Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (blaNDM and blaKPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.

Diagnostic Accuracy of BD Phoenix CPO Detect for Carbapenemase Production in 190 Enterobacteriaceae Isolates.

The rapid and accurate detection of carbapenemase-producing Enterobacteriaceae (CPE) is necessary for patient management and infection control measures. We compared the performance of the BD Phoenix CPO Detect with that of a homemade Carba NP assay and a modified carbapenem inactivation method (mCIM) by challenging all 3 assays with 190 isolates of Enterobacteriaceae with meropenem MICs of >0.125 mg/liter. A total of 160 isolates produced KPC-, IMI-1-, NDM-, IMP-, and OXA-type carbapenemases, while 30 isolates were negative for carbapenemase production. The sensitivity and specificity were 90.6% (95% confidence interval [CI], 85.0% to 94.7%) and 100.0% (95% CI, 88.4% to 100.0%), respectively, for the Carba NP; 100.0% (95% CI, 97.7% to 100.0%) and 96.7% (95% CI, 82.7% to 99.9%), respectively, for the mCIM; and 89.4% (95% CI, 83.5% to 93.7%) and 66.7% (95% CI, 47.2% to 82.7%), respectively, for the BD Phoenix CPO Detect. In particular, the BD CPO Detect failed to detect a significant number of CPE with IMI-1. While the BD Phoenix CPO Detect is able to classify carbapenemases and is built into routine susceptibility testing with the potential to reduce the time to CPE detection, its low specificity means that a positive result will need confirmatory testing by another method.

Direct costs associated with febrile neutropenia in inpatients with hematological diseases in Singapore.

PURPOSE: This prospective cohort study aims to investigate the direct hospitalization costs incurred during febrile neutropenia (FN) in inpatients with underlying hematological conditions and also to elucidate the factors associated with a high cost of managing febrile neutropenia. METHODS: Patients with underlying hematological conditions and documented FN were recruited between October 2008 and February 2011. FN-related costs included all costs incurred from the first day of FN until the last day of antibiotics prescribed. Relevant clinical factors were analyzed using generalized estimating equation models to elucidate the factors that were associated with higher costs of FN. RESULTS: A total of 175 patients were recruited with 303 documented episodes of FN. In non-transplant patients, 75.6 % of the FN episodes occurred. The median and mean cost incurred for each FN episode was USD9,060 (interquartile range = USD5,047-16,631) and USD15,298 (standard deviation ± USD17,459), respectively, accounting for approximately 38 % of the median total hospitalization cost and 37 % of the mean total hospitalization cost. The ward charges (44.1 %) constituted the largest component of the cost, followed by the laboratory charges (27.3 %) and medications (18.7 %), of which antimicrobials constituted 9.6 % of the cost of FN. The factors associated with higher costs of FN include cytomegalovirus reactivation (p < 0.001), longer duration of antibiotics (p < 0.001), lower absolute neutrophil count nadir (p < 0.001), allogeneic stem cell transplantation (p < 0.01), and diagnosis of invasive fungal infection (p < 0.05). CONCLUSION: The economic cost of management of FN in hematology inpatients is considerable and in addition to the overall risk of mortality for this condition. Strategies to reduce FN or ameliorate its costs are essential for this group of patients.

An optimized algorithm with improved turnaround time for detection of carbapenemase-producing Enterobacterales using the NG Test CARBA 5 in a routine laboratory.

Introduction. Rapid and reliable detection of carbapenemase-producing Enterobacterales (CPE) from surveillance cultures is critical in supporting a good infection control programme. We implemented a new algorithm for CPE detection incorporating the NG Test CARBA 5 in January 2019.Aim. Our goals were to compare turnaround time (TAT), costs and staff requirements between the old and new algorithm, and to evaluate the performance of the CARBA 5 test directly on colonies grown on CARBA Smart agar.Methodology. We analysed and compared the TAT of CPE surveillance cultures processed using the old and new CPE screening algorithm. The total actual reagent costs and staff requirements for the new CPE algorithm were compared with the estimated costs and staff requirements of the old CPE algorithm.Results. Of 197 isolates included in the evaluation of the new algorithm, 64 were positive for carbapenemases by both CARBA 5 and Xpert Carba-R assay. Of the 133 that were negative, two were found to harbour NDM and IMI genotypes. Significant improvements in TAT were achieved with 88.7 % of cultures with CPE, reported on the same day as growth was observed on CARBA Smart agar compared to none in the old algorithm. The new algorithm incurred lower costs and, based on our workload, the new algorithm is estimated to save 28.9 man-hours annually.Conclusion. CARBA 5 performs well on colonies growing on CARBA Smart agar and significant improvements in TAT can be achieved without incurring additional costs or staff requirements.

A Prediction Tool for the Presence of Ceftriaxone-Resistant Uropathogens upon Hospital Admission.

Antimicrobial resistance among uropathogens is a particularly pressing problem in the Asia-Pacific region. The objectives of this study were to determine the incidence and susceptibility of uropathogens upon hospital admission and to develop a risk-scoring model to predict the presence of ceftriaxone-resistance uropathogens (CrP). This was a retrospective observational cohort study of patients with a positive urine culture within 48 h of presentation at National University Hospital, Singapore between June 2015 and August 2015. Escherichia coli was the most common uropathogen isolated (51.7%), followed by Klebsiella pneumonia (15.1%) and Pseudomonas aeruginosa (8.2%). Overall, 372 out of 869 isolates (42.8%) were resistant to ceftriaxone. Hospitalization for ≥2 days within past 30 days, antibiotic use within the past 3 months and male gender were associated with the presence of CrP. A risk score based on these parameters successfully predicted CrP with an area under the curve of 0.68. The risk score will help clinicians to accurately predict antibiotic resistance at the individual patient level and allow physicians to safely prescribe empiric ceftriaxone in patients at low risk of CrP, thus reducing the antibiotic selection pressure that is driving carbapenem resistance in hospitals throughout Asia.

