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Antibiotic escalations are frequently guided by fever persistence. Unnecessary antibiotic escalation is associated with resistance induction. We examined whether fever persistence is associated with adverse outcomes among medical inpatients with sepsis. In a single-center prospective cohort study, we included consecutive medical inpatients with suspected or documented bacterial infections. Data were collected on days 0, 2, 4, and 30 days from episode onset. We examined the association between fever persistence at 4 days and 30-day mortality on univariate and multivariate analysis. Inappropriate empirical antibiotic treatment (IAET) was defined for patients with microbiologically documented infections (MDIs). Odds ratios (ORs) are presented with 95 % confidence intervals (CIs). A total of 1,621 patients were included. Among patients with MDIs, 38/206 (18.4 %) given appropriate empiric therapy had continued fever on day 4, compared to 64/231 (27.7 %) of patients receiving IAET, OR 0.59, 95 % CI 0.37-0.93. Fever persistence was not associated with mortality after adjustment for other risk factors. Among patients with presumed sepsis who did not have MDIs, persistent fever was significantly associated with 30-day mortality on a multivariate analysis, adjusted OR 2.77 (95 % CI 1.78-4.31). Other risk factors for mortality included older age, nosocomial infections, malignancy, dyspnea, shock, decreased albumin, and elevated creatinine. For patients with MDIs, fever persistence for up to 4 days is a marker of IAET, but is not associated with mortality, and should not, in itself, trigger antibiotic escalation. For patients without MDIs, fever persistence should trigger careful re-evaluation, as it is associated with mortality. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2012; 18: 18-29 Abstract Colistin has been re-introduced into clinical practice for the treatment of carbapenem-resistant Gram-negative bacteria. Studies in the last decade attempted to reconstruct the path that present-day medications undergo prior to clinical use. In this review, we summarize the results of recent clinical studies. Colistin was associated with lower mortality than no effective treatment and higher unadjusted mortality than β-lactams in non-randomized clinical studies. However, it was administered to sicker patients with carabapenem-resistant bacteria. Overall, nephrotoxicity rates were not higher with colistin in these studies, and colistin-induced nephrotoxicity is reversible in most patients. The emergence of colistin resistance has been described in high-use settings. Synergy with carbapenem, rifampin and other antibiotics has been reported in vitro. Randomized controlled trials are ongoing or in planning to assess this and other aspects of colistin use in clinical practice. [ABSTRACT FROM AUTHOR]