Clostridium difficile infection (CDI) continues to possess a significant disease burden in the United States (US) as well as all over the world. Given the increase in severity and recurrence rate, the decrease in cure rate, and the fact that the virulent ribotype 027 strain remains one of the most commonly identified strains in the US, the Infectious Diseases Society of America (IDSA) published a clinical practice guideline in February 2018 moving away from metronidazole as the first-line treatment for initial CDI and recommending either oral vancomycin or fidaxomicin. The aim of this study is to evaluate the clinical data available comparing the efficacy of primary treatment of CDI between those two antibiotics. We performed a PubMed, PubMed Central, and ScienceDirect database search without restriction to regions, publication types, or languages. A comprehensive literature search was performed from January 1, 1980 up to March 20, 2018. We used the following keywords in different combinations: Clostridium difficile, Clostridium difficile infection, CDI, C. diff, C. difficile, fidaxomicin, vancomycin, pseudomembranous colitis, and antibiotic-associated colitis. The search was limited to human studies. Data were independently extracted by two reviewers with disagreements resolved by a third author. We pooled an odds ratio (OR) on two primary outcomes: Clinical cure rate and rate of recurrence during the follow-up period. The computer search was also supplemented with manual searches by the authors of the retrieved review articles and primary studies. The search phrase "((Clostridium difficile) AND vancomycin) AND fidaxomicin" had the highest yield results. We identified four observational studies with a total of 2,303 patients with CDI that met our inclusion criteria. Compared with vancomycin, fidaxomicin use was associated with a significantly lower recurrence of CDI with a pooled OR of 0.47 (95% confidence interval (CI), 0.37 - 0.60, I2 = 0). On the other hand, there was no significant association of fidaxomicin use with CDI cure rate compared to vancomycin with a pooled OR of 1.22 (95% CI, 0.93 - 1.60, I2 = 0). In light of the recently updated clinical practice guidelines by the IDSA, our review suggests that fidaxomicin has a more sustained clinical response with a statistically significant lower recurrence rate. Although fidaxomicin appears to be the better drug with statistical significance, its cost-effectiveness continues to be an ongoing controversy. More randomized clinical trials are needed to shed light on this matter to assess if there is any clinical significance in fidaxomicin superiority.

BACKGROUND: Evidence supporting beta-lactam plus vancomycin synergy for methicillin-resistant (MRSA) continues to grow. Current evidence demonstrates that combination therapy is associated with shorter time to blood sterilization than vancomycin monotherapy. However, this combination has not been reported as salvage therapy for persistent MRSA bacteremia. CASE REPORT: We report a case of an 81-year-old male who was successfully treated with vancomycin plus nafcillin after failing vancomycin monotherapy, daptomycin monotherapy, and daptomycin plus gentamicin combination therapy. The patient originally presented with sepsis from a suspected urinary tract infection. Blood cultures drawn on days 1, 3, 5, 15, 19, 23, and 28 remained positive for MRSA despite multiple antimicrobial therapy changes. On day 29, therapy was changed to vancomycin plus nafcillin. Blood cultures drawn on day 32 remained negative. After 11 days, nafcillin was changed to piperacillin-tazobactam due to an infected decubitus ulcer. The combination was continued for 42 days after achieving blood sterility, 71 days after the patient originally presented. Evidence regarding salvage therapy for persistent bacteremia is sparse and is limited to case reports and case series. CONCLUSION: This case report supports that vancomycin plus an anti-staphylococcal beta-lactam combination should be further studied as salvage therapy for persistent MRSA bacteremia.

No description available.

