Chronic medical conditions associated with invasive pneumococcal diseases in inpatients in teaching hospitals in São Paulo city: Estimating antimicrobial susceptibility and serotype-coverage of pneumococcal vaccines

Background: Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. Methods: A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others RESULTS: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. Conclusion: Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly. Keywords: Antimicrobial resistance; Chronic diseases; Comorbidity; Invasive pneumococcal diseases; Pneumococcal conjugate vaccine; Pneumococcal serotypes; Pneumococcal vaccine.

Chronic medical conditions associated with invasive pneumococcal diseases in inpatients in teaching hospitals in São Paulo city: Estimating antimicrobial susceptibility and serotype-coverage of pneumococcal vaccines

ABSTRACT Background: Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. Methods: A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others Results: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. Conclusion: Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly.

MRSA outbreak in a Neonatal Intensive Care Unit in a developed country: importance of rapid detection of reservoirs and implementation of intervention measures

ABSTRACT We described a MRSA bloodstream infection outbreak that was rapidly identified and controlled in a Neonatal Intensive Care Unit after implementation of a bundle of measures, including PCR-screening and HCW decolonization. We found 35% of healthcare workers(HCW) colonized with S. aureus by PCR, one of them that presented skin lesion positive for MSSA (same clone and spa type than two patients). Our findings raise the hypothesis that the outbreak could be related to HCW colonization.

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: children and adolescents / Consenso Brasileiro de Nutrição em Transplante de Células-Tronco Hematopoiéticas: crianças e adolescentes

ABSTRACT The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Children and Adolescents was developed by dietitians, physicians, and pediatric hematologists from 10 Brazilian reference centers in hematopoietic stem cell transplantation. The aim was to emphasize the importance of nutritional status and body composition during treatment, as well as the main characteristics related to patient´s nutritional assessment. This consensus is intended to improve and standardize nutrition therapy during hematopoietic stem cell transplantation. The consensus was approved by the Brazilian Society of Bone Marrow Transplantation.

RESUMO O Consenso Brasileiro de Nutrição em Transplante de Células-Tronco Hematopoiéticas: crianças e adolescentes foi elaborado com a participação de nutricionistas, médicos nutrólogos e médicos hematologistas pediátricos de 10 centros brasileiros que são referência em transplante de células-tronco hematopoiéticas. O objetivo foi salientar a importância do estado nutricional e da composição corporal durante o tratamento, bem como as principais características relacionadas à avaliação nutricional do paciente. As intenções, ao se estabelecer o consenso, foram aprimorar e padronizar a terapia nutricional durante o transplante de células-tronco hematopoiéticas. O consenso foi aprovado pela Sociedade Brasileira de Transplante de Médula Óssea.

Diagnostic value of pediatric blood culture bottles for acute postoperative endophthalmitis

OBJECTIVE: To report our experience using conventional culture methods (CM) and pediatric blood culture bottles (PBCBs) for vitreous sample culture of acute postoperative endophthalmitis. METHODS: A retrospective study was conducted at the Department of Ophthalmology, Hospital das Clinicas, HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, BR, from January 2010 to December 2015, and it included 54 patients with clinically suspected acute postoperative endophthalmitis. Vitreous samples were obtained by vitreous tap or vitrectomy. Samples from January 2010 to December 2011 were cultivated in CM, whereas samples from January 2012 to December 2015 were inoculated in PBCBs. The measured outcome was the yield of positive cultures. RESULTS: Twenty cases were included in the CM group, and 34 cases were included in the PBCB group. The yield of positive cultures in PBCBs (64.7%) was significantly higher than that in conventional CM (35%, p=0.034). Staphylococcus epidermidis and Streptococcus viridans were the two most commonly found agents. CONCLUSION: PBCBs can be used successfully in clinically suspected endophthalmitis. The method showed a higher yield of positive cultures than the conventional method. This technique appears to have several advantages over the traditional method: it saves time, as only one medium needs to be inoculated; transportation to a laboratory is easier than in the traditional method, and there is no need to maintain a supply of fresh agar media. The use of PBCBs may be recommended as the primary method for microbiological diagnosis and is especially suitable for office settings and remote clinics.

