Implementation of an Automated Antibiotic Time-out at a Comprehensive Cancer Center.

Background: Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established.

Methods: An antimicrobial time out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center.

The Growing Threat of NDM-Producing Escherichia coli With Penicillin-Binding Protein 3 Mutations in the United States-Is There a Potential Role for Durlobactam?

We report identification of 5 patients with infections caused by NDM-5-producing Escherichia coli harboring PBP3 mutations that showed reduced susceptibility to aztreonam-avibactam and cefiderocol. Durlobactam, a novel diazabicyclooctane β-lactamase inhibitor, demonstrated minimum inhibitory concentrations ranging from 0.5 to 2 µg/mL supporting future investigations into a potential role in clinical management.

Aminoglycoside Pharmacokinetics in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

Background: There are few studies describing aminoglycoside pharmacokinetics during continuous renal replacement therapy (CRRT).

Objective: To characterize the effect of CRRT on aminoglycoside clearance and volume of distribution ().

Methods: Retrospective observational pharmacokinetic study of adult critically ill oncologic patients who received a first dose of amikacin or tobramycin during CRRT between February 2012 and May 2017.

Contemporary Perspective on the Treatment of Acinetobacter baumannii Infections: Insights from the Society of Infectious Diseases Pharmacists.

The purpose of this narrative review is to bring together the most recent epidemiologic, preclinical, and clinical findings to offer our perspective on best practices for managing patients with A. baumannii infections with an emphasis on carbapenem-resistant A. baumannii (CRAB).

Effect of High-Dose Posaconazole on Serum Levels in Adult Patients with Hematologic Malignancy.

Posaconazole (POS) appears to have dose-proportional pharmacokinetics; however, there is a paucity of real-life data. We retrospectively evaluated 67 patients with hematologic cancer who had POS dose increases from 300 mg/day to either 400 mg/day ( = 52) or 300 mg twice daily (BID) ( = 15) and for whom POS serum levels were measured. Median POS levels were 840 ng/ml, 1,625 ng/ml, and 2,710 ng/ml for the dosages of 300 mg/day, 400 mg/day, and 300 mg BID, respectively.

Clinical Outcomes Associated With Linezolid Resistance in Leukemia Patients With Linezolid-Resistant Bacteremia.

Background: Coagulase-negative staphylococci, including , are the most common cause of bloodstream infection in cancer patients. Linezolid resistance is increasingly identified in but whether such resistance alters the clinical course of infections is unknown. The purpose of this study was to assess the clinical impact of linezolid resistance in leukemia patients with bloodstream infection.

Real-Life Assessment of the Safety and Effectiveness of the New Tablet and Intravenous Formulations of Posaconazole in the Prophylaxis of Invasive Fungal Infections via Analysis of 343 Courses.

Posaconazole is the preferred mold-active azole for prophylaxis against invasive fungal infections (IFIs) in patients with hematological malignancy. Delayed-release tablet and intravenous formulations of posaconazole have recently become available, but clinical data are limited. We sought to examine the real-world pharmacokinetics and prophylactic effectiveness of the new formulations of posaconazole given as prophylaxis for patients with hematological malignancy.

Daptomycin non-susceptible Enterococcus faecium in leukemia patients: Role of prior daptomycin exposure.

Objectives: We sought to determine the association between previous daptomycin exposure and daptomycin non-susceptible Enterococcus faecium (DNSEf) bloodstream infections (BSI) in adult leukemia patients.

Methods: We retrospectively identified adult (≥18 years old) leukemia patients with Enterococcus spp. bacteremia at The University of Texas MD Anderson Cancer Center (MDACC) from 6/1/2013 to 7/22/2015.

Predicting the risk of nephrotoxicity in patients receiving colistimethate sodium: a multicentre, retrospective, cohort study.

Objectives: With increasing rates of infections caused by MDR Gram-negative organisms, clinicians resort to older agents such as colistimethate sodium (CMS) despite a significant risk of nephrotoxicity. Several risk factors for CMS-associated nephrotoxicity have been reported, but they have yet to be validated. We compared the performance of published mathematical models in predicting the risk of CMS-associated nephrotoxicity.

High Rates of Nonsusceptibility to Ceftazidime-avibactam and Identification of New Delhi Metallo-β-lactamase Production in Enterobacteriaceae Bloodstream Infections at a Major Cancer Center.

Resistance to the novel β-lactam/β-lactamase inhibitor combination ceftazidime-avibactam (CAZ-AVI) among carbapenem-resistant Enterobacteriaceae (CRE) has infrequently been reported in the United States. We report unexpectedly high rates of resistance to CAZ-AVI in CRE bloodstream isolates at our institution associated with the nonoutbreak spread of New Delhi metallo-β-lactamase in diverse Enterobacteriaceae species.

Antifungal agents and liver toxicity: a complex interaction.

