Vital Signs: Health Care-Associated Legionnaires' Disease Surveillance Data From 20 States and a Large Metropolitan Area-United States, 2015.

BACKGROUND: Legionnaires' disease, a severe pneumonia, is typically acquired through inhalation of aerosolized water containing Legionella bacteria. Legionella can grow in the complex water systems of buildings, including health care facilities. Effective water management programs could prevent the growth of Legionella in building water systems. METHODS: Using national surveillance data, Legionnaires' disease cases were characterized from the 21 jurisdictions (20 U.S. states and one large metropolitan area) that reported exposure information for ≥90% of 2015 Legionella infections. An assessment of whether cases were health care-associated was completed; definite health care association was defined as hospitalization or long-term care facility residence for the entire 10 days preceding symptom onset, and possible association was defined as any exposure to a health care facility for a portion of the 10 days preceding symptom onset. All other Legionnaires' disease cases were considered unrelated to health care. RESULTS: A total of 2,809 confirmed Legionnaires' disease cases were reported from the 21 jurisdictions, including 85 (3%) definite and 468 (17%) possible health care-associated cases. Among the 21 jurisdictions, 16 (76%) reported 1-21 definite health care-associated cases per jurisdiction. Among definite health care-associated cases, the majority (75, 88%) occurred in persons aged ≥60 years, and exposures occurred at 72 facilities (15 hospitals and 57 long-term care facilities). The case fatality rate was 25% for definite and 10% for possible health care-associated Legionnaires' disease. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Exposure to Legionella from health care facility water systems can result in Legionnaires' disease. The high case fatality rate of health care-associated Legionnaires' disease highlights the importance of case prevention and response activities, including implementation of effective water management programs and timely case identification.

Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA.

The effect of second-generation pneumococcal conjugate vaccines on invasive pneumococcal disease (IPD) strain distributions have not yet been well described. We analysed IPD isolates recovered from children aged <5 years through Active Bacterial Core surveillance before (2008-2009; n = 828) and after (2011-2013; n = 600) 13-valent pneumococcal conjugate vaccine (PCV13) implementation. We employed conventional testing, PCR/electrospray ionization mass spectrometry and whole genome sequence (WGS) analysis to identify serotypes, resistance features, genotypes, and pilus types. PCV13, licensed in February 2010, effectively targeted all major 19A and 7F genotypes, and decreased antimicrobial resistance, primarily owing to removal of the 19A/ST320 complex. The strain complex contributing most to the remaining ß-lactam resistance during 2011-2013 was 35B/ST558. Significant emergence of non-vaccine clonal complexes was not evident. Because of the removal of vaccine serotype strains, positivity for one or both pilus types (PI-1 and PI-2) decreased in the post-PCV13 years 2011-2013 relative to 2008-2009 (decreases of 32-55% for PI-1, and >95% for PI-2 and combined PI-1 + PI-2). ß-Lactam susceptibility phenotypes correlated consistently with transpeptidase region sequence combinations of the three major penicillin-binding proteins (PBPs) determined through WGS analysis. Other major resistance features were predictable by DNA signatures from WGS analysis. Multilocus sequence data combined with PBP combinations identified progeny, serotype donors and recipient strains in serotype switch events. PCV13 decreased the frequency of all PCV13 serotype clones and concurrently decreased the frequency of strain subsets with resistance and/or adherence features conducive to successful carriage. Our results serve as a reference describing key features of current paediatric IPD strains in the USA after PCV13 implementation.

Seasonal isolation of microalgae from municipal wastewater for remediation and biofuel applications.

AIMS: The objective of the study was to isolate the microalgae strains from treated municipal wastewater in both summer and winter seasons in order to identify strains better suited for nutrient remediation and biofuel production under either cooler or warmer temperatures. METHODS AND RESULTS: Fifty-six strains in total were isolated and identified by DNA sequencing from effluent samples collected from a local wastewater treatment plant during the summer and winter of 2011. Screening of 41 isolates based on the fatty acid productivity at either 22 or 10°C resulted in the selection of 12 strains organized into two groups of 6-the M (mild) and C (cool) groups, respectively. Four of the C-group strains were isolated from the winter sample, while four of the M-group isolates were isolated from the summer sample. Fatty acid pools in M-group strains were heavily regulated in response to growth temperature while C-group strains were more insensitive. In three of the six C-group strains, the rates of biomass and fatty acid productivity at 10°C exceeded the corresponding rates at 22°C. Conversely, M group were always more productive at 22 compared to 10°C. Mixotrophic strategies to enhance productivity were generally unsuccessful in M-group strains at 22°C but proved to be more effective in C-group cultures at 10°C. CONCLUSIONS: In general, C-group strains appeared better suited for growth in municipal wastewater at 10°C, while M-group strains were better suited at 22°C. On balance, C-group isolates were more likely to come from winter wastewater samples while M-group strains were more likely to come from the summer sample. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results demonstrate that the effects of temperature on microalgal growth for wastewater remediation can be mitigated somewhat by isolation and careful selection of strains adapted to seasonal wastewater conditions.

