The aim of this study was to investigate the association between regional macrolide resistance in Streptococcus pyogenes and macrolide use in Finland. During 1997-2001, a total of 50,875 S. pyogenes isolates were tested for erythromycin susceptibility in clinical microbiology laboratories throughout Finland. The local erythromycin resistance levels were compared with the regional consumption data of all macrolides pooled and, separately, with the use of azithromycin. The regional resistance rates of 1 year were compared with the regional consumption of the previous year and with the average rates of use for the 2 previous years. A linear mixed model for repeated measures was used in modeling the association. A statistically significant association existed between regional erythromycin resistance in S. pyogenes and consumption of macrolides; association with azithromycin use alone was not found.

Eleven clinical isolates of Streptococcus pneumoniae, isolated in Finland during 1996 to 2000, had an unusual macrolide resistance phenotype. They were resistant to macrolides and streptogramin B but susceptible, intermediate, or low-level resistant to lincosamides. No acquired macrolide resistance genes were detected from the strains. The isolates were found to have mutations in domain V of the 23S rRNA or ribosomal protein L4. Seven isolates had an A2059C mutation in two to four out of the four alleles encoding the 23S rRNA, two isolates had an A2059G mutation in two alleles, one isolate had a C2611G mutation in all four alleles, and one isolate had a 69 GTG 71 -to-69 TPS 71 substitution in ribosomal protein L4.Streptococcus pneumoniae (pneumococcus) is an important pathogen in respiratory tract infections, meningitis, and septicemia both in children and adults. There has been an increase in the prevalence of macrolide-resistant pneumococci over the last decade. In Finland, the prevalence has increased from 0.6% in 1988 to 1990 to 11.2% in 2000 according to the Finnish Study Group for Antimicrobial Resistance (unpublished data [http://www.mmm.fi/elintarvikkeet_elaimet/julkaisut_tiedotteet /finres99en.htm]).In streptococci, there are two well-characterized macrolide resistance mechanisms: target site modification and active drug efflux. Target site modification is mediated by the methylases encoded by the erm (erythromycin ribosome methylation) genes (22,30). Methylation of A2058 of the peptidyl transferase loop of 23S rRNA causes resistance to 14-, 15-, and 16-membered ring macrolides; lincosamides; and streptogramin B: the macrolide-lincosamide-streptogramin B (MLS B ) phenotype (30). The expression of the erm genes can be either constitutive or inducible (31). The active efflux mechanism, encoded by the mef (macrolide efflux) genes, is more specific and causes resistance only to 14-and 15-membered ring macrolides: the M phenotype (3,25).Among Finnish clinical isolates of pneumococci, we found a novel type of macrolide resistance, which did not fit into the two phenotypes described above. These strains were resistant to 14-, 15-, and 16-membered ring macrolides and to streptogramin B and were susceptible, intermediate, or low-level resistant to clindamycin (a lincosamide). Also, these strains did not carry mef(A) or erm(B) resistance genes (9). Tait-Kamradt et al. (26, 27) described mutations in the peptidyl transferase loop of the 23S rRNA and ribosomal protein L4 as a cause of a new resistance type in pneumococci with a similar phenotype. The mutations were obtained first in vitro after subsequent passages in azithromycin-containing broth, and later such mutations were found in clinical isolates. The number of alleles encoding 23S rRNA was confirmed to be four. Mutations in 23S rRNA causing macrolide resistance have been described also in other bacteria such as Propionibacterium and Mycobacterium species (13,18).In this study, we describe a new point mutation in a pneumococcal 23S rRNA-encoding gene as a ca...

The prevalence of isolates of Streptococcus pneumoniae (pneumococcus) that are resistant to antimicrobial agents is increasing globally. We studied the connection between antimicrobial resistance of pneumococci and regional use of antimicrobial agents in Finland. In 1997, a total of 6106 pneumococcal isolates were identified in clinical microbiology laboratories in Finland. Most of the pneumococci were isolated from respiratory tract samples, 8% were from blood culture samples, and 0.5% were from cerebrospinal fluid samples. The regional levels of resistance for pneumococci in 1997 were compared with the regional rates of use of antimicrobial agents from 1995 through 1996. We found that resistance to macrolides correlated highly significantly with macrolide use (P=.006). A significant correlation was also found between resistance to trimethoprim-sulfamethoxazole and trimethoprim-sulfamethoxazole use (P=.043). We did not find a correlation between penicillin resistance and the use of any antimicrobial agent. The positive correlation between macrolide-resistant pneumococci and the use of macrolides is worrying, because macrolides are used worldwide in the treatment of patients with respiratory tract infections, which are often caused by pneumococci.

