In vitro evaluation of the antimicrobial activity of ceftaroline against cephalosporin-resistant isolates of Streptococcus pneumoniae.

Increasing pneumococcal resistance to extended-spectrum cephalosporins warrants the search for novel agents with activity against such resistant strains. Ceftaroline, a parenteral cephalosporin currently in phase 3 clinical development, has demonstrated potent in vitro activity against resistant gram-positive organisms, including penicillin-resistant Streptococcus pneumoniae. In this study, the activity of ceftaroline was evaluated against highly cefotaxime-resistant isolates of pneumococci from the Active Bacterial Core surveillance program of the Centers for Disease Control and Prevention and against laboratory-derived cephalosporin-resistant mutants of S.

Novel approaches to the identification of Streptococcus pneumoniae as the cause of community-acquired pneumonia.

Current diagnostic tests lack sensitivity for the identification of the bacterial etiology of pneumonia. Attempts during the past 2 decades to improve sensitivity of detection of bacterial constituents in blood by use of antibody-antigen complexes and polymerase chain reaction have been disappointing. Recent data using pneumococcal conjugate vaccines as probes suggest that increased levels of both C-reactive protein and procalcitonin may be useful adjuncts to chest radiographs in the selection of patients with presumed bacterial pneumonia for inclusion in clinical trials.

A disease model descriptive of progression between chronic obstructive pulmonary disease exacerbations and community-acquired pneumonia: roles for underlying lung disease and the pharmacokinetics/pharmacodynamics of the antibiotic.

Patients with chronic obstructive pulmonary disease (COPD) may progress to community-acquired pneumonia (CAP), but there has been no formal study of the factors responsible. We studied the influence of severity of underlying lung disease, pathogen characteristics and the ratio of the area under the concentration-time curve from 0-24h to minimum inhibitory concentration (AUC24/MIC), i.e.

Interaction between influenza virus and Streptococcus pneumoniae in severe pneumonia.

The contribution of bacterial superinfection to influenza-associated pneumonia morbidity and mortality is evident from the 1918 and 1957 influenza pandemics, and is supported by a number of murine model studies. Murine model studies have also assisted in helping to expand our understanding of the pathogenesis of the interaction between the influenza virus and subsequent susceptibility to pneumococcal superinfections. The purported impact that the pneumococcal conjugate vaccine has had on reducing the burden of confirmed influenza-associated pneumonia, as well as upon all-cause clinical pneumonia, provides additional clinical evidence of the role of superimposed pneumococcal infections as a cause of severe pneumonia in children.

Interspecies recombination occurs frequently in quinolone resistance-determining regions of clinical isolates of Streptococcus pyogenes.

Fluoroquinolone resistance in Streptococcus pyogenes has been reported only anecdotally, but a recent Belgian surveillance study found a rate of nonsusceptibility of 5.4%. From an analysis of these isolates, we show that interspecies horizontal gene transfer within the parC quinolone resistance-determining region is a frequent phenomenon that might contribute to fluoroquinolone resistance.

Serotype 6C is associated with penicillin-susceptible meningeal infections in human immunodeficiency virus (HIV)-infected adults among invasive pneumococcal isolates previously identified as serotype 6A in South Africa.

A newly described pneumococcal serotype (6C) is indistinguishable from serotype 6A when using the conventional Quellung serotyping method. Serotype 6A isolates were screened by polymerase chain reaction (PCR) for the wciN region of the capsular locus. This study detected serotype 6C among invasive pneumococcal disease (IPD) isolates from national laboratory-based surveillance (2005-2006) in South Africa.

Antimicrobial susceptibility and molecular epidemiology of Streptococcus pneumoniae isolated from Shanghai, China.

In this study, the antimicrobial resistance profiles of pneumococci isolated from respiratory specimens of patients from Shanghai, China, in 2004 and 2005 are described. Non-susceptible rates to penicillin and erythromycin among paediatric isolates (n=122) were 63.1% and 94.

Influenza guideline for South Africa--update 2008.

Objective: The South African Thoracic Society, in conjunction with interested stakeholders, published a Guideline for Influenza Management in Adults in 1999. This year the South African Thoracic Society (SATS) identified the need to revise that guideline for the following reasons: * To indicate the viral strains that are to be incorporated into the vaccine for the 2008 season * To add important new data regarding treatment of influenza * To add a section on influenza in children * To clarify issues in managing and preventing influenza in HIV-infected individuals.

Influenza Virus: The influenza virus genus belongs to the family orthomyxoviridae.

