Addressing resistance evolution in Pseudomonas aeruginosa using pharmacodynamic modelling: application to meropenem dosage and combination therapy.

Isolates of Pseudomonas aeruginosa (n = 208) were collected from an 810-bed hospital in Connecticut, USA. A model employing the pharmacokinetic properties of meropenem, susceptibility results and Monte Carlo simulation was used to analyse four different dosing regimens of meropenem at pharmacodynamic endpoints. Cumulative fraction of response (CFR) was assessed at bacteriostatic and bactericidal endpoints for the entire population of isolates, as well as for isolates from principal anatomical sites. CFR was also evaluated at endpoints shown to suppress emergence of resistance in 'susceptible'P. aeruginosa with either monotherapy or combination therapy. The bacteriostatic/bactericidal CFR of meropenem 1 g every 8 h (q8h), 2 g q8h, 1 g q8h infused over 3 h (3-h INF), and 2 g q8h 3-h INF were 76%/73%, 80%/76%, 77%/75% and 79%/78%, respectively. At the monotherapeutic suppressive endpoint, CFRs against susceptible isolates were 21%, 35%, 32% and 50%, respectively. When combination therapy with an aminoglycoside was simulated, the CFRs for the same regimens were 50%, 64%, 65% and 79%, respectively. Bactericidal CFRs for all regimens against wound isolates were significantly higher (p <0.03 for each regimen) than CFRs for the entire population. Meropenem 2 g q8h with a 3-h infusion in combination with an aminoglycoside provides the greatest likelihood of P. aeruginosa coverage, and may help to prevent development of resistance, although local MIC data are essential to inform therapeutic decisions.

Multi-state survey of healthcare-associated infections in acute care hospitals in Brazil.

BACKGROUND: Healthcare-associated infections (HCAIs) challenge public health in developing countries such as Brazil, which harbour social inequalities and variations in the complexity of healthcare and regional development. AIM: To describe the prevalence of HCAIs in hospitals in a sample of hospitals in Brazil. METHODS: A prevalence survey conducted in 2011-13 enrolled 152 hospitals from the five macro-regions in Brazil. Hospitals were classified as large (≥200 beds), medium (50-199 beds) or small sized (<50 beds). Settings were randomly selected from a governmental database, except for 11 reference university hospitals. All patients with >48 h of admission to the study hospitals at the time of the survey were included. Trained epidemiologist nurses visited each hospital and collected data on HCAIs, subjects' demographics, and invasive procedures. Univariate and multivariate techniques were used for data analysis. FINDINGS: The overall HCAI prevalence was 10.8%. Most frequent infection sites were pneumonia (3.6%) and bloodstream infections (2.8%). Surgical site infections were found in 1.5% of the whole sample, but in 9.8% of subjects who underwent surgical procedures. The overall prevalence was greater for reference (12.6%) and large hospitals (13.5%), whereas medium- and small-sized hospitals presented rates of 7.7% and 5.5%, respectively. Only minor differences were noticed among hospitals from different macro-regions. Patients in intensive care units, using invasive devices or at extremes of age were at greater risk for HCAIs. CONCLUSION: Prevalence rates were high in all geographic regions and hospital sizes. HCAIs must be a priority in the public health agenda of developing countries.

Methicillin-Resistant Staphylococcus aureus from Brazilian Dairy Farms and Identification of Novel Sequence Types.

