Inappropriate empirical antimicrobial treatment in bloodstream infections patients in the era of multidrug resistance / Terapia Empírica Inapropriada no Tratamento de Infecções de Corrente Sanguínea na Era da Multirresistência Antimicrobiana / Tratamiento antimicrobiano empírico inadecuado en pacientes con infecciones del torrente sanguíneo

Background and objectives: Bloodstream infection (BSI) by multidrug-resistant Pseudomonas aeruginosa is a severe infection. This study aimed to evaluate and identify the predictors of mortality in patients who had bloodstream infection by carbapenem-resistant P. aeruginosa. Methods: This is a retrospective cohort study, approved by Committee of Ethics in Research with Human Participants, which included 87 consecutive patients hospitalized in a referral hospital in Brazil. Clinical and demographic information about each patient were obtained from hospital records. The Student's T-test was used to compare continuous variables and x2 or Fisher's exact tests to compare categorical variables. To determine independent risk factors for 30-day mortality, a multiple logistic regression model was used. A survival curve was constructed using the Kaplan­Meier method. Results: Among the patients, 87.3% use antibiotics previously, 60.9% received inadequate empirical treatment, and the 30-day mortality rate was 57.5%. Inappropriate antibiotic empirical therapy was independently associated with a 30-days death and mortality rate. Conclusion: These findings can show some insights about the relationship between higher mortality and inappropriate empirical therapy for patients with BSI by P. aeruginosa. There is a need for better diagnostic tests and infection control programs should focus on de-escalation the antibiotic inappropriate therapy, mainly in BSI caused by carbapenem-resistant P. aeruginosa.(AU)

Justificativa e objetivos: Infecção da corrente sanguínea (ICS) por Pseudomonas aeruginosa multirresistente é grave. Este estudo teve como objetivo avaliar e identificar os preditores de mortalidade em pacientes admitidos em uma Unidade de Terapia Intensiva que apresentaram infecção da corrente sanguínea por P. aeruginosa resistente aos carbapenêmicos. Métodos: Trata-se de um estudo de coorte retrospectivo, aprovado pelo Comitê de Ética em Pesquisa com Seres Humanos, que incluiu 87 pacientes consecutivos internados em um hospital de referência no Brasil. As informações clínicas e demográficas de cada paciente foram obtidas através de análise dos prontuários dos pacientes. O teste T de Student foi usado para comparar variáveis contínuas e o teste x2 ou exato de Fisher para comparar variáveis categóricas. Para determinar fatores de risco independentes para mortalidade em 30 dias, foi utilizado um modelo de regressão logística múltipla. Uma curva de sobrevida foi construída pelo método de Kaplan-Meier. Resultados: Do total de pacientes, 87,3% faziam uso prévio de antibióticos, 60,9% receberam tratamento empírico inadequado e a mortalidade em 30 dias foi de 57,5%. A terapia empírica inadequada foi fator de risco independente para mortalidade. Conclusão: Esses achados revelam alguns insights sobre a relação entre maior mortalidade e terapia empírica inadequada para pacientes com ICS por P. aeruginosa. Além disso, destacam a necessidade de melhores testes diagnósticos e os programas de controle de infecção devem se concentrar na redução da terapia inadequada com antibióticos, principalmente na ICS causada por P. aeruginosa resistente a carbapenêmicos.(AU)

Justificación y objetivos: La infección del torrente sanguíneo por Pseudomonas aeruginosa multirresistente es grave. Este estudio tuvo como objetivo evaluar e identificar predictores de mortalidad en pacientes ingresados en una Unidad de Cuidados Intensivos que presentaban infección del torrente sanguíneo por P. aeruginosa resistente a carbapenémicos. Métodos: Se trata de un estudio de cohorte retrospectivo, aprobado por el Comité de Ética en Investigación con Participantes Humanos, que incluyó 87 pacientes consecutivos ingresados en un hospital de referencia en Brasil. La información clínica y demográfica de cada paciente se obtuvo mediante el análisis de las historias clínicas de los pacientes. Se utilizó la prueba t de Student para comparar variables continuas y x2 o prueba exacta de Fisher para comparar variables categóricas. Para determinar los factores de riesgo independientes para la mortalidad a los 30 días, se utilizó un modelo de regresión logística múltiple. Se construyó una curva de supervivencia utilizando el método de Kaplan-Meier. Resultados: Del total de pacientes, el 87,3% utilizaba antibióticos previamente, el 60,9% recibió tratamiento empírico inadecuado y la tasa de mortalidad a los 30 días fue del 57,5%. La terapia empírica inadecuada fue un factor de riesgo independiente de mortalidad. Conclusión: Estos hallazgos revelan algunos conocimientos sobre la relación entre el aumento de la mortalidad y la terapia empírica inadecuada para los pacientes con infección del torrente sanguíneo por P. aeruginosa. Además, destacan la necesidad de mejores pruebas de diagnóstico y los programas de control de infecciones deben centrarse en reducir la terapia con antibióticos inapropiados, particularmente en infección del torrente sanguíneo causados por P. aeruginosa resistente a carbapenémicos.(AU)

