[Streptococcus pneumoniae and beta-lactam antibiotic agents]. / Streptococcus pneumoniae i beta-laktaminski antibiotiski lekovi.

Pneumococcus has been known for over 100 years. Despite an intensive research, the problem of pneumococcal diseases has not yet been solved. During the last few decades, the incidence of pneumococcal pneumonia has declined, but the S. pneumoniae is today the main, or one of the most frequent, causative agents of meningitis, sinusitis, otitis media and conjunctivitis. Besides, cases of pneumococcal appendicitis, tubo-ovarian abscess, haemolytico-uremic syndrome, cellulitis and urinary infections have been described. Therefore, it is very important from medical point of view to follow-up its sensitivity to antibacterial drugs. Unfortunately, during the latest decades, an increase in percentage of resistant clinical isolates has been registered. It is obvious that the investigation of the sensitivity of pneumococci, that is, of their resistance to beta-lactam antibiotics is essential. The examination of the interaction between pneumococci and penicillin has resulted in significant discoveries concerning the mechanism of the effect of penicillin as well as the impact of penicillin-binding proteins, lipoteichoic acid and choline-residues in the cell wall. A particular contribution as regards the effect of penicillin has been achieved by linking murein hydrolases (autolythic enzymes) with the expression of bactericidal effect of penicillin. Besides, the model of pneumococcal resistance to penicillin together with the model of meticillin resistance of staphylococci enabled the perception of the new mechanism of bacteria resistance to beta-lactam antibiotics. Given the pathogenic potential of pneumococci and the increase of clinical isolates resistant to antibiotics, it can be concluded that immunoprophylaxis is of great importance. Although several polyvalent vaccines are being used, there are still unsolved problems whose solution will improve the safety of their application, contribute to a better efficiency and enable a widespread application of antipneumococcal vaccines.

[Is penicillin still the drug of choice in the treatment of diseases caused by beta-hemolytic streptococci?]. / Da li je penicilin jos lek izbora u lecenju oboljenja izazvanih beta-hemolytickim streptokokama?

During the last ten years a new pathomorphosis of streptococci was noticed and described in the USA, Europe and New Zealand. It was expressed by the rise of virulence of beta haemolytic streptococci (BHS) and development of new clinical and epidemiological features. In such circumstances it appears to be very relevant to examine the susceptibility of BHS to penicillin, which is still considered as a drug of choice for the most of streptococcal diseases. Therefore it was decided: 1. to make an analysis of continuous susceptibility testing of BHS to penicillin and 2. to test the possibility of induction and selection of penicillin resistant mutants in vitro. Penicillin susceptibility was examined by broth dilution method Penicillin tolerant strains were separated on the basis of MBC/MIC ratio MBC/MIC > 16 and construction of "killing curves". The possibility of induction and selection of penicillin resistant mutants was tested by subcultivation technique. MIC values for BHS groups: A, B, C and G were: 0.015, 0.060, 0.015 and 0.030 micrograms/ml respectively. The percentage of penicillin tolerant strains was in the range of 3% for group A BHS to 33% for group G BHS. After 60 subcultures in liquid medium containing increasing concentrations of penicillin. MIC values were raised by 2-32 times in comparison with parental strains. As the maximal induced MIC values were 1 and 2 micrograms/ml (one group G and three groups B BHS strains) it can be concluded that BHS at least in vitro expressed penicillin resistance. Although the obtained results are encouraging (there is so far no penicillin resistant clinical isolates), the increasing percent of penicillin tolerant strains and the possibility to induce penicillin resistance in vitro should be considered as a very serious warning. That makes further investigation of the development of penicillin tolerance and resistance mechanisms very current.