Comparison of available methods to evaluate cefiderocol susceptibility in Acinetobacter spp.

Recently, considerable uncertainty has arisen concerning the appropriate susceptibility testing for cefiderocol in gram-negative bacilli, particularly in the context of its application to Acinetobacter spp. The optimal method for assessing the susceptibility levels of Acinetobacter spp. to cefiderocol remains a subject of debate due to substantial disparities observed in the values obtained through various testing procedures. This study employed four minimum inhibitory concentration (MIC) methodologies and the disk diffusion to assess the susceptibility of twenty-seven carbapenem resistant (CR)-Acinetobacter strains to cefiderocol. The results from our study reveal significant variations in the minimum inhibitory concentration (MIC) values obtained with the different methods and in the level of agreement in interpretation categories between the different MIC methods and the disk diffusion test. Among the MIC methods, there was relatively more consistency in reporting the interpretation categories. For European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, the categorical agreement (CA) for MIC methods ranged between 66.7 and 81.5%. On the other hand, the essential agreement (EA) values were as low as 18.5-29.6%. The CA between MIC methods and disk diffusion was 81.5%. These results emphasize the need for a reliable, accurate, and clinically validated methodology to effectively assess the susceptibility of Acinetobacter spp. to cefiderocol. The wide variability observed in our study highlights the importance of standardizing the susceptibility testing process for cefiderocol to ensure consistent and reliable results for clinical decision-making.

Genomics and Antimicrobial Susceptibility of Clinical Pseudomonas aeruginosa Isolates from Hospitals in Brazil.

Pseudomonas aeruginosa, an opportunistic pathogen causing infections in immunocompromised patients, usually shows pronounced antimicrobial resistance. In recent years, the frequency of carbapenemases in P. aeruginosa has decreased, which allows use of new beta-lactams/combinations in antimicrobial therapy. Therefore, the in vitro evaluation of these drugs in contemporary isolates is warranted. We evaluated the antimicrobial susceptibility and genomic aspects of 119 clinical P. aeruginosa isolates from 24 different hospitals in Brazil in 2021-2022. Identification was performed via MALDI-TOF-MS, and antimicrobial susceptibility was identified through broth microdilution, gradient tests, or disk diffusion. Whole-genome sequencing was carried out using NextSeq equipment. The most active drug was cefiderocol (100%), followed by ceftazidime-avibactam (94.1%), ceftolozane-tazobactam (92.4%), and imipenem-relebactam (81.5%). Imipenem susceptibility was detected in 59 isolates (49.6%), and the most active aminoglycoside was tobramycin, to which 99 (83.2%) isolates were susceptible. Seventy-one different sequence types (STs) were detected, including twelve new STs described herein. The acquired resistance genes blaCTX-M-2 and blaKPC-2 were identified in ten (8.4%) and two (1.7%) isolates, respectively. Several virulence genes (exoSTUY, toxA, aprA, lasA/B, plcH) were also identified. We found that new antimicrobials are effective against the diverse P. aeruginosa population that has been circulating in Brazilian hospitals in recent years.

Compassionate use of cefiderocol to treat tissue infection caused by MDR-pseudomonas aeruginosa in a critically-ill patient / Uso compasivo de cefiderocol en el tratamiento de pseudomona multirresistentes en paciente crítico

BACKGROUND: One of the newest antibiotics against multidrug-resistant (MDR) bacteria is Cefiderocol, a siderophore cephalosporin able to overcome most resistance mechanisms, including metallo-beta-lactamases. Several studies are being carried to prove its clinical benefit. CASE PRESENTATION: A 55-year-old male patient was admitted in the ICU undergoing septic shock due to surgical wound infection. Multidrug-resistant Pseudomonasputida grew in blood cultures and Pseudomonas aeruginosa grew in soft tissue cultures. He was treated with colistin and tobramycin, developing nephro and ototoxicity. Compassionate use of cefiderocol was ordered, and the infection was cured within 14 days. CONCLUSIONS: This is the first evidence of cefiderocol treatment in a soft tissue infection within a surgical wound infection. Our experience with cefiderocol in surgical wound infection suggests that it may be helpful in treating infections at that level, but more clinical trials are still needed.

ANTECEDENTES: Uno de los antibióticos más nuevos contra las bacterias multirresistentes (MDR) es el cefiderocol, una cefalos- porina siderófora capaz de superar la mayoría de los mecanismos de resistencia, incluidas las metalobetalactamasas. Se están realizando varios estudios para demostrar su beneficio clínico. PRESENTACIÓN DEL CASO: Paciente masculino de 55 años que ingresó en la UCI con shock séptico por infección de herida quirúrgica. Pseudomonas putida multirresistente creció en hemocultivos y Pseudomonas aeruginosa crecieron en cultivos de tejidos blandos. Fue tratado con colistina y tobramicina, desarrollando nefro y ototoxicidad. Se indicó cefiderocol y la infección se curó en 14 días. CONCLUSIONES: Esta es la primera evidencia de cefiderocol en el tratamiento de una infección de partes blandas dentro de una infección de herida quirúrgica. Nuestra experiencia con cefiderocol en infección de herida quirúrgica sugiere que puede ser útil en el tratamiento de infecciones a ese nivel, pero aún se necesitan más ensayos clínicos.