The relationship between macrolide resistance in Streptococcus pneumoniae and consumption of oral macrolides in Republic of Croatia and City of Zagreb

The aim of this study was to investigate the relationship between increased resistance of Streptococcus pneumoniae to macrolides and use of macrolides in Croatia from 2001 to 2008, with the special emphasis on differences in outpatient consumption of macrolides in City of Zagreb and total consumption in Republic of Croatia. Zagreb Institute of Public Health in collaboration with Croatian Drug Agency collected and analyzed data on outpatient consumption of drugs by use of standardized methods of drug monitoring. The number of defined daily doses (DDD) and DDD per 1000 inhabitants per day (DDD/1000/day) was calculated. Upper respiratory isolates of S. pneumoniae were collected and antibiotics susceptibility was tested during October, November and December in the eight year study period. The City of Zagreb led in drug consumption in Croatia according to counties, followed by Sibenik-Knin County and Dubrovnik-Neretva County. Outpatient utilization of macrolides was high in the City of Zagreb and varied from 4.67 in 2001 to 3.98 DDD/1000/day in 2008, while in the rest of Croatia varied from 2.12 to 2.92 DDD/1000/day. The observed macrolide resistance in S. pneumoniae significantly raised in 2005 in the City of Zagreb from 22 to 39%, and in 2008 was 38%. The significant increase in macrolide resistance in the rest of Croatia was observed in 2007 and 2008, from 25% in 2005 to 34% in 2007 and 40% in 2008. Further study is needed to clear whether the clonal spreading of resistant strains from Zagreb to other parts of Croatia is responsible for increasing macrolide resistance in Croatia, or genetically unrelated strains caused the high macrolide resistance due to increased macrolide consumption at national level.