Risk factors and prognosis of complicated urinary tract infections caused by Pseudomonas aeruginosa in hospitalized patients: a retrospective multicenter cohort study.

PURPOSE: Complicated urinary tract infections (cUTIs) are among the most frequent health-care-associated infections. In patients with cUTI, Pseudomonas aeruginosa deserves special attention, since it can affect patients with serious underlying conditions. Our aim was to gain insight into the risk factors and prognosis of P. aeruginosa cUTIs in a scenario of increasing multidrug resistance (MDR). METHODS: This was a multinational, retrospective, observational study at 20 hospitals in south and southeastern Europe, Turkey, and Israel including consecutive patients with cUTI hospitalized between January 2013 and December 2014. A mixed-effect logistic regression model was performed to assess risk factors for P. aeruginosa and MDR P. aeruginosa cUTI. RESULTS: Of 1,007 episodes of cUTI, 97 (9.6%) were due to P. aeruginosa. Resistance rates of P. aeruginosa were: antipseudomonal cephalosporins 35 of 97 (36.1%), aminoglycosides 30 of 97 (30.9%), piperacillin-tazobactam 21 of 97 (21.6%), fluoroquinolones 43 of 97 (44.3%), and carbapenems 28 of 97 (28.8%). The MDR rate was 28 of 97 (28.8%). Independent risk factors for P. aeruginosa cUTI were male sex (OR 2.61, 95% CI 1.60-4.27), steroid therapy (OR 2.40, 95% CI 1.10-5.27), bedridden functional status (OR 1.79, 95% CI 0.99-3.25), antibiotic treatment within the previous 30 days (OR 2.34, 95% CI 1.38-3.94), indwelling urinary catheter (OR 2.41, 95% CI 1.43-4.08), and procedures that anatomically modified the urinary tract (OR 2.01, 95% CI 1.04-3.87). Independent risk factors for MDR P. aeruginosa cUTI were age (OR 0.96, 95% CI 0.93-0.99) and anatomical urinary tract modification (OR 4.75, 95% CI 1.06-21.26). Readmission was higher in P. aeruginosa cUTI patients than in other etiologies (23 of 97 [23.7%] vs 144 of 910 [15.8%], P=0.04), while 30-day mortality was not significantly different (seven of 97 [7.2%] vs 77 of 910 [8.5%], P=0.6). CONCLUSION: Patients with P. aeruginosa cUTI had characteristically a serious baseline condition and manipulation of the urinary tract, although their mortality was not higher than that of patients with cUTI caused by other etiologies.

Resistance mechanisms of multiresistant Pseudomonas aeruginosa strains from Germany and correlation with hypermutation.

In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with beta-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.

beta-Lactamase induction and cell wall recycling in gram-negative bacteria.

beta-Lactams with the ability to induce beta-lactamase in gram-negative bacteria bind to essential penicillin-binding proteins (PBPs) after entering the periplasmic space. This leads to inactivation of transpeptidase activities and thereby a decrease in the number of peptide cross-links, allowing further degradation of murein by soluble lytic transglycosylases. If all DD-carboxypeptidases (PBP 4, 5, 6a and 6b) are inhibited as well, the degradation product aD-pentapeptide (N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic-acid-D-alanyl-D- alanine) accumulates, which is the case with inducing beta-lactams such as imipenem. These molecules in addition to tri- and tetrapeptides (N-acetylglucosaminyl-1,6-anhydro-N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic-acid-[D-alanine]) which are the usual degradation products of peptidoglycan, are released into the cytoplasm and displace the UDP-pentapeptide (UDP-N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic-acid-D-alanyl-D-alanine) from the DNA-binding protein AmpR, converting it into an activator of AmpC beta-lactamase expression.