Streptococcus pyogenes Erythromycin Resistance in Italy
To the Editor: Streptococcus pyogenes resistance to erythromycin began to emerge as a serious problem worldwide in the early 1990s. In some areas in Italy, 30% to 40% of strains have beome resistant (1-3). Throughout Italy, the use of macrolides, particularly the newest ones (azithromycin and clarithromycin), has increased in the treatment of infections caused by Group A streptococci. This therapeutic approach is contrary to current guidelines, which recommend using betalactam antibiotics as first-choice therapy and reserving macrolides only for patients allergic to betalactams.
In 1997 in Finland, a decrease was observed in the use of macrolide antibiotics in ambulatory patients from 2.40 defined daily doses per 1,000 inhabitants in 1991 to 1.38 in 1992. Subsequently, the maintenance of doses at 1.28 to 1.74 defined daily doses resulted in a substantial decrease in the percentage of group A streptococcal resistance to erythromycin, reported as 16.5% in 1992, 19% in 1993, 15.6% in 1994, 10% in 1995, and 8.6% in 1996 (4). These data prompted us to evaluate such phenomena in our geographic area, the urban area of Genoa, Italy (approximately 120,000 inhabitants).
From January 1991 to June 1998, 311 (6.1%) of 5,117 strains of S. pyogenes throat swabs from patients with pharyngotonsillitis were isolated. We observed a higher number of group A streptococci isolates from throat swabs starting in 1996 than we had in 1991 to 1995 (chi-square = 35.653, p <0.0001). All isolates were tested for susceptibility to penicillin and erythromycin by standard susceptibility tests (broth microdilution) as recommended by the National Committee for Clinical Laboratory Standards. All isolates were susceptible to penicillin. From 1991 to 1996, the percentage of S. pyogenes resistant or with intermediate resistance to erythromycin increased from 0% to 50% (1992, 6%; 1993, 13%; 1994, 14%; 1995, 24%; 1996, 50%). In 1997 and the first half of 1998, resistance to erythromycin decreased to 39% and 34%, respectively. The number of resistant strains before 1996 was significantly lower than from 1996 to 1998 (chi-square = 50.386, p <0.0001). Analysis of antibiotic consumption in our district showed an increase in the use of macrolides (erythromycin and the new compounds clarithromycin and azithromycin) from 0.445 defined daily dose per 1,000 inhabitants in 1994 to 1.140 in 1996. In 1997 and in the first half of 1998, consumption decreased to 0.9 and 0.8, respectively; we observed a correlation between the number of resistant isolates and the defined daily dose increase (correlation [R2] = 0.795, p = 0.0153).
S. pyogenes resistance to erythromycin rose from 6% to 50% in only 4 years and then rapidly decreased from 50% to 34% in an 18-month period, corresponding to a 57% decrease in defined daily dose (from 1.41 in 1996 to 0.8 in the first half of 1998). Our data suggest that S. pyogenes resistance to erythromycin is associated with frequency of macrolide use.