18 September 2002 20:10 GMT

by Bea Perks

[caption and credit]

Loughborough, UK - The surveillance of antimicrobial-resistant pathogens, which pose a grave population-wide risk, relies on methods that were originally designed for other purposes, says Swedish microbiologist Gunnar Kahlmeter. And because their broader use is not necessarily valid, he urges change.

Bacterial pathogens have long been pigeon-holed into three categories - susceptible, intermediate, and resistant - with respect to antimicrobial susceptibility, says Kahlmeter. When this categorization system was developed, he notes, it was meant as "nothing more than an instrument for directing antimicrobial chemotherapy in patients."

However, with the worldwide rapid increase of acquired antimicrobial resistance, the results of susceptibility testing are now used for a growing number of additional purposes, says Kahlmeter, who is based at the National Institute for Infectious Disease Control in Stockholm. They are also used to predict the outcome of antimicrobial therapy in future patients, for instance, and to facilitate epidemiological intervention.

Epidemiological intervention can be achieved, Kahlmeter says, through early detection of bacteria with particularly "unwanted or feared" resistance mechanisms in hospitals (for example, methicillin-resistant Staphylococcus aureus, MRSA) or in the wider community (for example, multiresistant Mycobacterium tuberculosis). Intervention can also be achieved by the early detection of trends in resistant frequencies and the identification of factors responsible for directing those trends.

Such data are collected by governmental and international bodies worldwide, and they form the basis of national antibiotic policies and interventions, Kahlmeter told delegates at this morning's symposium, Controversies in antibiotic susceptibility testing, at the 151st Ordinary Meeting of the Society for General Microbiology here at Loughborough University.

These bodies are termed "breakpoint committees" because they monitor antimicrobial resistance according to a measure called the breakpoint - the concentration of an antibiotic that can be achieved at the site of infection during a course of treatment. It is the response of bacteria to the concentration of antibiotic that determines whether the organisms will be characterized as susceptible, intermediate, or resistant.

But the breakpoint method was designed to measure clinical outcome in a single patient, stresses Kahlmeter, and it is not always possible to extrapolate these data to epidemiological applications - which are vital when tracking the spread of a resistant strain through a population. Despite current attempts to refine the method in line with "modern pharmacodynamic principles," he says, drawbacks remain.

To address the problem, Kahlmeter proposes the development of two sets of breakpoints: a "clinical breakpoint" based on pharmacology, pharmacodynamics, and clinical evidence of therapeutic success; and an "epidemiologic breakpoint" based on phenotypic or genotypic detection of "true" resistance.

Kahlmeter is chairman of a recently established pan-European body called EUCAST, the European Committee for Antimicrobial Susceptibility Testing, set up by the European Society of Clinical Microbiology and Infectious Diseases.

Europe has six major breakpoint committees, including the British Society for Antimicrobial Chemotherapy, which co-hosted this morning's symposium. These committees each have more than 25 years experience in setting breakpoints, Kahlmeter says, but they all employ different analytical methods to fulfill their roles. The role of EUCAST will be to "bring them together in a coherent setting in Europe," he said.

Kahlmeter is keen to stress that EUCAST will not simply replace everything that has gone before. "The basic strategy is that rather than trying to build a new committee, we'll try to build on the 25 x 6 years of experience," he said. "It's no use trying to create a committee in competition with the national committees."

Kahlmeter's plans were praised by Peter Hawkey, professor of microbiology at the University of Birmingham. Sensitivity/resistance testing is sometimes regarded as "stamp collecting" and "very tedious," said Hawkey, but it is absolutely essential.

"If we get it wrong - the wrong breakpoints and the wrong technique - patients get treatment late and inappropriately," he said. "Gunnar Kahlmeter has the unenviable task of trying to sort Europe out."

Picture caption and credit:
Scanning Electron Micrograph of Mycobacterium tuberculosis, NIAID/NIH.

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See also:
What is antibiotic resistance and how can we measure it?
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Trends in Microbiology, 2000, 8:12:554-559

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Current Opinion in Pharmacology, 2002, 2:5:487-492

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Current Opinion in Microbiology, 2000, 3:5:496-501

Antibiotic-resistant enterococci: the mechanisms and dynamics of drug introduction and resistance
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Microbes and Infection, 2002, 4:2:215-224
 

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