Viktorija O. Barr

Treating complicated carbapenem-resistant enterobacteriaceae infections with ceftazidime/avibactam: a retrospective study with molecular strain characterisation

Ceftazidime/avibactam (CAZ/AVI) is the first antimicrobial agent with activity against carbapenem-resistant Enterobacteriaceae (CRE) approved by the US Food and Drug Administration (FDA). Notably, human clinical outcome data for this indication are limited. Therefore, a retrospective study was performed to evaluate the clinical outcomes and bacterial genomic characteristics of patients hospitalised at a tertiary medical centre with CRE infections treated for the first time with CAZ/AVI. From a total of 44 patients with CRE infections, 6 patients were treated with CAZ/AVI. The duration of CAZ/AVI treatment ranged from 7 days to 28 days. Five patients achieved clinical cure, however two relapsed with the same carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain within 3 weeks of completion of CAZ/AVI treatment. In addition, one patient with CR-Kp pneumonia experienced clinical failure despite having a documented CAZ/AVI-susceptible CR-Kp strain [minimum inhibitory concentration (MIC) = 2 mg/L]. Consequently, the overall rate of unsuccessful outcome in this small cohort of patients was 50%. All strains carried KPC-3, OXA-9 and different TEM and SHV β-lactamases, but none carried the intrinsically avibactam-resistant class B metallo-β-lactamases. No obvious differences in antibiotic resistance genes were observed. This study provides an early glimpse of the clinical outcomes of patients with CR-Kp infections treated with CAZ/AVI. Findings of clinical failure and relapse in patients with no prior exposure to CAZ/AVI and with documented susceptibility to CAZ/AVI highlight the urgent need for well-designed clinical studies evaluating the effectiveness of CAZ/AVI in the treatment of CRE infections.

A Review of Antiviral and Antifungal Use and Safety during Pregnancy.

Antiviral and antifungal use in pregnancy presents challenges because of the paucity of clinical and safety data for many agents in these classes. If untreated, viral and fungal infections can have deleterious effects on both maternal and fetal health. Understanding the use and risks of these medications in pregnancy is vital to provide appropriate care. This article reviews the current literature for the use of antiviral and antifungals, the pharmacokinetics of these agents, and their safety in pregnancy.

Implementation of a cefazolin-based stewardship pathway for methicillin-susceptible Staphylococcus aureus bloodstream infections paired with infectious diseases consultation

Methicillin-susceptible Staphylococcus aureus (MSSA) infections have been successfully treated both with cefazolin and antistaphylococcal penicillins; cefazolin appears effective in MSSA bloodstream infections (BSIs). Thus, our antimicrobial stewardship programme (ASP) implemented a clinical pathway supporting cefazolin use in MSSA-BSIs and restricting oxacillin use to infectious diseases (ID) consultation due to cefazolins lower cost and more convenient dosing. This before and after quasi-experimental study was conducted to describe the impact on outcomes and process of care measures associated with implementing this pathway among patients with MSSA-BSI. Definitive treatment with cefazolin increased over the study period from 17.3% to 69.8% post-implementation. Clinical failure (5.8% vs. 2.3%; P = 0.62) and in-hospital mortality (3.8% vs. 0%; P = 0.50) were rare pre- and post-implementation. Median hospital length of stay among survivors was similar between pre- and post-implementation periods (P = 0.31). Duration of bacteraemia [median (IQR) 3 (2-4) days vs. 2 (2-3) days; P = 0.002] and rates of re-infection after culture clearance (9.6% vs. 0%; P = 0.06) were reduced post-implementation. Frequency of source control (P = 0.71) and time to source control (P = 0.52) were similar between study periods. Significant increases in ID consultations (33.3% [3/9] vs. 73.3% [22/30]; P = 0.047) and median (IQR) 24-h daily doses [2 (1-3) g vs. 6 (3-6) g; P < 0.01] were seen for patients treated with cefazolin post-implementation. ASPs may find implementation of a similar pathway to be an effective means of improving the care of patients infected with MSSA.

The Clinical Significance of Azole Antifungals’ Effects on the Liver and Transaminase Levels

Various case reports have been published regarding the incidence of hepatotoxicity and the triazoles. To date, of the more commonly used triazoles, voriconazole has been liked to the highest incidence of transaminase elevations followed by posaconazole, fluconazole, and itraconazole, respectively. Discontinuation of each of the drugs has been shown to resolve the increase of transaminase levels; however, no clear guidance has been suggested on as to when discontinuation of therapy is warranted. Close monitoring particularly patients of Asian decent, underlying liver disease, bone marrow, or lung transplant may be prudent as well as target drug monitoring (TDM) for posaconazole and voriconazole to help assess the necessity of alteration or discontinuation of therapy.

