Two-decade trends in primary Helicobacter pylori resistance to antibiotics in Bulgaria

Evaluating long-term trends in antibiotic resistance can predict earlier the short-term changes in resistance patterns. The aim of the present study was to compare primary resistance rates in 501 Helicobacter pylori strains in 2007 to 2009 to those in 1990 to 1995 (179 strains) and the antibiotic MICs to detect the 20-year resistance evolution. In 2007 to 2009, strains from children exhibited lower resistance rates to metronidazole (16.4%) and ciprofloxacin (2.7%) than those from adults (27.3% and 10.3%, respectively). In 2008 to 2009, more children (29.3%) harbored clarithromycin-resistant strains compared to the adults (17.4%). Overall clarithromycin resistance rate (19.4%) in 2007 to 2009 was much higher than that in 1990 to 1995 (6.2%). MIC90 of erythromycin in 1990 to 1995 was 142.2-fold lower than that of clarithromycin in 2007 to 2009. Clarithromycin MIC90 increased >42-fold since 2001 to 2004. Quinolone resistance rate increased 7.7-fold, being 9.2% in 2007 to 2009 versus 1.2% in 1990 to 1995, with a 5-fold increase in MIC90. Conversely, the amoxicillin resistance decreased from 3.2% in 1996 to 1999 to 0.4% in 2007 to 2009. The MIC90's of tetracycline remained stable but MIC50's of both metronidazole and tetracycline before 1996 decreased about 4-fold to 2007 to 2009. In conclusion, associations between the resistance evolution and patients' age groups as well as the national outpatient antibiotic use have been found. H. pylori resistance to antibiotics showed many long-term changes, with a more rapid evolution for clarithromycin than for the other antibiotics. Metronidazole and tetracycline did not show a resistance evolution but exhibited a decrease in MIC50 since 1990. The significant increase in ciprofloxacin resistance was found only by extending the study period to 20 years.