Studies on emergence and spread of antibiotic resistant Streptococcus pneumoniae

Streptococcus pneumoniae is one of the major contributors to mortality and morbidity around the world. It causes a wide variety of diseases ranging from uncomplicated respiratory infections to life-threatening invasive infections such as meningitis and septicemia. In recent years, the effectiveness of antibiotic therapy has been hampered by the increasing rates of resistant pneumococci. As antibiotic resistance increases, there is a growing need for interventions that minimize opportunities for development and spread of resistant pneumococci. The aim of this thesis was to learn more about emergence and spread of antibiotic resistant pneumococci using both theoretical and empirical methods.

Since the increasing prevalence of resistant pneumococci is mainly due to the spread of strains belonging to few clones, interventions for controlling pneumococcal transmission in the community were studied. Model predictions suggested that interventions for efficiently control organism transmission should include reduction of group sizes in the day-care centers. Simulations also indicated that it appears extremely difficult to reduce the rates of penicillin non-susceptible pneumococci by simply decreasing the penicillin consumption assumed that reduced penicillin susceptibility does not imply a fitness cost for the organism. Managing the penicillin resistance rates in pneumococci then probably requires a more restrictive use of penicillin together with other control measures such as vaccine programs. Although clonal spread is the primary mechanism for the rapid emergence of resistance in pneumococci, natural competence for genetic transformation also seems to be involved. Further molecular understanding of competence regulation is important to be able to prevent horizontal spread of resistance genes. Studying the competence regulation by theoretical means led to the conclusion that down-regulation of competence is probably caused by a repressor acting on the comCDE operon at the level of transcription.

Despite the globally emerging frequency of resistant pneumococci, we conclude in a prospective study that antimicrobial resistance in invasive pneumococci in southwest Sweden remains limited. Any correlations between resistance pattern and clinical parameters could not be revealed. However, the serotype distribution was observed to differ between strains with reduced susceptibility and fully susceptible strains as isolates with decreased susceptibility more frequently belonged to the serotypes included in the 7-valent vaccine.

List of scientific papers

I. Karlsson D, Jansson A, Normark BH, Nilsson P (2008). "An individual-based network model to evaluate interventions for controlling pneumococcal transmission" BMC Infect Dis 8: 83
https://pubmed.ncbi.nlm.nih.gov/18559109

II. Karlsson D (2010). "Probabilistic network modelling of the impact of penicillin consumption on pneumococcal spreading." (Submitted)

III. Karlsson D, Karlsson S, Gustafsson E, Normark BH, Nilsson P (2007). "Modeling the regulation of the competence-evoking quorum sensing network in Streptococcus pneumoniae." Biosystems 90: 211-223
https://pubmed.ncbi.nlm.nih.gov/17011700

IV. Backhaus E, Berg S, Trollfors B, Andersson R, Persson E, Claesson BE, Larsson P, Ek E, Jonsson L, Rådberg G, Johansson S, Ripa T, Karlsson D, Andersson K. (2007). "Antimicrobial susceptibility of invasive pneumococcal isolates from a region in south-west Sweden 1998-2001" Scand J Infect Dis 39: 19-27
https://pubmed.ncbi.nlm.nih.gov/17366008