/dr_sabiha_essack

Surveillance-­‐Based Treatment Guidelines for Infec7ons The South African Experience

Professor Sabiha Essack B. Pharm., M. Pharm., PhD Dean – Faculty of Health Sciences, UKZN Chair – South African Chapter of APUA essacks@ukzn.ac.za

Overview o

Mul$-­‐centre passive surveillance study n

o

Disease-­‐based ac$ve surveillance study n

o

An$bio$c use and resistance

Nosocomial infec$ons

Surveillance-­‐based clinical prac$ce, infec$on control & policy development

STGs and the EDL o

o o

o

Na$onal DoH implemented STGs and the EDL for common health problems at primary care and hospital level as part of the health policy.1 STGs were formulated by expert commiGees.

PK and PD, drug interac$ons, adverse effects, routes of administra$on, concentra$ons at anatomical sites and cost are considered in the development of STGs and the EDL. 2 An$microbial resistance nullifies these factors in the development of STGs for infec$ons.2

Mul7centre Surveillance Study Sample Sites and Size Mozambique Mozambique Mozambique Mozambique Mozambique 16 hospitals am t 3aaaa p rogressive lSwaziland evels o f h ealth care M Mp p pu u um ma a an n ng g ga a a M p u m a n g a Swaziland M M p u m lllll a a n g a Swaziland Swaziland Swaziland (district, regional, ter$ary)

      100 consecu$ve, ¢ n on-­‐repe$$ve i solates submiGed, ¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢¢ iden$fied F F F rrr e e ee e e and subjected to suscep$bility tes$ng S S S ttt a a a ttt e e e

¢ ¢ ¢ ¢ ¢ ¢

K K Kw w wa a a zzz u u u lll u u u N N Na a a ttt a a a lll      

Lesotho Lesotho Lesotho Lesotho Lesotho Lesotho

¢ ¢ ¢ ¢ ¢ ¢

     

Ó Ó Ó

Ó Ó Ó ¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢ Ó Ó ¢ ¢ ¢ Ó ¢ ¢ ¢ Ó Ó ¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢ ¢             ¢ ¢ ¢ ¢ ¢ ¢

E E Ea a as sss s ttttt e e er rrr rn n n C C Ca a ap p pe e e a e n C a p e E E E a e n C a p e

0

40

kilometres

80

Hospitals Hospitals Hospitals by by byType Type Type by Type Hospitals Hospitals Hospitals by Type    District ¢ ¢ ¢ ¢ ¢ ¢ Regional Ó Ó Ó Ó Ó Tertiary

Mul7centre Surveillance Study Methodology

• Iden$fica$on using the API system • An$bio$c suscep$bility determina$on using the Kirby Bauer disc diffusion method with MICs extrapolated on an automated reading system3.

• Isolates grouped according to their natural resistance profiles.

• Mean %suscep$bility and SD to each an$bio$c stra$fied within and across hospital levels.

• An$bio$c use data was calculated as daily defined dose DDD/1000 pa$ent days.

Mul7centre Surveillance Study Results % Species Isolated

4

Staphylococcus aureus

6

Streptococcus spp.

22

9

Enterococcus spp.

Escherichia coli 3 2

13

Citrobacter spp.

Klebsiella spp.

Enterobacter spp.

Proteus spp.

3

24

10 2

Pseudomonas spp.

Acinetobacter spp.

Mul7centre Surveillance Study Results (2) % Suscep7bility of Klebsiella spp., C. diversus & Proteus spp. (excl P. mirabilis) 100 90 80 70 60 % 50 40 30 20 10 0

88+13 84+25 95+10

72+29 64+19

53+15

57+31

96+9

99+2

50+31 District Regional Ter$ary

• 3% (40/1270) sensi$ve to all an$bio$cs.

• 6% (79/1270) resistant to a single agent.

• Remaining 91% were mul$-­‐resistant • SD ranged from 3-­‐55%

Mul7centre Surveillance Study Results (3) % MRSA, ESBL+ & AmpC Producers Isolated 40

33 34

35

28

30

23

25 % 20

22 District

17

Regional

15

Tertiary

9

10 5

1

3

0 MRSA

ESBL producing organisms

AmpC producing organisms

Ceftazidime Use and Resistance in Klebsiella spp., C. diversus ....

120

R2 = 0.6433

100

%Sensitivity

80

60

40

20

0 0

0.01

0.02

0.03

0.04

0.05

DDD/1000 patient days

0.06

0.07

0.08

0.09

Ac7ve, Disease-­‐Based Surveillance Study Sites, Sampling and Methodology o o

3 hospitals – 1 district, 1 regional & 1 ter$ary 100 each of each pathogen implicated in infec$ons of the: n n n n n

o

respiratory tract, viz., Streptococcus pyogenes, Streptococcus pneumoniae, Heamophilis influenzae and Moraxella catarrhalis, gastro-­‐intes$nal tract, viz., Salmonella spp., Salmonella typhi and Shigella spp., uro-­‐genital tract, viz., Escherichia coli and Proteus spp, skin, viz., Staphylococcus aureus and Streptococcus pyogenes, and nosocomial infec$ons, viz., Klebsiella spp., Citrobacter spp., Enterobacter spp, Serra@a spp, Acinetobacter spp., Pseudomonas spp. and , Enterococcus spp.

