The three major Spanish clones of penicillin-resistant Streptococcus pneumoniae are the most common clones recovered in recent cases of meningitis in Spain

Abstract

One hundred six isolates of Streptococcus pneumoniae recovered in Spain from patients with meningitis in 1997 and 1998 were characterized by multilocus sequence typing. A heterogeneous collection of genotypes was associated with meningitis in Spain: 65 different sequence types were resolved and, even at a genetic distance of 0.43, there were 37 distinct lineages. Thirty-eight percent of the isolates, including all isolates of serotypes 6B, 9V, 14, and 23F, were resistant to penicillin, and 24% of the isolates were members of the three major Spanish penicillin-resistant or multidrug-resistant clones of serotypes 6B, 9V, and 23F or serotype variants of these clones. These three clones (MICs, 1 to 2 microg of penicillin/ml) were the most common clones associated with pneumococcal meningitis in Spain during 1997 and 1998. Only two of the other clones associated with meningitis were penicillin resistant (MICs, 0.12 to 0.5 microg/ml). One of the two most prevalent penicillin-susceptible clones causing meningitis (serotype 3) has not been detected outside of Spain, whereas the other (serotype 18C) has been recovered from patients with meningitis in the United Kingdom, The Netherlands, and Denmark. The prevalence of meningitis caused by isolates of the three major Spanish penicillin-resistant or multiply antibiotic-resistant clones, which are now globally distributed, is disturbing and clearly establishes their ability to cause life-threatening disease.

FIG. 1

Dendrogram showing the relatedness of pneumococci from patients with meningitis. The dendrogram was constructed by the UPGMA method from the matrix of differences in the allelic profiles of the 106 isolates. STs that contain at least three isolates are labeled. Isolates that are resistant to penicillin are marked as follows: ∗, MIC = 0.12 or 0.25 μg/ml; ∗∗, MIC = 0.5 or 1 μg/ml; ∗∗∗, MIC > 1 μg/ml. The rectangles show clusters of closely related STs that, with three exceptions, expressed the same serotype. The serotypes of the isolates of these STs are shown, and the numbers of isolates with the serotypes are shown in parentheses. The cross-hatched rectangles denote the three major penicillin-resistant or multiply antibiotic-resistant clones (Spain^23F-1, Spain^6B-2, and France^9V-3). The serotypes of the penicillin-resistant isolates that have unique STs, including the isolates assigned to the Spain¹⁴-5 clone, are indicated.