Evaluation of MALDI-TOF mass spectrometry (VITEK-MS) compared to the ANC card (VITEK 2) for the identification of clinically significant anaerobes / Avaliação da espectrometria de massas MALDI-TOF (VITEK-MS) diante do cartão ANC (VITEK 2) na identificação de anaeróbios clinicamente significantes

ABSTRACT Introduction: The identification of anaerobic bacteria by conventional methods employed in clinical laboratories requires a lot of work and a long response time [turnaround time (TAT)]. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is an accurate, rapid and inexpensive technique with promising results for bacterial identification. Objective: To evaluate the MALDI-TOF mass spectrometry (VITEK-MS, bioMérieux, France) compared to the ANC card (VITEK 2, bioMérieux, France) for the identification of anaerobes, and also veriying the cost variation between both methodologies. Methods: 421 anaerobes were concomitantly identified by ANC (VITEK 2) and MALDI-TOF (VITEK MS). The conflicting results or those presenting low differentiation of the species were subjected to the 16S ribosomal ribonucleic acid (rRNA) sequencing. Results: Thirty-five strains were not identified by ANC (VITEK 2), and only one isolate was not identified by MALDI-TOF (VITEK MS). From the 386 anaerobes identified by the two methodologies, 97% agreement was observed on the identification of genus and species between the methodologies. Thirteen (3%) isolates were submitted to 16S sequencing. The agreement observed was 70% using ANC (VITEK 2) using 92% by MALDI-TOF (VITEK MS). Conclusion: Both methodologies showed an excellent performance for the identification of the strains tested with great differences in relation to cost-benefit. MALDI-TOF MS allowed 35 additional identifications and a saving of BRL$ 7,786 with the release of culture positive result five days ahead of the ANC (VITEK 2). TAT reduction may contribute to a successful clinical resolution.

RESUMO Introdução: A identificação das bactérias anaeróbias por métodos convencionais empregados nos laboratórios clínicos demanda muito trabalho e um longo tempo de resposta (TAT). A espectrometria de massa por ionização e dessorção a laser assistida por matriz (MALDI-TOF MS) é uma técnica precisa, rápida e barata, com resultados promissores para a identificação bacteriana. Objetivo: Avaliar a espectrometria de massas MALDI-TOF (VITEK MS, bioMérieux, France) diante do cartão ANC (VITEK 2, bioMérieux, France) para a identificação de anaeróbios, bem como verificar a variação de custos entre as metodologias. Métodos: Foram identificados 421 anaeróbios concomitantemente pelo ANC (VITEK 2) e pelo MALDI-TOF (VITEK MS). Os resultados discordantes ou que apresentaram baixa discriminação das espécies foram submetidos ao sequenciamento do 16S do ácido ribonucleico ribossonal (rRNA). Resultados: Trinta e cinco cepas não foram identificadas pelo ANC (VITEK 2), e somente um isolado ficou sem identificação pelo MALDI-TOF (VITEK MS). Dos 386 anaeróbios identificados pelas duas metodologias, a concordância na identificação de gênero e espécie foi observada em 97%. Treze (3%) isolados foram submetidos ao sequenciamento do 16S; a concordância observada foi de 70% com o ANC (VITEK 2) e 92% com MALDI-TOF (VITEK MS). Conclusão: Ambas as metodologias demonstraram ótimo desempenho para identificação das cepas testadas com grandes diferenças em relação ao custo-benefício. O MALDI-TOF MS permitiu 35 identificações adicionais e uma economia de R$ 7.786,00 com a liberação do resultado positivo da cultura cinco dias à frente do ANC (VITEK 2). A redução do TAT pode contribuir para uma resolução clínica bem-sucedida.

Burkholderia cepacia, cystic fibrosis and outcomes following lung transplantation: experiences from a single center in Brazil

OBJECTIVES: To evaluate the impact of Burkholderia cepacia complex colonization in cystic fibrosis patients undergoing lung transplantation. METHODS: We prospectively analyzed clinical data and respiratory tract samples (sputum and bronchoalveolar lavage) collected from suppurative lung disease patients between January 2008 and November 2013. We also subtyped different Burkholderia cepacia complex genotypes via DNA sequencing using primers against the recA gene in samples collected between January 2012 and November 2013. RESULTS: From 2008 to 2013, 34 lung transplants were performed on cystic fibrosis patients at our center. Burkholderia cepacia complex was detected in 13 of the 34 (38.2%) patients. Seven of the 13 (53%) strains were subjected to genotype analysis, from which three strains of B. metallica and four strains of B. cenocepacia were identified. The mortality rate was 1/13 (7.6%), and this death was not related to B. cepacia infection. CONCLUSION: The results of our study suggest that colonization by B. cepacia complex and even B. cenocepacia in patients with cystic fibrosis should not be considered an absolute contraindication to lung transplantation in Brazilian centers.

