14-Year Epidemiologic study of Pseudomonas aeruginosa bloodstream infection incidence and resistance in the Veterans Health Administration system, 2009-2022.

Background: Multidrug resistant Pseudomonas aeruginosa (PA) represents a serious threat to hospitalized patients. Characterizing the incidence of PA infection and degree of resistance can inform empiric treatment and preventative measures. Objectives: We sought to describe trends in incidence and resistance characteristics of PA bloodstream infections (BSI) observed within the Veterans Health Administration (VHA) system and identify factors contributing to higher observed mortality within this population. Methods: We characterized demographic and clinical features of unique patients among the VHA population presenting with their first episode of PA-BSI between 2009 and 2022 and summarized trends related to mortality and resistance phenotype based on year and geographical location. We additionally used logistic regression analysis to identify predictors of 30-day mortality among this cohort. Results: We identified 8039 PA-BSIs during the study period, 32.7% of which were hospital onset. Annual PA-BSI cases decreased by 35.8%, and resistance among all antimicrobial classes decreased during the study period, while the proportion of patients receiving early active treatment based on susceptibility testing results increased. Average 30-day mortality rate was 23.3%. Higher Charlson Comorbidity Index, higher mAPACHE score, VHA facility complexity 1b and hospital-onset cases were associated with higher mortality, and early active treatment was associated with lower mortality. Conclusions: PA-BSI resistance decreased across the VHA system during the study period. Further investigation of antimicrobial stewardship measures possibly contributing to the observed decreased resistance in this cohort and identification of measures to improve on the high mortality associated with PA-BSI in the VHA population is warranted.

Nicotine Metabolite Ratio Decreases After Switching Off Efavirenz-Based Therapy in People With HIV Who Smoke.

Rates of cigarette smoking in people with HIV (PWH) are two to three times higher than in people without HIV. Nicotine is metabolized by CYP2A6 and the nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine) is a measure of nicotine clearance. Higher NMR has been observed in PWH and is associated with lower quit rates. Efavirenz, a mainstay antiretroviral therapy (ART) globally, partially upregulates its own metabolism through CYP2A6. We hypothesized that efavirenz also upregulates nicotine metabolism by CYP2A6, resulting in a higher NMR, and switching to non-efavirenz ART would decrease the NMR, potentially leading to improved quit rates. We compared the NMR during and after efavirenz use among PWH in a longitudinal, multisite cohort. Eligibility criteria included: (i) active cigarette smoking, (ii) ART switched from efavirenz-based to non-efavirenz-based regimen, (iii) plasma available at pre- and post-ART switch, and (iv) viral suppression during study period. Plasma cotinine and 3-hydroxycotinine were measured by liquid chromatography-tandem mass spectrometry. T-tests compared the NMR on and off efavirenz. Samples were collected between 2010 and 2019 in 72 PWH. The mean NMR difference after switching to a non-efavirenz-based regimen was -0.24 (SD: 0.37, P < 0.001); 44 PWH had at least a 0.1 decrease in NMR. Effect modification by race was present; Black PWH had a larger mean decrease. Our findings suggest that previously observed higher NMR among PWH may be due to direct pharmacologic effects of ART. Assessing the effect of ART on the NMR suggests that avoiding nicotine metabolism inducers could potentially increase quit rates.

Association of COVID-19 coinfection with increased mortality among patients with Pseudomonas aeruginosa bloodstream infection in the Veterans Health Administration system.

