The rates of multidrug-resistant, extensively drug-resistant and pandrug-resistant isolates amongst non-fermenting Gram-negative bacilli, particularly Pseudomonas aeruginosa, have risen worldwide. The clinical consequence of resistance and the impact of adverse treatment on the outcome of patients with P. aeruginosa bacteraemia remain unclear. To better understand the predictors of mortality, the clinical consequence of resistance and the impact of inappropriate therapy on patient outcomes, we analysed the first episode of P. aeruginosa bacteraemia in patients from a Brazilian tertiary-care hospital during the period from May 2009 to August 2011. Antimicrobial susceptibility testing was conducted; phenotypic detection of metallo-b-lactamase (MBL) and PCR of MBL genes were performed on carbapenem-resistant strains. Amongst the 120 P. aeruginosa isolates, 45.8 % were resistant to carbapenem and 36 strains were tested for MBL detection. A total of 30 % were phenotypically positive and, of these, 77.8 % expressed an MBL gene, bla SPM-1 (57 %) and bla VIM -type (43 %). The resistance rates to ceftazidime, cefepime, piperacillin/tazobactam, carbapenem, fluoroquinolone and aminoglycoside were 55, 42.5, 35, 45.8, 44 and 44 %, respectively. Previous antibiotic use, length of a hospital stay ¢30 days prior to P. aeruginosa, haemodialysis, tracheostomy, pulmonary source of bacteraemia and Intensive Care Unit admission were common independent risk factors for antimicrobial resistance. Cefepime resistance, multidrug resistance and extensive drug resistance were independently associated with inappropriate therapy, which was an important predictor of mortality, being synergistic with the severity of the underlying disease.
Pseudomonas aeruginosa is an opportunistic pathogen that causes frequently nosocomial infections, currently becoming more difficult to treat due to the various resistance mechanisms and different virulence factors. The purpose of this study was to determine the risk factors independently associated with the development of bacteremia by carbapenem-resistant P. aeruginosa, the frequency of virulence genes in metallo-β-lactamases producers and to evaluate their ability to produce biofilm. We conducted a case–control study in the Uberlândia Federal University – Hospital Clinic, Brazil. Polymerase Chain Reaction was performed for metallo-β-lactamases and virulence genes. Adhesion and biofilm assays were done by quantitative tests. Among the 157 strains analyzed, 73.9% were multidrug-resistant, 43.9% were resistant to carbapenems, 16.1% were phenotypically positive for metallo-β-lactamases, and of these, 10.7% were positive for blaSPM gene and 5.3% positive for blaVIM. The multivariable analysis showed that mechanical ventilation, enteral/nasogastric tubes, primary bacteremia with unknown focus, and inappropriate therapy were independent risk factors associated with bacteremia. All tested strains were characterized as strongly biofilm producers. A higher mortality was found among patients with bacteremia by carbapenem-resistant P. aeruginosa strains, associated independently with extrinsic risk factors, however it was not evident the association with the presence of virulence and metallo-β-lactamases genes.
We described a comprehensive analysis of the molecular epidemiology of multidrug-resistant (MDR) P. aeruginosa. Molecular analysis included typing by Pulsed Field Gel Electrophoresis, identification of genes of interest through PCR-based assays and sequencing of target genes. Case-control study was conducted to better understand the prognostic of patients and the impact of inappropriate therapy in patients with bacteremia, as well as the risk factors of MDR infections. We observed a high rate of MDR isolates (40.7%), and 51.0% of them was independently associated with inappropriate antibiotic therapy. Bacteremia was detected in 66.9% of patients, and prolonged hospital stay was expressive in those resistant to fluoroquinolone. Plasmid-mediated quinolone resistance genes (PMQR), qnrS1 and aac(6’)Ib-cr, were detected in two different nosocomial isolates (5.3%), and the aac(6’)-Ib7 variant was detected at a high frequency (87.5%) in those negative to PMQR. The presence of mutations in gyrA and parC genes was observed in 100% and 85% of selected isolates, respectively. Isolates harboring PMQR genes or mutations in gyrA and parC were not closely related, except in those containing SPM (São Paulo metallo-β-lactamase) clone. In addition, there is no study published in Brazil to date reporting the presence of Pseudomonas aeruginosa isolates harboring both qnrS1 and aac(6’)Ib-cr genes, with alarming frequency of patients with inappropriate therapy.
The bacterial factors associated with bacteremia by multidrug-resistant and extensively drug-resistant P. aeruginosa, including overexpression of efflux pumps, AmpC overproduction, and loss/alteration of the OprD porin in isolates that are non-Metallo-β-Lactamase producing were analyzed in a retrospective study. Molecular analyses included strain typing by Pulsed Field Gel Electrophoresis and identification of key genes via qualitative and quantitative PCR-based assays. Previous use of carbapenems and tracheostomy was independently associated with the development of bacteremia by extensively drug-resistant and multidrug-resistant strains of P. aeruginosa. A high consumption of antimicrobials was observed, and 75.0% of the isolates contained amplicons with the blaSPM-1 and blaVIM genes. Of the 47 non-Metallo-β-Lactamase isolates, none had another type of carbapenemase. However, the isolates exhibited high rates of hyperproduction of AmpC, loss of the OprD porin (71.4%) and the presence of MexABOprM (57.1%) and MexXY (64.3%). This study suggests that in non-Metallo-β-Lactamase isolates, the association of intrinsic resistance mechanisms could contributes to the expression of multidrug-resistant/extensively drug-resistant phenotypes.
Potential drug-drug interactions associated with drugs currently proposed for COVID-19 treatment in patients receiving other treatments.
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