Healthcare-associated infections on the intensive care unit in 21 Brazilian hospitals during the early months of the coronavirus disease 2019 (COVID-19) pandemic: An ecological study.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis and may have affected healthcare-associated infection (HAI) prevention strategies. We evaluated the impact of the COVID-19 pandemic on HAI incidence in Brazilian intensive care units (ICUs). METHODS: In this ecological study, we compared adult patients admitted to the ICU from April through June 2020 (pandemic period) with the same period in 2019 (prepandemic period) in 21 Brazilian hospitals. We used the Wilcoxon signed rank-sum test in a pairwise analysis to compare the following differences between the pandemic and the prepandemic periods: microbiologically confirmed central-line-associated bloodstream infection (CLABSI) and ventilator-associated pneumonia (VAP) incidence density (cases per 1,000 central line and ventilator days, respectively), the proportion of organisms that caused HAI, and antibiotic consumption (DDD). RESULTS: We detected a significant increase in median CLABSI incidence during the pandemic: 1.60 (IQR, 0.44-4.20) vs 2.81 (IQR, 1.35-6.89) (P = .002). We did not detect a significant difference in VAP incidence between the 2 periods. In addition, we detected a significant increase in the proportion of CLABSI caused by Enterococcus faecalis and Candida spp during the pandemic, although only the latter retained statistical significance after correction for multiple comparisons. We did not detect a significant change in ceftriaxone, piperacillin-tazobactam, meropenem, or vancomycin consumption between the studied periods. CONCLUSIONS: There was an increase in CLABSI incidence in Brazilian ICUs during the first months of COVID-19 pandemic. Additionally, we detected an increase in the proportion of CLABSI caused by E. faecalis and Candida spp during this period. CLABSI prevention strategies must be reinforced in ICUs during the COVID-19 pandemic.

Virulomic Analysis of Multidrug-Resistant Klebsiella pneumoniae Isolates and Experimental Virulence Model Using Danio rerio (Zebrafish).

This study evaluates a possible correlation between multidrug-resistant Klebsiella pneumoniae strains and virulence markers in a Danio rerio (zebrafish) model. Whole-genome sequencing (WGS) was performed on 46 strains from three Brazilian hospitals. All of the isolates were colistin-resistant and harbored blaKPC-2. Ten different sequence types (STs) were found; 63% belonged to CC258, 22% to ST340, and 11% to ST16. The virulence factors most frequently found were type 3 fimbriae, siderophores, capsule regulators, and RND efflux-pumps. Six strains were selected for a time-kill experiment in zebrafish embryos: infection by ST16 was associated with a significantly higher mortality rate when compared to non-ST16 strains (52% vs. 29%, p = 0.002). Among the STs, the distribution of virulence factors did not differ significantly except for ST23, which harbored a greater variety of factors than other STs but was not related to a higher mortality rate in zebrafish. Although several virulence factors are described in K. pneumoniae, our study found ST16 to be the only significant predictor of a virulent phenotype in an animal model. Further research is needed to fully understand the correlation between virulence and sequence types.

A prospective study of treatment of carbapenem-resistant Enterobacteriaceae infections and risk factors associated with outcome.

BACKGROUND: To describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death. METHODS: A prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA). RESULTS: One hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the Bla KPC gene was found in 75.6 % of isolates, and 27 % of isolates were resistant to colistin. Mortality related to infection was 34.6 %, and was higher among patients with pneumonia (61.4 %). Combination therapy was used in 98 (77.2 %), and monotherapy in 22.8 %; 96.5 % of them were UTI patients. Shock, age, and dialysis were independent risk factors for death. There was no difference in infection-related death comparing colistin-susceptible and colistin-resistant infections (p = 0.46); neither in survival rate comparing the use of combination therapy with two drugs or more than two drugs (p = 0.32). CONCLUSIONS: CRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the bla KPC gene was the only carbapenemase found. Shock, dialysis, and age over 60 years were independent risk factors for death.

Fatores associados à mortalidade de pacientes com enterobactéria resistente aos carbapenêmicos / Factors associated with the mortality of patients with enterobacteriaceae arbapenem-resistant

As Enterobactérias resistentes aos carbapenêmicos (ERC) tornaram-se uma grave ameaça à saúde pública. Devido à produção de enzimas como a Klebsiella pneumoniae carbapenemase (KPC), essas bactérias desenvolveram uma alta taxa de resistência e elevada mortalidade aos pacientes infectados. Diante disso, o objetivo do presente estudo foi analisar os fatores associados à mortalidade de pacientes com ERC. Foi avaliado o histórico de 591 pacientes que apresentaram cultura positiva para bactérias resistentes aos carbapenêmicos internados no período entre Janeiro de 2012 e Julho de 2013. Os fatores associados à mortalidade dos pacientes com ERC foram: sexo, faixa etária, sítio de isolamento do microrganismo, unidade e tempo de internação, e característica clínica (infectados e colonizados). Anormalidade dos dados foi testada pelo teste de Shapiro-Wilk. Os dados foram apresentados em mediana (amplitude interquartílica). As associações foram feitas por meio do teste Qui-quadrado 2x2 e Quiquadrado de tendência. O nível de significância foi pré-estabelecido em P<0,05. O aumento da idade se associou com maior frequência de óbitos. Os sítios de isolamento: secreção traqueal e sangue foram os mais frequentes em pacientes que evoluíram a óbito. A internação em UTI também se associou com óbitos em pacientes com ERC, bem como um maior tempo de internação e a característica clínica de infectado. Por outro lado, sexo não foi um fator associado à mortalidade dos pacientes. Em conclusão, o presente estudo demonstrou haver associação entre faixa etária, sítio de isolamento do microrganismo, unidade e tempo de internação e característica clínica com a mortalidade de pacientes com ERC. Sugere-seque futuros estudos investiguem as mudanças na prevalência de casos de colonização e infecção por ERC em hospitais universitários e possam estabelecer estratégias de prevenção e controle...

Carbapenem-resistant Enterobacteriaceae (CRE) has become a severe threat to public health. Due to the production of enzymes such as Klebsiella pneumoniae carbapenemase (KPC), these bacteria developed a high rate of resistance and elevate mortality of infected patients. Given that, the goal of the present study was to analyze factors associated with mortality of patients with CRE. It was assessed the record of 591 patients that presented positive culture for CRE admitted from January 2012 to July 2013.Other factors associated with mortality of patients with CRE were: sex, age, microorganism isolation site, unit and length of stay, and clinical feature (infection and colonization). Data normality was testedby Shapiro-Wilk. Quantitative data was presented as median (interquartile range). The associations were made through 2x2 and tendency Chi-square test. Significance level was set at P<0.05. The increaseof age was associated with a high frequency of not survivors. The isolation site: lower respiratory tract and blood were more frequent in not survivor’s patients. ICU inpatients also were associated with CRE not survivors, as well as longer length of stay and the clinical feature of infection. On the other hand, sex was not a factor associated with the mortality of patients. In conclusion, the present study noted an association between age, microorganism isolation site, patient unit, length of stay and clinical feature with the mortality of CRE patients. It is suggested that future studies investigate the rate of prevalence changes of cases of colonization or infection for CRE in university hospitals and establish prevention and control strategies...

Multicenter Prospective Cohort Study of Renal Failure in Patients Treated with Colistin versus Polymyxin B.

Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for ≥48 h. A multicenter prospective cohort study was performed that included patients aged ≥18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 ± 1.3 and 2.4 ± 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P< 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48;P< 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations.