Drivers of antibiotic resistance in
Uganda and Zambia
Presentation to the Global Health Council,
Washington, DC, June 14, 2011
Alliance for the Prudent Use of Antibiotics
Susan D. Foster, PhD MA
Anibal Sosa, MD
C.F. Najjuka, MD
D. Mwenya, MSc
Objectives
Objective 1: Improve knowledge of antibiotic
use and resistance to provide baseline
information for design of interventions.
Objective 2: Analyze prescription and dispensing
of antibiotics to identify processes and
behaviors as targets for interventions.
Objective 3: Assess laboratory capacity to
conduct antibiotic surveillance and impact
policy and clinical practice.
Project approach
• Review of published and unpublished data on
resistance
• Hospital laboratory assessments: 29 laboratories and in
Uganda, and 17 laboratories in Zambia
• Team of 92 Ugandan medical students examined
10,172 outpatient records from 11 sites in Uganda
• Team of 16 Zambian pharmacy interns examined 4,218
outpatient records from 8 sites in Zambia
• Interviews with formal health staff and attendants at
drugshops and pharmacies
• Nearly 1,000 drug samples collected for quality testing
3
Uganda
92 Medical and
pharmacy students
trying out data entry
program
Medical and pharmacy students
picking up equipment and
getting per diems
4
Copies of questionnaires
being handed over to
students going to field
Visit to Mulago Hospital pediatric
ward (project pharmacist Annette
Naggayi on right, Matron in center,
and Gates foundation staff on left)
Meeting with medical student data
collectors after data collection had
ended
5
ARSANA
Project Site
Source: Hopkins et al, JID 2008;
197:510-18
6
7
8
Antibiotic resistance by drug
100
90
80
Resistance Rate %
70
Shigella
60
S. Pneumoniae
H. Influenzae
50
40
30
20
10
0
Chloramphenicol
Cotrimoxazole
Ampicillin
Nalidixic Acid
Antibiotic
9
S. pneumoniae and H.influenzae
resistance
rates
100
90
80
70
60
50
40
30
20
10
0
Uganda
Zambia
Source: Zambia, Ndola Hospital records; Uganda, Netspear data
10
Rapid rise in resistance to
cotrimoxazole in Uganda, 2001-2007
100
% resistance
80
60
40
20
0
2001
2005
2006
2007
Year
11
Cotrimoxazole – actual vs.
recommended dosage
6000
5000
Total dose (mg/kg)
4000
Cotrimoxazole
(actual)
3000
Cotrimoxazole
(48mg/kg/day)
2000
1000
0
<1
1
2
3
4
5
Age
12
Amoxicillin – actual vs recommended
dosage in Uganda
9000
8000
7000
Amoxicillin (actual)
Total dose (mg/kg)
6000
Amoxicillin (90
mg/kg/day)
Amoxicillin (75
mg/kg/day)
Amoxicillin (45
mg/kg/day)
5000
4000
3000
2000
1000
0
<1
1
2
3
Age
4
5
13
Antibiotic use in Zambia, by age
900
800
700
other antibiotic
600
ciprofloxacin
cotrimoxazole tab
500
other penicillin
Liquid
formulations
400
amoxicillin tab
cotrim syr
300
erythromycin syr
amoxicillin susp
200
100
0
0-5
6-12
13-21
21-35
36-55
56-98
14
Antibiotic use in Uganda by age
2500
2000
Other antibiotic
1500
Ciprofloxacin
Cotrimoxazole tab
Other penicillin
1000
Amoxicillin
500
0
0-5
6-12
13-21
21-35
36-55
56-98
age unknown
15
Antibiotics at a Ugandan drugshop
16
17
Diagnoses of pneumonia: Uganda
90
80
70
60
Not severe
50
Number
• 288 of 2347
(12.3%) children
under 6 had a
diagnosis of
pneumonia
• 95 (33%) were
judged to be
“severe” and 193
(66%) “not severe.”