The resistance patterns and macrolide resistance mechanisms of 910 Finnish invasive pneumococci isolated during 1999 and 2000 were studied. Macrolide resistance was detected in 6.9% of isolates. Penicillin resistance was detected in 1.5% of isolates, and penicillin intermediate resistance was detected in 4.0% of isolates. Active macrolide efflux, mediated by the mef(A) gene, was the most common macrolide resistance mechanism. Four macrolide-resistant isolates had mutations in rRNA or ribosomal protein L22.Streptococcus pneumoniae (pneumococcus) is among the major causative agents of several infectious diseases. In addition to upper respiratory tract infections, it is the most common cause of bacteremic pneumonia and, except during outbreak situations, the most common etiologic agent of bacterial meningitis in adult patients.The prevalence of antimicrobial-resistant pneumococci is on the increase. From a clinical point of view, the resistance of invasive isolates (those from cerebrospinal fluid and blood samples) is of greatest concern, since empirical antimicrobial therapy must be commenced for infections caused by these isolates. To avoid treatment failures, data on the resistance of the most common local causes of meningitis and septicemia should be available.The two most common mechanisms of macrolide resistance in pneumococci are ribosomal methylation caused by the erm(B) gene and active macrolide efflux mediated by the mef(A) gene (19,22). erm(B) causes the macrolide, lincosamide, streptogramin B resistance phenotype (MLS B phenotype), which means that the bacteria are resistant to 14-, 15-, and 16-membered-ring macrolides, lincosamides, and streptogramin B. mef(A) causes resistance to 14-and 15-membered-ring macrolides (M phenotype). In many studies, erm (B) has been shown to be the most common macrolide resistance gene in Europe, while mef(A) has been the most common macrolide resistance gene in North America (1, 4-6, 8-10, 17). Rare macrolide resistance mechanisms in pneumococci are ribosomal mutations and those mediated by the erm(TR) methylase gene (18,20,21).In the work described here, the resistance properties of 910 invasive pneumococci isolated in Finland were studied. The resistance mechanisms of macrolide-resistant isolates were detected. MATERIALS AND METHODSInvasive pneumococci (isolated from blood and cerebrospinal fluid samples) were consecutively collected during 1999 and 2000 from Finnish clinical microbiology laboratories (n ϭ 910 isolates total). Duplicate isolates were excluded from the study by removing repeat isolates recovered from the same patient within a period 3 months of the time of isolation of the first isolate. There were 471 isolates from 1999 and 439 isolates from 2000. The identification of the strains was confirmed by typical colony morphology and hemolysis on blood agar plates (Oxoid Ltd., Basingstoke, England) supplemented with 5% sheep blood. The strains were further tested for optochin susceptibility (Optochin Disk; Oxoid Ltd.), and to confirm unclear results, some o...

The aims of this study were to evaluate the resistance patterns and serotypes/groups of penicillin non-susceptible pneumococci (PNSP) in Finland, and to determine phenotypes and resistance mechanisms of the erythromycin-resistant isolates. A total of 1190 PNSP were collected during 1996-2000 in Finland. The MICs of 18 antimicrobials were determined by the agar plate dilution method, and PCR was used to study the resistance mechanisms of the macrolide-resistant isolates. For serotyping, counterimmunoelectrophoresis and latex agglutination were used. Erythromycin resistance increased from 32% in 1996 to 62% in 2000 among PNSP in Finland. Multiresistance (co-resistance to erythromycin, tetracycline and co-trimoxazole) was present in 22% of the isolates in 1996 and in 40% in 2000. The most common macrolide resistance phenotype was the MLS(B) phenotype (72%), 25% had the M phenotype and 3% the MS phenotype. The MLS(B) and M phenotypes increased in the same proportion during the study period. All the MLS(B) isolates had the erm(B) gene, the M isolates the mef(A) gene, and in 11 MS isolates, ribosomal mutations were the cause of resistance. The most common serotypes/groups were 14, 19 and 6. We found a significant increase in multiresistance among PNSP within a short period of time in Finland. Although pneumococcal resistance to erythromycin was 11% in 2000, the same figure was 50% among the PNSP. The rise in erythromycin resistance is worrying, as macrolides are commonly used as first- and second-line drugs in pneumococcal infections.