Emergence of a multiresistant serotype 19A pneumococcal strain not included in the 7-valent conjugate vaccine as an otopathogen in children

Context  Concern has been raised about the possible emergence of a bacterial strain that is untreatable by US Food and Drug Administration (FDA)–approved antibiotics and that causes acute otitis media (AOM) in children. Objective  To monitor continuing shifts in the strains of Streptococcus pneumoniae that cause AOM, with particular attention to capsular serotypes and antibiotic susceptibility, following the introduction of a pneumococcal 7-valent conjugate vaccine (PCV7). Design, Setting, and Patients  Prospective cohort study using tympanocentesis to identify S pneumoniae strains that caused AOM in children receiving PCV7 between September 2003 and June 2006. All children were from a Rochester, New York, pediatric practice. Main Outcome Measure  Determination of serotypes and antibiotic susceptibility of S pneumoniae causing AOM. Results  Among 1816 children in whom AOM was diagnosed, tympanocentesis was performed in 212, yielding 59 cases of S pneumoniae infection. One strain of S pneumoniae belonging to serotype 19A was a new genotype and was resistant to all antibiotics approved by the FDA for use in children with AOM. This strain was identified in 9 cases (2 in 2003-2004, 2 in 2004-2005, and 5 in 2005-2006). Four children infected with this strain had been unsuccessfully treated with 2 or more antibiotics, including high-dose amoxicillin or amoxicillin-clavulanate and 3 injections of ceftriaxone; 3 had recurrent AOM; and for 2 others, the infection was their first in life. The first 4 cases required tympanostomy tube insertion after additional unsuccessful antibiotic therapies. Levofloxacin was used in the subsequent 5 cases, with resolution of infection without surgery. Conclusion  In the years following introduction of PCV7, a strain of S pneumoniae has emerged in the United States as an otopathogen that is resistant to all FDA-approved antibiotics for treatment of AOM in children.      

Low Dosage and Long Treatment Duration of {beta}-Lactam: Risk Factors for Carriage of Penicillin-Resistant Streptococcus pneumoniae

Context.— The spread of drug-resistant Streptococcus pneumoniae in the community is a public health problem in developed and developing nations, but whether antibiotic use is responsible for the increase in drug resistance is not known. Objective.— To analyze the relationship between penicillin-resistant S pneumoniae (PR Sp) pharyngeal carriage and characteristics of -lactam use. Design.— Observational study of children attending 20 randomly sampled schools. Setting.— The Loiret, in the center of France. Participants.— A total of 941 children, 3 to 6 years old. Main Outcome Measure(s).— Pharyngeal carriage of S pneumoniae, antibiotic use, and medical events during the preceding 30 days. Pneumococcal penicillin G sodium minimal inhibitory concentrations and serotyping were performed. Results.— Medical illnesses and the use of antibiotics were not associated with PR Sp carriage. However, oral -lactam use was associated with an increased risk of PR Sp carriage (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.1-8.3; P=.03). Children treated by low daily doses of an oral -lactam (defined as lower than clinical recommendations) had an increased risk of PR Sp carriage, as compared with children who did not (OR, 5.9; 95% CI, 2.1-16.7; P =.002). A treatment of long duration (>5 days) with a -lactam was associated with an increased risk of PR Sp carriage (OR, 3.5; 95% CI, 1.3-9.8; P=.02). Conclusions.— Our results suggest that a low daily dose and a long duration of treatment with an oral -lactam contribute to the selective pressure in promoting pharyngeal carriage of PR Sp.      

Invasive pneumococcal disease among infants before and after introduction of pneumococcal conjugate vaccine

Context  Streptococcus pneumoniae is a serious infection in young infants. A heptavalent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 and recommended for all children aged 2 to 23 months. Objective  To determine the rates of invasive pneumococcal disease (IPD) in young infants before and after PCV7 was incorporated into the childhood immunization schedule in June 2000. Design, Setting, and Participants  A prospective, population-based study of infants aged 0 to 90 days who resided in areas in 8 US states with active laboratory surveillance for invasive S pneumoniae infections from July 1, 1997, to June 30, 2004. Main Outcome Measures  Rates of laboratory-confirmed IPD before (July 1, 1997-June 30, 2000) and after (July 1, 2001-June 30, 2004) PCV7 introduction, excluding a transition year (July 1, 2000-June 30, 2001). Results  There were 146 cases of IPD, 89 before and 57 after PCV7 introduction. Isolated bacteremia occurred in 94 cases (64%), pneumonia in 27 (18%), meningitis in 22 (15%), and septic arthritis and/or osteomyelitis in 3 (2%). Mean rates of IPD for infants aged 0 to 90 days decreased 40% from 11.8 (95% confidence interval [CI], 9.6-14.5) to 7.2 (95% CI, 5.6-9.4; P = .004) per 100 000 live births following PCV7 introduction. Among black infants, mean rates of IPD decreased significantly from 17.1 (95% CI, 11.9-24.6) to 5.3 (95% CI, 2.8-10.1; P = .001) per 100 000 live births, with a nonsignificant decrease from 9.6 (95% CI, 7.3-12.7) to 6.8 (95% CI, 4.9-9.4) per 100 000 live births for white infants. Rates of PCV7-serotype isolates decreased significantly from 7.3 (95% CI, 5.3-10.1) to 2.4 (95% CI, 1.6-3.8; P<.001) per 100 000 live births, while rates of non-PCV7 serotypes remained stable (P = .55). Conclusions  Since PCV7 introduction, rates of IPD in young infants have decreased significantly, providing evidence that vaccinating children aged 2 to 23 months has led to changes in pneumococcal carriage in infants too young to receive PCV7. With a significant decrease in rates of IPD among black infants, the previous racial difference has been eliminated.      

