Monica M. Farley

Risk Factors for Group B Streptococcal Disease in Adults

Group B streptococcus (Streptococcus agalactiae), a major cause of neonatal sepsis and meningitis in the United States, is an important cause of invasive bacterial infection in adults. An estimated 7600 cases of group B streptococcal disease occur annually among persons 15 years of age and older in the United States [1]; the incidence among those 60 years of age or older is 18/100 000 persons per year [2]. Among nonpregnant adults, skin and soft-tissue infections and bacteremia of uncertain source are the most common manifestations of invasive disease. The clinical spectrum also includes urosepsis, pneumonia, peritonitis, meningitis, septic arthritis, and endocarditis [2]. Despite nearly universal sensitivity of the organism to penicillin [3, 4], approximately 20% of cases of adult group B streptococcal disease are fatal [2]. Previous case series have indicated that chronic underlying conditions such as diabetes mellitus, cancer, and alcoholism are common among adults with group B streptococcal disease [5-11]. Reports of population-based studies have indicated that the rate of disease is significantly higher among persons with diabetes mellitus [2, 12], human immunodeficiency virus (HIV) infection [2], and cancer [2, 12]. These studies have also indicated that a substantial proportion of adult infections are nosocomially acquired. However, the magnitude of risk associated with specific patient characteristics has not been evaluated in a controlled study adjusting for the effect of multiple factors. In addition, specific determinants of community-acquired and nosocomial disease have not been assessed. Vaccines currently being developed for the prevention of neonatal group B streptococcal disease [13-16] may also be considered for the prevention of invasive infection in adults. Better knowledge of determinants of adult disease could be used to target such preventive efforts most effectively. We therefore did a casecontrol study comparing nonpregnant adults who had invasive group B streptococcal disease with patients hospitalized for other conditions. We report specific underlying conditions that were associated with community-acquired and nosocomial group B streptococcal infection and discuss the implications of these findings for the potential use of future vaccines. Methods Identification of Cases Active surveillance for invasive group B streptococcal infection was done in 1991 and 1992 in an aggregate population of 6.6 million persons using previously described methods [1]. The population included all residents of three counties in California (Alameda, Contra Costa, and San Francisco); eight counties in Georgia (Cobb, Clayton, Dekalb, Douglas, Fulton, Gwinnett, Newton, and Rockdale); and Baltimore City and Baltimore County, Maryland. Briefly, regional surveillance staff made biweekly calls to infection-control practitioners or designated contacts in the microbiology laboratories serving all acute-care hospitals in the surveillance areas for reports of sterile-site (for example, blood or cerebrospinal fluid) isolates of group B streptococcus. A case report form requesting information on demographic characteristics, site of isolation, and clinical syndrome was completed for each identified case. To ensure complete reporting, periodic audits of all laboratories were done. A case of invasive adult group B streptococcal disease was defined as isolation of group B streptococcus from a normally sterile site in a resident of a surveillance area who was 18 years of age or older and who was not pregnant or postpartum. If group B streptococcus was first isolated from a specimen obtained 2 or more days after hospital admission, the case was defined as nosocomial. Cases with positive cultures obtained from 1 June 1991 to 30 June 1992 in California and Georgia and from 1 November 1991 to 31 October 1992 in Maryland were eligible for inclusion. Selection of Controls For each case-patient, a listing of all patients hospitalized on the same day and of the hospital service to which they were admitted was obtained and reviewed. Controls were selected by identifying the three preceding patients admitted to the same general service (for example, medicine instead of oncology or surgery instead of orthopedic surgery) as the case-patient. If three appropriate controls could not be identified, admission lists for previous days were sequentially reviewed until three controls for each case-patient were enrolled. Data Collection We used standardized forms to abstract medical records for case-patients and controls. Information on demographic variables, outcome, outpatient medications, presenting signs and symptoms, underlying conditions, and the clinical syndrome associated with group B streptococcal infection was collected. For all cases, isolation of group B streptococcus from a sterile site was documented and information on isolation of other organisms from blood was obtained. For nosocomial