Species identification and antifungal susceptibility testing of Candida bloodstream isolates from population-based surveillance studies in two U.S. cities from 2008 to 2011.

Between 2008 and 2011, population-based candidemia surveillance was conducted in Atlanta, GA, and Baltimore, MD. Surveillance had been previously performed in Atlanta in 1992 to 1993 and in Baltimore in 1998 to 2000, making this the first population-based candidemia surveillance conducted over multiple time points in the United States. From 2,675 identified cases of candidemia in the current surveillance, 2,329 Candida isolates were collected. Candida albicans no longer comprised the majority of isolates but remained the most frequently isolated species (38%), followed by Candida glabrata (29%), Candida parapsilosis (17%), and Candida tropicalis (10%). The species distribution has changed over time; in both Atlanta and Baltimore the proportion of C. albicans isolates decreased, and the proportion of C. glabrata isolates increased, while the proportion of C. parapsilosis isolates increased in Baltimore only. There were 98 multispecies episodes, with C. albicans and C. glabrata the most frequently encountered combination. The new species-specific CLSI Candida MIC breakpoints were applied to these data. With the exception of C. glabrata (11.9% resistant), resistance to fluconazole was very low (2.3% of isolates for C. albicans, 6.2% for C. tropicalis, and 4.1% for C. parapsilosis). There was no change in the proportion of fluconazole resistance between surveillance periods. Overall echinocandin resistance was low (1% of isolates) but was higher for C. glabrata isolates, ranging from 2.1% isolates resistant to caspofungin in Baltimore to 3.1% isolates resistant to anidulafungin in Atlanta. Given the increase at both sites and the higher echinocandin resistance, C. glabrata should be closely monitored in future surveillance.

Incidence of macrolide resistance in Streptococcus pneumoniae after introduction of the pneumococcal conjugate vaccine: population-based assessment.

BACKGROUND: The prevalence of macrolide resistance in Streptococcus pneumoniae has risen in recent years after the introduction of new macrolides and their increased use. We assessed emergence of macrolide-resistant invasive S pneumoniae disease in Atlanta, GA, USA, before and after the licensing, in February 2000, of the heptavalent pneumococcal conjugate vaccine for young children. METHODS: Prospective population-based surveillance was used to obtain pneumococcal isolates and demographic data from patients with invasive pneumococcal disease. We calculated cumulative incidence rates for invasive pneumococcal disease for 1994-2002 using population estimates and census data from the US Census Bureau. FINDINGS: The incidence of invasive pneumococcal disease in Atlanta fell from 30.2 per 100,000 population (mean annual incidence 1994-99) to 13.1 per 100,000 in 2002 (p<0.0001). Striking reductions were seen in children younger than 2 years (82% decrease) and in those 2-4 years (71% decrease), age-groups targeted to receive pneumococcal conjugate vaccine. Significant declines were also noted in adults aged 20-39 (54%), 40-64 (25%), and 65 years and older (39%). Macrolide resistance in invasive S pneumoniae disease in Atlanta, after increasing steadily from 4.5 per 100,000 in 1994 to 9.3 per 100,000 in 1999, fell to 2.9 per 100,000 by 2002. Reductions in disease caused by mefE-mediated and erm-mediated macrolide-resistant isolates of conjugate-vaccine serotypes 6B, 9V, 19F, and 23F, and the vaccine-associated serotype 6A were also recorded. INTERPRETATION: Vaccines can be a powerful strategy for reducing antibiotic resistance in a community.

Decline in Pneumococcal Nasopharyngeal Carriage of Vaccine Serotypes After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Children in Atlanta, Georgia.

BACKGROUND: Streptococcus pneumoniae (SP) serotype distribution among nasopharyngeal (NP) carriage isolates changed significantly after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). We evaluated the impact on NP carriage and invasive disease of SP after the introduction of the 13-valent PCV (PCV13) in March 2010. METHODS: NP swabs were collected from children 6-59 months of age in an emergency department from July 2010 to June 2013. After broth enrichment, samples were cultured for SP and isolates were serotyped. Clinical and immunization records were reviewed. Findings during 6 sequential 6-month study periods were compared. Surveillance isolates of invasive disease isolates were reviewed. RESULTS: A total of 2048 children were enrolled, and 656 (32%) were SP carriers. Mean age of carriers was 27 months, 54% were males. Carriage was higher among day-care attendees (P < 0.01) and children with respiratory tract illnesses (P < 0.5) and otitis media (P < 0.01). Commonly carried serotypes included 35B (15.2%), 15B/C (14.2%), 19A (9.6%), 11A (8%), 23B (5.6%), 6C (5.3%), 21 (5%), and 15A (5%); 13.9% were PCV13 serotypes. The proportion of children with SP carriage remained stable but the serotype distribution changed during the study period. Among carriers, PCV13 serotypes declined from 29% (36/124) to 3% (3/99; P < 0.0001), predominantly because of decline of serotype 19A from 25.8% (32/124) to 3% (3/99; P < 0.0001); non-PCV13 serotypes (excluding 6C) increased from 68.4% (78/114) to 97% (95/98; P < 0.0001); serotype 35B significantly increased from 8.9% (11/124) to 25.3% (25/99; P < 0.05). Nonsusceptibility to ceftriaxone declined from 22.6% (28/124) to 0% (0/99; P < 0.0001), with a similar decline in penicillin nonsusceptibility. CONCLUSIONS: Introduction of PCV13 for universal infant use was associated with significant reductions in nasopharyngeal carriage of PCV13 serotypes and resistant strains. Carriage of non-PCV13 serotypes increased modestly, particularly serotype 35B. Further investigation is warranted to determine whether nonvaccine pneumococcal serotypes carried in the nasopharynx are associated with significant replacement disease.

