Antibiotic Stewardship- Preserving Today's Antibiotic Armamentarium Emerging PDR Gram-negative bacteria in South Africa Adrian Brink Clinical Microbiologist, Ampath National Laboratory Services, Milpark Hospital, Johannesburg and Department of Clinical Microbiology & Infectious Diseases, University of Witwatersrand, Johannesburg, South Africa Scope of the presentation • Why do we all need antibiotic stewardship as a matter of urgency • Global spread of extended spectrum beta-lactamases (ESBLs) • Global spread of carbapenem resistant Enterobacteriaceae (CRE) • Local spread of CRE • What is antibiotic stewardship • Practically, how to commence with a antibiotic stewardship programme (ASP) • Step 1: Develop an interdisciplinary team and define the roles and responsibilities of team members • Step 2: Do a survey of current practices • Step 3: Select strategies by which to execute an ASP • Step 4: Present results of ASP projects to the clinicians/medical staff • Conclusions Why do we all need antibiotic stewardship as a matter of urgency? β-lactamases produced by Enterobacteriaceae • Noteworthy β-lactamases produced by Gram-negative bacilli (GNB) such as E.coli and K.pneumoniae, causing significant infections worldwide include: • Extended-spectrum β-lactamases (ESBLs) • Carbapenemases • ESBLs hydrolize most beta-lactams and cause resistance except to the carbapenems: • 1st generation cephalosporins e.g cefazolin • 2nd generation cephalosporins e.g cefuroxime • 3rd generation cephalosporins e.g ceftriaxone, ceftazidime, cefotaxime • 4th generation cephalosporins e.g cefepime + Beta-lactam β-lactamase inhibitors e.g ampicillin-sulbactam, amoxycillin clavulanate and piperacillin-tazobactam + And are usually resistant to quinolones and aminoglycosides via additional genes carried with the ESBL gene ESBL –producing pathogens in intra-abdominal infections SMART (Study for the Monitoring of Antimicrobial Resistance Trends) 2004-2009 Resistance to following: -ceftriaxone 29.7% -cefotaxime 28.7% -ciprofloxacin 22.5% South Africa -levofloxacin 21.1% (n=1218 GNB) E.coli 7.6% ESBL+ K.pneumoniae 41.2% ESBL+ MDR Rate: ≥ 3 classes: K. pneumoniae 27.9% Enterobacter spp 14.9% E.coli 4.9% . Brink et al. Surg Infect 2012;13:1-7 Comparative international ESBL rate in complicated Intra-Abdominal Infections: SMART . Brink et al. Surg Infect 2012;13:1-7 β-lactamases produced by Enterobacteriaceae • Carbapenem resistance amongst Enterobacteriaceae can be conferred by several genetic mechanisms but epidemiologically, the most important of these result in the production of β-lactamases (carbapenemases) which hydrolyse carbapenems and most other beta-lactams • The carbapenemases belong to different classes and include: • Klebsiella pneumoniae carbapenemases (KPC) • Metallo-beta-lactamases (MBL), such as • Verona integron-encoded MBLs (VIM) • New Delhi Metallo-β-lactamases (NDM-1) • OXA-48-like carbapenemases such as OXA-48, OXA-181 etc Global spread of KPC-producing bacteria BBBBBBBBBBNNNN X NNNNNNN • Combination therapy for such pathogens? N • Conclusions N South Africa BBBBBBBBBBNNNN NNNNNNNMMMMMMMMMMMMMMMM MMM Nordmann et al. Emerg Infect Dis 2011; 17:1791-1798 MMMMMM (Reproduced with permission). N Brink et al. J Clin Micro 2012;50:525-527 N N N Global spread of NDM-producing bacteria South Africa Nordmann et al. Emerg Infect Dis 2011;17: 1791-1798 (Reproduced with permission) Brink et al. J Clin Micro 2012;50:525-527 Spread of OXA-48-like producing bacteria in the EU, ME and Africa South Africa Nordmann et al. Emerg Infect Dis 2011;17: 1791-1798 (Reproduced with permission) Brink et al. J Clin Micro 2013;51:369-372