Neisseria meningitidis intermediately resistant to penicillin and causing invasive disease in South Africa in 2001 to 2005.

Neisseria meningitidis strains (meningococci) with decreased susceptibility to penicillin (MICs, >0.06 microg/ml) have been reported in several parts of the world, but the prevalence of such isolates in Africa is poorly described. Data from an active national laboratory-based surveillance program from January 2001 through December 2005 were analyzed.

Apnea and its possible relationship to immunization in ex-premature infants.

This study compared the characteristics of infants hospitalized with apnea that participated in a vaccine trial compared with two control groups which consisted of 100 infants randomly selected from the same vaccine trial and 52 consecutively born very low birth weight (VLBW) infants. A total of 23 infants were admitted with apnea of whom 19 weighed <1500 g at birth and all were born at <37 weeks gestation. More of the VLBW infants in the apnea group had neonatal neurological complications compared with the VLBW control group (p=0.

Emergence of levofloxacin-non-susceptible Streptococcus pneumoniae and treatment for multidrug-resistant tuberculosis in children in South Africa: a cohort observational surveillance study.

Background: Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa.

Methods: 21,521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003.

Molecular basis and clonal nature of increasing pneumococcal macrolide resistance in South Africa, 2000-2005.

The prevalence and molecular epidemiology of pneumococcal macrolide resistance in South Africa was investigated. Minimum inhibitory concentrations and serotypes of pneumococcal isolates causing invasive disease from 2000-2005 (n=15982), collected through a national laboratory-based surveillance system, were determined. Randomly selected isolates from 2005 (51%; 260/508) had resistance mechanisms determined, and clonality was investigated by pulsed-field gel electrophoresis (PFGE) (n=64) and multilocus sequence typing (n=7).

Impact of cotrimoxazole on non-susceptibility to antibiotics in Streptococcus pneumoniae carriage isolates among HIV-infected mineworkers in South Africa.

Objectives: To investigate risk factors for pneumococcal carriage and non-susceptibility among HIV-infected mineworkers in South Africa.

Methods: In a cross-sectional study, HIV clinic attendees were questioned about risk factors for pneumococcal carriage and antimicrobial non-susceptibility. Oropharyngeal and nasopharyngeal swabs were taken for pneumococcal culture, serotyping and susceptibility testing.

Risk factors for antibiotic resistance in Streptococcus pneumoniae.

Streptococcus pneumoniae (the pneumococcus) is the leading vaccine-preventable cause of death in children and adults. The management of pneumococcal infections is complicated by the development of resistance to antimicrobials. Risk factors for increased resistance include young age, isolation from the upper respiratory tract, hospitalisation, residence in an urban area, day care attendance, previous exposure to antibiotics, female gender, exposure to specific serotypes and clones, HIV infection and exposure to a class of drug to which resistance can be easily selected from a susceptible population of organisms.

Virulence characteristics of Klebsiella and clinical manifestations of K. pneumoniae bloodstream infections.

We studied 455 consecutive episodes of Klebsiella pneumoniae bacteremia occurring in 7 countries. Community-acquired pneumonia and an invasive syndrome of liver abscess, meningitis, or endophthalmitis occurred only in Taiwan and South Africa. Infections by K1 and K2 capsular serotype, the mucoid phenotype, and aerobactin production were important determinants of virulence.

Emergence of endemic serogroup W135 meningococcal disease associated with a high mortality rate in South Africa.

Background: In the African meningitis belt, Neisseria meningitidis serogroup W135 has emerged as a cause of epidemic disease. The establishment of W135 as the predominant cause of endemic disease has not been described.

Methods: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000-2005.

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.

Comparison of the effects of macrolides, amoxicillin, ceftriaxone, doxycycline, tobramycin and fluoroquinolones, on the production of pneumolysin by Streptococcus pneumoniae in vitro.

Objectives: To compare the effects of subinhibitory concentrations of amoxicillin, ceftriaxone, azithromycin, clarithromycin, erythromycin, telithromycin, clindamycin, ciprofloxacin, moxifloxacin, tobramycin and doxycycline on pneumolysin production by a macrolide-susceptible strain and two macrolide-resistant strains [erm(B) or mef(A)] of Streptococcus pneumoniae.

Methods: Pneumolysin was assayed using a functional procedure based on the influx of Ca(2+) into human neutrophils.

Results: Only the macrolides/macrolide-like agents caused significant attenuation of the production of pneumolysin, which was evident with all three strains of the pneumococcus.