The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992-2000.

To examine trends in the incidence and epidemiology of cryptococcosis, active, population-based surveillance was conducted during 1992-2000 in 2 areas of the United States (the Atlanta, Georgia, and Houston, Texas, metropolitan areas; combined population, 7.4 million). A total of 1491 incident cases were detected, of which 1322 (89%) occurred in HIV-infected persons. The annual incidence of cryptococcosis per 1000 persons with AIDS decreased significantly during the study period, from 66 in 1992 to 7 in 2000 in the Atlanta area, and from 24 in 1993 to 2 in 1994 in the Houston area. Poisson regression analysis revealed that African American persons with AIDS were more likely than white persons with AIDS to develop disease. Less than one-third of all HIV-infected persons with cryptococcosis were receiving antiretroviral therapy before diagnosis. Our findings suggest that HIV-infected persons who continue to develop cryptococcosis in the era of highly active antiretroviral therapy (HAART) in the United States are those with limited access to health care. More efforts are needed to expand the availability of HAART and routine HIV care services to these persons.

The Georgia Emerging Infections Program: monitoring trends in invasive pneumococcal disease.

The active, population-based surveillance system of the Georgia EIP has provided valuable insights into the characteristics of invasive pneumococcal disease in Georgia and continues to provide an important mechanism to assess the impact of the newly introduced PCV7 vaccine. The problem of antimicrobial resistance has been carefully documented among isolates from invasive pneumococcal disease in all age groups, particularly young children. Fluoroquinolone resistance is now present in our area and will require close monitoring in the coming months and years. Over 80% of invasive pneumococcal disease and over 85% of penicillin and cefotaxime resistant invasive disease occurring in young children in our surveillance area involve serotypes included in the new conjugate vaccine approved for use in children. Preliminary data suggest an early decline in invasive pneumococcal disease in young children has occurred since the introduction of the conjugate vaccine and the effect upon the prevalence of antimicrobial resistance remains to be determined. The high rates of invasive pneumococcal disease, the significant associated morbidity and mortality and antimicrobial resistance highlight the need for enhanced prevention measures in both adults and children. Ongoing surveillance in the Georgia EIP will allow accurate measurement of the impact of prevention efforts, provide essential information on trends in antimicrobial resistance and document any changes in the pneumococcal serotypes responsible for invasive disease in the conjugate vaccine era.

Socioeconomic and racial disparities of pediatric invasive pneumococcal disease after the introduction of the 7-valent pneumococcal conjugate vaccine.

BACKGROUND: Racial differences have been well described for invasive pneumococcal disease (IPD), but little information exists on how race interacts with community socioeconomic factors. METHODS: The Active Bacterial Core surveillance/Emerging Infections Program performed active surveillance for IPD in the 20-county Metropolitan Atlanta area. All IPD cases among children younger than 5 years from 2001 to 2009 were geocoded and linked to census tract-level socioeconomic measures from the 2000 US Census. Race- and socioeconomic-specific average annual incidence rates per 100,000 population were calculated. Trends in IPD incidence were determined by χ² tests for trend. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using Poisson regression. RESULTS: IPD incidence among the total population of children increased as percentage of household poverty increased (P = 0.002), as median household income decreased (P < 0.001), as wealth decreased (P = 0.018) and as percentage of individuals with less than a high school education increased (P = 0.023). After stratifying by race, there was no significant linear trend between socioeconomic characteristics and IPD incidence among white children; among black children, however, IPD incidence decreased as socioeconomic conditions worsened. Despite adjusting for sex and socioeconomic factors, the IPD rate remained higher among black children compared with white children (RR = 1.60; 95% CI: 1.39-1.84). Differences in RR of IPD associated with highest poverty and lowest wealth noted in 2001 [RR = 2.71 (95% CI: 2.17-3.39) and 1.80 (95% CI: 1.09-2.96), respectively] declined in 2009 [RR = 1.33 (95% CI: 0.90-1.96) and 0.76 (95% CI: 0.48-1.19), respectively]. CONCLUSIONS: Although socioeconomic disparities in IPD incidence exist among children, the association between socioeconomic characteristics and IPD rates may differ by race and may change over time. Community-level socioeconomic factors did not account for racial differences in IPD incidence.

