Lee H. Harrison

Bacterial Meningitis in the United States in 1995

BACKGROUND Before the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants. METHODS Data were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance. RESULTS On the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria monocytogenes, 0.2; and H. influenzae, 0.2. Group B streptococcus was the predominant pathogen among newborns, N. meningitidis among children 2 to 18 years old, and S. pneumoniae among adults. Pneumococcal meningitis had the highest case fatality rate (21 percent) and in 36 percent of cases was caused by organisms that were not susceptible to penicillin. From these data, we estimate that 5755 cases of bacterial meningitis were caused by these five pathogens in the United States in 1995, as compared with 12,920 cases in 1986, a reduction of 55 percent. The median age of persons with bacterial meningitis increased greatly, from 15 months in 1986 to 25 years in 1995, largely as a result of a 94 percent reduction in the number of cases of H. influenzae meningitis. CONCLUSIONS Because of the vaccine-related decline in meningitis due to H. influenzae type b, bacterial meningitis in the United States is now a disease predominantly of adults rather than of infants and young children.

Sustained Reductions in Invasive Pneumococcal Disease in the Era of Conjugate Vaccine

BACKGROUND Changes in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children. METHODS Laboratory-confirmed IPD cases were identified during 1998-2007 by 8 active population-based surveillance sites. We compared overall, age group-specific, syndrome-specific, and serotype group-specific IPD incidence in 2007 with that in 1998-1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations. RESULTS Overall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively (P< .01 all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively (P< .01 for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups (P< .05), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006-2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old. CONCLUSIONS Dramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD.

Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis.

BACKGROUND Group B streptococcal infections are a leading cause of neonatal mortality, and they also affect pregnant women and the elderly. Many cases of the disease in newborns can be prevented by the administration of prophylactic intrapartum antibiotics. In the 1990s, prevention efforts increased. In 1996, consensus guidelines recommended use of either a risk-based or a screening-based approach to identify candidates for intrapartum antibiotics. To assess the effects of the preventive efforts, we analyzed trends in the incidence of group B streptococcal disease from 1993 to 1998. METHODS Active, population-based surveillance was conducted in selected counties of eight states. A case was defined by the isolation of group B streptococci from a normally sterile site. Census and live-birth data were used to calculate the race-specific incidence of disease; national projections were adjusted for race. RESULTS Disease in infants less than seven days old accounted for 20 percent of all 7867 group B streptococcal infections. The incidence of early-onset neonatal infections decreased by 65 percent, from 1.7 per 1000 live births in 1993 to 0.6 per 1000 in 1998. The excess incidence of early-onset disease in black infants, as compared with white infants, decreased by 75 percent. Projecting our findings to the entire United States, we estimate that 3900 early-onset infections and 200 neonatal deaths were prevented in 1998 by the use of intrapartum antibiotics. Among pregnant girls and women, the incidence of invasive group B streptococcal disease declined by 21 percent. The incidence among nonpregnant adults did not decline. CONCLUSIONS Over a six-year period, there has been a substantial decline in the incidence of group B streptococcal disease in newborns, including a major reduction in the excess incidence of these infections in black infants. These improvements coincide with the efforts to prevent perinatal disease by the wider use of prophylactic intrapartum antibiotics.

Cigarette Smoking and Invasive Pneumococcal Disease

Background Approximately half of otherwise healthy adults with invasive pneumococcal disease are cigarette smokers. We conducted a population-based case–control study to assess the importance of cigarette smoking and other factors as risk factors for pneumococcal infections. Methods We identified immunocompetent patients who were 18 to 64 years old and who had invasive pneumococcal disease (as defined by the isolation of Streptococcus pneumoniae from a normally sterile site) by active surveillance of laboratories in metropolitan Atlanta, Baltimore, and Toronto. Telephone interviews were conducted with 228 patients and 301 control subjects who were reached by random-digit dialing. Results Fifty-eight percent of the patients and 24 percent of the control subjects were current smokers. Invasive pneumococcal disease was associated with cigarette smoking (odds ratio, 4.1; 95 percent confidence interval, 2.4 to 7.3) and with passive smoking among nonsmokers (odds ratio, 2.5; 95 percent confidence interval, 1.2 ...

A large outbreak of Clostridium difficile‐associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased Fluoroquinolone use

BACKGROUND AND OBJECTIVE Fluoroquinolones have not been frequently implicated as a cause of Clostridium difficile outbreaks. Nosocomial C. difficile infections increased from 2.7 to 6.8 cases per 1000 discharges (P < .001). During the first 2 years of the outbreak, there were 253 nosocomial C. difficile infections; of these, 26 resulted in colectomy and 18 resulted in death. We conducted an investigation of a large C. difficile outbreak in our hospital to identify risk factors and characterize the outbreak. METHODS A retrospective case-control study of case-patients with C. difficile infection from January 2000 through April 2001 and control-patients matched by date of hospital admission, type of medical service, and length of stay; an analysis of inpatient antibiotic use; and antibiotic susceptibility testing and molecular subtyping of isolates were performed. RESULTS On logistic regression analysis, clindamycin (odds ratio [OR], 4.8; 95% confidence interval [CI95], 1.9-12.0), ceftriaxone (OR, 5.4; CI95, 1.8-15.8), and levofloxacin (OR, 2.0; CI95, 1.2-3.3) were independently associated with infection. The etiologic fractions for these three agents were 10.0%, 6.7%, and 30.8%, respectively. Fluoroquinolone use increased before the onset of the outbreak (P < .001); 59% of case-patients and 41% of control-patients had received this antibiotic class. The outbreak was polyclonal, although 52% of isolates belonged to two highly related molecular subtypes. CONCLUSIONS Exposure to levofloxacin was an independent risk factor for C. difficile-associated diarrhea and appeared to contribute substantially to the outbreak. Restricted use of levofloxacin and the other implicated antibiotics may be required to control the outbreak

Incidence of Bloodstream Infections Due to Candida Species and In Vitro Susceptibilities of Isolates Collected from 1998 to 2000 in a Population-Based Active Surveillance Program

ABSTRACT To determine the incidence of Candida bloodstream infections (BSI) and antifungal drug resistance, population-based active laboratory surveillance was conducted from October 1998 through September 2000 in two areas of the United States (Baltimore, Md., and the state of Connecticut; combined population, 4.7 million). A total of 1,143 cases were detected, for an average adjusted annual incidence of 10 per 100,000 population or 1.5 per 10,000 hospital days. In 28% of patients, Candida BSI developed prior to or on the day of admission; only 36% of patients were in an intensive care unit at the time of diagnosis. No fewer than 78% of patients had a central catheter in place at the time of diagnosis, and 50% had undergone surgery within the previous 3 months. Candida albicans comprised 45% of the isolates, followed by C. glabrata (24%), C. parapsilosis (13%), and C. tropicalis (12%). Only 1.2% of C. albicans isolates were resistant to fluconazole (MIC, ≥64 μg/ml), compared to 7% of C. glabrata isolates and 6% of C. tropicalis isolates. Only 0.9% of C. albicans isolates were resistant to itraconazole (MIC, ≥1 μg/ml), compared to 19.5% of C. glabrata isolates and 6% of C. tropicalis isolates. Only 4.3% of C. albicans isolates were resistant to flucytosine (MIC, ≥32 μg/ml), compared to <1% of C. parapsilosis and C. tropicalis isolates and no C. glabrata isolates. As determined by E-test, the MICs of amphotericin B were ≥0.38 μg/ml for 10% of Candida isolates, ≥1 μg/ml for 1.7% of isolates, and ≥2 μg/ml for 0.4% of isolates. Our findings highlight changes in the epidemiology of Candida BSI in the 1990s and provide a basis upon which to conduct further studies of selected high-risk subpopulations.

Epidemiology of Invasive Group B Streptococcal Disease in the United States, 1999-2005

CONTEXT Group B streptococcus is a leading infectious cause of morbidity in newborns and causes substantial disease in elderly individuals. Guidelines for prevention of perinatal disease through intrapartum chemoprophylaxis were revised in 2002. Candidate vaccines are under development. OBJECTIVE To describe disease trends among populations that might benefit from vaccination and among newborns during a period of evolving prevention strategies. DESIGN AND SETTING Analysis of active, population-based surveillance in 10 states participating in the Active Bacterial Core surveillance/Emerging Infections Program Network. MAIN OUTCOME MEASURES Age- and race-specific incidence of invasive group B streptococcal disease. RESULTS There were 14,573 cases of invasive group B streptococcal disease during 1999-2005, including 1348 deaths. The incidence of invasive group B streptococcal disease among infants from birth through 6 days decreased from 0.47 per 1000 live births in 1999-2001 to 0.34 per 1000 live births in 2003-2005 (P < .001), a relative reduction of 27% (95% confidence interval [CI], 16%-37%). Incidence remained stable among infants aged 7 through 89 days (mean, 0.34 per 1000 live births) and pregnant women (mean, 0.12 per 1000 live births). Among persons aged 15 through 64 years, disease incidence increased from 3.4 per 100,000 population in 1999 to 5.0 per 100,000 in 2005 (chi2(1) for trend, 57; P < .001), a relative increase of 48% (95% CI, 32%-65%). Among adults 65 years or older, incidence increased from 21.5 per 100,000 to 26.0 per 100,000 (chi2(1) for trend, 15; P < .001), a relative increase of 20% (95% CI, 8%-35%). All 4882 isolates tested were susceptible to penicillin, ampicillin, and vancomycin, but 32% and 15% were resistant to erythromycin and clindamycin, respectively. Serotypes Ia, Ib, II, III, and V accounted for 96% of neonatal cases and 88% of adult cases. CONCLUSIONS Among infants from birth through 6 days, the incidence of group B streptococcal disease was lower in 2003-2005 relative to 1999-2001. This reduction coincided with the release of revised disease prevention guidelines in 2002. However, the disease burden in adults is substantial and increased significantly during the study period.

