In this geographically defined population, dramatic changes in the outcome of invasive pneumococcal disease occurred during the past 13 years. We observed a significant decrease in the overall case-fatality rate for IPD, and this was primarily explained by a decrease in the case-fatality rate among adults aged ≥65 years and among patients with invasive pneumonia. In addition, we observed a significant decrease in the mortality rate for IPD over time.
Multiple factors may explain the decreases in the case-fatality and mortality rates for IPD in Olmsted County. Age, sex, and Charlson comorbidity index score were included in our logistic regression model and did not affect the significant association between time and case-fatality rate. Increasing PPV-23 coverage over time and/or PCV-7 coverage (via a herd effect of PCV-7 in adults) may have led to less-severe disease among patients and could have affected the case-fatality rate for IPD. Although we did not know PPV-23 vaccination rates for Olmsted County, estimated PPV-23 coverage among adults aged ≥65 years in Minnesota (based on the Behavioral Risk Factor Surveillance Survey data) increased significantly over time, from 40% in 1995, to 52% in 1999, and to 71% in 2006 [15
]. Among the patients who died of IPD in our study, we did not observe a significant difference in the number of patients who were up to date with PPV-23 vaccination for 1995–1999 versus 2001–2007; however, the absolute numbers were low. Estimated PCV-7 coverage (i.e., receipt of ≥3 doses) in Minnesota (based on National Immunization Survey data) also increased significantly over time, from 48% in 2002, to 77% in 2004, and to 93% in 2006 [16
]. Other factors that may have affected the case-fatality rate for IPD over time include improved hospital care, more rapid antibiotic administration in patients with suspected pneumonia, changes in severity of illness, and/or changes in pneumococcal serotype, although these variables were not measured in our study.
The ABC surveillance team previously published data on the outcome of IPD in adults. They reported a decrease in the mortality rate for IPD (from 6.9 deaths per 100,000 persons in 1998–1999 to 5.7 deaths per 100,000 persons in 2002–2003) in the United States among adults aged ≥50 years; however, the case-fatality rate increased from 15.7% in 1998 to 19.5% in 2003 [7
]. The increase in the case-fatality rate was thought to be related to a higher proportion of patients with comorbidities over time. A recent update using the ABC surveillance database reported an overall IPD case-fatality rate of 10.3% (6500 estimated deaths among 63,067 estimated cases) in 1997–1999, which increased to an overall IPD case-fatality rate of 11.7% (4850 estimated deaths among 41,550 estimated cases) in 2005 (P
<.001, by χ2
]. The reason for the significant difference between the changing case-fatality rate over time in the Olmsted County population (i.e., a decreased IPD case-fatality rate) versus the ABC surveillance population (i.e., an increased IPD case-fatality rate) is not clear; however, many variables probably contribute, including increasing comorbidities in the ABC surveillance population, the different populations studied, and different methods of both case and death ascertainment.
Our study has several important strengths. First, we report IPD outcome data in a different population than the ABC surveillance group; thus, our data may be compared with data for other populations in the United States that are similar to the Olmsted County population. Second, our study was performed in a geographically isolated population in a region where medical care is mainly self-contained in the community, thus allowing essentially complete ascertainment of all IPD cases and accurate outcome data. Incomplete case ascertainment is a potential problem in studies that rely on disease reporting. Third, all original inpatient and outpatient medical records were available for review, allowing us to abstract accurate outcome data. Finally, our study was performed during a 13-year period in a stable population using consistent data abstraction methods.
Our study also has several potential limitations. First, the Olmsted County population is similar to the US white population, and our findings should only be generalized to similar populations in the United States. Second, given the low number of deaths in our study (n = 19), we could not analyze other variables in the logistic regression model that may have been associated with case fatality (such as pneumococcal vaccination and individual comorbidities). Third, although we demonstrated significant decreases in the case-fatality and mortality rates for IPD in Olmsted County, we were unable to study all potential variables that could account for these changes. Additional prospective observational studies are necessary for additional study of these variables. Fourth, although data for 180 (94%) of 191 patients with IPD were available for review, the remaining 11 patients (6%) with IPD did not authorize use of their records for research. This is an unavoidable source of potential bias in all studies, and it could have affected our results if a disproportionate number of patients with IPD who had not authorized the use of their records died in the later time period, although this would be unlikely. Finally, although the culture methods at Mayo Clinic microbiology laboratory remained the same during the 13-year period, the Olmsted Medical Center microbiology laboratory changed from a manual blood culture system to an automated system in 2001; however, this did not likely have a major effect on the number of IPD cases detected.
In conclusion, we observed a significant decrease in the overall case-fatality rate for IPD from 1995–1999 to 2001–2007 in Olmsted County, with the greatest decreases noted among adults aged ≥65 years and among those with invasive pneumonia. In addition, the mortality rate for IPD decreased during these intervals. These findings are novel and deserve additional investigation.