Mendelson - Antibiotic drug resistance-What is the problem, and what we can do about it

86 Pages·2015·7.69 MB·English

by  Marc Mendelson

Antibiotic Drug Resistance.
What is the problem,
and what can we do about it?
Marc Mendelson
Division of Infectious Diseases and HIV Medicine
Groote Schuur Hospital, University of Cape Town
3rd Annual Regulatory Workshop • 8th Sept 2015 • ABR – The problem & solutions
Disclosure of Interests
• MSD - Travel Grants to attend European Congress on
Clinical Microbiology and Infectious Diseases
(ECCMID) – 2013, 2014, 2015
• Sanofi, GSK, Aspen, MSD – speaker honoraria (non-
promotional lectures)
• Pfizer – Advisory board for Pneumococcal vaccines
Antibiotics are life-saving medicines
Survival – Patients with Septic Shock
82%
77%
n = 2,731
70%
61%
57%
50%
43%
32%
26%
19%
9%
5%
Time to Appropriate Antimicrobial Rx following Onset of Hypotension (Hrs)
Kumar et al. Crit Care Med. 2006 Jun;34(6):1589-96.
The Problem
Antibiotic use drives the
emergence of antibiotic resistance
LepperPM et al. AntimicrobAgents Chemother2002;46:2920-5.
First reported cases of bacterial
resistance to key antibiotics
[First organism reported to be resistant]
Bars represent the amount
of time taken for bacteria
to develop resistance
after market introduction
Green year = Market introduction
Red year = 1stresistance case
reported
Slide courtesy of Ramanan Laximanarayan

Metagenomic analysis of 30,000 year old permafrost samples
– b-Lactam resistance - bla
TEM
– Tetracycline resistance -
TetM
– Vancomycin resistance -
VanX
– Aminoglycoside-antibiotic-
modifying acetyltransferase
AAC(3) ribosome
methyltransferase
– Macrolide, lincosamide and
type B streptogramin
antibiotic resistance – Erm
Horizontal Gene Transfer
Slide courtesy of Dr Adrian Brink
Antibiotic use selects out
resistant bacteria
Antibiotic
replication
Sensitive bacterium
Resistant bacterium