Antimicrobial Resistance Patterns of Outpatient Staphylococcus aureus Isolates.

Importance: Oral non-ß-lactam antibiotics are commonly used for empirical therapy of Staphylococcus aureus infections, especially in outpatient settings. However, little is known about potential geographic heterogeneity and temporal trends in the prevalence of S aureus resistance to non-ß-lactams in the US. Objective: To characterize the spatiotemporal trends of resistance to non-ß-lactam antibiotics among community-onset S aureus infections, including regional variation in resistance rates and geographical heterogeneity in multidrug resistance. Design, Setting, and Participants: This cross-sectional study used data from Veterans Health Administration clinics collected from adult outpatients with S aureus infection in the conterminous 48 states and Washington, DC, from January 1, 2010, to December 31, 2019. Data were analyzed from January to November 2023. Exposures: Resistance to lincosamides (clindamycin), tetracyclines, sulfonamides (trimethoprim-sulfamethoxazole [TMP-SMX]), and macrolides. Main Outcomes and Measures: Spatiotemporal variation of S aureus resistance to these 4 classes of non-ß-lactam antibiotics, stratified by methicillin-resistant S aureus (MRSA) and methicillin-sensitive S aureus (MSSA), and subdivided by regions of the US (Northeast, Midwest, South, and West). Trend tests and bivariate mapping were used to determine significant changes in resistant proportions over time and identify counties where rates of resistance to multiple non-ß-lactams were high. Results: A total of 382 149 S aureus isolates from 268 214 unique outpatients (mean [SD] age, 63.4 [14.8] years; 252 910 males [94.29%]) were analyzed. There was a decrease in the proportion of MRSA nationwide, from 53.6% in 2010 to 38.8% in 2019. Among MRSA isolates, we observed a significant increase in tetracycline resistance (from 3.6% in 2010 to 12.8% in 2019; P for trend < .001) and TMP-SMX resistance (from 2.6% in 2010 to 9.2% in 2019; P for trend < .001), modest and not significant increases in clindamycin resistance (from 24.2% in 2010 to 30.6% in 2019; P for trend = .34), and a significant decrease in macrolide resistance (from 73.5% in 2010 to 60.2% in 2019; P for trend < .001). Among MSSA isolates, significant upward trends in clindamycin, tetracyclines, and TMP-SMX resistance were observed. For example, tetracycline resistance increased from 3.7% in 2010 to 9.1% in 2019 (P for trend < .001). Regional stratification over time showed that the Northeast had slightly higher rates of clindamycin resistance but lower rates of tetracycline resistance, while the South had notably higher rates of resistance to tetracyclines and TMP-SMX, particularly among MRSA isolates. Bivariate mapping at the county scale did not indicate clear regional patterns of shared high levels of resistance to the 4 classes of antimicrobials studied. Conclusions and Relevance: In this study of outpatient S aureus isolates, MRSA became less common over the 10-year period, and MRSA isolates were increasingly resistant to tetracyclines and TMP-SMX. Geographic analysis indicated no spatial overlap in counties with high rates of resistance to both tetracyclines and TMP-SMX. Examining the regional spatial variation of antibiotic resistance can inform empirical therapy recommendations and help to understand the evolution of S aureus antibiotic resistance mechanisms.

Characterizing Ertapenem Neurotoxicity: A Systematic Review and Experience at a Tertiary Medical Center.

Ertapenem-induced neurotoxicity has not been well characterized and is potentially underreported. We conducted a systematic review of the literature and included 11 additional cases from the University of Washington Medicine health system. A total of 125 individual patient cases were included in the data analysis. The mean age was 72 years, and 62% and 42% of patients had renal dysfunction and preexisting central nervous system (CNS) conditions, respectively. Only 15% of patients received inappropriately high ertapenem dosing based on kidney function. Patients developed neurological signs and symptoms after a median of 4 days (interquartile range, 3-9 days). The most common clinical features were seizures (70%), altered level of consciousness or delirium (27%), and hallucinations (17%). An estimated incidence in our health system was 1 in 102 courses of ertapenem. Ertapenem neurotoxicity should be suspected when a patient with renal dysfunction or predisposing CNS conditions develops neurological signs and symptoms, especially within several days after initiating the antibiotic. This study underscores the need for a large prospective study to assess the true incidence and outcomes of ertapenem neurotoxicity.

