Schuetz, Audrey N.

SUMMARY This document outlines a comprehensive practical approach to a laboratory quality management system (QMS) by describing how to operationalize the management and technical requirements described in the ISO 15189 international standard. It provides a crosswalk of the ISO requirements for quality and competence for medical laboratories to the 12 quality system essentials delineated by the Clinical and Laboratory Standards Institute. The quality principles are organized under three main categories: quality infrastructure, laboratory operations, and quality assurance and continual improvement. The roles and responsibilities to establish and sustain a QMS are outlined for microbiology laboratory staff, laboratory management personnel, and the institution's leadership. Examples and forms are included to assist in the real-world implementation of this system and to allow the adaptation of the system for each laboratory's unique environment. Errors and nonconforming events are acknowledged and embraced as an opportunity to improve the quality of the laboratory, a culture shift from blaming individuals. An effective QMS encourages “systems thinking” by providing a process to think globally of the effects of any type of change. Ultimately, a successful QMS is achieved when its principles are adopted as part of daily practice throughout the total testing process continuum.

Abstract Background Bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is associated with inadequate empirical therapy and substantial mortality in neutropenic patients. Strategies are needed to identify neutropenic patients at high risk of these infections. Methods From April 2014 to September 2016, we collected perianal swabs, both at admission and weekly thereafter, from patients undergoing hematopoietic stem cell transplantation (HSCT). Patients received prophylactic levofloxacin while neutropenic. Swabs were plated onto selective agar, colonies were identified and underwent antimicrobial susceptibility testing, and phenotypic ESBL testing and polymerase chain reaction for β-lactamase genes were performed on ceftriaxone-resistant Enterobacteriaceae. We then determined the prevalence of pre-transplant ESBL-E colonization and risk of ESBL-E bacteremia. Colonizing and bloodstream isolates from patients with ESBL-E bacteremia underwent multilocus sequence typing and pulsed-field gel electrophoresis. Results We analyzed 312 patients, including 212 allogeneic and 100 autologous HSCT recipients. Ten percent (31/312) of patients had pre-transplant ESBL-E colonization. Susceptibility rates of colonizing ESBL-E were: levofloxacin, 25%; cefepime, 9%; piperacillin-tazobactam, 84%; and meropenem, 97%. Of 31 patients colonized with ESBL-E pre-transplant, 10 (32%) developed ESBL-E bacteremia during their transplant admission, compared to 1 (0.4%) of 281 patients not colonized with ESBL-E (P < .001). All bloodstream ESBL-E were levofloxacin-resistant and colonizing and bloodstream isolates from individual patients had identical genotypic profiles. Conclusions HSCT recipients who are colonized with levofloxacin-resistant ESBL-E pre-transplant and receive levofloxacin prophylaxis have high rates of bacteremia from their colonizing strain during neutropenia. Assessing for ESBL-E colonization in neutropenic patients could lead to optimization of empirical antibacterial therapy.

Introduction Mycobacterial spindle cell pseudotumour (MSP) is a rare disease characterised by tumour-like local proliferation of spindle-shaped histiocytes containing acid-fast positive mycobacteria. The aim of this literature review is to describe the clinical parameters and treatment outcomes of patients with MSP. Methods A literature search was conducted using the search terms related to mycobacteria and spindle cell tumours. A previously unreported stem cell transplant recipient from our institution diagnosed with MSP was also included. Demographics, comorbidities, site of infection, treatment and clinical outcomes were analysed. Results Fifty-one patients were analysed. Twenty-six (51%) had HIV infection. Mycobacterium avium complex was the most frequent organism isolated in 24 (47.1%) followed by Mycobacterium tuberculosis complex in eight (16%) cases. Lymph nodes were the most common site of infection (45.1%). Twenty (39.2%) patients received antimycobacterial agents, 12 (23.5%) underwent surgical resection and six (11.8%) received antimycobacterial agents plus surgery. Treatment was successful in 24 (47.1%) patients and failed in 15 (29.4%); 13 of these 15 patients died. Antimycobacterial therapy was significantly associated with successful outcome compared with surgical resection or no treatment (P<0.001). Conclusion MSP is a rare condition associated primarily with immunodeficiencies. Antimycobacterial therapy is significantly associated with successful outcome.

