Skip to main content Accessibility help

A Novel Risk Factor Associated With Colonization by Carbapenemase-Producing Enterobacteriaceae: Use of Proton Pump Inhibitors in Addition to Antimicrobial Treatment

  • Vincent C. C. Cheng (a1) (a2), Jonathan H. K. Chen (a1), Simon Y. C. So (a1), Sally C. Y. Wong (a1), Pui-Hing Chau (a3), Lisa M. W. Wong (a2), Radley H. C. Ching (a2), Modissa M. L. Ng (a2), Wan-Mui Lee (a2), Ivan F. N. Hung (a4), Pak-Leung Ho (a1) and Kwok-Yung Yuen (a1)...



To study the association between gastrointestinal colonization of carbapenemase-producing Enterobacteriaceae (CPE) and proton pump inhibitors (PPIs).


We analyzed 31,526 patients with prospective collection of fecal specimens for CPE screening: upon admission (targeted screening) and during hospitalization (opportunistic screening, safety net screening, and extensive contact tracing), in our healthcare network with 3,200 beds from July 1, 2011, through December 31, 2015. Specimens were collected at least once weekly during hospitalization for CPE carriers and subjected to broth enrichment culture and multiplex polymerase chain reaction.


Of 66,672 fecal specimens collected, 345 specimens (0.5%) from 100 patients (0.3%) had CPE. The number and prevalence (per 100,000 patient-days) of CPE increased from 2 (0.3) in 2012 to 63 (8.0) in 2015 (P<.001). Male sex (odds ratio, 1.91 [95% CI, 1.15–3.18], P=.013), presence of wound or drain (3.12 [1.70–5.71], P<.001), and use of cephalosporins (3.06 [1.42–6.59], P=.004), carbapenems (2.21 [1.10–4.48], P=.027), and PPIs (2.84 [1.72–4.71], P<.001) in the preceding 6 months were significant risk factors by multivariable analysis. Of 79 patients with serial fecal specimens, spontaneous clearance of CPE was noted in 57 (72.2%), with a median (range) of 30 (3–411) days. Comparing patients without use of antibiotics and PPIs, consumption of both antibiotics and PPIs after CPE identification was associated with later clearance of CPE (hazard ratio, 0.35 [95% CI, 0.17–0.73], P=.005).


Concomitant use of antibiotics and PPIs prolonged duration of gastrointestinal colonization by CPE.

Infect Control Hosp Epidemiol 2016;1418–1425


Corresponding author

Address correspondence to Kwok-Yung Yuen, State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region, China (