Verification of acoustic streaming measurement accuracy via particle image velocimetry considering the interrogation window aspect ratio.

This study measured Rayleigh and Schlichting streaming velocities via particle image velocimetry (PIV) in a standing wave field. Emphasis was placed on balancing high measurement accuracy with high spatial resolution in the boundary layer region. We aimed to achieve high resolution and enhanced measurement accuracy, typically a trade-off, by significantly increasing the aspect ratio of the interrogation window in the flow direction during PIV post-processing. The experiment operated under conditions with a duct axis streaming velocity of approximately 8.3×10-3 m/s in the measurement area. Increasing the aspect ratio from 1 to 21 reduced the standard deviation across the entire radial direction, which served as the accuracy index, from 8.05×10-3 m/s to 5.23×10-4 m/s (94% reduction). Additionally, the method's validity was confirmed through synthetic images with particles of known velocity. This verification demonstrated a decrease in the standard deviation comparable to the experimental images (97% reduction), aligning the analyzed velocity's radial distribution with the known streaming velocity distribution.

Assessing the potential for improved predictive capacity of antimicrobial resistance in outpatient Staphylococcus aureus isolates using seasonal and spatial antibiograms.

BACKGROUND: While the use of cumulative susceptibility reports, antibiograms, is recommended for improved empiric therapy and antibiotic stewardship, the predictive ability of antibiograms has not been well-studied. While enhanced antibiograms have been shown to better capture variation in susceptibility profiles by characteristics such as infection site or patient age, the potential for seasonal or spatial variation in susceptibility has not been assessed as important in predicting likelihood of susceptibility. METHODS: Utilizing Staphylococcus aureus isolates obtained in outpatient settings from a nationwide provider of care, the Veterans Health Administration, and a local provider of care, the University of Iowa Hospitals and Clinics, standard, seasonal and spatial antibiograms were created for five commonly used antibiotic classes: cephalosporins, clindamycin, macrolides, tetracycline, trimethoprim/sulfamethoxazole. RESULTS: A total of 338,681 S. aureus isolates obtained in VHA outpatient settings from 2010 to 2019 and 6,817 isolates obtained in UIHC outpatient settings from 2014 to 2019 were used to generate and test antibiograms. Logistic regression modeling determined the capacity of these antibiograms to predict isolate resistance to each antibiotic class. All models had low predictive capacity, with areas under the curve of < 0.7. CONCLUSIONS: Standard antibiograms are poor in predicting S. aureus susceptibility to antibiotics often chosen by clinicians, and seasonal and spatial antibiograms do not provide an improved tool in anticipating non-susceptibility. These findings suggest that further refinements to antibiograms may be necessary to improve their utility in informing choice of effective antibiotic therapy.

Clinicians' interpretation of thresholds in hospital antibiograms for gram-negative rod infections: A survey and contingent valuation study of hospitalists.

Clinical guidelines suggest that hospital antibiograms are a key component when deciding empiric therapy, but little is known about how often clinicians use antibiograms and how they influence clinicians' empiric therapy decisions. We surveyed hospitalists at seven healthcare systems in the United States on their reported practices related to antibiograms and their hypothetical prescribing for four clinical scenarios associated with gram-negative rod pathogens. Each was given a randomly assigned antibiogram susceptibility percentage, and we used contingent valuation analysis to assess whether the antibiogram susceptibility percentage was associated with prescribing practices. Of the 193 survey responders, only 52 (26.9%) respondents reported using antibiograms more than monthly. Across all four clinical scenarios, there was no evidence that antibiogram susceptibility levels influenced antibiotic prescribing practices. With limited utilization and no evidence that they influenced practice, antibiograms may have a limited role in hospitalist care delivery for common gram-negative rod infections.

Clinical Characteristics, Treatment, and Outcomes of Veterans with Cerebrospinal Fluid Culture Positive for Gram-Negative Rod Bacteria: A Retrospective Analysis over 18 Years in 125 Veterans Health Administration Hospitals.

