Cynthia G. Whitney

Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults

Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.

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.

Update of Practice Guidelines for the Management of Community-Acquired Pneumonia in Immunocompetent Adults

The Infectious Diseases Society of America (IDSA) produced guidelines for community-acquired pneumonia (CAP) in immunocompetent adults in 1998 and again in 2000 [1, 2]. Because of evolving resistance to antimicrobials and other advances, it was felt that an update should be provided every few years so that important developments could be highlighted and pressing questions answered. We addressed those issues that the committee believed were important to the practicing physician, including suggestions for initial empiric therapy for CAP. In some cases, only a few paragraphs were needed, whereas, in others, a somewhat more in-depth discussion was provided. Because many physicians focus on the tables rather than on the text of guidelines, it was decided that all of the information dealing with the initial empiric treatment regimens should be in tabular format with footnotes (tables 1–3). The topics selected for updating have been organized according to the headings used in the August 2000 CAP guidelines pub-

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.).

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.

U.S. Hospitalizations for Pneumonia after a Decade of Pneumococcal Vaccination

BACKGROUND The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into the U.S. childhood immunization schedule in 2000 has substantially reduced the incidence of vaccine-serotype invasive pneumococcal disease in young children and in unvaccinated older children and adults. By 2004, hospitalizations associated with pneumonia from any cause had also declined markedly among young children. Because of concerns about increases in disease caused by nonvaccine serotypes, we wanted to determine whether the reduction in pneumonia-related hospitalizations among young children had been sustained through 2009 and whether such hospitalizations in older age groups had also declined. METHODS We estimated annual rates of hospitalization for pneumonia from any cause using the Nationwide Inpatient Sample database. The reason for hospitalization was classified as pneumonia if pneumonia was the first listed diagnosis or if it was listed after a first diagnosis of sepsis, meningitis, or empyema. Average annual rates of pneumonia-related hospitalizations from 1997 through 1999 (before the introduction of PCV7) and from 2007 through 2009 (well after its introduction) were used to estimate annual declines in hospitalizations due to pneumonia. RESULTS The annual rate of hospitalization for pneumonia among children younger than 2 years of age declined by 551.1 per 100,000 children (95% confidence interval [CI], 445.1 to 657.1), which translates to 47,000 fewer hospitalizations annually than expected on the basis of the rates before PCV7 was introduced. The rate for adults 85 years of age or older declined by 1300.8 per 100,000 (95% CI, 984.0 to 1617.6), which translates to 73,000 fewer hospitalizations annually. For the three age groups of 18 to 39 years, 65 to 74 years, and 75 to 84 years, the annual rate of hospitalization for pneumonia declined by 8.4 per 100,000 (95% CI, 0.6 to 16.2), 85.3 per 100,000 (95% CI, 7.0 to 163.6), and 359.8 per 100,000 (95% CI, 199.6 to 520.0), respectively. Overall, we estimated an age-adjusted annual reduction of 54.8 per 100,000 (95% CI, 41.0 to 68.5), or 168,000 fewer hospitalizations for pneumonia annually. CONCLUSIONS Declines in hospitalizations for childhood pneumonia were sustained during the decade after the introduction of PCV7. Substantial reductions in hospitalizations for pneumonia among adults were also observed. (Funded by the Centers for Disease Control and Prevention.).

Postvaccine Genetic Structure of Streptococcus pneumoniae Serotype 19A from Children in the United States