Simultaneous remediation of nutrients from liquid anaerobic digestate and municipal wastewater by the microalga Scenedesmus sp. AMDD grown in continuous chemostats.

AIMS: The primary aim of this study was to investigate the capacity of a microalga, Scenedesmus sp. AMDD, to remediate nutrients from municipal wastewater, either as the sole nutrient source or after blending with wastewater obtained from the anaerobic digestion of swine manure. A complimentary aim was to study and define the effects of these wastewaters on microalgal growth, biomass productivity and composition which have important implications for a commercial biofuels production system. METHODS AND RESULTS: A microalga, Scenedesmus sp. AMDD, was grown in continuous chemostats in municipal wastewater or wastewater supplemented with 1·6× or 2·4× higher levels of nitrogen (N) obtained through supplementation with anaerobic digestates. Biomass productivity increased with increasing nutrient supplementation, but was limited by light at high cell densities. Cellular quotas of carbon (C), nitrogen and phosphorus (P) all increased in direct proportion to their concentrations in the combined wastewaters. At higher cell densities, total carbohydrate decreased while protein increased. Fatty acid content remained relatively constant. Under high nutrient levels, the fatty acid profiles contained a higher concentration of polyunsaturated fatty acids at the expense of monounsaturated fatty acids. Chlorophyll a was 2·5 times greater in the treatment of greatest nutrient supplementation compared to the treatment with the least. Ammonium (NH4(+)) and phosphate (PO4(3-)) were completely removed by algal growth in all treatments and with maximal removal rates of 41·2 mg N l(-1) d(-1) and 6·7 mg P l(-1) d(-1) observed in wastewater amended with 2·4× higher N level. SIGNIFICANCE AND IMPACT OF THE STUDY: The study is the first to report stable, long-term continuous algal growth and productivity obtained by combining wastewaters of different sources. The study is supported by detailed analyses of the composition of the cultivated biomass and links composition to the nutrient and light availabilities in the cultures. Simultaneous remediation of these wastes by algal growth is discussed as a strategy for the valorization of the biomass.

Use of serology and urine antigen detection to estimate the proportion of adult community-acquired pneumonia attributable to Streptococcus pneumoniae.

Streptococcus pneumoniae is a common cause of community-acquired pneumonia (CAP) but existing diagnostic tools have limited sensitivity and specificity. We enrolled adults undergoing chest radiography at three Indian Health Service clinics in the Southwestern United States and collected acute and convalescent serum for measurement of PsaA and PspA titres and urine for pneumococcal antigen detection. Blood and sputum cultures were obtained at the discretion of treating physicians. We compared findings in clinical and radiographic CAP patients to those in controls without CAP. Urine antigen testing showed the largest differential between CAP patients and controls (clinical CAP 13%, radiographic CAP 17%, control groups 2%). Serological results were mixed, with significant differences between CAP patients and controls for some, but not all changes in titre. Based on urine antigen and blood culture results, we estimated that 11% of clinical and 15% of radiographic CAP cases were due to pneumococcus in this population.

Measuring the incidence of adult community-acquired pneumonia in a Native American community.

Few population-based studies have investigated the epidemiology of adult community-acquired pneumonia (CAP). We aimed to determine the incidence of CAP in a population at high-risk for pneumococcal disease and to evaluate a standardized method for interpreting chest radiographs adapted from the World Health Organization paediatric chest radiograph interpretation guidelines. We reviewed radiology records at the two healthcare facilities serving the White Mountain Apache tribe to identify possible pneumonia cases > or =40 years of age. We categorized patients with clinical criteria and a physician diagnosis of pneumonia as clinical CAP and those with clinical criteria and an acute infiltrate as radiographic CAP. We identified 100 (27/1000 person-years) and 60 (16/1000 person-years) episodes of clinical and radiographic CAP, respectively. The incidence of CAP increased with age. Both radiographic and clinical CAP were serious illnesses with more than half of patients hospitalized. Our case definitions and methods may be useful for comparing data across studies and conducting vaccine trials.

Increased rainfall is associated with increased risk for legionellosis.

Legionnaires' disease (LD) is caused by Legionella species, most of which live in water. The Mid-Atlantic region experienced a sharp rise in LD in 2003 coinciding with a period of record-breaking rainfall. To investigate a possible relationship, we analysed the association between monthly legionellosis incidence and monthly rainfall totals from January 1990 to December 2003 in five Mid-Atlantic states. Using negative binomial model a 1-cm increase in rainfall was associated with a 2.6% (RR 1.026, 95% CI 1.012-1.040) increase in legionellosis incidence. The average monthly rainfall from May to September 1990-2002 was 10.4 cm compared to 15.7 cm from May to September 2003. This change in rainfall corresponds to an increased risk for legionellosis of approximately 14.6% (RR 1.146, 95% CI 1.067-1.231). Legionellosis incidence increased during periods of increased rainfall; identification of mechanisms that increase exposure and transmission of Legionella during rainfall might lead to opportunities for prevention.

Detection of resistance to gatifloxacin and moxifloxacin in Streptococcus pneumoniae with the VITEK 2 instrument.