DNA similarity studies were used to determine the species of thirty-one strains of bacteria isolated from the hemolymph of infected larvae from Mexico and throughout Central and South America. Twenty-one of the strains were determined to be <I>Paenibacillus popilliae</I> and ten were found to be more closely related to <I>Paenibacillus lentimorbus</I>. Only one of the <I>P. popilliae</I> strains, an isolate from Mexico, was resistant to the antibiotic vancomycin, a trait characteristic of <I>P. popilliae</I> strains from other geographic areas. As expected, all <I>P. lentimorbus</I> strains were sensitive to vancomycin. The polymerase chain reaction (PCR) was used to amplify a portion of a ligase gene necessary for vancomycin resistance in the Mexican strain. Sequencing of the amplicon revealed a sequence identical to that obtained from a North American strain of <I>P. popilliae</I> previously described. The ability of <I>P. popilliae</I> and the inability of <I>P. lentimorbus</I> to grow on medium supplemented with 2% sodium chloride has been used as a phenotypic trait for differentiating between the two species. Approximately 86% of the <I>P. popilliae</I> strains were capable of growth on medium supplemented with 2% sodium chloride and 60% of the <I>P. lentimorbus</I> strains were not capable of growth on this medium. Microscopic examination revealed that all of the Mexican and Central and South American strains of <I>P. popilliae</I> and <I>P. lentimorbus</I> produced a parasporal body. PCR was used to amplify two different regions of the <I>cry18Aa1</I> gene encoding the paraspore in all of the isolates. One primer pair, CryBP2, detected the <I>cry18Aa1</I> gene in 17 of the 21 <I>P. popilliae</I> strains and in all ten of the <I>P. lentimorbus</I> strains. The second primer pair, CryBP4, detected the parasporal gene in 20 of the 21 <I>P. popilliae</I> strains and in all ten of the <I>P. lentimorbus</I> strains. Thirty of the thirty-one <I>P. popilliae</I> and <I>P. lentimorbus</I> strains produced amplicons of approximately 616 bp with the CryBP4 primers. The CryBP4 primers did not detect the paraspore gene in one of the <I>P. popilliae</I> strains. The CryBP2 primer pair produced amplicons of three different sizes, indicating possible variability in the parasporal proteins of <I>P. popilliae</I> and <I>P. lentimorbus</I>. Eleven of the <I>P. popilliae</I> strains produced CryBP2 amplicons approximately 660 bp in size and six of the <I>P. popilliae</I> strains produced CryBP2 amplicons approximately 1100 bp in size. The <I>cry</I> gene was not detected in four of the <I>P. popilliae</I> strains with the CryBP2 primers. The <I>P. lentimorbus</I> strains produced CryBP2 amplicons approximately 750 bp in size. Three PCR products representing the variable CryBP2 amplicon sizes were sequenced and compared to the published <I>cry18Aa1</I> gene sequence. Sequencing data revealed that the Central and South American CryBP2 amplicons are similar to the published <I>cry18Aa1</I> sequence, however, the 1100 bp amplicon has a 453 bp insert that is not found in the published <I>cry18Aa1</I> gene sequence. Paraspores are produced by <I>P. popilliae</I> and <I>P. lentimorbus</I> and is not a reliable phenotypic trait for differentiation between the two species. The ability of Mexican and Central and South American strains of <I>P. lentimorbus</I> to produce paraspores supports the previous findings of a North American group of <I>P. lentimorbus</I> strains that were also capable of producing paraspores. Except for one Mexican strain of <I>P. popilliae</I>, the Central and South American strains of <I>P. popilliae</I> are sensitive to vancomycin. This was unexpected since all North American strains of <I>P. popilliae</I> are vancomycin resistant. Vancomycin resistance could be useful in identifying strains of <I>P. popilliae</I> from North America but not for identifying strains of <I>P. popilliae</I> from Central and South America. So far, no vancomycin resistant strains of <I>P. lentimorbus</I> have been identified. There was variability in the ability of these organisms to grow on medium supplemented with 2% sodium chloride so the usefulness of this trait is debatable. However, the majority of <I>P. popilliae</I> strains from Mexico and Central and South America will grow on medium supplemented with 2% sodium chloride and the majority of the <I>P. lentimorbus</I> strains from these same areas will not grow on this medium. North American strains of <I>P. popilliae</I> and <I>P. lentimorbus</I> also showed variability of growth on medium supplemented with 2% sodium chloride. / Master of Science

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with no known cure. Despite years of study, the etiology of SLE is still unclear. Both genetic and environmental factors have been implicated in the disease mechanisms. Gut microbiota as an environmental factor and the immune system interact to maintain tissue homeostasis, but whether this interaction is involved in the pathogenesis of SLE is unclear. In a classical model of lupus nephritis, MRL/lpr, we found decrease of Lactobacillales but increase of Lachnospiraceae in the gut microbiota. Increasing Lactobacillales in the gut by suppling a mixture of 5 Lactobacillus strains improved renal function of these mice and prolonged their survival. Further studies revealed that MRL/lpr mice possessed a "leaky" gut, which was reversed by increased Lactobacillus colonization. Inside the kidney, oral Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. To remove Lachnospiraceae that was higher in lupus-prone mice than controls, we administered vancomycin orally to MRL/lpr mice after disease onset from 9 to 15 weeks of age. Vancomycin functions by removing Gram-positive bacteria such as Lachnospiraceae but sparing Lactobacillus spp. The treatment during active lupus reshaped the gut microbiota and significantly ameliorated systemic autoimmunity and kidney histopathology at 15 weeks of age. However, when vancomycin treatment was initiated from a very early age, the beneficial effect was not observed. Strikingly, mice given vancomycin only at the young age exhibited an even worse disease outcome. Indeed, regulatory B (Breg) cells were found to be reduced after the vancomycin treatment at young age. Importantly, adoptive transfer of Breg cells at 6-7 weeks of age rescued the beneficial effect, which indicates that Breg cells, inducible by vancomycin-sensitive gut microbiota, plays an important role in suppressing lupus disease initiation and progression. Finally, we demonstrated that bacterial DNA from the gut microbiota might be the inducer of Breg cells, as bacterial DNA administration at young age reproduced the beneficial effect seen in the Breg adoptive transfer experiment. Future studies are required to examine the clinical efficacy of targeting gut microbiota as a novel treatment against SLE. / Ph. D.

