International guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin are considered second-line agents. Our objective was to assess the evidence for the efficiency and safety of all vasopressors in septic shock. Systematic review and meta-analysis. We searched electronic database of MEDLINE, CENTRAL, LILACS and conference proceedings up to June 2014. We included randomized controlled trials comparing different vasopressors for the treatment of adult patients with septic shock. Primary outcome was all-cause mortality. Other clinical and hemodynamic measurements were extracted as secondary outcomes. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) were pooled. Thirty-two trials (3,544 patients) were included. Compared to dopamine (866 patients, 450 events), norepinephrine (832 patients, 376 events) was associated with decreased all-cause mortality, RR 0.89 (95% CI 0.81-0.98), corresponding to an absolute risk reduction of 11% and number needed to treat of 9. Norepinephrine was associated with lower risk for major adverse events and cardiac arrhythmias compared to dopamine. No other mortality benefit was demonstrated for the comparisons of norepinephrine to epinephrine, phenylephrine and vasopressin / terlipressin. Hemodynamic data were similar between the different vasopressors, with some advantage for norepinephrine in central venous pressure, urinary output and blood lactate levels. Evidence suggests a survival benefit, better hemodynamic profile and reduced adverse events rate for norepinephrine over dopamine. Norepinephrine should be regarded as the first line vasopressor in the treatment of septic shock.

Tigecycline is a novel glycylcycline that exhibits broad-spectrum antibacterial activity. Recently, the US FDA issued a warning concerning increased mortality with tigecycline in randomized controlled trials (RCTs). We conducted a systematic review and meta-analysis of RCTs that compared tigecycline with any other antibiotic regimen for the treatment of any infection. A comprehensive search, without publication status or other restrictions, was conducted. The primary outcome was overall 30 day mortality. The secondary outcome included clinical and microbiological failure, superinfections and adverse events (AEs). The trials’ risks of bias and their effects on results were assessed. Two reviewers independently extracted the data. Individual trials’ relative risks (RRs) were pooled using a fixed effect meta-analysis. Fifteen trials (7654 patients) were included. Overall mortality was higher with tigecycline compared with other regimens [RR 1.29, 95% confidence interval (CI) 1.02–1.64, without heterogeneity]. The type of infection assessed and the trials’ reported risks of bias did not affect this result. Clinical failure was significantly higher with tigecycline (RR 1.16, 95% CI 1.06–1.27) and non-statistically significant higher rates of microbiological failure were demonstrated (RR 1.13, 95% CI 0.99–1.30). Development of septic shock was significantly more frequent with tigecycline (RR 7.01, 95% CI 1.27–38.66). Superinfections were significantly more common with tigecycline and so were AEs, including all AEs and AEs requiring discontinuation. In the light of the increased mortality, probably explained by decreased clinical and microbiological efficacy, clinicians should avoid tigecycline monotherapy in the treatment of severe infections and reserve it as a last-resort drug.

Antibiotic prophylaxis is recommended in cardiac surgery. Current debate concerns the type of antibiotic(s), dosing and the duration of prophylaxis. Systematic review of randomized controlled trials comparing one antibiotic regimen versus another in cardiac surgery. We searched The Cochrane Library, PubMed, LILACS, conference proceedings and bibliographies. Two reviewers independently extracted the data. The primary outcome was deep sternal wound infections (DSWIs). Meta-analysis was performed using the Mantel–Haenszel fixed-effect method. Risk ratios (RRs) with 95% confidence intervals (95% CIs) are reported. Fifty-nine trials were included. There were no significant differences in DSWI or all other categories of surgical site infections (SSIs) for antibiotic prophylaxis with β-lactams comprising a Gram-negative spectrum of coverage versus prophylaxis targeting Gram-positive bacteria, but the former led to a significantly lower rate of post-operative pneumonia (RR 0.68, 95% CI 0.51–0.90) and all-cause mortality (RR 0.66, 95% CI 0.47–0.92). In trials comparing different antibiotic regimens for different durations, prophylaxis duration of ≤24 h post-operation led to higher rates of DSWI (RR 1.83, 95% CI 1.25–2.66), any sternal SSI, surgical interventions for SSI and endocarditis compared with longer duration prophylaxis. There was no advantage of regimens lasting >48 h post-operation. In the comparison of glycopeptides versus β-lactams, an advantage of glycopeptides was observed when comparators were given for similar duration and for β-lactams when given for a longer duration than the glycopeptides. There was no significant advantage of high antibiotic dosing. Evidence supports second- or third-generation cephalosporins for cardiac surgery prophylaxis and points at a possible advantage of prophylaxis prolongation up to 48 h post-operatively.

Chloramphenicol is an old broad-spectrum antibiotic. We assessed its efficacy and safety. This was a systematic review and meta-analysis. Electronic databases were searched to identify randomized controlled trials (RCTs) that assessed patients, of any age, with systemic bacterial infections that can cause sepsis and compared chloramphenicol alone versus other antibiotics. No restrictions on the date of publication, language or publication status were applied. The primary outcome assessed was overall mortality. Sixty-six RCTs fulfilled the inclusion criteria, and these included 9711 patients. We found a higher mortality with chloramphenicol for respiratory tract infections [risk ratio (RR) 1.40, 95% CI 1.00–1.97] and meningitis (RR 1.27, 95% CI 1.00–1.60), both without heterogeneity. The point estimate was similar for enteric fever, without statistical significance. No statistically significant difference was found between chloramphenicol and other antibiotics regarding treatment failure, except for enteric fever (RR 1.46, 95% CI 1.07–2.00, without heterogeneity). This difference derived mainly from studies comparing chloramphenicol with fluoroquinolones (RR 1.85, 95% CI 1.07–3.2). There were no statistically significant differences between chloramphenicol and other antibiotics in terms of adverse events, including haematological events, except for anaemia, which occurred more frequently with chloramphenicol (RR 2.80, 95% CI 1.65–4.75, I² = 0%), and gastrointestinal side effects, which were less frequent with chloramphenicol (RR 0.67, 95% CI 0.46–0.99, I² = 0%). Many of the studies included were sponsored by pharmaceutical companies marketing the comparator drug to chloramphenicol, and this might have influenced the results. Chloramphenicol cannot be recommended as a first-line treatment for respiratory tract infections, meningitis or enteric fever as alternatives are probably more effective. Chloramphenicol is as safe as treatment alternatives for short antibiotic courses. RCTs are needed to test this treatment against MDR organisms when better alternatives do not exist.