Skip to main content Accessibility help

A Systematic Review of the Burden of Multidrug-Resistant Healthcare-Associated Infections Among Intensive Care Unit Patients in Southeast Asia: The Rise of Multidrug-Resistant Acinetobacter baumannii

  • Nattawat Teerawattanapong (a1) (a2), Pornpansa Panich (a3), Disorn Kulpokin (a3), Siriwat Na Ranong (a4), Khachen Kongpakwattana (a2), Atibodi Saksinanon (a2), Bey-Hing Goh (a2) (a5) (a6), Learn-Han Lee (a2) (a5) (a6), Anucha Apisarnthanarak (a7) and Nathorn Chaiyakunapruk (a2) (a5) (a8) (a9)...

To summarize the clinical burden (cumulative incidence, prevalence, case fatality rate and length of stay) and economic burden (healthcare cost) of healthcare-associated infections (HAIs) due to multidrug-resistant organisms (MDROs) among patients in intensive care units (ICUs) in Southeast Asia.


Systematic review.


We conducted a comprehensive literature search in PubMed, EMBASE, CINAHL, EconLit, and the Cochrane Library databases from their inception through September 30, 2016. Clinical and economic burdens and study quality were assessed for each included study.


In total, 41 studies met our inclusion criteria; together, 22,876 ICU patients from 7 Southeast Asian countries were included. The cumulative incidence of HAI caused by A. baumannii (AB) in Southeast Asia is substantially higher than has been reported in other regions, especially carbapenem-resistant AB (CRAB; 64.91%) and multidrug-resistant AB (MDR-AB) (58.51%). Evidence of a dose–response relationship between different degrees of drug resistance and excess mortality due to AB infections was observed. Adjusted odds ratios were 1.23 (95% confidence interval [CI], 0.51–3.00) for MDR-AB, 1.72 (95% CI, 0.77–3.80) for extensively drug-resistant AB (XDR-AB), and 1.82 (95% CI, 0.55–6.00) for pandrug-resistant AB (PDR-AB). There is, however, a paucity of published data on additional length of stay and costs attributable to MDROs.


This review highlights the challenges in addressing MDROs in Southeast Asia, where HAIs caused by MDR gram-negative bacteria are abundant and have a strong impact on society. With our findings, we hope to draw the attention of clinicians and policy makers to the problem of antibiotic resistance and to issue a call for action in the management of MDROs.

