title: Beta-lactam plus macrolides or beta-lactam alone for community-acquired pneumonia: A systematic review and meta-analysis.
abstract: It is unclear whether in the treatment of community-acquired pneumonia (CAP) beta-lactam plus macrolide antibiotics lead to better survival than beta-lactam alone. We report a systematic review and meta-analysis. Trials and observational studies published in English were included, if they provided sufficient data on odds ratio for all-cause mortality for a beta-lactam plus macrolide regimen compared with beta-lactam alone. Two investigators independently searched for eligible articles. Of 514 articles screened, 14 were included: two open-label randomized controlled trials (RCTs) comprising 1975 patients, one non-RCT interventional study comprising 1011 patients and 11 observational studies comprising 33 332 patients. Random-model meta-analysis yielded an odds ratio for all-cause death for beta-lactam plus macrolide compared with beta-lactam alone of 0.80 (95% CI 0.69-0.92, P = 0.002) with substantial heterogeneity (I(2)  = 59%, P for heterogeneity = 0.002). Severity-based subgroup analysis and meta-regression revealed that adding macrolide had a favourable effect on mortality only for severe CAP. Of the two RCTs, one suggested that macrolide plus beta-lactam lead to better outcome compared with beta-lactam alone, while the other did not. Subgrouping based on study design, that is, RCT versus non-RCT, which was almost identical to subgrouping based on severity, revealed substantial inter-subgroup heterogeneity. Compared with beta-lactam alone, beta-lactam plus macrolide may decrease all-cause death only for severe CAP. However, this conclusion is tentative because this was based mainly on observational studies.
authors.affiliation: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. horitano@yokohama-cu.ac.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Horita
authors.affiliation: Department of Pulmonology, Tohoku Rosai Hospital, Sendai, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Otsuka
authors.affiliation: Department of Infectious Diseases, Respiratory and Digestive Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Shusaku
authors.initials: S
authors.lastname: Haranaga
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Ho
authors.initials: H
authors.lastname: Namkoong
authors.affiliation: Department of Respiratory Medicine, Japanese Red Cross Sendai Hospital, Sendai, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Miki
authors.affiliation: Department of Internal Medicine I, Kawasaki Medical School, Okayama, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miyashita
authors.affiliation: National Hospital Organization Okinawa National Hospital, Okinawa, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Higa
authors.affiliation: Department of Respiratory Medicine, Saka General Hospital, Miyagi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Hemodialysis and Surgery, Chemotheraphy Research Institute, International University of Health and Welfare, Ichikawa, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
authors.affiliation: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017714:Community-Acquired Infections / Q000188:drug therapy*; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D047090:beta-Lactams
keywords: anti-inflammatory effect; antibiotics; infectious disease; meta-regression; mortality