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Objective: To determine the prevalence, outcomes, and predictors of multidrug-resistant nosocomial lower respiratory tract infections (LRTI) in patients in an ICU. Methods: This was an observational cohort study involving patients with nosocomial LRTI (health care-associated pneumonia, hospital-acquired pneumonia, or ventilator-associated pneumonia). Data were prospectively collected between 2015 and 2019. The multidrugresistant pathogens (MDRPs) identified in the isolates studied included resistant to extended-spectrum cephalosporin-resistant and carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa, carbapenem-resistant Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus at microbiological diagnosis. Results: During the study period, 267 patients in the ICU were diagnosed with LRTI, microbiological confirmation of LRTI having been obtained in 237. Of these, 146 (62%) had at least one MDRP isolate. Patients infected with MDRP were found to have poorer outcomes than patients infected with susceptible strains, such as prolonged mechanical ventilation (18.0 days vs. 12.0 days; p < 0.001), prolonged ICU length of stay (23.0 days vs.16.0 days; p < 0.001), and higher mortality (73% vs. 53%; p < 0.001) when compared with patients infected with susceptible strains. Hospital length of stay ≥ 5 days (OR = 3.20; 95% CI: 1.39-7.39; p = 0.005) and prolonged use vasoactive drugs (OR = 3.15; 95% CI: 1.42-7.01; p = 0.004) were independent predictors of LRTI caused by MDRPs (LRTI-MDRP). The presence of LRTI-MDRP was found to be an independent predictor of death (OR = 2.311; 95% CI: 1.091-4.894; p = 0.028). Conclusions: Prolonged use of vasoactive drugs and prolonged hospital length of stay were independent predictors of LRTI-MDRP in this population of critically ill patients with very poor outcomes. [ABSTRACT FROM AUTHOR]

Objective: To analyze the impact that the 2009 changes in tuberculosis treatment in Brazil had on the rates of cure, tuberculosis recurrence, mortality, treatment abandonment, and multidrug-resistant tuberculosis (MDR-TB). Methods: An ordinary least squares regression model was used in order to perform an interrupted time series analysis of secondary data collected from the Brazilian Tuberculosis Case Registry Database for the period between January of 2003 and December of 2014. Results: The 2009 changes in tuberculosis treatment in Brazil were found to have no association with reductions in the total number of cases (β = 2 .17; 9 5% C I: - 3.80 t o 8 .14; p = 0 .47) and in the number of new cases (β = -0.97; 95% CI: -5.89 to 3.94; p = 0.70), as well as having no association with treatment abandonment rates (β = 0.40; 95% CI: -1.12 to 1.93; p = 0.60). The changes in tuberculosis treatment also showed a trend toward an association with decreased cure rates (β = -4.14; 95% CI: -8.63 to 0.34; p = 0.07), as well as an association with increased mortality from pulmonary tuberculosis (β = 0.77; 95% CI: 0.16 to 1.38; p = 0.01). Although there was a significant increase in MDR-TB before and after the changes (p < 0.0001), there was no association between the intervention (i.e., the changes in tuberculosis treatment) and the increase in MDR-TB cases. Conclusions: The changes in tuberculosis treatment were unable to contain the decrease in cure rates, the increase in treatment abandonment rates, and the increase in MDR-TB rates, being associated with increased mortality from pulmonary tuberculosis during the study period. [ABSTRACT FROM AUTHOR]

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Purpose: The development of multidrug resistance is a problem in chemotherapy for many tumors. In vitro models of multidrug resistance require adapted cell strains that are conventionally produced from parental lines by chronic low dose drug exposure. Because adjunctive intravesical chemotherapy for superficial bladder cancer uses short courses of high dose treatment, we investigated whether such exposure of the RT112 cell line (Catalogue No. ACC 418, Deutsche Sammlung von Mikroorganismen und Zellkulturen, Braunschweig, Germany) to mitomycin C, which is a common intravesical agent, would elicit multidrug resistance. Materials and Methods: Three 1-hour exposures to graded concentrations were done at 3-week intervals. The highest mitomycin C concentrations permitting recovery in cultures and, therefore, available for examination were 3.13 and 1.06 μg/ml. Cross-resistance to epirubicin in surviving cultures was visualized by confocal microscopy and quantified by MTT residual viable biomass assay. Spheroids were made by the agarose technique and exposed to high dose mitomycin C to assess the probability that the relevant concentrations might be found clinically in some cell layers of a superficial lesion. Results: Resistance was induced by 3 short drug exposures. The evidence for this was functional (MTT assay) and by intracellular localization. Toxicity to an alternative multidrug resistance class drug was lowered in surviving clones and nuclear exclusion of the drug was noted. Spheroid experiments showed sharp gradients of incorporated drug across the outermost layers of cells, suggesting that a proportion of cells in clinical superficial bladder cancer would be exposed to drug at concentrations that generated the resistant clones in these experiments. Conclusions: We report multidrug resistance induction using 2 independent methodologies. The results have implications for the development of experimental models and the likelihood of resistance resulting from clinical regimens. Brief exposure can elicit detectable resistance. It is arguable that selective rather than instructive mechanisms are involved, and the levels of drug required are likely to exist in a superficial transitional cell carcinoma frond exposed at its surface to high drug concentrations. [Copyright &y& Elsevier]