eWe evaluated the in vitro activity of polymyxin B plus imipenem, meropenem, or tigecycline against six KPC-2-producing Enterobacteriaceae strains with high MICs for these antimicrobial agents. Polymyxin B with carbapenems, especially meropenem, were the most active combinations for Klebsiella pneumoniae and Enterobacter cloacae regardless of the polymyxin B concentration used in the time-kill assay. This combination was also synergistic against two Serratia marcescens strains that are intrinsically resistant to polymyxins. Polymyxin B and tigecycline also presented synergistic activity in most experiments. KPC-2-producing members of the family Enterobacteriaceae have emerged as a major cause of hospital-acquired infections worldwide, and antimicrobial therapy is frequently restricted to polymyxins (1). Some preclinical and clinical studies have suggested that colistin or polymyxin B (PMB) in combination with another antimicrobial agent, particularly with carbapenems against isolates presenting low-level resistance to these agents, may be superior to monotherapy (2, 3). However, the benefit of combining a carbapenem for isolates with high-level resistance to these antibiotics is less clear (2, 3).Because of pharmacokinetic characteristics of polymyxins, treatment of KPC-2-producing Enterobacteriaceae is even more challenging when MICs for these antibiotics are elevated (2 mg/ liter) but still within the susceptibility range, or higher, characterizing resistance (4). Finally, there has been some debate regarding the efficacy of tigecycline (TGC), another agent commonly used in combination with polymyxins, using standard dose regimes, when the MIC is near (1 mg/liter) the FDA breakpoint (2 mg/liter) or above (2, 5).In the presence of these "adverse" profiles, bacterial clearance could mostly rely on the efficacy of antimicrobial combinations. Thus, to provide some support for therapeutic decisions, we evaluated the in vitro activity of PMB in combination with imipenem (IPM), meropenem (MEM), and TGC against KPC-2-producing Enterobacteriaceae isolates with high MICs for PMB, carbapenems, and TGC.Six strains recovered from clinical specimens (urine, blood, and respiratory secretions), including two Klebsiella pneumoniae strains, two Enterobacter cloacae strains, and two Serratia marcescens strains, previously characterized as KPC-2-producing isolates by gene sequencing and belonging to unrelated clones by pulsed-field gel electrophoresis (PFGE) (6), were selected. Isolates with MICs of Յ2 mg/liter determined by broth microdilution were considered susceptible to polymyxin B (7).A time-kill assay (TKA) was performed by inoculating 5 ϫ 10 6 CFU/ml of the organisms into 10 ml of fresh cation-adjusted Mueller-Hinton broth, and the results are displayed in Table 1. We evaluated nine combinations with PMB against six genetically unrelated strains of KPC-2-producing Enterobacteriaceae with "unfavorable" antibiotic susceptibility profile, i.e., decreased susceptibility or resistance to PMB and/or TGC and high-level resistanc...

O aumento gradativo da incidência de infecções fúngicas é resultado de vários fatores e, um deles, é o número crescente de pacientes com imunossupressão severa. Apesar de novos medicamentos estarem sendo introduzidos para minimizar este problema, o desenvolvimento de resistência diante das drogas antifúngicas se tornou evidente, em especial nos pacientes que recebem tratamentos longos, ou que estão recebendo antifúngicos de forma profilática, onde, em ambos os casos, pode haver mudanças na microbiota humana, dando origem a um ambiente favorável às espécies resistentes. As características farmacológicas, a frequência e, em particular, os mecanismos de resistência para atual classe de agentes antifúngicos são debatidos nesta revisão.

O sangue é composto por várias substâncias, onde cada uma delas tem uma função. Dentre essas substâncias, encontram-se as proteínas denominadas fatores de coagulação, que ajudam a estancar sangramentos quando ocorre o rompimento dos vasos sanguíneos. Desequilíbrios, erros na formação ou deficiências destas proteínas, podem ocasionar desordens de hiper ou hipocoagulação. Neste artigo serão abordadas as tromboses e hemofilias assim como o tratamento e a prevenção.