Are our options running out?

1. Are our options running out? Antibiotic resistance among in- and outpatients attending Lashkar-Gah hospital, Afghanistan

2. Antimicrobial resistance • Antimicrobial resistance (AMR) is defined as “resistance of a microorganism to an antimicrobial drug that was originally effective for treatment of infections caused by it” • It represents a considerable public health threat: • Requires longer and more expensive treatment • Negatively affects patient outcomes • Erodes our armamentarium of drugs against microorganisms

3. Global context • Poor availability of AMR data all over the world, especially in developing country settings • Suspicions that Asia has the highest level of AMR • Current consensus about a clear correlation between anarchic, unregulated use of antibiotics and levels of AMR

4. Afghan context • Unregulated market of antibiotics (subquality, self-medication…) • High pressure from patients to obtain antibiotics from the prescriber (often IV drugs!) • Over-prescription in hospitals AND private practice • Suspected therapeutic failures in MSF-Hospital

5. MSF-Afghanistan context:Poor therapeuticoutcomes… In Lashkar-Gahhospital (Helmand): Unexplainedhighpaediatricmortality rates LashkarGahHospital (Helmand)

6. MSF-Afghanistan context:Overuse of antibiotics… Over-prescriptions of antimicrobialdrugsamong all outpatient consultations Ahmad Shah Baba hospital (Kabul): Cf. studySaharBajis: “Antimicrobial use in a district hospital in Kabul, Afghanistan – are we too high?“

7. How to assess AMR reality? How to collect data? Option 1? Install a bacteriologylab for routine bacteriologyand … be patient 2-3 yearsto obtainaggregated data? Option 2? Collectenoughbacteriafromvoluntaryinhabitants (such as in- and outpatients of an « MSF-hospital »)and screen for resistance… 4 months We’ve chosen Option 2 … for a first statement

8. Methods • Study conducted in Lashkar-Gah hospital (Helmand), Afghanistan • Screening of normal flora was chosen • Adult and paediatric in- and outpatients requested to provide a stool and/or nasopharyngeal swab sample • Bacteria cultured from these samples and tested for AMR

9. Screening of normal flora- limitations • Everyone of us is carrying thousands of millions of bacteria. We are reservoirs. • Sepsis is the most often due to an intrusion of one of these bacteria in our bloodstream. • The bacteria we “carry” can be used as indicators for levels of AMR among pathogenic bacteria. HOWEVER… this is not the same as resistance testing of pathogens in a routine laboratory

10. RESULTS

11. Bacterialspecies isolation • Screening of normal flora: Participants recruited IPD / OPD Adult / Paediatric 2077 Stoolsamples 692 Nasopharyngealswabs 1762 482 E. coli isolates 173 S. pneumoniae isolates 115 H. influenzae isolates 447 Enterococcus species isolates 259 S. aureus isolates

12. Levels of AMR E. coli as indicator species: proportion of patients with a resistant organism (N=114) ß-Lactamins Aminoglycos. Quinol. Others. ESBL Chloramphenicol Nitrofurantoin Nitrofurantoin Amikacine Netilmicine Tigecycline Amoxi / Clav Pipera / Tazo Cefoxitin Imipenem Meropenem

13. How to become an AMR specialist?Interpretation of resistance in a population of species ONLY SUSCEPTIBLE STRAINS 0% R A FEW RESISTANT STRAINS Imperfectbellcurve + shifting to the left (diametersbecomingsmaller) shift 8% R A nice bell curve taking place on the right of the graph MAINLY RESISTANT STRAINS Bell curve has disappeared Most of the strains are on the left 80% R

14. E. coli: Penicillins & ß-lactamaseinhibitors R S R S R I S R S I S R I S R

15. C2 E. coli &Cephalosporins S R C3 R I S I R S I S R C4 R I S R S Cephamycines

16. E. coli & Quinolones R I S Ofloxacine Ciprofloxacine Levofloxacine Moxifloxacine

17. E.coli & Aminoglycosides R I S Gentamicine Tobramycine Netilmicine Amikacine

18. E. coli & Penems Imipenem R I S Meropenem R I S

19. Chloramphenicol E. coli & other antibiotics R S Tigecycline R I S

20. Resistance in S. pneumoniae(N=64) Screening by oxacilline shows a decreased susceptibility to penicillin MICs to Penicillin could be tested: 16 strains were oxa-R…. MIC values are <= 2 mg/l Thus: decreased susceptibility, but no high level of resistance

21. Discussion • A wake-up call to MSF: our protocols and standard treatment guidelines risk to be outdated ?

22. Discussion • Diagnosis of AMR underfield conditions is a bottle-neck – study shows the feasibility of laboratory screening of AMR in normal flora, but not as matter of routine => Haemoculture as routine feasible? • Holistic management of AMR (rational drug use, infection control, improved diagnostics) isrequired to avert public healthdisaster

23. LashkarGah team July 2013 In MSF-compound Thanks toeverybody ! It has been a incredible challengenot possible without a huge involvement of everyone ! Boost Hospital LashkarGah

24. Special thanks Health promotion: Caroline Zahndt Abdul Bashir And all their wonderful TEAM! Management: Catherine Van Overloop Gabriele Rossi (« SuperMedco ») Gbane (« huge support for end phase ») Lab: Dr Wardak Bismillah Sher Agah Baryalai LuxOR: Rafael Van den Bergh Rony Zachariah And all the TEAM! OCB-Medical Depatment: Michel Van Herp Pascale Chaillet Logistics / Supply: Ann, Ben, Ryan, Antoine, Bazir, … Sorry for anyone I would have forgotten !!!! MSF-Supply Diana & Sonia