Molecular Detection of Class 1 Integron-Associated Gene Cassettes in KPC-2-Producing Klebsiella pneumoniae Clones by Whole-Genome Sequencing.

The dissemination of antimicrobial resistance genes and the bacterium that harbor them have increasingly become a public concern, especially in low- and middle-income countries. The present study used whole-genome sequencing to analyze 10 KPC-2-producing Klebsiella pneumoniae isolates obtained from clinical specimens originated from Brazilian hospitals. The study documents a relevant "snapshot" of the presence of class 1 integrons in 90% of the strains presenting different gene cassettes (dfrA30, dfrA15, dfrA12, dfrA14, aadA1, aadA2, and aac(6')Iq), associated or not with transposons. Two strains presented nonclassical integron (lacking the normal 3'conserved segment). In general, most strains showed a complex resistome, characterizing them as highly resistant. Integrons, a genetically stable and efficient system, confer to bacteria as highly adaptive and low cost evolution potential to bacteria, even more serious when associated with high-risk clones, indicating an urgent need for control and prevention strategies to avoid the spread of resistance determinants in Brazil. Despite this, although the class 1 integron identified in the KPC-2-producing K. pneumoniae clones is important, our findings suggest that other elements probably have a greater impact on the spread of antimicrobial resistance, since many of these important genes were not related to this cassette.

Hypervirulence and biofilm production in KPC-2-producing Klebsiella pneumoniae CG258 isolated in Brazil.

In this study, we describe the frequency of virulence genes in Klebsiella pneumoniae carbapenemase-2-producing Klebsiella pneumoniae (KPC-KP), including hypervirulent (hv) and hypermucoviscous (hm) strains by whole-genome sequencing. We also evaluate the capacity for biofilm formation by using phenotypic techniques. The occurrence of several virulence genes (fimABCDEFGHIK, mrkABCDFHJ, ecpA, wabG, entB, ugE, irp1, irp2, traT, iutA and ureADE) and a high frequency of hvhmKPC-KP isolates was found. Most hospital-associated lineages of KPC-KP belong to the international clonal group 258 (CG258). Biofilm formation was a constant feature among 90.9 % of KPC-KP strains. This report suggests a close relationship between ST437 and weak biofilm production, given that all weakly biofilm-producing strains belonged to this sequence type. This also supports the dissemination of KPC-KP containing numerous virulence determinants belonging to the biofilm-producing CG258 type in Brazil, including hv and hm strains. These factors allow this pathogen to cause infections, leading to its rapid expansion and persistence in hospital settings.

High frequency of the combined presence of QRDR mutations and PMQR determinants in multidrug-resistant Klebsiella pneumoniae and Escherichia coli isolates from nosocomial and community-acquired infections.

Plasmid-mediated quinolone resistance (PMQR) determinants combined with mutations in quinolone resistance-determining regions (QRDRs) and clonal dissemination were investigated in 40 fluoroquinolone-resistant Klebsiella pneumoniae and Escherichia coli isolates from nosocomial and community-acquired infections. We observed nucleotide substitutions in gyrA (Ser83Ile, Val37Leu, Lys154Arg, Ser171Ala, Ser19Asn, Ile198Val, Ser83Tyr, Ser83Leu, Asp87Asn and Asp87Gly) and parC genes (Ser80Ile, Glu84Lys, Ala129Ser, Val141Ala and Glu84Gly). Two novel substitutions were detected in the gyrA gene (Val37Leu and Ile198Val). The presence of PMQR genes predominated in community isolates (55.5 %). In addition to the frequent presence of the class 1 integron in isolates from community-acquired infections, the genetic similarity results obtained by PFGE showed high genomic diversity. This study suggests that management of multidrug-resistant Enterobacteriaceae isolates from the community are a possible source of genetic mobile elements that carry genes that confer resistance to fluoroquinolones. More attention should be paid to the surveillance of community-acquired infections.

