Abstract In the present study, we report the incidence of septic shock syndrome associated with methicillin-resistant Staphylococcus aureus in a child who initially presented influenza-like illness and developed septic shock shortly after 48 h of hospitalization, and eventually died within a few hours of the onset of sepsis. S. aureus isolated from the blood culture was characterized as the community-associated strain carrying the staphylococcal cassette chromosome mec (SCCmec) type IV element. Therefore, it is important to better understand the community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections and their potential association with influenza for early diagnosis and successful treatment of this fatal disease.

ABSTRACT Bloodstream infections (BSIs) are serious infections associated with high rates of morbidity and mortality. Every hour delay in initiation of an effective antibiotic increases mortality due to sepsis by 7%. Turnaround time (TAT) for conventional blood cultures takes 48 h, forcing physicians to streamline therapy by exposing patients to broad-spectrum antimicrobials. Our objective was (1) to evaluate the accuracy and TAT of an optimized workflow combining direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and in-house real-time polymerase chain reaction (PCR) for bacterial identification and antimicrobial resistance profiling directly from positive blood bottles for diagnosing bloodstream infections and (2) to verify the effect of reporting results to medical staff. A total of 103 BSI episodes from 91 patients admitted to three hospitals in São Paulo, Brazil were included. TAT from molecular versus conventional methods was measured and compared. Our protocol showed an overall agreement of 93.5% for genus and 78.5% for species identification; 74.2% for methicillin resistance detection, 89.2% for extended-spectrum β-lactamase profiling, 77.8% for metallo-β-lactamase profiling, and 100% for carbapenemase profile and vancomycin-resistance detection when compared with conventional testing. TAT of molecular sample processing according to our protocol was 38 h shorter than conventional methods. Antimicrobial interventions were possible in 27 BSI episodes. Antimicrobial discontinuation was achieved in 12 BSI episodes while escalation of therapy occurred in 15 episodes. Antimicrobial therapy was inadequate in three (12%) BSI episodes diagnosed using results of molecular testing. Our in-house rapid protocol for identifying both bacteria and antimicrobial resistance provided rapid and accurate results, having good agreement with conventional testing results. These results could contribute to faster antimicrobial therapy interventions in BSI episodes.

A total of 124 Neisseria gonorrhoeae isolates recovered during a 12-year period (2003-2015) from outpatients assisted at Centro de Referência e Treinamento DST/AIDS-CRT of São Paulo city, Brazil, were analysed. The following resistance rates were observed: penicillin-59.6%, ciprofloxacin-15.3%, and azithromycin-6.7%. Although reduced susceptibility to these drugs was observed since 2003, no ceftriaxone-resistant isolates were detected. Ciprofloxacin- and azithromycin non-susceptible isolates were grouped in 11 clusters. Mutations were detected in GyrA and ParC of isolates 124 and 260, and a C2611T substitution on 23S rRNA alleles was also observed in isolate 260. Both isolates belonged to ST1901/ST6210 (MSLT/NG-MAST schemes).

ABSTRACT Febrile Neutropenia represents a medical emergency and the use of appropriate antimicrobial therapy is essential for a better outcome. Although being time-consuming, conventional cultures and antimicrobial susceptibility tests remain the golden standard practices for microbiology identification. Final reports are typically available within several days. Faster diagnostic tools, such as species identification trough Matrix Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) and molecular techniques might help to shorten time to diagnostic and also guide definitive therapy in this scenario. Here we present a case in which the use of a diagnostic molecular workflow combining MALDI-TOF and real-time PCR for relevant genes codifying antibiotic resistant integrated with instant communication report, led to a tailored and more appropriate treatment in a patient presenting with febrile neutropenia.

Resumo Objetivo: a resistência bacteriana hospitalar a múltiplos antibióticos é uma grande preocupação mundial. O objetivo deste estudo foi conhecer os agentes multidroga-resistentes (MDR), materiais clínicos, origem e evolução, e correlaciona-los à sensibilidade bacteriana e ao consumo de antimicrobianos. Métodos: foram avaliadas 9.416 bactérias de origem nosocomial, em um hospital terciário, durante o período de 1999 a 2008. Foram definidas como MDR as bactérias Gram-negativas (BGN) que apresentaram resistência a duas ou mais classes/grupos de antibióticos. Resultados: as BGN MDR tiveram um aumento global de 3,7 vezes no final do período (p<0,001). O Acinetobacter baumannii foi o mais prevalente (36,2%). Durante o período do estudo, houve um aumento significativo de 4,8 e 14,6 para A. baumannii e K. pneumoniae (p<0,001), respectivamente. Sessenta e sete por cento das BGN MDR foram isoladas em unidade de terapia intensiva. A resistência do A. baumannii aos carbapenêmicos aumentou de 7,4 para 57,5% durante o período, concomitante ao aumento do consumo. Conclusão: durante essa década, houve uma prevalência de BGN e um aumento gradual das BGN MDR. Houve um aumento da resistência aos carbapenêmicos de 50,1% durante o estudo.

