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The major mechanism of fluoroquinolone (FQ) resistance in Pseudomonas aeruginosa (PSA) is modification of target proteins in DNA gyrase and topoisomerase IV, most commonly the gyrA and parC subunits. The objective of this study was to determine risk factors for PSA with and without gyrA or parC mutations.
Two adult academic acute-care hospitals
Case 1 study participants had a PSA isolate on hospital day 3 or later with any gyrA or parC mutation; case 2 study participants had a PSA isolate on hospital day 3 or later without these mutations. Controls were a random sample of all inpatients with a stay of 3 days or more.
Each case group was compared to the control group in separate multivariate models on the basis of demographics and inpatient antibiotic exposure, and risk factors were qualitatively compared.
Of 298 PSA isolates, 172 (57.7%) had at least 1 mutation. Exposure to vancomycin and other agents with extended Gram-positive activity was a risk factor for both cases (case 1 odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04–1.13; OR, 1.14; 95% CI, 1.03–1.26; case 2 OR, 1.09; 95% CI, 1.03–1.14; OR, 1.13; 95% CI, 1.01–1.25, respectively).
Exposure to agents with extended Gram-positive activity is a risk factor for isolation of PSA overall but not for gyrA/parC mutations. FQ exposure is not associated with isolation of PSA with mutations.
Staphylococcus aureus is a cause of community- and healthcare-acquired infections and is associated with substantial morbidity, mortality, and costs. Vancomycin minimum inhibitory concentrations (MICs) among S. aureus have increased, and reduced vancomycin susceptibility (RVS) may be associated with treatment failure. We aimed to identify clinical risk factors for RVS in S. aureus bacteremia.
Academic tertiary care medical center and affiliated urban community hospital.
Cases were patients with RVS S. aureus isolates (defined as vancomycin E-test MIC >1.0 μg/mL). Controls were patients with non-RVS S. aureus isolates.
Of 392 subjects, 134 (34.2%) had RVS. Fifty-eight of 202 patients (28.7%) with methicillin-susceptible S. aureus (MSSA) isolates had RVS, and 76 of 190 patients (40.0%) with methicillin-resistant S. aureus (MRSA) isolates had RVS (P = .02). In unadjusted analyses, prior vancomycin use was associated with RVS (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.00–4.32; P = .046). In stratified analyses, there was significant effect modification by methicillin susceptibility on the association between vancomycin use and RVS (P = .04). In multivariate analyses, after hospital of admission and prior levofloxacin use were controlled for, the association between vancomycin use and RVS was significant for patients with MSSA infection (adjusted OR, 4.02; 95% CI, 1.11–14.50) but not MRSA infection (adjusted OR, 0.87; 95% CI, 0.36–2.13).
A substantial proportion of patients with S. aureus bacteremia had RVS. The association between prior vancomycin use and RVS was significant for patients with MSSA infection but not MRSA infection, suggesting a complex relationship between the clinical and molecular epidemiology of RVS in S. aureus.
Prior-approval antimicrobial stewardship programs (ASPs) improve patient outcomes and decrease antimicrobial resistance. These benefits would be limited if physicians circumvented ASP efforts. We evaluated whether prescribers wait until after the prior-approval period to order restricted antimicrobial therapy that is in conflict with guidelines or unnecessary.
A cross-sectional study design and a retrospective cohort study design.
A tertiary care, academic medical center with a prior-approval ASP that was active between 8 AM and 10 PM.
We evaluated whether there was an increase in the proportion of orders for antimicrobial therapy that involve restricted (vs nonrestricted) antimicrobials during the first hour that the ASP is inactive (ie, the first hour that prior approval is not required), compared with the remainder of the day. We also evaluated whether restricted antimicrobial therapy ordered during this first hour is less likely to be continued when the ASP becomes active the next day, compared with that ordered during the preceding hour.
A greater proportion of the antimicrobial therapy orders placed between 10:00 PM and 10:59 PM were for restricted agents, compared with orders placed during other periods (57.0% vs 49.9%; P = .02). Surgical patients for whom antimicrobial therapy orders were placed between 10:00 PM and 10:59 PM were less likely to have that antimicrobial therapy continued, compared with patients whose therapy was ordered between 9:00 PM and 9:59 PM (60.0% vs 98.1%; P <.001). Nonsurgical patients whose therapy orders were placed between 10:00PM and 10:59 PM were also less likely to have the ordered antimicrobial therapy continued, compared with patients whose therapy was ordered between 9:00 PM and 9:59 PM (70.8% vs 84.2%; P = .01).
Physicians avoid having to obtain prior approval for therapy involving restricted antimicrobials by waiting until restrictions are no longer active to place orders. Compared with restricted antimicrobial therapy ordered when the ASP is active, these courses of therapy are less often continued by the ASP, suggesting that they are more likely to be in conflict with guidelines or unnecessary.
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