The aim of this study was to investigate the phenotypic and genotypic diversity and anti-microbial resistance among staphylococci of dairy herds that originated from Paraiba State, north-eastern Brazil, a region where such studies are rare. Milk samples (n = 552) were collected from 15 dairy farms. Isolates were evaluated for anti-microbial susceptibility by Kirby-Bauer disc diffusion method. Confirmation of methicillin-resistant Staphylococcus aureus (MRSA) was performed using multiplex PCR targeting mecA and nuc genes in addition to phenotypic assay based on PBP-2a latex agglutination. Clonal relatedness of isolates was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) genotyping. Staphylococci were detected in 269 (49%) of the samples. Among these, 65 (24%) were S. aureus. The remaining 204 isolates were either coagulase-negative staphylococci (n = 188; 70%) or coagulase positive other than S. aureus (n = 16; 6%). Staphylococci were cultured in seven (35%) of the 20 hand swab samples, from which five isolates were S. aureus. The isolates were most commonly resistant against penicillin (43%), ampicillin (38%) and oxacillin (27%). The gene mecA was detected in 21 S. aureus from milk and in one isolate from a milker's hand. None of the isolates were resistant to vancomycin. PFGE findings showed high clonal diversity among the isolates. Based on MLST, we identified a total of 11 different sequence types (STs 1, 5, 6, 83, 97, 126, 1583, 1622, 1623, 1624 and 1625) with four novel STs (ST1622-ST1625). The findings show that MRSA is prevalent in milk from semi-extensive dairy cows in north-eastern Brazil, and further investigation on its extent in various types of milk production systems and the farm-to-table continuum is warranted.

Analysis of the clonal diversity of Staphylococcus aureus methicillin-resistant strains isolated at João Pessoa, state of Paraíba. Brazil.

To investigate the clonal diversity of Staphylococcus aureus strains isolated at João Pessoa, State of Paraíba, Brazil, digested genomic DNA were studied by pulsed-field gel electrophoresis (PFGE) in nine methicillin-resistant strains (MRSA) and three methicillin-sensitive strains (MSSA), selected among 67 isolates based on their antimicrobial susceptibility and epidemiology. The isolates were obtained between April and November 1992 from the Hospital of the Federal University of Paraíba, located in João Pessoa. Two MRAS isolates from the Oswaldo Cruz Hospital, São Paulo, Brazil, including an epidemic strain previously detected from different hospitals at the country were used as control. Five different patterns, were demonstrated by MRSA isolated in João Pessoa and these patterns were described in several epidemiologically unrelated hospitals in São Paulo. Our results suggest the interstate dissemination of a MRSA clone in João Pessoa which is similar to that described in other cities of Brazil.

Influencia da vacinacao BCG na infeccao experimental de camundongos por Yersinia enterocolitica. / Yersinia enterocolitica infection in mice after BCG immunization

Avaliacao da resistencia de camundongos albinos, vacinados com BCG, a infeccao com Yersinia enterocolitica, utilizando-se para este fim as sub-amostras Brasil e Glaxo da vacina BCG, inoculadas pelas vias subcutanea, intraperitoneal e oral. A inoculacao com Yersinia enterocolitica foi realizada pela via intraperitoneal injetando-se aproximadamente 500 DL50. Os camundongos vacinados pelas vias subcutanea e intraperitoneal foram reinfectados com BCG, pela via intraperitoneal, quando era mais intensa a hipersensibilidade tuberculinica o decrescimo na mortalidade foi significativo (P < 0,01). A amostra Glaxo induziu um nivel de resistencia mais pronunciado do que o observado com a amostra Brasil

Estudo comparativo de técnicas de detecçäo de amostras de Staphylococcus aureus resistentes à meticilina / Comparison of screening methods for detection of methicillin-resistant Staphylococcus aureus strains

Foi realizado um estudo comparativo entre diferentes métodos disponíveis, incluindo técnicas tradicionais e avançadas, para a detecçäo de amostras de Staphylococcus aureus resistentes à meticilina (MRSA), enfatizando-se aspectos como: sensibilidade, rapidez, custos e aplicabilidade como procedimentos de rotina em microbiologia clínica. Foram utilizadas 12 amostras de S. aureus selecionadas entre linhagens isoladas de pacientes internos no Hospital Universitário "Lauro Wanderley" (HU/UFPb), comparando-se as seguintes técnicas: a)Método de difusäo em discos, b)Triagem em agar incorporado de NaCl e oxacilina, c)Sistema automatizado Microscan, d)Sistem E-Test de determinaçäo da CIM e)Sistema Crystal MRSA ID. Os resultados demonstraram que as amostras testadas puderam ser identificadas como MRSA havendo vantagens e desvantagens nos métodos avaliados quando utilizados em situaçöes específicas, considerando-se as facilidades de interpretaçäo, custos e acurácia de cada teste