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Background: Pseudomonas aeruginosa (PSA) infection often occurs in immunocompromised patients, which also face an increased risk of multidrug-resistant (MDR) bacteria. A deeper knowledge of the risk factors for MDR-PSA infection in this patient population may help to choose appropriate empirical antibiotic therapy. Methods: a single-center case-control (1:2) retrospective study that included 48 patients with underlying immunosuppression developing MDR-PSA infection (cases) and 96 patients also immunocompromised that were infected with non-MDR-PSA (controls) was conducted. Both groups were matched by site of infection, clinical features and type of immunosuppression. Risk factors for MDR-PSA were assessed by logistic regression. Clinical outcomes were also compared between both groups. Results: immunosuppression was due to solid cancer in 63 (43.8%) patients, solid organ transplantation in 39 (27.1%), hematological disease in 35 (24.3%) and other causes in 7 (4.9%). Independent risk factors for MDR-PSA infection were diabetes mellitus (odds ratio [OR]: 4.74; 95% confidence interval [CI]: 1.63−13.79; p = 0.004), antibiotic therapy in the previous 3 months (OR: 5.32; 95% CI: 1.93−14.73; p = 0.001), previous MDR-PSA colonization (OR: 42.1; 95% CI: 4.49−394.8; p = 0.001) and septic shock (OR: 3.73; 95% CI: 1.36−10.21; p = 0.010). MDR-PSA cases were less likely to receive adequate empirical therapy (14 [29.2%] vs. 69 [71.9%]; p < 0.001). 30-day clinical improvement was less common in MDR-PSA cases (25 [52.1%] vs. 76 [79.2%]; p = 0.001). Conclusions: diabetes mellitus, previous MDR-PSA colonization, prior receipt of antibiotics and septic shock acted as risk factors for developing MDR-PSA infections in immunocompromised patients, who have a poorer outcome than those infected with non-MDR-PSA strains.

CrpP enzymes have been recently described as a novel ciprofloxacin-resistance mechanism. We investigated by whole genome sequencing the presence of crpP -genes and other mechanisms involved in quinolone resistance in MDR/XDR- Pseudomonas aeruginosa isolates ( n = 55) with both ceftolozane-tazobactam susceptible or resistant profiles recovered from intensive care unit patients during the STEP (Portugal) and SUPERIOR (Spain) surveillance studies. Ciprofloxacin resistance was associated with mutations in the gyrA and parC genes. Additionally, plasmid-mediated genes ( qnrS2 and aac(6')-Ib-cr ) were eventually detected. Ten chromosomal crpP-like genes contained in related pathogenicity genomic islands and 6 different CrpP (CrpP1-CrpP6) proteins were found in 65% (36/55) of the isolates. Dissemination of CrpP variants was observed among non-related clones of both countries, including the CC175 (Spain) high-risk clone and CC348 (Portugal) clone. Interestingly, 5 of 6 variants (CrpP1-CrpP5) carried missense mutations in an amino acid position (Gly7) previously defined as essential conferring ciprofloxacin resistance, and decreased ciprofloxacin susceptibility was only associated with the novel CrpP6 protein. In our collection, ciprofloxacin resistance was mainly due to chromosomal mutations in the gyrA and parC genes. However, crpP genes carrying mutations essential for protein function (G7, I26) and associated with a restored ciprofloxacin susceptibility were predominant. Despite the presence of crpP genes is not always associated with ciprofloxacin resistance, the risk of emergence of novel CrpP variants with a higher ability to affect quinolones is increasing. Furthermore, the spread of crpP genes in highly mobilizable genomic islands among related and non-related P. aeruginosa clones alert the dispersion of MDR pathogens in hospital settings.