Summary Objective: a resistance of hospital-acquired bacteria to multiple antibiotics is a major concern worldwide. The objective of this study was to investigate multidrugresistant (MDR) bacteria, clinical specimens, origin of specimen and trends, and correlate these with bacterial sensitivity and consumption of antimicrobials. Methods: 9,416 bacteria of nosocomial origin were evaluated in a tertiary hospital, from 1999 to 2008. MDR was defined for Gram-negative bacteria (GNB) as resistance to two or more classes/groups of antibiotics. Results: GNB MDR increased by 3.7 times over the study period (p<0.001). Acinetobacter baumannii was the most prevalent (36.2%). Over the study period, there were significant 4.8-fold and 14.6-fold increases for A. baumannii and K. pneumoniae (p<0.001), respectively. Sixty-seven percent of isolates of MDR GNB were isolated in intensive care units. The resistance of A. baumannii to carbapenems increased from 7.4 to 57.5% during the study period and concomitant with an increased consumption. Conclusion: that decade showed prevalence of GNB and a gradual increase in MDR GNB. There was an increase in carbapenem resistance of 50.1% during the study.

Since antimicrobial resistance among uropathogens against current first line agents has affected the management of severe urinary tract infection, we determined the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures using Monte Carlo simulation for five antimicrobials (ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem) commonly prescribed as initial empirical treatment of inpatients with severe community acquired urinary tract infections. Minimum inhibitory concentration determination by Etest was performed for 205 Brazilian community urinary tract infection Escherichia coli strains from 2008 to 2012 and 74 E. coli bloodstream strains recovered from a surveillance study. Pharmacodynamic exposure was modeled via a 5000 subject Monte Carlo simulation. All isolates were susceptible to ertapenem and meropenem. Piperacillin/tazobactam, ceftriaxone and ciprofloxacin showed 100%, 97.5% and 83.3% susceptibility among outpatient isolates and 98.6%, 75.7% and 64.3% among inpatient isolates, respectively. Against outpatient isolates, all drugs except ciprofloxacin (82.7% in aggressive and 77.6% in conservative scenarios) achieved high cumulative fraction of response: car-bapenems and piperacillin/tazobactam cumulative fraction of responses were close to 100%, and ceftriaxone cumulative fraction of response was 97.5%. Similar results were observed against inpatients isolates for carbapenems (100%) and piperacillin/tazobactam (98.4%), whereas ceftriaxone achieved only 76.9% bactericidal cumulative fraction of response and ciprofloxacin 61.9% (aggressive scenario) and 56.7% (conservative scenario) respectively. Based on this model, standard doses of beta-lactams were predicted to deliver sufficient pharmacodynamic exposure for outpatients. However, ceftriaxone should be avoided for inpatients and ciprofloxacin empirical prescription should be avoided in both inpatients and outpatients with complicated urinary tract infection.

The increased frequency and dissemination of enterobacteria resistant to various antimicrobials is currently worldwide concern. In January 2010, a 94-year-old patient with chronic lymphocytic leukemia was admitted to the University Hospital. This patient died 21 days after hospitalization due to the clinical worsening. Klebsiella pneumoniae producing of extended-spectrum β-lactamases (ESBLs) was isolated of urine culture. This bacterium demonstrated resistance to ceftazidime, ciprofloxacin, levofloxacin, ertapenem and imipenem. Susceptibility to cefoxitin, cefepime, meropenem, colistin and tigecycline. This study reports the first case of infection by Klebsiella pneumoniae carrying the bla kpc gene in the State of Mato Grosso do Sul, Brazil.

