Penicillin resistance among invasive pneumococci is not common in Finland. Penicillin resistance was detected in only 1.5% of the isolates, and intermediate resistance was detected in 4.0%. Trimethoprim-sulfamethoxazole resistance was the most common type of resistance among the isolates tested, occurring in 7.5% of the isolates; and erythromycin resistance was the second most common, occurring in 6.9% of the isolates. Resistance to tetracycline and chloramphenicol occurred in a few percent of the isolates, but the drugs often used against invasive pneumococcal infections, such as ceftriaxone, vancomycin, and meropenem, have remained effective. Rifampin resistance occurred in very few isolates. Rifampin is a great inducer of mutation-derived resistance, which is the reason why it is not used as a monotherapy in the treatment of patients.
According to our previous study of penicillin-nonsusceptible pneumococci, the MLSB
phenotype is the most common macrolide resistance phenotype in Finland (12
). Interestingly, in the present study, the majority of the macrolide-resistant isolates were of the M phenotype. This is of note, since the MLSB
phenotype has proven to be dominant in several earlier European studies, while the M phenotype has been shown to be dominant in North America (1
). Recently, however, a study from Germany showed that the M phenotype was the most common phenotype among invasive pneumococci in that country as well (14
Seven macrolide-resistant isolates had the MS phenotype and did not carry any of the genes studied. For the three isolates with mutations in 23S rRNA, erythromycin MICs were between 8 and 128 μg/ml, depending of the number of mutated alleles. The telithromycin MICs for those isolates were low. Interestingly, for the isolate with a 12-bp insertion in the gene encoding ribosomal protein L22, the telithromycin MIC was as high as 2 μg/ml. This is of note, as none of the other mutations detected in this study or in a previous study (13
) led to telithromycin MICs this high. In the study by Tait-Kamradt et al. (20
), the telithromycin MIC was 3.12 μg/ml for a pneumococcal isolate with an 18-bp insertion in the gene encoding ribosomal protein L4. Interestingly, in both of these cases, similar kinds of mutations were behind the high MICs.
In Finland, treatment guidelines for meningitis recommend the use of ceftriaxone as the first-line empirical treatment. For defined cases of pneumococcal meningitis, penicillin G is considered the drug of choice for the treatment of infections caused by penicillin-susceptible strains. Penicillin is also regarded as the first-line therapy for defined cases of pneumococcal sepsis or pneumonia. The resistance patterns of invasive pneumococcal isolates detected in this study indicate that these guidelines are still valid in Finland.
The question of empirical treatment for community-acquired pneumonia remains difficult, as penicillin is not effective against Mycoplasma pneumoniae
and Chlamydia pneumoniae
, the two important microbes causing atypical pneumonia. If one of these agents is suspected, macrolides are recommended as the first-line choice for outpatients with pneumonia in Finland. According to this study and data from the Finnish Study Group for Antimicrobial Resistance, both penicillin and macrolide resistance are more common among pneumococci from noninvasive infections (mainly respiratory tract isolates) than among those from invasive infections. In 2000, the rate of penicillin nonsusceptibility was 8% and the rate of macrolide resistance was 11% among all pneumococci in Finland (Finnish Study Group for Antimicrobial Resistance, unpublished data). Typically, macrolide resistance is of a higher grade than penicillin resistance in pneumococci. In particular, the erm
(B) methylase gene and some of the ribosomal gene mutations cause very high grade resistance. Therefore, treatment failures are to be expected if macrolide-resistant pneumococcal pneumonia is treated empirically with macrolides. This may lead to bacteremia and invasive disease. The answer to treatment may well be in the new drugs, such as telithromycin and the new fluoroquinolones, which are still effective against the main causative agents of community-acquired bacterial pneumonia (7
In conclusion, invasive pneumococci were comparably susceptible in Finland in 1999 and 2000. Trimethoprim-sulfamethoxazole and macrolide resistance were the most common, while penicillin nonsusceptibility remained uncommon and multiresistance was rare. Active efflux was the most common macrolide resistance mechanism. Four isolates were found to have ribosomal mutations conferring macrolide resistance. The results of this study indicate that most of the drugs conventionally used against pneumococcal infections are still effective against invasive diseases caused by pneumococci in Finland.