Clinical and Molecular Epidemiology of Multidrug-Resistant P. aeruginosa Carrying aac(6')-Ib-cr, qnrS1 and blaSPM Genes in Brazil.

We described a comprehensive analysis of the molecular epidemiology of multidrug-resistant (MDR) P. aeruginosa. Molecular analysis included typing by Pulsed Field Gel Electrophoresis, identification of genes of interest through PCR-based assays and sequencing of target genes. Case-control study was conducted to better understand the prognostic of patients and the impact of inappropriate therapy in patients with bacteremia, as well as the risk factors of MDR infections. We observed a high rate of MDR isolates (40.7%), and 51.0% of them was independently associated with inappropriate antibiotic therapy. Bacteremia was detected in 66.9% of patients, and prolonged hospital stay was expressive in those resistant to fluoroquinolone. Plasmid-mediated quinolone resistance genes (PMQR), qnrS1 and aac(6')Ib-cr, were detected in two different nosocomial isolates (5.3%), and the aac(6')-Ib7 variant was detected at a high frequency (87.5%) in those negative to PMQR. The presence of mutations in gyrA and parC genes was observed in 100% and 85% of selected isolates, respectively. Isolates harboring PMQR genes or mutations in gyrA and parC were not closely related, except in those containing SPM (São Paulo metallo-ß-lactamase) clone. In addition, there is no study published in Brazil to date reporting the presence of Pseudomonas aeruginosa isolates harboring both qnrS1 and aac(6')Ib-cr genes, with alarming frequency of patients with inappropriate therapy.

The nares as a CA-MRSA reservoir in the healthy elderly.

INTRODUCTION: The frequency of methicillin-resistant Staphylococcus aureus (MRSA) has increased in the community. This study evaluated the prevalence of MRSA and community-acquired (CA)-MRSA in 120 healthy elderly. METHODS: The MRSA were evaluated for the presence of the IS256, mecA, agr, icaA, icaD, fnbB , and pvl genes with PCR. RESULTS: Frequency of S. aureus and MRSA colonization was 17.8% and 19%, respectively. CA-MRSA isolate showed SCC mec IV, fnbB+ , and icaD+ . CONCLUSIONS: CA-MRSA was detected, with genotype determined as SCC mec type IV/IS256/ fnbB+ / icaA / icaD+ / bbp-/agr2 / bap / pvl, characterizing this population as a possible reservoir of this organism in the community.

Microorganisms contaminating ticks collected at natural reserves or wild animals / Microrganismos contaminantes de carrapatos coletados em reservas naturais ou animais selvagens

This work investigated microorganisms responsible for the contamination and death of ticks from natural reserves and wild animals and later kept in the Laboratory of Ixodology in the Veterinary School of the Federal University of Uberlândia. Such investigation aimed prevention of tick death in the laboratory but also search for microorganisms to be used in the biological control of ticks. From four tick samples of Amblyomma genus, the following agents were isolated: Staphylococus sp, Gram positive bacillus, filamentous fungi of the genera Aspergillus and Penicillium, and a yeast identified as Non-albicans Candida and Cryptococcus sp. Even though the source of contamination of these ticks is uncertain, this study displayed the necessity of to better evaluating the spread of pathogens by ticks, as well as those known to be transmitted solely during tick feeding.

Neste trabalho foram investigados microrganismos responsáveis pela colonização e morte de carrapatos provenientes de reservas naturais ou animais selvagens e mantidos posteriormente no Laboratório de Ixodologia da Faculdade de Medicina Veterinária da Universidade Federal de Uberlândia. Esta investigação se fez necessária para tentar prevenir mortalidade de carrapatos no laboratório, mas também para contribuir com a busca por microrganismos que poderiam ser utilizados no controle biológico do ácaro. Foram isolados de cinco amostras de carrapatos do gênero Amblyomma os seguintes microrganismos: Staphylococus sp, bacilos Gram positivos, fungos filamentosos dos gêneros Aspergillus e Penicillium, além de leveduras identificadas como Candida não-albicans e Cryptococcus sp. Mesmo que a origem da contaminação dos carrapatos com estes microrganismos seja incerta este trabalho indica a necessidade de se avaliar melhor a difusão de outros patógenos por carrapatos, além daqueles transmitidos com a hematofagia.

Nosocomial infections in a Brazilian neonatal intensive care unit: a 4-year surveillance study.