Pseudo-outbreak of Rhizobium radiobacter infection resulting from laboratory contamination of saline solution.

We report a pseudo-outbreak of Rhizobium radiobacter infections resulting from contamination by a saline dispenser in the microbiology laboratory. Isolates from clinical specimens had identical antimicrobial susceptibilities and electrophoretic fingerprints. The episode resolved with autoclaving of the dispenser. This demonstrates the importance of timely, thorough investigation of unusual organisms, particularly when they appear as a cluster.

An evaluation of the recovery of mycobacteria from urine specimens using the automated Mycobacteria Growth Indicator Tube system (BACTEC MGIT 960).

The Mycobacteria Growth Indicator Tube (MGIT 960) system was evaluated against Lowenstein-Jensen (LJ) medium and the BACTEC 460 TB system for the recovery of mycobacteria from 1393 consecutive urine specimens. The MGIT had a sensitivity of 91.3% [95% confidence interval (CI), 83.2-99.4] when the combination of BACTEC 460 and LJ medium was used as the reference method. The mean time for positivity for MGIT and BACTEC 460 was 19.3 days and 20 days, respectively, while that for LJ medium was 35 days.The incidence of contamination was highest for LJ medium (n=148), followed by MGIT 960 (n=81), and BACTEC 460 had the lowest incidence of contamination (n=50). In conclusion, the isolation of mycobacteria from urine specimens by the MGIT 960 is comparable to that of the BACTEC 460 TB system and solid media.

Uncovering what lies beneath a Salmonella enterica empyema.

A 67-year-old woman with myelodysplastic syndrome (MDS) and transfusional haemosiderosis developed Salmonella empyema caused by direct extension from splenic abscesses. She was successfully treated with antibiotics, pleural decortication and splenectomy. She had presented with fever after being treated for presumed pneumonia and parapneumonic effusion 2 months prior. CT scan showed splenic abscesses eroding through the diaphragm causing a left pleural empyema. Pleural fluid and spleen bacterial cultures grew Salmonella enterica. She was treated with 4 weeks of antibiotics and underwent surgical pleural decortication and splenectomy in the same sitting. She made a good postoperative recovery. Patients with severe iron overload are susceptible to various types of bacterial sepsis, including salmonellosis. It is unusual for enteric bacterial such as Salmonella to present with empyema, and should prompt a search for intra-abdominal infection. Pleural decortication and splenectomy can be performed during the same surgical sitting and can lead to good surgical outcomes.

Antimicrobial stewardship auditing of patients reviewed by infectious diseases physicians in a tertiary university hospital.

BACKGROUND: The optimal way for antimicrobial stewardship programs (ASPs) to interact with existing infectious disease physician (IDP) services within the same institution is unknown. In our institution, IDPs and our prospective audit and feedback ASP operate independently, with occasionally differing recommendations offered for the same inpatient. We performed a retrospective audit on inpatients that had been reviewed by both IDPs and ASP within a 7-day period, focusing on cases where different therapy-modifying recommendations had been offered. We analyzed the outcomes in inpatients where the ASP recommendations were accepted and compared these with the inpatients where the IDP recommendations were accepted instead. Outcomes assessed were 30-day mortality post-ASP review, unplanned re-admission within 30 days post-discharge from hospital, and clinical deterioration at 7 days post-ASP review. FINDINGS: There were 143 (18.9%) patients where differing recommendations had been offered, with primary physicians accepting 69.9% of ASP recommendations. No significant differences in terms of demographics, clinical characteristics, 30-day mortality, and re-admission rates were observed, although clinical deterioration rates were lower in patients where the ASP recommendation was accepted (8.0% vs. 27.9%; p = 0.002). On multivariate analysis, hematology-oncology inpatients were associated with unplanned readmission. Increasing age and hematology-oncology inpatients were associated with clinical deterioration 7 days post-recommendation, whereas acceptance of ASP recommendations was protective. No characteristic was independently associated with 30-day mortality. CONCLUSION: In conclusion, independent reviews by both IDPs and ASPs can be compatible within large tertiary hospitals, providing primary physicians even in situations of conflicting recommendations viable alternative antimicrobial prescribing advice.

Specialist trainees on rotation cannot replace dedicated consultant clinicians for antimicrobial stewardship of specialty disciplines.

Our prospective-audit-and-feedback antimicrobial stewardship (AS) program for hematology and oncology inpatients was switched from one led by dedicated clinicians to a rotating team of infectious diseases trainees in order to provide learning opportunities and attempt a "de-escalation" of specialist input towards a more protocol-driven implementation. However, process indicators including the number of recommendations and recommendation acceptance rates fell significantly during the year, with accompanying increases in broad-spectrum antibiotic prescription. The trends were reversed only upon reverting to the original setup. Dedicated clinicians play a crucial role in AS programs involving immunocompromised patients. Structured training and adequate succession/contingency planning is critical for sustainability.