A Case of New Delhi Metallo-ß-Lactamase-Producing Enterobacter and a Review of Cases in the United States From January 2009 to September 2022.

Antimicrobial resistance is a growing problem. Novel resistance mechanisms continue to emerge, and the pipeline of antimicrobial development struggles to keep up. Antimicrobial stewardship and proper infection control are key in preventing the spread of these infections. A case of a carbapenem-resistant Enterobacter cloacae complex urinary isolate was identified in an 81-year-old male patient at the San Antonio Veterans Affairs hospital, Texas, USA. The patient was placed on isolation, and further testing of the isolate to other antibiotics requested. The purpose of this study is to analyze the details of reports of such cases and to review at-risk populations and appropriate treatment for resistant organisms.

Clinical utility of methicillin-resistant Staphylococcus aureus nasal PCR to streamline antimicrobial use in treatment of diabetic foot infection with or without osteomyelitis.

BACKGROUND: Diabetic Foot Infection (DFI) guidelines recommend empiric methicillin-resistant Staphylococcus aureus (MRSA)-targeted therapy in settings where there is high prevalence of MRSA infections or in cases of severe infection; however, they do not provide recommendations for de-escalation. This approach has the potential to increase unnecessary use of broad-spectrum antibiotics; therefore, additional strategies are needed to optimize appropriate antibiotic use. This study evaluates the effect of MRSA nasal PCR testing on MRSA-targeted antibiotic use and clinical outcomes in patients with DFI. METHODS: This was a retrospective quasi-experimental study of patients admitted to South Texas Veterans Health Care System for DFI, with or without osteomyelitis (OM), who had an MRSA nasal PCR and culture data. Eligible patients were identified from the Corporate Data Warehouse and reviewed via electronic health record. Patients were allocated into two groups: PRE (5/1/2019-4/30/2020) and POST (12/1/2020-11/30/2021) protocol implementation for de-escalation or avoidance of MRSA-targeted antibiotics. The primary outcome was median (interquartile range [IQR]) hours of empiric inpatient MRSA-targeted antibiotic therapy. A Wilcoxon Rank Sum test was used to assess the difference between the groups for the primary outcome. Secondary outcomes included the proportion of patients needing MRSA coverage added back for MRSA after de-escalation, hospital readmission, length of hospital stay (LOS), patient mortality, and acute kidney injury. RESULTS: A total of 151 patients were included (83 PRE; 68 POST). Most patients were male (98% PRE; 97% POST) with a median age of 64 (IQR, 56-72) years. Incidence of MRSA in DFI in the cohort was 14.7% overall (12% PRE and 17.6% POST). MRSA was detected via nasal PCR in 12% of patients 15.7% PRE and 7.4% POST). After protocol implementation, there was a significant decrease in empiric MRSA-targeted antibiotic therapy use, from a median of 72 (IQR, 27-120) hours in the PRE group, to 24 (IQR, 12-72) hours in the POST group (p < 0.01). No significant differences were found for other secondary outcomes. CONCLUSION: This study of patients presenting to a Veterans Affairs (VA) hospital with DFI identified a statistically significant decrease in median duration of MRSA-targeted antibiotic use post-protocol implementation. This suggests a favorable effect of MRSA nasal PCR for de-escalation or avoidance of MRSA-targeted antibiotics in DFI.

Comparative-Effectiveness of Oral Beta-Lactams and Fluoroquinolones for Stepdown Therapy in Patients with Enterobacterales Bloodstream Infections: A Retrospective Cohort Study.

