M to the antibiotic regimen was associated with significant reduction in in-hospital mortality independent of multiple co-variates (adjusted odds ratio of death in those on macrolide 0.27; 95% CI 0.09–0.85; p = 0.024). |
| Goncalves-Pereira et al.2022 [96] | Portugal | 797 | Prospective multicenter study of hospitalized patients with pneumococcal CAP (bacteremic or non-bacteremic) with at least one comorbidity | ICU and non-ICU | Assessment of the benefit of BLM therapy versus non-BLM therapy in cases with and without bacteremia | - | Patients with bacteremia had higher 30-day all-cause mortality and BLM was beneficial only in patients with bacteremia (30-day all-cause mortality 18.9% versus 36.1%, aHR 0.49; 95% CI 0.30–0.80; p = 0.004). After 1-year follow-up, patients with bacteremia who had BLM still had a lower all-cause mortality (31.3% versus 48.1%; p = 0.009). |
| Chowers et al. 2023 [78] |
Israel | 2016 | Part of an ongoing prospective population-based active surveillance study of adult cases with bacteremic pneumococcal pneumonia. | ICU and non-ICU cases | BLM versus other antibiotic therapy with no macrolide | Patients classified as no-risk, at-risk, and high-risk of invasive pneumococcal disease | Macrolide therapy for as short as two days was protective against mortality (OR 0.549; 95% CI 0.391–0.771). |
Abbreviations: ICU (intensive care unit); BL (beta-lactam); BLM (beta-lactam/macrolide combination FQ (fluoroquinolone); PSI (pneumonia severity index); CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥ 65 years); OR (odds ratio); aHR (adjusted hazards ratio).