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- ItemSomente MetadadadosDesenvolvimento e avaliação de duas técnicas para estudo de sinergia de combinações de antimicrobianos frente à Pseudomonas aeruginosa multirresistente(Universidade Federal de São Paulo (UNIFESP), 2021) Santos, Gerlan Da Rocha [UNIFESP]; Kiffer, Carlos Roberto Veiga [UNIFESP]; Universidade Federal de São PauloThe Metallo-β-lactamases (MβLs) enzymes identified in Pseudomonas aeruginosa are increasing sources of resistance, causing hydrolysis to almost all classes of β-lactams, except aztreonam. In addition, MβL-producing P. aeruginosa pose a significant threat to Brazilian health system, especially the Sao Paulo metallo-β-lactamase enzyme (SPM-1). In the presente study, we performed in vitro tests of drug combinations for MβL- and EsβL- (Extended-spectrum β-lactamase) producing P. aeruginosa in order to evaluate their synergistic activity. Initially, the presence of blaSPM-1, blaIMP, blaVIM, blaCTX-M e blaGES-1 genes was confirmed by the polymerase chain reaction (PCR) technique. The minimum inhibitory concentrations (MICs) for some antibiotics and isolates were determined by the broth microdilution or agar dilution method. Then epsilometer crossing tests were performed. In order to interpret the epsilometer crossing test results, the Fraction inhibitory concentration index (FICI) was calculated and the combinations were defined as: synergy (≤0,5), additive (0,5-1), no effect (1-4), and antagonism (≥4). Two of the best performing combinations were also studied by time-kill assay: ceftolozane/tazobactam-aztreonam (C/T-ATM) and ceftolozane/tazobactam-fosfomycin (C/T-FOS). A 88.8% synergy (24/27) was detected for C/T-FOS and 14.8% (4/27) for C/T-ATM by epsilometer crossing test. In comparison, C/T-FOS combination presented synergistic activity in one (1/6) by the time-kill assay. The C/T-ATM combination showed no activity against the six isolates tested by TK assay. In the context of increased resistance to carbapenems among P. aeruginosa, techniques that aim to analyze the synergistic effect and combinations of antimicrobials must studied and the findings may help identifying new treatment options.