1. Surveillance of Antibiotic Resistance at Sihanouk Hospital Center of HOPE (2007-2013) Phe Thong, MD; Erika Vlieghe, MD PhD; Lim Kruy, MD; Veng Chhunheng, MD; Kham Chun, MLT; Sovan Ieng, MD; Birgit De Smet, MSc; Jan Jacobs, MD PhD Workshop on Biodiversity Nov 17-18, 2014, USH, Phnom Penh Sihanouk Hospital Center of HOPE, Phnom Penh, Cambodia Institute for Tropical Medicine (ITM), Antwerp, Belgium

2. Background Bloodstream infection (BSI) is an important cause of morbidity and mortality worldwide. Early administration of adequate antibiotic therapy is essential to improve outcome – based on knowledge of local bacterial pathogens and their resistance patterns (Ibrahim 2000) In Cambodia, surveillance data on blood stream infections or other invasive infections are not widely available so far. 2005: Start microbiology laboratory services 07/2007: Start surveillance of bloodstream infections (sepsis) 2 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

3. Materials and methods Designs: Descriptive of surveillance data Systematic blood cultures: all patients presenting at SHCH with ‘Systemic Inflammatory Response Syndrome (SIRS) Sampling 10 ml blood (2 bottles) – Culture in BacTalert vials (bioMérieux, Marcy l'Etoile, France) – Incubated for 7 days at 35°C – Visual inspection of the chromogenic growth indicator. 3 At least 2 of the following criteria: Temperature > 38°C or <36°C Pulse rate > 90/min Respiratory rate >20/min WBC >12,000/mm3 or <4,000/mm3 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

4. Chromogenic growth indicator 4 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

5. Materials and methods Identification to the species level: standard microbiological techniques Antibiotic susceptibilities: disk diffusion, breakpoints according to CLSI guidelines – Additional E-test (for penicillin susceptibility in S. pneumoniae ) – Additional double disk test for ESBL-screening External quality control (ITM Antwerp, Belgium) 5 * CLSI: Clinical and Laboratory Standards Institute. Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

6. Data collection Blood culture request form contains demographic and basic clinical data Microbiological laboratory data recorded in a laboratory logbook. Data entered and stored in the hospital electronic database Positive blood cultures: patients are traced, additional data on treatment and outcome collected A monthly report is made and communicated in the hospital 6 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

7. Results Between 7/2007 and 12/2013 – 14291 blood cultures samples received from 10352 patients. Sex: 54.1% female Median age=45 years old (IQR=31 – 59) – 1249 clinically significant organisms (CSO) Average yield 8.8 % 90 % is community-acquired infection 7 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

8. Number of bacterial culture; SHCH: 2007 - 2013 8 Results Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

9. Positivity rate of blood culture 9 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

10. Key pathogens (N=1249) 10 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

11. Key pathogens (n=1249) 11 E. coli: 29% S. aureus: 9% Salmonella spp: 17% Burkholderia pseudomallei: 10% Klebsiella sp:7% Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

12. Hospital outbreak of Burkholderia cepacia Search for source of infection: - Connector of Bag of Ringer Lactate grew B. cepacia - Bag of Ringer Lactate used for flushing grew B. cepacia De Smet et al. Clin Microbio Infect. 2013 Sep;19(9):832-7

13. Community Outbreak of Salmonella Paratyphi A 13 2007-2010: 2 cases in 4 year 2011-2013: 83 cases in 3 years (74 cases in 2013!!) Vlieghe, Eurosurveillance 2013 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

14. 14 Resistance patterns of Escherichia coli (E. coli) 2007 – 2013; n=365 *Note: ESBL test available only from 2010 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

15. Resistance paterns of Klebsiella pneumoniae (2007-2013); n=82 15 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013 *Note: ESBL test available only from 2010 Emergence of Carbapenema-producing Klebsiella pneumonia in our hospital.

16. Resistance patterns of Salmonella Typhi 2008 – 2013; n=53 16 *DCS: Decrease ciprofloxacin susceptibility (Nalidixic acid resistance) Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

17. 17 Resistance Staphyloccocus aureus (SHCH; 2007 – 2013) Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

18. Discussion and Conclusions (Community-acquired) BSI among Cambodian adults – mainly Gram negative organisms – predominantly E.coli, Salmonella sp. and B. pseudomallei. Surveillance helps also to discover outbreaks High rate of antibiotic resistance especially gram negative pathogens (E. coli) Limitation: single hospital surveillance, possible population selection bias. Nation wide surveillance and control of antimicrobial resistance and its driving forces is highly needed. 18 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

19. Thanks to… All patients All staff and management of SHCH Our dedicated colleagues of the FA3 agreement project on Antibiotic Resistance – SHCH: Phe Thong, Heng Chhun Veng, Kruy Lim, Chun Kham, Sopheak Thai, Elen Mailing, Syna Teav – ITM: Jan Jacobs, Erika Vlieghe, Birgit De Smet, Lut Lynen, Johan van Griensven, Nathalie Lorent Funder: DGDC (Belgian government) 19 Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013

20. Resistance Staphyloccocus aureus (SHCH; 2007 – 2013) 20 Years2007200820092010201120122013Average N=1104131920231714 MRSA0%15%21%25%23%53%21%26% Lincomycin0%54%42%32%64%88%79%56% SMX/TPM25%15%17%15%14%35%15%17% Ciprofloxacin0%46%16%21%32%63%31%32% Vancomycin0% Thong Phe, Antibiotic surveillance in SHCH 2007 - 2013