Prevention of nosocomial infection in cardiac surgery by decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate: a randomized controlled trial

Context  Nosocomial infections are an important cause of morbidity and mortality after cardiac surgery. Decolonization of endogenous potential pathogenic microorganisms is important in the prevention of nosocomial infections. Objective  To determine the efficacy of perioperative decontamination of the nasopharynx and oropharynx with 0.12% chlorhexidine gluconate for reduction of nosocomial infection after cardiac surgery. Design, Setting, and Participants  A prospective, randomized, double-blind, placebo-controlled clinical trial conducted at the Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands, between August 1, 2003, and September 1, 2005. Of 991 patients older than 18 years undergoing elective cardiothoracic surgery during the study interval, 954 were eligible for analysis. Intervention  Oropharyngeal rinse and nasal ointment containing either chlorhexidine gluconate or placebo. Main Outcome Measures  Incidence of nosocomial infection, in addition to the rate of Staphylococcus aureus nasal carriage and duration of hospital stay. Results  The incidence of nosocomial infection in the chlorhexidine gluconate group and placebo group was 19.8% and 26.2%, respectively (absolute risk reduction [ARR], 6.4%; 95% confidence interval [CI], 1.1%-11.7%; P = .002). In particular, lower respiratory tract infections and deep surgical site infections were less common in the chlorhexidine gluconate group than in the placebo group (ARR, 6.5%; 95% CI, 2.3%-10.7%; P = .002; and 3.2%; 95% CI, 0.9%-5.5%; P = .002, respectively). For the prevention of 1 nosocomial infection, 16 patients needed to be treated with chlorhexidine gluconate. A significant reduction of 57.5% in S aureus nasal carriage was found in the chlorhexidine gluconate group compared with a reduction of 18.1% in the placebo group (P<.001). Total hospital stay for patients treated with chlorhexidine gluconate was 9.5 days compared with 10.3 days in the placebo group (ARR, 0.8 days; 95% CI, 0.24-1.88; P = .04). Conclusion  Decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate appears to be an effective method to reduce nosocomial infection after cardiac surgery. Trial Registration  clinicaltrials.gov Identifier: NCT00272675      

Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage

Rosalyn J. Singleton, MD, MPH; Thomas W. Hennessy, MD, MPH; Lisa R. Bulkow, MS; Laura L. Hammitt, MD; Tammy Zulz, BS; Debby A. Hurlburt, RN; Jay C. Butler, MD; Karen Rudolph, PhD; Alan Parkinson, PhD

JAMA. 2007;297:1784-1792.

Context  With routine childhood vaccination using heptavalent pneumococcal conjugate vaccine, one concern has been the potential for emergence and expansion of replacement disease caused by serotypes not contained in the heptavalent conjugate vaccine.

Objective  To determine whether replacement disease is associated with the overall decline in invasive pneumococcal disease among Alaska Native children.

Design, Setting, and Patients  Alaska statewide longitudinal population-based laboratory surveillance of invasive Streptococcus pneumoniae infections from January 1, 1995, through December 31, 2006.

Main Outcome Measures  Incidence and types of pneumococcal disease in children younger than 2 years.

Results  In the first 3 years after introduction of routine vaccination with heptavalent pneumococcal conjugate vaccine, overall invasive pneumococcal disease decreased 67% in Alaska Native children younger than 2 years (from 403.2 per 100 000 in 1995-2000 to 134.3 per 100 000 per year in 2001-2003, P<.001). However, between 2001-2003 and 2004-2006, there was an 82% increase in invasive disease in Alaska Native children younger than 2 years to 244.6/100 000 (P = .02). Since 2004, the invasive pneumococcal disease rate caused by nonvaccine serotypes has increased 140% compared with the prevaccine period (from 95.1 per 100 000 in 1995-2000 to 228.6 in 2004-2006, P = .001). During the same period, there was a 96% decrease in heptavalent vaccine serotype disease. Serotype 19A accounted for 28.3% of invasive pneumococcal disease among Alaska children younger than 2 years during 2004-2006. There was no significant increase in nonvaccine disease in non–Native Alaska children younger than 2 years.

