ABSTRACT
Polymyxin-carbapenem-resistant Klebsiella pneumoniae (PCR-Kp) with pan (PDR)- or extensively drug-resistant phenotypes has been increasingly described worldwide. Here, we report a PCR-Kp outbreak causing untreatable infections descriptively correlated with bacterial genomes. Hospital-wide surveillance of PCR-Kp was initiated in December-2014, after the first detection of a K. pneumoniae phenotype initially classified as PDR, recovered from close spatiotemporal cases of a sentinel hospital in Rio de Janeiro. Whole-genome sequencing of clinical PCR-Kp was performed to investigate similarities and dissimilarities in phylogeny, resistance and virulence genes, plasmid structures and genetic polymorphisms. A target phenotypic profile was detected in 10% (12/117) of the tested K. pneumoniae complex bacteria recovered from patients (8.5%, 8/94) who had epidemiological links and were involved in intractable infections and death, with combined therapeutic drugs failing to meet synergy. Two resistant bacterial clades belong to the same transmission cluster (ST437) or might have different sources (ST11). The severity of infection was likely related to patients' comorbidities, lack of antimicrobial therapy and predicted bacterial genes related to high resistance, survival, and proliferation. This report contributes to the actual knowledge about the natural history of PCR-Kp infection, while reporting from a time when there were no licensed drugs in the world to treat some of these infections. More studies comparing clinical findings with bacterial genetic markers during clonal spread are needed.
Subject(s)
Klebsiella Infections , Polymyxins , Humans , Polymyxins/pharmacology , Polymyxins/therapeutic use , Klebsiella pneumoniae , Klebsiella Infections/drug therapy , Klebsiella Infections/epidemiology , Klebsiella Infections/genetics , Brazil , Genome, Bacterial , Disease Outbreaks , Carbapenems/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests , beta-Lactamases/genetics , Bacterial Proteins/geneticsABSTRACT
A clinical-epidemiological score to predict CR-GNB sepsis to guide empirical antimicrobial therapy (EAT), using local data, persists as an unmet need. On the basis of a case-case-control design in a prospective cohort study, the predictive factors for CR-GNB sepsis were previously determined as prior infection, use of mechanical ventilation and carbapenem, and length of hospital stay. In this study, each factor was scored according to the logistic regression coefficients, and the ROC curve analysis determined its accuracy in predicting CR-GNB sepsis in the entire cohort. Among the total of 629 admissions followed by 7797 patient-days, 329 single or recurrent episodes of SIRS/sepsis were enrolled, from August 2015 to March 2017. At least one species of CR-GNB was identified as the etiology in 108 (33%) episodes, and 221 were classified as the control group. The cutoff point of ≥3 (maximum of 4) had the best sensitivity/specificity, while ≤1 showed excellent sensitivity to exclude CR-GNB sepsis. The area under the curve was 0.80 (95% CI: 0.76-0.85) and the number needed to treat was 2.0. The score may improve CR-GNB coverage and spare polymyxins with 22% (95% CI: 17-28%) adequacy rate change. The score has a good ability to predict CR-GNB sepsis and to guide EAT in the future.
ABSTRACT
BACKGROUND: The emergence and spread of antimicrobial resistance and infectious agents have challenged hospitals in recent decades. Our aim was to investigate the circulation of target infectious agents using Geographic Information System (GIS) and spatial-temporal statistics to improve surveillance and control of healthcare-associated infection and of antimicrobial resistance (AMR), using Klebsiella pneumoniae complex as a model. METHODS: A retrospective study carried out in a 450-bed federal, tertiary hospital, located in Rio de Janeiro. All isolates of K. pneumoniae complex from clinical and surveillance cultures of hospitalized patients between 2014 and 2016, identified by the use of Vitek-2 system (BioMérieux), were extracted from the hospital's microbiology laboratory database. A basic scaled map of the hospital's physical structure was created in AutoCAD and converted to QGis software (version 2.18). Thereafter, bacteria according to resistance profiles and patients with carbapenem-resistant K. pneumoniae (CRKp) complex were georeferenced by intensive and nonintensive care wards. Space-time permutation probability scan tests were used for cluster signals detection. RESULTS: Of the total 759 studied isolates, a significant increase in the resistance profile of K. pneumoniae complex was detected during the studied years. We also identified two space-time clusters affecting adult and paediatric patients harbouring CRKp complex on different floors, unnoticed by regular antimicrobial resistance surveillance. CONCLUSIONS: In-hospital GIS with space-time statistical analysis can be applied in hospitals. This spatial methodology has the potential to expand and facilitate early detection of hospital outbreaks and may become a new tool in combating AMR or hospital-acquired infection.
Subject(s)
Cross Infection/epidemiology , Drug Resistance, Multiple, Bacterial , Geographic Information Systems , Klebsiella Infections/epidemiology , Brazil , Data Interpretation, Statistical , Humans , Klebsiella pneumoniae/drug effects , Phenotype , Retrospective Studies , Spatio-Temporal Analysis , Tertiary Care CentersABSTRACT
Várias alterações hematológicas estão presentes em indivíduos infectados pelo vírus da imunodeficiência humana (HIV), sendo que a incidência de citopenias parece aumentar com a progressão da doença. Dentre as principais alterações, destaca-se a diminuição progressiva do número de linfócitos no sangue periférico, principalmente da subpopulação T helper (CD3+/CD4+ ), levando esses indivíduos a um quadro de imunodeficiência celular. Objetivando investigar as principais alterações imunológicas e hepatológicas em indivíduos infectados pelo HIV, foram analisadas amostras de sangue periférico de 100 indivíduos soropositivos para o HIV (60 homens e 40 mulheres), procurando correlacionar os níveis de linfócitos TCD4 com os diversos parâmetros hematológicos, tais como: a leucometria, contagem de linfócitos, contagem de plaquetas e dosagem de hemoglobina. Os parâmetros hematológicos foram determinados por analisadores hematológicos e a subpopulação linfocitária pela citometria de fluxo após sua marcação com anticorpos monoclonais específicos. Os resultados demonstraram que 25% dos casos apresentaram contagem de linfócitos TCD4 ≥ 500/mm³, em 55% dos casos a contagem esteve entre 499 e 200/mm³ e inferior a 200/mm³ em 30% dos casos. Correlacionando os níveis de linfócitos TCD4 com as alterações hematológicas, observou-se que a linfopenia mostrou-se mais acentuada no grupo de indivíduos cujas contagens de células TCD4 estavam inferiores a 200/mm³, correspondendo a 18% dos casos. A contagem de plaquetas mostrou-se dentro dos limites de normalidade na maioria dos casos; a trombocitopenia, entretanto, esteve presente em 29% dos casos, dos quais 20% apresentaram níveis de linfócitos TCD4 menores que 200/mm³. A anemia por sua vez esteve presente em 20% das mulheres e em 50% dos homens, correlacionando mais com baixas contagens de linfócitos TCD4. Com estes dados, concluímos que os valores da contagem de linfócitos TCD4 de certo modo correlacionou-se com as variações do quadro hematológico, apresentando na maioria dos casos, citopenias, tais como a anemia, a trombocitopenia e a linfopenia, mostrando a importância destes exames no acompanhamento de indivíduos infectados pelo HIV.
