Identifying Effective Durations of Antibiotic Therapy for the Treatment of Carbapenem-resistant Enterobacterales Bloodstream Infections: A Multicenter Observational Study.

In a propensity-score-weighted cohort of 183 adults with carbapenem-resistant Enterobacterales bacteremia at 24 US hospitals, patients receiving short courses of active therapy (7-10 days, median 9 days) experienced similar odds of recurrent bacteremia or death within 30 days as those receiving prolonged courses of active therapy (14-21 days, median 14 days).

Successful Treatment of Persistent Burkholderia cepacia Complex Bacteremia with Ceftazidime-Avibactam.

We report our clinical experience treating a 2-month-old infant with congenital diaphragmatic hernia who experienced prolonged bacteremia with Burkholderia cepacia complex (Bcc) despite conventional antibiotic therapy and appropriate source control measures. The infection resolved after initiation of ceftazidime-avibactam. Whole-genome sequencing revealed that the isolate most closely resembled B. contaminans and identified the mechanism of resistance that likely contributed to clinical cure with this agent. Ceftazidime-avibactam should be considered salvage therapy for Bcc infections if other treatment options have been exhausted.

The Use of a Combination Antibiogram to Assist with the Selection of Appropriate Antimicrobial Therapy for Carbapenemase-Producing Enterobacteriaceae Infections.

Combination antibiograms can be used to evaluate organism cross-resistance among multiple antibiotics. As combination therapy is generally favored for the treatment of carbapenemase-producing Enterobacteriaceae (CPE), combination antibiograms provide valuable information about the combination of antibiotics that achieve the highest likelihood of adequate antibiotic coverage against CPE.

Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum ß-lactamase bacteremia.

BACKGROUND: The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum ß-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem. METHODS: Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort. RESULTS: A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45). CONCLUSIONS: PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to ß-lactam/ß-lactamase inhibitor combinations in development, as limited clinical data are available for these agents.

Treatment of multidrug-resistant Gram-negative infections in children.

Antibiotic resistance in conjunction with the erosion of the drug development pipeline may lead us into a bleak future, a "post-antibiotic era." Because of a shortage of studies addressing treatment options for multidrug-resistant Gram-negative (MDRGN) infections in children, data must be extrapolated from the adult literature. However, even adult studies are limited by significant methodological flaws. We are in urgent need of pediatric specific pharmacokinetic/pharmacodynamic data for agents with activity against MDRGN infections as well as improved clinical outcomes studies. For the time being, we must rely on in vitro studies, observational data, and clinical experience to guide our therapeutic decisions. In this review, we discuss treatment considerations for infections caused by extended-spectrum ß-lactamase-producing organisms, AmpC ß-lactamase-producing organisms, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii in the pediatric population.

Outcomes of children with enterobacteriaceae bacteremia with reduced susceptibility to ceftriaxone: do the revised breakpoints translate to improved patient outcomes?

BACKGROUND: In 2010, the Clinical and Laboratory Standards Institute (CLSI) revised and lowered the ceftriaxone minimum inhibitory concentration breakpoints for Enterobacteriaceae and removed the requisite extended spectrum ß-lactamase phenotypic testing for organisms with elevated minimum inhibitory concentrations. The impact that these recommendations have on clinical outcomes of children have not been previously evaluated. METHODS: We conducted a retrospective study to compare clinical outcomes between children treated with ceftriaxone and those treated with broader spectrum ß-lactams for Enterobacteriaceae bacteremia with reduced susceptibility (minimum inhibitory concentrations 4-8 µg/mL) to ceftriaxone according to the new CLSI interpretive criteria. Mortality and microbiological relapse were evaluated using a multivariable logistic regression model. RESULTS: There were a total of 783 unique children with Enterobacteriaceae bacteremia during the study period. Using the CLSI breakpoints before 2010, 76 children would have had clinical isolates resistant to ceftriaxone. With the revised breakpoints, 229 Enterobacteriaceae isolates would no longer be susceptible to ceftriaxone (>300% increase). Of the 136 children who met eligibility criteria, 63 children received ceftriaxone and 73 children received broader spectrum ß-lactams. There was no difference in 30-day mortality (odds ratio 0.81, 95% confidence interval: 0.31-2.59) or microbiological relapse (odds ratio 0.97, 95% confidence interval: 0.36-2.66) between the groups. CONCLUSIONS: Our findings do not support the proposed clinical benefit of more conservative CLSI breakpoints. The revised breakpoints promote increased broad-spectrum ß-lactam use. The need for lowered ceftriaxone breakpoints against Enterobacteriaceae in children needs to be reevaluated in larger prospective studies.