In a double-blind multicentre study the efficacy and safety of a single-dose treatment with pefloxacin (800 mg) was compared with a five-day treatment regimen of 960 mg co-trimoxazole twice daily in the therapy of acute uncomplicated cystitis in women. In order to maintain blindness, patients in the pefloxacin group received placebo to complement the full number of tablets. Nine centres were involved; 155 patients received pefloxacin and 161 patients received co-trimoxazole. Of these, 140 patients treated with pefloxacin and 145 with co-trimoxazole were considered valid for efficacy and safety analysis. At the first follow-up, after seven to ten days, 97.1% of the pefloxacin group and 95.2% of the co-trimoxazole group were bacteriologically cured. At the second follow-up visit, after 28 to 42 days, the urine culture was negative in 95.0% of the pefloxacin group and 90.3% of the co-trimoxazole group. A single dose of 800 mg pefloxacin was demonstrated to be as safe and at least as effective as a five-day regimen of co-trimoxazole in the treatment of uncomplicated cystitis.

Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) have been considered prevalent pathogens in foot infections. However, whether empiric therapy directed against these organisms is necessary, and in whom to consider treatment, is rather unclear. The aim of this study was to develop predictive algorithms for forecasting the probability of isolating these organisms in the infected wounds of patients in a population where the prevalence of resistant pathogens is low. This was a retrospective study of regression model-based risk factor analysis that included 140 patients who presented with infected, culture positive foot ulcers to two urban hospitals. A total of 307 bacteria were identified, most frequently MRSA (11.1%). P. aeruginosa prevalence was 6.5%. In the multivariable analysis, amputation (odds ratio (OR) 5.75, 95% confidence interval (CI) 1.48–27.63), renal disease (OR 5.46, 95% CI 1.43–25.16) and gangrene (OR 2.78, 95% CI 0.82–9.59) were identified as risk factors associated with higher while diabetes (OR 0.07, 95% CI 0.01–0.34) and Infectious Diseases Society of America infection severity >3 (OR 0.18, 95% CI 0.03–0.65) were associated with lower odds of P. aeruginosa isolation (C statistic 0.81). Similar analysis for MRSA showed that amputation was associated with significantly lower (OR 0.29, 95% CI 0.09–0.79) risk, while history of MRSA infection (OR 5.63, 95% CI 1.56–20.63) and osteomyelitis (OR 2.523, 95% CI 1.00–6.79) was associated with higher odds of isolation (C statistic 0.69). We developed two predictive nomograms with reasonable to strong ability to discriminate between patients who were likely of being infected with P. aeruginosa or MRSA and those who were not. These analyses confirm the association of some, but also question the significance of other frequently described risk factors in predicting the isolation of these organisms.

Background During the first three months of the COVID 19 pandemic, our facility cared for an influx of patients. At the peak, the daily census exceeded 200 patients with COVID 19. Surveillance for healthcare acquired infections (HAIs) continued throughout this time. Despite the acuity of the patients and the frequent use of antibiotics, the rates of Clostridioides difficile lab ID (CDI) events remained relatively stable. We sought to determine the validity of this rate. Methods To determine if cases of CDI were missed, we compared the 3-month rate per 10,000 patient days in 2020 to the same time-period in 2019 (March, April, and May). The number of tests ordered during the two periods was also compared. Additionally, the Doctor of Pharmacy from our antibiotic stewardship team reviewed all orders for oral Vancomycin to determine if empiric CDI treatment was initiated without confirmatory testing. Results The CDI rate for the 3 months in 2019 was zero compared to 0.48 per 10,000 patient days during the peak of the pandemic. The number of tests increased in the 2020 period to 17.5 per 10,000 patient days versus 15.8 in the 2019 period. Three patients received oral Vancomycin, each of whom had valid indications. Conclusions Based on this data, CDI cases were not underreported. We speculate that the lack of an increase in CDI rates may be attributed to: Increased hand hygiene by staff – compliance increased to 91 % in 2020 compared to 83 % in 2019,enhanced attention to cleaning and high level disinfection, and Improved adherence to use of personal protective equipment.

BackgroundTorsades de pointes is a life-threatening ventricular tachycardia associated with prolongation of the QT interval. Many diseases and medications have been implicated as potentially prolonging the QT interval, but little data exists regarding the means of quantifying this risk. The aim of this study was to describe the impact of commonly used antimicrobials on the QT interval in hospitalized patients.MethodsDemographic, diseases, laboratory, medication administration history and ECG recording data were collected from the electronic records of adult patients admitted, from July 2018 to December 2018, to two urban hospitals. A model for the QT interval comprised of four sub-models: gender, heart rate, circadian rhythm, and the drug and disease effects. Fixed and random effects with between occasion variability were estimated for the parameters. A Bayesian approach using the NUTS in STAN was used via the brms package in the R® software.ResultsData from 1,353 patients were used with baseline characteristics shown in Table 1. Observed vs. predicted plots based on the training (Figure 1A) and validation data set (Figure 1B) showed a great fit. The parameters for QTc0, α, gender, and circadian rhythm were accurately identified (Table 2). Similarly, the model correctly described the expected impact of acute or chronic diseases on the QT interval. Uncertainty interval estimates (Figure 2) show that patients treated with fluconazole and levofloxacin are likely to present with a QT interval [mean (95% CI) of 6.84 (0.22,21.45) and 5.05 (0.15, 16.70), respectively], that is > 5 ms longer vs. no treatment, the minimum cutoff that should evoke further risk assessment of QT interval prolongation.ConclusionThe model developed correctly describes the impact baseline risk factors have on the QT interval. Point estimates of QT interval prolongation show that patients treated with fluconazole and levofloxacin may be at considerable risk; while those treated with azithromycin or ciprofloxacin are more likely to be at an insignificant risk for QT interval prolongation during hospital admission. Further workup to quantify the impact of concomitant treatment with these and other at-risk medications is underway. Disclosures All authors: No reported disclosures.

ACOG Committee Opinion #797 proposed intrapartum vancomycin dosing guidelines in the absence of thorough evaluation of its risk versus benefit profile on the maternal and neonatal systems. The previously published serum and cord-blood concentration–time data of vancomycin given to mothers in the intrapartum period was analyzed in this work with a two-compartment pharmacokinetic (PK) model. Monte Carlo simulation was used to establish exposure for the studied population for doses of 1000 mg to 2000 mg every 8 h for gestational ages (GA) of 33 to 40 weeks and for birth times up to 4-hour intervals. Probabilities of target attainment (PTA) were calculated for efficacy and toxicity indices unique to the peripartum maternal and neonatal population. Neonatal evaluations indicate uniformly high PTAs for the evaluated dosing regimens when the efficacy target is considered. On the other hand, the PTAs for potentially nephrotoxic exposure is expected to reach undesirable levels when three or more doses were to be administered. The risk is profoundly high in GA below 36 weeks and birth times beyond 20 h after the initiation of intrapartum prophylaxis and with doses greater than 1250 mg. Maternal vancomycin exposures seem reasonable up to two intrapartum doses given at 8 h intervals when the dose is kept to 1250 mg or less. Most mothers (up to 83%) who receive three or more doses of the commonly administered regimens are subjected to nephrotoxic exposures. Thus, it appears that the current recommendations by #797 for dosing of vancomycin pose considerable risk to mother and newborn alike, especially in cases with lengthy duration of preterm labor. Capping of doses at 1250 mg may be considered to minimize the need for therapeutic drug monitoring (TDM) interventions. Alternatively, and irrespective of the baseline maternal renal function, TDM for all cases requiring more than two doses of 1500 mg or higher must be assured.