Telithromycin resistance in Streptococcus pneumoniae is conferred by a deletion in the leader sequence of erm(B) that increases rRNA methylation.

A telithromycin-resistant clinical isolate of Streptococcus pneumoniae (strain P1501016) has been found to contain a version of erm(B) that is altered by a 136-bp deletion in the leader sequence. By allele replacement mutagenesis, a second strain of S. pneumoniae (PC13) with a wild-type erm(B) gene was transformed to the telithromycin-resistant phenotype by introduction of the mutant erm(B) gene.

Long-term effect of pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae--and associated interactions with Staphylococcus aureus and Haemophilus influenzae colonization--in HIV-Infected and HIV-uninfected children.

After a primary series of 3 doses, it was found that a 9-valent pneumococcal conjugate vaccine no longer reduces nasopharyngeal colonization by vaccine serotypes in children 5.3 years of age. In addition, human immunodeficiency virus (HIV)-infected children (n=81) had a higher prevalence of colonization by Streptococcus pneumoniae and Haemophilus influenzae (71.

Introduction: historical perspective and development of amoxicillin/clavulanate.

Infections are currently ranked as the leading global burden of disease with respiratory diseases playing the most significant role. Antibiotic resistance remains a serious problem, as it was even 50 years ago. The 1970s saw the introduction of a number of important new antimicrobial agents, such as amoxicillin, but despite a high level of clinical success, a serious mechanism of resistance had emerged which could render the penicillins inactive - beta-lactamase production.

Seasonality, incidence, and repeat human metapneumovirus lower respiratory tract infections in an area with a high prevalence of human immunodeficiency virus type-1 infection.

Background: There is limited information regarding the epidemiology of human metapneumovirus (hMPV) from Africa, despite it being identified as a common pathogen in children with pneumonia.

Objectives: Determine the epidemiology of severe hMPV-associated lower respiratory tract infection (LRTI) in human immunodeficiency virus type-1 (HIV) infected and uninfected children.

Methods: Nasopharyngeal aspirate samples from children hospitalized for LRTI between January 2000 and December 2002 were analyzed for common respiratory viruses using an immunofluorescence assay; and 2715 available nasopharyngeal aspirate samples were tested for hMPV by reverse-transcriptase polymerase chain reaction targeting its fusion protein.

Streptococcus pneumoniae bacteraemia: pharmacodynamic correlations with outcome and macrolide resistance--a controlled study.

There are few data on macrolide pharmacodynamics in pneumococcal infections. We evaluated pneumococcal area under the inhibitory concentration-time curve (AUIC) values at the point of hospital admission in 59 bacteraemic patients failing in the community and in 98 bacteraemic controls without macrolide exposure. The area under the 24-h concentration-time curve (AUC24) was calculated for each patient using age, weight and daily dose; using minimum inhibitory concentrations (MICs), the values of AUIC (i.

Bacteraemic pneumococcal pneumonia: impact of HIV on clinical presentation and outcome.

Objectives: The objectives of this study were to investigate the clinical and laboratory features, hospital course and outcome of patients with bacteraemic pneumococcal pneumonia, comparing HIV with non-HIV patients, as well as HIV patients from different parts of the world.

Methods: This was a multicentre prospective observational study of consecutive adult cases with bacteraemic pneumococcal pneumonia in 10 countries on 6 continents.

Results: A total of 768 cases were recruited, of which 200 were HIV-infected; 166 were from South Africa.

Meningococcal disease in South Africa, 1999-2002.

We describe the epidemiology of invasive meningococcal disease in South Africa from August 1999 through July 2002, as reported to a laboratory-based surveillance system. Neisseria meningitidis isolates were further characterized. In total, 854 cases of laboratory-confirmed disease were reported, with an annual incidence rate of 0.

Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies.

Estimates of minimum protective antibody concentrations for vaccine preventable diseases are of critical importance in assessing whether new vaccines will be as effective as those for which clinical efficacy was shown directly. We describe a method for correlating pneumococcal anticapsular antibody responses of infants immunized with pneumococcal conjugate (PnC) vaccine (Prevenar) with clinical protection from invasive pneumococcal disease (IPD). Data from three double blind controlled trials in Northern Californian, American Indian and South African infants were pooled in a meta-analysis to derive a protective concentration of 0.

Clinical impact of antibiotic resistance in respiratory tract infections.

Streptococcus pneumoniae is the most common causative pathogen of community-acquired respiratory tract infections. In vitro evidence indicates that S. pneumoniae is increasingly resistant to commonly prescribed antimicrobial agents including the macrolides.