BACKGROUND The introduction of the 7-valent conjugate pneumococcal vaccine (PCV7) in children may result in serotype replacement. We estimated the rate of increase of invasive pneumococcal disease (IPD) caused by serotype 19A in children <5 years old and determined the genetic composition of these isolates. METHODS Cases of IPD between July 1999 and June 2004 were identified through the Active Bacterial Core Surveillance. Serotype 19A isolates obtained from children <5 years old between January 2003 and June 2004 were characterized by serotyping, antibiotic susceptibility testing, and pulsed-field gel electrophoresis (PFGE). Select isolates representing homologous PFGE clusters were subjected to multilocus sequence typing, and eBURST was used to delineate clonal groups. RESULTS Between July 1999 and June 2004, the overall rate of IPD decreased from 23.3 to 13.1 cases/100,000 population (P<.00001). In children <5 years old, the rate decreased from 88.7 to 22.4 cases/100,000 population (P<.00001), whereas the rate in persons > or =5 years old decreased from 18.4 to 12.4 cases/100,000 population (P<.0001). The rate of serotype 19A IPD in children <5 years old increased significantly from 2.6 cases/100,000 population in 1999-2000 to 6.5 cases/100,000 population in 2003-2004; this was accompanied by significant increases in penicillin nonsusceptibility (P=.008) and multidrug resistance (P=.002) among serotype 19A isolates. As was observed during the pre-PCV7 era, clonal complex (CC) 199 predominated within serotype 19A, representing approximately 70% of invasive serotype 19A isolates from children <5 years old during 2003-2004. New serotype 19A genotypes were observed during 2003-2004, including 6 CCs that were not found among pneumococcal serotype 19A isolates during surveillance in 1999. CONCLUSION Serotype 19A is, at present, the most important cause of IPD by replacement serotypes, and it is increasingly drug resistant. CC199 is the predominant CC among type 19A serotypes in children <5 years old. Our data suggest that some of the increase in rates of infection with serotype 19A may be due to serotype switching within certain vaccine type strains.