Plasmid-mediated mcr-1 in carbapenem-susceptible Escherichia coli ST156 causing a blood infection: an unnoticeable spread of colistin resistance in Brazil?

OBJECTIVE: We describe an IncX4 pHC891/16mcr plasmid carrying mcr-1 in a colistin-resistant and carbapenem-susceptible E. coli isolate (HC891/16), ST156, which caused a blood infection in a Brazilian patient with gallbladder adenocarcinoma. METHODS: Strain HC891/16 was subjected to whole genome sequencing using the MiSeq Platform (Illumina, Inc., USA). Assembly was performed using Mira and ABACAS. RESULTS: The isolates showed resistance only to ciprofloxacin, ampicillin and cefoxitin, and whole-genome sequencing revealed the presence of aac(6')Ib-cr and blaTEM1. CONCLUSION: Our findings warn of the possible silent dissemination of colistin resistance by carbapenem-susceptible mcr-1 producers, as colistin susceptibility is commonly tested only among carbapenem-resistant isolates.

Emergence of colistin resistance in the largest university hospital complex of São Paulo, Brazil, over five years

Abstract Colistin resistance involving Gram-negative bacilli infections is a challenge for health institutions around of the world. Carbapenem-resistance among these isolates makes colistin the last therapeutic option for this treatment. Colistin resistance among Enterobacteriaceae, Acinetobacter spp., and Pseudomonas spp. was evaluated between 2010 and 2014 years, at Hospital das Clínicas, São Paulo, Brazil. Over five years 1346 (4.0%) colistin resistant Gram-negative bacilli were evaluated. Enterobacteriaceae was the most frequent (86.1%) pathogen isolated, followed by Acinetobacter spp. (7.6%), and Pseudomonas spp. (6.3%). By temporal analysis there was a trend for an increase of colistin resistance among Enterobacteriaceae, but not among non-fermentative isolates. Among 1346 colistin resistant isolates, carbapenem susceptibility was observed in 21.5%. Colistin resistance in our hospital has been alarmingly increased among Klebsiella pneumoniae isolates in both KPC positive and negative, thus becoming a therapeutic problem.

Extensive cervical lymphadenitis mimicking bacterial adenitis as the first presentation of Kawasaki disease / Extensa linfadenite cervical mimetizando adenite bacteriana como primeira manifestação da doença de Kawasaki

Cervical adenitis >1.5cm in diameter is the less frequently observed criteria in patients with Kawasaki disease and it is usually found in association with other symptoms during the acute phase. Moreover, the finding of fever and lymphadenitis with intense local signs of inflammation and phlegmon is rarely seen as the initial manifestation of Kawasaki disease. We report the case of a 7-year-old boy who had cervical lymphadenitis with adjacent cellulitis and phlegmon mimicking bacterial adenitis as the first presentation of Kawasaki disease. The patient had fever, cervical lymphadenitis with adjacent cellulitis, and severe headache. Cefadroxil was prescribed based on the clinical diagnosis of bacterial adenitis. Because he remained febrile and phlogistic signs worsened, after 1 day of hospitalization, antibiotics were administrated intravenously (ceftriaxone and oxacillin). The computed tomography of the neck showed primary infectious/inflammatory process. On the fourth day, the patient had dry and scaly lips, and treatment with oxacillin was replaced by clindamycin because the patient was still febrile. On the ninth day, he presented non-exudative bilateral conjunctival injection. On the tenth day of febrile disease, a rash appeared on his trunk, hands and feet. Patient’s symptoms resolved after intravenous administration of immunoglobulin (2g/kg/dose), and he was discharged 2 days later. On the 14th day, the patient had lamellar desquamation of fingers. Kawasaki disease should be considered as a differential diagnosis in children with febrile cervical lymphadenitis unresponsive to empiric antibiotics even if they have adjacent cellulitis and phlegmon.