Introduction: The number of antifungal agents has sharply increased in recent decades. Antifungals differ in their spectrum of activity, pharmacokinetic/pharmacodynamic properties, dosing, safety-profiles and costs. Risk of developing antifungal associated hepatotoxicity is multifactorial and is influenced by pre-existing liver disease, chemical properties of the drug, patient demographics, comorbidities, drug-drug interactions, environmental and genetic factors.

Use of Ceftolozane/Tazobactam in the Treatment of Multidrug-resistant Pseudomonas aeruginosa Bloodstream Infection in a Pediatric Leukemia Patient.

Multidrug-resistant Pseudomonas aeruginosa is of increasing concern in pediatric patients. Ceftolozane/tazobactam is a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant Pseudomonas; however, no data exist on its use in children. This report summarizes the treatment of a multidrug-resistant P.

Probable Nonconvulsive Status Epilepticus With the Use of High-Dose Continuous Infusion Ceftazidime.

Multidrug resistant (MDR) bacterial infections are a major concern of health care providers due to their increasing incidence and associated mortality. In some cases, few or no antibiotics have preserved activity. Beta-lactam administration via continuous infusion can optimize time over minimum inhibitory concentration (MIC).

Switching to anidulafungin from caspofungin in cancer patients in the setting of liver dysfunction is associated with improvement of liver function tests.

Background: Anidulafungin does not undergo hepatic metabolism like the other echinocandins. Therefore, there is a perception that anidulafungin may be less hepatotoxic or less likely to exacerbate existing liver damage. This has not been substantiated in the literature.

Development of a combination antibiogram for Pseudomonas aeruginosa bacteremia in an oncology population.

Purpose: Development of a combination antibiogram to identify combinations of antibiotics that have the highest likelihood of attaining one active agent in the empiric management of presumed Pseudomonas aeruginosa bacteremia.

Methods: Patients with cancer and P. aeruginosa bacteremia from January 1 to December 31, 2012 were included in this analysis.

First-dose pharmacokinetics of aminoglycosides in critically ill haematological malignancy patients.

The primary objective of this study was to determine the volume of distribution (Vd) (L/kg) of intravenous aminoglycosides (AGs) in critically ill haematological malignancy patients. Secondary objectives were to determine the body weight (actual, ideal, adjusted or lean) that yields the most precise estimate of Vd when normalised in L/kg as well as the frequency that current first-dose strategies result in post-distributional peak concentrations (C(peak)) within the target range (tobramycin 16-24 mg/L; amikacin 32-48 mg/L). In total, 58 AG doses were included (tobramycin, n = 34; amikacin, n = 24).

Switching from posaconazole suspension to tablets increases serum drug levels in leukemia patients without clinically relevant hepatotoxicity.

We evaluated posaconazole serum concentrations and hepatotoxicity in 12 leukemia patients who transitioned from posaconazole suspension to tablets. Patients who switched to tablets had significantly increased posaconazole concentrations (median: suspension, 748 ng/ml; tablet, 1,910 ng/ml; P < 0.01) without clinically relevant hepatotoxicity.

The use of fidaxomicin for treatment of relapsed Clostridium difficile infections in patients with cancer.

Objectives: To report our experience with the use of fidaxomicin (FDX), an oral macrocyclic antibiotic, in cancer patients with Clostridium difficile infection (CDI).

Methods: A single-center retrospective case series was conducted at The University of Texas MD Anderson Cancer Center. Patients with CDI treated with FDX from May 2011 to January 2013 were identified via the pharmacy database.

Antimicrobial stewardship in patients with cancer.

Consensus guidelines recommend antimicrobial stewardship in all hospitals with the following goals in mind: appropriate and judicious use of antimicrobial agents leading to increased drug safety, reduced antimicrobial utilization, reduction in the development and selection of resistant organisms, cost containment, and improved patient outcomes. Patients with cancer, especially those with hematologic malignancies and neutropenia, develop serious infections often and receive antimicrobial therapy frequently. Consequently, there is considerable opportunity to practice antimicrobial stewardship in this population.

The safety of amphotericin B lipid complex in patients with prior severe intolerance to liposomal amphotericin B.

The tolerability of amphotericin B lipid complex in patients with previous severe infusion reactions to liposomal amphotericin B is unclear. We reviewed the charts of 40 such patients at a tertiary care cancer center and found that amphotericin B lipid complex administration was uneventful in 34 patients (85% [95% confidence interval, 69%-93%]).

Antibiotic therapy of methicillin-resistant Staphylococcus aureus in critical care.

The treatment of methicillin-resistant Staphylococcus aureus (MRSA) in the critically ill patient is challenging. Data for treatment of critically ill patients are often lacking because many such patients are excluded from industry-sponsored prospective randomized clinical trials. Infections due to MRSA are common in the critical care setting.