The need for macrolides in hospitalised community-acquired pneumonia: propensity analysis

Abstract

on behalf of the TREAT Study Group ABSTRACT: The present study compared b-lactam macrolide (''combination'') therapy versus b-lactam alone (''monotherapy'') for hospitalised community-acquired pneumonia, using propensity scores to adjust for the differences between patients.A prospective multinational observational study was carried out. Baseline patient and infection characteristics were used to develop a propensity score for combination therapy. Patients were matched by the propensity score (three decimal point precision) and compared with 30-day mortality and hospital stay. The propensity score was used as a covariate in a logistic model for mortality.Patients treated with monotherapy (n5169) were older (mean¡SD age 70.6¡17.3 versus 65.0¡19.6 yrs), had a higher chronic diseases score and a different clinical presentation compared with patients treated with combination therapy (n5282). Unadjusted mortality was significantly higher with monotherapy (37 (22%) out of 169 versus 21 (7%) out of 282). Only 27 patients in the monotherapy group could be matched to 27 patients in the combination group using the propensity score. The mortality in these groups was identical, with three (11%) demises each. The multivariable odds ratio for mortality associated with combination therapy, adjusted for the propensity score and the Pneumonia Severity Index, was 0.69 (95% confidence interval 0.32-1.48).The benefit of combination therapy versus monotherapy cannot be reliably assessed in observational studies, since the propensity to prescribe these regimens differs markedly.

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

“…However, there are no randomized controlled trials comparing a single ␤-lactam with the same drug supplemented with a macrolide, and these recommendations are largely supported by observational studies of selected populations which have shown lower mortality rates for patients treated with ␤-lactam-macrolide combination therapy than those for patients treated with ␤-lactam monotherapy (21,35,74,180,301). However, other studies failed to show a benefit of macrolide-containing combinations (58,223). The synergy between ␤-lactams and macrolides against S. pneumoniae is not documented in vitro (172) or in vivo (115), although macrolides inhibit the production of the pneumococcal toxin, pneumolysin (8).…”

A review of macrolide based regiments for community-acquired pneumonia.

“…A study from three centers in Germany, Israel, and Italy compared mortality in CAP patients who received either a β -lactam (n=169) or a β -lactam plus a macrolide (n=282). 26 The mortality was 22% vs 7% (P=0.0001), respectively, but when the authors adjusted for confounding factors using propensity score matching to account for differences in each group, they were only able to compare 27 patients in each group, erasing any statistical difference. The differences they accounted for, and for which they excluded patients from analysis, were septic shock, mental status changes, and having an infiltrate on chest radiograph.…”

Diretrizes brasileiras para pneumonia adquirida na comunidade em adultos imunocompetentes - 2009

“…(87) Although most guidelines recommend empirical antibiotic coverage of atypical pathogens, there is controversy regarding the level of scientific evidence on which this practice is based. A recently published observational study involving hospitalized patients (n = 201) revealed that previous outpatient treatment with a beta-lactam antibiotic correlated with an increased possibility (approximately three times greater) of an atypical pathogen being present, whereas the possibility of pneumococci being present was reduced to one third.…”

“…(83,90) However, the validity of such observational studies is questionable. (87) Further prospective studies of such patients, comparing beta-lactam mono therapy with beta-lactam-macrolide combination therapy and electing the mortality rate as the primary outcome measure, are needed.…”