Conclusions  Alaska Native children are experiencing replacement invasive pneumococcal disease with serotypes not covered by heptavalent pneumococcal conjugate vaccine. The demonstration of replacement invasive pneumococcal disease emphasizes the importance of ongoing surveillance and development of expanded valency vaccines.

     

Staphylococcus aureus endocarditis: a consequence of medical progress

Context  The global significance of infective endocarditis (IE) caused by Staphylococcus aureus is unknown. Objectives  To document the international emergence of health care–associated S aureus IE and methicillin-resistant S aureus (MRSA) IE and to evaluate regional variation in patients with S aureus IE. Design, Setting, and Participants  Prospective observational cohort study set in 39 medical centers in 16 countries. Participants were a population of 1779 patients with definite IE as defined by Duke criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to December 2003. Main Outcome Measure  In-hospital mortality. Results  S aureus was the most common pathogen among the 1779 cases of definite IE in the International Collaboration on Endocarditis Prospective-Cohort Study (558 patients, 31.4%). Health care–associated infection was the most common form of S aureus IE (218 patients, 39.1%), accounting for 25.9% (Australia/New Zealand) to 54.2% (Brazil) of cases. Most patients with health care–associated S aureus IE (131 patients, 60.1%) acquired the infection outside of the hospital. MRSA IE was more common in the United States (37.2%) and Brazil (37.5%) than in Europe/Middle East (23.7%) and Australia/New Zealand (15.5%, P<.001). Persistent bacteremia was independently associated with MRSA IE (odds ratio, 6.2; 95% confidence interval, 2.9-13.2). Patients in the United States were most likely to be hemodialysis dependent, to have diabetes, to have a presumed intravascular device source, to receive vancomycin, to be infected with MRSA, and to have persistent bacteremia (P<.001 for all comparisons). Conclusions  S aureus is the leading cause of IE in many regions of the world. Characteristics of patients with S aureus IE vary significantly by region. Further studies are required to determine the causes of regional variation.      

Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine

Context  A conjugate vaccine targeting 7 pneumococcal serotypes was licensed for young children in 2000. In contrast to the 23-valent polysaccharide vaccine used in adults, the 7-valent conjugate vaccine affects pneumococcal carriage and transmission. Early after its introduction, incidence of invasive pneumococcal disease declined among older adults, a group at high risk for pneumococcal disease. Objective  To determine among adults aged 50 years or older whether incidence of invasive pneumococcal disease, disease characteristics, or the spectrum of patients acquiring these illnesses have changed over the 4 years since pneumococcal conjugate vaccine licensure. Design, Setting, and Population  Population-based surveillance of invasive pneumococcal disease in 8 US geographic areas (total population, 18 813 000), 1998-2003. Main Outcome Measures  Incidence of invasive pneumococcal disease by pneumococcal serotype and other characteristics; frequency among case patients of comorbid conditions and other factors influencing mortality. Results  Incidence of invasive pneumococcal disease among adults aged 50 years or older declined 28% (95% confidence interval [CI], –31% to –24%), from 40.8 cases/100 000 in 1998-1999 to 29.4 in 2002-2003. Among those aged 65 years or older, the 2002-2003 rate (41.7 cases/100 000) was lower than the Healthy People 2010 goal (42 cases/100 000). Among adults aged 50 years or older, incidence of disease caused by the 7 conjugate vaccine serotypes declined 55% (95% CI, –58% to –51%) from 22.4 to 10.2 cases/100 000. In contrast, disease caused by any of the 16 serotypes only in polysaccharide vaccine did not change, and disease caused by serotypes not in either vaccine increased somewhat, from 6.0 to 6.8 cases/100 000 (13%; 95% CI, 1% to 27%). Between 1998-1999 and 2002-2003, the proportion of case-patients with human immunodeficiency virus infection increased from 1.7% (47/2737) to 5.6% (124/2231) (P<.001), and those with any comorbid condition that is an indication for pneumococcal polysaccharide vaccination increased from 62.3% (1842/2955) to 72.0% (1721/2390) (P<.001). Conclusions  Our findings indicate that use of conjugate vaccine in children has substantially benefited older adults. However, persons with certain comorbid conditions may benefit less than healthier persons from the indirect effects of the new vaccine.      

