INCIDENCE OF BACTERIAL COLONISATION IN HOSPITALISED PATIENTS WITH DRUG-RESISTANT TUBERCULOSIS

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INCIDENCE OF BACTERIAL COLONISATION IN HOSPITALISED PATIENTS WITH DRUG-RESISTANT TUBERCULOSIS 1 Research Associate, Drug Utilisation Research Unit, Nelson Mandela University 2 Human Sciences Research Council, Post-doctoral fellow 3 Department of Microbiology, Nelson Mandela University 4 Drug Utilisation Research Unit, Nelson Mandela University 5 Department of Pharmacy, Nelson Mandela University R Gaida 1,2, J Black 1, S Govender 3, D Annear 3 and I Truter 4,5

BACKGROUND Hospital acquired infections (HAIs) cornerstone of Infection Control Programmes Neglected and under-practiced in South Africa 1 Tuberculosis (TB) burden in South Africa - ~ 295 000 new notified cases in 2015, 10 000 of these being multidrug resistant and rifampicin-resistant cases 2 Lack of literature concerning nosocomial infections in TB hospital settings http://zululandobserver.co.za/103679/tb-awarenesscomes-under-the-spotlight-this-month/ 1. Lowman, W. 2016. Active surveillance of hospital-acquired infections in South Africa: implementation, impact and challenges. South African Medical Journal, 106(5). 2. World Health Organisation. 2016. Global TB Report: Annex 2 Country Profiles. Available at http://www.who.int/tb/publications/global_report/gtbr2016_annex2.pdf?ua=1 [Date accessed: 06/08/2017].

BACKGROUND Extended spectrum beta-lactamase (ESBL) producing bacteria Carbapenem resistance on the increase 1,2,3 Vancomycin-resistant enterococci (VRE) 4 1. Bamford, C., Badenhorst, L., Duse, A.G., Hoosen, A.A., Nchabeleng, M., Oliver, S., Perovic, O., Sein, P.P., Simpson, J., Wadula, J. and Wasserman, E. 2007. Antimicrobial susceptibility patterns of selected invasive pathogens from public sector hospitals in South Africa, 2007. South African Journal of Epidemiology and Infection, 24(2): 28-30. 2. Ehlers, M.M., Veldsman, C., Makgotlho, E.P., Dove, M.G., Hoosen, A.A. and Kock, M.M. 2009. Detection of bla SHV,bla TEM, and bla CTX-M antibiotic resistance genes in randomly selected bacterial pathogens from the Steve Biko Academic Hospital. FEMS Immunology and Medical Microbiology, 56(3): 191-196. 3. Usha, G., Chunderika, M., Prashini, M., Willem, S.A. and Yusuf, E.S. 2008. Characterization of extended-spectrum β-lactamases in Salmonella spp. At a tertiary hospital in Durban, South Africa. Diagnostic Microbiology and Infectious Disease, 62(1): 86-91. 4. Mahabeer, Y., Lowman, W., Govind, C.N., Swe-swe-han, K. and Mlisana, K.P. 2016. First outbreak of vancomycin-resistant Enterococcus in a haematology unit in Durban, South Africa. Southern African Journal of Infectious Diseases, 31(1): 20-24.

AIM To determine the spectrum of bacterial colonisation in drugresistant TB patients upon admission and during hospitalisation

Data collection METHODOLOGY Matched 1:3 each patient transferred from an acute facility matched with three patients from the community Specialised drug resistant TB hospital Demographic information, recent medical care, antibiotic or invasive device exposure over the last month collected at baseline Nasal, groin and rectal swabs at admission and every four weeks during hospitalisation Samples stored at 4 C until transported to the National Health Laboratory Service Identification and antimicrobial susceptibility testing of isolates using culture and VITEK-MS system (National Health Laboratory Service) August to December 2016 Prospective, case control study PCR and DNA sequencing for detection carbapenem resistant genes Microsoft Excel

METHODOLOGY Ethics Nelson Mandela Metropolitan University Research Ethics Committee (Human) H15-HEA-PHA-017 Eastern Cape Department of Health EC_2016RP1_50 Declaration of Helsinki 1 1. World Medical Association. 2013. Declaration of Helsinki: ethical principles for medical research involving human subjects: 1-8.