Adenite cervical >1,5cm é o critério menos frequentemente observado em pacientes com doença de Kawasaki e manifesta-se habitualmente em associação com os demais sintomas da fase aguda. Entretanto, linfadenite febril isolada com intensos sinais flogísticos e flegmão é raramente observada como primeira manifestação da doença de Kawasaki. Assim, relatou-se aqui um caso de uma criança que apresentou linfadenite cervical com celulite adjacente e flegmão mimetizando adenite bacteriana como primeira manifestação da doença de Kawasaki. Paciente previamente hígido, 7 anos, masculino, iniciou quadro de febre, adenite cervical com celulite adjacente e cefaleia intensa, sendo prescrita cefadroxila devido ao diagnóstico clínico de linfadenite bacteriana. Por se manter febril e com piora dos sinais flogísticos, após 1 dia foi internado para receber antibioticoterapia endovenosa (oxacilina e ceftriaxona). Tomografia computadorizada da região cervical mostrou processo infeccioso/inflamatório primário. No quarto dia, apresentou lábios ressecados e descamativos, sendo a oxacilina substituída por clindamicina devido à persistência da febre e sinais flogísticos. No nono dia, iniciou hiperemia ocular não exsudativa. No décimo dia de febre, apresentou exantema em tronco, membros, mãos e pés. Recebeu gamaglobulina endovenosa (2g/kg/dose), evoluiu com resolução dos sintomas e, após 2 dias, recebeu alta hospitalar. No 14odia, apresentou descamação lamelar dos dedos das mãos. Portanto, doença de Kawasaki deve ser considerada no diagnóstico diferencial das linfadenites cervicais febris na infância não responsivas à antibioticoterapia empírica, mesmo que esteja presentes celulite adjacente e flegmão.

Smqnr VARIANTS IN CLINICAL ISOLATES OF Stenotrophomonas maltophilia IN BRAZIL / Variantes de Smqnr de isolados clínicos de Stenotrophomonas maltophilia no Brasil

SUMMARY Stenotrophomonas maltophilia contains a novel chromosomally-encoded qnr gene named Smqnr that contributes to low intrinsic resistance to quinolone. We described Smqnr in 13 clinical isolates of S. maltophilia from two Brazilian hospitals, over a 2-year period. The strains were identified by API 20 NE (bioMérieux, France). Susceptibility by microdilution method to trimetroprim/sulfamethoxazole, ciprofloxacin, levofloxacin, minocycline, ceftazidime, chloramphenicol and ticarcillin/clavulanate was performed according to CLSI. PCR detection of Smqnr gene was carried out. The sequence of Smqnr was compared with those deposited in GenBank. Pulsed-field gel electrophoresis (PFGE) of all strains was performed. Thirteen Smqnr positives isolates were sequenced and three novel variants of Smqnr were identified. All 13 Smqnr isolates had distinguishable patterns by PFGE. This is the first report of Smqnr in S. maltophilia isolated in Brazil. .

RESUMO S. maltophilia contem um novo gene qnr cromossômico denominado Smqnr que contribui para baixa resistência intrínseca a quinolonas. Descrevemos Smqnr em 13 isolados clínicos de S. maltophilia de dois hospitais brasileiros, ao longo do período de dois anos. Os isolados foram identificados pela API 20 NE (bioMérieux, França). Susceptibilidade pelo método de microdiluição dos seguintes antibióticos trimetroprim/sulfametoxazol, ciprofloxacina, levofloxacina, minociclina, ceftazidima, cloranfenicol e ticarcilina/clavulanato foi realizada segundo o CLSI. Detecção do gene de Smqnr foi realizada por PCR. A sequência de Smqnr foi comparada com aquelas depositadas no GenBank. Foi realizada eletroforese em gel de campo pulsado (PFGE) de todos os isolados. Treze isolados contendo Smqnr foram sequenciados e identificados três variantes do gene Smqnr. Todos os 13 isolados de Smqnr apresentaram diferentes padrões por PFGE. Este é o primeiro relato de Smqnr em isolados de S. maltophilia no Brasil. .