Chronic conditions, functional limitations, and special health care needs of school-aged children born with extremely low-birth-weight in the 1990s

Context  Information on the school-age functioning and special health care needs of extremely low-birth-weight (ELBW, <1000 g) children is necessary to plan for medical and educational services. Objective  To examine neurosensory, developmental, and medical conditions together with the associated functional limitations and special health care needs of ELBW children compared with normal-birth-weight (NBW) term-born children (controls). Design, Setting, and Participants  A follow-up study at age 8 years of a cohort of 219 ELBW children born 1992 to 1995 (92% of survivors) and 176 NBW controls of similar sociodemographic status conducted in Cleveland, Ohio. Main Outcome Measures  Parent Questionnaire for Identifying Children with Chronic Conditions of 12 months or more and categorization of specific medical diagnoses and developmental disabilities based on examination of the children. Results  In logistic regression analyses adjusting for sociodemographic status and sex, ELBW children had significantly more chronic conditions than NBW controls, including functional limitations (64% vs 20%, respectively; odds ratio [OR], 8.1; 95% confidence interval [CI], 5.0-13.1; P<.001), compensatory dependency needs (48% vs 23%, respectively; OR, 3.0; 95% CI, 1.9-4.7; P<.001), and services above those routinely required by children (65% vs 27%, respectively; OR, 5.4; 95% CI, 3.4-8.5; P<.001). These differences remained significant when the 36 ELBW children with neurosensory impairments were excluded. Specific diagnoses and disabilities for ELBW vs NBW children included cerebral palsy (14% vs 0%, respectively; P<.001), asthma (21% vs 9%; OR, 3.0; 95% CI, 1.6-5.6; P = .001), vision of less than 20/200 (10% vs 3%; OR, 3.1; 95% CI, 1.2-7.8; P = .02), low IQ of less than 85 (38% vs 14%; OR, 4.5; 95% CI, 2.7-7.7; P<.001), limited academic skills (37% vs 15%; OR, 4.2; 95% CI, 2.5-7.3; P<.001), poor motor skills (47% vs 10%; OR, 7.8; 95% CI, 4.5-13.6; P<.001), and poor adaptive functioning (69% vs 34%; OR, 6.5; 95% CI, 4.0-10.6; P<.001). Conclusion  The ELBW survivors in school at age 8 years who were born in the 1990s have considerable long-term health and educational needs.      

Immunogenicity and safety of a combination pneumococcal-meningococcal vaccine in infants: a randomized controlled trial

Context  The success of conjugate vaccines in decreasing invasive disease due to Streptococcus pneumoniae and group C Neisseria meningitidis has placed pressure on crowded infant immunization schedules, making development of combination vaccines a priority. Objective  To determine the safety and immunogenicity of a combination 9-valent pneumococcal–group C meningococcal conjugate candidate vaccine (Pnc9-MenC) administered as part of the routine UK infant immunization schedule at ages 2, 3, and 4 months. Design, Setting, and Participants  Phase 2 randomized controlled trial conducted from August 2000 to January 2002 and enrolling 240 healthy infants aged 7 to 11 weeks from 2 UK centers, with home follow-up visits at ages 2, 3, 4, and 5 months. Intervention  Pnc9-MenC (n = 120) or monovalent group C meningococcal conjugate vaccine (MenC) (n = 120) administered in addition to routine immunizations (diphtheria and tetanus toxoids and whole-cell pertussis [DTwP], Haemophilus influenzae type b [Hib] polyribosylribitol phosphate-tetanus toxoid protein conjugate, oral polio vaccine). Main Outcome Measures  Group C meningococcal immunogenicity measured by serum bactericidal titer (SBT) 1 month following the third dose; rates of postimmunization reactions. Results  MenC component immunogenicity was reduced in the Pnc9-MenC vs the MenC group (geometric mean SBT, 179 [95% confidence interval {CI}, 133-243] vs 808 [95% CI, 630-1037], respectively; P<.001). The proportion with group C meningococcal SBT greater than 1:8 was lower in the Pnc9-MenC vs the MenC group (95% vs 100%, P = .05). The geometric mean concentration of antibodies to concomitantly administered Hib vaccine was reduced in the Pnc9-MenC vs the MenC group (2.11 [95% CI, 1.57-2.84] µg/mL vs 3.36 [95% CI, 2.57-4.39] µg/mL; P = .02), as were antibodies against diphtheria (0.74 [95% CI, 0.63-0.87] µg/mL vs 1.47 [95% CI, 1.28-1.69] µg/mL; P<.001). Pnc9-MenC was immunogenic for each of 9 contained pneumococcal serotypes, with responses greater than 0.35 µg/mL observed in more than 88% of infants. Increased irritability and decreased activity were observed after the third dose in the Pnc9-MenC group. Conclusions  Pnc9-MenC combination vaccine administered to infants at ages 2, 3, and 4 months demonstrated reduced group C meningococcal immunogenicity compared with MenC vaccine. The immunogenicity of concomitantly administered Hib and DTwP vaccines was also diminished. The Pnc9-MenC vaccine was safe and immunogenic for all contained pneumococcal serotypes. The reduced MenC immunogenicity may limit the development of the Pnc9-MenC vaccine.      

