Navegando por Palavras-chave "Polymyxins"
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- ItemSomente MetadadadosEfeito de um antimicrobiano na microbiota duodenal; e na evolução clínica de lactentes hospitalizados por diarréia aguda e persistente: um ensaio clínico duplo-cego randomizado(Universidade Federal de São Paulo (UNIFESP), 2000) Tahan, Soraia [UNIFESP]; Morais, Mauro Batista de [UNIFESP]O objetivo do estudo foi avaliar o efeito da polimixina oral na microbiota duodenal e na evolução clínica de lactentes hospitalizados com quadros graves de diarréia aguda e persistente. Este estudo duplo-cego randomizado, incluiu 25 lactentes menores de um ano de idade, hospitalizados com diarréia aguda e persistente. Os pacientes foram randomizados para receber o tratamento com polimixina oral (10mg/kg/d) ou placebo por sete dias. Ambos os grupos receberam a mesma dieta (semi-elementar). Culturas de aspirado duodenal, incluindo pesquisa de aeróbios e anaeróbíos, e cultura de fezes, foram realizadas antes e após sete dias do tratamento. Cinco pacientes foram excluídos durante o decorrer do estudo. Os percentuais de pacientes que apresentaram proliferação bacteriana no intestino delgado (PBID) no grupo polimixina foram, respectivamente, 61,5 por cento (8113) antes do tratamento e 76,9 por cento (lOll3) após o tratamento. No grupo controle, estes valores foram, respectivamente, 71,4 por cento (5/7) e 57,1 por cento(4/7), antes e após o tratamento. No grupo polimixina, a Escherichia coli enteropatogênica clássica (EPEC) foi encontrada em 57,1 por cento (7113) dos pacientes antes do tratamento e em O,O por cento após tratamento. No grupo controle EPEC foi isolada em 57,1 por cento (4/7) dos pacientes antes do tratamento e em 14,3 por cento (2/7) após o tratamento. A duração, em dias, da diarréia após o início do estudo foi de 4,0 ñ 1,9 no grupo polimixina e em 3,8 ñ 2,3 no grupo controle (p=O,88). A média de ganho ponderar no final do ensaio foi 371 ñ 267g. no grupo polimixina e 276 ñ 244g. para o grupo controle (p=O,441). Cura clínica, no 4' dia, foi observada em 30,7 por cento (4113) no grupo polimixina e em 42,8 por cento (3/7) no grupo controle (p=O,651). Conclui-se que a polimixina por via oral não teve efeito em reduzir a proliferação bacteriana no intestino delgado e na evolução clínica de lactentes hospitalizados com diarréia aguda e persistente grave.
- ItemAcesso aberto (Open Access)Effect of polymyxin B-containing regimens on renal function for the treatment of carbapenem-resistant Enterobacteriacea mediastinitis(Elsevier Brazil, 2018) Abboud, Cely Saad; Rao, Gauri G.; Souza, Ercilia E.; Zavascki, Alexandre P.; Kiffer, Carlos [UNIFESP]A retrospective cohort study, were evaluated: polymyxin B plus aminoglycosides or polymyxin B plus other antibiotics. Any degree of acute kidney injury occurred in 26 (86.6%) patients. The median time to acute kidney injury was 6.0 (95% CI 3-14) days in the polymyxin-aminoglycoside containing regimen group, against 27.0 (95% CI 6-42) days in the polymyxin with other antimicrobial combinations group (p = 0.03). Polymyxin B with aminoglycosides group progressed faster to any degree of renal dysfunction. (C) 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license.
- ItemSomente MetadadadosEmergence of polymyxin B resistance in a polymyxin B-susceptible KPC-producing Klebsiella pneumoniae causing bloodstream infection in a neutropenic patient during polymyxin B therapy(Elsevier Science Inc, 2018) Zavascki, Alexandre P.; Girardello, Raquel [UNIFESP]; Magagnin, Cibele M.; Antochevis, Laura C.; Maciel, Rafael A.; Palmeiro, Jussara K. [UNIFESP]; Gales, Ana C. [UNIFESP]The emergence of resistance to polymyxins in KPC-producing Klebsiella pneumoniae isolates has been a major clinical problem. This study evaluated the molecular mechanisms associated with polymyxin B (PMB) resistance that emerged in a previously PMB-susceptible KPC-2-producing K. pneumoniae during PMB therapy for a bloodstream infection in a neutropenic patient. The first isolate (PMB-susceptible) was obtained while the patient was receiving meropenem and other isolates were recovered from 2 sets of blood cultures in different dates while the patient was receiving PMB therapy (4 of 6 blood cultures bottles yielded isolates with full PMB resistance). The population analysis profile of the first isolate revealed the growth of resistant subpopulations with PFGE profile distinct from the parental isolate but undistinguishable from those obtained in subsequent days under PMB exposure. Resistant subpopulations were obtained from all parental PMB-susceptible and in one PMB-resistant isolate recovered from the patient. The molecular mechanism observed in the hetero-resistant subpopulations (IS1-like in mgrB-promoter region, increased rstB transcription with no mutation and non-identified mechanism) differed from those found in the PMB-resistant isolates, in which no mutation or transcriptional alterations were detected. This study showed that the mechanism of resistance to PMB that emerged during PMB therapy was not related to those observed in subpopulations selected in vitro from PMB-susceptible isolates recovered from the patient. The absence of mutations in the former isolates may be due to adaptive resistance occurred because of sub-optimal PMB levels as well as amikacin and meropenem used in combination. (C) 2017 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosInfluência do sistema de transporte de fosfato de alta afinidade Pst na resistência as