Activity of ceftolozane/tazobactam, imipenem/relebactam and ceftazidime/avibactam against clinical Gram-negative isolates-SMART United States 2019-21.

Background: Ongoing national and international surveillance efforts are critical components of antimicrobial stewardship, resistance monitoring, and drug development programs. In this report, we summarize the results of ceftolozane/tazobactam, imipenem/relebactam, ceftazidime/avibactam and comparator agent testing against 10 509 Enterobacterales and 2524 collected by USA clinical laboratories in 2019-21 as part of the SMART global surveillance programme.

Methods: MICs were determined by CLSI broth microdilution and interpreted using 2023 CLSI M100 breakpoints.

Assessment of mortality stratified by meropenem minimum inhibitory concentration in patients with Enterobacteriaceae bacteraemia: A patient-level analysis of published data.

In 2010, the Clinical and Laboratory Standards Institute (CLSI) lowered carbapenem breakpoints to reduce the proportion of 'susceptible' organisms that produced carbapenemases. Few studies have evaluated the effect of this change on clinical outcomes. This systematic review aimed to evaluate the effect of carbapenem MICs on 30-day mortality from pooled patient-level data from studies of patients treated with carbapenems across a range of meropenem MICs.

Sulfamethoxazole/trimethoprim versus fluoroquinolones for the treatment of Stenotrophomonas maltophilia bloodstream infections.

Objectives: Stenotrophomonas maltophilia causes high mortality rates, especially in bloodstream infections (BSIs) where there is a lack of comparative data with fluoroquinolones (FQs) and sulfamethoxazole/trimethoprim (SXT). The objective of this study was to evaluate outcomes in patients with S. maltophilia BSI who were treated with FQs versus SXT.

Use of High-Dose Oral Valacyclovir During an Intravenous Acyclovir Shortage: A Retrospective Analysis of Tolerability and Drug Shortage Management.

Introduction: In late 2011, a shortage of IV acyclovir led to the need to empirically substitute high-dose oral valacyclovir (HDVA) to conserve IV acyclovir for patients with confirmed herpes simplex virus (HSV) meningitis or encephalitis. This report describes the management of the most recent national IV acyclovir shortage by the Antimicrobial Stewardship Program (ASP) at Northwestern Memorial Hospital (NMH), Chicago, IL, USA, and the use of HDVA. Secondarily, we assessed the safety and tolerability of HDVA as an alternate to IV acyclovir during this shortage.

Use of organism identification by 16S ribosomal RNA polymerase chain reaction to shorten antimicrobial length of therapy.

Background: Organism detection by 16S ribosomal RNA (rRNA) PCR followed by amplicon sequencing identification may help guide antimicrobial treatment in culture-negative patients. The objectives of this study were to assess the effect of a positive versus negative 16S rRNA PCR on antibiotic length of therapy (LOT) and rate of antibiotic discontinuation.

Methods: Patients with a sterile site, direct-specimen 16S rRNA PCR negative, and suspected active infection were matched 1:1 with 16S rRNA PCR positive patients based on specimen site and retrospectively evaluated.

Impact of body mass index on clinical outcomes in patients with gram-negative bacteria bloodstream infections.

Introduction: Excess body mass index (BMI) is associated with a higher risk of death in many disease states, yet less is known about the impact of higher BMIs on clinical outcomes of serious bacterial infections. We sought to quantify the risk of all-cause mortality and/or organ failure following Gram negative bacteria bloodstream infections (GNBSI) according to BMI.

Materials And Methods: We retrospectively reviewed the charts of patients with confirmed GNBSI who received ≥48 h of active antimicrobial therapy.

Prediction of inventory sustainability during a drug shortage.

Purpose: A methodology for predicting how long the on-hand inventory of a given medication will last during a supply shortage is described; a practical example of application of the methodology is provided.

Methods: Single-site data on consumption of i.v.

Tree-Based Models for Predicting Mortality in Gram-Negative Bacteremia: Avoid Putting the CART before the Horse.

Increasingly, infectious disease studies employ tree-based approaches, e.g., classification and regression tree modeling, to identify clinical thresholds.

Disposition of linezolid or daptomycin in Enterococcal bloodstream infections according to vancomycin resistant Enterococcus colonization.

Vancomycin resistant Enterococcus (VRE) colonized patients are likely to receive VRE targeted Gram-positive antibiotics and may not be de-escalated appropriately once final cultures are available. A retrospective cohort study was conducted in VRE-colonized and non-VRE colonized patients with Enterococcal bloodstream infections. Of 101 patients (n = 50 VRE-colonized; n = 51 non-colonized), empiric therapy with linezolid or daptomycin was started more often in VRE-colonized than non-colonized patients (n = 8, 15.

Knowledge and attitudes of doctor of pharmacy students regarding the appropriate use of antimicrobials.

Pharmacists are key partners in antimicrobial stewardship efforts, yet their degree of education on and attitudes toward this topic during training are not well documented. An electronic survey measuring knowledge and attitudes regarding antimicrobial use and resistance was administered to graduating pharmacy students at 12 US schools of pharmacy. Of 1445 pharmacy students, 579 (40%) completed the survey.