Near-fatal heat stroke during the 1995 heat wave in Chicago

Chicago sustained a heat wave from 12 July to 20 July 1995 that resulted in more than 600 excess deaths [1] and 3300 excess emergency department visits [2]. Daily temperatures ranged from 33.9 to 40.0 C, and on 13 July, the heat index peaked at 48.3 C [1]; the maximum number of emergency department visits occurred 24 hours later. The medical examiners office reported the maximum number of deaths on 15 July [1, 2]. The peak number of admissions to area intensive care units occurred on 15 July (Figure 1). Critically ill persons were admitted with classic heat stroke, defined by a body temperature greater than 40.6 C in the presence of altered mental status and anhidrosis [1]. Figure 1. Relation between admissions to the intensive care unit (ICU) (bar graph) and the heat index (line chart) during the height of the heat wave. Heat stroke has been classified as exertional or classic. Exertional heat stroke is precipitated by heavy exertion in very hot and humid climates and is usually seen in otherwise healthy young persons [3]. Classic heat stroke results from unabated exposure to high temperatures and humidity. Elderly persons with premorbid conditions are likely to experience classic heat stroke. Despite the high incidence of heat-related deaths reported annually in the United States [4], the literature on the clinical features of classic heat stroke is limited. Lactic acidosis, renal failure, rhabdomyolysis, and disseminated intravascular coagulation, well described in exertional heat stroke, are reported as uncommon or of minor consequence in classic heat stroke [3, 5-7]. The numerous persons who presented with near-fatal classic heat stroke during the Chicago heat wave provided an opportunity to analyze the clinical course of this condition. We sought to describe the course of patients admitted to the intensive care unit with classic heat stroke. Excessive functional disability identified in survivors of the acute phase of the illness prompted a 1-year follow-up to assess delayed functional outcome and mortality. Methods Medical Record Review Twelve of 24 area hospitals permitted us access to patient records. We obtained institutional review board approval, which allowed us to contact patients for 1-year follow-up. Patients were identified by review of emergency department records, intensive care unit logs, and medical records discharge codes. Records of all patients admitted to each intensive care unit from 12 July to 20 July 1995 were reviewed. Enrollment criteria were 1) absence of vigorous physical activity during the heat wave; 2) alteration of mental status [coma, delirium, lethargy, disorientation, or seizures documented by paramedics and emergency department physicians]; 3) recorded core body temperature of more than 40.6 C or documented evidence of cooling before the first recorded temperature and a reliable history of compatible environmental exposure [1, 5, 8, 9]; and 4) hot, dry, flushed skin. Data were recorded by using a predesigned data collection form. Major components of this form were demographic characteristics, Glasgow coma score, temperature, and clinical condition at presentation; maximum Acute Physiology and Chronic Health Evaluation (APACHE) II score in the first 24 hours; length of intensive care unit and hospital stay; functional level and disposition at discharge; laboratory data; and results of radiography, electrocardiography, and echocardiography. Data on the presence or absence of air conditioning was obtained from paramedic encounter sheets. Information about when the patient was last seen was obtained from paramedic reports or emergency department history. The medical history was obtained from admission history and physical examination and was verified by the medical records of the patients personal physician, when available, or outpatient prescription medication, as recorded on the paramedic report. Organ system dysfunction was assessed by evaluation of serial laboratory results. The chart reviewer assessed neurologic impairment at discharge from documentation of the patients neurologic status at discharge. Follow-up A modified Stanford Health Assessment Questionnaire was used to score functionality [10, 11]. Components of this tool assess performance of activities of daily living. Survivors were contacted 1 year after discharge and were interviewed by telephone to complete the modified Stanford Health Assessment Questionnaire. If the patient was unable to respond, a caretaker estimated their level of function by using the same questionnaire. If telephone contact could not be made, tracking was attempted through mail, health care providers, or acquaintances identified in the medical record. Deaths were investigated in the aforementioned manner and by a search of the Cook County Medical Examiner logs. Data that allowed completion of the modified Stanford Health Assessment Questionnaire at the time of hospital discharge were abstracted from the charts of patients whose outcomes were known at 1 year. Data Analysis Data are presented as the mean SD except when they did not fit tests for normality and the mean did not accurately describe the data. In these instances, data are presented as the median and interquartile range. We used n to denote the number of values averaged when data were not available on all 58 study patients. Nominal data were compared by using chi-square analysis or the Fisher exact test of contingency tables. Continuous data were compared and correlations were made by using analysis of variance, the t-test, the Spearman rank test, and the Wilcoxon signed-rank test. Admission laboratory values and follow-up values were compared, and correlations were performed between laboratory tests to determine whether abnormalities were related. To determine the effect of functional disability and age on survival, survival analysis was performed by using Kaplan-Meier plots with the Mantel-Cox log-rank test and the Cox proportional-hazards model. Statistical analysis was performed by using StatView 4.5 (Abacus Concepts, Berkeley, California). Role of Funding Source Neither of our funding sources, the Park Ridge Health Foundation or the University of Chicago Clinical Research Center, participated in collection, analysis, and interpretation of the data or in preparation of the manuscript. The decision to publish this report was not influenced by the funding sources. Results Epidemiology Fifty-eight patients met the inclusion criteria. Patients who met the case definition of classic heat stroke but were not admitted to the intensive care unit were excluded from further analysis. Demographic characteristics of the patients are presented in Table 1. Forty-seven patients (83%) were found at home, and 77% were last seen within 12 hours of rescue (range, 2 to 42 hours; n = 39). The environments in which patients were found lacked air conditioning in 40 instances (69%). Three patients had air conditioners that were turned off, and 1 patient had the unit on at the time of rescue. In 14 cases, the presence or absence of air conditioning was not documented. Forty-three of 50 patients had medical insurance (Medicare [44%], private insurance [18%], private insurance and Medicare [14%], Medicaid [10%], and self-pay [14%]). Insurance data were not available for eight patients. Table 1. Demographic Characteristics of the 58 Study Patients Chronic medical conditions were documented in 52 patients (Table 2). The most common comorbid conditions were hypertension and alcohol abuse. Before admission, 47 patients were taking at least 1 of 18 medications (Table 2). Sixteen patients were found to be taking medications that predispose to the development of heat stroke (diuretics [13 patients], phenothiazines [2 patients], or both [1 patient]). An additional 2 patients tested positive for cocaine, a substance known to increase heat production. Table 2. Preexisting Medical Conditions (52 Patients) and Medications (47 Patients) Presenting temperature, time to cooling, and APACHE II scores are shown in Table 3. Methods of cooling in the emergency department included antipyretic agents (15 patients), water or fan (24 patients), groin and axillary ice packs (34 patients), cooling blanket (19 patients), gastric lavage with cool saline (6 patients), cold intravenous fluids (17 patients), and ice bath (1 patient). The median hospital stay was 9 days (interquartile range, 13 days), and the median intensive care unit stay was 4 days (interquartile range, 5 days). Twelve patients died (20.7%). Table 3. Presenting Body Temperature, Time to Cooling, and APACHE II Data in 58 Patients* Organ System Dysfunction Cardiovascular Findings Presenting electrocardiography showed sinus tachycardia (71%), normal sinus rhythm (8.5%), supraventricular tachycardia (8.5%), atrial fibrillation (8.5%), and multifocal atrial tachycardia (3%). Hypovolemic shock was suggested by physical examination in 17 of 58 patients. In the first 24 hours, 3.8 2.1 L (range, 0.6 to 13.5 L) of fluid was infused. Six patients had central venous pressure measured within the first 24 hours; the mean was 12 6 cm H2O (range, 7 to 20 cm H2O). Fourteen of 43 patients underwent echocardiography early in the hospital course. Among these 14 patients, findings included normal left ventricular systolic function (7 patients), concentric left ventricular hypertrophy (4 patients), mild left ventricular dysfunction (1 patient), moderate to severe left ventricular dysfunction (4 patients), left-sided chamber enlargement (4 patients), and mitral regurgitation (3 patients). Six patients had one of the following findings: right ventricular hypertrophy, aortic insufficiency, tricuspid regurgitation, pericardial effusion, paradoxical septal-wall movement, and aneurysm. Two patients underwent follow-up echocardiography; one had normalization of previously noted moderate to severe left ventricular dysfunction and resolution of pericardial effusion. This patient also und

