FiRe works – the Finnish Study Group for Antimicrobial Resistance (FiRe)

A.Nissinen1, P. Huovinen2
1
Clinical Microbiology Laboratory, Central Hospital of Middle Finland, Jyväskylä, Finland
2 Antimicrobial Research Laboratory, National Public Health Institute, Turku, Finland

The Finnish Study Group for Antimicrobial Resistance (FiRe), a network founded in 1991, has established a standard routine susceptibility testing method that yields reliable and comparable results for both diagnostic and epidemiological purposes. Results from FiRe show that the proportion of Streptococcus pneumoniae with resistance to macrolides is increasing and decreasing susceptibility of salmonella isolates to fluoroquinolones is being seen among isolates of foreign origin, but the prevalence of MRSA has remained low in Finland and multiresistant Mycobacterium tuberculosis is rare.

Each year in Finland, five million patients with infectious diseases are seen by doctors working in primary health care and hundreds of thousands of infectious disease patients are treated in hospitals. Over 200 000 bacterial isolates are tested for antimicrobial susceptibility in the 28 major clinical microbiology laboratories of the Finnish Study Group for Antimicrobial Resistance (FiRe) each year. FiRe, a network dedicated to research into the prevalence of resistance in bacteria isolated from humans, was founded in Finland in 1991.

During its first few years the main task for FiRe was to study antimicrobial resistance by sampling the bacteria that are clinically most important (1-4). Bacterial collection was centralised (isolates were sent to the reference laboratory for further studies) and the susceptibility tests were carried out using the same method, mainly the mean inhibitory concentration (MIC) plate dilution method. Because sampling studies are labour intensive, the next step was to standardise all bacterial susceptibility testing methods employed by the clinical microbiology laboratories.

Standardised routine susceptibility testing

One of the goals of FiRe, to establish a standard routine susceptibility testing method that yields reliable and comparable results for both diagnostic and epidemiological purposes, was achieved in 1996 (5-8). In principle, this method (FiRe Standard) is equivalent to the National Committee for Clinical Laboratory Standards (NCCLS) disk diffusion method. The interpretative breakpoints for susceptibility and resistance published by NCCLS are used with only a few exceptions and the breakpoints are updated each year. In addition to Mueller Hinton agar, Iso Sensitest agar (Oxoid) is accepted as the susceptibility medium by the FiRe standard method.

The comparability of the susceptibility test results is assessed by comparing the inhibition zone diameter distributions of patient strains and control bacterial strains from different laboratories. The results of such comparisons indicate good agreement between laboratories (unpublished data). The comparability of the results is in most cases good even between laboratories that use different culture media. In addition to these comparisons and routine external quality control programmes, the performance of the FiRe laboratories when testing for types of resistance that can be difficult to detect has been demonstrated by special surveys (5,7). For example, the detection of methicillin resistant Staphylococcus aureus (MRSA) in FiRe laboratories has been studied by three consecutive distributions of a set of S. aureus strains with different degrees of resistance to oxacillin. Susceptibility testing of Haemophilus influenzae is now under way. Such studies help us to recognise the positive and negative features of the FiRe standard and, if necessary and possible, to modify the standard further.

All of the Finnish clinical microbiology laboratories take part in the process of studying and developing the FiRe standard. Diagnostic laboratories provided the impulse for creating a common standard method. The problems and needs that arise in clinical laboratory work are discussed twice a year in meetings of the laboratory representatives, when points to be developed are also agreed.

Bacterial resistance

Bacteria studied in 1998 by the FiRe laboratories showed no big problems in susceptibility, but some worrying developments were found. Firstly, the proportion of Streptococcus pneumoniae with resistance to macrolides is increasing (table). Should this trend continue, the treatment of pneumonia will become more difficult; macrolides are among the drugs recommended for the treatment of community acquired pneumonia. In addition, decreasing susceptibility of salmonella isolates to fluoroquinolones is being seen among isolates of foreign origin (9). We also have grounds for optimism, however, as the prevalence of MRSA has remained low in Finland and multiresistant Mycobacterium tuberculosis is rare. The complete summary of the resistance surveillance by the FiRe network has been published as a part of the FINRES 1999 report (www.mmm.fi/english/veterinary/publications/).

Table. Selected susceptibility test results from the FINRES 1999 report.