Background: This study compares treatment failure for patients who received oral beta-lactams (BLs) and fluoroquinolones (FQs) for stepdown treatment of Enterobacterales bloodstream infections (BSIs). Methods: We conducted a single-center, retrospective, age- and sex-matched, cohort study, at a Veterans Affairs (VA) hospital in South Texas. Eligible patients were at least 18 years of age with a monomicrobial BSI treated with a single oral BL or FQ antibiotic. Treatment failure was defined as recurrence or all-cause mortality within 90 days of documented BSI. Bivariate (chi-square, Fisher's Exact, and Wilcoxon Rank Sum) and multivariate (logistic regression) statistical tests were used to compare groups. Results: A total of 130 patients were included in this study, with 65 patients per group. Groups were well balanced with respect to exact age, sex assigned at birth, Caucasian race, source control, intensive care unit admission, and Charlson Comorbidity Index. Importantly, 60% of patients in the BL group had cultures that were resistant to FQs and 71% were prescribed cefpodoxime. Patients in the BL group had higher median (interquartile range [IQR]) Pitt bacteremia scores than those in the FQ group: 2 (1-4) vs. 1 (1-2), p=0.04. Patients in the BL group also had a higher median (IQR) duration of intravenous (IV) antibiotics than those in the FQ group: 5 (3-7) vs. 4 (3-5), p=0.02. Treatment failure was statistically comparable for patients in the BL and FQ groups: 15% vs. 12%, p=0.61. This finding was consistent in a multivariate logistic regression model with group (BL vs. FQ) as the independent variable, treatment failure as the dependent variable, and Pitt bacteremia score and duration of IV antibiotics as covariates (OR: 0.76, 95% CI: 0.27-2.18). One patient in the FQ group experienced Clostridioides difficile infection. Conclusion: This study suggests that BLs may be as effective as FQs for oral stepdown treatment of Enterobacterales BSI without the potential associated risks. Furthermore, in the setting of FQ-resistant Enterobacterales BSI secondary to urinary source, third generation oral cephalosporins (i.e., cefpodoxime) may be reasonable alternatives.

Correlation Between Patients With Methicillin-Resistant Staphylococcus aureus (MRSA) Nares Colonization and MRSA Diabetic Foot Infections.

Infectious Diseases Society of America diabetic foot infection (DFI) guidelines indicate empiric methicillin-resistant Staphylococcus aureus (MRSA) coverage for patients with a history of MRSA infection, when local prevalence of MRSA is high, or infection is clinically severe. These recommendations may lead to overutilization of empiric MRSA coverage, which can result in serious consequences. A strong negative predictive value (NPV) has been reported in literature for pneumonia, and recently, for all anatomical sites of infection. While these findings are promising, further validation is needed before clinicians may confidently use MRSA nares to guide empiric therapy for DFIs. A retrospective electronic medical record review was completed between October 1, 2013 and October 1, 2019. Patients met inclusion criteria if they were at least 18, admitted with a DFI, had MRSA nares test results, and DFI cultures. Patients were excluded if pregnant or MRSA infection within 1 year prior to index admission for DFI. A total of 200 patients met inclusion criteria. The majority of study participants were male with a mean age of 63. NPV of MRSA nares for MRSA DFIs was determined to be 94% and positive predictive value 58%. Sensitivity and specificity were 56% and 94%, respectively. Results of this study are consistent with prior literature supporting strong correlation of NPV for MRSA nares. The DFIs evaluated suggest a strong NPV of MRSA nares for MRSA DFIs, which may allow for faster de-escalation of empiric anti-MRSA antibiotic therapy and lower risk of adverse events associated with anti-MRSA therapy.

Clinical impact of implementation of rapid diagnostic testing of blood cultures with Staphylococcus aureus on patient outcomes.

Rapid diagnostic testing in microbiology labs shortens the time to identification of bacteria in blood cultures. Cepheid® GeneXpert® MRSA/SA PCR can be used to distinguish MRSA and MSSA from non-Staphylococcus aureus organisms in blood cultures. This study aims to determine if implementation of MRSA/SA PCR for blood culture pathogen identification, plus daily antimicrobial stewardship intervention, can reduce time to appropriate therapy, vancomycin duration, 30 day mortality, and 90 day recurrence in veterans. A total of 113 patients in the pre-implementation cohort and 73 patients in the post-implementation cohort were evaluated. Time to appropriate therapy was decreased from 49.8 (pre-implementation) to 20.6 (post-implementation) hours. There was a numerically shorter median duration of vancomycin therapy in the post-implementation group. There was no difference in 30 day mortality or 90 day recurrence between groups. Use of MRSA/SA PCR can improve antimicrobial use when combined with once-daily antimicrobial stewardship review.

Comparing the Clinical Utility of Rapid Diagnostics for Treatment of Bloodstream Infections Using Desirability of Outcome Ranking Approach for the Management of Antibiotic Therapy (DOOR-MAT).

