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INCREASING PREVALENCE RATE OF MACROLIDE RESISTANT STREPTOCOCCUS PYOGENES IN THAILAND: A DECADE REVIEW Nattapong Jitrungruengnij1,2 , Tanittha Chatsuwan3 , Rachaneekorn Nadsasarn2, Suvaporn Anulgulruengkit1,2, Thanyawee Puthanakit1,2, Chitsanu Pancharoen1,2 1 Department 2 Research of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Unit in Pediatric Infectious Diseases and Vaccine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 3 Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Streptococcus pyogenes (GAS) infection Clinical: Pyogenic, Exotoxin, Invasive GAS, Immune process Treatment: First-line: Penicillin Allergic to penicillin: Macrolide Clindamycin Duration: 10 days Drug susceptibility: Some area of the world have strain resistant to macrolides. In Redbook 2015 Prevalence of Erythromycin resistant GAS USA , 1990-2010 Korea, 2001 Serbia, 2009 5% 19% China, 2004-2011 41% 98 % Italy , 2013 9% Japan, 2011-2013 62% Mexico , 1990-2010 5% Israel , 2011 <1% Thailand ??? % Limited publication Laos, 2004-2013 8% Brazil , 2008-2012 15% Objectives • Primary: to study the prevalence of drug resistance of GAS in KCMH, particularly macrolides • Secondary: to study antibiotics prescription and duration for GAS infections in KCMH Methodology: Retrospective descriptive study Population • Age < 18 years old • Duration: year 2006- 2015 Inclusion Criteria • • Data Culture positive for S. pyogenes Clinical Diagnosis of S. pyogenes infection (ICD-10) • • Antibiotic susceptibility was determined by disk diffusion method and MIC strip & breakpoint as per CLSI Method Sensitivity Intermediate resistant Penicillin MIC < 0.12 - - Erythromycin Disk (15mcg) > 21 mm 16-20 mm < 15 mm Clindamycin Disk (2mcg) > 19 mm 16-18 mm < 15 mm Clinical Data: age, sex, underlying disease, diagnosis, treatment Results: Patient data • Sex: Male 64%(77) • Age: Median 6.9 years, IQR 2 Months-18 years Clinical syndromes No. of case 30 Scarlet fever Skin infections Skin 25 2 1 3 2 Scarlet 20 9 Otitis media 15 Bacteremia 10 Pneumonia 5 (n=121) 0 Necrotizing fasciitis 0-1 1-2 2-5 5-10 >10 47 Pharyngitis 0-1 1-2 2-5 5-10 >10 57 Year(s) (age) Jan-Feb Mar-Apr May-Jun July-Aug Sep-Oct Nov-Dec Jan-Feb Mar-Apr May-Jun July-Aug Sep-Oct Nov-Dec Jan-Feb Mar-Apr May-Jun July-Aug Sep-Oct Nov-Dec Jan-Feb Mar-Apr May-Jun July-Aug Sep-Oct Nov-Dec Jan-Feb Mar-Apr May-Jun July-Aug Sep-Oct Nov-Dec Jan-Feb Mar-Apr May-Jun July-Aug Sep-Oct Nov-Dec Jan-Feb Mar-Apr May-Jun July-Aug Sep-Oct Nov-Dec Jan-Feb Mar-Apr May-Jun July-Aug Sep-Oct Nov-Dec Jan-Feb Mar-Apr May-Jun July-Aug Sep-Oct Nov-Dec Jan-Feb Mar-Apr May-Jun Case number Clinical syndromes distribution 18 17 16 15 14 septicemia 13 12 NF 11 10 pneumonia 9 8 7 pharyngitis 6 5 otitis media 4 3 Scarlet 2 1 Skin infection 0 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Year Microbiologic data: source of specimen ET-tube suction 1 Sterile site 3 Sputum 1 Blood 3 Ear swab 9 Throat swab 49 Total 121 Non sterile site 118 Pus Swab 58 GAS: Antibiotics resistant rate % resistance 50 46.5 45 40 35 31 Erythromycin 29.6 Clindamycin 30 25 20 15 10 5 0 Erythromycin and clindamycin 14.3 14.3 Penicillin 8.6 4.3 0 4.8 0 2006-2009 0 2010-2012 0 2013-2015 Year The rate of resistance is increasing rapidly GAS: Antibiotics prescription 60 other Number of cases 50 clindamycin macrolides 40 Cephalosporins cephalosporins 30 Amoxicillin 20 Cloxacillin 10 0 pneumonia otitis media skin infections scarlet pharyngitis invasive GAS cloxacillin amoxicillin Duration of Antibiotics skin infection scarlet fever Mean treatment Incomplete treatment* 7.6 days 9.9 days 20% 15% *incomplete treatment: skin infection is <7 days, Scarlet fever <10 days. Discussions • S. pyogenes is 100% susceptible to Penicillin but less susceptible to Erythromycin and Clindamycin especially in Asia. Country Year no % resistance Penicillin Erythromycin Clindamycin 5.2% 41.3% 98.4% N/A 34.8% 98.4% 61.9% 46.5% 12% 31% USA1 Korea2 1999-2010 174 1998 92 0% 0% China3 2004-2011 125 2011-2013 142 0% 0% 71 0% Japan4 Thailand* 2013-2015 % resistance 1. Villaseñor-Sierra A., et al., Int J Infect Dis. 2012 Mar;16(3):e178-81 2. Cha S., et al., J Infect Chemother. 2001 Jun;7(2):81-6. 3. Zhou W., et al., Indian J Med Microbiol. 2014 Jul-Sep;32(3):290-3 4. Sakata H.,J Infect Chemother. 2015 May;21(5):398-401. Discussions % Erythromycin resistant Macrolide use/1000children-years • In Serbia, the increase in macrolide resistant GAS significantly correlated with consumption of macrolide.* • In Italy, the reduction of OPD macrolides prescription significantly correlated with the decrease of erythromycin resistant gas.+ year *Mijac V, et al., Epidemiol Infect. 2015 Feb;143(3):648-52. +Gagliotti C, et al. Acta Paediatr. 2015 Sep;104(9):e422-4 year Conclusions • The prevalence of macrolide resistant GAS has been rising from 10 to 50% in the last 3 years but none in penicillin. • Amoxicillin remains a drug of choice for scarlet fever and pharyngitis caused by GAS. Acknowledgement