Impact of Penicillin Susceptibility on Medical Outcomes for Adult Patients with Bacteremic Pneumococcal Pneumonia

The impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia was evaluated in a retrospective cohort study conducted during population-based surveillance for invasive pneumococcal disease in the greater Atlanta region during 1994. Of the 192 study patients, 44 (23%) were infected with pneumococcal strains that demonstrated some degree of penicillin nonsusceptibility. Compared with patients infected with penicillin-susceptible pneumococcal strains, patients whose isolates were nonsusceptible had a significantly greater risk of in-hospital death due to pneumonia (relative risk [RR], 2.1; 95% confidence interval [CI], 1-4.3) and suppurative complications of infection (RR, 4.5; 95% CI, 1-19.3), although only risk of suppurative complications remained statistically significant after adjustment for baseline differences in severity of illness. Among adults with bacteremic pneumococcal pneumonia, infection with penicillin-nonsusceptible pneumococci is associated with an increased risk of adverse outcome.

The Influence of Chronic Illnesses on the Incidence of Invasive Pneumococcal Disease in Adults

Pneumococcal disease is more frequent and more deadly in persons with certain comorbidities. We used 1999 and 2000 data from the Active Bacterial Core surveillance (ABCs) and the National Health Interview Survey (NHIS) to determine rates of invasive pneumococcal disease in healthy adults (> or =18 years old) and in adults with various high-risk conditions. The risks of invasive pneumococcal disease in persons with specific chronic illnesses was compared with that in healthy adults, controlling for age, race, and the other chronic illnesses. Overall incidence rates, in cases/100,000 persons, were 8.8 in healthy adults, 51.4 in adults with diabetes, 62.9 in adults with chronic lung disease, 93.7 in adults with chronic heart disease, and 100.4 in adults who abused alcohol. Among the high-risk groups evaluated, risk was highest in adults with solid cancer (300.4), HIV/AIDS (422.9), and hematological cancer (503.1). Incidence rates increased with advancing age in adults with chronic lung disease, diabetes, and solid cancer. Black adults had higher incidence rates than white adults, both in healthy adults and in adults with chronic illnesses. These data support recommendations to provide pneumococcal vaccine to persons in these at-risk groups and underscore the need for better prevention strategies for immunocompromised persons.