Pneumococcal carriage and invasive disease in children before introduction of the 13-valent conjugate vaccine: comparison with the era before 7-valent conjugate vaccine.

BACKGROUND: Nasopharyngeal (NP) carriage and invasive pneumococcal disease (IPD) attributable to serotypes in the 7-valent pneumococcal conjugate vaccine (PCV7) declined dramatically after vaccine introduction, whereas non-PCV7 serotypes increased modestly. Characteristics of pneumococcal carriage and IPD among children in Atlanta, GA, were compared during 2 time periods: before PCV7 introduction and before 13-valent PCV (PCV13) introduction. METHODS: NP swabs from 231 and 451 children 6-59 months old receiving outpatient medical care were obtained in 1995 and 2009, respectively. A total of 202 and 47 IPD cases were identified in children younger than 5 years of age in 1995 and in 2008 to 2009, respectively, through active, population-based surveillance in Atlanta. Isolates were serotyped, sequence-typed (ST) and tested for antimicrobial susceptibility. RESULTS: Forty percent (93/231) of children in 1995 and 31% (139/451) in 2009 were colonized with Streptococcus pneumoniae; 60% and 0.7% were PCV7 serotypes, respectively. In 1995, PCV7 serotypes accounted for 83% and 19A accounted for 5% of IPD compared with no PCV7 serotypes and 19A accounting for 49% of IPD in 2009 (P < 0.001). In 2009, PCV13 serotypes accounted for 22% of carriage (mostly 19A) and 60% of invasive isolates (P < 0.001). ST320 accounted for 66% and 52% of 19A carriage and IPD isolates in 2009, respectively; all ST320 isolates were multidrug-resistant. No ST320 NP or IPD isolates were identified before PCV7. CONCLUSIONS: Serotype distribution among NP and IPD isolates in Atlanta has shifted to non-PCV7 serotypes; 19A was the leading serotype for both. The multidrug-resistant ST320 strain was responsible for two-thirds of 19A carriage isolates and half of IPD isolates. The predominance of serotype 19A in carriage and IPD among children in Atlanta highlights the potential direct and indirect benefits anticipated by implementation of PCV13 in the community.

Effectiveness of the 7-valent pneumococcal conjugate vaccine in children with sickle cell disease in the first decade of life.

BACKGROUND: The incidence of and mortality from invasive pneumococcal disease are significantly higher in children with sickle cell disease than in the general pediatric population. The objective of this population-based study was to assess the effect of pneumococcal conjugate vaccine on rates of invasive pneumococcal disease among children with sickle cell disease. PATIENTS AND METHODS: Records, including the history of pneumococcal conjugate vaccine administration, of 1247 children born after 1983 residing in metropolitan Atlanta, Georgia, with confirmed hemoglobinopathies were linked to an active surveillance database for invasive pneumococcal disease for the period of January 1, 1995, through January 1, 2003. The incidence of invasive pneumococcal disease and the percentage of rate reduction were estimated before and after pneumococcal conjugate vaccine licensure. Survival analysis was used to estimate the effect of pneumococcal conjugate vaccine on invasive pneumococcal disease rates while accounting for herd immunity. RESULTS: A significant decline in invasive pneumococcal disease in children with sickle cell disease < or = 10 years of age was noted after pneumococcal conjugate vaccine licensure, from 1.7 infections per 100 person-years (1995-2000) to 0.5 infections per 100 person-years (2001-2002), which represents a 68% reduction. The effectiveness of > or = 1 dose of pneumococcal conjugate vaccine was estimated by crude analysis to be 84.5% and by stratified survival analysis to be 81.4% when controlling for the presence of herd immunity in the 2 years after pneumococcal conjugate vaccine licensure. Serotype 6A invasive pneumococcal disease represented 36% of invasive pneumococcal disease before pneumococcal conjugate vaccine licensure and 0% after pneumococcal conjugate vaccine licensure, suggesting a protective effect against this pneumococcal conjugate vaccine-related serotype. CONCLUSIONS: Invasive pneumococcal disease significantly decreased in children with sickle cell disease < or = 10 years of age after pneumococcal conjugate vaccine licensure. Pneumococcal conjugate vaccine was effective even when controlling for herd immunity. Extending guideline recommendations for catch-up vaccination beyond 4 years of age should be considered.