Hide All
1. Tzouvelekis, LS, Markogiannakis, A, Psichogiou, M, Tassios, PT, Daikos, GL. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clin Microbiol Rev 2012;25:682707.
2. Villegas, MV, Pallares, CJ, Escandon-Vargas, K, et al. Characterization and clinical impact of bloodstream infection caused by carbapenemase-producing Enterobacteriaceae in seven Latin American countries. PLOS ONE 2016;11:e0154092.
3. Won, SY, Munoz-Price, LS, Lolans, K, et al. Emergence and rapid regional spread of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. Clin Infect Dis 2011;53:532540.
4. Morris, D, Boyle, F, Morris, C, et al. Inter-hospital outbreak of Klebsiella pneumoniae producing KPC-2 carbapenemase in Ireland. J Antimicrob Chemother 2012;67:23672372.
5. Weterings, V, Zhou, K, Rossen, JW, et al. An outbreak of colistin-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae in the Netherlands (July to December 2013), with inter-institutional spread. Eur J Clin Microbiol Infect Dis 2015;34:16471655.
6. Delory, T, Seringe, E, Antoniotti, G, et al. Prolonged delay for controlling KPC-2-producing Klebsiella pneumoniae outbreak: the role of clinical management. Am J Infect Control 2015;43:10701075.
7. Schwaber, MJ, Lev, B, Israeli, A, et al. Containment of a country-wide outbreak of carbapenem-resistant Klebsiella pneumoniae in Israeli hospitals via a nationally implemented intervention. Clin Infect Dis 2011;52:848855.
8. Hayden, MK, Lin, MY, Lolans, K, et al. Prevention of colonization and infection by Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae in long-term acute-care hospitals. Clin Infect Dis 2015;60:11531161.
9. Johnson, AP, Woodford, N. Global spread of antibiotic resistance: the example of New Delhi metallo-beta-lactamase (NDM)-mediated carbapenem resistance. J Med Microbiol 2013;62:499513.
10. Ho, PL, Li, Z, Lai, EL, Chiu, SS, Cheng, VC. Emergence of NDM-1-producing Enterobacteriaceae in China. J Antimicrob Chemother 2012;67:15531555.
11. Cheng, VC, Chan, JF, Wong, SC, et al. Proactive infection control measures to prevent nosocomial transmission of carbapenem-resistant Enterobacteriaceae in a non-endemic area. Chin Med J (Engl) 2013;126:45044509.
12. Rossini, A, Di Santo, SG, Libori, MF, Tiracchia, V, Balice, MP, Salvia, A. Risk factors for carbapenemase-producing Enterobacteriaceae colonization of asymptomatic carriers on admission to an Italian rehabilitation hospital. J Hosp Infect 2016;92:7881.
13. Cheng, VC, Tai, JW, Chen, JH, et al. Proactive infection control measures to prevent nosocomial transmission of vancomycin-resistant enterococci in Hong Kong. J Formos Med Assoc 2014;113:734741.
14. Cheng, VC, Chen, JH, So, SY, et al. Use of fluoroquinolones is the single most important risk factor for the high bacterial load in patients with nasal and gastrointestinal colonization by multidrug-resistant Acinetobacter baumannii . Eur J Clin Microbiol Infect Dis 2015;34:23592366.
15. Cheng, VC, Chen, JH, Poon, RW, et al. Control of hospital endemicity of multiple-drug-resistant Acinetobacter baumannii ST457 with directly observed hand hygiene. Eur J Clin Microbiol Infect Dis 2015;34:713718.
16. Cheng, VC, Tai, JW, Wong, LM, et al. Effect of proactive infection control measures on benchmarked rate of hospital outbreaks: an analysis of public hospitals in Hong Kong over 5 years. Am J Infect Control 2015;43:965970.
17. Cheng, VC, Tai, JW, Li, WS, et al. Implementation of directly observed patient hand hygiene for hospitalized patients by hand hygiene ambassadors in Hong Kong. Am J Infect Control 2016;44:621624.
18. Cheng, VC, Chau, PH, Lee, WM, et al. Hand-touch contact assessment of high-touch and mutual-touch surfaces among healthcare workers, patients, and visitors. J Hosp Infect 2015;90:220225.
19. Ho, PL, Cheung, YY, Wang, Y, et al. Characterization of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae from a healthcare region in Hong Kong. Eur J Clin Microbiol Infect Dis 2016;35:379385.
20. Cheng, VC, Chen, JH, Wong, SC, Ho, PL, Yuen, KY. Gastrointestinal colonization with multiple New Delhi metallo-beta-lactamase-producing Enterobacteriaceae isolates in the same patient: a potential challenge in outbreak investigation. J Hosp Infect 2016;92:108109.