cases, additional information was obtained on medications administered and procedures done in the hospital before the first positive group B streptococcal specimen was collected. For controls matched to case-patients with nosocomial infection, this additional information was abstracted for the same number of days after admission as for the matched case-patient. Statistical Analysis We used the chi-square test to compare proportions of categorical variables among case-patients. We did matched univariate and multiple conditional logistic regression analyses [17] using the Statistical Analysis System procedure PHREG [18] to estimate the risk for group B streptococcal disease associated with individual underlying conditions and exposures. Potential interaction among the variables associated with disease was evaluated by including two-way interaction and main-effect terms in multivariate models. We used stepwise selection, incorporating variables that were significant (P < equals 0.05) in the univariate analysis, to identify a final model for nosocomial disease. To ensure that the risk associated with the underlying conditions was assessed after we controlled for age, we forced a categorical variable that coded for age into the community-acquired model and then used stepwise selection to determine the other variables in the final model. Results Chart abstractions were completed for 219 of the 290 (76%) case-patients identified by surveillance (97 from Baltimore, 72 from the San Francisco metropolitan area, and 50 from the Atlanta metropolitan area) and for 645 matched controls from 54 hospitals (2.9 controls per case-patient). Seventy-one case-patients identified by surveillance were not included in the study for the following reasons: the hospital chart was not available for review (50 case-patients), the hospital did not participate in the study (9 case-patients), a sterile-site group B streptococcal culture could not be documented (5 case-patients), the patient was not admitted to the hospital (3 case-patients), the hospital closed (2 case-patients), or the patient died in the emergency department (2 case-patients). Information from the surveillance case report form indicates that the age and sex distribution and mortality rate of the cases not included did not significantly differ from those of the case-patients included in the study. Proportions of case-patients and controls with selected demographic characteristics and underlying medical conditions are listed in Table 1. The age range for case-patients was 22 to 99 years (median age, 68 years), and the age range for controls was 18 to 99 years (median age, 60 years). Case-patients who died during the hospitalization that was studied died a median of 5 days after collection of the specimen from which group B streptococcus was isolated (range, 0 to 187 days). Table 1. Characteristics and Selected Underlying Medical Conditions Reported for Nonpregnant Adults with Invasive Group B Streptococcal Infection and Hospital-Matched Controls Characteristics of Invasive Group B Streptococcal Disease Site of Isolation Group B streptococcus was isolated from blood in 201 cases (92%). Other sites of isolation included synovial fluid (6 cases), peritoneal fluid (6 cases), pleural fluid (4 cases), and cerebrospinal fluid (2 cases). It was also isolated from an abscess, bone, bone marrow, bronchial washing, intervertebral disc-space fluid, gall bladder, and liver tissue (1 case each). More than one site of isolation could be reported for each case. Polymicrobial Bacteremia Polymicrobial bacteremia, defined as the isolation of other bacterial species from blood cultures collected on the same day as a positive blood culture for group B streptococcus, was identified in 53 of 201 case-patients (26%) with group B streptococcal bacteremia. Staphylococcus aureus was isolated from 24 case-patients and was the only additional organism isolated from 17 case-patients. The age distribution, mortality rate, and proportion of nosocomial cases were similar between case-patients with polymicrobial bacteremia and those with bacteremia caused only by group B streptococcus. Clinical Syndromes The clinical syndromes associated with group B streptococcal infection in case-patients are listed in Table 2. Seven of the 19 case-patients with cellulitis were women with a history of breast cancer in whom cellulitis was associated with invasive group B streptococcal infection. Five of these 7 case-patients had cellulitis of the arm or chest wall on the side of a mastectomy done 3 months to 12 years before admission, 1 had cellulitis of the chest wall opposite the site of the previous mastectomy, and 1 had cellulitis of the arm after axillary node dissection. Table 2. Clinical Syndromes Associated with Group B Streptococcal Infection among 219 Nonpregnant Adults Characteristics Associated with In-Hospital Death Age was associated with in-hospital mortality. Case-patients 65 years of age or older were significantly more likely to die of group