INTRODUCTION: Report the incidence of nosocomial infections, causative microorganisms, risk factors associated with and antimicrobial susceptibility pattern in the NICU of the Uberlândia University Hospital. METHODS: Data were collected through the National Healthcare Safety Network surveillance from January 2006 to December 2009. The patients were followed five times/week from their birth to their discharge or death. RESULTS: The study included 1,443 patients, 209 of these developed NIs, totaling 293 NI episodes, principally bloodstream infections (203; 69.3%) and conjunctivitis (52; 17.7%). Device-associated infection rates were as follows: 17.3 primary bloodstream infections per 1,000 central line-days and 3.2 pneumonias per 1000 ventilator-days. The mortality rate in neonates with NI was 11.9%. Mechanical ventilation, total parenteral nutrition, orogastric tube, previous antibiotic therapy, use of CVC and birth weight of 751-1,000g appeared to be associated with a significantly higher risk of NI (p < 0.05). In multiple logistic regression analysis for NI, mechanical ventilation and the use of CVC were independent risk factors (p < 0.05). Coagulase- negative Staphylococcus (CoNS) (36.5%) and Staphylococcus aureus (23.6%) were the most common etiologic agents isolated from cultures. The incidences of oxacillin-resistant CoNS and S. aureus were 81.8% and 25.3%, respectively. CONCLUSIONS: Frequent surveillance was very important to evaluate the association of these well-known risk factors with NIs and causative organisms, assisting in drawing the attention of health care professionals to this potent cause of morbidity.

Nosocomial infections in a Brazilian neonatal intensive care unit: a 4-year surveillance study / Infecções hospitalares em uma unidade de terapia intensiva neonatal brasileira: vigilância de quatro anos

INTRODUCTION: Report the incidence of nosocomial infections, causative microorganisms, risk factors associated with and antimicrobial susceptibility pattern in the NICU of the Uberlândia University Hospital. METHODS: Data were collected through the National Healthcare Safety Network surveillance from January 2006 to December 2009. The patients were followed five times/week from their birth to their discharge or death. RESULTS: The study included 1,443 patients, 209 of these developed NIs, totaling 293 NI episodes, principally bloodstream infections (203; 69.3 percent) and conjunctivitis (52; 17.7 percent). Device-associated infection rates were as follows: 17.3 primary bloodstream infections per 1,000 central line-days and 3.2 pneumonias per 1000 ventilator-days. The mortality rate in neonates with NI was 11.9 percent. Mechanical ventilation, total parenteral nutrition, orogastric tube, previous antibiotic therapy, use of CVC and birth weight of 751-1,000g appeared to be associated with a significantly higher risk of NI (p < 0.05). In multiple logistic regression analysis for NI, mechanical ventilation and the use of CVC were independent risk factors (p < 0.05). Coagulase- negative Staphylococcus (CoNS) (36.5 percent) and Staphylococcus aureus (23.6 percent) were the most common etiologic agents isolated from cultures. The incidences of oxacillin-resistant CoNS and S. aureus were 81.8 percent and 25.3 percent, respectively. CONCLUSIONS: Frequent surveillance was very important to evaluate the association of these well-known risk factors with NIs and causative organisms, assisting in drawing the attention of health care professionals to this potent cause of morbidity.

INTRODUÇÃO: Relatar a incidência das infecções hospitalares, microrganismos causadores, fatores de risco associados e o padrão de susceptibilidade aos antimicrobianos na UTI neonatal do Hospital Universitário de Uberlândia. MÉTODOS: Realizou-se vigilância National Healthcare Safety Network de janeiro de 2006 a dezembro de 2009. Os pacientes foram acompanhados cinco vezes por semana desde o seu nascimento até a alta ou óbito. RESULTADOS: O estudo incluiu 1.443 pacientes dos quais 209 desenvolveram infecção hospitalar, totalizando 293 episódios de IHs, com destaque para as infecções de corrente sanguínea (203; 69,3 por cento) e conjuntivite (52; 17,7 por cento). As taxas de infecção associadas a dispositivos foram as seguintes: 17,3 infecções da corrente sanguínea primária por 1.000 CVC dia e 3,2 pneumonias por 1.000 ventiladores-dia. A taxa de mortalidade em recém-nascidos com infecções hospitalares foi de 11,9 por cento. A ventilação mecânica, nutrição parenteral total, sonda orogástrica, antibioticoterapia prévia, uso de CVC e peso de 751-1.000g pareceu estar associado com um risco significativamente maior de IH (p < 0,05). Na análise de regressão logística múltipla para IH, ventilação mecânica e uso de CVC foram fatores de risco independentes (p < 0,05). Staphylococcus coagulase-negativo (SCoN) (36,5 por cento) e Staphylococcus aureus (23,6 por cento) foram os agentes etiológicos mais comumente isolados. A incidência de SCoN e S. aureus resistente à oxacilina foram de 81,8 por cento e 25,3 por cento, respectivamente. CONCLUSÕES: Uma vigilância frequente foi importante para avaliar a associação de fatores de risco bem conhecidos com as IHs e etiologia com a finalidade de chamar a atenção dos profissionais de saúde para esta grande causa de morbidade.

