Laboratory Based Antimicrobial Resistance Surveillance for

Nosocomial Bacteria

Phenotypic and genotypic based methods

Olga PerovicOlga Perovic, Principal Pathologist

Head of EQA Reference Unit/National Institute for Communicable Diseases/NHLS/WITS

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Antimicrobial Resistance

• In recent times we have been facing a global problem of emergence of antimicrobial resistance which has spread throughout the world in developed and in developing countries. Considering the world as global village, it is obvious that resistance travel easily and quickly.

• There is no antimicrobial agent to which resistance has not developed over time. Increasing antimicrobial resistance presents a major threat to public health in relation to: a) reduced effectiveness of antimicrobial treatment options, b) increased morbidity and mortality as a direct result of resistance, c) increased healthcare expenditure.

• Infectious diseases account for 45% of deaths in low-income countries.

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Who Global Strategy

• Global strategies were introduced by WHO with two important priorities in mind: a) to organize surveillance to determine the extent of the problem and b) to educate clinicians and the public on the appropriate use of antibiotics.

• Different countries have developed a variety of well known global surveillance programs over time.

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Surveillance networks

• The surveillance networks such as the Alexander Project, EARSS, CDC-NNIS, MYSTIC, PROTECT, SENTRY, and TSN have been established to monitor patterns of antimicrobial resistance of bacterial organisms.

• It is recognized that surveillance of the prevalence of antimicrobial resistance of organisms should be performed at local institutional level.

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Prevalence of nosocomial infections

The European Prevalence of Infection (EPIC) study, a 1-day point prevalence survey of the incidence and origin of nosocomial infection in 1417 intensive care units (ICUs) in 17 western European countries, reported that 21% of the patients in ICUs had a nosocomial infection.

Nosocomial infections continue to plague European ICUs; the European Study of Gram-Negative Infections (ESGNI) study, which assessed the prevalence of nosocomial infections after major heart surgery during 2001 in 17 hospitals from 7 European countries, found an overall infection rate of 9.9%.

The ESGNI, a 1-day prevalence survey conducted in ICUs in 42 institutions in 13 European countries in 2002, found an overall infection rate of 26.8% for postoperative patients after major heart surgery in the United States, estimates indicate more than 2 million nosocomial infections each year 90,000 deaths/year due to nosocomial infections Annual hospital costs of US$5.7 billion (2001 dollars).

LARS-insight

• The heterogeneity in case selection, data management and description of denominator population has barred the comparison of nosocomial resistance occurrence between geographical regions in South Africa.

• The proposed plan will therefore solicit the collaboration of existing surveillance initiatives of centers from different parts of South Africa in order to promote their integration into a standardized system at national level.

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CA-MRSA

• The increased prevalence of both community acquired and healthcare-associated MRSA has an impact on the management of serious infections, including cSSSI, pneumonia, and bacteraemia.

• Six types of SCCmec• Types I, II, III: HA-MRSA

• Types IV, V, VI: CA-MRSA

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Important facts about MRSA and MSSAinfections

• MRSA is prevalent in both uncomplicated and complicated skin and skin-structure infections; a common causative pathogen in many types of pneumonia: healthcare-associated, hospital-acquired, and ventilator-associated

• Bacteraemia can be community-acquired, healthcare associated, or hospital-acquired; the incidence of MRSA bacteraemia is increasing in many European countries, and MRSA bacteraemia has significantly lower survival than MSSA bacteraemia

What about Klebsiella spp.?The clinical outcome of infections due to extended spectrum β-lactamaseproducing (ESBL) Enterobacteriaceae

Authors: O. Perovic, A. Brink, G. Richards, C. Feldman at 26th ICC-Toronto

The current proposal spells out the following vision

• LARS becomes a national stand for estimates on the health and economic burden aspects of antimicrobial resistance in various geographic regions in order to assist clinicians, hospital administrators, founders and guidelines and policy makers.

• LARS will establish a functional integrated AMR surveillance system.

• LARS will develop an information system that links national networks by providing comparable and validated data on the prevalence and spread of major invasive bacteria with clinically and epidemiologically relevant antimicrobial resistance in South Africa.

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Way forwardDuring planning phase the effort should focus on

A. selection of indicator pathogens (hospital-acquired, B. case definitions, C. the harmonization of breakpoints and inhibition zone

diameters using guidelines approved by the Clinical Laboratory Standards Institute (CLSI),

D. decisions on laboratory methods and standards, E. the choice of clinical samples, and F. issues of quality control and assurance. This coordination action will not only improve comparability

between laboratories but also foster the introduction of successful practices as well as new standards in laboratory methods.

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Primary objectives• To establish laboratory-based antimicrobial resistance

surveillance (LARS) system for nosocomial pathogens at National Institute for Communicable Diseases. – The proposal for future coordination with the cohort of

reliable data on the incidence of AMR in different geographical regions. A community-acquired pathogens surveillance system has been in place as GERMS-SA; we will propose to join as additional surveillance; also this system proposes to support the SASCM (South African Society of Clinical Microbiology).

– We will identify a limited number of nosocomial bacterial pathogens such as Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa or Acinetobacter baumannii, to monitor trends in resistance.

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Cont. – A laboratory based antimicrobial resistance

surveillance system will be established at NICD/Antimicrobial Resistance Reference Unit (AMRRU) starting with phenotypic methods and latter genotypic characterization of mechanisms of resistance. This unit will collaborate with satellite NICD Unit in Cape Town.

– To describe prevalence of Staphylococcus aureusand Klebsiella pneumoniae at sentinel sites, by age and to describe trends in frequency of resistance

– To identify MIC50 and MIC90 on all antimicrobials tested.

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Cont. • To tie together the potential of national laboratory-based surveillance

network for antimicrobial surveillance. – To evaluate current laboratory information system (LIS) at NHLS and ability to

provide information on AMR by setting up CDW-Corporate Data Warehouse. We will standardize data entry and improve denominator information. Proposal for this project is in process. This project will provide guidance to institute technical consistency and to standardize reporting of AST at the national level.

• To establish network encompassing national and global data on the antimicrobial resistance. – To expand network for national surveillance systems. With following details:

• To collect isolates compare and validated AMR data.• To analyze trends in the time and place• To provide AMR data from sentinel sites for treatment guidelines.• To provide feedback to all parties.• To provide information on clinically and epidemiologically relevant AMR.

– LARS plans to collaborate surveillance systems such as GARP, APUA and to develop workstations in South Africa.

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Secondary objectives

• To form a coordination group compile of participants from sentinel sites involved in antimicrobial resistance surveillance.

• To estimate impact of antimicrobial resistance on patients well-being and public health.

• To develop models that would predict dynamics of spread of resistance in various regions country wide.

• To disseminate the findings and knowledge to the all levels including patients, clinicians, public and all eligible persons interested in the field.

AMRRU

• To be able to initiate whole process and to evaluate current laboratory techniques and procedures in use we propose a stepwise approach. First step will be to allocate sentinel sites that will submit isolates to AMRRU at NICD.

• Principal investigator and sites investigators will form coordinating group (CG). CG will identify limited number of hospital-acquired pathogens as indicators for hospital acquired antimicrobial resistance (two are proposed-Staphylococcus aureus and Klebsiella pneumoniae).

• Results of this study will be published upon CG agreement.

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Organizational structure-provisional integration in GERMS-SA

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Abbreviations: BFT-Universitas Hospital Bloemfontein, CHBH-Chris Hani Baragwanath Hospital, CMJAH-

Charlotte Maxeke Johannesburg Academic Hospital, GSH-Groote Schuur Hospital, HJH-Helen Joseph Hospital,

SBAH-Steve Biko Academic Hospital, TBH-Tygerberg Hospital

Methods

• Selection of organisms – Staphylococcus aureus and Klebsiella pneumoniae isolates

from blood culture.

• Study design– Multicentre, active, prospective, cross-sectional study of

antimicrobial susceptibility patterns among selected Gram-positive and Gram-negative organisms from sterile site.

• Sentinel sites– Approximately 6 centers in the South Africa will be

enrolled

• Data collection– LCRF

In conclusion-Outline of the whole project

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Actual Show Gantt for

# List of

Activities

Start D

uration

Done 1 2 3 4 5 6

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Submission of

proposal for review

GERMS-SA,

SASCM, NHLS Feb

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3 Selection of CG Pending

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Sending of

specimens April %

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10 Activity 10 6

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