| Congresso Brasileiro de Microbiologia 2023 | Resumo: 522-2 | ||||
Resumo:Cefiderocol is a new antibiotic that has brought hope to the fight against multidrug resistant Gram-negative bacilli. This antibiotic has a cephalosporin moiety and a catechol-type siderophore, which has the ability to bind to iron, facilitating its entry into the bacterial cell by using iron transporters. In acute bacterial infections, the human innate immune system minimizes available free iron, which leads the bacteria to upregulate iron transporters which would facilitate the cefiderocol entrance in the bacterial cells. This condition has to be mimicked for the in vitro susceptibility test by broth microdilution (BMD), which is achieved by the depletion of iron in the culture media. The susceptibility profile can be determined by disk diffusion (DD) method without altering iron concentrations, however a broad range of area of technical uncertainty (ATU) was set for Enterobacterales (18-22 mm) and for Pseudomonas aeruginosa (14-22 mm) according to EUCAST. For Acinetobacter spp., there is insufficient evidence to establish clinical breakpoints but a halo ≥17 mm would correspond to a minimum inhibitory concentration (MIC) ≤2 mg/L, which indicates susceptibility by PK-PD breakpoints. Considering that there is such a large range of ATU, it is necessary to evaluate the correlation between DD and MIC of cefiderocol, in order to correctly resolve those isolates that fall into the ATU, whether it should be reported as resistant or a different methodology should be performed, as recommended by BrCAST/EUCAST. The aim of this study was to evaluate the correlation between both methodologies for clinical isolates of Enterobacterales, P. aeruginosa and Acinetobacter spp. A total of 22 Enterobacterales (17 Klebsiella pneumoniae, 3 Enterobacter spp., 2 Klebsiella oxytoca, 1 Proteus mirabilis), 8 P. aeruginosa and 7 Acinetobacter spp. were submitted to cefiderocol DD and BMD assays. In order to prepare the medium for BMD, cation adjusted Mueller-Hinton broth was cation depleted with of Chelex 100 resin by agitation at room temperature for 4 hours. Then, the medium was filtered to remove Chelex 100, and calcium, magnesium, and zinc were added at concentrations of 22.5 mg/L, 11.25 mg/L and 0.56 mg/L, respectively. The medium was filtered and iron concentration was measured. After confirmation of iron depletion, microtitre plates were prepared with cefiderocol powder and the isolates were inoculated. For Enterobacterales, the categorical agreement was 47.8% (11/23), although it is important to mention that 10 out of 23 isolates were in the ATU. These 10 isolates were all categorized as resistant by DD and as susceptible by BMD. Without taking into consideration the isolates in the ATU, there was only one major and one very major discrepancies (Figure 1A). For P. aeruginosa, the categorical agreement was 100% (8/8), with four isolates in the ATU. Among these, three were resistant and one was susceptible (Figure 1B). Considering the PK-PD breakpoint for Acinetobacter spp., there was only one major discrepancy (Figure 1C). There was a good correlation between DD and BMD for P. aeruginosa and, interestingly, all Enterobacterales in the ATU were susceptible by BMD. These preliminary results demonstrate that isolates that fall into the ATU, when using DD method, should be tested by BMD in order to confirm the susceptibility profile. Palavras-chave: cefiderocol, broth microdilution, disk diffusion, multidrug resistance, Gram-negative bacilli Agência de fomento:Instituto Nacional de Pesquisa em Resistência a Antimicrobianos (INPRA) CNPq 465718/2014-0; Fundo de Incentivo à Pesquisa e Eventos (FIPE) do Hospital de Clínicas de Porto Alegre (HCPA). | |||||