A presente nota pesquisa demonstra que o uso das informações de receituário ou prescrição médica tem fundamental valor para a compreensão das correlações da dinâmica da resistência bacteriana comunitária. Além disso, a análise dos dados gerada pode ajudar a estabelecer medidas e políticas de saúde pública mais adequadas para o controle e a otimização do consumo de antimicrobianos. Para isso, o artigo usa como base o modelo lógico desenvolvido pelo Projeto EUREQA voltado para aquisição, classificação, interpretação e análise das informações relacionadas à prescrição dos antimicrobianos de uso oral.

This study demonstrates that the use of information from medical prescriptions is essential for understanding the dynamics of community bacterial resistance. The resulting analysis can also influence and help establish more adequate public health policies on the control and optimization of antimicrobial use. The article demonstrates the use of a logical model developed by the EUREQA project for acquisition, classification, interpretation, and analysis of data from prescriptions for oral antimicrobial use.

A presente nota pesquisa demonstra que o uso das informações de receituário ou prescrição médica tem fundamental valor para a compreensão das correlações da dinâmica da resistência bacteriana comunitária. Além disso, a análise dos dados gerada pode ajudar a estabelecer medidas e políticas de saúde pública mais adequadas para o controle e a otimização do consumo de antimicrobianos. Para isso, o artigo usa como base o modelo lógico desenvolvido pelo Projeto EUREQA voltado para aquisição, classificação, interpretação e análise das informações relacionadas à prescrição dos antimicrobianos de uso oral.

This study demonstrates that the use of information from medical prescriptions is essential for understanding the dynamics of community bacterial resistance. The resulting analysis can also influence and help establish more adequate public health policies on the control and optimization of antimicrobial use. The article demonstrates the use of a logical model developed by the EUREQA project for acquisition, classification, interpretation, and analysis of data from prescriptions for oral antimicrobial use.

O carcinoma de cabeça e pescoço é 6ª maior causa de mortes por neoplasia no mundo. Nas últimas décadas, tem-se associado a relação da infecção pelo Papilomavírus Humano (HPV) e seu envolvimento na etiologia desta doença, bem como acontece com o câncer de colo de útero. OBJETIVO: A caracterização molecular dos tipos de HPV diagnosticados na mucosa oral de mulheres que apresentavam alterações citológicas compatíveis com lesão escamosa no colo uterino. MÉTODOS: Foram estudadas 409 amostras cérvico-vaginais e de cavidade oral de mulheres internas no Presídio Feminino da cidade de São Paulo. A correlação entres lesões cervicais e orais foram avaliadas em 27 mulheres que apresentavam lesões pré-malignas e malignas no colo uterino pela caracterização molecular dos tipos de HPV por PCR/ RFLP e Sequenciamento. RESULTADOS: Das 27 (6,67%) amostras compatíveis com LSIL e HSIL no colo uterino, 22 (81,48%) apresentaram infecção pelo HPV de alto risco oncogênico, sendo o HPV 59 o mais prevalente, dentre elas, três amostras (11,1%) evidenciaram alterações celulares compatíveis com displasia leve na cavidade oral. CONCLUSÃO: Nosso estudo sugere uma relação entre o desenvolvimento de lesões da cavidade oral e a infecção pelo HPV, independentemente do tipo viral presente.

Carcinoma of the head and neck is the 6th cause of death by cancer in the world. In recent decades the human papillomavirus (HPV) has been implicated in the etiology of this disease. OBJECTIVE: To characterize the types of HPV detected in the oral mucosa in women with cytological abnormalities suggesting intraepithelial squamous lesions in the uterine cervix. METHODS: four-hundred-nine cervical-vaginal and oral pap-smears of women interned in a Female Prison in São Paulo were examined. The relationship between cervical and oral lesion was analyzed by PCR/RFLP and DNA sequencing. RESULTS: Of 27 (6.67%) specimens showing cervical cytological abnormalities suggesting LSIL and HSIL, 22 (81.48%) had oncogenic high-risk HPV infection, of which HPV 59 was the most prevalent. Three (11.1%) samples showed cytological changes suggesting mild dysplasia in the oral cavity. CONCLUSION: Our study suggests an association between carcinoma of the oral cavity and HPV infection, regardless of the virus type.

The nosocomial transmission of tuberculosis is a serious occupational health problem. An effective prevention of this disease includes environmental measures to avoid its dissemination and to reduce the amount of droplet nuclei in the air. It is a descriptive study that aimed to describe the necessary structure for the implementation of an isolation room with negative air pressure for patients with tuberculosis. The units were projected with HVAC system with temperature control at 22 ± 2ºC, air recirculation system, HEPA filters, twenty two air changes per hour and negative air pressure. After repairs and the implementation of the environmental control the functioning of the respiratory isolation was monitored for 12 months. In the event of the negative air pressure becoming neutral the manometers in the room would display the filters saturation level and the need for their replacement. Soon after that the negative air pressure could be restarted. The isolation unit implementation required an investment of US$ 75,000.00 being the monthly repair cost US$ 550.00. The respiratory isolation unit requires specific management strategies so as to ensure the protection of healthcare workers and patients.