Community-Acquired Methicillin-Resistant Staphylococcus aureus in Children With No Identified Predisposing Risk

Context.— Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections in children have occurred primarily in individuals with recognized predisposing risks. Community-acquired MRSA infections in the absence of identified risk factors have been reported infrequently. Objectives.— To determine whether community-acquired MRSA infections in children with no identified predisposing risks are increasing and to define the spectrum of disease associated with MRSA isolation. Design.— Retrospective review of medical records. Patients.— Hospitalized children with S aureus isolated between August 1988 and July 1990 (1988-1990) and between August 1993 and July 1995 (1993-1995). Setting.— The University of Chicago Children's Hospital. Main Outcome Measures.— Prevalence of community-acquired MRSA over time, infecting vs colonizing isolates, and risk factors for disease. Results.— The number of children hospitalized with community-acquired MRSA disease increased from 8 in 1988-1990 to 35 in 1993-1995. Moreover, the prevalence of community-acquired MRSA without identified risk increased from 10 per 100000 admissions in 1988-1990 to 259 per 100000 admissions in 1993-1995 (P<.001), and a greater proportion of isolates produced clinical infection. The clinical syndromes associated with MRSA in children without identified risk were similar to those associated with community-acquired methicillin-susceptible S aureus. Notably, 7 (70%) of 10 community-acquired MRSA isolates obtained from children with an identified risk were nonsusceptible to at least 2 drugs, compared with only 6 (24%) of 25 isolates obtained from children without an identified risk (P=.02). Conclusions.— These findings demonstrate that the prevalence of community-acquired MRSA among children without identified risk factors is increasing.      

Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials

Context  The benefits of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) are still a matter of debate. Objective  To combine data from all randomized trials conducted with abciximab in STEMI. Data Sources  Formal searches of electronic databases (MEDLINE, PubMed) from from January 1990 to December 2004. Study Selection  We examined all completed, published, randomized trials of abciximab in STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, facilitated angioplasty, stenting, fibrinolysis, IIb-IIIa inhibitors, and abciximab. Data Extraction  Information on study design, type and dosage of drugs, inclusion and exclusion criteria, number of patients, and clinical outcome was extracted by 2 investigators. Disagreements were resolved by consensus. Data Synthesis  Eleven trials were analyzed, involving 27115 patients (12 602 [46.5%] in the abciximab group, 14 513 [53.5%] in the control group). When compared with the control group, abciximab was associated with a significant reduction in short-term (30 days) mortality (2.4% vs 3.4%, P = .047) and long-term (6-12 months) mortality (4.4% vs 6.2%, P = .01) in patients undergoing primary angioplasty but not in those treated with fibrinolysis or in all trials combined. Abciximab was associated with a significant reduction in 30-day reinfarction, both in all trials combined (2.1% vs 3.3%, P<.001), in primary angioplasty (1.0% vs 1.9%, P = .03), and in fibrinolysis trials (2.3% vs 3.6%, P<.001). Abciximab did not result in an increased risk of intracranial bleeding (0.61% vs 0.62%, P = .62) but was associated with an increased risk of major bleeding complications when combined with fibrinolysis (5.2% vs 3.1%, P<.001) but not with primary angioplasty (4.7% vs 4.1%, P = .36). Conclusions  This meta-analysis shows that, when compared with the control group, adjunctive abciximab for STEMI is associated with a significant reduction in 30-day and long-term mortality in patients treated with primary angioplasty but not in those receiving fibrinolysis. The 30-day reinfarction rate is significantly reduced in patients treated with either fibrinolysis or primary angioplasty. A higher risk of major bleeding complications is observed with abciximab in association with fibrinolysis.      

Effects of antibiotic therapy on outcomes of patients with coronary artery disease: a meta-analysis of randomized controlled trials

Context  Although Chlamydia pneumoniae infection has been associated with the initiation and progression of atherosclerosis, results of clinical trials investigating antichlamydial antibiotics as adjuncts to standard therapy in patients with coronary artery disease (CAD) have been inconsistent. Objective  To conduct a meta-analysis of clinical trials of antichlamydial antibiotic therapy in patients with CAD. Data Sources  The MEDLINE and Cochrane Central Register of Controlled Trials databases were searched from 1966 to April 2005 for English-language trials of antibiotic therapy in patients with CAD. Bibliographies of retrieved articles were searched for further studies. Presentations at major scientific meetings (2003-2004) were also reviewed. Search terms included antibacterial agents, myocardial infarction, unstable angina, and coronary arteriosclerosis. Study Selection  Eligible studies were prospective, randomized, placebo-controlled trials of antichlamydial antibiotic therapy in patients with CAD that reported all-cause mortality, myocardial infarction, or unstable angina. Of the 110 potentially relevant articles identified, 11 reports enrolling 19 217 patients were included. Data Extraction  Included studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points. End points of interest included all-cause mortality, myocardial infarction (MI), and a combined end point of MI and unstable angina. Data Synthesis  Event rates were combined using a random-effects model. Antibiotic therapy had no impact on all-cause mortality among treated vs untreated patients (4.7% vs 4.6%; odds ratio [OR], 1.02; 95% confidence interval [CI], 0.89-1.16; P = .83), on the rates of MI (5.0% vs 5.4%; OR, 0.92; 95% CI, 0.81-1.04; P = .19), or on the combined end point of MI and unstable angina (9.2% vs 9.6%; OR, 0.91; 95% CI, 0.76-1.07; P = .25). Conclusion  Evidence available to date does not demonstrate an overall benefit of antibiotic therapy in reducing mortality or cardiovascular events in patients with CAD.      

