Ceftolozane/tazobactam for the treatment of multidrug resistant Pseudomonas aeruginosa: experience from the Balearic Islands.

A prospective, descriptive observational study of consecutive patients treated with ceftolozane/tazobactam in the reference hospital of the Balearic Islands (Spain), between May 2016 and September 2017, was performed. Demographic, clinical, and microbiological variables were recorded. The later included resistance profile, molecular typing, and whole genome sequencing of isolates showing resistance development. Fifty-eight patients were treated with ceftolozane/tazobactam. Thirty-five (60.3%) showed respiratory tract infections, 21 (36.2%) received monotherapy, and 37 (63.8%) combined therapy for ≥ 72 h, mainly with colistin (45.9%). In 46.6% of the patients, a dose of 1/0.5 g/8 h was used, whereas 2/1 g/8 h was used in 41.4%. In 56 of the cases (96.6%), the initial Pseudomonas aeruginosa isolates recovered showed a multidrug resistant (MDR) phenotype, and 50 of them (86.2%) additionally met the extensively drug resistant (XDR) criteria and were only susceptible colistin and/or aminoglycosides (mostly amikacin). The epidemic high-risk clone ST175 was detected in 50% of the patients. Clinical cure was documented in 37 patients (63.8%) and resistance development in 8 (13.8%). Clinical failure was associated with disease severity (SOFA), ventilator-dependent respiratory failure, XDR profile, high-risk clone ST175, negative control culture, and resistance development. In 6 of the 8 cases, resistance development was caused by structural mutations in AmpC, including some mutations described for the first time in vivo, whereas in the other 2, by mutations in OXA-10 leading to the extended spectrum OXA-14. Although further clinical experience is still needed, our results suggest that ceftolozane/tazobactam is an attractive option for the treatment of MDR/XDR P. aeruginosa infections.

Linezolid in late-chronic prosthetic joint infection caused by gram-positive bacteria.

Linezolid may be an interesting alternative for prosthetic joint infection (PJI) due to its bioavailability and its antimicrobial spectrum. However, experience in this setting is scarce. The aim of the study was to assess linezolid's clinical and microbiological efficacy, and also its tolerance. This was a prospective, multicenter, open-label, non-comparative study of 25 patients with late-chronic PJI caused by Gram-positive bacteria managed with a two-step exchange procedure plus 6 weeks of linezolid. Twenty-two (88%) patients tolerated linezolid without major adverse effects, although a global decrease in the platelet count was observed. Three patients were withdrawn because of major toxicity, which reversed after linezolid stoppage. Among patients who completed treatment, 19 (86%) demonstrated clinical and microbiological cure. Two patients presented with clinical and microbiological failure, and one showed clinical cure and microbiological failure. In conclusion, linezolid showed good results in chronic PJI managed with a two-step exchange procedure. Tolerance seems acceptable, though close surveillance is required.