Abstract
Objectives
Carbapenem-resistant Pseudomonas aeruginosa (CR-PSA) imposes great limitations on empirical therapeutic choices, which are further complicated by metallo-β-lactamase production. ...This study evaluated in vitro antimicrobial synergy of ceftolozane/tazobactam in combination with aztreonam and fosfomycin against MDR PSA.
Methods
MICs were determined by broth microdilution and gradient strips. The effect of ceftolozane/tazobactam+aztreonam and ceftolozane/tazobactam+fosfomycin combinations were tested against 27 MDR PSA isolates carrying blaSPM-1 (n = 13), blaIMP (n = 4), blaVIM (n = 3), blaGES-1 (n = 2) and blaCTX-M-like (n = 2), and 3 isolates with no acquired β-lactamase production detected by gradient diffusion strip crossing (GDSC). Six genetically unrelated SPM-1-producing isolates were also evaluated by time–kill analysis (TKA).
Results
All CR-PSA isolates harbouring blaSPM-1, blaGES-1 and blaIMP-1 were categorized as resistant to ceftolozane/tazobactam, meropenem and fosfomycin, with 70% being susceptible to aztreonam. Synergism for ceftolozane/tazobactam+fosfomycin and ceftolozane/tazobactam+aztreonam combinations was observed for 88.9% (24/27) and 18.5% (5/27) of the isolates by GDSC, respectively. A 3- to 9-fold reduction in ceftolozane/tazobactam MICs was observed, depending on the combination. Ceftolozane/tazobactam+fosfomycin was synergistic by TKA against one of six SPM-1-producing isolates, with additional non-synergistic bacterial density reduction for another isolate. Aztreonam peak concentrations alone demonstrated a ≥3 log10 cfu/mL reduction against all six isolates, but all strains were within the susceptible range for the drug. No antagonism was observed.
Conclusions
In the context of increasing CR-PSA and the genetic diversity of resistance mechanisms, new combinations and stewardship strategies may need to be explored in the face of increasingly difficult to treat pathogens.
•Combined therapies have been evaluated against MβL-producing P. aeruginosa isolates.•TLc + AT combination presented synergistic effect against SPM-1-producing strains.•TLc+ C/T combination presented ...antagonistic effect against SPM-1-producing strains.
Minimal inhibitory concentrations (MICs) of ticarcillin/clavulanic acid (TLc), ceftolozane/tazobactam (C/T), and aztreonam (AT) were determined for 6 SPM-1-producing Pseudomonas aeruginosa (PSA) using Etest® strips and the synergistic effect of such antimicrobials against was evaluated by gradient diffusion strip crossing (GDSC) test. The fraction inhibitory concentration indexes (FICI) were calculated and showed a synergistic (n = 3) and additive (n = 2) effects of TLc + AT against SPM-1 producers, while TLc + C/T combination caused no effect. Average MIC reduction of TLc and AT by GDSC was 3-fold and 2-fold dilutions, respectively. Thus, TLc + AT might be a candidate as a combination therapy to treat SPM-1-producing PSA infections.
O objetivo desse trabalho foi analisar a diversidade genética de isolados de H. capsulatumno Brasil. Foram selecionadas amostras sequenciadas de H. capsulatum para os genesarf(Fator de ribosilação ...ADP) e ole(delta-9 fatty aciddesaturase), provenientes de diversos estados do país. Os dados foram obtidos no Centro Nacional de Informação Biotecnológica (NCBI-National Center for Biotechnology Information). Foram incluídas 79 amostras de H. capsulatum sendo que destas, 45 (57%)eram sequências do gene arfe 34 (43%)eram sequências do gene ole. Dentre as 45amostras do genearf, 29 (64,4%) eram de origem clínica,12 (26,7%) de origem ambiental e quatro (8,9%) de origem veterinária. As 34 (100%) amostras do gene ole eram de origem clínica. A análise do gene arf demonstrou que similaridade das amostras variou de 61 a 99%. Entretanto, observamos uma similaridade menor (44%) entre quatro amostras provenientes do Rio de Janeiro. De acordo com a análise filo genética, as sequências parciais do gene ole demonstraram elevados níveis similaridade, variando de 62 a 99%. Os isolados de H. capsulatum demonstraram grande semelhança entre si quando analisamos o gene ole assim como o gene arf, independente da região geográfica do país.
O objetivo desse trabalho foi analisar a diversidade genética de isolados de H. capsulatum no Brasil. Foram selecionadas amostras sequenciadas de H. capsulatum para os genes arf (Fator de ribosilação ...ADP) e ole (delta-9 fatty acid desaturase), provenientes de diversos estados do país. Os dados foram obtidos no Centro Nacional de Informação Biotecnológica (NCBI - National Center for Biotechnology Information). Foram incluídas 79 amostras de H. capsulatum sendo que destas, 45 (57%) eram sequências do gene arf e 34 (43%) eram sequências do gene ole. Dentre as 45 amostras do gene arf, 29 (64,4%) eram de origem clínica, 12 (26,7%) de origem ambiental e quatro (8,9%) de origem veterinária. As 34 (100%) amostras do gene ole eram de origem clínica. A análise do gene arf demonstrou que similaridade das amostras variou de 61 a 99%. Entretanto, observamos uma similaridade menor (44%) entre quatro amostras provenientes do Rio de Janeiro. De acordo com a análise filogenética, as sequências parciais do gene ole demonstraram elevados níveis similaridade, variando de 62 a 99%. Os isolados de H. capsulatum demonstraram grande semelhança entre si quando analisamos o gene ole assim como o gene arf, independente da região geográfica do país.
