Acute pyelonephritis is a frequent cause of morbidity, with a wide variation in duration of therapy. We performed a systematic review of all randomized controlled trials (RCTs) comparing ≤7 days treatment with a longer course. Electronic databases were searched to identify RCTs that assessed adults treated for pyelonephritis, comparing a 7 day or shorter versus longer therapy. Primary outcome was clinical failure at the end of the long treatment arm (EOT). Secondary outcomes included clinical failure at the end of follow-up (EOF), microbiological failure, all-cause mortality, the development of resistance and adverse events. Clinical failure at EOT did not significantly differ between the two treatment arms [relative risk (RR) 0.63, 95% CI 0.33–1.18, I² = 41%]. Results did not differ when including studies comparing only fluoroquinolones, reducing the heterogeneity (RR 0.76, 95% CI 0.49–1.17, I² = 0%). We found no difference between the short and long treatment arms regarding clinical failure at EOF, even in a small subgroup of bacteraemic patients. No difference was found between the arms regarding microbiological failure at EOF, except in a subgroup of studies with a high percentage of patients with urogenital abnormalities, where microbiological failure at EOF was significantly higher in the short treatment arm (RR 1.78, 95% CI 1.02–3.10, I² = 21%). Adverse events were similar between the arms. Seven days of treatment for acute pyelonephritis is equivalent to longer treatment in terms of clinical failure and microbiological failure, including in bacteraemic patients. In patients with urogenital abnormalities, the evidence, although weak, suggests that longer treatment is required.

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.

Background: Patients with complicated urinary tract infections (cUTIs) frequently receive broad-spectrum antibiotics. We aimed to determine the prevalence and predictive factors of multidrug-resistant gram-negative bacteria in patients with cUTI. Methods: This is a multicenter, retrospective cohort study in south and eastern Europe, Turkey and Israel including consecutive patients with cUTIs hospitalised between January 2013 and December 2014. Multidrug-resistance was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. A mixed-effects logistic regression model was used to determine predictive factors of multidrug-resistant gram-negative bacteria cUTI. Results: From 948 patients and 1074 microbiological isolates, Escherichia coli was the most frequent microorganism (559/1074), showing a 14.5% multidrug-resistance rate. Klebsiella pneumoniae was second (168/1074) and exhibited the highest multidrug-resistance rate (54.2%), followed by Pseudomonas aeruginosa (97/1074) with a 38.1% multidrug-resistance rate. Predictors of multidrug-resistant gram-negative bacteria were male gender (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.20–2.29), acquisition of cUTI in a medical care facility (OR, 2.59; 95%CI, 1.80–3.71), presence of indwelling urinary catheter (OR, 1.44; 95%CI, 0.99–2.10), having had urinary tract infection within the previous year (OR, 1.89; 95%CI, 1.28–2.79) and antibiotic treatment within the previous 30 days (OR, 1.68; 95%CI, 1.13–2.50). Conclusions: The current high rate of multidrug-resistant gram-negative bacteria infections among hospitalised patients with cUTIs in the studied area is alarming. Our predictive model could be useful to avoid inappropriate antibiotic treatment and implement antibiotic stewardship policies that enhance the use of carbapenem-sparing regimens in patients at low risk of multidrug-resistance.

The clinical characteristics of internal medicine ward (IMW) patients with candidemia are unclear. The aim of this study was to define the clinical characteristics of candidemic IMW patients and to study the incidence, species distribution, and outcomes of these patients compared to surgical and intensive care unit (ICU) candidemic patients. A retrospective cohort of candidemic patients in IMWs, general surgery wards, and an ICU at Beilinson Hospital during the period 2007-2014 was analyzed. A total of 118 patients with candidemia were identified in six IMWs, two general surgery wards, and one ICU in the hospital. Candida albicans was the leading causative agent (41.1%). Higher proportions of Candida parapsilosis and Candida tropicalis isolates were observed in the IMW patients. IMW patients were significantly older, with poorer functional capacity, and had more frequently been exposed to antibiotic therapy within 90 days, in particular β-lactam-β-lactamase inhibitor combinations and cephalosporins. At onset of candidemia, a significantly lower number of IMW patients were mechanically ventilated (p48h. IMW candidemic patients account for a substantial proportion of candidemia cases and have unique characteristics and high mortality rates.