ANTIMICROBIAL USE AND RESISTANCE SURVEILLANCE PILOT PROJECT – LESSONS

FROM THE DURBAN SITEGray AL, Essack SY, Deedat F, Pillay T,

van Maasdyk J, Holloway K, Sorensen TL, Sturm AW

Dept. Pharmacology and Dept. Medical Microbiology, Nelson R Mandela School of Medicine, School of Pharmaceutical Sciences,

Univ. KwaZulu-Natal, Durban, South Africa,

WHO/EDM, Geneva

Abstract Problem Statement: The World Health Organization’s global strategy for containing antimicrobial resistance

recommends the development of methodologies that will enable developing countries to identify and track resistance trends in specific infections and geographical locations. Standard methods for such surveillance systems do not exist for resource-constrained settings.

Objectives: To investigate the association between antibiotic use and resistance over time in respiratory tract infections in the Inner West metropolitan area of Durban.

Design: Retrospective, time series analysis of antimicrobial use data and antimicrobial resistance of selected isolates.Setting and population: 7 randomly selected private pharmacies, 7 convenience sampled private dispensing

practitioners and 7 randomly selected state-operated nurse-managed primary health care clinics.Methods: Antimicrobial use data were obtained from prescription records at sites representing a broad spectrum of socio-

economic conditions and prescriber types. Sputum specimens were obtained from consenting patients presenting with self-reported cough with or without fever at 4 sites in the selected geographical locale. Cultures positive for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were subjected to MIC determinations against ampicillin, erythromycin, chloramphenicol, cotrimoxazole and ciprofloxacin by means of agar dilution. NCCLS breakpoints were applied to determine resistance.

Outcome measures: Percentage of patients seen (or prescriptions dispensed) in which an antimicrobial was prescribed; antimicrobial usage in Defined Daily Doses per 100 patients seen; percentage susceptibility of selected isolates.

Results: High usage of older antimicrobial agents was seen in public sector clinics and lower usage of a wide range of agents, including newer broad-spectrum antimicrobials, in the private sector. Percentage resistance of selected isolates by time series per quarter showed an decreasing level of resistance amongst pneumococci to ampicillin and erythromycin, but continuously total resistance to cotrimoxazole. Increasing trends in resistance to ampicillin were shown amongst H influenzae, but decreasing trends in resistance to cotrimoxazole.

Conclusions: Although no direct relationship between resistance levels and antimicrobial usage could be shown, the feasibility of establishing a system to generate data of this sort was demonstrated. Further analysis over time is planned.

Study funded by: World Health Organization.

Background• In September 2001 the WHO released

the Global Strategy for Containment of Antimicrobial Resistance (WHO/CDS/CSR/DRS/2001.2)– This document identified 67 interventions

targeted at different groups – It also identified the need for linked

surveillance of antimicrobial resistance and use, in order to assess these interventions

• Not clear how to achieve this in resource-constrained setting

Objectives• To investigate the association between

antibiotic use and resistance over time in respiratory tract infections in the Inner West metropolitan area of Durban, South Africa

Methods – resistance• Sputum specimens

• consenting patients with self-reported cough, with or without fever

• 4 convenience sampled sites• Public and private sector

• Standard laboratory work-up– Selective cultures for:

• Streptococcus pneumoniae• Haemophilus influenzae • Moraxella catarrhalis

– MIC determinations • ampicillin, erythromycin, chloramphenicol, cotrimoxazole and

ciprofloxacin • agar dilution• standard NCCLS breakpoints

Methods – antimicrobial use• Retrospective prescription audit

(2 weeks’ Rx per month)– 7 randomly selected private pharmacies (stratified by socio-

economic status of area; data from original prescriptions)– 7 convenience sampled private dispensing practitioners

(stratified by socio-economic area; data from clinical records)

– 7 randomly selected primary health care clinics (stratified by size; data from daily clinic registers)

• Data analysis – % patients seen (or prescriptions dispensed) in which an

antimicrobial was prescribed– antimicrobial usage in Defined Daily Doses per 100 patients

seen (clinics and doctors) or prescriptions dispensed (pharmacies)

– % susceptibility of selected isolates - all by time series

S. pneumoniae – resistance(ciprofloxacin not tested)

0

20

40

60

80

100

% re

sist

ance

Q4 '02 Q1 '03 Q2 '03 Q3 '03 Q4 '03

Cotrimoxazole Ampicillin RifampicinChloramphenicol Erythromycin

H. Influenzae – resistance(no resistance to erythromycin or ciprofloxacin)

0

20

40

60

80

100

% re

sist

ance

Q4 '02 Q1 '03 Q2 '03 Q3 '03 Q4 '03

Cotrimoxazole Ampicillin Rifampicin Chloramphenicol

Antimicobial use – overallFacility type Total

patients seen or

prescriptions dispensed

Antimicrobial-containing

prescriptions

% AM Rx

Pharmacies (prescriptions)

19 979 2 400 12.0

Clinics 84 390 14 096 16.7

Dispensing practitioners

23 420 3 003 12.8

Antimicrobial use - cotrimoxazole

05

101520253035

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Months (Q4 '02 = 1-3)

Cotr

imox

azol

e D

DD/1

00pt

Pharmacies Clinics Doctors

Winter

Antimicrobial use - quinolones

02468

10121416

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Months (Q4 '02 = 1-3)

Qui

nolo

ne D

DD

/100

pt

Pharmacies Clinics Doctors

Winter

Antimicrobial use – all antimicrobials

0

50

100

150

200

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Months (Q4 '02 = 1-3)

All

AM

DD

D/10

0pt

Pharmacies Clinics Doctors

Winter

Conclusions and Acknowledgements• Although no direct relationship between resistance

levels and antimicrobial usage could be shown, the feasibility of establishing a system to generate data of this sort was demonstrated

• Given the differences in antimicrobial use patterns in different settings, interventions to contain the development of resistance will have to be carefully tailored for each setting

Thanks to: WHO/EDM for funding this pilot project, the fieldworkers and laboratory staff, the staff at the facilities, for allowing us access to their patients and their data, the patients who provided sputum samples