The modified Hodge test is a useful tool for ruling out Klebsiella pneumoniae carbapenemase

OBJECTIVE: Enterobacteriaceae bacteria harboring Klebsiella pneumoniae carbapenemase are a serious worldwide threat. The molecular identification of these pathogens is not routine in Brazilian hospitals, and a rapid phenotypic screening test is desirable. This study aims to evaluate the modified Hodge test as a phenotypic screening test for Klebsiella pneumoniae carbapenemase. METHOD: From April 2009 to July 2011, all Enterobacteriaceae bacteria that were not susceptible to ertapenem according to Vitek2 analysis were analyzed with the modified Hodge test. All positive isolates and a random subset of negative isolates were also assayed for the presence of blaKPC. Isolates that were positive in modified Hodge tests were sub-classified as true-positives (E. coli touched the ertapenem disk) or inconclusive (distortion of the inhibition zone of E. coli, but growth did not reach the ertapenem disk). Negative results were defined as samples with no distortion of the inhibition zone around the ertapenem disk. RESULTS: Among the 1521 isolates of Enterobacteriaceae bacteria that were not susceptible to ertapenem, 30% were positive for blaKPC, and 35% were positive according to the modified Hodge test (81% specificity). Under the proposed sub-classification, true positives showed a 98% agreement with the blaKPC results. The negative predictive value of the modified Hodge test for detection was 100%. KPC producers showed high antimicrobial resistance rates, but 90% and 77% of these isolates were susceptible to aminoglycoside and tigecycline, respectively. CONCLUSION: Standardizing the modified Hodge test interpretation may improve the specificity of KPC detection. In this study, negative test results ruled out 100% of the isolates harboring Klebsiella pneumoniae carbapenemase 2. The test may therefore be regarded as a good epidemiological tool.

Diferença de tempo de positividade: método útil no diagnóstico de infecção de corrente sanguínea relacionada com cateter? / Differential time to positivity: a useful tool for the diagnosis of catheter-related infections?

INTRODUÇÃO: As infecções de corrente sanguínea relacionadas com cateter (ICSRCs) apresentam impacto significativo na morbidade e na mortalidade de pacientes internados, além de elevar custos hospitalares. A utilização de equipamentos automatizados no processamento de hemoculturas gerou uma alternativa para diagnóstico de ICSRC por meio da análise da diferença de tempo de positividade (DTP) entre hemoculturas pareadas (coletadas simultaneamente) de sangue periférico e sangue de cateter. Um diagnóstico acurado e rápido dessas infecções pode otimizar as condutas clínicas e terapêuticas, poupando a retirada precoce dos cateteres. OBJETIVOS: Avaliar na rotina a DTP como ferramenta auxiliar no diagnóstico de ICSRC e determinar os principais microrganismos isolados. MÉTODOS: Foram avaliadas retrospectivamente hemoculturas coletadas no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC/FMUSP) de maio a agosto de 2008. Somente amostras que apresentaram DTP maior que 120 minutos foram consideradas possíveis ICSRCs pelo critério laboratorial. RESULTADOS: A seção processou 11.017 hemoculturas aeróbias durante o período de estudo; somente 5% foram coletadas de forma pareada. Destas, 148 (28%) foram positivas, sendo 9% com crescimento somente em sangue periférico, 41% somente em sangue de cateter e 50% em ambas as amostras com 88% de homologia de microrganismos identificados. A DTP apresentou valores acima de 120 minutos em 50% dos casos e os microrganismos mais isolados foram Staphylococcus aureus (22%), Candida spp. (18%), Klebsiella spp. (7%) e Enterobacter spp. (7%). CONCLUSÃO: A determinação da DTP como ferramenta auxiliar no diagnóstico de ICSRC é viável e fácil de ser executada em laboratórios de rotina com automação, porém o processo de coleta das amostras pareadas deve ser rigidamente padronizado.

INTRODUCTION: Not only do catheter related bloodstream infections (CRBSIs) have considerable impact on morbidity and mortality in hospitalized patients, but they also raise hospital costs. The use of automated equipment in blood culture processing has allowed an alternative diagnosis of CRBSI by analyzing the differential time to positivity (DTP) of paired blood cultures (collected simultaneously) of peripheral blood and catheter blood. A rapid and accurate diagnosis of these infections may optimize clinical and therapeutic management, which prevents early catheter removal. OBJECTIVES: To assess DTP as an auxiliary tool for the diagnosis of CRBSI as well as to determine the main isolated microorganisms. METHODS: We evaluated blood cultures that had previously been collected in the complex Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC/FMUSP) from May to August 2008. According to the laboratory criteria, only DTP higher than 120 minutes was regarded as possible CRBSI. RESULTS: During the investigation period 11,017 aerobic blood cultures were processed, from which only 5% were paired samples. One hundred forty-eight (28%) samples were positive, from which 9% showed growth in peripheral blood, 41% only in catheter blood and 50% in both blood samples with 88% homology of identified microorganisms. DTP higher than 120 minutes occurred in 50% of the cases. The most common isolated microorganisms were: Staphylococcus aureus (22%), Candida spp. (18%), Klebsiella spp (7%). and Enterobacter spp (7%). CONCLUSION: The determination of the DTP as an auxiliary tool for the diagnosis of CRBSI is feasible and easily performed in clinical laboratories with automation, although the process of paired sample collection must be rigidly standardized.