A group of 72 pneumococcal isolates resistant or intermediate to levofloxacin and 124 pneumococcal isolates susceptible to fluoroquinolones were tested by the VITEK 2 instrument using investigational test cards and by a broth microdilution reference method. The VITEK 2 instrument performed well, detecting 52 of 60 (86.7%) gatifloxacin-resistant isolates and 22 of 23 moxifloxacin-resistant isolates, and did not falsely classify any susceptible isolates as resistant.

The international infections in pregnancy study: group B streptococcal colonization in pregnant women.

BACKGROUND: Heavy colonization with group B streptococcus (GBS) has been associated with increased risk of preterm birth and neonatal sepsis; the burden of neonatal GBS disease varies geographically. To determine whether variation in heavy colonization and GBS serotypes could contribute to geographic differences in disease burden, we assessed the prevalence of heavy colonization and the distribution of serotypes in asymptomatic pregnant women in multiple countries. METHODS: Cervical, lower vaginal and urine samples were collected from women attending seven prenatal clinics in six countries. Light colonization was defined as GBS isolation from Lim broth only; heavy colonization was isolation from urine or sheep blood agar plates. Isolates were serotyped using capillary precipitation. RESULTS: GBS was present in 11.3% of 1308 participants (range 7.1-21.7%); 5.0% were heavily colonized (0.4-18.8%) and 6.4% were lightly colonized (2.9-8.0%). Serotypes III and V were most common (both 17.2%). Serotypes VII and VIII were found in one study center. CONCLUSIONS: The prevalence of heavy colonization and GBS serotypes varied significantly among our study centers. Whether this variation could in part explain geographic differences in neonatal morbidity and mortality is a hypothesis that needs further study.

Activity of daptomycin against recent North American isolates of Streptococcus pneumoniae.

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.

Multistate evaluation of invasive pneumococcal diseases in adults with human immunodeficiency virus infection: serotype and antimicrobial resistance patterns in the United States.

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.

Macrolide resistance among invasive Streptococcus pneumoniae isolates.

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.

Randomized trial of the quantitative and functional antibody responses to a 7-valent pneumococcal conjugate vaccine and/or 23-valent polysaccharide vaccine among HIV-infected adults.

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.

Rethinking recommendations for use of pneumococcal vaccines in adults.

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.

Factors associated with self-reported pneumococcal immunization among adults 65 years of age or older in the Minneapolis-St. Paul metropolitan area.

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.

Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995-1998: Opportunities for prevention in the conjugate vaccine era.

CONTEXT: Pneumococcal polysaccharide vaccine is recommended for elderly persons and adults with certain chronic illnesses. Additionally, a recently licensed pneumococcal 7-valent conjugate vaccine has been recommended for use in young children and could dramatically change the epidemiology of pneumococcal disease. OBJECTIVES: To assess pneumococcal disease burden in the United States, estimate the potential impact of new vaccines, and identify gaps in vaccine recommendations. DESIGN AND SETTING: Analysis of data from the Active Bacterial Core Surveillance (ABCs)/Emerging Infections Program Network, an active, population-based system in 9 states. PATIENTS: A total of 15 860 cases of invasive pneumococcal disease occurring between January 1, 1995, and December 31, 1998. MAIN OUTCOME MEASURES: Age- and race-specific pneumoccocal disease incidence rates per 100 000 persons, case-fatality rates, and vaccine preventability. RESULTS: In 1998, overall incidence was 23.2 cases per 100 000, corresponding to an estimated 62 840 cases in the United States. Incidence was highest among children younger than 2 years (166.9) and adults aged 65 years or older (59.7). Incidence among blacks was 2.6 times higher than among whites (95% confidence interval [CI], 2.4-2.8). Overall, 28.6% of case-patients were at least 65 years old and 85.9% of cases in this age group were due to serotypes included in the 23-valent polysaccharide vaccine; 19.3% of case-patients were younger than 2 years and 82.2% of cases in this age group were due to serotypes included in the 7-valent conjugate vaccine. Among patients aged 2 to 64 years, 50.6% had a vaccine indication as defined by the Advisory Committee on Immunization Practices (ACIP). The case-fatality rate among patients aged 18 to 64 years with an ACIP indication was 12.1% compared with 5.4% for those without an indication (relative risk, 2.2; 95% CI, 1.7-2.9). CONCLUSIONS: Young children, elderly persons, and black persons of all ages are disproportionately affected by invasive pneumococcal disease. Current ACIP recommendations do not address a subset of persons aged 18 to 64 years but do include those at highest risk for death from invasive pneumococcal disease.

Evaluation of a medium (STGG) for transport and optimal recovery of Streptococcus pneumoniae from nasopharyngeal secretions collected during field studies.

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.

Clonal groups of penicillin-nonsusceptible Streptococcus pneumoniae in Baltimore, Maryland: a population-based, molecular epidemiologic study.

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.

The emergence of Streptococcus pneumoniae resistant to macrolide antimicrobial agents: a 6-year population-based assessment.

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.

Activities of clinafloxacin, gatifloxacin, gemifloxacin, and trovafloxacin against recent clinical isolates of levofloxacin-resistant Streptococcus pneumoniae.

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.