Clinical Implications of Antibiotic Resistance in Acute Respiratory Infections

Glavni bakterijski uzročnici respiratornih infekcija Streptococcus pneumoniae, betahemolitički streptokok grupe A (BHS-A), Haemophilus infl uenzae i Moraxella catarrhalis dugo su bili dobro osjetljivi na antibiotike. Široka upotreba antibiotika dovela je, međutim, do razvoja mnogih mehanizama rezistencije na razne antibiotike. U liječenju respiratornih infekcija osobito je bitan razvoj rezistencije na betalaktamske i makrolidne antibiotike. U Hrvatskoj 29% pneumokoka pokazuje umjerenu i 3% visoku rezistenciju na penicilin, dok je na makrolide rezistentno 27% pneumokoka. BHS-A ne pokazuje rezistenciju na penicilin, ali rezistencija na makrolide u Hrvatskoj iznosi 14%. Gotovo svi izolati M. catarrhalis i mnogi sojevi Haemophilusa infl uenzae (10% u Hrvatskoj) proizvode beta-laktamaze, što ih čini rezistentnima na amoksicilin, ali ne i na kombinaciju amoksicilina i inhibitora beta-laktamaza. In vitro osjetljivost uzročnika na antibiotik primijenjen u liječenju bitan je povoljni čimbenik u korist domaćina, no ishod infekcije ovisi i o intrinzičnoj patogenosti uzročnika te obrambenim snagama domaćina. Farmakokinetika (PK) i farmakodinamika (PD) antibiotika može znatno utjecati na djelotvornost in vivo te se PK/PD-parametri sve više prihvaćaju u određivanju doziranja antibiotika i korekciji graničnih koncentracija pri testiranju in vitro. Porast rezistencije na antibiotike među respiratornim patogenima zasada nije doveo do dramatičnog porasta smrtnosti od respiratornih infekcija, no smrtni je ishod samo grubi pokazatelj ishoda infekcije.The major bacterial respiratory pathogens Streptococcus pneumoniae, group A streptococcus (GAS), Haemophilus infl uenzae and Moraxella catarrhalis were considered sensitive to antibiotics for a long time. The overuse of antibiotics has, however, led to the development of numerous resistance mechanisms to various antibiotics. The increasing resistance to beta-lactams and macrolides is of special interest in the treatment of respiratory infections. In Croatia, 29% of pneumococci are moderately and 3% highly resistant to penicillin, while resistance to macrolides is 27%. There is no penicillin resistance in GAS, but resistance to macrolides in Croatia is 14%. Almost all strains of M. catarrhalis and many strains of Haemophilus infl uenzae (10% in Croatia) produce beta-lactamases and are therefore resistant to amoxicillin, but not to the amoxicillin and beta-lactamase inhibitor combinations. In vitro sensitivity of the causing agent is very important for the successful therapy, but the outcome of the disease also depends on the intrinsic virulence of the microorganism and host defence capability. Pharmacokinetic (PK) and pharmacodynamic (PD) parameters signifi cantly infl uence the in vivo effi cacy of an antibiotic and are increasingly used to improve antibiotic dosing and in vitro testing. So far the increase of antibiotic resistance in respiratory pathogens has not been followed by a dramatic increase in mortality due to respiratory infections. However, death is only a crude indicator of the outcome of the disease