polimixinas e virulência de Pseudomonas aeruginosa(Universidade Federal de São Paulo (UNIFESP), 2012) Xavier, Danilo Elias [UNIFESP]; Gales, Ana Cristina [UNIFESP]Pseudomonas aeruginosa e um patogeno oportunista mais comumente associado a infeccoes em pacientes hospitalizados e a infeccoes respiratorias cronicas em pacientes com fibrose cistica. Sua versatilidade metabolica, capacidade de adaptacao e habilidade em adquirir mecanismos de resistencia aos antimicrobianos fazem com que seja considerada uma grande preocupacao nos servicos de assistencia a Saúde. O frequente isolamento de P. aeruginosa multirresistentes fez com que as polimixinas, que ainda permanecem eficazes contra P. aeruginosa, viessem a ser utilizadas como uma das ultimas opcoes terapeuticas para o tratamento de infeccoes causadas por esse tipo de patogeno. Contudo, a resistencia as polimixinas, anteriormente pouco relatada devido ao seu desuso, vem sendo observada apos a sua recente reIntrodução e crescente uso na pratica clinica. O principal mecanismos de resistencia as polimixinas em Gram negativos e a diminuicao da interacao eletrostatica da droga com a parede celular bacteriana, consequencia da adicao do grupo 4 amino-ʟ-arabinose (Ara-4N) ao lipideo A e reducao da carga negativa. O operon arn codifica as enzimas responsaveis pela sintese, transporte e ligacao do grupo Ara-4N ao lipideo A e sua expressao e governada por sistemas de regulacao genicas de dois componentes (TCS), como PhoPQ, PmrAB e ParRS, que ativados por estimulos ambientais, como baixa concentracao de Mg2+, sao responsaveis pela resistencia as polimixinas. Mutacoes nesses TCS tem sido observadas entre isolados clinicos de P. aeruginosa exibindo alto grau de resistencia as polimixinas, enquanto mutantes laboratoriais apresentam um grau de resistencia menor. Assim, acredita-se que existam outros determinantes de resistencia as polimixinas associados aos TCS entre as amostras clinicas. Este estudo avaliou o impacto do sistema de transporte de fosfato de alta afinidade Pst no fenotipo de resistencia as polimixinas e na virulencia de P. aeruginosa. A delecao do sistema Pst nao produziu efeito significativo no fenotipo de resistencia as polimixinas na cepa selvagem de P. aeruginosa PAK ou em associacao com o determinante de resistencia as polimixina pmrAB12. Entretanto, a delecao de Pst resultou na diminuicao da sensibilidade as polimixinas em mutantes com PhoQ nulo. Alem disso, a delecao de PhoQ e/ou PstCAB resultou na atenuacao da virulencia de P. aeruginosa em modelo de infeccao de embrioes de peixe-zebra. O sistema Pst de Gram negativos esta acoplado ao sistema de dois componentes PhoRB, que responde a deplecao de fosfato inorganico no meio, regulando a expressao de genes que, na sua maioria, estao envolvidos na assimilacao de fosfato, formando o regulon PHO. O presente estudo apresenta evidencias da interacao do regulon PHO com o sistema PhoPQ, contribuindo para a resistencia as polimixinas por um mecanismo dependente de PhoQ nulo, alem da influencia do regulon PHO na expressao de fatores de virulencia em P. aeruginosa
- ItemAcesso aberto (Open Access)Influência dos Métodos de Sensibilidade aos Antimicrobianos no Uso Clínico das Polimixinas(Universidade Federal de São Paulo (UNIFESP), 2010-05-04) Silva, Itacy Gonçalves de Siqueira e [UNIFESP]; Gales, Ana Cristina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Acinetobacter spp. e Pseudomonas aeruginosa are important pathogens that cause infections in Brazilian hospitals and have become resistant to almost every available antimicrobial. Thereby, the clinical indication of parenteral use of polymyxin has been reestablished in recent years. Therefore, the clinical laboratory of microbiology need be able to perform reliable susceptibility antimicrobial tests. Objective: Analyze the influence of susceptibility antimicrobial tests in the clinical use of polymyxins. Material and Methods: Nine P. aeruginosa and 10 Acinetobacter spp. strains were tested to polymyxin susceptibility. The results of agar dilution, broth microdilution and Etest were compared, according CSLI. The influence of culture medium, calcium concentration, inoculum concentration and incubation time in the susceptibility antimicrobial test was evaluated. Results: There was good agreement between different polymyxin antimicrobial susceptibility methods for Acinetobacter spp isolates, but not for P. aeruginosa. It was observed 100% of agreement between Iso-sensitest and Müeller-Hinton medium through agar dilution and Etest for Acinetobacter spp. isolates. Through broth microdilution occurred 90% of agreement for polymyxin B and 60% for colistin. Between P. aeruginosa isolates, Etest had greater MIC variation when using different culture mediuns. In general, BHI medium had low MICs comparing with Müller- Hinton. The calcium concentration increase in the culture medium promoted MICs elevation in ±1Log2 of dilution, for both microrganisms. Etest had 55,6% (polymyxin B) and 88,9% (colistin) of minor error, and 11,1% of major error in polymyxin B. Inoculum size had greater influence in agar dilution, with minor error rates of 10% (polymyxin B) and 30% (colistin) for Acinetobacter spp. isolates, and 33,3% (polymyxin B) and 66,6% (colistin) for P. aeruginosa isolates. Different time incubations caused MICs variation only between P. aeruginosa isolates. Etest method had 33,3% (polymyxin B) and 44,4%(colistin) of minor error. Through agar dilution, the minor error rate was 11,1% with incubation time variation.