Objective: Pseudomonas aeruginosa bloodstream infection (PA-BSI) and COVID-19 are independently associated with high mortality. We sought to demonstrate the impact of COVID-19 coinfection on patients with PA-BSI. Design: Retrospective cohort study. Setting: Veterans Health Administration. Patients: Hospitalized patients with PA-BSI in pre-COVID-19 (January 2009 to December 2019) and COVID-19 (January 2020 to June 2022) periods. Patients in the COVID-19 period were further stratified by the presence or absence of concomitant COVID-19 infection. Methods: We characterized trends in resistance, treatment, and mortality over the study period. Multivariable logistic regression and modified Poisson analyses were used to determine the association between COVID-19 and mortality among patients with PA-BSI. Additional predictors included demographics, comorbidities, disease severity, antimicrobial susceptibility, and treatment. Results: A total of 6,714 patients with PA-BSI were identified. Throughout the study period, PA resistance rates decreased. Mortality decreased during the pre-COVID-19 period and increased during the COVID-19 period. Mortality was not significantly different between pre-COVID-19 (24.5%, 95% confidence interval [CI] 23.3-28.6) and COVID-19 period/COVID-negative (26.0%, 95% CI 23.5-28.6) patients, but it was significantly higher in COVID-19 period/COVID-positive patients (47.2%, 35.3-59.3). In the modified Poisson analysis, COVID-19 coinfection was associated with higher mortality (relative risk 1.44, 95% CI 1.01-2.06). Higher Charlson Comorbidity Index, higher modified Acute Physiology and Chronic Health Evaluation score, and no targeted PA-BSI treatment within 48 h were also predictors of higher mortality. Conclusions: Higher mortality was observed in patients with COVID-19 coinfection among patients with PA-BSI. Future studies should explore this relationship in other settings and investigate potential SARS-CoV-2 and PA synergy.

Can Electronic Clinical Decision Support Systems Improve the Diagnosis of Urinary Tract Infections? A Systematic Review and Meta-Analysis.

Background: Urinary tract infection (UTI) is a commonly misdiagnosed infectious syndrome. Diagnostic stewardship interventions can reduce rates of asymptomatic bacteriuria treatment but are often labor intensive, and thus an automated means of reducing unnecessary urine testing is preferred. In this systematic review and meta-analysis, we sought to identify studies describing interventions utilizing clinical decision support (CDS) to optimize UTI diagnosis and to characterize the effectiveness of these interventions. Methods: We conducted a comprehensive electronic search and manual reference list review for peer-reviewed articles published before July 2, 2021. Publications describing an intervention intending to enhance UTI diagnosis via CDS were included. The primary outcome was urine culture test rate. Results: The electronic search identified 5013 studies for screening. After screening and full-text review, 9 studies met criteria for inclusion, and a manual reference list review identified 5 additional studies, yielding a total of 14 studies included in the systematic review. The most common CDS intervention was urinalysis with reflex to urine culture based on prespecified urinalysis parameters. All 9 studies that provided statistical comparisons reported a decreased urine culture rate postintervention, 8 of which were statistically significant. A meta-analysis including 4 studies identified a pooled urine culture incidence rate ratio of 0.56 (95% confidence interval, .52-.60) favoring the postintervention versus preintervention group. Conclusions: In this systematic review and meta-analysis, CDS appeared to be effective in decreasing urine culture rates. Prospective trials are needed to confirm these findings and to evaluate their impact on antimicrobial prescribing, patient-relevant outcomes, and potential adverse effects.

Tailored Treatment Based on Helicobacter pylori Genetic Markers of Resistance Is Associated With Higher Eradication Success.

INTRODUCTION: Increasing antimicrobial resistance with Helicobacter pylori infection has focused efforts to tailor eradication therapy based on identifying genetic markers of resistance to predict antimicrobial susceptibility. METHODS: In this retrospective study, we report the effect of routine inclusion of antimicrobial susceptibility testing and recommendations for eradication therapy with gastric specimens with H. pylori . RESULTS: The use of a recommended treatment regimen based on genetic markers of resistance was associated with an 84% rate of eradication success and 4.4 greater odds of eradication relative to unrecommended treatment. DISCUSSION: This is the first study describing the use of H. pylori genetic resistance testing as standard of care.

Prevention and treatment of COVID-19 in patients with benign and malignant blood disorders.