Herd immunity and pneumococcal conjugate vaccine: a quantitative model.

Invasive pneumococcal disease in older children and adults declined markedly after introduction in 2000 of the pneumococcal conjugate vaccine for young children. An empirical quantitative model was developed to estimate the herd (indirect) effects on the incidence of invasive disease among persons >or=5 years of age induced by vaccination of young children with 1, 2, or >or=3 doses of the pneumococcal conjugate vaccine, Prevnar (PCV7), containing serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. From 1994 to 2003, cases of invasive pneumococcal disease were prospectively identified in Georgia Health District-3 (eight metropolitan Atlanta counties) by Active Bacterial Core surveillance (ABCs). From 2000 to 2003, vaccine coverage levels of PCV7 for children aged 19-35 months in Fulton and DeKalb counties (of Atlanta) were estimated from the National Immunization Survey (NIS). Based on incidence data and the estimated average number of doses received by 15 months of age, a Poisson regression model was fit, describing the trend in invasive pneumococcal disease in groups not targeted for vaccination (i.e., adults and older children) before and after the introduction of PCV7. Highly significant declines in all the serotypes contained in PCV7 in all unvaccinated populations (5-19, 20-39, 40-64, and >64 years) from 2000 to 2003 were found under the model. No significant change in incidence was seen from 1994 to 1999, indicating rates were stable prior to vaccine introduction. Among unvaccinated persons 5+ years of age, the modeled incidence of disease caused by PCV7 serotypes as a group dropped 38.4%, 62.0%, and 76.6% for 1, 2, and 3 doses, respectively, received on average by the population of children by the time they are 15 months of age. Incidence of serotypes 14 and 23F had consistent significant declines in all unvaccinated age groups. In contrast, the herd immunity effects on vaccine-related serotype 6A incidence were inconsistent. Increasing trends of non-vaccine serotypes, in particular 19A, were noted in most unvaccinated age groups, but these increases were substantially smaller than the concurrent decreases among the vaccine serotypes. Also, the model estimated PCV7 to have a greater (p=0.014) indirect impact on the incidence of invasive pneumococcal disease caused by all vaccine serotypes among African-Americans of all ages than for whites. Thus, conjugate vaccines may be able to induce herd effects even in situations where vaccine coverage is far from complete or with schedules using fewer than 3 or 4 doses. Because the model was based on incidence rates and PCV7 coverage in Atlanta, our findings should be validated in other geographic areas.

Genotype-specific carriage of Neisseria meningitidis in Georgia counties with hyper- and hyposporadic rates of meningococcal disease.

Carriage of Neisseria meningitidis in a Georgia county with hypersporadic incidence of meningococcal disease ("hypersporadic county") and in a county with no cases of meningococcal disease was determined by a cross-sectional pharyngeal culture study of high school students. Among 2730 students from whom culture samples were obtained, meningococcal carriage was 7.7% (140/1818) in the hypersporadic county and 6.1% (56/912) in the comparison county. Carriage rates by serogroup and genetic type (i.e., electrophoretic type [ET]) did not differ significantly between counties, but apartment or mobile home residency was a risk factor for carriage in the hypersporadic county. Although most cases of meningococcal disease in the hypersporadic county were caused by members of the serogroup C ET-37 clonal group, no ET-37 meningococcal isolates were recovered from carriers in this county. However, 38% of all meningococcal isolates recovered from carriers in both counties were members of the serogroup Y ET-508 clonal group, an emerging cause of meningococcal disease in Georgia and throughout the United States during 1996-2001. Shifts in carriage and transmission of meningococcal strains with different pathogenic potential are important determinants of meningococcal disease incidence.

Aggregated antibiograms and monitoring of drug-resistant Streptococcus pneumoniae.

Community-specific antimicrobial susceptibility data may help monitor trends among drug-resistant Streptococcus pneumoniae and guide empiric therapy. Because active, population-based surveillance for invasive pneumococcal disease is accurate but resource intensive, we compared the proportion of penicillin-nonsusceptible isolates obtained from existing antibiograms, a less expensive system, to that obtained from 1 year of active surveillance for Georgia, Tennessee, California, Minnesota, Oregon, Maryland, Connecticut, and New York. For all sites, proportions of penicillin-nonsusceptible isolates from antibiograms were within 10 percentage points (median 3.65) of those from invasive-only isolates obtained through active surveillance. Only 23% of antibiograms distinguished between isolates intermediate and resistant to penicillin; 63% and 57% included susceptibility results for erythromycin and extended-spectrum cephalosporins, respectively. Aggregating existing hospital antibiograms is a simple and relatively accurate way to estimate local prevalence of penicillin-nonsusceptible pneumococcus; however, antibiograms offer limited data on isolates with intermediate and high-level penicillin resistance and isolates resistant to other agents.