Patient risk factors for outer membrane permeability and KPC-producing carbapenem-resistant Klebsiella pneumoniae isolation: results of a double case–control study

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Abstract
Background In the 1,200-bed university hospital “Umberto I” in Rome, Italy, we observed a dramatic substitution of a precedingly well-documented Klebsiella pneumoniae clone (ST37) with ertapenem resistance by outer membrane permeability modification (Porin-ER-Kp) with a new K. pneumoniae strain expressing carbapenem resistance due to K. pneumoniae carbapenemase production (KPC-CR-Kp). A case–case–control study was carried out to evaluate risk factors for Porin-ER-Kp and KPC-CR-Kp isolation. Methods All patients with hospital-acquired K. pneumoniae isolation between July 2008 and June 2011 were included. Two case groups including patients harbouring KPC-CR-Kp and Porin-ER-Kp were analysed, with a third control group from whom carbapenem-susceptible K. pneumoniae (CS-Kp) were isolated. Results Forty-four KPC-CR-Kp cases, 39 Porin-ER-Kp cases and 60 CS-Kp controls were analysed. During the 3-year study, a specific Porin-ER-Kp endemic clone (ST37) was substituted by a new KPC-CR-Kp clone (ST512). Breakthrough bacteraemias occurred in 21 out of 26 KPC-CR-Kp group bloodstream infections (BSIs); nine of these developed during carbapenem therapy and seven with colistin and/or tigecycline therapy. In 13 Porin-ER-Kp BSIs, breakthrough bacteraemias developed in eight patients and four during carbapenem therapy. In the multivariable analysis, KPC-CR-Kp isolates were associated with carbapenems [odds ratio (OR) 7.74; 95 % confidence interval (CI) 1.70–35.2; p < 0.01) and endoscopy (OR 6.71; 95 % CI 1.25–36.0; p < 0.03). Porin-ER-Kp independent risk factors included second-generation cephalosporins (OR 25.7; 95 % CI 3.20–206.8; p < 0.01), carbapenems (OR 19.1; 95 % CI 4.34–83.9; p < 0.001), acute renal failure (OR 7.17; 95 % CI 1.33–38.6; p < 0.03), endoscopy (OR 6.12; 95 % CI 1.46–25.6; p < 0.02) and third-generation cephalosporins (OR 5.3; 95 % CI 1.34–20.9; p < 0.02). Conclusions Porin-ER-Kp strains needed major antimicrobial pressure compared to KPC-CR-Kp to express resistance. KPC-CR-Kp substituted Porin-ER-Kp strains, causing more infections. KPC-CR-Kp breakthrough bacteraemia occurred even under therapy with tigecycline or colistin, underlining that an antibiotic stewardship programme is needed urgently.

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