Pathogenicity of clinical Acinetobacter baumannii isolates in a Galleria mellonella host model according to bla(OXA-40) gene and epidemiological outbreak status.

Clinical studies have suggested that blaOXA-40-positive Acinetobacter baumannii isolates are associated with poor patient outcomes; however, reasons for unfavorable outcomes are difficult to discern in clinical studies. The objective of this study was to assess the virulence of carbapenem-resistant A. baumannii according to blaOXA-40 and epidemiological outbreak status in a Galleria mellonella model.

Clinical implications of antiretroviral drug interactions with warfarin: a case-control study.

Objectives: Warfarin, a frequently prescribed anticoagulant with a narrow therapeutic index, is susceptible to drug-drug interactions with antiretroviral therapy (ART). This study compared the warfarin maintenance dose (WMD) between patients receiving and not receiving ART and evaluated predictors of warfarin dosage among those on ART.

Methods: This was a case-control (1:2) study.

Successful treatment of extensively drug-resistant Acinetobacter baumannii peritoneal dialysis peritonitis with intraperitoneal polymyxin B and ampicillin-sulbactam.

Objective: To describe a case of extensively drug-resistant (XDR) Acinetobacter baumannii peritoneal dialysis (PD)-associated peritonitis successfully treated with combination antibiotics, including intraperitoneal polymyxin B, with retention of the catheter.

Case Summary: A 54-year-old woman with end-stage renal disease receiving chronic PD and recent antibiotic and hospital exposure presented with abdominal pain, nausea, and vomiting. She was found to have XDR A.

Evaluation of clinical outcomes in patients with bloodstream infections due to Gram-negative bacteria according to carbapenem MIC stratification.

Predictive modeling suggests that actual carbapenem MIC results are more predictive of clinical patient outcomes than categorical classification of the MIC as susceptible, intermediate, or resistant. Some have speculated that current CLSI guidelines' suggested thresholds are too high and that clinical success is more likely if the MIC value is ≤1 mg/liter for certain organisms. Patients treated with carbapenems and with positive blood cultures for Pseudomonas aeruginosa, Acinetobacter baumannii, or extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria were considered for evaluation in this clinical retrospective cohort study.

Prospective approach to managing antimicrobial drug shortages.

Antimicrobial drug shortages continue to increase, with few new therapeutic options available. Nationally, proposals have been offered to alleviate drug shortages; however, these recommendations are unlikely to effect change in the near future. Thus, antimicrobial stewardship leaders in acute care hospitals must develop a prospective management strategy to lessen the impact of these shortages on patient care.

The impact of anti-infective drug shortages on hospitals in the United States: trends and causes.

Anti-infective shortages pose significant logistical and clinical challenges to hospitals and may be considered a public health emergency. Anti-infectives often represent irreplaceable life-saving treatments. Furthermore, few new agents are available to treat increasingly prevalent multidrug-resistant pathogens.

Life-years gained with meropenem over ciprofloxacin in penicillin-allergic patients with gram-negative bacilli sepsis: results of a probabilistic model.

Study Objective: To compare meropenem with ciprofloxacin for treatment of gram-negative bacilli sepsis in penicillin-allergic patients in the intensive care unit (ICU) to determine if increased anaphylaxis risk with meropenem precluded its use when weighed against risks of inactive therapy with ciprofloxacin.

Design: A decision model constructed from probability distributions from the literature and data from a local ICU antibiogram. A probabilistic sensitivity analysis was performed to evaluate uncertainty in variable estimates by using one-way analyses, two-way analyses, and Monte Carlo simulation.

Impact of carbapenem resistance and receipt of active antimicrobial therapy on clinical outcomes of Acinetobacter baumannii bloodstream infections.

Nosocomial Acinetobacter baumannii bloodstream infections occur with significant prevalence and mortality. The relationship between carbapenem resistance in A. baumannii and patient outcomes remains unclear.

Impact of the FDA warning of potential ceftriaxone and calcium interactions on drug use policy in clinical practice.

Objective: In September 2007, the FDA issued an alert recommending that ceftriaxone and calcium-containing solutions should not be administered to any patient within 48 h of each other. Due to the widespread use of ceftriaxone, significant concern was expressed by the greater healthcare community about the warning, which the FDA eventually retracted in April of 2009. We sought to quantify the impact of the warning on healthcare institutions.

Genetic Mechanisms of Antimicrobial Resistance of Acinetobacter baumannii.

Objective: To summarize published data identifying known genetic mechanisms of antibiotic resistance in Acinetobacter baumannii and the correlating phenotypic expression of antibiotic resistance.

Data Sources: MEDLINE databases (1966-July 15, 2010) were searched to identify original reports of genetic mechanisms of antibiotic resistance in A. baumannii.

Evaluation of hepatotoxicity with off-label oral-treatment doses of voriconazole for invasive fungal infections.

The approved treatment dose of intravenous voriconazole is a weight-based dose of 4 mg/kg of body weight twice daily; the approved oral dosing is fixed at 200 mg twice daily. In our institution, patients frequently receive oral high-dose voriconazole at 4 mg/kg twice daily. It is unknown if higher doses are associated with increased hepatotoxicity.