- ItemSomente MetadadadosOld antibiotics for multidrug-resistant pathogens: from in vitro activity to clinical outcomes(Elsevier Science Bv, 2017) Kaye, Keith S.; Gales, Ana C. [UNIFESP]; Dubourg, GregoryAntimicrobial resistance is a major and emerging threat worldwide. New antimicrobials have been unable to meet the resistance challenge, and treatment options are limited for a growing number of resistant pathogens. More and more clinicians are relying on older antimicrobials for the treatment of multidrug-resistant (MDR) bacteria. Some older antimicrobials have maintained excellent in vitro activity against highly resistant pathogens. In some instances, use of older agents is limited by unfavourable pharmacokinetic/pharmacodynamic characteristics and/or toxicities. In general, clinical data pertaining to the use of older agents for the treatment of MDR pathogens are scarce. Research efforts should be focused on the evaluation of older agents for the treatment of MDR pathogens as well as evaluating how these agents perform in complex patient populations with various and multiple co-morbid conditions. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
- ItemAcesso aberto (Open Access)Uso de polimixina em pacientes submetidos a transplante: avaliação de eficácia e nefrotoxicidade(Universidade Federal de São Paulo (UNIFESP), 2009-08-26) Mostardeiro, Marcelo Mileto [UNIFESP]; Camargo, Luis Fernando Aranha [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Polymyxins are old antimicrobials which had their use discontinued for many years because of nephrotoxicity and neurotoxicity description. The development of multirresistant gram negative bacteria in special P aeruginosa and A baumanii all over the world is a matter of fact and we have observed its growth in international epidemiologic surveys since the 90’s. Until now we don´t have studies that demonstrate renal dysfunction tax in transplanted patients because of polymyxin use, nevertheless we know that renal function contribute in a statistical significant manner for receptors survive in long term. Methods: We have retrospectively searched for all solid organ transplanted patients and who have used polymyxins from January 2001 to December 2007 in 2 teaching hospitals in São Paulo city, Brazil. The main study objective was to define the nephrotoxicity percentage. For evaluating this variable we choosed 2 renal function definitions (first criteria and second criteria) and applied them in all studied patients with the objective of comparing them each other and with the literature. First criteria was defined as serum creatinine > 2 mg/dl after polymyxin introduction in those patients with acute renal dysfunction, or 50% serum creatinine increase in relation to value before polymyxin was given in those patients with previous nephotoxicity. In both situations described above we also considered renal dysfunction if 50% decrease in estimated creatinine clearance by Cockcroft & Gault methodology occurred, or progression to dialysis therapy. Second criteria was defined as any serum creatinine increase. Results: We identified 92 solid organ transplanted patients who used polymyxins. The majority of them received renal or renal/pancreas grafts (90.2%), and the organs transplanted were from deceased donors in 70,7%. The main site of infection were urinary tract infection (UTI) (41.3%), followed by surgical site infection (SSI) (17.4%) and pneumonia (16.3%). P aeruginosa were the main etiologic agent present in 76.1% of isolates. Microbiologic cure occurred in 25 patients (100%), clinical cure in 71 patients (77.2%), and in hospital mortality occurred in 21 patients (22.8%). Fourty four patients (47.8%) presented nephrotoxicity according to any of the 2 adopted criteria, 30 patients (32.6%) according to the first criteria, and 44 patients (47.8%) according to the second criteria. Multivariate analysis show statistical significant association among UTI and protection for renal dysfunction [p 0.02; OR 0.24; IC 95% (0.07 – 0.86)], and greater mean polymyxin utilization time (p 0.03) as a risk factor for renal dysfunction by the first criteria. Conclusions: The 32.6% percentage of renal dysfunction is still high, but lower than that reported in the 60’s and 70’s. Polymyxin utilization is effective principally for the treatment of UTI in solid organ transplanted patients, its use should be judicious and for shorter time as possible.