Risk factors and clinical significance of endemic ertapenem resistant Klebsiella pneumoniae isolates in hospitalized patients

Ertapenem-resistant Klebsiella pneumoniae (ER-Kp) is an emerging healthcare-associated pathogen. In order to identify risk factors associated to ER-Kp acquisition the records of 100 patients with K. pneumoniae isolation from July 2008 to December 2009 were reviewed. Thirty-eight patients with ER-Kp (28 infected, 10 colonized) and 62 patients with ertapenem-susceptible K. pneumoniae (ES-Kp) (43 infected, 19 colonized) were included. Multilocus sequence typing (MSLT) and porin gene investigation in 25 ER-Kp strains showed that 24 belonged to the ST37 lineage, expressing the novel OmpK36 variant and not producing the OmpK35 due to a non-sense mutation. Breakthrough bacteraemias occurred in 13 (52%) out of 25 bloodstream infections (BSIs), five (55%) out of nine were in ER-Kp group and four (80%) of these developed during carbapenem therapy. In the 16 ES-Kp BSIs breakthrough bacteraemias developed in eight patients (50%), but only one (12%) during carbapenem therapy. Logistic regression analysis showed that carbapenems (OR= 12,9; 95%CI 3,09 – 53,7; p<0.001), 2nd generation cephalosporins (OR= 11.8; 95%CI 1.87 – 74.4; p<0.01), endoscopy (OR= 5.59; 95%CI 1.32 – 23.6; p<0.02), acute renal failure (OR= 5.32; 95%CI 1.13 – 25.1; p=0.034) and 3rd generation cephalosporins (OR= 4.15; 95%CI 1.09 – 15.8; p<0.01) were independent risk factors for ER-Kp acquisition. Although not significant, among the 71 infected patients mortality was higher in ER-Kp (39.3%) than ES-Kp (27.9%). Our findings confirm that prior use of certain antimicrobials, specifically carbapenems and cephalosporins are primary independent risk factors for the development of ertapenem resistance.