Temporal trends of invasive Streptococcus pneumoniae serotypes and antimicrobial resistance patterns in Spain from 1979 to 2007

Abstract

Temporal trends of serotypes from invasive pneumococcal disease (IPD) in Spain from 1979 to September 2007 under antibiotic and vaccine pressure were analyzed. A significant trend in pneumococcal conjugate 7-valent vaccine (PCV7) serotypes (except serotype 4) was found, whereby the prevalence increased from the early 1980s and decreased in the 2000s for all but serotype 23F, which began decreasing in the late 1980s. Among the major non-PCV7 serotypes, a significant decrease was observed for serotypes 1, 5, and 7F in the 1980s. From the late 1990s, serotypes 1, 5, 6A, 7F, and 19A increased significantly, while serotypes 3 and 8 showed similar but nonsignificant trends over time. The incidence of IPD cases was 10.7/100,000 for the period 1996 to 2006, with reporting coverage ranging from 18% to 43%. A significant decrease in IPD incidence due to PCV7 serotypes was observed, while the incidence of non-PCV7 serotypes increased, with the consequence that there was no clear pattern in the overall incidence of IPD. Penicillin nonsusceptibility was correlated with the proportion of PCV7 serotypes. Erythromycin nonsusceptibility increased in association with long-half-life macrolide consumption and then decreased in 2004 to 2007. The increase in PCV7 serotypes and antibiotic nonsusceptibility related to antibiotic consumption in the 1980s and 1990s was reversed in the 2000s, probably as a result of PCV7 immunization. The decrease in IPD incidence due to PCV7 serotypes was mirrored by an increase in that of non-PCV7 serotypes. The impact of various preventive/therapeutic strategies on pneumococcal evolution is serotype dependent, and the dynamics remain unpredictable.

FIG. 1.

Temporal trends of serotypes that were included (a) and the most prevalent serotypes not included (b) in PCV7 among invasive isolates, 1979 to 2007. Best fits were always with a cubic function. The statistical information is as follows: serotype 4, r² = 0.207, P = 0.115; serotype 6B, r² = 0.457, P = 0.001; serotype 9V, r² = 0.686, P < 0.001; serotype 14, r² = 0.758, P < 0.001; serotype 18C, r² = 0.483, P = 0.001; serotype 19F, r² = 0.533, P < 0.001; serotype 23F, r² = 0.672, P < 0.001; serotype 1, r² = 0.841, P < 0.001; serotype 3, r² = 0.145, P = 0.262; serotype 5, r² = 0.530, P = 0.023; serotype 6A, r² = 0.371, P = 0.008; serotype 7F, r² = 0.676, P < 0.001; serotype 8, r² = 0.213, P = 0.106; serotype 19A, r² = 0.855, P < 0.001.

FIG. 2.

PCV7 serotype and penicillin/erythromycin resistance patterns, 1979 to 2007.

FIG. 3.

Non-PCV7 serotype and penicillin/erythromycin resistance patterns, 1979 to 2007.

FIG. 4.

Serotypes and nonsusceptibility to antibiotics in relation to antibiotic consumption and PCV7 distribution. (a) Antibiotic consumption (DDD/1,000 inhabitants/day and doses/1,000 inhabitants ≤59 months of age/year), 1979 to 2007. Symbols: solid line with open squares, aminopenicillins; solid line with filled diamonds, oral cephalosporins; solid line with asterisks, t.i.d. macrolides; dashed line with filled circles, b.i.d. macrolides; dashed line with filled triangles, o.d. macrolides; solid line with open circles, fluoroquinolones; dashed line with open squares, PCV7 distribution. (b) Percentages (bars) of serotypes included in PCV7 among invasive isolates and percentages of penicillin (filled squares) and erythromycin (asterisks) nonsusceptibility among invasive isolates, 1979 to 2007.

FIG. 5.

Numbers of IPD cases annually, per epidemiological year: all serotypes, PCV7 serotypes, and nonvaccine serotypes. (a) Crude numbers. (b) Numbers adjusted for ascertainment (31).