Temporal trends in infective endocarditis: a population-based study in Olmsted County, Minnesota

Context  Limited data exist regarding population-based epidemiologic changes in incidence of infective endocarditis (IE). Objective  To evaluate temporal trends in the incidence and clinical characteristics of IE. Design, Setting, and Patients  Population-based survey using the resources of the Rochester Epidemiology Project of Olmsted County, Minnesota. One hundred seven IE episodes occurred in 102 Olmsted County residents between 1970 and 2000. The modified Duke criteria were used to validate the diagnosis of definite or possible IE. Main Outcome Measures  Incidence of IE, proportion of patients with underlying heart disease, and causative microorganisms and clinical characteristics. Results  Age- and sex-adjusted incidence of IE ranged from 5.0 to 7.0 cases per 100 000 person-years during the study period and did not change significantly over time (P = .42 for trend). Infective endocarditis caused by viridans group streptococci was the most common organism-specific subgroup, with an annual adjusted incidence of 1.7 to 3.5 cases per 100 000; in comparison, IE due to Staphylococcus aureus had an annual adjusted incidence of 1.0 to 2.2 cases per 100 000. No time trend was detected for either pathogen group (P = .63 and P = .66, respectively). An increasing temporal trend was observed in the proportions of prosthetic valve IE cases (P = .09). Among people with underlying heart disease, there was an increasing temporal trend in mitral valve prolapse (P = .04) and a decreasing trend in rheumatic heart disease (P = .08). However, the absolute numbers were small. There was no time trend in rates of valve surgery or 6-month mortality during the study period (P = .97 and P = .59, respectively). Conclusions  In this community-based temporal trend study, we found no substantial change in the incidence of IE over the past 3 decades. Viridans group streptococci continue to outnumber S aureus as the most common causative organisms of IE in this population.      

Trends in suicide ideation, plans, gestures, and attempts in the United States, 1990-1992 to 2001-2003

Context  Little is known about trends in suicidal ideation, plans, gestures, or attempts or about their treatment. Such data are needed to guide and evaluate policies to reduce suicide-related behaviors. Objective  To analyze nationally representative trend data on suicidal ideation, plans, gestures, attempts, and their treatment. Design, Setting, and Participants  Data came from the 1990-1992 National Comorbidity Survey and the 2001-2003 National Comorbidity Survey Replication. These surveys asked identical questions to 9708 people aged 18 to 54 years about the past year’s occurrence of suicidal ideation, plans, gestures, attempts, and treatment. Trends were evaluated by using pooled logistic regression analysis. Face-to-face interviews were administered in the homes of respondents, who were nationally representative samples of US English-speaking residents. Main Outcome Measure  Self-reports about suicide-related behaviors and treatment in the year before interview. Results  No significant changes occurred between 1990-1992 and 2001-2003 in suicidal ideation (2.8% vs 3.3%; P = .43), plans (0.7% vs 1.0%; P = .15), gestures (0.3% vs 0.2%; P = .24), or attempts (0.4%-0.6%; P = .45), whereas conditional prevalence of plans among ideators increased significantly (from 19.6% to 28.6%; P = .04), and conditional prevalence of gestures among planners decreased significantly (from 21.4% to 6.4%; P = .003). Treatment increased dramatically among ideators who made a gesture (40.3% vs 92.8%) and among ideators who made an attempt (49.6% vs 79.0%). Conclusions  Despite a dramatic increase in treatment, no significant decrease occurred in suicidal thoughts, plans, gestures, or attempts in the United States during the 1990s. Continued efforts are needed to increase outreach to untreated individuals with suicidal ideation before the occurrence of attempts and to improve treatment effectiveness for such cases.      