100
Severe
40
30
20
10
0
<1
1
2
3
4
5
Age
18
Availability of drugs needed to treat
pneumonia in Uganda
Rarely, 12%
Always, 39%
Frequently OOS,
14%
Most of the
time, 35%
19
Ineffective treatment of pneumonia in
Uganda
Why do so many die despite treatment?
• Cotrimoxazole is the most often used antibiotic (38.7%)
• S.pneumoniae ABR to cotrimoxazole exceeds 80-90% in
Uganda (and Zambia)
• 88 children (30.5%) received cotrimoxazole alone
• no antibiotic was recorded for 19 children (7%)
• So about 37% of children with pneumonia received
potentially ineffective antibiotic therapy for
pneumonia.
20
Rates of failure of TLC by drug: Uganda
100
90
80
70
60
50
81
Passed TLC
83
89
4
Ciprofloxacin
1
Cotrimoxazole
40
30
20
10
12
0
Amoxicillin
N=270 samples (tablets and capsules only) collected at sites around
Uganda; overall failure rate was 6.3%
Failed TLC
Malaria / pneumonia overlap
• Uganda research: It is difficult for many clinicians to
distinguish between malaria and pneumonia in young
children
– Källander K, Nsungwa-Sabiiti J & Peterson S (2004)
Symptom overlap for malaria and pneumonia. Acta Tropica
90, 211–214.
• For 186 (64.6%) of the Ugandan children diagnosed
with pneumonia, a clinical diagnosis of malaria was
also recorded
– 177 (61.5%) received at least one antimalarial
• Conversely, 65% of malaria cases also received one or
more antibiotic, of which 55% was cotrimoxazole.
22
Malaria / pneumonia overlap
• Uganda research: It is difficult for many clinicians to
distinguish between malaria and pneumonia in young
children
– Källander K, Nsungwa-Sabiiti J & Peterson S (2004)
Symptom overlap for malaria and pneumonia. Acta Tropica
90, 211–214.
• For 186 (64.6%) of the Ugandan children diagnosed
with pneumonia, a clinical diagnosis of malaria was
also recorded
– 177 (61.5%) received at least one antimalarial
• Conversely, 65% of malaria cases also received one or
more antibiotic, of which 55% was cotrimoxazole.
23
Overdiagnosis of malaria by age and
malaria transmission zone in Uganda
medium to high,
<5
12%
very high, 5+
34%
very high, <5
10%
medium to high,
5+
44%
Over ¾ of overdiagnosed cases were in older
children and adults, not in the under 5s
24
Summary of findings
• Resistance to the most common drug for
respiratory infections – cotrimoxazole – is
nearly 100% (S.pneumoniae)
• Antibiotic use is much higher in Uganda than
Zambia – the malaria effect?
• Antibiotic susceptibility data are scarce and
mostly urban
25
Summary of findings cont’d.
• Laboratory capacity is generally poor and patchy
– but some centers doing AST could be upgraded to
monitor treatment effectiveness and guide therapy
choices
– Data could be collected and used to ensure effective
treatment and guidelines
– A cost-effective way to collect essential data
• Malaria is driving antibiotic use, especially in
Uganda – nearly 20% of antibiotics are prescribed
for malaria in adults
– Major savings to be made in both antibiotics and
Coartem
26
Summary of findings, cont’d.
• Amoxicillin is used, but not for those who need it
most
– Used for older children and adults
– Cost is higher (at least twice or more) than cotrim.
• Dosing of amoxicillin was too low for children above
1 – guidelines are known, but not followed
• Amoxicillin is fragile and needs careful handling
• Few syrups and suspensions “child friendly”
formulations are in use
• Issues with under-dosing and administration
27
Summary of findings, cont’d
• Quality of drugs was generally good – few
expired, none counterfeit
– all contained active ingredient (some
mislabeled)
– Most failures were amoxicillin – stability issues
• Health providers in both formal and informal
sector are eager to improve their antibiotic
prescription practices – keen for information and
training
28