We performed a nested case-control study (ratio of 1:4) on the emergence of tigecycline-resistant multidrug-resistant Klebsiella pneumoniae (TR-MDRKP) isolates among patients who initially presented with a tigecycline-susceptible MDRKP isolate. Out of 260 patients, 24 (9%) had a subsequent clinical culture positive for a TR-MDRKP isolate within the 90-day follow-up period. On logistic regression analyses, receipt of tigecycline (adjusted odds ratio [OR], 5.06; 95% confidence interval [CI], 1.80 to 14.23; P ؍ 0.002) was the only independent predictor of subsequent isolation of a TR strain.T igecycline, a minocycline derivative, remains one of the few therapeutic options for the treatment of infections caused by multidrug-resistant Klebsiella pneumoniae (MDRKP) isolatesincluding Klebsiella pneumoniae carbapenemase (KPC) producers-and other Gram-negative organisms (1, 2). Of concern, tigecycline nonsusceptibility (i.e., tigecycline resistance [TR]) among Klebsiella pneumoniae isolates has been reported from different continents and ranged between 0% and 11.5% in a recent large study (3-6). Furthermore, several recent case studies identified patients who were treated with tigecycline for an initially tigecycline-susceptible MDRKP (TS-MDRKP) infection but from whom a TR-MDRKP strain was subsequently isolated (7-10). However, the potential of in vivo emergence of TR among MDRKP isolates has so far not been systematically investigated to our knowledge. We intended to study the rates of and risk factors for the in vivo emergence of TR among Klebsiella pneumoniae isolates in a large population of patients who initially presented with a TS-MDRKP.We performed a nested case-control study on the subsequent emergence of TR among all patients from whom a TS-MDRKP strain was previously isolated at a tertiary care center between January 2008 and July 2011. MDRKP was defined as the presence of either an extended-spectrum -lactamase (ESBL)-or KPCproducing Klebsiella pneumoniae isolate, determined as per Clinical and Laboratory Standards Institute (CLSI) guidelines on ESBL testing, carbapenem resistance patterns, and Hodge test results, respectively (11, 12). Food and Drug Administration (FDA) breakpoints were applied to interpret the results of tigecycline susceptibility testing using the disc diffusion method and Etest (susceptible if the zone diameter is Ն19 mm and the isolate MIC is Յ2 g/ml, respectively).A case was defined as a patient from whom a TR-MDRKP was isolated between Ͼ48 h and Ͻ90 days after the day a TS-MDRKP strain was isolated (zero time). A control was defined as a patient from whom a TS-MDRKP strain was isolated during the study period but with no subsequent TR-MDRKP strains. Controls were matched to cases based on the isolate's resistance mechanism (ESBL versus KPC) but otherwise randomly selected in a 1:4 ratio. Cases were compared to controls with regard to a variety of demographic and clinical characteristics. We also recorded (i) all antibiotic exposures within 90 days before zero time and (ii) all antib...
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.
A 42-year-old healthy woman presented with fever and photophobia with rapid progression to diplopia, dysphonia, and tongue deviation. The cerebral spinal fluid had pleocytosis, but cerebrospinal fluid and blood cultures were negative. Cerebrospinal fluid polymerase chain reaction was positive for Listeria monocytogenes. Brain imaging was consistent with rhomboencephalitis. She was successfully treated with a combination of ampicillin plus trimethoprim-sulfamethoxazole. We present this case to highlight the syndrome of listeria rhomboencephalitis and the evolving treatment options.
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