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PROBLEM OF ANTIBIOTIC RESISTANCE IN A DEVELOPING COUNTRY

PROBLEM OF ANTIBIOTIC RESISTANCE IN A DEVELOPING COUNTRY. DR.ALTAF AHMED Head of Clinical Microbiology Chairman CSSD Liaquat National Hospital, Karachi General Secretary Infectious Diseases Society of Pakistan. Antibiotic resistance in Pakistan. Epidemiology – GLOBAL/LOCAL-

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PROBLEM OF ANTIBIOTIC RESISTANCE IN A DEVELOPING COUNTRY

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  1. PROBLEM OF ANTIBIOTIC RESISTANCE IN A DEVELOPING COUNTRY DR.ALTAF AHMED Head of Clinical Microbiology Chairman CSSD Liaquat National Hospital, Karachi General Secretary Infectious Diseases Society of Pakistan

  2. Antibiotic resistance in Pakistan • Epidemiology – GLOBAL/LOCAL- • MRSA/VRE/ Pneumo/ESBL/ MDR typhoid/MDR-TB • Reasons? • WHAT CAN BE DONE?

  3. Infectious diseases still account for 45% of deaths in low-income countries and for almost one in two premature deaths worldwide. • Most of these deaths (about 90%) are due to six diseases: • acute respiratory infection (mainly pneumonia), • diarrhoeal disease, • HIV/AIDS, • tuberculosis, • malaria • measles.

  4. Use of antibiotics Where antibiotics are used Types of use Questionable use ------------------------------------------------------------------------------------ Human use (50%) 20% Hospital ---------------------------- 20-50% Unneccesary 80% Community ------------------------------------------------------------------------------------ Agricultural use (50%) 20% Therapeutic --------------------------------- 40-80% Highly 80% Prophylactic/growth questionable. promoation.

  5. GRAM POSITIVES

  6. MRSA IN PAKISTAN

  7. MRSA PAKISTAN • Ghulam Mujtaba Siddiquei, Karamat Ahmed Karamat, Abdul Hannan. PAF Hospital SargodhaPakistan J Pathol. 1999;10(2):26-8. • 372 strains of Staphylococcus aureus were isolated • 1995 / 1996. • 22.3% (MRSA). • This prevalence of MRSA in Pakistan should not go without our serious concern. • Hafiz S, A.Ahmed et al.Methicillin resistant Staphylococcus aureus : a multicentre studyJPMA; 2002;52(7):312-4. • Result: 42% (MRSA) • No Vancomycin resistance was encountered.

  8. MRSA IN LAHORE 4%VRSA? • Nizam Khatoon, Hussain Bukhari S M,et al. (Mayo Hospital Lahore)Biomedica 2002;18:49-52. • 350 positive cultures for Staphylococcus aureus, 135 were found to be methicillin resistant (38.5%). • Mulazim Hussain Bukhari et al. • Mayo Hospital Lahore Pak J Med Sci. 2004;20(3):229-33 • 350 positive S.aureus cultures, 135 were found to be Methicillin resistant (38.5%) • Showed susceptibility 96%, 94% and 86% to Vancomycin, Teicoplanin and Fucidic acid respectively.

  9. MRSA IN KARACHI Dr. Amtul Hafeez, 1994 43% JPMC Dr. Afia Zafar, 2003 40% AKUH Dr. Altaf Ahmed, 2004 36% LNH SALEEM HAFIZ, 2002 42% SIUT

  10. Status of VRSA • No VRSA--Ayaz Hussain Qureshi et al. AMC Rawalpindi, Pak J Med Sci, 2004;20:361-4

  11. Nasal Carriage of MRSA in Pakistan • Muhammad Saeed Anwar, et al.Staphylococcus Aureus and MRSA nasal carriage in general populationJCPSP; 2004;14(11):661-4. • Nasal swabs from 1660 subjects from the community were studied. • 246 (14.82%) samples were positive for growth of S. aureus (nasal carriers of S. aureus). • Out of 246 S. aureus isolates, 48 (19.51%) isolates were (MRSA).

  12. Prevalence of MRSA in Asia Pacific Region 2003/2004

  13. Staphylococcus aureus bacteraemia due to MRSA, by region (England & Wales, 1991- 2003) source: routine laboratory reporting to CDSC

  14. One of the lowest • Denmark has only 0.2% MRSA BMJ 1998; 317:620 WHY?

  15. Trend in Rate of VRE • Tariq Butt et al.Emergence of Vancomycin resistant enterococci faecium in northern Pakistan 2004; 54:275-6. • VRE in LNH :- • 9 CASES, All from nephro • All died • LINEZOLID?