Global epidemiology of meningococcal disease

As reviewed in this paper, meningococcal disease epidemiology varies substantially by geographic area and time. The disease can occur as sporadic cases, outbreaks, and large epidemics. Surveillance is crucial for understanding meningococcal disease epidemiology, as well as the need for and impact of vaccination. Despite limited data from some regions of the world and constant change, current meningococcal disease epidemiology can be summarized by region. By far the highest incidence of meningococcal disease occurs in the meningitis belt of sub-Saharan Africa. During epidemics, the incidence can approach 1000 per 100,000, or 1% of the population. Serogroup A has been the most important serogroup in this region. However, serogroup C disease has also occurred, as has serogroup X disease and, most recently, serogroup W-135 disease. In the Americas, the reported incidence of disease, in the range of 0.3-4 cases per 100,000 population, is much lower than in the meningitis belt. In addition, in some countries such as the United States, the incidence is at an historical low. The bulk of the disease in the Americas is caused by serogroups C and B, although serogroup Y causes a substantial proportion of infections in some countries and W-135 is becoming increasingly problematic as well. The majority of meningococcal disease in European countries, which ranges in incidence from 0.2 to 14 cases per 100,000, is caused by serogroup B strains, particularly in countries that have introduced serogroup C meningococcal conjugate vaccines. Serogroup B also predominates in Australia and New Zealand, in Australia because of the control of serogroup C disease through vaccination and in New Zealand because of a serogroup B epidemic. Based on limited data, most disease in Asia is caused by serogroup A and C strains. Although this review summarizes the current status of meningococcal disease epidemiology, the dynamic nature of this disease requires ongoing surveillance both to provide data for vaccine formulation and vaccine policy and to monitor the impact of vaccines following introduction.

Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995-1997.

OBJECTIVES This study examined epidemiologic factors affecting mortality from pneumococcal pneumonia in 1995 through 1997. METHODS Persons residing in a surveillance area who had community-acquired pneumonia requiring hospitalization and Streptococcus pneumoniae isolated from a sterile site were included in the analysis. Factors affecting mortality were evaluated in univariate and multivariate analyses. The number of deaths from pneumococcal pneumonia requiring hospitalization in the United States in 1996 was estimated. RESULTS Of 5837 cases, 12% were fatal. Increased mortality was associated with older age, underlying disease. Asian race, and residence in Toronto/Peel, Ontario. When these factors were controlled for, increased mortality was not associated with resistance to penicillin or cefotaxime. However, when deaths during the first 4 hospital days were excluded, mortality was significantly associated with penicillin minimum inhibitory concentrations of 4.0 or higher and cefotaxime minimum inhibitory concentrations of 2.0 or higher. In 1996, about 7000 to 12,500 deaths occurred in the United States from pneumococcal pneumonia requiring hospitalization. CONCLUSIONS Older age and underlying disease remain the most important factors influencing death from pneumococcal pneumonia. Mortality was not elevated in most infections with beta-lactam-resistant pneumococci.

Bacterial Meningitis in the United States, 1998-2007

BACKGROUND The rate of bacterial meningitis declined by 55% in the United States in the early 1990s, when the Haemophilus influenzae type b (Hib) conjugate vaccine for infants was introduced. More recent prevention measures such as the pneumococcal conjugate vaccine and universal screening of pregnant women for group B streptococcus (GBS) have further changed the epidemiology of bacterial meningitis. METHODS We analyzed data on cases of bacterial meningitis reported among residents in eight surveillance areas of the Emerging Infections Programs Network, consisting of approximately 17.4 million persons, during 1998-2007. We defined bacterial meningitis as the presence of H. influenzae, Streptococcus pneumoniae, GBS, Listeria monocytogenes, or Neisseria meningitidis in cerebrospinal fluid or other normally sterile site in association with a clinical diagnosis of meningitis. RESULTS We identified 3188 patients with bacterial meningitis; of 3155 patients for whom outcome data were available, 466 (14.8%) died. The incidence of meningitis changed by -31% (95% confidence interval [CI], -33 to -29) during the surveillance period, from 2.00 cases per 100,000 population (95% CI, 1.85 to 2.15) in 1998-1999 to 1.38 cases per 100,000 population (95% CI 1.27 to 1.50) in 2006-2007. The median age of patients increased from 30.3 years in 1998-1999 to 41.9 years in 2006-2007 (P<0.001 by the Wilcoxon rank-sum test). The case fatality rate did not change significantly: it was 15.7% in 1998-1999 and 14.3% in 2006-2007 (P=0.50). Of the 1670 cases reported during 2003-2007, S. pneumoniae was the predominant infective species (58.0%), followed by GBS (18.1%), N. meningitidis (13.9%), H. influenzae (6.7%), and L. monocytogenes (3.4%). An estimated 4100 cases and 500 deaths from bacterial meningitis occurred annually in the United States during 2003-2007. CONCLUSIONS The rates of bacterial meningitis have decreased since 1998, but the disease still often results in death. With the success of pneumococcal and Hib conjugate vaccines in reducing the risk of meningitis among young children, the burden of bacterial meningitis is now borne more by older adults. (Funded by the Emerging Infections Programs, Centers for Disease Control and Prevention.).