Optimal management for patients with bacterial ventriculitis/meningitis due to Gram-negative rods (GNRs) has yet to be well investigated. We assessed the clinical characteristics, treatment, and outcomes of patients with a positive cerebrospinal fluid (CSF) culture for GNRs. We conducted a retrospective cohort study of all patients with a positive CSF culture within the Veterans Health Administration (VHA) system during 2003-2020. Clinical and microbiological characteristics between the true meningitis and contamination groups were compared. Of the 5919 patients with positive CSF cultures among 125 nationwide VHA acute-care hospitals, 297 (5.0%) were positive for GNRs. Among 262 patients analyzed, 156 (59.5%) were assessed as patients with true meningitis, and 106 (40.5%) were assessed as patients with contaminated CSF cultures. Patients with true meningitis had a significantly higher CSF protein (median 168 vs 57 mg/dL, p < 0.001), CSF white blood cell count (median 525 vs 3/µL, p = 0.008) and percentage of neutrophils in CSF (median 88 vs 4%, p < 0.001). Enterobacterales were more common in the true meningitis group, while unidentified GNR or polymicrobial CSF cultures were more common in the contamination group. The all-cause 90-day mortality was 25.0% (39/156) in patients with true meningitis and 10.4% (11/106) in those with contaminated CSF cultures. None of the 11 patients with contaminated CSF cultures who died were considered due to missed meningitis. More than 40% of patients with a positive CSF culture with GNR did not receive treatment without negative consequences. Careful clinical judgment is required to decide whether to treat such patients.

Spatiotemporal distribution of community-acquired phenotypic extended-spectrum beta-lactamase Escherichia coli in United States counties, 2010-2019.

Using data from the Veterans' Health Administration from 2010 to 2019, we examined the distribution and prevalence of community-acquired phenotypic extended-spectrum ß-lactamase (ESBL) E. coli in the United States. ESBL prevalence slowly increased during the study period, and cluster analysis showed clustering in both urban and rural locations.

The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research.

Objective: We performed a systematic literature review and meta-analysis on the effectiveness of coronavirus disease 2019 (COVID-19) vaccination against post-COVID conditions (long COVID) among fully vaccinated individuals. Design: Systematic literature review/meta-analysis. Methods: We searched PubMed, Cumulative Index to Nursing and Allied Health, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to June 2, 2023, for studies evaluating the COVID-19 vaccine effectiveness (VE) against post-COVID conditions among fully vaccinated individuals who received two doses of COVID-19 vaccine. A post-COVID condition was defined as any symptom that was present four or more weeks after COVID-19 infection. We calculated the pooled diagnostic odds ratio (DOR) (95% confidence interval) for post-COVID conditions between fully vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% x (1-DOR). Results: Thirty-two studies with 775,931 individuals evaluated the effect of vaccination on post-COVID conditions, of which, twenty-four studies were included in the meta-analysis. The pooled DOR for post-COVID conditions among fully vaccinated individuals was 0.680 (95% CI: 0.523-0.885) with an estimated VE of 32.0% (11.5%-47.7%). Vaccine effectiveness was 36.9% (23.1%-48.2%) among those who received two doses of COVID-19 vaccine before COVID-19 infection and 68.7% (64.7%-72.2%) among those who received three doses before COVID-19 infection. The stratified analysis demonstrated no protection against post-COVID conditions among those who received COVID-19 vaccination after COVID-19 infection. Conclusions: Receiving a complete COVID-19 vaccination prior to contracting the virus resulted in a significant reduction in post-COVID conditions throughout the study period, including during the Omicron era. Vaccine effectiveness demonstrated an increase when supplementary doses were administered.

Persistence of potential ST398 MSSA in outpatient settings among US veterans, 2010-2019.

Novel ST398 methicillin susceptible Staphylococcus aureus (MSSA) in the United States was first observed in New York City (2004-2007); its diffusion across the country resulted in changing treatment options. Utilizing outpatient antimicrobial susceptibility data from the Veterans Health Administration from 2010 to 2019, the spatiotemporal prevalence of potential ST398 MSSA is documented.

Patient outcomes following home-based outpatient parenteral antimicrobial therapy and facility-based outpatient parenteral antimicrobial therapy: a systematic review and meta-analysis.