Fatores de risco associados à colonização por Candida spp em neonatos internados em uma Unidade de Terapia Intensiva Neonatal brasileira / Risk factors associated with colonization by Candida spp in neonates hospitalized in a Neonatal Intensive Care Unit in Brazil

Os objetivos desse estudo foram investigar a participação de Candida albicans e não-albicans como agente de colonização e sepse, bem como os fatores de risco associados aos neonatos internados na Unidade de Terapia Intensiva Neonatal do Hospital de Clínicas da Universidade Federal de Uberlândia. Foi realizada vigilância epidemiológica pelo sistema National Healthcare Safety Network no período entre agosto de 2007 e abril de 2008. A taxa de incidência de sepse com critério microbiológico foi de 6,7/1.000 paciente/dia, constatando-se apenas um caso de candidemia. Aproximadamente, 19 por cento dos neonatos estavam colonizados por Candida, identificadas como Candida albicans (50 por cento) e Candida não-albicans (50 por cento). Os fatores de risco significantes para colonização por Candida spp foram a idade gestacional entre 26 e 30 semanas, o uso prévio de antibiótico e o cateter vascular central umbilical. A mortalidade total foi de 11,8 por cento nos neonatos internados durante o período de estudo com sepse, porém o recém-nascido com candidemia não evoluiu para óbito.

The objectives of this study were to investigate the participation of Candida albicans and non-albicans as colonization and sepsis agents, along with the risk factors associated with the neonates in the neonatal intensive care unit of the clinical hospital of the Federal University of Uberlândia. Epidemiological surveillance was implemented through the National Healthcare Safety Network between August 2007 and April 2008. The incidence rate for sepsis with microbiological criteria was 6.7/1,000 patients/day, which was shown as only one case of candidemia. Approximately 19 percent of the neonates were colonized by Candida, which was identified as Candida albicans (50 percent) and Candida not-albicans (50 percent). The significant risk factors for Candida spp colonization were gestational age of between 26 and 30 weeks, previous antibiotic use and umbilical central vascular catheter. The overall mortality among the neonates hospitalized with sepsis over the study period was 11.8 percent. However, the neonate with candidemia did not die.

Incidência e etiologia de infecções de corrente sanguínea associadas a cateter vascular central em neonatos críticos / Incidence and etiology of bloodstream infection associated of central vascular catheter in critical neonates

Os objetivos do estudo foram avaliar os fatores de risco associados à infecção de corrente sangüínea, o uso de diferentes tipos de cateter vascular central (CVC) e a etiologia destas infecções. Foi realizada análise microbiológica no sítio de inserção do CVC, na ponta, no canhão do cateter e na narina e a identificação dos microrganismos isolados foi realizada por técnicas clássicas. Foram incluídos 115 neonatos em uso de CVC na investigação, no período de abril a outubro de 2007. Foi observado que 7,8% dos neonatos apresentaram infecção de corrente sangüínea associada a CVC, com destaque para os inseridos por flebotomia (7,8/1000 cateteres-dia). Embora a densidade de utilização do Cateter Central de Inserção Periférica (PICC) tenha sido a mais alta, a inserção por flebotomia foi responsável pela maior taxa de infecção de corrente sangüínea associada a CVC. A hospitalização > 14 dias e a colonização da ponta do cateter > 103 UFC/ml foram os fatores de risco estatisticamente significantes para estas infecções, sendo que a narina (33%) e a pele na área de inserção do cateter (22%) foram potenciais sítios de origem da infecção e o Staphylococcus coagulase negativa (SCoN) foi o agente mais freqüente (44,4%). Conclui-se que o PICC foi o CVC com maior densidade de utilização na unidade, embora a taxa de infecção de corrente sangüínea associada a flebotomia tenha sido a mais expressiva.