Multidrug-resistant Pseudomonas aeruginosa bloodstream infections: risk factors and mortality.
ABSTRACT We retrospectively studied patients diagnosed with P. aeruginosa bloodstream infections (BSIs) in two Italian university hospitals. Risk factors for the isolation of multidrug-resistant (MDR) or non-MDR P. aeruginosa in blood cultures were identified by a case-case-control study, and a cohort study evaluated the clinical outcomes of such infections. We identified 106 patients with P. aeruginosa BSI over the 2-year study period; 40 cases with MDR P. aeruginosa and 66 cases with non-MDR P. aeruginosa were compared to 212 controls. Independent risk factors for the isolation of MDR P. aeruginosa were: presence of central venous catheter (CVC), previous antibiotic therapy, and corticosteroid therapy. Independent risk factors for non-MDR P. aeruginosa were: previous BSI, neutrophil count <500/mm3, urinary catheterization, and presence of CVC. The 21-day mortality rate of all patients was 33·9%. The variables independently associated with 21-day mortality were presentation with septic shock, infection due to MDR P. aeruginosa, and inadequate initial antimicrobial therapy.
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ABSTRACT: Our aims were to identify (i) risk factors associated with the acquisition of multidrug-resistant (MDR, to 3 or more classes of antimicrobials) Proteus mirabilis isolates responsible for bloodstream infections (BSIs) and (ii) the impact on mortality of such infections. Risk factors for acquiring MDR P. mirabilis BSIs were investigated in a case-case-control study; those associated with mortality were assessed by comparing survivors and nonsurvivors in a cohort study. The population consisted of 99 adult inpatients with P. mirabilis BSIs identified by our laboratory over an 11-year period (1999 to 2009), 36 (33.3%) of which were caused by MDR strains, and the overall 21-day mortality rate was 30.3%. Acquisition of an MDR strain was independently associated with admission from a long-term care facility (odds ratio [OR], 9.78; 95% confidence interval [CI], 1.94 to 49.16), previous therapy with fluoroquinolones (OR, 5.52; 95% CI, 1.30 to 23.43) or oxyimino-cephalosporins (OR, 4.72; 95% CI, 1.31 to 16.99), urinary catheterization (OR, 3.89; 95% CI, 1.50 to 10.09), and previous hospitalization (OR, 2.68; 95% CI, 10.4 to 6.89). Patients with MDR P. mirabilis BSIs received inadequate initial antimicrobial therapy (IIAT, i.e., treatment with drugs to which the isolate displayed in vitro resistance) more frequently than those with non-MDR infections; they also had increased mortality and (for survivors) longer post-BSI-onset hospital stays. In multivariate regression analysis, 21-day mortality was associated with septic shock at BSI onset (OR, 12.97; 95% CI, 32.2 to 52.23), P. mirabilis isolates that were MDR (OR, 6.62; 95% CI, 16.4 to 26.68), and IIAT (OR, 9.85; 95% CI, 26.7 to 36.25), the only modifiable risk factor of the 3. These findings can potentially improve clinicians' ability to identify P. mirabilis BSIs likely to be MDR, thereby reducing the risk of IIAT--a major risk factor for mortality in these cases--and facilitating the prompt implementation of appropriate infection control measures.Antimicrobial Agents and Chemotherapy 03/2012; 56(6):3224-31. · 4.57 Impact Factor
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ABSTRACT: Pseudomonas aeruginosa is intrinsically resistant to a variety of antimicrobials and can develop resistance during anti-pseudomonal chemotherapy both of which compromise treatment of infections caused by this organism. Resistance to multiple classes of antimicrobials (multidrug resistance) in particular is increasingly common in P. aeruginosa, with a number of reports of pan-resistant isolates treatable with a single agent, colistin. Acquired resistance in this organism is multifactorial and attributable to chromosomal mutations and the acquisition of resistance genes via horizontal gene transfer. Mutational changes impacting resistance include upregulation of multidrug efflux systems to promote antimicrobial expulsion, derepression of ampC, AmpC alterations that expand the enzyme's substrate specificity (i.e., extended-spectrum AmpC), alterations to outer membrane permeability to limit antimicrobial entry and alterations to antimicrobial targets. Acquired mechanisms contributing to resistance in P. aeruginosa include β-lactamases, notably the extended-spectrum β-lactamases and the carbapenemases that hydrolyze most β-lactams, aminoglycoside-modifying enzymes, and 16S rRNA methylases that provide high-level pan-aminoglycoside resistance. The organism's propensity to grow in vivo as antimicrobial-tolerant biofilms and the occurrence of hypermutator strains that yield antimicrobial resistant mutants at higher frequency also compromise anti-pseudomonal chemotherapy. With limited therapeutic options and increasing resistance will the untreatable P. aeruginosa infection soon be upon us?Frontiers in Microbiology 01/2011; 2:65.
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ABSTRACT: Several studies have suggested that resistance determinants usually reduce virulence. However, their contribution to decrease bloodstream infections is unclear. Our aim was to identify risk factors of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) bacteremia and to assess the prevalence of XDR-PA bacteremia. A retrospective study of PA bloodstream infections in our patient population with at least one clinical sample isolate due to PA (2006-2007) was carried out. A total of 2,131 patients with PA clinical samples were detected. Among 1,657 patients with susceptible-PA isolates, 95 developed PA-susceptible bacteremia. Concomitantly, among 474 patients with multidrug-resistant (MDR)-PA isolates, 265 with XDR-PA, and 209 with non-XDR MDR-PA, 43 developed XDR-PA bacteremia and 13 non-XDR MDR-PA bacteremia, respectively. Pulsed-field gel electrophoresis (PFGE) revealed the clonal nature of the two predominant XDR-PA phenotypes and genetic heterogeneity in non-XDR MDR-PA phenotypes. The proportion of XDR-PA bacteremia was higher than the proportion of bacteremia in the susceptible-PA population (16 % vs. 6 %; p < 0.001). A logistic regression model identified prior exposure to fluoroquinolones [odds ratio (OR) 2.80; 95 % confidence interval (CI) 1.02 to 7.70] as the independent variable associated with XDR-PA bacteremia. Our study suggests that XDR-PA strains have a greater ability to develop bacteremia. It remains unclear as to whether this invasive capacity depends on clonal traits or on other virulence determinants.European Journal of Clinical Microbiology 05/2012; 31(10):2791-7. · 3.02 Impact Factor