In this systematic literature review and meta-analysis, we did not find a statistically significant difference in readmission and treatment failure rates between home-based and facility-based OPAT. Optimal patient selection for appropriate OPAT location appears to be more important than the location itself for the best OPAT outcome.

Diagnostic Accuracy of Hospital Antibiograms in Predicting the Risk of Antimicrobial Resistance in Enterobacteriaceae Isolates: A Nationwide Multicenter Evaluation at the Veterans Health Administration.

BACKGROUND: Many clinical guidelines recommend that clinicians use antibiograms to inform empiric antimicrobial therapy. However, hospital antibiograms are typically generated by crude aggregation of microbiologic data, and little is known about an antibiogram's reliability in predicting antimicrobial resistance (AMR) risk at the patient-level. We aimed to assess the diagnostic accuracy of antibiograms as a tool for selecting empiric therapy for Escherichia coli and Klebsiella spp. for individual patients. METHODS: We retrospectively generated hospital antibiograms for the nationwide Veterans Health Administration (VHA) facilities from 2000 to 2019 using all clinical culture specimens positive for E. coli and Klebsiella spp., then assessed the diagnostic accuracy of an antibiogram to predict resistance for isolates in the following calendar year using logistic regression models and predefined 5-step interpretation thresholds. RESULTS: Among 127 VHA facilities, 1 484 038 isolates from 704 779 patients for E. coli and 671 035 isolates from 340 504 patients for Klebsiella spp. were available for analysis. For E. coli and Klebsiella spp., the discrimination abilities of hospital-level antibiograms in predicting individual patient AMR were mostly poor, with the areas under the receiver operating curve at 0.686 and 0.715 for ceftriaxone, 0.637 and 0.675 for fluoroquinolones, and 0.576 and 0.624 for trimethoprim-sulfamethoxazole, respectively. The sensitivity and specificity of the antibiogram varied widely by antimicrobial groups and interpretation thresholds with substantial trade-offs. CONCLUSIONS: Conventional hospital antibiograms for E. coli and Klebsiella spp. have limited performance in predicting AMR for individual patients, and their utility in guiding empiric therapy may be low.

High-Fat-Diet Suppressed Ketone Body Utilization for Lipogenic Pathway in Brown Adipose Tissues.

Brown adipose tissue (BAT) consumes excess lipids and produces lipid metabolites as ketone bodies. These ketone bodies are then recycled for lipogenesis by the enzyme acetoacetyl-CoA synthetase (AACS). Previously, we found that a high-fat diet (HFD) upregulated AACS expression in white adipose tissue. In this study, we investigated the effects of diet-induced obesity on AACS in BAT. When 4-week-old ddY mice were fed a HFD or high-sucrose diet (HSD) for 12 weeks, a significant decrease in Aacs, acetyl-CoA carboxylase-1 (Acc-1), and fatty acid synthase (Fas) expression was observed in the BAT of the HFD group, whereas expression was not affected in the HSD group. In vitro analysis showed decreased Aacs and Fas expression in rat primary-cultured brown adipocytes following isoproterenol treatment for 24 h. In addition, the suppression of Aacs by siRNA markedly decreased the expression of Fas and Acc-1 but did not affect the expression of uncoupling protein-1 (UCP-1) or other factors. These results suggested that HFD may suppress ketone body utilization for lipogenesis in BAT and that AACS gene expression may be important for regulating lipogenesis in BAT. Therefore, the AACS-mediated ketone body utilization pathway may regulate lipogenesis under conditions of excess dietary fat.

Effects of Antibacterial Agents on Cancerous Cell Proliferation.

Myelosuppression, a side effect of anticancer drugs, makes people more susceptible to infectious diseases by compromising the immune system. When a cancer patient develops a contagious disease, treatment with an anticancer drug is suspended or postponed to treat the infectious disease. If there was a drug that suppresses the growth of cancer cells among antibacterial agents, it would be possible to treat both infectious diseases and cancer. Therefore, this study investigated the effect of antibacterial agents on cancer cell development. Vancomycin (VAN) had little effect on cell proliferation against the breast cancer cell, MCF-7, prostate cancer cell, PC-3, and gallbladder cancer cell, NOZ C-1. Alternatively, Teicoplanin (TEIC) and Daptomycin (DAP) promoted the growth of some cancer cells. In contrast, Linezolid (LZD) suppressed the proliferation of MCF-7, PC-3, and NOZ C-1 cells. Therefore, we found a drug that affects the growth of cancer cells among antibacterial agents. Next, when we examined the effects of the combined use of existing anticancer and antibacterial agents, we found VAN did not affect the growth suppression by anticancer agents. However, TEIC and DAP attenuated the growth suppression of anticancer agents. In contrast, LZD additively enhanced the growth suppression by Docetaxel in PC-3 cells. Furthermore, we showed that LZD inhibits cancer cell growth by mechanisms that involve phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway suppression. Therefore, LZD might simultaneously treat cancer and infectious diseases.

