Our S. pneumoniae QC data demonstrate a high degree of correlation for serotyping and antibiotic susceptibility testing between four pneumococcal reference laboratories. One hundred ninety isolates representing 43 serotypes and 29 serogroups were exchanged from 1999 through 2008, with only eight discrepant serotyping results occurring. The overall modal MIC concordance within 1 log2 dilution was 99.3% for penicillin, regardless of the method used. Overall modal MIC concordance for testing by BMD and agar dilution was >96% for all the antibiotics except erythromycin (92.1%) and clindamycin (89.5%). The greatest variance in MIC concordance occurred between the Etest and BMD methods for macrolides and SXT; however, categorical concordance remained high.
Previous reports describing international proficiency testing exercises for antimicrobial susceptibility testing, particularly for the detection of penicillin-nonsusceptible pneumococci, have used the oxacillin disk diffusion screening method (3
). The ICS QC program did not report results for oxacillin disk diffusion screening; however, the rates of modal MIC and categorical concordance were 100% and 99%, respectively, for penicillin, regardless of test method. Similar high levels of concordance were noted in phase II of a Latin American study, where the rates of MIC and categorical concordance for penicillin were 93.3% and 93.6%, respectively, (9
). In another large international quality assurance exercise distributed by the United Kingdom National External Quality Assurance Scheme to the European Antimicrobial Resistance Surveillance System (EARSS) laboratories, concordance for penicillin-nonsusceptible isolates using the MIC method was 94%, whereas it was 79% for non-MIC-based methods (3
). Concordance in the EARSS quality assurance exercise was based on two categories: susceptible and nonsusceptible.
Differences in methodologies while using the BMD and Etest resulted in lower rates of modal MIC concordance for erythromycin (73.9%), clindamycin (65.5%), and SXT (80%). Similar results for erythromycin (68.7%) were reported in the Latin American study (9
). The wide variation in MICs was most likely due to the CO2
environment required for testing of S. pneumoniae
with the Etest. A decrease in the pH of the agar resulting from the CO2
environment decreases the activity of macrolides, producing an elevated MIC (6
Detection of emerging antibiotic resistance is an important function of reference laboratories. Participation in international external quality assurance (EQA) programs may provide insight into resistance rate variability between countries by examining the microbiological procedures being performed in each lab (11
). The isolates selected for the ICS QC panels represented a wide range of MICs to ensure that each laboratory is able to detect resistance and accurately determine MICs, regardless of the method used. Comparison of data is more difficult when different methods are used; however, our MIC data demonstrated very good categorical concordance on the basis of CLSI breakpoints. In the ICS QC program, MIC data (as well as the test method used) are collected to ensure that analysis of the data will be possible over time as changes in the antibiotic breakpoints occur.
Reports describing programs that evaluate pneumococcal serotyping are limited (8
). Konradsen et al. (8
) evaluated the quality of serotyping of pneumococci among 11 reference laboratories in Europe and found a serotype concordance of 95%. An international EQA program developed to monitor and support ongoing laboratory performance of serotyping and antibiotic susceptibility testing for S. pneumoniae
in Latin America found overall rates of serotype concordance of 88% and 93.8% for phase I (1994 to 1998) and phase II (1999 to 2005) of the program, respectively (9
). These results are comparable to the overall serotyping concordance of 95.8% that we identified in the ICS QC program. A total of 38 different serotypes, including three nonencapsulated strains, were selected for the European study (8
), in contrast to the 43 serotypes represented in the ICS comparisons. The types of discrepancies noted in the European study were similar to those reported here and included the assignment of the wrong serotype within a serogroup, the misidentification of nontypeable or rough strains of S. pneumoniae
, not screening for all possible serotypes when cross-reactions with shared factors occur, and some unexplained discrepancies. Few factoring errors were noted in the Latin American EQA program. The two shared-factor serotype discrepancies reported in this study emphasize the importance of screening isolates in all relevant antisera.
Serotyping of invasive isolates provides valuable information concerning the dynamics of pneumococcal disease in relation to vaccine uptake (8
). The assignment of the correct serotype within a serogroup remains vital, as not all serotypes are represented in the current vaccines (8
). Serotype distribution will continue to be an important outcome measure as new generations of capsule-based vaccines are introduced.
The results reported here demonstrate that the ICS S. pneumoniae QC program is a successful collaboration of reference labs which has proven to be sustainable over a span of 9 years. Sharing the workload associated with the selection, distribution, and analysis of the survey panels among the participants is a significant factor in the sustainability of this program. High concordance of both the serotyping and susceptibility results indicates that the reference laboratories are producing high-quality results which are comparable internationally and can detect seroprevalence and antibiotic resistance changes over time.
The ICS QC program has expanded to include other organisms. In 2005, the ICS S. pneumoniae QC program was used as a model to establish the ICS QC program for serotyping of Haemophilus influenzae and serogrouping of Neisseria meningitidis. These QC programs ensure that the quality of microbiological testing of these three important pathogens, all of which cause vaccine-preventable disease, remains high. External QC programs will continue to be a key component of quality surveillance systems.