INTRODUCTIONBeta-lactam/beta-lactamase inhibitor combination antimicrobials (BLBLIs) are among the most controversial classes of antibiotic agents available for the treatment of infections caused by extended-spectrum-beta-lactamase (ESBL)-producing Gram-negative bacteria (ESBL-GNR). Piperacillin-tazobactam (PTZ) is one of the most frequently utilized antibiotic agents for empirical Gram-negative bacterial coverage and remains active against a large proportion of ESBL-GNR strains. Furthermore, good antimicrobial stewardship practices encourage the use of carbapenem-sparing treatment regimens for infections due to ESBL-GNR. As rapid diagnostics are increasingly used in the clinical microbiology laboratory and have the capability of detecting CTX-M type or other ESBL resistance mechanisms, this issue continues to be pertinent. Some data imply reduced efficacy of PTZ against ESBLs. Several factors may affect a clinician's choice to use BLBLIs, including the isolate's MIC, the site and severity of infection, and the type of resistance mechanism. These factors are explored in this review of the pros and cons of BLBLI treatment of invasive infections due to ESBL-producing bacteria, as well as how laboratories should report results for BLBLIs for these organisms as they relate to antimicrobial stewardship. In this Point-Counterpoint, Audrey Schuetz provides the pro point of view and Sergio Reyes and Pranita Tamma provide the con, counterpoint view.

ABSTRACT Although carbapenems are effective for treating serious multidrug-resistant Pseudomonas aeruginosa infections, carbapenem-resistant P. aeruginosa (CRPA) is now being reported worldwide. Ceftolozane-tazobactam (C/T) demonstrates activity against many multidrug-resistant isolates. We evaluated the activity of C/T and compared its activity to that of ceftazidime-avibactam (C/A) using a well-characterized collection of non-carbapenemase-producing CRPA isolates. Forty-two non-carbapenemase-producing CRPA isolates from a previous study (J. Y. Lee and K. S. Ko, Int J Antimicrob Agents 40:168–172, 2012, https://doi.org/10.1016/j.ijantimicag.2012.04.004 ) were included. All had been previously shown to be negative for bla IMP , bla VIM , bla SPM , bla GIM , bla SIM , and bla KPC by PCR. In the prior study, expression of oprD , ampC , and several efflux pump genes had been defined by quantitative reverse transcription-PCR. Here, antimicrobial susceptibility was determined by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Time-kill curve assays were performed using three C/T- and C/A-susceptible CRPA isolates. Among 42 non-carbapenemase-producing CRPA isolates, overall susceptibility to C/T was 95.2%, compared to 71.4%, 42.9%, 23.8%, 21.4%, and 2.4% for C/A, ceftazidime, piperacillin-tazobactam, cefepime, and meropenem, respectively. The C/T resistance rate was significantly lower than that of C/A among isolates showing decreased oprD and increased mexB expression (5.1% versus 25.6%, P = 0.025, and 4.3% versus 34.8%, P = 0.022, respectively). In time-kill curve studies, C/T was less bactericidal than C/A against an isolate with decreased oprD and increased ampC expression. C/T was active against 95.2% of non-carbapenemase-producing CRPA clinical isolates. No apparent correlation of C/T MIC values with specific mutation-driven resistance mechanisms was noted.

ABSTRACT Eighty Gram-negative bacilli (54 Enterobacteriaceae and 26 nonfermenting Gram-negative bacilli) obtained from multiple institutions in the United States were distributed in a blinded manner to seven testing laboratories to compare their performance of a test for detection of carbapenemase production, the Carba NP test. The Carba NP test was performed by all laboratories, following the Clinical and Laboratory Standards Institute (CLSI) procedure. Site-versus-site comparisons demonstrated a high level of consistency for the Carba NP assay, with just 3/21 site comparisons yielding a difference in sensitivity ( P < 0.05). Previously described limitations with bla OXA-48-like carbapenemases and bla OXA carbapenemases associated with Acinetobacter baumannii were noted. Based on these data, we demonstrate that the Carba NP test, when implemented with the standardized CLSI methodology, provides reproducible results across multiple sites for detection of carbapenemases.