Contemporary clinical profile and outcome of prosthetic valve endocarditis

Context  Prosthetic valve endocarditis (PVE) is associated with significant mortality and morbidity. The contemporary clinical profile and outcome of PVE are not well defined. Objectives  To describe the prevalence, clinical characteristics, and outcome of PVE, with attention to health care–associated infection, and to determine prognostic factors associated with in-hospital mortality. Design, Setting, and Participants  Prospective, observational cohort study conducted at 61 medical centers in 28 countries, including 556 patients with definite PVE as defined by Duke University diagnostic criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to August 2005. Main Outcome Measure  In-hospital mortality. Results  Definite PVE was present in 556 (20.1%) of 2670 patients with infective endocarditis. Staphylococcus aureus was the most common causative organism (128 patients [23.0%]), followed by coagulase-negative staphylococci (94 patients [16.9%]). Health care–associated PVE was present in 203 (36.5%) of the overall cohort. Seventy-one percent of health care–associated PVE occurred within the first year of valve implantation, and the majority of cases were diagnosed after the early (60-day) period. Surgery was performed in 272 (48.9%) patients during the index hospitalization. In-hospital death occurred in 127 (22.8%) patients and was predicted by older age, health care–associated infection (62/203 [30.5%]; adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.08-2.44; P = .02), S aureus infection (44/128 [34.4%]; adjusted OR, 1.73; 95% CI, 1.01-2.95; P = .05), and complications of PVE, including heart failure (60/183 [32.8%]; adjusted OR, 2.33; 95% CI, 1.62-3.34; P<.001), stroke (34/101 [33.7%]; adjusted OR, 2.25; 95% CI, 1.25-4.03; P = .007), intracardiac abscess (47/144 [32.6%]; adjusted OR, 1.86; 95% CI, 1.10-3.15; P = .02), and persistent bacteremia (27/49 [55.1%]; adjusted OR, 4.29; 95% CI, 1.99-9.22; P<.001). Conclusions  Prosthetic valve endocarditis accounts for a high percentage of all cases of infective endocarditis in many regions of the world. Staphylococcus aureus is now the leading cause of PVE. Health care–associated infection significantly influences the clinical characteristics and outcome of PVE. Complications of PVE strongly predict in-hospital mortality, which remains high despite prompt diagnosis and the frequent use of surgical intervention.      

Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial

Context  The effect of antihypertensive drugs on cardiovascular events in patients with coronary artery disease (CAD) and normal blood pressure remains uncertain. Objective  To compare the effects of amlodipine or enalapril vs placebo on cardiovascular events in patients with CAD. Design, Setting, and Participants  Double-blind, randomized, multicenter, 24-month trial (enrollment April 1999-April 2002) comparing amlodipine or enalapril with placebo in 1991 patients with angiographically documented CAD (>20% stenosis by coronary angiography) and diastolic blood pressure <100 mm Hg. A substudy of 274 patients measured atherosclerosis progression by intravascular ultrasound (IVUS). Interventions  Patients were randomized to receive amlodipine, 10 mg; enalapril, 20 mg; or placebo. IVUS was performed at baseline and study completion. Main Outcome Measures  The primary efficacy parameter was incidence of cardiovascular events for amlodipine vs placebo. Other outcomes included comparisons of amlodipine vs enalapril and enalapril vs placebo. Events included cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke or transient ischemic attack, and new diagnosis of peripheral vascular disease. The IVUS end point was change in percent atheroma volume. Results  Baseline blood pressure averaged 129/78 mm Hg for all patients; it increased by 0.7/0.6 mm Hg in the placebo group and decreased by 4.8/2.5 mm Hg and 4.9/2.4 mm Hg in the amlodipine and enalapril groups, respectively (P<.001 for both vs placebo). Cardiovascular events occurred in 151 (23.1%) placebo-treated patients, in 110 (16.6%) amlodipine-treated patients (hazard ratio [HR], 0.69; 95% CI, 0.54-0.88 [P = .003]), and in 136 (20.2%) enalapril-treated patients (HR, 0.85; 95% CI, 0.67-1.07 [P = .16]. Primary end point comparison for enalapril vs amlodipine was not significant (HR, 0.81; 95% CI, 0.63-1.04 [P = .10]). The IVUS substudy showed a trend toward less progression of atherosclerosis in the amlodipine group vs placebo (P = .12), with significantly less progression in the subgroup with systolic blood pressures greater than the mean (P = .02). Compared with baseline, IVUS showed progression in the placebo group (P<.001), a trend toward progression in the enalapril group (P = .08), and no progression in the amlodipine group (P = .31). For the amlodipine group, correlation between blood pressure reduction and progression was r = 0.19, P = .07. Conclusions  Administration of amlodipine to patients with CAD and normal blood pressure resulted in reduced adverse cardiovascular events. Directionally similar, but smaller and nonsignificant, treatment effects were observed with enalapril. For amlodipine, IVUS showed evidence of slowing of atherosclerosis progression.      

Use and costs of medical care for children and adolescents with and without attention-deficit/hyperactivity disorder