Streptococcus pneumoniae: sensibilidade a penicilina e moxifloxacina / Streptococcus pneumoniae: susceptibility to penicillin and moxifloxacin

OBJETIVO: Determinar a concentração inibitória mínima (CIM) de penicilina parenteral e moxifloxacina contra cepas de Streptococcus pneumoniae isoladas em um centro hospitalar. Métodos: Estudo in vitro prospectivo de 100 isolados de S. pneumoniae coletados de pacientes tratados entre outubro de 2008 e julho de 2010 no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, em São Paulo (SP). Os isolados foram obtidos de culturas do trato respiratório e de amostras de sangue não relacionadas a infecções meníngeas e foram testados quanto à suscetibilidade a penicilina e moxifloxacina por E test. As interpretações categóricas de CIM foram baseadas em padrões atualizados. RESULTADOS: Todos os isolados foram suscetíveis a penicilina parenteral (CIM < 2 µg/mL) e, consequentemente, eram também suscetíveis a amoxicilina, ampicilina, cefalosporinas de terceira e quarta geração e ertapenem. Quanto à moxifloxacina, 99 por cento das cepas de S. pneumoniae também foram suscetíveis, e somente uma teve CIM = 1,5 µg/mL (intermediário). Conclusões: Nossos resultados mostraram altas taxas de sensibilidade a penicilina parenteral e moxifloxacin nos isolados de S. pneumoniae não relacionados a meningite, o que difere de relatos internacionais. Relatos sobre resistência a penicilina devem ser baseados em pontos de corte atualizados para isolados não relacionados a meningite a fim de guiar a escolha terapêutica antimicrobiana e melhorar a predição dos desfechos clínicos.

OBJECTIVE: To determine the minimum inhibitory concentrations (MICs) of parenteral penicillin and moxifloxacin against Streptococcus pneumoniae strains isolated at a hospital center. METHODS: In-vitro, prospective study involving 100 S. pneumoniae isolates collected from patients who had been treated, between October of 2008 and July of 2010, at the Hospital das Clínicas complex of the University of São Paulo School of Medicine, located in the city of São Paulo, Brazil. The isolates were obtained from respiratory tract cultures or blood samples unrelated to meningeal infections, and they were tested for penicillin and moxifloxacin susceptibility by E-test. The MIC category interpretations were based on updated standards. RESULTS: All isolates were fully susceptible to parenteral penicillin (MIC < 2 µg/mL), and, consequently, they were also susceptible to amoxicillin, ampicillin, third/fourth generation cephalosporins, and ertapenem. Of the S. pneumoniae strains, 99 percent were also susceptible to moxifloxacin, and only one strain showed an MIC = 1.5 µg/mL (intermediate). CONCLUSIONS: Our results showed high susceptibility rates to parenteral penicillin and moxifloxacin among S. pneumoniae isolates unrelated to meningitis, which differs from international reports. Reports on penicillin resistance should be based on updated breakpoints for non-meningitis isolates in order to guide the selection of an antimicrobial therapy and to improve the prediction of the clinical outcomes.

Stenotrophomonas maltophilia: resistência emergente ao SMX-TMP em isolados brasileiros: uma realidade / Stenotrophomonas maltophilia: emerging resistance to TMP-SMX in Brazilian isolate: a reality