Effectiveness of Ultraviolet-C Disinfection on Hospital-Onset Gram-Negative Rod Bloodstream Infection: A Nationwide Stepped-Wedge Time-Series Analysis.

BACKGROUND: The effectiveness of enhanced terminal room cleaning with ultraviolet C (UV-C) disinfection in reducing gram-negative rod (GNR) infections has not been well evaluated. We assessed the association of implementation of UV-C disinfection systems with incidence rates of hospital-onset (HO) GNR bloodstream infection (BSI). METHODS: We obtained information regarding UV-C use and the timing of implementation through a survey of all Veterans Health Administration (VHA) hospitals providing inpatient acute care. Episodes of HO-GNR BSI were identified between January 2010 and December 2018. Bed days of care (BDOC) was used as the denominator. Over-dispersed Poisson regression models were fitted with hospital-specific random intercept, UV-C disinfection use for each month, baseline trend, and seasonality as explanatory variables. Hospitals without UV-C use were also included to the analysis as a nonequivalent concurrent control group. RESULTS: Among 128 VHA hospitals, 120 provided complete survey responses with 40 reporting implementations of UV-C systems. We identified 13 383 episodes of HO-GNR BSI and 24 141 378 BDOC. UV-C use was associated with a lower incidence rate of HO-GNR BSI (incidence rate ratio: 0.813; 95% confidence interval: .656-.969; P = .009). There was wide variability in the effect size of UV-C disinfection use among hospitals. CONCLUSIONS: In this large quasi-experimental analysis within the VHA System, enhanced terminal room cleaning with UV-C disinfection was associated with an approximately 19% lower incidence of HO-GNR BSI, with wide variability in effectiveness among hospitals. Further studies are needed to identify the optimal implementation strategy to maximize the effectiveness of UV-C disinfection technology.

The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post-COVID-19 conditions: A systematic literature review and meta-analysis.

Background: Although multiple studies have revealed that coronavirus disease 2019 (COVID-19) vaccines can reduce COVID-19-related outcomes, little is known about their impact on post-COVID-19 conditions. We performed a systematic literature review and meta-analysis on the effectiveness of COVID-19 vaccination against post-COVID-19 conditions (ie, long COVID). Methods: We searched PubMed, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to April 27, 2022, for studies evaluating COVID-19 vaccine effectiveness against post-COVID-19 conditions among individuals who received at least 1 dose of Pfizer/BioNTech, Moderna, AstraZeneca, or Janssen vaccine. A post-COVID-19 condition was defined as any symptom that was present 3 or more weeks after having COVID-19. Editorials, commentaries, reviews, study protocols, and studies in the pediatric population were excluded. We calculated the pooled diagnostic odds ratios (DORs) for post-COVID-19 conditions between vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% × (1 - DOR). Results: In total, 10 studies with 1,600,830 individuals evaluated the effect of vaccination on post-COVID-19 conditions, of which 6 studies were included in the meta-analysis. The pooled DOR for post-COVID-19 conditions among individuals vaccinated with at least 1 dose was 0.708 (95% confidence interval (CI), 0.692-0.725) with an estimated vaccine effectiveness of 29.2% (95% CI, 27.5%-30.8%). The vaccine effectiveness was 35.3% (95% CI, 32.3%-38.1%) among those who received the COVID-19 vaccine before having COVID-19, and 27.4% (95% CI, 25.4%-29.3%) among those who received it after having COVID-19. Conclusions: COVID-19 vaccination both before and after having COVID-19 significantly decreased post-COVID-19 conditions for the circulating variants during the study period although vaccine effectiveness was low.