Infect Control Hosp Epidemiol 2018;39:525–533

Corresponding author
Address correspondence to Nathorn Chaiyakunapruk, PharmD, PhD, Center of Pharmaceutical Outcomes Research (CPOR), Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand (
Hide All
1. HAI data and statistics. Centers for Disease Control and Prevention website. Published 2016. Accessed November 28, 2016.
2. Klevens, RM, Edwards, JR, Richards, CL Jr, et al. Estimating health care-associated infections and deaths in US hospitals, 2002. Public Health Rep 2007;122:160166.
3. Marchetti, A, Rossiter, R. Economic burden of healthcare-associated infection in US acute care hospitals: societal perspective. J Med Econ 2013;16:13991404.
4. Ling, ML, Apisarnthanarak, A, Madriaga, G. The burden of healthcare-associated infections in Southeast Asia: a systematic literature review and meta-analysis. Clin Infect Dis 2015;60:16901699.
5. Magill, SS, Edwards, JR, Bamberg, W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014;370:11981208.
6. Laxminarayan, R, Duse, A, Wattal, C, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis 2013;13:10571098.
7. Antimicrobial resistance: global report on surveillance 2014. World Health Organization website. Published 2014. Accessed November 28, 2016.
8. Lim, C, Takahashi, E, Hongsuwan, M, et al. Epidemiology and burden of multidrug-resistant bacterial infection in a developing country. Elife 2016;5:e18082. doi: 10.7554/eLife.18082.
9. Kollef, MH, Fraser, VJ. Antibiotic resistance in the intensive care unit. Ann Intern Med 2001;134:298314.
10. Allegranzi, B, Bagheri Nejad, S, Combescure, C, et al. Burden of endemic healthcare-associated infection in developing countries: systematic review and meta-analysis. Lancet 2011;377:228241.
11. Liberati, A, Altman, DG, Tetzlaff, J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 2009;6(7):e1000100. doi: 10.1371/journal.pmed.1000100.
12. Magiorakos, AP, Srinivasan, A, Carey, RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012;18:268281.
13. von Elm, E, Altman, DG, Egger, M, et al. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008;61:344349.
14. Turner, P, Pol, S, Soeng, S, et al. High prevalence of antimicrobial-resistant gram-negative colonization in hospitalized Cambodian infants. Pediatr Infect Dis J 2016;35:856861.
15. Chong, SJ, Ahmed, S, Tay, JM, Song, C, Tan, TT. 5 year analysis of bacteriology culture in a tropical burns ICU. Burns 2011;37:13491353.
16. Lukac, PJ, Bonomo, RA, Logan, LK. Extended-spectrum beta-lactamase-producing Enterobacteriaceae in children: old foe, emerging threat. Clin Infect Dis 2015;60:13891397.
17. Kock, R, Becker, K, Cookson, B, et al. Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe. Euro Surveill 2010;15:19688.
18. Dantes, R, Mu, Y, Belflower, R, et al. National burden of invasive methicillin-resistant Staphylococcus aureus infections, United States, 2011. JAMA Intern Med 2013;173:19701978.
19. Hidron, AI, Edwards, JR, Patel, J, et al. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol 2008;29:9961011.
20. Choi, JY, Kwak, YG, Yoo, H, et al. Trends in the distribution and antimicrobial susceptibility of causative pathogens of device-associated infection in Korean intensive care units from 2006 to 2013: results from the Korean Nosocomial Infections Surveillance System (KONIS). J Hosp Infect 2016;92:363371.
21. Chim, H, Tan, BH, Song, C. Five-year review of infections in a burn intensive care unit: high incidence of Acinetobacter baumannii in a tropical climate. Burns 2007;33:10081014.
22. Inchai, J, Pothirat, C, Liwsrisakun, C, Deesomchok, A, Kositsakulchai, W, Chalermpanchai, N. Ventilator-associated pneumonia: epidemiology and prognostic indicators of 30-day mortality. Jpn J Infect Dis 2015;68:181186.
23. Esterly, JS, Griffith, M, Qi, C, Malczynski, M, Postelnick, MJ, Scheetz, MH. Impact of carbapenem resistance and receipt of active antimicrobial therapy on clinical outcomes of Acinetobacter baumannii bloodstream infections. Antimicrob Agents Chemother 2011;55:48444849.
24. Shorr, AF, Zilberberg, MD, Micek, ST, Kollef, MH. Predictors of hospital mortality among septic ICU patients with Acinetobacter spp. bacteremia: a cohort study. BMC Infect Dis 2014;14:572.
25. Janahiraman, S, Aziz, MN, Hoo, FK, et al. Resistance patterns of multidrug resistant Acinetobacter baumannii in an ICU of a tertiary care hospital, Malaysia. Pak J Med Sci 2015;31:13831388.
26. Thatrimontrichai, A, Techato, C, Dissaneevate, S, et al. Risk factors and outcomes of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia in the neonate: a case-case-control study. J Infect Chemother 2016;22:444449.
27. Apisarnthanarak, A, Pinitchai, U, Thongphubeth, K, Yuekyen, C, Warren, DK, Fraser, VJ. A multifaceted intervention to reduce pandrug-resistant Acinetobacter baumannii colonization and infection in 3 intensive care units in a Thai tertiary care center: a 3-year study. Clin Infect Dis 2008;47:760767.
