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Quantifying the benefit of early antibiotic treatment is crucial for decision making and can be assessed only in observational studies. We performed a systematic review of prospective studies reporting the effect of appropriate empirical antibiotic treatment on all-cause mortality among adult inpatients with sepsis. Two reviewers independently extracted data. Risk of bias was assessed using the Newcastle-Ottawa score. We calculated unadjusted odds ratios (ORs) with 95% confidence intervals for each study and extracted adjusted ORs, with variance, methods, and covariates being used for adjustment. ORs were pooled using random-effects meta-analysis. We examined the effects of methodological and clinical confounders on results through subgroup analysis or mixed-effect meta-regression. Seventy studies were included, of which 48 provided an adjusted OR for inappropriate empirical antibiotic treatment. Inappropriate empirical antibiotic treatment was associated with significantly higher mortality in the unadjusted and adjusted comparisons, with considerable heterogeneity occurring in both analyses (I 2 > 70%). Study design, time of mortality assessment, the reporting methods of the multivariable models, and the covariates used for adjustment were significantly associated with effect size. Septic shock was the only clinical variable significantly affecting results (it was associated with higher ORs). Studies adjusting for background conditions and sepsis severity reported a pooled adjusted OR of 1.60 (95% confidence interval ‫؍‬ 1.37 to 1.86; 26 studies; number needed to treat to prevent one fatal outcome, 10 patients [95% confidence interval ‫؍‬ 8 to 15]; I 2 ‫؍‬ 46.3%) given 34% mortality with inappropriate empirical treatment. Appropriate empirical antibiotic treatment is associated with a significant reduction in all-cause mortality. However, the methods used in the observational studies significantly affect the effect size reported. Methods of observational studies assessing the effects of antibiotic treatment should be improved and standardized.Sepsis affects 1.1 to 2.4 per 1,000 people per year and 20 to 42% of these patients die in hospital, with these rates probably underestimating the contribution of hospital-acquired infections (3, 16, 61). Septicemia and pneumonia combined are the sixth most common causes of death in the United States (36). Antibiotic treatment for the first 24 to 48 h is largely empirical (i.e., provided without evidence on the causative pathogen or its susceptibilities), and it is common wisdom that appropriate empirical antibiotic treatment (i.e., matching the in vitro susceptibilities of the isolated pathogens) reduces mortality. Physicians thus strive to achieve appropriate empirical antibiotic treatment for inpatients with suspected infections, and many times this is at the cost of administering superfluous and unnecessary antibiotics. Such treatment is associated with resistance development (83, 97) and side effects with no benefit.Estimates of the potential benefit of appropriate em...

Appropriate empirical antibiotic treatment was associated with a significant reduction in fatality in patients with bloodstream infection.

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Antibiotic prophylaxis for neutropenic patients undergoing cytotoxic therapy reduces mortality. Mortality was substantially reduced when analysis was limited to fluoroquinolones. Antibiotic prophylaxis, preferably with a fluoroquinolone, should be considered for neutropenic patients.

Background Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited. Methods This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative, or distant complications; and readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%. Results We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in 3 centers in Israel and Italy. The source of the infection was urinary in 411 of 604 patients (68%); causative pathogens were mainly Enterobacteriaceae (543/604 [90%]). A 7-day difference in the median duration of covering antibiotics was achieved. The primary outcome occurred in 140 of 306 patients (45.8%) in the 7-day group vs 144 of 298 (48.3%) in the 14-day group (risk difference, –2.6% [95% confidence interval, –10.5% to 5.3%]). No significant differences were observed in all other outcomes and adverse events, except for a shorter time to return to baseline functional status in the short-course therapy arm. Conclusions In patients hospitalized with gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was noninferior to 14 days. Reducing antibiotic treatment for uncomplicated gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention. Clinical Trials Registration NCT01737320.