Yes / Highly branched poly(N-isopropylacrylamide) (HB-PNIPAM), functionalized with vancomycin at the chain ends, acted as a bacterial adhesive and was incorporated into polyurethane foams to form semi-interpenetrating networks. The poly(N-isopropylacrylamide) was labelled with a solvatochromic dye, Nile red. It was found that the thermal response of the polymer was dependent on architecture and temperature dependent color changes were observed within the foam. The foams had open pore structures and the presence of the HB-PNIPAM substantially reduced the shrinkage of the foam as the temperature was increased upto 20 °C. The foams were selectively adhesive for Staphylococcus aureus (Gram-positive bacteria) compared to Pseudomonas aeruginosa (Gram-negative bacteria) and the presence of S. aureus was indicated by increased fluorescence intensity (590 to 800 nm).

O paciente grande queimado está entre os de maior risco de contrair infecção hospitalar, sendo que, aproximadamente 80% dos óbitos nestes pacientes são decorrentes de infecção. Devido à prevalência de S. aureus meticilina resistente (MRSA) nas unidades de queimados prescreve-se a vancomicina como fármaco de 1ª linha. Entretanto como a farmacocinética se encontra profundamente alterada geralmente ocorre a falência terapêutica e surgimento de resistência antimicrobiana. O objetivo do presente estudo foi monitorar as concentrações plasmáticas através da análise em CLAE-UV e realizar a modelagem farmacocinética da vancomicina, administrada nestes pacientes. Para tanto, validou-se método analítico que se mostrou linear, preciso, exato e suficientemente sensível para o monitoramento das concentrações plasmáticas da vancomicina nos pacientes. Investigaram-se 9 pacientes adultos grandes queimados após cirurgia de debridamento; os pacientes foram informados em detalhes sobre o estudo e assinaram o TCLE, e incluídos no protocolo. Coletaram amostras sangüíneas seriadas para a farmacocinética (PK solutions 2.0). A estatística descritiva (Microsoft Excell, Office for Windows, versão 2000) forneceu os resultados expressos através da média +/- DP: 16 mg/L±11, para o pico (referência 20-40mg/L) e 2,6 mg/L±1,5 para o vale (referência,5-10mg/L), abaixo da CME nestes pacientes. Os parâmetros farmacocinéticos foram o volume aparente de distribuição que se mostrou aumentado em cerca de 3,5 vezes, (1,4 L/Kg ± 0,8 versus 0,33-0,45L/kg, referência, a depuração plasmática mostrou-se aumentada em cerca de 2,5 vezes (3,2±1,65 mL/min.kg versus 1,3 - 1,5mL/min.kg, referência, enquanto a constate de eliminação e a meia-vida biológica se mantiveram inalteradas. Este estudo indica que o regime posológico e tipo de infusão endovosa devam ser revistos, utilizando a farmacocinética como ferramenta importante. Recomenda-se ainda que a terapia dose ajustada seja baseada no controle terapêutico destes pacientes em todas as fases da internação, principalmente após cada cirurgia de debridamento. / Nosocomial infections shows high incidence in burn patient, and approximately 80% of mortality of them is due to severe infections and sepse. High prevalence of methycilin resistant S. aureus (MRSA) occurs in the intensive care units for burn patients and vancomycin is largely prescribed as first choice drug for severe infections and sepse. In general occurs therapeutic fail, since the pharmacokinetics is altered in these patients and arise the antimicrobial resistance. The main of the present study was to perform therapeutic plasma vancomycin monitoring by HPLC-UV and also PK- modelling after 1g every 12 hours, 1 hour infusion. Bioanalitical method was validated showing good linearity, precision, accuracy, good stability and robustness. Additionally method required 200&#181;L of plasma and showed sensitivity enough for vancomycin plasma monitoring. Nine large burn patients were included in the study after they signed the informed written consent term to participate of the protocol. The follow up was done after debridment surgery. Blood samples were collected from