RESULTS 37 patients nine transfers and 28 community admissions Female patients 78.37% (n=29) Average age of population - 35.08±9.62 years 13 patients colonised upon admission 32% - community (9/28) 44% - other institutions (4/9)

No. of patients PATIENT SPECIFICS N=37 35% 16 65% 14 12 10 HIV Positive HIV Negative 8 6 4 2 0 10-19 20-29 30-39 40-49 50-59 60-69 Age Range (years)

Antimicrobials prescribed ANTIBIOTICS PRESCRIBED DURING HOSPITALISATION Penicillin 3% Terizidone 90% Pyrazinamide 93% Aminosalicylic acid 55% Moxifloxacin 45% Linezolid 62% Levofloxacin 66% Isoniazid 45% Ethionamide 62% Ethambutol 45% Clofazimine 24% Bedaquiline 76% Amikacin 45% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Percentage of patients prescribed antimicrobial

ESBL PRODUCING BACTERIAL ISOLATES 1.56% 1.56% 1.56% 1.56% 3.13% 1.56% 23.44% K. pneumoniae E. coli Staphylococcus aureus Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Proteus mirabilis Citrobacter freundii Klebsiella oxytoca Citrobacter braakii 65.63% N=64

BACTERIAL ISOLATES The high number of K. pneumoniae isolates are of concern Carbapenemase producing genes not detected in isolates with reduced carbapenem susceptibility (Proteus mirabilis and K pneumoniae) No VRE isolated, while two patients had methicillin resistant Staphylococcus aureus colonisation at admission Seven participants died during the course of the study none were attributed to nosocomial infection

ANTIMICROBIAL ANTIMICROBIAL SUSCEPTIBILITIES PERCENTAGE RESISTANCE MIC RANGE HOSPITAL-ACQUIRED ISOLATES (mg/l) BASELINE ISOLATES (n=13) (n=49) PENICILLINS/CEPHALOSPORINS AMPICILLIN 16-32 100 100 AMOXICILLIN 16-32 76.9 77.6 PIPERACILLIN/TAZOBACTAM 64-128 23.1 57.1 CEFUROXIME 64 100 100 CEFUROXIME AXETIL 64 100 100 CEFOXITINE 16-32 76.9 77.6 CEFOTAXIME 2-64 100 100 CEFTAZIDIME 16-32 100 100 CEFEPIME 16-32 92.3 100 CARBAPENEMS ERTAPENEM 1 - >32 7.7 0 IMPIPENEM 8-32 0 0 MEROPENEM 16-32 7.7 0 AMINOGLYCOSIDES AMIKACIN 32-64 53.9 77.6 GENTAMYCIN 8-16 46.2 69.4 FLUOROQUINOLONES CIPROFLOXACIN 2-4 100 100 OTHER TIGECYCLINE 8 23.1 22.4 NITROFURANTOIN 512 53.9 22.4 COLISTIN 16 7.7 0 SULPHAMETHOXAZOLE/TRIMETHOPRIM 320 92.3 100

CONCLUSION Insight into the spectrum of bacterial pathogen colonisation Prior exposure to healthcare facilities put patients at higher risk of being colonised Enterobacteriaceae were the most prevalent nosocomial pathogens colonising TB patients Prolonged admission drug resistant-tb patients at higher risk of colonisation with other drug-resistant pathogens Guidance for Antibiotic Stewardship and Infection Control Programmes

ACKNOWLEDGEMENTS Funder: Inter-professional Research Unit Nelson Mandela University My co-authors John Black Sharlene Govender Dale Annear Ilse Truter Janssen and NDoH

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