Prevention of antibiotic-nonsusceptible Streptococcus pneumoniae with conjugate vaccines.

BACKGROUND: Streptococcus pneumoniae (pneumococcus) caused approximately 44000 US invasive pneumococcal disease (IPD) cases in 2008. Antibiotic nonsusceptibility complicates IPD treatment. Using penicillin susceptibility breakpoints adopted in 2008, we evaluated antibiotic-nonsusceptible IPD trends in light of the introductions of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 and a 13-valent pneumococcal conjugate vaccine (PCV13) in 2010. METHODS: IPD cases were defined by isolation of pneumococcus from a normally sterile site in individuals residing in Active Bacterial Core surveillance (ABCs) areas during 1998-2008. Pneumococci were serotyped and tested for antibiotic susceptibility using broth microdilution. RESULTS: During 1998-2008, ABCs identified 43198 IPD cases. Penicillin-nonsusceptible strains caused 6%-14% of IPD cases, depending on age. Between 1998-1999 and 2008, penicillin-nonsusceptible IPD rates declined 64% for children aged <5 years (12.1-4.4 cases per 100000), and 45% for adults aged ≥65 (4.8-2.6 cases per 100000). Rates of IPD nonsusceptible to multiple antibiotics mirrored these trends. During 2007-2008, serotypes in PCV13 but not PCV7 caused 78%-97% of penicillin-nonsusceptible IPD, depending on age. CONCLUSIONS: Antibiotic-nonsusceptible IPD rates remain below pre-PCV7 rates for children <5 and adults ≥65 years old. PCV13 vaccines hold promise for further nonsusceptibility reductions.

Impact of USA300 methicillin-resistant Staphylococcus aureus on clinical outcomes of patients with pneumonia or central line-associated bloodstream infections.

BACKGROUND: The USA300 methicillin-resistant Staphylococcus aureus (MRSA) strain, which initially emerged as a cause of community-associated infections, has recently become an important pathogen in healthcare-associated infections (HAIs). However, its impact on patient outcomes has not been well studied. We evaluated patients with invasive MRSA infections to assess differences in outcomes between infections caused by USA100 and those caused by USA300. METHODS: Population-based data for invasive MRSA infections were used to identify 2 cohorts: (1) nondialysis patients with central line-associated bloodstream infections (CLABSIs) and (2) patients with community-onset pneumonia (PNEUMO) during 2005-2007 from 6 US metropolitan areas. Medical records of patients with confirmed MRSA USA100 or USA300 infection were reviewed. Logistic regression and, when appropriate, survival analysis was performed to evaluate mortality, early and late complications, and length of stay. RESULTS: A total of 236 and 100 patients were included in the CLABSI and PNEUMO cohorts, respectively. USA300 was the only independent predictor of early complications for PNEUMO patients (odds ratio [OR], 2.6; P = .02). Independent predictors of CLABSI late complications included intensive care unit (ICU) admission before MRSA culture (adjusted OR [AOR], 2.1; P= .01) and Charlson comorbidity index (AOR, 2.6; P = .003), but not strain type. PNEUMO patients were significantly more likely to die if they were older (P = .02), black (P < .001), or infected with USA100 strain (P = .02), whereas those with CLABSI were more likely to die if they were older (P < .001), had comorbidities (P < .001), or had an ICU admission before MRSA culture (P = .001). CONCLUSIONS: USA300 was associated with early complications in PNEUMO patients. However, it was not associated with mortality for either PNEUMO or CLABSI patients. Concerns regarding higher mortality from HAIs caused by USA300 may not be warranted.

Invasive pneumococcal disease and pandemic (H1N1) 2009, Denver, Colorado, USA.

Pneumococcal pneumonia was a complication during previous influenza pandemics but was not evident initially during pandemic (H1N1) 2009. During October 2009 in Denver, Colorado, USA, invasive pneumococcal disease (IPD) and pandemic (H1N1) 2009 peaked simultaneously, which suggests a link. We compared cases of IPD in October 2009 with cases in February 2009, the most recent peak month of seasonal influenza. During October 2009, we observed 58 IPD cases, which was 3× the average number of IPD cases that usually occur in October in Denver. Patients with IPD in October 2009 were younger and more likely to have chronic lung disease than patients who had IPD in February 2009; a total of 10/47 patients had influenza, and 33/53 patients had influenza-like illness. Thus, ≈17%-62% cases of IPD may have been associated with pandemic (H1N1) 2009. Pneumococcal disease prevention strategies should be emphasized during future influenza pandemics.

