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.

3

Project approach• Review of published and unpublished data on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

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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

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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

)

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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.

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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.

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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

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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