Appropriateness of Beta-Lactam Allergy Record Updates After an Allergy Service Consult:

Background: Many patients with a self-reported penicillin allergy go on to tolerate beta-lactam antibiotics. Allergy specialists may be consulted to determine the nature and extent of the allergy. However, electronic allergy records must be appropriately updated such that recommendations are carried forward. Objective: To determine the percentage of patients who have their electronic allergy record updated after an allergy service consult (ASC). Methods: This was a retrospective study of patients with at least 1 documented beta-lactam allergy and had an ASC during (inpatient) or prior to (outpatient) hospital admission at Northwestern Memorial Hospital and Prentice Women’s Hospital in Chicago, Illinois. Results: Within the study period, a total of 26 526 patients were identified as having a documented antibiotic allergy, with 21 657 patients (81.6% of patients with allergies) having a listed beta-lactam allergy. Of these patients, 1689 (7.8%) patients were identified as having an ASC during or prior to admission, with 598 patients meeting inclusion criteria. Changes in the allergy record were recommended by the ASC for 62% (n = 371) of patients; however, the allergy record was updated after the ASC in 74.9% (n = 278) of patients. Conclusion: ASC recommendations to delabel a patient as beta-lactam allergic must result in updating the allergy record in order to optimize future treatment. Given the low proportion of allergy-labeled patients tested, programs outside formal ASCs should be considered.

Switch to atovaquone and subsequent re-challenge with trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis in a kidney transplant population

Kidney transplant recipients who are switched to atovaquone (ATO) from trimethoprim‐sulfamethoxazole (TMP/SMX) for Pneumocystis jirovecii pneumonia (PJP) prophylaxis because of adverse events or complications may miss opportunities to be re‐challenged with TMP/SMX, the first‐line agent. This single‐site, retrospective study assessed kidney transplant recipients for documented reasons for switching from TMP/SMX to alternate PJP prophylaxis and outcomes of TMP/SMX re‐challenge. Out of 166 patients, 155 initially received TMP/SMX; of these, 31 were switched to ATO for various reasons. Fourteen patients receiving ATO were re‐challenged with TMP/SMX; all were successfully re‐initiated on TMP/SMX therapy. Most patients switched to ATO post kidney transplant secondary to non‐hypersensitivity reasons should be re‐challenged with TMP/SMX because of the advantages it provides over other agents.

Analysis of an Infectious Diseases Pharmacist on Call Pager Program to Inform Educational Efforts

Background: An on call infectious diseases (ID) pharmacist may be used as a resource for physicians, pharmacists, and other health care providers to help answer questions regarding anti-infective agents. Objective: To assess type, requestor, resources dedicated, and temporal trends of questions received through an ID pharmacist on call pager program. A secondary objective was to gather insight as to how this information was utilized to inform educational initiatives. Methods: This was a retrospective study of questions received by the ID pharmacist on call via pager at a large academic medical center. Question data were documented in a central database and analyzed to assess temporal trends and question type, and qualitatively analyzed to determine areas for targeted educational efforts. Results: The ID pharmacist on call recorded 545 questions during the 1-year study period; questions were composed of various antimicrobial agent–related queries, including antibiotic spectrum and selection (n = 251, 46.1%), dosing of antimicrobials (n = 195, 35.8%), and drug monitoring (n = 26, 4.8%). Targeted educational initiatives secondary to questions received included pharmacist education regarding the use of polymyxin antibiotics and antibiotic dosing protocol updates. Conclusions: An ID pharmacist on call pager program was utilized to inquire about antibiotic spectrum and selection for the majority of questions. Records of questions received may be utilized to direct educational efforts and create or revise targeted resources for pharmacists and other clinicians.

Impact of Accelerate Pheno System on Time to Antimicrobial Stewardship Intervention in Patients with Gram-Negative Blood Stream Infections

Abstract Background Rapid diagnostic tests in combination with antimicrobial stewardship interventions have been shown to improve antimicrobial therapy-related outcomes in patients with blood stream infections (BSIs). The Accelerate Pheno™ System (APS) has a potential advantage over many currently approved rapid diagnostic tests in that it can quickly provide both identification and antimicrobial susceptibility (AS) information. This study aimed to explore the impact of utilization of the APS when compared with VITEK-2 on time to simulated antimicrobial stewardship service intervention (ASTEW-I) in patients with Gram-negative BSIs. Potential impact of availability of ASTEW-I based on time of day was also examined. Methods Consecutive patients with Gram-negative rod blood stream isolates were enrolled during a 3 month time frame (February-May 2017). The standard of care (SOC) laboratory protocol consisted of matrix-assisted laser desorption ionization time of flight (MALDI-TOF) for pathogen identification and VITEK-2 for AS results. Antimicrobial susceptibility reporting on the electronic health record was performed once daily in the morning. The isolates that were analyzed through SOC measures were also simultaneously tested on the APS. Time to ASTEW-I was simulated utilizing AS reporting time and availability of personnel for ASTEW-I based on time of day. Results 27 patients with positive blood cultures for Gram-negative rods were enrolled in the study. Mean decrease in time to simulated ASTEW-I with APS was 18 hours (95% CI 11.5–24.6) for 8 hour stewardship coverage. When stewardship coverage was extended to 16 hours, the mean decrease in time to ASTEWI-I with APS was 21.4 hours (95% CI 14.3–28.5). Both time differences were found to be statistically significant (P < 0.001). Conclusion In a cohort of patients with Gram-negative bacteremia, when compared with SOC, ASTEW-I guided by APS significantly shortened the time to potential antimicrobial optimization. This improvement occurred even when antimicrobial stewardship support was limited to an 8 hour work day.Figure 1: Protocol with simulated time difference for 8 hour stewardship service Disclosures C. Qi, Accelerate Diagnostics: Investigator, Research support