  16. High incidence of penicillin Resistant S. Pneumoniae in R.T.I Japan 54% Spain 65.6% France 66.5 % USA 34.1% % Isolates Results of international surveillance study presented in 15thAasia pacific congress on diseases of the chest Dec 1999

  17. Penicillin resistant Streptococcus pneumoniae, LNH, Karachi- 2005 % Sensitive R I S

  18. ESBLS • EXTENDED SPECTRUM BETA LACTAMASES

  19. Evolution of -Lactamase Plasmid-mediated TEM and SHV Enzymes Third-generation cephalosporins Ampicillin 1980s 1983 1965 1970s 1987 2001 >150 ESBLs worldwide TEM-1 E. coli S. paratyphi TEM-1 Reported in 28 gram-negativespecies ESBL in Europe ESBL inUnitedStates 1963

  20. Some Speciesin which ESBLs are Found • Klebsiella • Escherichia coli • Enterobacter • Proteus • Salmonella • Citrobacter • Pseudomonas • Acinetobacter • and others!!! Numbers are increasing every week Bradford PA. Clin MicrobiolRev. 2001;14:933

  21. Evolution of ß-lactamases No. of enzymes Bush K. Clin Infect Dis 2001;32:1085

  22. Extended Spectrum Beta- Lactamase(ESBL) producing Nosocomial GNRs 30% AKU, Karachi Jabeen K, Zafar A, Hasan R JPMA 2003 37% PIMS, Islamabad Shah A, Hasan F, Ahmed S. Pak J Med Science. 2003 45% AMC, Rawalpindi Rafi A, Qureshi AH. JAMC2003

  23. SLIDE DONATED BY DR. AFIA, AKUH

  24. SLIDE DONATED BY DR.AFIA, AKUH

  25. PAN RESISTANCE,LNH2004 -2005 AcinetobacterPs.aeruginosa Medical ICU 38 14 Surgical ICU 23 08

  26. ESBL Producers usually do not respond to Penicillins, All Cephalosporins and Aztreonam.

  27. TYPHOID • MULTI DRUG RESISTANT TYPHOID • FLOUROQUINOLONE RESISTANT TYPHOID

  28. Ciprofloxacin Treatment Failure in Typhoid Fever Rawalpindi, Pakistan • Tariq Butt, et al.*Armed Forces Institute of Pathology, Rawalpindi, Pakistan • Emerging Infec Dis., 2003; Vol: 9, No. 12 • Inadequacy of the current laboratory guidelines for detection of this resistance. • The spread of this resistance would leave only the less effective but more expensive, third-generation cephalosporins for treatment of typhoid. • Fluoroquinolone resistance must be identified early, and these drugs must be used judiciously. Otherwise, society may be faced with the prospect of untreatable typhoid fever.

  29. LNH Co-trimoxazole Ampicillin Ciprofloxacin Chloramphenicol

  30. Nalidixic acid resistance S.typhi-Rawalpindi Study • 17% of the isolates were resistant to nalidixic acid. • Nalidixic acid disc diffusion and MIC estimation by E-test were 100% comparable. • Isolates which were resistant to nalidixic acid had raised MIC values against Ciprofloxacin. • Anjum P, Qureshi A H, Rafi S. Fluroquinolone resistance in Typhoidal Salmonella and its detection by Nalidixic acid disc diffusionJPMA 2004;54(6):295-301.

  31. Ciprofloxacin MIC by E test MIC ug/ml No % 0.12 2 3 0.19 4 6 0.25 26 39 0.38 19 29 0.50 6 9 0.75 4 6 1.0 4 6 1.5 1 2 E Test Strip LNH STUDY of 200 isolates

  32. Nalidixic acid /Ciprofloxacin-resistant (MIC 1.0) (MIC 0.25)

  33. Multi-drug resistant Tuberculosis in Northern Pakistan, 2004 • Results:325 clinical specimens. • 15% isolates were resistant to a single drug, 28% were multi-drug resistant including 7% which were resistant to all the four drugs. • Rifampicin 32%, isoniazid 37%, streptomycin 19% and ethambutol 17%. • Butt T, Ahmad R N, Kazmi S Y, Rafi N. Multi-drug resistant Tuberculosis in Northern PakistanJPMA 2004;54(9):469-72.

  34. Resistant Tuberculosis in Southern Pakistan1995-2005 Badar F.1995;2:Infec Dis.Soc.Mednews Antibiotic susceptibility report, AKUH IDJ, 2005;14:30.

  35. Thai study • Antimicrobial resistance in the developing world is most likely related to the frequent unrestricted use of over-the-counter drugs without medical supervision. 1 Hoge CW, Gambel JM, Srijan A, et al. Trends in antibiotic resistance among diarrheal pathogens isolated in Thailand over 15 years. Clin Infect Dis 1998;26:341-345.

  36. PROBLEMS OF ANTIBIOTIC THERAPY • 40% of the antibiotics produced each year are used in animals. • Growth enhancers in cattle and poultry • Trout and Salmon farms • As aerosols to fruit trees – sprays from planes – people receiving small but repeated doses of antibiotics Chicken feed heavily loaded with tetracycline

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