Extensively drug-resistant Pseudomonas aeruginosa: clinical features and treatment with ceftazidime/avibactam and ceftolozane/tazobactam in a tertiary care university hospital center in Portugal – A cross-sectional and retrospective observational study

Abstract

IntroductionExtensively drug-resistant Pseudomonas aeruginosa (XDR-PA) is a growing concern due to its increasing incidence, limited therapeutic options, limited data on the optimal treatment, and high mortality rates. The study aimed to characterize the population, the outcome and the microbiological characteristics of XDR-PA identified in a Portuguese university hospital center.MethodsAll XDR-PA isolates between January 2019 and December 2021 were identified. XDR-PA was defined as resistance to piperacillin-tazobactam, third and fourth generation cephalosporins, carbapenems, aminoglycosides and fluoroquinolones. A retrospective analysis of the medical records was performed.ResultsOne hundred seventy-eight individual episodes among 130 patients with XDR-PA detection were identified. The most common sources of infection were respiratory (32%) and urinary tracts (30%), although skin and soft tissue infections (18%) and primary bacteremia (14%) were also prevalent. Colonization was admitted in 64 cases. Several patients had risk factors for complicated infections, most notably immunosuppression, structural lung abnormalities, major surgery, hemodialysis or foreign intravascular or urinary devices. XDR-PA identification was more frequent in male patients with an average age of 64.3 ± 17.5 years. One non-susceptibility to colistin was reported. Only 12.4% were susceptible to aztreonam. Ceftazidime-avibactam (CZA) was susceptible in 71.5% of the tested isolates. Ceftolozane-tazobactam (C/T) was susceptible in 77.5% of the tested isolates. Antibiotic regimens with XDR-PA coverage were reserved for patients with declared infection, except to cystic fibrosis. The most frequently administered antibiotics were colistin (41 cases), CZA (39 cases), and C/T (16 cases). When combination therapy was used, CZA plus colistin was preferred. The global mortality rate among infected patients was 35.1%, significantly higher in those with hematologic malignancy (50.0%, p < 0.05), followed by the ones with bacteremia (44.4%, p < 0.05) and those medicated with colistin (39.0%, p < 0.05), especially the ones with respiratory infections (60.0%). Among patients treated with CZA or C/T, the mortality rate seemed to be lower.DiscussionXDR-PA infections can be severe and difficult to treat, with a high mortality rate. Even though colistin seems to be a viable option, it is likely less safe and efficient than CZA and C/T. To the best of the authors’ knowledge, this is the first description of the clinical infection characteristics and treatment of XDR-PA in Portugal.

Extensively and multidrug-resistant bacterial strains: case studies of antibiotics resistance

“…Of the total 130 patients, 35.1% of infected patients died; those with hematologic malignancy had a significantly higher death rate (50.0%, p < 0.05), followed by those with bacteremia (44.4%, p < 0.05) and those taking colistin (39.0%, p < 0.05), especially those with respiratory infections (60.0%). One non-susceptibility to colistin case was also reported ( Mendes Pedro et al, 2024 ).…”

“…XDR P. aeruginosa (XDR-PA) infections can have a high fatality rate, be extremely dangerous, and highly challenging to treat ( Ahani Azari and Fozouni, 2020 ). Mendes Pedro et al (2024) carried out a retrospective study on the patient records. The goals of the study were to describe the XDR-PA population, outcomes, and microbiological features found in a Portuguese university hospital center.…”

“…The goals of the study were to describe the XDR-PA population, outcomes, and microbiological features found in a Portuguese university hospital center. Resistance to carbapenems, aminoglycosides, third- and fourth-generation cephalosporins, piperacillin-tazobactam, and fluoroquinolones constituted the definition of XDR-PA ( Mendes Pedro et al, 2024 ).…”

Friends or foes? Novel antimicrobials tackling MDR/XDR Gram-negative bacteria: a systematic review

“…While C/T has received approval for several pathologies caused by Gram-negative pathogens, it is most commonly referred to as a viable treatment alternative for MDR/XDR Pseudomonas aeruginosa strains. Resistance patterns to C/T, as to most antimicrobials, vary from country to country, but recently published studies report effectiveness in more than 75% of cases (Venuti et al, 2023;Karlowsky et al, 2024;Mendes Pedro et al, 2024). However, a 2023 multicenter study focusing on various infections caused by MDR Pseudomonas aeruginosa (HAP, VAP, wound infections, UTI, IAI, catheter-related BSI) showcases that C/T does not provide significant differences regarding clinical outcome, when compared to CZA (Almangour et al, 2023).…”