Impact of multidrug resistance on Pseudomonas aeruginosa ventilator-associated pneumonia outcome: predictors of early and crude mortality

Abstract

The prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa has increased over the past decade and a significant rise in these isolates in ventilator-associated pneumonia (VAP) has been observed. However, the impact of MDR on VAP outcome has not been analysed in depth. We investigated the risk factors for early and crude mortality in a retrospective study of microbiologically and clinically documented VAP. Ninety-one VAP episodes in 83 patients were included, 31 caused by susceptible P. aeruginosa and 60 by MDR strains, of which 42 (70 %) were extensively drug-resistant (XDR) P. aeruginosa. Thirteen episodes concomitantly presented P. aeruginosa bacteraemia, in seven of which the origin was the respiratory tract. Whereas susceptible P. aeruginosa episodes were more likely than MDR episodes to receive adequate empirical (68 % vs. 30 %; p < 0.001) and definitive antimicrobial therapy (96 % vs. 50 %; p < 0.001), susceptible P. aeruginosa VAP presented a trend towards early mortality (29 % vs. 15 %; p = 0.06). A logistic regression model with early mortality as the dependent variable identified multiorgan dysfunction syndrome (MODS) [odds ratio (OR) 10.4; 95 % confidence interval (CI) 1.7-63.5; p = 0.01] and inadequate antibiotic therapy (OR 4.27; 95 % CI 0.98-18.4; p = 0.052) as independent risk factors for early mortality. A similar analysis identified MODS (OR 4.31; 95 % CI 1.14-16.2; p = 0.03) as the only independent predictor of crude mortality. The severity of acute illness clinical presentation was the main predictor of mortality. Despite adequate antibiotic therapy, susceptible P. aeruginosa seems to cause major early mortality. Although adequate therapy is essential to treat VAP, the severity of acute illness is a more important factor than drug resistance.

Clinical and economic consequences of hospital-acquired resistant and multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis

“…(2011)SPM-1-producing imipenem resistant P. aeruginosa (5)60%0.59[68]Non-SPM-1-producing susceptible P. aeruginosa (24)75%Gasink et al (2006)Fluoroquinolone resistant P. aeruginosa (320)24%0.004[64]Fluoroquinolone susceptible P. aeruginosa (527)16%Hirakata et al . (2003) bla IMP -positive P. aeruginosa (69)30.4%0.41[69] bla IMP -negative P. aeruginosa (247)25.5%Lautenbach et al (2010)Imipenem resistant P. aeruginosa (253)17%0.01[63]Imipenem susceptible P. aeruginosa (2289)13%Morales et al (2012)MDR P. aeruginosa f (134)25%< 0.05[49]Susceptible P. aeruginosa (149)13%Resistant P. aeruginosa (119)22%<0.05Susceptible P. aeruginosa (149)13%Peña et al (2013)Non-MDR P. aeruginosa (27)55%0.33[56]MDR P. aeruginosa g (56)50%Scheetz et al (2006)Fluoroquinolone resistant P. aeruginosa (79)32%0.731[65]Fluoroquinolone susceptible P. aeruginosa (136)29%Tam et al (2010)MDR P. aeruginosa h (25)56%0.001…”

Stress responses as determinants of antimicrobial resistance in Pseudomonas aeruginosa: multidrug efflux and more

“…This latter effect is, in part, attributable to (i) the organism's intrinsically high resistance to many antimicrobials (Giamarellos-Bourboulis et al 2006) and (ii) the development of increased, particularly multidrug, resistance in health care settings (Bodro et al 2013(Bodro et al , 2014Chaisathaphol and Chayakulkeeree 2014;Chen et al 2013;Chittawatanarat et al 2014;Folgori et al 2014;Medell et al 2012;Pena et al 2013;Pourakbari et al 2012;Xiao et al 2012), both of which complicate antipseudomonal chemotherapy (Chaisathaphol and Chayakulkeeree 2014;Chittawatanarat et al 2014;Chung et al 2011;Folgori et al 2014;Hirsch et al 2012;Hirsch and Tam 2010;Kallen et al 2010;Keen et al 2010; Kerr and Snelling the Multidrug and Toxic Compound Export family, and the Resistance Nodulation Division (RND) family (Li and Nikaido 2009). While examples of all of these have been reported in P. aeruginosa (Poole 2013), by far the most significant contributors to resistance to clinically relevant agents and in clinical isolates are in the RND family (Poole 2001(Poole , 2004a(Poole , 2004b(Poole , 2005b(Poole , 2007Poole and Srikumar 2001).…”

Penicillin-Binding Protein 3 Is Essential for Growth of Pseudomonas aeruginosa

“…In addition, individuals with cystic fibrosis (CF) are highly susceptible to chronic pseudomonal lung infections (5,6), and the pathogen plays a critical role in the morbidity and mortality of CF patients (7). The rate of mortality of patients infected nosocomially with P. aeruginosa is very high, with rates reported to be from ϳ30 to 50% (8)(9)(10). The emergence of clinical isolates of P. aeruginosa that exhibit resistance to one or more antibiotics, including fluoroquinolones, carbapenems, and a fourth-generation cephalosporin (cefepime) that is currently the antibiotic of choice for pseudomonal infections (11), severely limits treatment options (12)(13)(14)(15)(16)(17).…”