Revisiting the need for vaccine prevention of late-onset neonatal group B streptococcal disease: a multistate, population-based analysis.

BACKGROUND: Intrapartum antibiotic prophylaxis for neonatal group B streptococcal disease (GBS) effectively prevents disease among infants <7 days old, but there are no prevention strategies for late-onset GBS disease (onset on days 7-89 of life). We describe trends in late-onset GBS over a 16-year period to characterize disease burden and estimate vaccine preventability. METHODS: We conducted active, population-based surveillance for invasive late-onset GBS disease in 10 states from 1990 to 2005. A case was defined by GBS isolation from a normally sterile site on day 7-89 of life in a surveillance area resident. Incidence rates were calculated per 1000 resident live births. RESULTS: We identified 1726 cases; 26% presented with meningitis, and the case fatality ratio was 4.3%. Incidence was similar throughout the study period. Incidence among black infants was approximately 3 times that among non-black infants; the disparity persisted when data were stratified by gestational age. We estimate approximately 1300 cases of late-onset GBS occur annually in the United States. Birth at <37 weeks gestation was common among case-infants (49%) and was associated with elevated case fatality (relative risk: 3.8; 95% confidence interval: 1.1-13.2). Of 653 serotyped isolates, serotypes III (53%), IA (24%), and V (13%) predominated. During 2003-2005, 81 (36%) of the 227 cases caused by serotypes III, IA, and V were born before 34 weeks gestation. CONCLUSIONS: The late-onset GBS disease burden remains substantial. A trivalent vaccine could be an effective prevention strategy. Because many cases were born preterm, reducing the opportunity for transplacental antibody transfer, adolescent immunization should be considered.

Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case-control study.

BACKGROUND: When seven-valent pneumococcal conjugate vaccine was introduced in the USA, many children were vaccinated on schedules that differed from those tested in clinical trials. Our aim was to assess the effectiveness of the vaccine against various pneumococcal serotypes, and to measure the effectiveness of the recommended dose schedule and of catch-up and incomplete schedules. METHODS: Invasive disease, defined as isolation of pneumococcus from a sterile site, was identified in children aged 3-59 months through the US Centers for Disease Control and Prevention's Active Bacterial Core surveillance. We tested isolates for serotype and antimicrobial susceptibility. Three controls, matched for age and zip code were selected for each case. We calculated the matched odds ratio for vaccination using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness was calculated as one minus the adjusted matched odds ratio times 100%. FINDINGS: We enrolled 782 cases and 2512 controls. Effectiveness of one or more doses against vaccine serotypes was 96% (95% CI 93-98) in healthy children and 81% (57-92) in those with coexisting disorders. It was 76% (63-85) against infections that were not susceptible to penicillin. Vaccination prevented disease caused by all seven vaccine serotypes, and by vaccine-related serotype 6A. Several schedules were more protective than no vaccination; three infant doses with a booster were more protective against vaccine-type disease than were three infant doses alone (p=0.0323). INTERPRETATION: The seven-valent pneumococcal conjugate vaccine prevents invasive disease in both healthy and chronically ill children. The vaccine is effective when used with various non-standard schedules.

An assessment of the screening method to evaluate vaccine effectiveness: the case of 7-valent pneumococcal conjugate vaccine in the United States.