Methodology -­‐ as for mul$centre surveillance study

Ac7ve Disease-­‐Based Surveillance Study Results – Nosocomial Infec7ons 50+29 54+40 36+21

%

100 90 80 70 60 50 40 30 20 10 0

% Sensitivity of K. pneumoniae, Acinetebacter spp. & P. aeruginosa p<0,001 across all antibiotics p<0,001 for K. pneumoniae, 0.003 for P aeruginosa

piperacillin tazobactam

cefepime

meropenem

K. pneumoniae P. aeruginosa Acinetobacter spp.

• Implicated in hospital-acquired pneumonia, ventilator associated pneumonia • Empiric therapy: • Either piperacillin-tazobactam, cefepime, carbapenem4

Conclusions and Recommenda7ons o

o o

o

STGs and EDL for infec$ons were compiled by expert commiGees without the availability of surveillance data.

Microbial ae$ology of the disease, an$bio$c use and an$bio$c resistance impact on treatment guidelines.1 Resistance profiles amongst bacteria vary too much to allow a na$onal an$bio$c policy as proposed in the STGs and EDL. Treatment guidelines, treatment algorithms and an7bio7c policies should be formulated by evalua7ng the suscep7bility pa[erns of common causa7ve organisms obtained from large scale, representa7ve, quality-­‐assured, ac7ve disease-­‐based surveillance studies.

Uses of Surveillance Surveillance: o o o o o

o o

o

Improves the quality of empirical an$microbial treatment Guides the formula$on of an$microbial policies & use Educates all an$microbial users, including the public Prospec$vely monitors the efficacy of an$microbials Informs hospital infec$on control in preven$ng the dissemina$on of resistant organisms Iden$fies resistance problems and recommends solu$ons Guides the development of new an$microbial agents by the pharmaceu$cal industry Monitors the evolu$on of resistance locally & interna$onally to allow early interven$on.5

Uses of Surveillance (2) Surveillance: o o o o o o o

o

Assists pa$ent diagnosis Guides treatment of individual pa$ents Informs local & na$onal drug policies & guidelines Focuses local infec$on control in hospitals & communi$es Enables infec$on control to be regional, na$onal & global Can improve tes$ng in pa$ent care laboratories Supports sen$nel laboratories in areas with minimal resources Enhances safety of pa$ents in par$cipa$ng centres6

Surveillance in Global Ini7a7ves to Contain An7bio7c Resistance o o o o o o

o

o

The WHO Global Strategy for the Containment of An$bio$c Resistance US -­‐ “Public Heath Ac$on Plan to Combat An$microbial Resistance” UK -­‐ “Resistance to An$bio$cs” by the House of Lords Select CommiGee on Science and Technology EU -­‐ “Copenhagen Recommenda$ons Report on the EU Conference on the Microbial Threat”.

India – “Na$onal Policy for Containment of An$microbial Resistance” Kenya – Na$onal Policy on Infec$on Control published by Ministry of Health GARP-­‐Kenya and CDDEP convened a policy development workshop in March 2011.

South Africa –Medicines Control Council Conference 2003, with the theme “An$microbial Resistance-­‐Facing the Reality” and the mission cited as “appropriate an$microbial policies for public health”.

Vietnam – member of ReACT SEA, a regional plamorm for policy & programmes Cri7cal to all these ini7a7ves is surveillance which provides evidence for empirical treatment decisions and provides epidemiological data to inform containment strategies.7

Acknowledgements o

Medical Research Council

o

Na$onal Research Founda$on

o

Ms Cathy Connolly, Department of Biosta$cs, MRC, Durban

References 1.

2.

3.

4.

5.

6.

7.

The Na$onal Department of Health. (1998). Standard treatment guidelines and essen$al drugs list. The Na$onal Department of Health. South Africa.

Blondeau JM, Tillotson GS. (1999). Formula to help select ra$onal an$microbial therapy (FRST): its applica$on to community-­‐ and hospital-­‐ acquired urinary tract infec$ons. Interna@onal Journal of An@microbial Agents 12, 145-­‐150.

Clinical and Laboratory Standards Ins$tute. 2005. Methods for dilu$on an$microbial suscep$bility tests for bacteria that grow aerobically. 6th edi$on.

Approved standard. M7-­‐A6, Wayne, P.A., USA. The Na$onal Department of Health. (2006). Standard treatment guidelines and essen$al drugs list. The Na$onal Department of Health. South Africa.

Masterton, R., Craven, D., Rello, J., Streulens, M. et al. 2007. Hospital-­‐acquired pneumoniae guidelines in Europe: a review of their status and future development. Journal of An@microbial Chemotherapy 60, 206-­‐213.

Masterson, R.G. 2000. Surveillance studies: how they can help the management of infec$on. Journal of An@microbial Chemotherapy 46 Topic T2, 53-­‐58.

O’Brien, T.F. & Stelling, J. 2011. Integrated Mul$level Surveillance of the World’s Infec$ng Microbes & their Resistance to An$microbial Agents. Clinical Microbiology Reviews 24, 281-­‐295