28. Ng, E, Earnest, A, Lye, DC, Ling, ML, Ding, Y, Hsu, LY. The excess financial burden of multidrug resistance in severe gram-negative infections in Singaporean hospitals. Ann Acad Med Singapore 2012;41:189193.
29. Vincent, JL, Rello, J, Marshall, J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009;302:23232329.
30. Smith, PW. Seasonal incidence of Acinetobacter infection. J Infect Dis 1979;140:275276.
31. McDonald, LC, Banerjee, SN, Jarvis, WR. Seasonal variation of Acinetobacter infections: 1987–1996. Nosocomial Infections Surveillance System. Clin Infect Dis 1999;29:11331137.
32. Trottier, V, Segura, PG, Namias, N, King, D, Pizano, LR, Schulman, CI. Outcomes of Acinetobacter baumannii infection in critically ill burned patients. J Burn Care Res 2007;28:248254.
33. Roberts, SA, Findlay, R, Lang, SD. Investigation of an outbreak of multi-drug resistant Acinetobacter baumannii in an intensive care burns unit. J Hosp Infect 2001;48:228232.
34. Simor, AE, Lee, M, Vearncombe, M, et al. An outbreak due to multiresistant Acinetobacter baumannii in a burn unit: risk factors for acquisition and management. Infect Control Hosp Epidemiol 2002;23:261267.
35. Rock, C, Harris, AD, Johnson, JK, Bischoff, WE, Thom, KA. Infrequent air contamination with Acinetobacter baumannii of air surrounding known colonized or infected patients. Infect Control Hosp Epidemiol 2015;36:830832.
36. Blot, S, Koulenti, D, Dimopoulos, G, et al. Prevalence, risk factors, and mortality for ventilator-associated pneumonia in middle-aged, old, and very old critically ill patients. Crit Care Med 2014;42:601609.
37. Weiner, LM, Webb, AK, Limbago, B, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014. Infect Control Hosp Epidemiol 2016;37:12881301.
38. Poulikakos, P, Tansarli, GS, Falagas, ME. Combination antibiotic treatment versus monotherapy for multidrug-resistant, extensively drug-resistant, and pandrug-resistant Acinetobacter infections: a systematic review. Eur J Clin Microbiol Infect Dis 2014;33:16751685.
39. Harris, PN, Le, BD, Tambyah, P, et al. Antiseptic body washes for reducing the transmission of methicillin-resistant Staphylococcus aureus: a cluster crossover study. Open Forum Infect Dis 2015;2:ofv051.
40. Ling, ML, Tee, YM, Tan, SG, et al. Risk factors for acquisition of carbapenem resistant Enterobacteriaceae in an acute tertiary care hospital in Singapore. Antimicrob Resist Infect Control 2015;4:26.
41. Vasudevan, A, Mukhopadhyay, A, Goh, EY, Li, J, Tambyah, PA. Risk factors for infection/colonization caused by resistant gram-negative bacilli in critically ill patients (an observational study of 1633 critically ill patients). Prev Med 2013;57:S70S73.
42. Vasudevan, A, Chuang, L, Jialiang, L, Mukhopadhyay, A, Goh, EY, Tambyah, PA. Inappropriate empirical antimicrobial therapy for multidrug-resistant organisms in critically ill patients with pneumonia is not an independent risk factor for mortality: results of a prospective observational study of 758 patients. J Glob Antimicrob Resist 2013;1:123130.
43. Oh, HM, Tan, TY, Chua, GH, Li, J, Meng, QS. The impact of active surveillance cultures in reducing methicillin-resistant Staphylococcus aureus infections in a surgical intensive care unit in Singapore. BMC Proc 2011;5:P233.
44. Kurup, A, Chlebicka, N, Tan, KY, et al. Active surveillance testing and decontamination strategies in intensive care units to reduce methicillin-resistant Staphylococcus aureus infections. Am J Infect Control 2010;38:361367.
45. Donaldson, AD, Razak, L, Liang, LJ, Fisher, DA, Tambyah, PA. Carbapenems and subsequent multiresistant bloodstream infection: does treatment duration matter? Int J Antimicrob Agents 2009;34:246251.
46. Kwa, AL, Low, JG, Lee, E, Kurup, A, Chee, HL, Tam, VH. The impact of multidrug resistance on the outcomes of critically ill patients with gram-negative bacterial pneumonia. Diagn Microbiol Infect Dis 2007;58:99104.
47. Ling, ML, Ang, A, Wee, M, Wang, GC. A nosocomial outbreak of multiresistant Acinetobacter baumannii originating from an intensive care unit. Infect Control Hosp Epidemiol 2001;22:4849.
48. Ng, SP, Gomez, JM, Lim, SH, Ho, NK. Reduction of nosocomial infection in a neonatal intensive care unit (NICU). Singapore Med J 1998;39:319323.
49. Tan, KW, Tay, L, Lim, SH. An outbreak of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit in Singapore: a 20-month study of clinical characteristics and control. Singapore Med J 1994;35:277282.
50. Boonyasiri, A, Thaisiam, P, Permpikul, C, et al. Effectiveness of chlorhexidine wipes for the prevention of multidrug-resistant bacterial colonization and hospital-acquired infections in intensive care unit patients: a randomized trial in Thailand. Infect Control Hosp Epidemiol 2016;37:245253.
51. Chusri, S, Silpapojakul, K, McNeil, E, Singkhamanan, K, Chongsuvivatwong, V. Impact of antibiotic exposure on occurrence of nosocomial carbapenem-resistant Acinetobacter baumannii infection: a case control study. J Infect Chemother 2015;21:9095.