La transmisión intrahospitalaria de la tuberculosis es un problema de salud en el trabajo y las medidas efectivas de control incluyen controles ambientales destinados a prevenir la diseminación de la enfermedad y reducir la cantidad de partículas infecciosas en el aire. Este estudio se realizó con el objetivo de describir la estructura necesaria para implementar y operar una unidad de aislamiento para la tuberculosis con presión de aire negativa. La unidad fue diseñada con un sistema de climatización con control de temperatura de 22 ± 2 º C, recirculación del aire, filtros HEPA, veinte cambios de airepor horaypresión negativa. Después del proceso de reforma e implementación de los controles ambientales, el funcionamiento del aislamiento respiratorio fue monitoreado durante doce meses. Las ocasiones en que la presión negativa se convirtió en neutra fueron identificadas por manómetros en las habitaciones y en los filtros, señalando saturación y necesidad de sustitución. En seguida, la presión negativa fue restablecida. La inversión para instalar el aislamiento fue de U$S 75.000,00 y el costo de mantenimiento mensual es de U$S 550,00. La unidad requiere estrategias de gestión adecuadas para garantizar la protección de los profesionales de la salud y de los pacientes.

A transmissão intra-hospitalar da tuberculose consiste em um problema de saúde ocupacional, e as medidas de controle efetivas incluem os controles ambientais que visam prevenir a disseminação dessa doença e reduzir as partículas infecciosas aéreas.Trata-se de um estudo descritivo, realizado com o objetivo de descrever a estrutura necessária para implantar e operacionalizar uma unidade de isolamento para tuberculose com pressão negativa do ar. A unidade foi projetada com um sistema de climatização com controle de temperatura de 22 ± 2ºC, recirculação do ar, filtragem HEPA, 20 trocas de ar por hora e pressão negativa. Após a reforma da unidade e a implantação dos controles ambientais, o funcionamento do isolamento respiratório foi monitorizado por 12 meses. As ocasiões em que a pressão negativa se tornou neutra foram identificadas pelos manômetros nos quartos e nos filtros, indicando a saturação deles e sua substituição. Em seguida, a pressão negativa foi restabelecida. O investimento para a implantação do isolamento foi de 75 mil dólares e o custo mensal de manutenção, 550 dólares. A unidade requer gerenciamento apropriado para assegurar a proteção dos profissionais da saúde e demais pacientes.

OBJECTIVES: To examine the spatial distribution of Streptococcus pneumoniae and its clonal patterns collected between 2002 and 2006 in São Paulo, Brazil. METHODS: As part of an observational study in São Paulo city, Brazil, S. pneumoniae isolates routinely cultured from blood, respiratory specimens, or cerebrospinal and other profound fluids were selected. Additionally, only isolates with either penicillin (PEN) intermediate (I) or resistant (R) status on routine antibiogram were included, in order to obtain a higher probability of clonal isolates. A single I/R S. pneumoniae isolate per patient was included and submitted to genotypic determination by pulsed field gel electrophoresis (PFGE). Minimum inhibitory concentrations (MICs) were determined for the isolates by Etest® to PEN and other antimicrobials. Each isolate was geocoded in a digital map. The Kernel function and ratio methods between total isolates vs. clones were used in order to explore possible cluster formations. RESULTS: Seventy-eight (78) S. pneumoniae community isolates from two major outpatient centers in São Paulo, Brazil, were selected from the databank according to their penicillin susceptibility profile, i.e. R or I to penicillin assessed by oxacillin disc diffusion. Of these, 69 were submitted to PFGE, 65 to MIC determination, and 48 to spatial analytical procedures. Preliminary spatial analysis method showed two possible cluster formation located in southwest and southeast regions of the city. CONCLUSION: Further analyses are required for precisely determining the existence of S. pneumoniae clusters and their related risk factors. Apparently there is a specific transmission pattern of S. pneumoniae clones within certain regions and populations. GIS and spatial methods can be applied to better understand epidemiological patterns and to identify target areas for public health interventions.