drivers of antibiotic resistance in uganda and zambia presentation to the global health council,...
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Drivers of antibiotic resistance in Uganda and ZambiaPresentation to the Global Health Council, Washington, DC, June 14, 2011
Alliance for the Prudent Use of Antibiotics
Susan D. Foster, PhD MAAnibal Sosa, MDC.F. Najjuka, MDD. 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.
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Project approach• Review of published and unpublished data on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
4
92 Medical and pharmacy students trying out data entry program
Medical and pharmacy students picking up equipment and getting per diems
Uganda
5
Meeting with medical student data collectors after data collection had ended
Visit to Mulago Hospital pediatric ward (project pharmacist Annette Naggayi on right, Matron in center, and Gates foundation staff on left)
Copies of questionnaires being handed over to students going to field
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ARSANA Project Site
Source: Hopkins et al, JID 2008; 197:510-18
7
8
9
Antibiotic resistance by drug
Chloramphenicol Cotrimoxazole Ampicillin Nalidixic Acid0
10
20
30
40
50
60
70
80
90
100
ShigellaS. PneumoniaeH. Influenzae
Antibiotic
Resis
tanc
e Ra
te %
10
S. pneumoniae and H.influenzae resistance rates
S. pneumoniae
: Chlor
S. pneumoniae
: Cotri
m
S.pneumoniae
: Amox
H. influenzae
: Chlor
H. influenzae
: Cotri
m
H. influenzae
: Amox
0102030405060708090
100
UgandaZambia
Source: Zambia, Ndola Hospital records; Uganda, Netspear data
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Rapid rise in resistance to cotrimoxazole in Uganda, 2001-2007
2001 2005 2006 20070
20
40
60
80
100
Year
% re
sist
ance
12
Cotrimoxazole – actual vs. recommended dosage
<1 1 2 3 4 50
1000
2000
3000
4000
5000
6000
Cotrimoxazole (ac-tual)
Cotrimoxazole (48mg/kg/day)
Age
Tota
l dos
e (m
g/kg
)
13
Amoxicillin – actual vs recommended dosage in Uganda
<1 1 2 3 4 50
1000
2000
3000
4000
5000
6000
7000
8000
9000
Amoxicillin (actual)
Amoxicillin (90 mg/kg/day)
Amoxicillin (75 mg/kg/day)
Amoxicillin (45 mg/kg/day)
Age
Tota
l dos
e (m
g/kg
)
14
Antibiotic use in Zambia, by age
0-5 6-12 13-21 21-35 36-55 56-980
100
200
300
400
500
600
700
800
900
other antibioticciprofloxacincotrimoxazole tabother penicillinamoxicillin tabcotrim syrerythromycin syramoxicillin susp
Liquid formulations
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Antibiotic use in Uganda by age
0-5 6-12 13-21 21-35 36-55 56-98 age unknown0
500
1000
1500
2000
2500
Other antibioticCiprofloxacinCotrimoxazole tabOther penicillinAmoxicillin
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Antibiotics at a Ugandan drugshop
17
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Diagnoses of pneumonia: Uganda
• 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.”
<1 1 2 3 4 50
10
20
30
40
50
60
70
80
90
100
Not severeSevere
Age
Num
ber
19
Availability of drugs needed to treat pneumonia in Uganda
Always; 39%
Most of the time; 35%
Frequently OOS; 14%
Rarely; 12%
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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.
Rates of failure of TLC by drug: Uganda
Amoxicillin Ciprofloxacin Cotrimoxazole0
10
20
30
40
50
60
70
80
90
100
12
41
81
83 89 Passed TLCFailed TLC
N=270 samples (tablets and capsules only) collected at sites around Uganda; overall failure rate was 6.3%
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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
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.
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Overdiagnosis of malaria by age and malaria transmission zone in Uganda
medium to high, <512%
very high, <510%
medium to high, 5+
44%
very high, 5+34%
Over ¾ of overdiagnosed cases were in older children and adults, not in the under 5s
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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
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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
27
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
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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