INTRODUÇÃO: Stenotrophomonas maltophilia é um importante patógeno hospitalar emergente, naturalmente resistente aos carbapenêmicos, que possui sulfametoxazol/trimetoprima (SMX-TMP) como opção terapêutica. Porém, relatos de resistência a essa droga começaram a aparecer. OBJETIVO: Avaliar o perfil de sensibilidade das cepas de S. maltophilia e comparar os resultados obtidos por diferentes metodologias. MÉTODOS: As cepas isoladas na rotina microbiológica do Hospital das Clínicas de São Paulo em 2007 foram avaliadas quanto ao perfil de suscetibilidade por disco-difusão e microdiluição. Respeitando a padronização do Clinical and Laboratory Standard Institute (CLSI), SMX-TMP e levofloxacino foram testados pelas duas técnicas, bem como a tigeciclina, interpretada segundo a agência norte-americana Food and Drug Administration (FDA). Ticarcilina/clavulanato, ceftazidima, imipenem, meropenem e moxifloxacino foram avaliados apenas por microdiluição. O percentual de correlação entre as metodologias foi analisado pelo programa WHONET®. RESULTADOS: Das 126 cepas, 1,6 por cento apresentaram resistência a SMX-TMP; 2,4 por cento, a levofloxacino; 23 por cento, a ticarcilina/clavulanato; 54 por cento, a ceftazidima. Todas apresentaram concentração inibitória mínima (CIM) < 2 µg/mL para tigeciclina e 96,8 por cento, CIM < 2 µg/mL para moxifloxacino. O índice de concordância categórica entre as metodologias foi de 100 por cento para SMX-TMP e de 89,6 por cento para levofloxacino. DISCUSSÃO E CONCLUSÃO: Embora SMX-TMP seja a droga de escolha para o tratamento de infecções por S. maltophilia, há possibilidade de resistência a esse antibiótico, dificultando a decisão terapêutica empírica, sendo fundamental a realização do teste de sensibilidade. A técnica de disco-difusão demonstrou boa correlação com a microdiluição. Entre as novas opções terapêuticas, tigeciclina e moxifloxacino apresentaram boa atividade in vitro.

INTRODUCTION: Stenotrophomonas maltophilia is an important emerging nosocomial pathogen naturally resistant to carbapenems. Although trimethoprim/sulfamethoxazole (TMP-SMX) is commonly used as a treatment option, resistance to this drug has been recently reported. OBJECTIVE: To evaluate the susceptibility profile of S. maltophilia strains and compare the results obtained by different methods. METHODS: As to susceptibility profile, all strains, which had been routinely isolated at Hospital das Clínicas, São Paulo, in 2007, were evaluated through disk diffusion and microdilution. In accordance with the Clinical and Laboratory Standard Institute (CLSI), TMP-SMX and levofloxacin were tested through both techniques, as well as tigecycline, which was interpreted in conformity with Food and Drug Administration (FDA) regulations. Ticarcillin/clavulanate, ceftazidime, imipenem, meropenem and moxifloxacin were evaluated only through microdilution. The correlation between these methods was assessed by WHONET®. RESULTS: 1.6 percent of 126 strains were resistant to TMP-SMX, 2.4 percent to levofloxacin, 23 percent to ticarcillin/clavulanate, and 54 percent to ceftazidime. All strains showed minimum inhibitory concentration (MIC) < 2 µg/mL for tigecycline and 96.8 percent MIC < 2 µg/mL for moxifloxacin. The correlation index between both methods was 100 percent for TMP-SMX and 89.6 percent for levofloxacin, respectively. DISCUSSION AND CONCLUSION: Although TMP-SMX is the standard treatment for S. maltophilia infections, there may be resistance to this antibiotic, which hinders the therapeutic approach, hence the significance of susceptibility tests. The disk diffusion technique showed a good correlation with microdilution. Among the new therapeutic options, both tigecycline and moxifloxacin presented significant activity in vitro.

Carbapenem stewardship: positive impact on hospital ecology

INTRODUCTION: Excessive group 2 carbapenem use may result in decreased bacterial susceptibility. OBJECTIVE: We evaluated the impact of a carbapenem stewardship program, restricting imipenem and meropenem use. METHODS: Ertapenem was mandated for ESBL-producing Enterobacteriaceae infections in the absence of non-fermenting Gram-negative bacilli (GNB) from April 2006 to March 2008. Group 2 carbapenems were restricted for use against GNB infections susceptible only to carbapenems and suspected GNB infections in unstable patients. Cumulative susceptibility tests were done for nosocomial pathogens before and after restriction using Clinical and Laboratory Standards Institute (CLSI) guide-lines.Vitek System or conventional identification methods were performed and susceptibility testing done by disk diffusion according to CLSI.Antibiotic consumption (t-test) and susceptibilities (McNemar's test) were determined. RESULTS: The defined daily doses (DDD) of group 2 carbapenems declined from 61.1 to 48.7 DDD/1,000 patient-days two years after ertapenem introduction (p = 0.027). Mean ertapenem consumption after restriction was 31.5 DDD/1,000 patient-days. Following ertapenem introduction no significant susceptibility changes were noticed among Gram-positive cocci. The most prevalent GNB were P. aeruginosa, Klebsiella pneumoniae, and Acinetobacter spp. There was no change in P. aeruginosa susceptibility to carbapenems. Significantly improved P. aeruginosa and K. pneumoniae ciprofloxacin susceptibilities were observed, perhaps due to decreased group 2 carbapenem use. K. pneumoniae susceptibility to trimethoprim-sulfamethoxazole improved. CONCLUSION: Preferential use of ertapenem resulted in reduced group 2 carbapenem use, with a positive impact on P. aeruginosa and K. pneumoniae susceptibility.