Decisions regarding which rapid diagnostic test (RDT) for bloodstream infections to implement remain challenging given the diversity of organisms detected by different platforms. We used the desirability of outcome ranking management of antimicrobial therapy (DOOR-MAT) as a framework to compare two RDT platforms on potential desirability of antimicrobial therapy decisions. An observational study was performed at University of Maryland Medical System comparing Verigene blood culture (BC) to GenMark Dx ePlex blood culture ID (BCID) (research use only) panels on blood cultures from adult patients. Positive percent agreement (PPA) between each RDT platform and Vitek MS was calculated for comparison of on-panel targets. Theoretical antimicrobial decisions were made based on RDT results, taking into consideration patient parameters, antimicrobial stewardship practices, and local infectious diseases epidemiology. DOOR-MAT with a partial credit scoring system was applied to these decisions, and mean scores were compared across platforms using a paired t test. The study consisted of 160 unique patients. The Verigene BC PPA was 98.6% (95% confidence interval [CI], 95.1 to 99.8), and ePlex BCID PPA was 98% (95% CI, 94.3 to 99.6). Among the 31 organisms not on the Verigene BC panels, 61% were identified by the ePlex BCID panels. The mean (standard deviation [SD]) DOOR-MAT score for Verigene BC was 86.8 (28.5), while that for ePlex BCID was 91.9 (23.1) (P = 0.01). Both RDT platforms had high PPA for on-panel targets. The ePlex BCID was able to identify more organisms than Verigene, resulting in higher mean DOOR-MAT scores.

Validation of Available Extended-Spectrum-Beta-Lactamase Clinical Scoring Models in Predicting Drug Resistance in Patients with Enteric Gram-Negative Bacteremia Treated at South Texas Veterans Health Care System.

Extended-spectrum-beta-lactamase (ESBL)-producing Enterobacteriaceae are increasingly common; however, predicting which patients are likely to be infected with an ESBL pathogen is challenging, leading to increased use of carbapenems. To date, five prediction models have been developed to distinguish between patients infected with ESBL pathogens. The aim of this study was to validate and compare each of these models to better inform antimicrobial stewardship. This was a retrospective cohort study of patients with Gram-negative bacteremia treated at the South Texas Veterans Health Care System over 3 months from 2018 to 2019. We evaluated isolate, clinical syndrome, and score variables for the five published prediction models/scores: Italian "Tumbarello," Duke, University of South Carolina (USC), Hopkins clinical decision tree, and modified Hopkins. Each model was assessed using the area under the receiver operating characteristic curve (AUROC) and Pearson correlation. One hundred forty-five patients were included for analysis, of which 20 (13.8%) were infected with an ESBL Escherichiacoli or Klebsiella spp. The most common sources of infection were genitourinary (55.8%) and gastrointestinal/intraabdominal (24.1%), and the most common pathogen was E. coli (75.2%). The prediction model with the strongest discriminatory ability (AUROC) was Tumbarello (0.7556). The correlation between prediction model score and percent ESBL was strongest with the modified Hopkins model (R2 = 0.74). In this veteran population, the modified Hopkins and Duke prediction models were most accurate in discriminating between Gram-negative bacteremia patients when considering both AUROC and correlation. However, given the moderate discriminatory ability, many patients with ESBL Enterobacteriaceae (at least 25%) may still be missed empirically.

Fluoroquinolone Restriction as an Effective Antimicrobial Stewardship Intervention.

PURPOSE OF REVIEW: Fluoroquinolones are a commonly prescribed antibiotic class that has come under scrutiny in recent years due to mounting evidence of association between adverse drug events, C. difficile infection and isolation of antibiotic-resistant bacteria. RECENT FINDINGS: Inpatient antimicrobial stewardship (AMS) programs have a toolbox of potential interventions to curb inappropriate antibiotic use, prevent antibiotic-associated adverse drug events, and avoid unnecessary costs of care. Fluoroquinolone restriction policies in the acute care setting have demonstrated beneficial effects, including decreased rates of C. difficile infection and ESBL-producing Enterobacteriaceae. However, a simple blanket restriction policy may "squeeze the antibiotic balloon" and will likely be insufficient if not implemented in conjunction with other AMS interventions. There is a growing body of evidence to support formulary restriction of fluoroquinolones in the acute care setting to decrease rates of C. difficile infection and development of ESBL-producing organisms. Data on how to best implement these restrictions or how to implement outside of acute care settings is limited.