21. Swaminathan, M, Sharma, S, Poliansky Blash, S, et al. Prevalence and risk factors for acquisition of carbapenem-resistant Enterobacteriaceae in the setting of endemicity. Infect Control Hosp Epidemiol 2013;34:809817.
22. Zhao, ZC, Xu, XH, Liu, MB, Wu, J, Lin, J, Li, B. Fecal carriage of carbapenem-resistant Enterobacteriaceae in a Chinese university hospital. Am J Infect Control 2014;42:e61e64.
23. Ben-David, D, Masarwa, S, Navon-Venezia, S, et al. Carbapenem-resistant Klebsiella pneumoniae in post-acute-care facilities in Israel. Infect Control Hosp Epidemiol 2011;32:845853.
24. Yang, J, Ye, L, Guo, L, et al. A nosocomial outbreak of KPC-2-producing Klebsiella pneumoniae in a Chinese hospital: dissemination of ST11 and emergence of ST37, ST392 and ST395. Clin Microbiol Infect 2013;19:E509E515.
25. Zheng, R, Zhang, Q, Guo, Y, et al. Outbreak of plasmid-mediated NDM-1-producing Klebsiella pneumoniae ST105 among neonatal patients in Yunnan, China. Ann Clin Microbiol Antimicrob 2016;15:10.
26. Cheng, VC, Tai, JW, Ng, ML, et al. Extensive contact tracing and screening to control the spread of vancomycin-resistant Enterococcus faecium ST414 in Hong Kong. Chin Med J (Engl) 2012;125:34503457.
27. Guerra, B, Fischer, J, Helmuth, R. An emerging public health problem: acquired carbapenemase-producing microorganisms are present in food-producing animals, their environment, companion animals and wild birds. Vet Microbiol 2014;171:290297.
28. Morrison, BJ, Rubin, JE. Carbapenemase producing bacteria in the food supply escaping detection. PLoS One 2015;10:e0126717.
29. Cheng, VC, Wong, SC, Ho, PL, Yuen, KY. Strategic measures for the control of surging antimicrobial resistance in Hong Kong and mainland of China. Emerg Microbes Infect 2015;4:e8.
30. Cheng, VC, Li, IW, Wu, AK, et al. Effect of antibiotics on the bacterial load of meticillin-resistant Staphylococcus aureus colonisation in anterior nares. J Hosp Infect 2008;70:2734.
31. Papadimitriou-Olivgeris, M, Marangos, M, Fligou, F, et al. Risk factors for KPC-producing Klebsiella pneumoniae enteric colonization upon ICU admission. J Antimicrob Chemother 2012;67:29762981.
32. Gagliotti, C, Giordani, S, Ciccarese, V, et al. Risk factors for colonization with carbapenemase-producing Klebsiella pneumoniae in hospital: a matched case-control study. Am J Infect Control 2014;42:10061008.
33. Lubbert, C, Lippmann, N, Busch, T, et al. Long-term carriage of Klebsiella pneumoniae carbapenemase-2-producing K pneumoniae after a large single-center outbreak in Germany. Am J Infect Control 2014;42:376380.
34. Jackson, MA, Goodrich, JK, Maxan, ME, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut 2016;65:749756.
35. Dang, TT, Majumdar, SR, Marrie, TJ, Eurich, DT. Recurrent pneumonia: a review with focus on clinical epidemiology and modifiable risk factors in elderly patients. Drugs Aging 2015;32:1319.
36. Janarthanan, S, Ditah, I, Adler, DG, Ehrinpreis, MN. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol 2012;107:10011010.
37. Kwok, CS, Arthur, AK, Anibueze, CI, Singh, S, Cavallazzi, R, Loke, YK. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol 2012;107:10111019.
38. Corleto, VD, Festa, S, Di Giulio, E, Annibale, B. Proton pump inhibitor therapy and potential long-term harm. Curr Opin Endocrinol Diabetes Obes 2014;21:38.
39. Fung, IC, Cairncross, S. How often do you wash your hands? A review of studies of hand-washing practices in the community during and after the SARS outbreak in 2003. Int J Environ Health Res 2007;17:161183.

A Novel Risk Factor Associated With Colonization by Carbapenemase-Producing Enterobacteriaceae: Use of Proton Pump Inhibitors in Addition to Antimicrobial Treatment

  • Vincent C. C. Cheng (a1) (a2), Jonathan H. K. Chen (a1), Simon Y. C. So (a1), Sally C. Y. Wong (a1), Pui-Hing Chau (a3), Lisa M. W. Wong (a2), Radley H. C. Ching (a2), Modissa M. L. Ng (a2), Wan-Mui Lee (a2), Ivan F. N. Hung (a4), Pak-Leung Ho (a1) and Kwok-Yung Yuen (a1)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed