Search

Streptococcus pneumoniae remains the most common cause of community-acquired pneumonia and bacterial meningitis in older adults. Current recommendations from CDC's Advisory Committee on Immunization Practices suggest providing pneumococcal polysaccharide vaccine to all adults age 65 and older and to persons age 2 to 64 with chronic illnesses that place them at higher risk for pneumococcal disease. In addition, vaccination status should be assessed for residents of nursing homes and long-term care facilities on admission and vaccine administered as needed. Although the polysaccharide vaccine is safe, effective against invasive disease, and cost-effective, many older adults have not yet received the vaccine. Use of standing orders is encouraged as a way to improve vaccine delivery. Research into new vaccines to prevent pneumococcal disease in older adults is ongoing.

Persons with acquired immunodeficiency syndrome (AIDS) have a higher incidence of invasive pneumococcal disease (IPD) than other adults, and many receive long-term trimethoprim-sulfamethoxazole (TMP-SMZ) prophylactic therapy. We used 1998-1999 data from the Active Bacterial Core surveillance of the Emerging Infections Program Network to compare IPD infections between adults aged 18-64 years with human immunodeficiency virus (HIV) infection and other adults. Of 2346 patients with IPD, 416 (18%) had HIV or AIDS (HIV/AIDS). Certain serotypes (serotypes 6A, 6B, 9N, 9V, 18C, 19A, 19F, and 23F) were more common among patients with HIV/AIDS than in adults with no underlying disease (P<.05, vs. serotype 4), even when TMP-SMZ-nonsusceptible isolates were excluded. HIV/AIDS (adjusted odds ratio [aOR], 1.93; 95% confidence interval [CI], 1.44-2.59), immunocompromising conditions other than HIV/AIDS (aOR, 1.56; 95% CI, 1.12-2.18), and black race (aOR, 1.50; 95% CI, 1.20-1.88) were independent risk factors for infection with these serotypes. HIV/AIDS was not an independent risk factor for TMP-SMZ nonsusceptibility. Vulnerability to certain serotypes among adults with HIV/AIDS may have implications in prevention strategies.

Daptomycin MICs at which 50% of isolates were inhibited (MIC(50)s) and MIC(90)s determined by the NCCLS broth microdilution method were both 0.25 microg/ml (range, 0.06 to 2 microg/ml) for 350 pneumococcal isolates. MICs determined by E test strips on commercially prepared Mueller-Hinton sheep blood agars with different calcium contents were 2 to 3 dilutions higher than those determined by strips that contained daptomycin plus calcium. Daptomycin zone diameters varied little on the same media.

Theseven-valent pneumococcal conjugated polysaccharide vaccine PC7V was licensed for use among children in 2000. Since 90 serotypes of pneumococci exist, an increase in nonvaccine serotypes could occur through immune selection for capsular type switching. Eleven hundred sixty-eight invasive isolates (24 serotypes), recovered primarily from pediatric patients (855 isolates = 73%) and 22 reference strains of known multilocus sequence types (STs) were subjected to macrorestriction profiling (pulsed-field gel electrophoresis [PFGE]). The correlation of 187 ST results (including 49 newly discovered STs) with the PFGE data assigned 1,042 (89.2%) study isolates to 46 defined clonal complexes or genetic lineages based on related multilocus STs (BURST). Seventeen clonal complexes were represented by 2 to 10 related allelic profiles (STs), while 33 lineages (including reference strains) consisted of single STs with 4 or fewer allelic identities to other STs found in the study. Expansion of the BURST analysis to a global analysis of all known pneumococcal STs (as of 27 November 2002) reduced the number of single ST lineages from 33 to 8, and the number of multi-ST clonal complexes was reduced from 17 to 13. In this work, we established the basic genetic structure within individual serotypes prior to PC7V use. The resultant database will be useful for detecting potential selective effects of this vaccine in postvaccine surveillance.

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

Objective: To measure the association between the disinfection of municipal drinking water with monochloramine and the occurrence of hospital-acquired legionnaires' disease (LD)., Setting: One hundred sixty-six U.S. hospitals., Design: Survey of 459 members of the Society for Healthcare Epidemiology of America (SHEA) for hospital features; endemic- and outbreak-related, hospital-acquired LD; the source of the hospital water supply; and the methods of disinfection used by the hospitals and municipal water treatment plants., Results: SHEA members representing 166 (36%) of 459 hospitals responded; 33 (20%) reported one or more episodes of hospital-acquired LD during the period from 1994 to 1998 and 23 (14%) reported an outbreak of hospital-acquired LD during the period from 1989 to 1998. Hospitals with an occurrence of hospital-acquired LD had a higher census (median, 319 vs 221; P = .03), more acute care beds (median, 500 vs 376; P = .04), and more intensive care unit beds (median, 42 vs 24; P = .009) than did other hospitals. They were also more likely to have a transplant service (74% vs 42%; P = .001) and to perform surveillance for hospital-acquired disease (92% vs 61%; P = .001). After adjustment for the presence of a transplant program and surveillance for legionnaires' disease, hospitals supplied with drinking water disinfected with monochloramine by municipal plants were less likely to have sporadic cases or outbreaks of hospital-acquired LD (odds ratio, 0.20; 95% confidence interval, 0.07 to 0.56) than were other hospitals., Conclusion: Water disinfection with monochloramine by municipal water treatment plants significantly reduces the risk of hospital-acquired LD.

Invasive pneumococcal disease occurs 2-3-fold more often among Navajo adults than among adults in the general United States population. The objective of this observational study was to determine the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) among Navajo adults. Active surveillance identified cases of invasive pneumococcal disease during 1996-1997. Three control patients per case patient were matched according to underlying medical conditions, sex, age, and location of medical care. Effectiveness was calculated by regression analysis of case-control sets and by indirect cohort methodology. Diabetes and alcoholism occurred in 41% and 43% of 108 case patients, respectively; 62% of case patients and 64% of control patients were immunized. Overall vaccine effectiveness was 26% (95% confidence interval [CI], -29% to 58%); 15% (95% CI, -116% to 67%) for patients with diabetes and -5% (95% CI, -141% to 54%) for patients with alcoholism. Overall vaccine effectiveness, as determined by use of the indirect cohort methodology, was 35% (95% CI, -33% to 69%). PPV23 was not significantly effective among Navajo adults and may be inadequate to prevent serious pneumococcal disease in this population.

Background: Guidelines are increasingly recommending preventive services starting at 50 years of age, and policymakers are considering such a recommendation for pneumococcal polysaccharide vaccination. The finding that pneumococcal vaccination is cost-saving for people 65 years of age or older raises the question of the vaccination's implications for other older adults, especially black people, whose disease incidence exceeds that of nonblack people, and those with high-risk conditions., Objective: To assess the implications of vaccinating black and nonblack people 50 through 64 years of age against invasive pneumococcal disease., Design: Cost-effectiveness analysis., Data Sources: Published literature for vaccination effectiveness and cost estimates; data on disease incidence and case-fatality rates from the Centers for Disease Control and Prevention., Target Population: Hypothetical cohort 50 through 64 years of age with the 1995 U.S. age distribution., Time Horizon: Lifetime., Perspective: Societal., Intervention: Pneumococcal polysaccharide vaccination compared with no vaccination., Outcome Measures: Incremental medical costs and health effects, in quality-adjusted life-years per vaccinee., Results of Base-Case Analysis: Vaccination saved medical costs and improved health among high-risk black people (27.55 dollars savings per vaccinee) and nonblack people (5.92 dollars savings per vaccinee), excluding survivors' future costs. For low-risk black and nonblack people and the overall general population, vaccination cost 2477 dollars, 8195 dollars, and 3434 dollars, respectively, to gain 1 year of healthy life., Results of Sensitivity Analysis: Excluding survivors' future costs, in the general immunocompetent population, cost per quality-adjusted life-year in global worst-case results ranged from 21 513 dollars for black people to 68 871 dollars for nonblack people; in the high-risk population, cost ranged from 11 548 dollars for black people to 39 000 dollars for nonblack people. In the global best case, vaccination was cost-saving for black and nonblack people in the general immunocompetent and high-risk populations, excluding survivors' future costs. The cost-effectiveness range was narrower in probabilistic sensitivity analyses, with 95% probabilistic intervals ranging from cost-saving to 1594 dollars for black people and from cost-saving to 12 273 dollars for nonblack people in the general immunocompetent population. Costs per quality-adjusted life-year for low-risk people with case-fatality rates from 1998 were 2477 dollars for black people and 8195 dollars for nonblack people, excluding survivors' medical costs., Conclusions: These results support the current recommendation to vaccinate high-risk people and provide useful information for considering extending the recommendation to the general population 50 through 64 years of age. Lack of evidence about the effectiveness of revaccination for people 65 years of age or older, when disease risks are higher, argues for further research to guide vaccination policy.

Background: The pneumococcal vaccine is widely underused. Patient education is one mechanism not widely explored for increasing vaccination rates., Objective: To evaluate the effects of a culturally appropriate patient education videotape on pneumococcal vaccination rates among the clinic population of an inner-city public hospital., Methods: Randomized, controlled trial comparing (1) a videotape-brochure group who both viewed the videotape and received a low-literacy brochure, (2) a videotape only group, and (3) a control group., Results: Of 2,962 charts reviewed, 558 patients were randomized. The study population was 94% black, 73% female, and elderly (mean age 63.0 years) and 64% had less than a high school education. Patients in the videotape-brochure group were 2.5 (1.8, 3.5 95% CI) times more likely to discuss the vaccine with their physician (p < .001) and 3.5 (1.9, 6.5 95% CI) times more likely to receive the vaccine (p < .001) than the control group. The videotape-brochure group was 1.6 (1.2, 2.1 95% CI) times more likely to discuss the vaccine (p < .001) and 2.3 (1.4, 3.8 95% CI) times more likely to receive the vaccine (p = .002) than the video only group. Patients in the video only group were 1.6 (1.1, 2.3 95% CI) times more likely to discuss the vaccine with their physician than the control group (p = .041) but were not more likely to receive the vaccine., Conclusion: A culturally appropriate videotape along with a low-literacy brochure significantly increased pneumococcal vaccination rates and physician-patient discussion about the vaccine. These significant outcomes were not observed with use of videotape alone and were likely attributable to the effect of the brochure. We recommend that patient education initiatives to increase vaccination rates not focus solely on audiovisual media.

Pneumococcal infections increase each winter, a phenomenon that has not been well explained. We conducted population-based active surveillance for all cases of invasive pneumococcal disease in seven states; plotted annualized weekly rates by geographic location, age, and latitude; and assessed correlations by time-series analysis. In all geographic areas, invasive pneumococcal disease exhibited a distinct winter seasonality, including an increase among children in the fall preceding that for adults and a sharp spike in incidence among adults each year between December 24 and January 7. Pneumococcal disease correlated inversely with temperature (r -0.82 with a 1-week lag; p<0.0001), but paradoxically the coldest states had the lowest rates, and no threshold temperature could be identified. The pattern of disease correlated directly with the sinusoidal variations in photoperiod (r +0.85 with a 5-week lag; p<0.0001). Seemingly unrelated seasonal phenomena were also somewhat correlated. The reproducible seasonal patterns in varied geographic locations are consistent with the hypothesis that nationwide seasonal changes such as photoperiod-dependent variation in host susceptibility may underlie pneumococcal seasonality, but caution is indicated in assigning causality as a result of such correlations.

Resistance of Streptococcus pneumoniae to antibiotics is increasing throughout the United States, with substantial variation among geographic regions. We show that patterns of geographic variation are best explained by the intensity of selection for resistance, which is reflected by differences between the proportions of resistance within individual serotypes, rather than by differences between the frequencies of particular serotypes. Using a mathematical transmission model, we analyzed temporal trends in the proportions of singly and dually resistant organisms and found that pneumococcal strains resistant to both penicillin and erythromycin are increasing faster than strains singly resistant to either. Using the model, we predict that by 1 July 2004, in the absence of a vaccine, 41% of pneumococci at the Centers for Disease Control and Prevention (CDC)'s Active Bacterial Core surveillance (ABCs) sites, taken together, will be dually resistant, with 5% resistant to penicillin only and 5% to erythromycin only.

We compared the hypothetical effects of the 23-valent polysaccharide pneumococcal vaccine with new vaccines on preventing invasive and noninvasive pneumococcal disease in persons >or=65 years. We estimated how much disease would occur if no polysaccharide vaccine were in use and used this baseline to compare the polysaccharide, a 7-valent conjugate vaccine, and hypothetical common antigen vaccine. The polysaccharide, conjugate, and common antigen vaccines prevented 10.6, 10.7, and 17.7% of invasive disease and 4.3, 5.6, and 10.0% of pneumonia, respectively. Superior effectiveness of new vaccines was dependent upon a presumed longer duration of protection than the 23V-PPV and effectiveness against noninvasive pneumonia. Our results suggest that new vaccines could improve disease prevention.

In contrast to earlier pneumococcal vaccines, conjugate vaccines hold promise for reducing pneumococcal morbidity and mortality in infants and young children. The first commercially available conjugate vaccine formulation, which targets seven serotypes, was licensed in the US and other countries in 2000; this vaccine is now part of routine infant immunization in the US. Demand has been high and greater than vaccine supply. Clinical trials indicate that conjugate vaccines are highly efficacious against invasive pneumococcal disease and modestly efficacious against otitis media and pneumonia. In carriage studies conjugate vaccines reduced vaccine-type carriage but led to an increase in carriage of other serotypes. Remaining questions include whether less frequent transmission of vaccine serotypes will mean less disease in unvaccinated children and adults or if nonvaccine serotypes will begin to cause more disease. Monitoring disease burden after widespread use in the US is critical for understanding the effects of the vaccine. In addition making pneumococcal vaccines available for children in developing countries should be a high priority.

The activity of AZD2563 against 250 highly resistant pneumococci and 267 drug-susceptible isolates was determined. The AZD2563 MICs for 50 and 90% of the strains tested were 1 and 2 micro g/ml and 0.5 and 1 micro g/ml, respectively, for the two isolate groups. These MICs were within 1 log(2) dilution of those of linezolid.

Treatment of infections with drug-resistant strains of Streptococcus pneumoniae (pneumococcus) may fail; whether drug resistance is associated with an increase in the number of serious infections in the community is unknown. We evaluated the relationship between the proportion of antimicrobial-resistant S. pneumoniae isolates and the number of cases of invasive pneumococcal disease. Linear regression models included 1996 county-level data from 38 counties participating in the US Centers for Disease Control and Prevention's Active Bacterial Core Surveillance. Separate models evaluated hospitalized children aged <5 years, nonhospitalized children aged <5 years, adults aged 18-64 years, and adults aged >64 years. The proportion of isolates resistant to > or =3 drug classes was associated with invasive disease in both hospitalized (P=.06) and nonhospitalized (P=.001) children. The proportion of multidrug-resistant pneumococcal isolates did not predict invasive cases among adults. The increasing prevalence of multidrug-resistant pneumococci among children may be leading to an increase in invasive disease.

Monitoring antibiotic-resistant pneumococcal strains not covered by the 7-valent conjugate vaccine is an important priority. The Centers for Disease Control and Prevention's Active Bacterial Core Surveillance identified 68 invasive penicillin-nonsusceptible serotype 35B (PN35B) isolates recovered from 1995 to 2001 from patients residing in the states of California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New York, Oregon, Tennessee, and Texas. Nonsusceptible isolates accounted for 69% of all serotype 35B isolates recovered during this time. Twelve (18%) of the 68 PN35B isolates recovered since 1995 were obtained from pediatric patients. These 68 isolates exhibited penicillin MICs of 0.25-2 microg/mL and reduced susceptibility to cefotaxime. Representative PN35B isolates exhibited a common chromosomal macrorestriction profile and identical penicillin-binding-protein gene restriction profiles characteristic of penicillin-resistant strains, and they shared a unique 7-locus sequence type that included 3 new alleles. The mosaic pbp2b and divergent ddl sequences were suggestive of interspecies recombination at the ddl-pbp2b chromosomal region.

When an outbreak of conjunctivitis was identified at a rural New England college early in 2002, the college health center medical staff used various information management and communication systems to alert the community to the situation. They called upon the state Department of Human Services and the Centers for Disease Control and Prevention to help them understand and manage the outbreak. Technological systems already in place at the college allowed for rapid collection of data by means of a survey delivered over the Internet and a carriage study facilitated by a Web-based appointment and communication system. Within days, the data were collected and analyzed and an immediate response to contain the outbreak was launched.

We used population-based data to evaluate how often groups of randomly selected clinical laboratories accurately estimated the prevalence of resistant pneumococci and captured trends in resistance over time. Surveillance for invasive pneumococcal disease was conducted in eight states from 1996 to 1998. Within each surveillance area, we evaluated the proportion of all groups of three, four, and five laboratories that estimated the prevalence of penicillin-nonsusceptible pneumococci (%PNSP) and the change in %PNSP over time. We assessed whether sentinel groups detected emerging fluoroquinolone resistance. Groups of five performed best. Sentinel groups accurately predicted %PNSP in five states; states where they performed poorly had high between-laboratory variation in %PNSP. Sentinel groups detected large changes in prevalence of nonsusceptibility over time but rarely detected emerging fluoroquinolone resistance. Characteristics of hospital-affiliated laboratories were not useful predictors of a laboratory's %PNSP. Sentinel surveillance for resistant pneumococci can detect important trends over time but rarely detects newly emerging resistance profiles.

The proportion of relapses and reinfections that are potentially preventable by vaccine in human immunodeficiency virus (HIV)-infected persons with recurrent pneumococcal disease is unknown. Isolates from HIV-infected individuals from Baltimore with recurrent pneumococcal invasive disease were collected from 1 January 1995 through 31 December 2000. Serotyping and pulsed-field gel electrophoresis were performed. From 1 January 1995 through 31 December 1998, 14.9% (404/2717) of those who had a pneumococcal infection were HIV infected. The recurrence rate among HIV-infected individuals was 6.4-fold higher than that among individuals without HIV infection (P<.01). Among recurrent infections in 41 individuals, there were 42 reinfections and 6 relapses. All relapses and 91% (70/77) of reinfections were due to serotypes covered by the 23-valent pneumococcal polysaccharide vaccine. Reinfection was more common than relapse among HIV-infected individuals with recurrent pneumococcal disease. Although a substantial proportion of recurrent pneumococcal infections was potentially preventable by vaccine, creating an effective vaccine may be challenging for this population.

We assessed the distribution of the clonal groups (as determined by pulsed-field gel electrophoresis) of penicillin-nonsusceptible Streptococcus pneumoniae that caused invasive pneumococcal infection in the Baltimore metropolitan area during 1995 and 1996. Although S. pneumoniae caused invasive disease in individuals from a variety of demographic groups and locations, strains isolated during the season in which respiratory infections are most common were more likely to be from clonal groups associated with penicillin resistance than from other groups.

Background: While the Advisory Committee on Immunization Practices recommends a standing order as the most effective mechanism to increase pneumococcal and influenza vaccination rates, Georgia's Medical Practice Act does not authorize nurses to screen, order, and administer adult vaccines in inpatient settings., Methods: The setting was a 1000-bed public teaching hospital in metropolitan Atlanta. A 1-month intervention (INT1) included four wards randomized to intervention or control. A 5-month hospital-wide intervention (INT2) followed INT1. The intervention used was provider reminder with in-service training. Chart review was the measure used. The main outcome was pneumococcal vaccination prior to discharge., Results: During INT1, 534 patients (296 intervention and 238 control) were discharged. Of the 534 patients, 475 (89.0%) were African American, 188 (35.2%) were uninsured, and the median age was 48 (range 19 to 96). Of the 205 intervention patients with vaccine indications and no contraindications, 78 of 205 (38%) were vaccinated compared to 7 of 143 (4.9%) of the control patients (p<0.001). During INT2, 879 patient charts were reviewed. Patient demographics were similar to INT1. However, of 554 eligible patients, 16% were vaccinated, significantly higher than control floors during INT1 (p<0.001). Although nurses initiated the form almost 70% of the time, physicians assessed fewer than 35% of patients with indications., Conclusions: Significantly higher proportions of high-risk patients were vaccinated through the use of a preprinted nurse screening and physician order form. However, a significant percentage of patients did not receive the vaccine owing to the physician's failure to order it. In these cases, use of standing orders would have further increased vaccination rates while also promoting a more sustainable program.

We examined the epidemiology of invasive penicillin-resistant Streptococcus pneumoniae (PRSP) infections among residents of the Baltimore metropolitan area from 1995 through 1997. During this period, the proportion PRSP cases increased 42%, from 5.7% to 8.1% of cases. PRSP rates were highest among persons aged <5 and > or =65 years, black patients, and urban dwellers. However, the proportion of PRSP cases was higher among white persons (10%) than it was among black persons (5%) and among residents of suburban counties (10%) versus urban counties (6%). PRSP cases were more common in November-April (8%) than they were in May-October (5%), particularly for persons aged > or =65 years (10% vs. 1%). By use of logistic regression, white race, suburban residence, and winter respiratory season were found to be independent predictors of infection with PRSP. The incidence of PRSP is increasing in Baltimore, and the seasonality of PRSP suggests that recent antibiotic use, which is more common in winter months, may rapidly affect the prevalence of resistant pneumococcal infections.

In a double-blinded, randomized trial, human immunodeficiency virus (HIV)-infected adults with > or = 200 CD4 cells/microl received placebo (PL), 7-valent conjugate, or 23-valent pneumococcal polysaccharide (PS) vaccine in one of the following two-dose combinations given 8 weeks apart: conjugate-conjugate, conjugate-polysaccharide, placebo-polysaccharide, placebo-placebo. A total of 67 persons completed the study. Neither significant increases in HIV viral load nor severe adverse reactions occurred in any group. After controlling for confounders, when compared with persons receiving placebo-polysaccharide, persons receiving conjugate-conjugate and conjugate-polysaccharide had higher antibody concentrations (serotypes 4, 6B, 9V and serotype 23F, respectively) and opsonophagocytic titers (functional antibody assay, serotypes 9V, 23F and serotypes 4, 6B, 9V, respectively) after the second dose (P<0.05). The second dose with either conjugate or polysaccharide following the first conjugate dose, however, produced no further increase in immune responses.

Context: Macrolide antibiotics, including erythromycin, clarithromycin, and azithromycin, are the mainstays of empirical pneumonia therapy. Macrolide resistance among Streptococcus pneumoniae, the most common cause of community-acquired pneumonia, is increasing in the United States. Whether resistance is a significant problem or whether macrolides remain useful for treatment of most resistant strains is unknown., Objective: To examine the epidemiology of macrolide-resistant pneumococci in the United States., Design and Setting: Analysis of 15 481 invasive isolates from 1995 to 1999 collected by the Centers for Disease Control and Prevention's Active Bacterial Core surveillance system in 8 states., Main Outcome Measures: Trends in macrolide use (1993-1999) and resistance and factors associated with resistance, including examination of 2 subtypes, the M phenotype, associated with moderate minimum inhibitory concentrations (MICs), and the MLS(B) phenotype, associated with high MICs and clindamycin resistance., Results: From 1993 to 1999, macrolide use increased 13%; macrolide use increased 320% among children younger than 5 years. Macrolide resistance increased from 10.6% in 1995 to 20.4% in 1999. M phenotype isolates increased from 7.4% to 16.5% (P<.001), while the proportion with the MLS(B) phenotype was stable (3%-4%). The median erythromycin MIC (MIC(50)) of M phenotype isolates increased from 4 microg/mL to 8 microg/mL. In 1999, M phenotype strains were more often from children than persons 5 years or older (25.2% vs 12.6%; P<.001) and from whites than blacks (19.3% vs 11.2%; P<.001)., Conclusions: In the setting of increasing macrolide use, pneumococcal resistance has become common. Most resistant strains have MICs in the range in which treatment failures have been reported. Further study and surveillance are critical to understanding the clinical implications of our findings.

Streptococcus pneumoniae remains a major cause of disease worldwide; the emergence of antibiotic-resistant strains emphasizes the importance of disease prevention by use of vaccines. Recent studies have provided information that is useful for the evaluation of current vaccine recommendations. Recommendations target most people who are at high risk for invasive pneumococcal disease. However, higher risk has also been identified for African Americans and smokers, but these groups are not specifically targeted by current recommendations. The vaccine is effective against invasive disease in immunocompetent people, although studies in immunocompromised subjects have found few subgroups in which the vaccine appears to be effective. Questions with regard to optimal timing and indications for revaccination remain a challenge, because the duration of protection and effectiveness of revaccination remain unknown. New pneumococcal vaccines appear promising but will need to be tested against the performance of the polysaccharide vaccine. Improving delivery of the currently available pneumococcal polysaccharide vaccine to adults who will benefit should be a high priority.

Background: As part of a 3-year demonstration project to improve pneumococcal polysaccharide vaccine (PPV) coverage among older adults, the Minnesota Department of Health conducted a baseline evaluation of knowledge, attitudes, and beliefs among the general public regarding PPV., Methods: A random-digit dialing telephone survey was conducted among community-dwelling adults age 65 years or older in three metropolitan counties in Minnesota during April through June 1998., Results: Three hundred fifty-three interviews were completed; self-reported PPV coverage was 59% (95% CI 54%, 64%). Nearly all (94%) respondents reported at least one medical visit in the past year. Unvaccinated respondents expressed willingness to be vaccinated if they knew about PPV's safety, dosage, and preventive role. In a final multivariate regression model, factors associated with PPV vaccination included awareness of PPV (OR 7.8; CI 2.1, 29.2; P = 0.002), opinion that receiving PPV is "very important" (OR 8.3; CI 3.2, 21.6; P < 0.001), awareness that Medicare covers PPV (OR 5.1; CI 1.9, 13.8; P = 0.001), physician ever offering PPV (OR 21.7; CI 6.2, 76.6; P < 0.001), and physician regularly offering PPV (OR 3.9; CI 1.1, 13.7; P = 0.03)., Conclusions: Respondents were significantly influenced by their physician offering PPV. Therefore, providers' practices are a critical target for improving PPV coverage. Educational efforts to inform patients about PPV and to address misconceptions (e.g., safety, efficacy, Medicare coverage) also may improve vaccination levels., (Copyright 2001 American Health Foundation and Academic Press.)

Field studies of Streptococcus pneumoniae (pneumococci) nasopharyngeal (NP) colonization are hampered by the need to directly plate specimens in order to ensure isolate viability. A medium containing skim milk, tryptone, glucose, and glycerin (STGG) has been used to transport and store NP material, but its ability to preserve pneumococci has not been evaluated. Our objective was to qualitatively and semiquantitatively evaluate the ability of STGG to preserve pneumococci in NP secretions. Entwined duplicate calcium alginate NP swab samples were obtained from children. One swab was plated directly onto a gentamicin blood agar plate; the other was placed in STGG. Growth from the directly plated specimen was compared with growth from an STGG aliquot immediately cultured or stored at -70 degrees C for 9 weeks, -20 degrees C for 9 weeks, or 4 degrees C for 5 days. Of 186 specimens, 96 (52%) were positive for pneumococci from the direct plating; 94 (98%) of these were positive from the fresh STGG specimen. Pneumococci were recovered from all 38 positive specimens frozen at -70 degrees C, all 18 positive specimens frozen at -20 degrees C, and 18 of 20 positive specimens stored at 4 degrees C. Recovery of pneumococci after storage of NP material in STGG medium at -70 degrees C is at least as good as that from direct plating. Storage at -20 degrees C is also acceptable. Storage at 4 degrees C for 5 days is not ideal.

Few data are available on the molecular subtypes of all penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) from a defined population base. Pulsed-field gel electrophoresis (PFGE), serotyping, and antibiotic susceptibility testing were performed for all available invasive PNSP isolates for which the penicillin (MIC) was > or =0.1 microg/ml from Baltimore, Md., during 1995-1996 (n = 143). The dendrogram analysis of PFGE patterns included 32 distinct clonal groups. Six major clonal groups included two-thirds of the PNSP strains. Major clonal groups 2, 3, 4, and 6 strains were genetically related to four previously described international clones and were all multidrug resistant. Major clonal group 3 was genetically related to the Tennessee(23F)-4 clone and contained all four strains for which the penicillin MIC was 8 microg/ml. Most of the clonal group 1 and 5 strains had intermediate susceptibility to penicillin and were rarely multidrug resistant. The latter clonal groups represent two previously undescribed penicillin-intermediate pneumococcal clones. Clonal group homogeneity was greater for serotype 9V, 19A, and 23F strains than for serotype 6A, 6B, 14, and 19F strains. The classification of PNSP strains into clonal groups is essential for future population-based epidemiologic studies of PNSP.

From 1994 through 1999, the available isolates (4148 isolates) from active population-based surveillance of invasive pneumococcal disease in metropolitan Atlanta were serotyped and were tested for antimicrobial susceptibility. Macrolide-resistant isolates were studied for the presence of ermAM (a ribosomal methylase gene), mefE (a macrolide efflux gene), and tetM (the class M tetracycline resistance gene). Macrolide resistance increased from 16% of all invasive isolates in 1994 to 32% in 1999. Of the macrolide-resistant pneumococcal isolates studied, 99% contained genomic copies of mefE or ermAM. Isolates with ermAM were mainly serotypes 6B, 23F, 14, or 19F and contained tetM; mefE-associated isolates were predominantly serotypes 14, 6A, or 19F, and most did not contain tetM. The frequency of the ermAM-mediated phenotype in invasive Streptococcus pneumoniae remained stable over the 6-year surveillance. However, the mefE-mediated phenotype increased from 9% in 1994 to 26% of all isolates in 1999 and was noted in new serotypes. By 1999, 93% of the mefE-containing strains had minimum inhibitory concentrations >/=8 microgram/mL. Dissemination of the mefE determinant accounted for the rapid increase in the rate of macrolide resistance in our S. pneumoniae population.

The activities of two investigational fluoroquinolones and three fluoroquinolones that are currently marketed were determined for 182 clinical isolates of Streptococcus pneumoniae. The collection included 57 pneumococcal isolates resistant to levofloxacin (MIC >/= 8 microg/ml) recovered from patients in North America and Europe. All isolates were tested with clinafloxacin, gatifloxacin, gemifloxacin, levofloxacin, and trovafloxacin by the National Committee for Clinical Laboratory Standards broth microdilution and disk diffusion susceptibility test methods. Gemifloxacin demonstrated the greatest activity on a per gram basis, followed by clinafloxacin, trovafloxacin, gatifloxacin, and levofloxacin. Scatterplots of the MICs and disk diffusion zone sizes revealed a well-defined separation of levofloxacin-resistant and -susceptible strains when the isolates were tested against clinafloxacin and gatifloxacin. DNA sequence analyses of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE from 21 of the levofloxacin-resistant strains identified eight different patterns of amino acid changes. Mutations among the four loci had the least effect on the MICs of gemifloxacin and clinafloxacin, while the MICs of gatifloxacin and trovafloxacin increased by up to six doubling dilutions. These data indicate that the newer fluoroquinolones have greater activities than levofloxacin against pneumococci with mutations in the DNA gyrase or topoisomerase IV genes. Depending upon pharmacokinetics and safety, the greater potency of these agents could provide improved clinical efficacy against levofloxacin-resistant pneumococcal strains.

Group B streptococcal (GBS) disease is a leading cause of morbidity and mortality among newborns. Many cases of newborn GBS disease can be prevented by the administration of intrapartum antibiotic prophylaxis. Current consensus guidelines for prevention of perinatal GBS disease have led to substantial declines in the incidence of GBS disease occurring in newborns <7 days of age (early-onset disease). Despite declines in the incidence of early-onset disease, approximately 20% of pregnant women are colonized with GBS at the time of labor and thus have the risk of transmitting the bacteria to their newborns. Consequently, continued and improved implementation of prevention efforts is essential. Infection control teams can contribute uniquely to prevention of perinatal GBS disease by serving as hospital champions of GBS disease prevention. In particular, teams can coordinate with administration and staff to encourage establishment and effective implementation of GBS prevention policies; facilitate improved laboratory processing of prenatal GBS screening specimens; monitor any adverse consequences of increased use of intrapartum antibiotics within the hospital; and investigate GBS cases that occur to determine whether they could have been prevented. By spearheading efforts to improve implementation of perinatal GBS disease prevention at the hospital level, hospital epidemiologists and infection control practitioners can play an important role in reducing the burden of early-onset GBS disease.

Objective: To provide recommendations for the management of community-acquired pneumonia and the surveillance of drug-resistant Streptococcus pneumoniae (DRSP)., Methods: We addressed the following questions: (1) Should pneumococcal resistance to beta-lactam antimicrobial agents influence pneumonia treatment? (2) What are suitable empirical antimicrobial regimens for outpatient treatment of community-acquired pneumonia in the DRSP era? (3) What are suitable empirical antimicrobial regimens for treatment of hospitalized patients with community-acquired pneumonia in the DRSP era? and (4) How should clinical laboratories report antibiotic susceptibility patterns for S pneumoniae, and what drugs should be included in surveillance if community-acquired pneumonia is the syndrome of interest? Experts in the management of pneumonia and the DRSP Therapeutic Working Group, which includes clinicians, academicians, and public health practitioners, met at the Centers for Disease Control and Prevention in March 1998 to discuss the management of pneumonia in the era of DRSP. Published and unpublished data were summarized from the scientific literature and experience of participants. After group presentations and review of background materials, subgroup chairs prepared draft responses, which were discussed as a group., Conclusions: When implicated in cases of pneumonia, S pneumoniae should be considered susceptible if penicillin minimum inhibitory concentration (MIC) is no greater than 1 microg/mL, of intermediate susceptibility if MIC is 2 microg/ mL, and resistant if MIC is no less than 4 microg/mL. For outpatient treatment of community-acquired pneumonia, suitable empirical oral antimicrobial agents include a macrolide (eg, erythromycin, clarithromycin, azithromycin), doxycycline (or tetracycline) for children aged 8 years or older, or an oral beta-lactam with good activity against pneumococci (eg, cefuroxime axetil, amoxicillin, or a combination of amoxicillin and clavulanate potassium). Suitable empirical antimicrobial regimens for inpatient pneumonia include an intravenous beta-lactam, such as cefuroxime, ceftriaxone sodium, cefotaxime sodium, or a combination of ampicillin sodium and sulbactam sodium plus a macrolide. New fluoroquinolones with improved activity against S pneumoniae can also be used to treat adults with community-acquired pneumonia. To limit the emergence of fluoroquinolone-resistant strains, the new fluoroquinolones should be limited to adults (1) for whom one of the above regimens has already failed, (2) who are allergic to alternative agents, or (3) who have a documented infection with highly drug-resistant pneumococci (eg, penicillin MIC > or =4 microg/mL). Vancomycin hydrochloride is not routinely indicated for the treatment of community-acquired pneumonia or pneumonia caused by DRSP.

To assess the genetic diversity of pneumococci causing serious disease within the United States, restriction profiles of 3 penicillin-binding protein (PBP)-gene amplicons and the dhf amplicon were examined in 241 recent sterile-site isolates from 7 population centers. This analysis provided markers useful for epidemiologic studies and was generally predictive of resistances to beta-lactam antibiotics and trimethoprim-sulfamethoxazole. Eight pulsed-field gel electrophoresis (PFGE) types, each representing 3-40 isolates, accounted for 134 of the 144 beta-lactam-resistant pneumococci (MICs >/=1 microgram/mL for penicillin, cefotaxime, or both). Five of these PFGE types contained subtypes highly related to subtypes of previously characterized pneumococcal clones. Within 4 of these PFGE types, the major composite PBP gene-dhf profile was highly related to the composite profile from the previously characterized related clone. Eight capsular serotypes were found among the 144 beta-lactam-resistant pneumococci. Divergent capsular types among isolates with identical PBP gene-dhf profiles and related PFGE types indicated several instances of capsular serotype switching.

Context: In 1994, surveillance by the Chicago Department of Public Health detected a growing trend in the proportion of invasive meningococcal infections caused by serogroup Y., Objective: To examine the emergence of serogroup Y meningococcal disease and compare its clinical characteristics with those of other meningococcal serogroups., Design: Population-based retrospective review of surveillance records; medical record review and cohort analysis of serogroup Y vs non-serogroup Y case patients., Setting: Chicago, III., Participants: City residents with Neisseria meningitidis isolated from a normally sterile site from January 1, 1991, through December 31, 1997; cohort analysis included those identified through March 31, 1996., Main Outcome Measures: Serogroup-specific incidence, demographics, and clinical outcomes., Results: We identified 214 case patients; 53 (25%) had serogroup Y. The attack rate of serogroup Y meningococcal disease increased from 0.04 cases per 100000 in 1991 to a peak of 0.82 cases per 100000 in 1995 and subsequently decreased to 0.26 cases per 100000 and 0.34 cases per 100000 in 1996 and 1997, respectively. Compared with patients infected by other serogroups, patients with serogroup Y were older (median age, 16 years vs 1 year; P = .001) and more likely to have a chronic underlying illness (prevalence ratio, 2.3; 95% confidence interval, 1.2-4.4). Outcome did not differ significantly between the 2 groups. Multilocus enzyme electrophoresis typing of isolates from 19 case patients identified 5 different types. We found no clustering among the enzyme types by age, race/ethnicity, community area, or time., Conclusions: Serogroup Y emerged as the most frequent cause of meningococcal disease in Chicago in 1995 and accounted for a substantial proportion of cases in 1996 and 1997. Current data suggest that the magnitude of serogroup Y meningococcal disease is sufficient for vaccine developers to incorporate serogroup Y into new vaccines.

Background: In July 1995, Chicago sustained a heat wave that resulted in more than 600 excess deaths, 3300 excess emergency department visits, and a substantial number of intensive care unit admissions for near-fatal heat stroke., Objective: To describe the clinical features of patients admitted to an intensive care unit with near-fatal classic heat stroke. Patients were followed for 1 year to assess delayed functional outcome and mortality., Design: Observational study., Setting: Intensive care units in the Chicago area., Patients: 58 patients admitted to the hospital from 12 July to 20 July 1995 who met the case definition of classic heat stroke., Measurements: The data collection tool was designed to compile demographic and survival data and to permit analysis of organ system function by abstracting data on physical examination findings, electrocardiography and echocardiography results, fluid resuscitation, radiography results, and laboratory findings. Data on functional status at discharge and at 1 year were collected by using a modified Stanford Health Assessment Questionnaire., Results: Patients experienced multiorgan dysfunction with neurologic impairment (100%), moderate to severe renal insufficiency (53%), disseminated intravascular coagulation (45%), and the acute respiratory distress syndrome (10%). Fifty-seven percent of patients had evidence of infection on admission. In-hospital mortality was 21%. Most survivors recovered near-normal renal, hematologic, and respiratory status, but disability persisted, resulting in moderate to severe functional impairment in 33% of patients at hospital discharge. At 1 year, no patient had improved functional status, and an additional 28% of patients had died., Conclusions: Near-fatal classic heat stroke is associated with multiorgan dysfunction. A high percentage of patients had infection at presentation. A high mortality rate was observed during acute hospitalization and at 1 year. In addition, substantial functional impairment at discharge persisted 1 year. The degree of functional disability correlated highly with survival at 1 year.

Use of rifampin is required for short-course treatment regimens for tuberculosis. Tuberculosis caused by isolates of M. tuberculosis with resistance to rifampin and susceptibility to isoniazid is unusual, but it has been recognized through surveillance. Patients with tuberculosis (cases) with rifampin mono-resistance were compared with HIV-matched controls with tuberculosis caused by a drug-susceptible isolate. A total of 77 cases of rifampin mono-resistant tuberculosis were identified in this multicenter study. Three were determined to be laboratory contaminants, and 10 cases had an epidemiologic link to a case with rifampin mono-resistant tuberculosis, suggesting primary acquisition of rifampin-resistant isolates. Of the remaining 64 cases and 126 controls, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, or history of incarceration. Cases were more likely to have a history of prior tuberculosis than were controls. Of the 38 cases and 74 controls with HIV infection, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, history of incarceration, or prior tuberculosis. Cases were more likely to have histories of diarrhea, rifabutin use, or antifungal therapy. Laboratory analysis of available isolates showed that there was no evidence of spread of a single clone of M. tuberculosis. Further studies are needed to identify the causes of the development of rifampin resistance in HIV-infected persons with tuberculosis and to develop strategies to prevent its emergence.

In 1996, the dominant (43%) strain of vancomycin-resistant enterococci (VRE; type A) at Massachusetts General Hospital was identified at Brigham and Women's Hospital (BWH). To characterize the epidemiology of infection with type A isolates of VRE at BWH, we collected demographic and clinical data for all patients from whom VRE were isolated from a clinical specimen through September 1996. The first clinical isolates from all BWH patients from whom VRE were isolated were typed by pulsed-field gel electrophoresis of SmaI digests of chromosomal DNA. Among patients hospitalized after the first patient at BWH infected with a type A isolate of VRE was identified, exposures were compared between patients who acquired type A isolates of VRE and those who acquired other types of VRE. Isolates from 99 patients identified to have acquired VRE were most commonly from blood (n = 27), urine (n = 19), or wounds (n = 19). Three months after the index patient arrived at BWH and at a time when > or =12 types of strains of VRE were present, type A isolates of VRE became dominant; 39 of 75 (52%) of the study cohort had acquired type A isolates of VRE. We found no association between the acquisition of type A isolates of VRE and transfer from another institution or temporal overlap by service, ward, or floor with patients known to have acquired type A isolates of VRE. By multivariate analysis, only residence in the medical intensive care unit (adjusted odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4 to 107) and the receipt of two or more antibiotics per patient-day (adjusted OR, 12.2; 95% CI, 1.2 to 9.0) were associated with the acquisition of strain A. This strain of VRE, dominant at two Boston hospitals, was associated with intensity of antibiotic exposures (i.e., two or more antibiotics per patient-day). We hypothesize that this strain may have unidentified properties providing a mechanism favoring its spread and dominance over other extant isolates, and further studies are needed to define these properties.

An outbreak of community-acquired Legionnaires' disease (LD) occurred in Providence, R.I., in fall 1993. To find the outbreak source, exposures of 17 case patients were compared to those of 33 matched controls. Case patients were more likely than controls to have visited a section of downtown (area A) during the 2 weeks before illness (11 [65%] versus 9 [27%]; matched odds ratio, 6.5; P = 0.01). Water samples were cultured from 27 aerosol-producing devices within area A. Legionella pneumophila serogroup 1 isolates underwent monoclonal antibody (MAb) subtyping and arbitrarily primed PCR (AP-PCR). All four L. pneumophila serogroup 1 isolates available from case patients who visited area A had identical MAb and AP-PCR patterns. Among 14 environmental isolates, 5 had MAb patterns that matched the case patient isolates, but only 1 had a matching AP-PCR pattern. This investigation implicates a cooling tower in area A as the outbreak source and illustrates the usefulness of AP-PCR for identifying sources of LD outbreaks.

A PCR assay was developed for detection of Streptococcus pneumoniae in clinical specimens including blood and paraffinized tissues. We were able to detect one organism of purified DNA or 4.5 colony-forming units in blood. The primers did not cross-react with other upper respiratory tract streptococci or with pathogens commonly found in clinical specimens. This assay was used in an investigation of an outbreak of severe illness characterized by septic shock and hemorrhage in previously healthy children. PCR detected S. pneumoniae in cerebrospinal fluid and autopsy tissues of the two infants who died. The findings from this assay indicated that PCR offers increased specificity and sensitivity over latex agglutination and counterimmunoelectrophoresis and should prove useful in the identification of additional cases of severe illness caused by S. pneumoniae.

Objective: To evaluate hospital-based practices for perinatal group B streptococcal disease prevention and to identify institutional factors related to the disease., Methods: We surveyed microbiology laboratories and obstetric programs during 1994 at hospitals in five states with active surveillance for invasive group B streptococcal disease. Institutions provided information on methods for detecting carriers and on obstetric policies for group B streptococcal disease prevention. We used linear regression to identify prevention practices and hospital characteristics that correlated with the number of cases of early-onset disease., Results: Of 295 hospitals, 247 (84%) laboratories and 154 (52%) obstetric programs completed the survey. Most (83%) laboratories performed group B streptococcal cultures on rectal and vaginal specimens, but only 12 (6%) used selective broth media. Among the obstetric programs, 54 (35%) had policies on some aspect of group B streptococcal disease prevention. Of the hospitals with policies, 21 (48%) recommended intrapartum antimicrobial prophylaxis for women with risk factors outlined by the 1992 ACOG statement. Adjusting for the number of births, there were more cases of early-onset group B streptococcal disease in institutions providing care for more African American women and for more women with no prenatal care. Institutions that had group B streptococcal screening policies had fewer early-onset cases., Conclusions: Many institutions with prevention policies followed practices that differed from those recommended in published prevention statements. Having any screening policy, however, was associated with reduced early-onset disease, independent of the risk profile of the patient population. Adopting prevention policies is most urgent for practices serving individuals at increased risk, such as African American women and women without prenatal care.

Arbitrarily primed PCR (AP-PCR) and pulsed-field gel electrophoresis (PFGE) subtyping were applied to clinical and environmental isolates from seven unrelated outbreaks of Legionnaires' disease. The patterns observed with each method matched patient isolates and the epidemiologically linked source of disease for each of the seven outbreaks. PFGE allowed more discrimination among various isolates, although AP-PCR usually gave comparable results. With both methods, certain patterns appeared to predominate in the comparison of the seven outbreaks. Of five clinical isolates not associated with the outbreaks, three gave profiles distinct from those observed in the outbreaks by both methods. This suggests that there are at least two predominant subtypes of Legionella pneumophila serogroup 1 associated with outbreaks. Investigations of outbreaks of legionellosis should employ either PFGE or AP-PCR in addition to monoclonal antibody analysis.

During 1992 the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) issued statements on prevention of group B streptococcal (GBS) disease. To assess prevention practices and identify barriers to preventing GBS disease, we surveyed obstetricians, family practitioners and general practitioners in Georgia during 1993. A standard questionnaire was mailed to 1190 clinicians in August and to nonresponders again in September. Of 436 (38%) physicians who responded, 192 (44%) provided obstetric care. Among these 192 obstetric care providers, 121 (63%) screened patients for GBS carriage antenatally. The most frequently cited reasons for not screening were "no clear guidelines" and "not cost-effective" (52 and 39%, respectively). Clinicians who screened patients were significantly more likely to believe that screening was cost-effective (P = 0.05). Of obstetric care providers who screened, only 9% obtained specimens using culture sites recommended by ACOG or AAP. Although most clinicians were aware that antenatal antibiotic treatment of carriers does not prevent perinatal GBS disease, 64% of those who screened reported that they gave oral antibiotics when carriage was detected during pregnancy. Of clinicians who reported using obstetric risk factors to guide prophylaxis choices, < 15% reported using intrapartum antibiotics for the conditions identified in the ACOG and AAP statements as those that suggest the need for prophylaxis when screening is not performed. Many Georgia obstetric care providers do not use effective practices to prevent perinatal GBS disease. Education on appropriate culture methods, obstetric risk factors and the cost effectiveness of prevention strategies might lead to more effective preventive practices.

The three-dimensional coordinates of points in the ribs of two supine relaxed males, holding their breath at functional residual capacity (FRC) and with their glottis closed at total lung capacity (TLC), were obtained from volumetric X-ray computed tomographical images. The orientation of planes that best fit the data for each rib at each lung volume and the circular arcs that fit the points in the planes of the ribs were determined, and average values of these geometrical parameters for ribs 3-7 are reported. The planes of the ribs at TLC can be described as displaced from the planes at FRC by a rotation about an axis that passes near the spine. The pump handle and bucket handle components of rotation are 11 and 13 degrees, respectively, for rib 3 and both decrease with increasing rib number to 7 and 10 degrees at rib 7. The angles between the axes of rotation and the midplane are approximately 35 degrees for all 5 ribs. The radii of the circular arcs fit to the data at TLC are slightly larger than those at FRC, and this suggests that there is a small component of rotation normal to the plane of the rib.