venous catheter at time dose interval to investigate the pharmacokinetics (PK solutions 2.0) and also to determine the peak and trough. Descriptive statistics was performed applying Microsoft Excell, Office for Windows, versão 2000. Data obtained were 16 mg/L±11 peak (reference 20-40mg/L) and 2.6 mg/L±1.5 trough that was lower than MEC since the reference ranges from 5 to 10mg/L). Pharmacokinetic parameters were volume apparent of distribution, that was increased by 3.5 times (1.4 L/Kg ± 0,8 against the reference values 0.33-0.45L/kg), plasma clearance was also increased by 2.5 times (3.2±1.7mL/min.kg versus 1.3 - 1.5mL/min.kg, reference values), while elimination rate constant and biological half-life remained unchanged in those patients. Based on data obtained in the study, author recommends a revision on dose schedule and also concerning intravenous drug infusion using the pharmacokinetics as a powerful tool and the therapeutic plasma vancomycin monitoring for dose adjustments in all phases of the follow up of burn patient, mainly after each surgery debridement.

O tratamento de infecções por Staphylococcus aureus tem sido problemático devido ao surgimento de cepas resistentes a múltiplios antibióticos. O antibiótico de escolha para o tratamento de infecções por S. aureus resistente a oxacilina é o glicopeptídeo vancomicina. Desde o primeiro isolamento de cepas com sensibilidade reduzida a vancomicina (VISA) em 1997, tem havido crescente preocupação com a disseminação da resistência a este antibiótico. Os mecanismos moleculares que levam à resistência de baixo nível a vancomicina ainda não foram elucidados. A detecção deste fenótipo na rotina de laboratório clínico é laboriosa, pois as técnicas disponíveis são de difícil execução e interpretação. Até agora, não há relato de transmissão horizontal de infecção por VISA, e todas as cepas com este fenótipo foram isoladas de pacientes que faziam o uso prolongado de vancomicina. Uma deficiência no locus regulador de genes acessórios (agr) foi postulado como fator de risco para a aquisição do fenótipo VISA por uma cepa sensível a este antibiótico. Para este estudo, foram selecionadas 47 cepas de S. aureus, com sensibilidades variadas a vancomicina, inclusive 5 cepas VISA isoladas no Brasil. Determinou-se nas cepas as concentrações inibitórias mínimas de vancomicina e oxacilina, a atividade hemolítica em ágar sangue de carneiro e de coelho, a capacidade de aderir ao poliestireno e o polimorfismo do locus agr. Determinou-se a integridade do locus agr por PCR-RFLP e sequenciamento de bases em 13 cepas representativas das 47 estudadas. A integridade do locus regulador acessório sarA também foi avaliada por sequenciamento de bases nestas 13 cepas. Foram escolhidas 18 cepas sensíveis a vancomicina com variadas características fenotípicas e estas foram submetidas à indução de resistência a vancomicina através da passagem seriada em concentrações crescentes deste antibiótico. A taxa de mutação que leva à capacidade de crescimento em 6 &#181;g/mL de vancomicina foi avaliada em 8 cepas através de ensaios de flutuação. Não observou-se correlação entre a aquisição de resistência a vancomicina com as atividades hemolíticas ou capacidade de adesão das cepas. A maioria das cepas (82,9%) apresentou-se como pertencente ao grupo polimórfico agr I, inclusive as cepas VISA. Duas cepas não conseguiram ser induzidas à resistência a vancomicina. O tempo levado para a aquisição de resistência não se correlacionou com nenhuma característica fenotípica ou genotípica de um grupo de cepas. A taxa de mutação que leva à capacidade de crescimento em 6&#181;g/mL de vancomicina apresentou-se maior para uma cepa pertencente ao clone endêmico brasileiro (CEB) cujo locus agr pertence ao grupo I e não apresentou variação de acordo com funcionalidade ou tipo do locus agr. Apenas uma das cepas VISA apresentou uma mutação no locus agr que o torna disfuncional. Os loci agr das outras cepas estudadas apresentaram-se íntegros. O locus sarA das cepas estudadas