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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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Conflict of interest

The authors declare that there is no actual or potential conflict of interest in relation to this article.

Ethical statement

The study was approved by the institutional review board (Department of Infectious Diseases, Sapienza University of Rome). All study participants gave informed written consent.

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Authors and Affiliations

  1. Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy

    G. B. Orsi, A. Bencardino, A. Vena, M. Falcone, A. Giordano & M. Venditti

  2. Department of Infectious, Parasitic and Immune Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy

    A. Carattoli & C. Venditti

Authors
  1. G. B. Orsi
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  2. A. Bencardino
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  3. A. Vena
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  4. A. Carattoli
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  5. C. Venditti
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  6. M. Falcone
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  7. A. Giordano
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  8. M. Venditti
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Correspondence to G. B. Orsi.

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Orsi, G.B., Bencardino, A., Vena, A. et al. Patient risk factors for outer membrane permeability and KPC-producing carbapenem-resistant Klebsiella pneumoniae isolation: results of a double case–control study. Infection 41, 61–67 (2013). https://doi.org/10.1007/s15010-012-0354-2

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  • DOI: https://doi.org/10.1007/s15010-012-0354-2

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