52. Inchai, J, Pothirat, C, Bumroongkit, C, Limsukon, A, Khositsakulchai, W, Liwsrisakun, C. Prognostic factors associated with mortality of drug-resistant Acinetobacter baumannii ventilator-associated pneumonia. J Intensive Care 2015;3:9.
53. Tong, SY, Holden, MT, Nickerson, EK, et al. Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting. Genome Res 2015;25:111118.
54. Apisarnthanarak, A, Pinitchai, U, Warachan, B, Warren, DK, Khawcharoenporn, T, Hayden, MK. Effectiveness of infection prevention measures featuring advanced source control and environmental cleaning to limit transmission of extremely drug-resistant Acinetobacter baumannii in a Thai intensive care unit: an analysis before and after extensive flooding. Am J Infect Control 2014;42:116121.
55. Chittawatanarat, K, Jaipakdee, W, Chotirosniramit, N, Chandacham, K, Jirapongcharoenlap, T. Microbiology, resistance patterns, and risk factors of mortality in ventilator-associated bacterial pneumonia in a Northern Thai tertiary-care university based general surgical intensive care unit. Infect Drug Resist 2014;7:203210.
56. Thatrimontrichai, A, Apisarnthanarak, A, Chanvitan, P, Janjindamai, W, Dissaneevate, S, Maneenil, G. Risk factors and outcomes of carbapenem-resistant Acinetobacter baumannii bacteremia in neonatal intensive care unit: a case-case-control study. Pediatr Infect Dis J 2013;32:140145.
57. Nakwan, NW, Patungkalo, W, Chokephaibulkit, K. Clinical features, risk factors, and outcome of carbapenem-resistant Acinetobacter baumannii bacteremia in a Thai neonatal intensive care unit. Asian Biomed 2012;6:473479.
58. Nakwan, N, Wannaro, J, Thongmak, T, et al. Safety in treatment of ventilator-associated pneumonia due to extensive drug-resistant Acinetobacter baumannii with aerosolized colistin in neonates: a preliminary report. Pediatr Pulmonol 2011;46:6066.
59. Sritippayawan, S, Sri-Singh, K, Prapphal, N, Samransamruajkit, R, Deerojanawong, J. Multidrug-resistant hospital-associated infections in a pediatric intensive care unit: a cross-sectional survey in a Thai university hospital. Int J Infect Dis 2009;13:506512.
60. Katherason, SG, Naing, L, Jaalam, K, et al. Prospective surveillance of nosocomial device-associated bacteremia in three adult intensive units in Malaysia. Trop Biomed 2010;27:308316.
61. Katherason, SG, Naing, L, Jaalam, K, et al. Ventilator-associated nosocomial pneumonia in intensive care units in Malaysia. J Infect Dev Ctries 2009;3:704710.
62. Katherason, SG, Naing, L, Jaalam, K, Ismail, A. Baseline assessment of intensive care-acquired nosocomial infection surveillance in three adult intensive care units in Malaysia. J Infect Dev Ctries 2008;2:364368.
63. Tan, CC, Zanariah, Y, Lim, KI, Balan, S. Central venous catheter-related blood stream infections: incidence and an analysis of risk factors. Med J Malaysia 2007;62:370374.
64. Boo, NY, Ng, SF, Lim, VK. A case-control study of risk factors associated with rectal colonization of extended-spectrum beta-lactamase producing Klebsiella sp. in newborn infants. J Hosp Infect 2005;61:6874.
65. Halder, D, Seng, QB, Malik, AS, Choo, KE. Neonatal septic arthritis. SE Asia J Trop Med Public Health 1996;27:600605.
66. Le, NK, Hf, W, Vu, PD, et al. High prevalence of hospital-acquired infections caused by gram-negative carbapenem resistant strains in Vietnamese pediatric ICUs. Medicine (Baltimore) 2016;95:e4099.
67. Schultsz, C, Bootsma, MC, Loan, HT, et al. Effects of infection control measures on acquisition of five antimicrobial drug-resistant microorganisms in a tetanus intensive care unit in Vietnam. Intensive Care Med 2013;39:661671.
68. Le, T, Nga, TTT, Minoru, A, Kirikae, T. Ventilation associated pneumonia caused by Acinetobacter baumannii at a tertiary hospital in Vietnam: clinical and molecular patterns. Am J Infect Control 2012;40:e53.
69. Gill, CJ, Mantaring, JB, Macleod, WB, et al. Impact of enhanced infection control at 2 neonatal intensive care units in the Philippines. Clin Infect Dis 2009;48:1321.
70. Litzow, JM, Gill, CJ, Mantaring, JB, et al. High frequency of multidrug-resistant gram-negative rods in 2 neonatal intensive care units in the Philippines. Infect Control Hosp Epidemiol 2009;30:543549.
71. Saharman, YR, Lestari, DC. Phenotype characterization of beta-lactamase producing Enterobacteriaceae in the intensive care unit (ICU) of Cipto Mangunkusumo Hospital in 2011. Acta Med Indones 2013;45:1116.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Infection Control & Hospital Epidemiology
  • ISSN: 0899-823X
  • EISSN: 1559-6834
  • URL: /core/journals/infection-control-and-hospital-epidemiology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
Type Description Title
Supplementary materials

Teerawattanapong et al. supplementary material

 Word (164 KB)
164 KB


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