apresentou-se íntegro e com polimorfismos funcionais agrupados de acordo com a linhagem clonal das cepas. Pôde-se concluir que a integridade funcional do locus agr não é uma condição sine qua non para a aquisição de resistência de baixo nível a vancomicina por parte de uma cepa sensível a este antibiótico. O grupo polimórfico agr II não tem maior predisposição à aquisição de resistência de baixo nível a vancomicina, como havia sido sugerido por alguns trabalhos disponíveis na literatura. / The treatment of staphylococcal infections has lately been a strenuous undertaking due to the resistance of Staphylococcus aureus to multiple antibiotics. The antimicrobial drug of choice for the treatment of methicillin resistant S. aureus (MRSA) is the glycopeptide vancomycin. Since the first isolation of S. aureus with reduced susceptibility to vancomycin (VISA) in 1997, there has been growing concern as to the dissemination of this resistance phenotype among isolates of this species. The molecular mechanisms that result in low level resistance to vancomycin have not yet been completely elucidated. The correct detection of this phenotype in the clinical laboratory is tricky, for the techniques available for this purpose are hard to execute and interpret. Until now, lateral transmission (dissemination) of VISA has not been reported and all strains bearing this phenotype have been isolated from patients who had been making prolonged use of vancomycin. A deficiency in the accessory gene regulator (agr) has been proposed as a risk factor for the acquisition of a VISA phenotype by a susceptible strain. For this study, 47 nosocomial VISA strains, that had been isolated in another study, were used. These strains were isolated from multiple geographical regions of Brazil, and included 5 VISA strains. The minimal inhibitory concentrations (MIC) of vancomycin and oxacillin, as well as haemolysis in sheep and rabbit agar, adhesion to polystyrene and agr polymorphism were determined in all of these strains. The integrity of the agr locus was determined by PCR-RFLP and by nucleotide sequencing in a sample of 13 strains chosen to be representative of the 47 strains studied. The integrity of the Staphylococcal accessory regulator sarA was also determined by nucleotide sequencing in these 13 strains. Another representative sample of 18 strains that were susceptible to vancomycin were submitted to induction of resistance to vancomycin by serial passage in increasing concentrations of this drug. The mutation rate of a mutation that leads to the ability of growing in a concentration of 6 &#181;g/mL of vancomycin was determined for 8 strains by fluctuation assays. There was no correlation between the acquisition of resistance to vancomycin with either haemolysis or adhesion to polystyrene. Most strains (82.9%) bore a group I agr polymorphism, including all of the VISA strains. Two strains could not be induced to resistance. The time taken for each strain to acquire resistance to vancomycin did not correlate with any phenotypic or genotypic characteristic pertaining to a group of strains. The rate of mutation that leads to the ability of growing in 6&#181;g/mL of vancomycin proved to be higher for a strain belonging to the Brazilian Endemic Clone (BEC) bearing an agr group I polymorphism, and did not vary according to presence or type of agr locus. Only one of the VISA strains presented a mutation in the agr locus that renders it disfunctional. The agr loci of the other strains studied presented themselves to be intact. The sarA loci of the strains evaluated were intact however presented functional polymorphisms that were groups according to the clonal lineage of the strains. It can thus be concluded that the functional integrity of the agr locus is not a sine qua non condition for the acquisition of low level resistance to vancomycin by a susceptible strain. Bearing of an agr group II polymorphism does not predispose a strain to acquire resistance to vancomycin, as has been previously suggested in literature.

