Antti Nissinen

Resistance to Erythromycin in Group A Streptococci

BACKGROUND The use of erythromycin in Finland nearly tripled from 1979 to 1989. In 1988, we observed an unusually high frequency of resistance to erythromycin in group A streptococci in one geographic region. Because routine testing does not detect the sensitivity of these organisms to antibiotics, we initiated a national study to evaluate the extent of this resistance. METHODS We studied 272 isolates of group A streptococci obtained from blood cultures from 1988 through 1990. In 1990 we collected from six regional laboratories 3087 consecutive isolates from throat swabs and 1349 isolates from pus samples. Resistance was indicated by growth on blood agar containing 2 micrograms of erythromycin per milliliter after incubation in 5 percent carbon dioxide. We also evaluated the clinical importance of erythromycin resistance in a retrospective study of consecutive patients with pharyngitis. RESULTS The frequency of resistance to erythromycin in group A streptococci from blood cultures increased from 4 percent in 1988 to 24 percent in 1990. From January to December 1990, the frequency of resistance in isolates from throat swabs increased from 7 percent to 20 percent, and resistance in isolates from pus increased from 11 percent to 31 percent. In four communities within 50 km of each other, the frequency of erythromycin resistance ranged from 2 to 5 percent to 26 to 44 percent. Several distinct DNA restriction profiles and serotypes were found among resistant isolates from the same area, suggesting a multiclonal origin. The treatment of pharyngitis with erythromycin failed in 9 of 19 patients infected with erythromycin-resistant group A streptococci, as compared with 1 of 26 patients with erythromycin-susceptible isolates (47 percent vs. 4 percent, P = 0.008). CONCLUSIONS In Finland since 1988 there has been a rapid and substantial increase in resistance to erythromycin in group A streptococci. The extent of this resistance is particularly serious since there are only a few alternative antibiotics available for peroral treatment of group A streptococcal infections.

Antimicrobial resistance in Neisseria gonorrhoeae in Finland, 1976 to 1995

Background and Objectives: The worldwide increase in antimicrobial resistance in Neisseria gonorrhoeae prompted the authors to evaluate the status and course of resistance in gonococci in Finland. Goals: The minimal inhibitory concentrations (MIC) of penicillin, tetracycline, spectinomycin, ciprofloxacin, ceftriaxone, and cefixime were tested for 337 consecutive clinicalN. gonorrhoeae isolates collected in 19 Finnish microbiology laboratories in 1993. Study Design: The results were compared with data obtained in three Finnish laboratories in 1986 and contrasted with the development of the incidence of gonorrhea and the prevalence of penicillinase‐producing N. gonorrhoeae (PPNG) in Finland, 1976 to 1995. The number of strains with an elevated MIC to ciprofloxacin was assessed by questionnaire. Results: A decrease, from more than 50% in 1986 to 20% in 1993, of strains susceptible to penicillin and tetracycline was observed. The prevalence of PPNG increased from 0% (1976) to 5.7% (1995). In 1995, two strains with a ciprofloxacin MIC of ≥ 32 μg/ml were reported. No resistance to ceftriaxone or spectinomycin was detected. Conclusions: In spite of the rarity of gonorrhea and the avail‐ability of efficient antimicrobials in Finland, monitoring of the antimicrobial resistance of N. gonorrhoeae remains important.

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

A nation-wide survey of the prevalence of antimicrobial resistance in Haemophilus influenzae was conducted on isolates collected in 1988-90 from middle ear fluid (MEF), blood, or cerebrospinal fluid (CSF) in infected children or throat samples of healthy children. Altogether 885 strains were examined regarding capsular type b, beta-lactamase production and the minimal inhibitory concentration (MIC) of ampicillin, cefaclor, erythromycin, tetracycline, chloramphenicol, trimethoprim and trimethoprim-sulfamethoxazole for these strains was determined by the agar dilution method. 99% (578/585) of MEF isolates, 93% (112/121) of throat isolates, but only 6% (10/179) of blood/CSF isolates were not of type b (Hib). The rate of beta-lactamase production was 11.4% among Hib strains, 8.0% among non-type b MEF isolates, and 4.5% among non-type b throat isolates. No increase in the prevalence of beta-lactamase production in H. influenzae has taken place in Finland since the early 1980s. Resistance to ampicillin among strains that lacked beta-lactamase activity was rare (0.2%). Of the non-type b MEF and throat isolates, 5.9% and 2.7%, respectively, were resistant to trimethoprim and 3.6% and 2.7%, respectively, to trimethoprim-sulfamethoxazole. Resistance to other drugs was rare (< 2%) in all isolate groups.