Patients with moderate to severe immunosuppression, a condition that is common in many hematologic diseases because of the pathology itself or its treatment, are at high risk for COVID-19 and its complications. While empirical data are sometimes conflicting, this heightened risk has been confirmed in multiple well-done studies for patients with hematologic malignancies, particularly those with B-cell lymphoid malignancies who received lymphocytotoxic therapies, those with a history of recent hematopoietic stem cell transplant and chimeric antigen receptor T-cell therapy, and, to a lesser degree, those with hemoglobinopathies. Patients with immunosuppression need to have a lower threshold for avoiding indoor public spaces where they are unable to effectively keep a safe distance from others, and wear a high-quality well-fitting mask, especially when community levels are not low. They should receive an enhanced initial vaccine regimen and additional boosting. Therapeutic options are available and immunosuppressed patients are prioritized per the NIH.

Using Preventive Health Alerts in the Electronic Health Record Improves Hepatitis C Virus Testing Among Infants Perinatally Exposed to Hepatitis C.

BACKGROUND: Perinatal exposure to hepatitis C virus (HCV) is a major public health issue, and poor testing rates leave many children with infection unidentified. We sought to use the electronic health record (EHR) to promote guideline-directed HCV testing among infants born to mothers with HCV infection in an urban, safety-net hospital system. METHODS: Our study population was identified using our EHR database, Epic. Children were included in the study if they had perinatal HCV exposure, were 18 months to 18 years of age and had at least 1 encounter in a primary or urgent care clinic during the study period. Our study included retrospective (October 2011 to February 2015) and prospective (February 2015 to May 2018) arms. Our EHR-based intervention was initiated in the prospective arm and recommended a one-time HCV antibody test at or after the age of 18 months using a health maintenance reminder. The health maintenance reminder activated a point-of-care alert and a linked HCV testing order set in all prespecified encounters during the intervention period. RESULTS: Median time to appropriate HCV testing decreased from 96.2 months preintervention to 9.1 months postintervention (P < 0.0001), and rate of completed antibody testing increased from 14% to 61% (P < 0.0001). CONCLUSIONS: Among children with perinatal HCV exposure, using a point-of-care alert within the EHR significantly increased the HCV antibody testing rate in accordance with American Academy of Pediatrics (AAP) recommendations. More effective EHR-based interventions combined with increased provider awareness of appropriate HCV testing in perinatally exposed infants is imperative.

Effectiveness of Shorter Versus Longer Durations of Therapy for Common Inpatient Infections Associated With Bacteremia: A Multicenter, Propensity-Weighted Cohort Study.

BACKGROUND: National guidelines for pneumonia (PNA), urinary tract infection (UTI), and acute bacterial skin and skin structure infection (ABSSSI) do not address treatment duration for infections associated with bacteremia. We evaluated clinical outcomes of patients receiving shorter (5-9 days) versus longer (10-15 days) duration of antibiotics. METHODS: This was a multicenter retrospective cohort study of inpatients with uncomplicated PNA, UTI, or ABSSSI and associated bacteremia. The primary outcome was clinical failure, a composite of rehospitalization, reinitiation of antibiotics, or all-cause mortality within 30 days of antibiotic completion. Secondary outcomes included individual components of the primary outcome, Clostridioides difficile infection, and antibiotic-related adverse effects necessitating change in therapy. A propensity score-weighted logistic regression model was used to mitigate potential bias associated with nonrandom assignment of treatment duration. RESULTS: Of 408 patients included, 123 received a shorter treatment duration (median 8 days) and 285 received a longer duration (median 13 days). In the propensity-weighted analysis, the probability of the primary outcome was 13.5% in the shorter group and 11.1% in the longer group (average treatment effect, 2.4%; odds ratio [OR], 1.25; 95% confidence interval [CI], .65-2.40; P = .505). However, shorter courses were associated with higher probability of restarting antibiotics (OR, 1.62; 95% CI, 1.01-2.61; P = .046) and C. difficile infection (OR, 4.01; 95% CI, 2.21-7.59; P < .0001). CONCLUSIONS: Shorter courses of antibiotic treatment for PNA, UTI, and ABSSSI with bacteremia were not associated with increased overall risk of clinical failure; however, prospective studies are needed to further evaluate the effectiveness of shorter treatment durations.