O paciente grande queimado está entre os de maior risco de contrair infecção hospitalar, sendo que, aproximadamente 80% dos óbitos nestes pacientes são decorrentes de infecção. Devido à prevalência de S. aureus meticilina resistente (MRSA) nas unidades de queimados prescreve-se a vancomicina como fármaco de 1ª linha. Entretanto como a farmacocinética se encontra profundamente alterada geralmente ocorre a falência terapêutica e surgimento de resistência antimicrobiana. O objetivo do presente estudo foi monitorar as concentrações plasmáticas através da análise em CLAE-UV e realizar a modelagem farmacocinética da vancomicina, administrada nestes pacientes. Para tanto, validou-se método analítico que se mostrou linear, preciso, exato e suficientemente sensível para o monitoramento das concentrações plasmáticas da vancomicina nos pacientes. Investigaram-se 9 pacientes adultos grandes queimados após cirurgia de debridamento; os pacientes foram informados em detalhes sobre o estudo e assinaram o TCLE, e incluídos no protocolo. Coletaram amostras sangüíneas seriadas para a farmacocinética (PK solutions 2.0). A estatística descritiva (Microsoft Excell, Office for Windows, versão 2000) forneceu os resultados expressos através da média +/- DP: 16 mg/L±11, para o pico (referência 20-40mg/L) e 2,6 mg/L±1,5 para o vale (referência,5-10mg/L), abaixo da CME nestes pacientes. Os parâmetros farmacocinéticos foram o volume aparente de distribuição que se mostrou aumentado em cerca de 3,5 vezes, (1,4 L/Kg ± 0,8 versus 0,33-0,45L/kg, referência, a depuração plasmática mostrou-se aumentada em cerca de 2,5 vezes (3,2±1,65 mL/min.kg versus 1,3 - 1,5mL/min.kg, referência, enquanto a constate de eliminação e a meia-vida biológica se mantiveram inalteradas. Este estudo indica que o regime posológico e tipo de infusão endovosa devam ser revistos, utilizando a farmacocinética como ferramenta importante. Recomenda-se ainda que a terapia dose ajustada seja baseada no controle terapêutico destes pacientes em todas as fases da internação, principalmente após cada cirurgia de debridamento. / Nosocomial infections shows high incidence in burn patient, and approximately 80% of mortality of them is due to severe infections and sepse. High prevalence of methycilin resistant S. aureus (MRSA) occurs in the intensive care units for burn patients and vancomycin is largely prescribed as first choice drug for severe infections and sepse. In general occurs therapeutic fail, since the pharmacokinetics is altered in these patients and arise the antimicrobial resistance. The main of the present study was to perform therapeutic plasma vancomycin monitoring by HPLC-UV and also PK- modelling after 1g every 12 hours, 1 hour infusion. Bioanalitical method was validated showing good linearity, precision, accuracy, good stability and robustness. Additionally method required 200&#181;L of plasma and showed sensitivity enough for vancomycin plasma monitoring. Nine large burn patients were included in the study after they signed the informed written consent term to participate of the protocol. The follow up was done after debridment surgery. Blood samples were collected from venous catheter at time dose interval to investigate the pharmacokinetics (PK solutions 2.0) and also to determine the peak and trough. Descriptive statistics was performed applying Microsoft Excell, Office for Windows, versão 2000. Data obtained were 16 mg/L±11 peak (reference 20-40mg/L) and 2.6 mg/L±1.5 trough that was lower than MEC since the reference ranges from 5 to 10mg/L). Pharmacokinetic parameters were volume apparent of distribution, that was increased by 3.5 times (1.4 L/Kg ± 0,8 against the reference values 0.33-0.45L/kg), plasma clearance was also increased by 2.5 times (3.2±1.7mL/min.kg versus 1.3 - 1.5mL/min.kg, reference values), while elimination rate constant and biological half-life remained unchanged in those patients. Based on data obtained in the study, author recommends a revision on dose schedule and also concerning intravenous drug infusion using the pharmacokinetics as a powerful tool and the therapeutic plasma vancomycin monitoring for dose adjustments in all phases of the follow up of burn patient, mainly after each surgery debridement.

