Studies on emergence and spread of antibiotic resistant Streptococcus pneumoniae

Sammanfattning: 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 south-west 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.