Increasing prevalence of extended-spectrum-betalactamase among Gram-negative bacilli in Latin America: 2008 update from the Study for Monitoring Antimicrobial Resistance Trends (SMART)

OBJECTIVES: This analysis of the Study for Monitoring Antimicrobial Resistance Trends (SMART) evaluated the susceptibility patterns of Enterobacteriaceae in Latin America in 2008, with emphasis on susceptibility trends of E. coli and K. pneumoniae. METHODS: Clinical isolates were recovered from intra-abdominal infections (IAI) from 23 centers in 10 Latin American countries. Isolates were sent to a central laboratory for confirmation of identification, antimicrobial susceptibility and ESBL testing, following the Clinical Laboratory Standards Institute (CLSI) guidelines. RESULTS: Of 1,003 Gram-negative bacilli collected from intra-abdominal infections, E. coli and K. pneumoniae were the most commonly isolated organisms, and 26.8 percent of E. coli and 37.7 percent of K. pneumoniae were ESBL positive. Ertapenem and imipenem were the most consistently active agents tested; 99 percent of ESBLpositive E. coli isolates were susceptible to ertapenem and 100 percent to imipenem as well, and 91 percent of ESBL-positive K. pneumoniae were susceptible to ertapenem and 98 percent to imipenem. Quinolones and cephalosporins were less active, achieving 1.5 percent to 76 percent inhibition against ESBL-producing E. coli and 3.5 percent to 61 percent inhibition against K. pneumoniae. CONCLUSIONS: Local and unit-specific surveillance data is particularly important for selection of empiric therapy and in community-acquired infections as they can help the clinician with antibiotic selection by providing guidance regarding the likely pathogens and their resistance profiles. Our data also confirm the increasing frequency with which ESBL-producing organisms are found in the community setting, with 31.4 percent of communityacquired and 24.9 percent of hospital-acquired infections found to produce ESBLs. Imipenem and ertapenem are the most active agents tested for ESBL-positive E. coli and K. pneumoniae.

Candidemia epidemiology and susceptibility profile in the largest Brazilian teaching hospital complex

INTRODUCTION: Although the spectrum of fungi causing bloodstream fungal infections continues to expand, Candida spp. remains responsible for the majority of these cases. OBJECTIVE: The purpose of this study was to characterize the candidemia epidemiology, species distribution and antifungal susceptibility patterns at a Brazilian tertiary teaching public hospital with 2,500 beds. METHODS: Records from the microbiology laboratory were used to identify patients with positive blood cultures during 2006. The in vitro activity of amphotericin B, caspofungin, itraconazole, fluconazole, voricanozole, and posaconazole were determined using the Etest method. RESULTS: One hundred and thirty-six cases of candidemia were identified and 100 strains were available for antifungal susceptibility testing. The overall incidence of candidemia was 1.87 cases/1.000 admissions and 0.27 cases/1.000 patient-days. Among the patients, 58.1 percent were male, and the median age was 40 years old. C. albicans was the most common species (52.2 percent), followed by C. parapsilosis (22.1 percent), C. tropicalis (14.8 percent), and C. glabrata (6.6 percent). All strains were susceptible to amphotericin B with a MIC90 of 0.5 µg/mL. Overall susceptibility for voriconozole, fluconazole, and caspofungin was > 97 percent with a MIC90 of 0.064, 4.0 and 1.0 µg/mL, respectively. For itraconazole the susceptibility rate was 81 percent with a MIC90 of 0.5 µg/mL. Posaconazole also demonstrated good in vitro activity with a MIC90 of 0.25 µg/mL. CONCLUSION: This is the first antifungal susceptibility report in our institution.