O gênero Staphylococcus está intimamente relacionado às infecções hospitalares onde existe a presença de implantes médicos, em especial os cateteres venosos centrais (CVC). Nestas infecções, a habilidade de formar biofilme é considerada um importante fator de virulência entre Staphylococcus. Biofilmes são agregados microbianos envolvidos por uma matriz polimérica extracelular que confere proteção contra a ação do sistema imunológico e ação dos antimicrobianos, dificultando assim o tratamento das infecções relacionadas a implantes médicos. Os objetivos deste estudo foram: (i) avaliar a formação de biofilme em 222 isolados de Staphylococcus spp. de CVC através de dois métodos fenotípicos [ágar Congo Red (ACR) e microplacas com cristal violeta] e estabelecer possíveis marcadores genéticos de formação de biofilme, através da pesquisa dos genes icaA, icaD, aap e atlE, (ii) estabelecer um teste de suscetibilidade através da técnica de microdiluição em caldo para avaliar a concentração inibitória mínima de vancomicina necessária para erradicar o biofilme formado (CMEB), e comparar estes valores com os resultados obtidos através da técnica de concentração inibitória mínima (CIM) em crescimento planctônico.Das 222 amostras analisadas, encontramos 64,5% (143/222) de isolados formadores de biofilme. A detecção de biofilme em S. epidermidis foi de 64,5% e 54% pelos métodos de microplaca e ACR respectivamente, utilizando microplacas com cristal violeta como padrão ouro. Encontramos os genes icaA e icaD na grande maioria (92% - 132/143) dos isolados produtores, o que confirma a importância destes genes na formação de biofilme. Em um total de 37 S. aureus a produção de biofilme ocorreu em 81,1% (30/37) dos isolados, sendo que entre os MRSA a taxa foi de 88,9% e entre os MSSA de 78,6%. Os genes icaA e icaD estavam presentes em 25/30 das amostras formadoras de biofilme. Nos demais Staphylococcus spp. coagulase negativos não epidermidis foi observada uma taxa de produção de biofilme de 35,6% (6/19). Os isolados formadores de biofilme foram classificados em três categorias: forte, moderado e fraco. Entre os isolados forte e moderadamente produtores de biofilme foram observados uma maior razão CMEB / CIM (> 32) frente à vancomicina. Entre isolados biofilme negativos, não encontramos diferenças nos valores de CMEB e CIM. Embora a forma de crescimento em biofilme no processo infeccioso já tenha sido bem comprovada, os laboratórios de microbiologia clínica realizam testes de suscetibilidade em isolados na forma xii planctônica. Desta forma, os resultados obtidos neste estudo, indicam que a CIM pode não ser o parâmetro mais adequado para guiar a terapêutica. Sendo assim, é extremamente importante avaliar a suscetibilidade à vancomicina, em casos de infecções relacionadas à CVC, na forma de biofilme bacteriano (CMEB). / Staphylococcus is closely related to hospital infections, where the presence of medical implants exists, here represented by central venous catheter (CVC). In these infections, the ability to form biofilm is considered an important virulence factor among Staphylococcus. Biofilms are structured communities of microbial species involved by an extracellular polymeric matrix, which protects against the immunologic system and antimicrobial actions, making it harder to treat those infections related to medical implants. The goals of this study were: (i) to evaluate the biofilm formation in 222 isolates of Staphylococcus spp. of CVC through both phenotypic methods [agar Congo Red (ACR) and microtiter plates] and establish possible genetic markers of biofilm formation, through the research of the icaA, icaD, aap and atlE genes, by PCR, (ii) establish susceptibility in biofilm, through of the microdilution test to evaluate the minimal inhibitory concentration of vancomycin to eradicate the biofilm formed - Minimal Biofilm Eradication Concentration (MBEC) and to compare these results with the values found to the Minimal Inhibitory Concentration (MIC) in growth planctonic. From the 222 analyzed samples, we found 64.5% (143/222) of isolates biofilm producers. The detection of the biofilm formation in the S. epidermidis was 64.5% and 54% by the microtiter plate and ACR methods, respectively, using microtiter plates as gold standard. We found icaA and icaD genes in most (92%) of the biofilm producing isolates, which confirms that those genes are essential for this kind of formation. In a total of 37 S. aureus, the biofilm production was observed in 81.1% (30/37) of the isolates. Concerning the MRSA we found 88.9% and among MSSA were observed 78.6% of biofilm-producing. The icaA and icaD genes were present in 25/30 of the samples biofilm producers. On the other Staphylococcus spp. coagulase negatives non-epidermidis, it was observed a number of 35.6% (6/19). The biofilm producing isolates were classified in three categories: strong, moderate and weak. Among the strong and moderate biofilm producing isolates, we could observe a higher ratio MBEC/MIC (>32) in relation to the vancomycin. Among negative biofilm isolates we found matching values for MBEC and MIC. Although the form of growth in biofilm among the infection process has already been well proven, the clinical microbiology laboratories perform susceptibility testing on isolates in the xiv planktonic form. Thus, the results of this study indicate that the MIC cannot be the most appropriate parameter to guide therapy. It is therefore extremely important to evaluate the susceptibility to vancomycin in cases of infection related to CVC, in the form of bacterial biofilms (MBEC).