Detecting Erythromycin Resistance in Streptococcus pyogenes: Reliability of the Disk Diffusion Method and the Breakpoint Susceptibility Testing Method

Erythromycin susceptibility of clinical Streptococcus pyogenes isolates was determined at 19 Finnish clinical microbiology laboratories by their routine disk diffusion method and by a screening method adapted from the breakpoint susceptibility testing method. Results obtained at 12 laboratories using 4 major variants of the disk method were further evaluated. From these laboratories, 286 consecutive resistant and 349 consecutive susceptible isolates were sent to the Antimicrobial Research Laboratory, Turku where the MIC of erythromycin was determined. 96% and 97% of the disk results were correct, as compared with MIC results, when general and laboratory-specific breakpoints, respectively, were used. The results of the screening method were comparable to those of the disk method.

Clinical microbiology laboratories do not always detect resistance of Haemophilus influenzae with disk or tablet diffusion methods

The performance of disk diffusion testing of Haemophilus influenzae was evaluated in 20 laboratories. Thirteen disk‐medium‐breakpoint‐inoculum modifications were used in Finnish clinical microbiology laboratories. The performance of various methods was evaluated by testing a susceptible control strain and one with non‐β‐lactamase‐mediated ampicillin resistance 10 times in 16 laboratories. Gaps in millimeters were measured between these two groups of results. The strains were separated by a gap of at least 5 mm in 8/16 laboratories testing ampicillin, in 7/15 laboratories testing cefaclor, in 5/16 laboratories testing cefuroxime, and in 15/16 laboratories testing trimethoprim‐sulfa. Detection of ampicillin resistance was better with 2.5 μg tablets than with 10 μg disks or 33 μg tablets. For MIC‐determinations, 785 isolates and their disk diffusion results were collected. None of the 12 clinical isolates with non‐β‐lactamase‐mediated ampicillin resistance was detected as resistant in the participating laboratories. The ampicillin and cefaclor results of the isolates were no better even when a laboratory was able to separate the control strains. Cefaclor results were unreliable because of poor disk diffusion‐MIC correspondence and incoherent breakpoint references. Interlaboratory variation of the zone diameters caused false intermediate results of cefuroxime‐susceptible strains. When ampicillin, cefaclor and cefuroxime were tested, the discrimination of laboratories using disks and tablets was equal, whereas the laboratories using paper disks were better able to detect trimethoprim‐sulfa resistance.

Antimicrobial susceptibility testing of Streptococcus pneumoniae and Haemophilus influenzae – Internal quality control as a quality tool on a national level

Knowledge of the quality and conformity of antimicrobial resistance data is important for comparing resistance rates regionally and over time. In this study, we have evaluated these features of the Finnish national susceptibility surveillance data for two respiratory tract pathogens, Streptococcus pneumoniae and Haemophilus influenzae. For this purpose internal quality control results for two isolates (S. pneumoniae ATCC 49619 and H. influenzae ATCC 49247) were analyzed from 21 clinical microbiology laboratories over a 3‐year period. The results show that standardization of the susceptibility testing methods has proceeded well. The number of protocols used for susceptibility testing has declined (from seventeen methods to two with S. pneumoniae and from eleven to three with H. influenzae) and the reproducibility is good. Nevertheless, we noticed that a few laboratories test and report susceptibility results without defined break‐points and even include antimicrobials with questionable therapeutic effect. Another non‐compliance with the standard was a lack of a regular control system to verify the attainment of the intended quality of results in some laboratories. Interlaboratory analysis of quality control results is a good way to evaluate the quality and conformity of national resistance data. Finnish laboratories have produced very reproducible and accurate susceptibility results in the pre‐EUCAST period, which ended in 2011.

Le Groupe de Travail Finlandais sur la Résistance Antimicrobienne (FiRe)

Cree en 1991, le reseau FiRe (Finnish Study Group for Antimicrobial Resistance) a mis au point une methode standardisee de routine pour tester la sensibilite des bacteries aux antibiotiques. Cette methode permet d’obtenir des resultats fiables et comparables que ce soit a des fins diagnostiques ou epidemiologiques. D’apres les derniers resultats, la proportion de Streptococcus pneumoniae resistant aux macrolides est en augmentation et on observe une baisse de sensibilite aux fluoroquinolones dans les souches de salmonella d’origine etrangere. Cependant, la prevalence des SARM demeure faible en Finlande et Mycobacterium tuberculosis multiresistant est rare.