Context  A shortage of data exists on medical care use by persons with attention-deficit/hyperactivity disorder (ADHD). Objective  To compare medical care use and costs among persons with and without ADHD. Design and Setting  Population-based cohort study conducted in Rochester, Minn. Subjects  All children born in 1976-1982 were followed up through 1995, using school and medical records to identify those with ADHD. The 4880 birth cohort members (mean age, 7.3 years) still residing in Rochester in 1987 were followed up in medical facility–linked billing databases until death, emigration, or December 31, 1995. Main Outcome Measures  Clinical diagnoses, likelihood and frequency of inpatient and outpatient hospitalizations, emergency department (ED) visits, and total medical costs (including ambulatory care), compared among individuals with and without ADHD. Results  Among the 4119 birth cohort members who remained in the area through 1995 (mean age, 15.3 years), 7.5% (n = 309) had met criteria for ADHD. Compared with persons without ADHD, those with ADHD were more likely to have diagnoses in multiple categories, including major injuries (59% vs 49%; P<.001) and asthma (22% vs 13%; P<.001). The proportion with any hospital inpatient, hospital outpatient, or ED admission was higher for persons with ADHD vs those without ADHD (26% vs 18% [P<.001], 41% vs 33% [P = .006], and 81% vs 74% [P = .005], respectively). The 9-year median costs for persons with ADHD compared with those without ADHD were more than double ($4306 vs $1944; P<.001), even for the subset with no hospital or ED admissions (eg, median 1987 costs, $128 vs $65; P<.001). The differences between individuals with and without ADHD were similar for males and females and across all age groups. Conclusion  In our cohort, compared with persons without ADHD, those with ADHD exhibited substantially greater use of medical care in multiple care delivery settings.      

Control of endemic methicillin-resistant Staphylococcus aureus: a cost-benefit analysis in an intensive care unit

Context  Despite the success of some countries in controlling endemic methicillin-resistant Staphylococcus aureus (MRSA), such programs have not been implemented for some hospitals with endemic infection because of concerns that these programs would be costly and of limited benefit. Objective  To compare the costs and benefits of an MRSA control program in an endemic setting. Design and Setting  Case-control study conducted at a medical intensive care unit (ICU) of a French university hospital with a 4% prevalence of MRSA carriage at ICU admission. Patients  Twenty-seven randomly selected patients who had ICU-acquired MRSA infection between January 1993 and June 1997, matched to 27 controls hospitalized during the same period without MRSA infection. Main Outcome Measures  Intensive care unit costs attributable to MRSA infection, computed from excess therapeutic intensity in cases using estimates from a cost model derived in the same ICU, were compared with costs of the control program, derived from time-motion study of nurses and physicians. The threshold for MRSA carriage that would make the control strategy dominant was determined; sensitivity analyses varied rates of MRSA transmission and ratio of infection to transmission, length of ICU stay, and costs of isolation precautions. Results  The mean cost attributable to MRSA infection was US $9275 (median, $5885; interquartile range, $1400-$16,720). Total costs of the control program ranged from $340 to $1480 per patient. A 14% reduction in MRSA infection rate resulted in the control program being beneficial. In sensitivity analyses, the control strategy was dominant for a prevalence of MRSA carriage on ICU admission ranging from 1% to 7%, depending on costs of control measures and MRSA transmission, for infection rates greater than 50% following transmission. Conclusions  In this example of a hospital with endemic MRSA infection, selective screening and isolation of carriers on ICU admission are beneficial compared with no isolation.      

Delivery of preventive services to older adults by primary care physicians

Context  Rates of preventive services remain below national goals. Objective  To identify characteristics of physicians and their practices that are associated with the quality of preventive care their patients receive. Design  Cross-sectional analysis of data on US physician respondents to the 2000-2001 Community Tracking Study Physician Survey linked to claims data on Medicare beneficiaries they treated in 2001. Physician variables included training and qualifications and sex. Practice setting variables included practice type, size, sources of revenue, and access to information technology. Analyses were adjusted for patient demographics and comorbidity, as well as community characteristics. Setting and Participants  Primary care delivered by 3660 physicians providing usual care to 24 581 Medicare beneficiaries aged 65 years and older. Main Outcome Measures  Proportion of eligible beneficiaries receiving each of 6 preventive services: diabetic monitoring with hemoglobin A_1c measurement or eye examinations, screening for colon or breast cancer, and vaccination for influenza or pneumococcus in 2001. Results  Overall, the proportion of beneficiaries receiving services was below national goals. Physician and, more consistently, practice-level characteristics were both associated with differences in the delivery of services. The strongest associations were with practice type and the percentage of practice revenue derived from Medicaid. For instance, beneficiaries receiving usual care in practices with less than 6% of revenue from Medicaid were more likely than those with more than 15% of revenue derived from Medicaid to receive diabetic eye examinations (48.9% vs 43%; P = .02), hemoglobin A_1c monitoring (61.2% vs 48.4%; P<.001), mammograms (52.1% vs 38.9%; P<.001), colon cancer screening (10.0% vs 8.5%; P = .60), and influenza (50.2% vs 39.2%; P<.001) and pneumococcal (8.2% vs 6.4%; P<.001) vaccinations. Other variables associated with delivery of preventive services after adjustment for patient and geographic factors included obtaining usual health care from a physician who worked in group practices of 3 or more, who was a graduate of a US or Canadian medical school, or who reported availability of information technology to generate preventive care reminders or access treatment guidelines. Conclusions  Delivery of routine preventive services is suboptimal for Medicare beneficiaries. However, patients treated within particular practice settings and by particular subgroups of physicians are at particular risk of low-quality care. Profiling these practices may help develop tailored interventions that can be directed to sites where the opportunities for quality improvement are greatest.