Increased antimicrobial resistance among nonvaccine serotypes of Streptococcus pneumoniae in the pediatric population after the introduction of 7-valent pneumococcal vaccine in the United States.

Background: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in the United States in February 2000. The PROTEKT US study evaluated serotype distribution, PCV7 coverage and antimicrobial susceptibility among Streptococcus pneumoniae isolates collected from children aged 0 to 14 years in 2000 through 2001 (year 1; n = 2033), 2002 through 2003 (year 3; n = 1740) and 2003 through 2004 (year 4; n = 1591).

Methods: Serotyping was performed by Neufeld Quellung reaction.

High-level telithromycin resistance in a clinical isolate of Streptococcus pneumoniae.

A rare clinical isolate of Streptococcus pneumoniae, highly resistant to telithromycin, contained erm(B) with a truncated leader peptide and a mutant ribosomal protein L4. By transformation of susceptible strains, this study shows that high-level telithromycin resistance is conferred by erm(B), wild type or mutant, in combination with a (69)GTG(71)-to-TPS mutation in ribosomal protein L4.

HIV and pneumococcal disease.

Purpose Of Review: To describe the impact of highly active antiretroviral therapy on the burden of pneumococcal disease and advances in our understanding of the impact of HIV on this disease.

Recent Findings: Although highly active antiretroviral therapy has reduced the burden of pneumococcal disease among HIV-infected adults, these infections remain far more common than in HIV uninfected adults. HIV-infected adults who smoke or have comorbidities are at particular risk.

Fitness costs of fluoroquinolone resistance in Streptococcus pneumoniae.

The fitness cost of the genes responsible for resistance to fluoroquinolones in clinical isolates of Streptococcus pneumoniae were estimated in vitro in a common genetic background. Naturally occurring parC, parE, and gyrA loci containing mutations in the quinolone-resistance-determining regions were introduced by transformation into S. pneumoniae strain R6 individually and in combinations.

Long-term immunogenicity and efficacy of a 9-valent conjugate pneumococcal vaccine in human immunodeficient virus infected and non-infected children in the absence of a booster dose of vaccine.

The long-term immunogenicity and vaccine efficacy (VE) of a 9-valent conjugate pneumococcal vaccine was studied in HIV infected and HIV non-infected children. VE against vaccine-serotype invasive pneumococcal disease following 6.16 years of follow-up persisted in HIV non-infected children (77.

World Health Organisation definition of "radiologically-confirmed pneumonia" may under-estimate the true public health value of conjugate pneumococcal vaccines.

The public health benefit of conjugate pneumococcal vaccine (PCV) in preventing pneumonia would only be appreciated if the tool used for measuring "pneumococcal pneumonia" had good sensitivity. Exploratory studies in South Africa indicate that the sensitivity of "radiologically-confirmed pneumonia" (CXR-AC) underestimates the burden of pneumococcal pneumonia prevented by PCV by as much as 63%. The use of alternate markers such as C-reactive protein enhance the ability of measuring the burden of pneumonia preventable by PCV.

Five-year cohort study of hospitalization for respiratory syncytial virus associated lower respiratory tract infection in African children.

Objectives: To describe the epidemiology of respiratory syncytial virus (RSV) associated lower respiratory tract infection (RSV-LRTI) hospitalizations in South African children over a 5-year period, and determine the impact of gestational age (GA) on the incidence of RSV-LRTI hospitalization.

Study Design: A cohort of 39,836 children, 6.47% of whom were HIV infected, enrolled into a phase 3 trial were prospectively studied for respiratory viruses when hospitalized for LRTI.

Pneumococcal coinfection with human metapneumovirus.

Background: Infection with the newly discovered human metapneumovirus (hMPV) may lead to hospitalization of children with lower respiratory tract infection (LRTI), although the pathogenesis thereof remains to be elucidated.

Methods: This hypothesis-generating study involved a cohort of children randomized to receive 9-valent conjugate pneumococcal vaccine or placebo and who were tested for hMPV infection when hospitalized for LRTI. By use of a nested reverse-transcription polymerase chain reaction assay targeted at amplifying a fragment of the hMPV fusion (F) protein gene, 202 such infections were identified among 2715 episodes of LRTI in children.

Prevalence of first-step mutants among levofloxacin-susceptible invasive isolates of Streptococcus pneumoniae in the United States.

By use of a PCR-restriction fragment length polymorphism assay, we screened 496 levofloxacin-susceptible invasive pneumococcal strains (MIC View Article and Find Full Text PDF