Invasive Group A Streptococcal Disease in Metropolitan Atlanta: A Population-Based Assessment

Active, population-based surveillance for invasive group A streptococcal (GAS) disease was conducted in laboratories in metropolitan Atlanta from 1 January 1994 through 30 June 1995. Clinical and laboratory records were reviewed and isolates characterized. One hundred and eighty-three cases of invasive GAS disease were identified (annual incidence, 5.2 cases/100,000). The incidence was highest among blacks (9.7/100,000 per year; relative risk (RR), 1.92; confidence interval (CI), 1.69-2.19; P < .0001) and the elderly, particularly nursing home residents (RR, 13.66; CI, 7.07-26.40; P < .0001). The mean age of patients was 41.3 years (range, 0-95 years). Skin and soft-tissue infections were most common. Mortality was 14.4%; risk of death was significantly higher for patients with streptococcal toxic shock syndrome (STSS) (RR, 9.73; CI, 3.34-29; P = .0008) and individuals infected with M-type 1 (RR, 7.40; CI, 1.5-16; P = .0084). Fourteen percent of invasive GAS infections were STSS and 3% were necrotizing fasciitis. Invasive GAS disease was associated with varicella infection in children (RR, 12.19; CI, 5.58-26.62; P < .0001). M (or emm) types included M1 (16%), M12 (12%), and M3 (11%). Continued study of GAS disease is essential to further define risk factors and risk of secondary cases and to develop effective prevention strategies.

Determining the Burden of Human Illness From Food Borne Diseases: CDC’s Emerging Infectious Disease Program Food Borne Diseases Active Surveillance Network (FoodNet)

Food borne diseases cause a significant burden of illness in the United States. The Food Borne Diseases Active Surveillance Network (FoodNet), established in 1995, continues to monitor the burden and causes of food borne diseases and provide much of the data to address this public health problem.

Dramatic Decrease in the Incidence of Salmonella Serotype Enteritidis Infections in 5 FoodNet Sites: 1996–1999

Salmonella serotype Enteritidis (SE) emerged as the most common Salmonella serotype among infected persons in the United States during the 1980s and 1990s, with infections reaching a peak in 1995. During the past decade, farm-to-table control measures have been instituted in the United States, particularly in regions with the highest incidence of SE infection. We report trends in the incidence of SE in the 5 original surveillance areas of the Foodborne Diseases Active Surveillance Network during 1996-1999: Minnesota, Oregon, and selected counties in California, Connecticut, and Georgia. Overall, the incidence of SE decreased 46% from 1996 to 1999. The greatest decrease was in Connecticut (71%), followed by northern California (50%), Minnesota (46%), and Oregon (13%). Although SE infection remains an important public health concern, there has been a remarkable decrease in its incidence. This decrease may be a result of targeted interventions, including on-farm control measures, refrigeration, and education efforts.

Recurrent Invasive Pneumococcal Disease: A Population-Based Assessment

We sought to define the risk of recurrence of invasive pneumococcal disease (IPD) and to define the characteristics of persons experiencing recurrent IPD through population-based surveillance. Cases of IPD were identified through the US Centers for Disease Control and Preventions Active Bacterial Core Surveillance. Recurrent episodes were defined as isolation of Streptococcus pneumoniae from any normally sterile site > or =30 days after initial positive culture. Among 13,924 persons who survived their initial episode of IPD, 318 (2.3%) experienced > or =1 subsequent episode, for 376 total recurrences. The recurrence rate was 1294 episodes per 100,000 person-years, or 50 times the annual incidence of IPD. In multivariable analysis, a higher risk of recurrence was seen in persons infected with human immunodeficiency virus and in children <5 years old with chronic illness. Most (92%) persons with recurrence had a vaccine indication. The risk of recurrence among certain persons with IPD is extremely high.

Population-Based Surveillance for Yersinia enterocolitica Infections in FoodNet Sites, 1996–1999: Higher Risk of Disease in Infants and Minority Populations

Active surveillance for laboratory-confirmed Yersinia enterocolitica (YE) infections was conducted at 5 Foodborne Diseases Active Surveillance Network (FoodNet) sites in the United States during 1996-1999. The annual incidence averaged 0.9 cases/100,000 population. After adjusting for missing data, the average annual incidence by race/ethnicity was 3.2 cases/100,000 population among black persons, 1.5 cases/100,000 population among Asian persons, 0.6 cases/100,000 population among Hispanic persons, and 0.4 cases/100,000 population among white persons. Incidence increased with decreasing age in all race/ethnicity groups. Black infants had the highest incidence (141.9 cases/100,000 population; range, 8.7 cases/100,000 population in Minnesota to 207.0 cases/100,000 population in Georgia). Seasonal variations in incidence, with a marked peak in December, were noted only among black persons. YE infections should be suspected in black children with gastroenteritis, particularly during November-February. Culturing for YE should be part of routine testing of stool specimens by clinical laboratories serving populations at risk, especially during the winter months.