Bacterium

Antimicrobial agent

Year   (Nr of strains studied)   resistance %

Streptococcus pneumoniae

Penicillin (I+R)

1988-90

(639)

1,7%

1995

(807)

6,4%

1997

(6106)

4.8%

1998

(5245)

4.7%

Erythromycin

1988-90

0,6%

1995

2,7%

1997

5,3%

1998

6,9%

Haemophilus influenzae

1998

(4576)

Ampicillin

22,8%

Amoxicillin-clavulanic acid

0,5%

Sulphatrimethoprim

13,3%

Tetracyclines

1,7%

Neisseria gonorrhoeae

Ciprofloxacin

1998

(118)

5,1%

Escherichia coli (community urine isolates)

1998

(35113)

Ampicillin

30,3%

Mecillinam

5,9%

Cephalothin

7,3%

Norfloxacin

3,5%

Nitrofurantoin

3,2%

Trimethoprim

23,7%

Salmonella species (foreign isolates)

Ciprofloxacin (MIC 0,125 mg/ml or more)

1995

(100)

3,9%

1996

(200)

4,7%

1997

(100)

10,3%

1998

(100)

16,7%

Salmonella species (domestic isolates)

Ciprofloxacin (MIC 0,125 mg/ml or more)

1995

(100)

0,0%

1996

(200)

1,0%

1997

(100)

4,3%

1998

(100)

2,0%

Enterococcus faecium (hospital isolates)

1998

(1742)

Ampicillin

65,5%

Vancomycin

3,4%

Nitrofurantoin

2,6%

Methicillin resistant Staphylococcus aureus (MRSA)

Blood culture isolates

1997

(746)

0,5%

1998

(717)

0,7%

All isolates and one MRSA per patient

1997

(32 529)

0,4%

1998

(26 677)

0,7%

Mycobacterium tuberculosis

1998

(421)

Isoniazid

2,9%

Rifampicin

1,0%

Streptomycin

1,7%

Ethambutol

0,2%

Isoniazid+rifampicin

0,7%

I = Intermediary resistant, R = Resistant
Our future aim is to adjust the pattern of antimicrobial agents in susceptibility testing to match the current care (Käypä hoito) clinical guidelines supplied by the Finnish Medical Society Duodecim, and by so doing, to support the widely accepted clinical guidelines. Trends in antibiotic prescribing in the community are monitored by the national MIKSTRA-programme (10; www.mikstra.fi). We are studying intensively the correlation of the use of the major antimicrobial agents and the development of resistance in the bacteria that are clinically most important (8). With all these measures we try to control bacterial resistance in Finland and maintain the effect of antimicrobial agents for future generations.

References1. Seppälä H, Nissinen A, Järvinen H, Huovinen S, Henriksson T, Herva E, et al. Emergence of erythromycin resistance in group A streptococci. N Engl J Med 1992; 326: 292-7.

2. Nissinen A, Herva E, Katila M-L, Kontiainen S, Liimatainen O, Oinonen S, et al. Antimicrobial resistance in Haemophilus influenzae isolated from blood, cerebrospinal fluid, middle ear fluid and throat samples of children. A nationwide study in Finland in 1988-1990. Scand J Infect Dis 1995; 27: 57-61.

3. Nissinen A, Leinonen M, Huovinen P, Herva E, Katila M-L, Kontiainen S, et al. Antimicrobial resistance of Streptococcus pneumoniae in Finland, 1987-1990. Clin Infect Dis 1995; 20: 1275-80.

4. Nissinen A, Grönroos P, Huovinen P, Herva E, Katila M-L, Klaukka T, et al. Development of beta-lactamase-mediated resistance to penicillin in pediatric middle-ear isolates of Moraxella catarrhalis in Finland, 1978-1993. Clin Infect Dis 1995; 21: 1193-6.

5. Manninen R, Leinonen M, Huovinen P, Nissinen A and the Finnish Study Group for Antimicrobial Resistance. Reliability of disk diffusion susceptibility testing of Streptococcus pneumoniae and adjustment of laboratory-specific breakpoints. J Antimicrob Chemother 1998; 41: 19-26.

6. Manninen R, Eerola E, Huovinen P. Disk diffusion susceptibility tests; need for laboratory-specific breakpoints. Scand J Infect Dis 1995; 27: 45-9.

7. Nissinen A, Seppälä H, Huovinen P, and the Finnish Study Group for Antimicrobial Resistance (FiRe). Detecting erythromycin resistance in Streptococcus pyogenes: reliability of the disk diffusion method and the breakpoint susceptibility testing method. Scand J Infect Dis 1995; 27: 52-56.

8. Seppälä H, Klaukka T, Vuopio-Varkila J, Muotiala A, Helenius H, Lager K, et al. The effects of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. N Engl J Med 1997; 337: 441-6.

9. Hakanen A, Siitonen A, Kotilainen P, Viljanen M, Huovinen P. Increasing fluoroquinolone resistance in Salmonella serotypes in Finland during 1995-1997. J Antimicrob Chemother 1999; 43: 145-8.

10. Rautakorpi U-M, Lumio J, Huovinen P, Klaukka T. Indication-based use of antimicrobials in Finnish primary health care. Description of a method for data collection and results of its application.Scand J Prim Health Care 1999; 17: 93-9

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