The screening method, which employs readily available data, is an inexpensive and quick means of estimating vaccine effectiveness (VE). We compared estimates of effectiveness of heptavalent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) using the screening and case-control methods. Cases were children aged 19-35 months with pneumococcus isolated from normally sterile sites residing in Active Bacterial Core surveillance areas in the United States. Case-control VE was estimated for 2001-2004 by comparing the odds of vaccination among cases and community controls. Screening-method VE for 2001-2009 was estimated by comparing the proportion of cases vaccinated to National Immunization Survey-derived coverage among the general population. To evaluate the plausibility of screening-method VE findings, we estimated attack rates among vaccinated and unvaccinated persons. We identified 1,154 children with IPD. Annual population PCV7 coverage with ≥1 dose increased from 38% to 97%. Case-control VE for ≥1 dose was estimated as 75% against all-serotype IPD (annual range: 35-83%) and 91% for PCV7-type IPD (annual range: 65-100%). By the screening method, the overall VE was 86% for ≥1 dose (annual range: -240-70%) against all-serotype IPD and 94% (annual range: 62-97%) against PCV7-type IPD. As cases of PCV7-type IPD declined during 2001-2005, estimated attack rates for all-serotype IPD among vaccinated and unvaccinated individuals became less consistent than what would be expected with the estimated effectiveness of PCV7. The screening method yields estimates of VE that are highly dependent on the time period during which it is used and the choice of outcome. The method should be used cautiously to evaluate VE of PCVs.

Use of surveillance data to estimate the effectiveness of the 7-valent conjugate pneumococcal vaccine in children less than 5 years of age over a 9 year period.

BACKGROUND: Case-control studies evaluating post-licensure effectiveness of conjugate vaccines can be laborious and costly. We applied an indirect cohort method to evaluate the effectiveness of seven-valent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) and compared the results to the effectiveness measured using a standard case-control study conducted during the same time period. METHODS: IPD cases among children 2-59 months old were identified through the Active Bacterial Core surveillance system during 2001-2009. We used logistic regression to calculate the odds ratio of vaccination (versus no vaccination) among cases (PCV7-type IPD cases) and non-cases (non-PCV7-type IPD cases), controlling for the presence of underlying conditions. Vaccine effectiveness (VE) was calculated as one minus the adjusted odds ratio. RESULTS: Among 4225 IPD cases reported during 2001-2009, 2680 (63%) had serotype information and vaccine history. Effectiveness of ≥ 1 dose of PCV7 against PCV7-types was 88% (95% confidence interval (CI) 78-94%) among children with comorbid conditions and 97% (95% CI 92-98%) among healthy children. Among healthy children, VE was higher in 2001-2003 (97%, 95% CI 95-98%) compared to 2004-2009 (81%, 95% CI 64-90%). The annual estimates of VE in 2004-2009 showed great variability and wide confidence intervals due to the small number of PCV7-type cases. CONCLUSIONS: An indirect cohort design using IPD surveillance data confirms the findings of the case-control study and, therefore, appears suitable for estimating PCV7 effectiveness. This method would be most useful shortly after vaccine introduction, and less useful in a setting of very high vaccine coverage and fewer vaccine-type cases.

Population snapshot of emergent Streptococcus pneumoniae serotype 19A in the United States, 2005.

BACKGROUND: Serotype 19A invasive pneumococcal disease (IPD) increased annually in the United States after the introduction of the 7-valent conjugate vaccine (PCV7). To understand this increase, we characterized serotype 19A isolates recovered during 2005. METHODS: IPD cases during 1998-2005 were identified through population-based surveillance. We performed susceptibility testing and multilocus sequence typing on 528 (95%) of 554 serotype 19A isolates reported in 2005. RESULTS: The incidence of IPD due to serotype 19A increased from 0.8 to 2.5 cases per 100,000 population between 1998 and 2005 (P < .05), whereas the overall incidence of IPD decreased from 24.4 to 13.8 cases per 100,000 population (P < .05). Simultaneously, the incidence of IPD due to penicillin-resistant 19A isolates increased from 6.7% to 35% (P < .0001). Of 151 penicillin-resistant 19A isolates, 111 (73.5%) belonged to the rapidly emerging clonal complex 320, which is related to multidrug-resistant Taiwan(19F)-14. The remaining penicillin-resistant strains were highly related to other clones of PCV7 serotypes or to isolates within major 19A clonal complex 199 (CC199). In 1999, only CC199 and 3 minor clones were apparent among serotype 19A isolates. During 2005, 11 multiple-isolate clonal sets were detected, including capsular switch variants of a serotype 4 clone. CONCLUSIONS: PCV7 ineffectiveness against serotype 19A, antibiotic resistance, clonal expansion and emergence, and capsular switching have contributed to the genetic diversity of 19A and to its emergence as the predominant invasive pneumococcal serotype in the United States.