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Background: Sepsis following transrectal ultrasound (TRUS)-guided prostate biopsy is a major complication. With the emergence of multidrug-resistant organisms, empirical use of carbapenem antibiotics has been increasing. This study, conducted in the Illawarra Shoalhaven Local Health District (ISLHD), Australia, quantifies how much we can spare carbapenem use., Methods: A retrospective audit of patients who underwent TRUS prostate biopsy and were admitted post-operatively with proven bacteraemia between January 2007 and April 2016., Results: Of 2719 TRUS procedures, 50 (1.84%) cases had bacteraemia. The most common isolate was Escherichia coli in 44 of 50 (88%) of which six of 50 (12%) were extended-spectrum beta-lactamase (ESBL)-producing. Sixteen different empirical antimicrobial regimens were used, to which 42 of 50 (84%) of isolates were susceptible. Eight (16%) isolates were resistant to the chosen empiric combination, with five switched over to appropriate treatment once antimicrobial sensitivity results became available. Empirical carbapenem was utilized in 12 of 50 (24%) patients with only two of the ESBL isolates covered. A further 10 of 50 patients received carbapenems during their admission. Carbapenems could have been avoided in 18 of 22 (82%). A total of 86% of organisms (n = 43) were susceptible to the combination of amoxicillin-clavulanate and gentamicin., Conclusion: Although the rates of bacteraemia with ESBL-producing organisms post-TRUS biopsy are increasing, use of carbapenem-free combination antimicrobials as empirical therapy appears to be safe and effective in our setting. Clinicians can utilize local resistance patterns to inform targeted and appropriate therapy for septic patients., (© 2019 Royal Australasian College of Surgeons.)

Importance: Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum β-lactamase producers., Objectives: To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae., Design, Setting, and Participants: Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study., Interventions: Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician., Main Outcomes and Measures: The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used., Results: Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group., Conclusions and Relevance: Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting., Trial Registration: anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.

Background: Gram-negative bacteria such as Escherichia coli or Klebsiella spp. frequently cause bloodstream infections. There has been a worldwide increase in resistance in these species to antibiotics such as third generation cephalosporins, largely driven by the acquisition of extended-spectrum beta-lactamase or plasmid-mediated AmpC enzymes. Carbapenems have been considered the most effective therapy for serious infections caused by such resistant bacteria; however, increased use creates selection pressure for carbapenem resistance, an emerging threat arising predominantly from the dissemination of genes encoding carbapenemases. Recent retrospective data suggest that beta-lactam/beta-lactamase inhibitor combinations, such as piperacillin-tazobactam, may be non-inferior to carbapenems for the treatment of bloodstream infection caused by extended-spectrum beta-lactamase-producers, if susceptible in vitro. This study aims to test this hypothesis in an effort to define carbapenem-sparing alternatives for these infections., Methods/design: The study will use a multicentre randomised controlled open-label non-inferiority trial design comparing two treatments, meropenem (standard arm) and piperacillin-tazobactam (carbapenem-sparing arm) in adult patients with bacteraemia caused by E. coli or Klebsiella spp. demonstrating non-susceptibility to third generation cephalosporins. Recruitment is planned to occur in sites across three countries (Australia, New Zealand and Singapore). A total sample size of 454 patients will be required to achieve 80% power to determine non-inferiority with a margin of 5%. Once randomised, definitive treatment will be for a minimum of 4 days, but up to 14 days with total duration determined by treating clinicians. Data describing demographic information, antibiotic use, co-morbid conditions, illness severity, source of infection and other risk factors will be collected. Vital signs, white cell count, use of vasopressors and days to bacteraemia clearance will be recorded up to day 7. The primary outcome measure will be mortality at 30 days, with secondary outcomes including days to clinical and microbiological resolution, microbiological failure or relapse, isolation of a multi-resistant organism or Clostridium difficile infection., Trial Registration: The MERINO trial is registered under the Australian New Zealand Clinical Trials Register (ANZCTR), reference number: ACTRN12613000532707 (registered 13 May 2013) and the US National Institute of Health ClinicalTrials.gov register, reference number: NCT02176122 (registered 24 June 2014).

Limited therapeutic options exist for the treatment of vancomycin-resistant Enterococcus (VRE) bacteremia; the most commonly used are daptomycin and linezolid. We attempted a systematic review and meta-analysis of the comparative efficacy of those two agents. Studies comparing daptomycin to linezolid treatment for VRE bacteremia, published until August 2012, were identified from the MEDLINE, EMBASE, CENTRAL, ISI Web of Science, and SCOPUS databases. All comparative studies on patients older than 18 years of age that provided mortality data were considered eligible for this systematic review and meta-analysis. Τhe primary outcome of the meta-analysis was 30-day all-cause mortality. Ten retrospective studies including 967 patients were identified. Patients treated with daptomycin had significantly higher 30-day all-cause mortality (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.08 to 2.40) and infection-related mortality (OR, 3.61; 95% CI, 1.42 to 9.20) rates than patients treated with linezolid. When data from all 10 studies were combined, overall mortality was also significantly increased among patients treated with daptomycin (OR, 1.41; 95% CI, 1.06 to 1.89). These findings were confirmed when odds ratios adjusted for potential confounders were pooled. Relapse rates among patients treated with daptomycin were also higher (OR, 2.51; 95% CI, 0.94 to 6.72), although this difference did not reach statistical significance. Adverse event rates were not significantly different between the two groups. Notwithstanding the absence of randomized prospective data, available evidence suggests that mortality rates may be higher with daptomycin than with linezolid among patients treated for VRE bacteremia.

Blood cultures (BC) are the most important tool in the diagnosis of bloodstream infections. However, false positive results are associated with increased laboratory costs and inappropriate antibiotic use. In order to determine the prevalence and location of blood cultures contaminated with coagulase-negative staphylococci (CNS), we performed a retrospective analysis of all blood cultures performed at St. Vincent's Hospital, Sydney during a 6-month period. From a total of 4234 patients with BC collected, CNS was isolated from 109 patients (2.6%). 94% of all CNS isolates (101/109) were contaminants. In the emergency department (ED), CNS isolates were significantly more likely to be contaminants (62/63, p<0.02) compared with the rest of the hospital, representing a 3.3% patient BC contamination rate. Treatment for a contaminant with vancomycin was significantly more likely to occur in ward patients (14/28, p<0.01) compared to the rest of the hospital. Duration of therapy did not differ across the hospital. Strategies to reduce the numbers of contaminants should be directed at medical staff in ED. Inappropriate vancomycin therapy could be curtailed by greater clinical microbiology liaison and vancomycin stewardship.