Seasonality of antibiotic-resistant streptococcus pneumoniae that causes acute otitis media: a clue for an antibiotic-restriction policy?

Abstract

Background: It is unclear whether reducing antibiotic prescriptions can reduce rates of resistance once resistance becomes prevalent. We attempted to determine whether reduced antibiotic consumption, which is observed yearly in children during the warm season, is associated with a reduction in antibiotic resistance in pneumococcal acute otitis media (AOM).

Methods: Antibiotic prescriptions and resistance were measured prospectively during 1999-2003 in 2 demographically distinct populations: Jewish and Bedouin children (aged <5 years) in southern Israel. Associations were assessed using seasonally clustered logistic regression models.

Results: The study included 236,466 prescriptions and 3609 pneumococcal isolates. Prescription rates decreased during the warm months by 36% and 15% in Jewish and Bedouin children, respectively (P < .001 for the season). Among Jewish children, higher resistance rates were observed during the cold than the warm months (P < .001 for each antibiotic). This difference remained significant after adjustment for age, ethnic group, study year, history of antibiotic use, and serotype. The difference was not observed in Bedouin children.

Conclusions: Rapid seasonal decline in resistant AOM-causing pneumococci occurred only in Jewish children, among whom a marked prescribing seasonality was noted, and not in Bedouin children, among whom prescription was less seasonal. The rapid seasonal decrease in resistance associated with markedly reduced antibiotic use suggests that drug-resistant pneumococci may pay a fitness cost.

Figure 1

Monthly distribution of antibiotic prescriptions for Bedouin and Jewish children <5 years old in southern Israel during 1998−2003. A and B, Monthly antibiotic prescription rates for Jewish (A) and Bedouin (B) children. C and D, Mean monthly antibiotic prescription rates (for individual months averaged across the entire study period) for Jewish (C) and Bedouin (D) children.

Figure 2

Monthly proportions of antibiotic-resistant Streptococcus pneumoniae (of all S. pneumoniae isolates) obtained during acute otitis media episodes from Bedouin and Jewish children aged <5 years in southern Israel from 1999 through 2003. PNSP, penicillin-nonsusceptible S. pneumoniae.

Figure 3

Proportions of antibiotic-resistant Streptococcus pneumoniae (of all S. pneumoniae isolates) obtained during acute otitis media episodes from Bedouin and Jewish children aged <5 years in southern Israel from 1999 through 2003. P values refer to hypothesis tests of an association between the odds of resistance and season (October through March vs. April through September) and were derived from multivariable logistic models. A, Isolates from Jewish children (n = 1401). B, Isolates from Bedouin children (n = 2205).

Figure 4

Relationship between prescription rates and proportions of antibiotic-resistant Streptococcus pneumoniae (of all S. pneumoniae isolates) in children from January 1999 through December 2003. For each month, the prescription rates of amoxicillin plus amoxicillin-clavulanate, azithromycin, and oral cephalosporins are plotted in relation to the respective resistance rates. The 60 months of the study period were divided into warm months (April through September, in red) and cold months (October through March, in blue). P values refer to hypothesis tests of an association between the odds of resistance and season (October through March vs. April through September) and were derived from multivariable logistic models. Odds ratios (ORs) with 95% confidence intervals (in parentheses) for increases of 10 prescriptions/1000 child-months are also provided. J, Jewish children; B, Bedouin children.

Figure 5

Seasonal distribution of common Streptococcus pneumoniae isolates that were penicillin nonsusceptible with a MIC ≥1.0 μg/mL (as a percentage of all S. pneumoniae isolates) obtained during acute otitis media episodes from Bedouin and Jewish children <5 years old in southern Israel from 1999 through 2003. P values refer to hypothesis tests of an association between the odds of resistance and season (October through March vs. April through September) and were derived from multivariable logistic models.

Figure 6

Monthly antibiotic resistance rates of Streptococcus pneumoniae isolates from middle ear fluid of Jewish children aged 6−29 months presenting with acute otitis media (AOM) from January 1999 through December 2003. Each point presents the summation of all isolates for the specific month during the entire 5-year period. P values refer to hypothesis tests of an association between the odds of resistance and season (October through March vs. April through September) and were derived from multivariable logistic models adjusted for history of AOM.