Emergence of the M phenotype of erythromycin-resistant pneumococci in South Africa.

Erythromycin-resistant pneumococci have been isolated in South Africa since 1978; however, from 1987 to 1996, resistance to macrolides was only detected in 270 (2.7%) of 9,868 blood or cerebrospinal fluid (CSF) pneumococcal isolates, most of which were obtained from the public sector. In South Africa, macrolide use in the public sector is estimated at 56% of that in the private sector. Most erythromycin-resistant strains (89%) exhibited resistance to erythromycin and clindamycin (macrolide-lincosamide-streptogramin B phenotype). In the United States, most erythromycin-resistant pneumococci exhibit the newly described M phenotype (resistance to erythromycin alone), associated with the mefE gene. The M phenotype in South Africa increased significantly in the last 10 years, from 1 of 5,115 to 28 of 4,735 of blood and CSF isolates received from 1987 to 1991 compared with 1992 to 1996 (p = 5 x 10(-7)). These data suggest that, although macrolide resistance in pneumococci remains low in the public sector, the mefE gene is rapidly emerging in South Africa

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. Among pneumococcal diagnostics currently under investigation, quantitative real-time polymerase chain reaction of respiratory secretions, as well as urinary antigen detection and pneumococcal surface adhesin A serological analysis for adults, are candidates for use in future clinical trials of antibiotic

'Atypical' bacteria are a common cause of community-acquired pneumonia in hospitalised adults

Objectives. To assess the proportion of cases of community· acquired pneumonia caused by 'atypical' bacteria, inclUding the recently discovered Chlamydia pneumoniae, and to compare the clinical, radiographic and laboratory features of patients with and without 'atypical' bacteria.Methods. A prospective serological study was carried out on consecutive adult pneumonia patients from July 1987 to July 1988. Acute and convalescent sera were tested in batches for antibodies against Legionella pneumophila serogroup 1, C. pneumoniae, Chlamydia psittaci, Coxiella burnetii (phase-2 antigen) and Mycoplasma pneumoniae (lgG and IgM). Records and chest radiographs were examined retrospectively.Results. Acute and convalescent sera were available from 113 patients. The records of 4 patients could not be traced and 17 patients did not fulfil the inclusion criteria. Thirty-two of these 92 patients (35,9%) were found to be infected with 'atypical' bacteria. The two most common organisms were C. pneumoniae (20,7%) and L. pneumophila (8,7%). There. were no differences in the clinical and radiographic features of patients with and without 'atypical' bacteria. Clinicians prescribed erythromycin or tetracyclines with equal frequency in the two groups.Conclusions. 'Atypical' bacteria, especially C. pneumoniae, are a common cause of community-acquired pneumonia in adults in South Africa. This is the first demonstration of an aetiological role of C. pneumoniae in this country. We confirmed the finding of other studies that there are no clinical, radiographic or laboratory features characteristic of 'atypical' bacterial infection in hospitalised patients. This has major implications for therapy, as these organisms respond to erythromycin and tetracyclines, but· not to β-lactam antibiotics

Surveillance of resistance in bacteria causing community‐acquired respiratory tract infections

Bacterial resistance to antibiotics in community‐acquired respiratory tract infections is a serious problem and is increasing in prevalence world‐wide at an alarming rate. Streptococcus pneumoniae, one of the main organisms implicated in respiratory tract infections, has developed multiple resistance mechanisms to combat the effects of most commonly used classes of antibiotics, particularly the β‐lactams (penicillin, aminopenicillins and cephalosporins) and macrolides. Furthermore, multidrug‐resistant strains of S. pneumoniae have spread to all regions of the world, often via resistant genetic clones. A similar spread of resistance has been reported for other major respiratory tract pathogens, including Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. To develop and support resistance control strategies it is imperative to obtain accurate data on the prevalence, geographic distribution and antibiotic susceptibility of respiratory tract pathogens and how this relates to antibiotic prescribing patterns. In recent years, significant progress has been made in developing longitudinal national and international surveillance programs to monitor antibiotic resistance, such that the prevalence of resistance and underlying trends over time are now well documented for most parts of Europe, and many parts of Asia and the Americas. However, resistance surveillance data from parts of the developing world (regions of Central America, Africa, Asia and Central/Eastern Europe) remain poor. The quantity and quality of surveillance data is very heterogeneous; thus there is a clear need to standardize or validate the data collection, analysis and interpretative criteria used across studies. If disseminated effectively these data can be used to guide empiric antibiotic therapy, and to support—and monitor the impact of—interventions on antibiotic resistance

Interrelationship of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus colonization within and between pneumococcal-vaccine naïve mother-child dyads

Background: A high prevalence of bacterial nasopharyngeal co-infections has been reported in children, however, such data is limited in adults. We examined the interaction of Haemophilus influenzae, Staphylococcus aureus and Streptococcus pneumoniae pharyngeal colonization in mother-child dyads. Methods: Pneumococcal-vaccine naïve children and their mothers had pharyngeal swabs undertaken at 1.6, 2.5, 3.5, 4.5, 7.4, 9.5, 12.5, 16.2 and 24.2 months of child’s age. Swabs were cultured for S. pneumoniae, H. influenzae and S. aureus using standard microbiologic methods. Multivariate generalized estimating equation-models were used to explore the associations of the three bacteria within and between children and their mothers. Results: In children, the observed probability of co-colonization was higher than expected. Well-defined associations in colonization between the bacteria were observed in children but not among mothers. In children, a synergistic association was observed between S. pneumoniae and H. influenzae (Adjusted odds ratio (AOR): 1.75, 95% CI: 1.32-2.32) and a negative association between S. pneumoniae and S. aureus (AOR: 0.51, 95% CI: 0.39-0.67) or H. influenzae and S. aureus (AOR: 0.24, 95% CI: 0.16-0.34) colonization. Additionally, all three bacteria had a higher likelihood of concurrent colonization. There was a strong association in colonization by the bacteria in children and their mothers, including increased likelihood of maternal colonization if the child was colonized by S. pneumoniae (AOR: 1.84, 95% CI: 1.28-2.63) and H. influenzae (AOR: 6.34, 95% CI: 2.24-18.0). Conclusions: The effects of immunization of children with pneumococcal-conjugate-vaccine in settings such as ours needs monitoring with regard to potential changes of pharyngeal bacterial ecology which could occur in vaccinated and –unvaccinated age-groups

Impact of 13-valent pneumococcal conjugate vaccine (PCV13) in a pandemic similar to the 2009 H1N1 in the United States

Background: High rates of bacterial coinfection in autopsy data from the 2009 H1N1 influenza (“flu”) pandemic suggest synergies between flu and pneumococcal disease (PD) during pandemic conditions, and highlight the importance of interventions like the 13-valent pneumococcal conjugate vaccine (PCV13) that may mitigate the impact of a pandemic. Methods: We used a decision-analytic model, estimated from published sources, to assess the impact of pediatric vaccination with PCV13 versus the 7-valent vaccine (PCV7) on PD incidence and mortality in a normal flu season (10% flu incidence) and in a pandemic similar to 2009-2010 H1N1 (20% flu incidence, mild virulence, high impact in children). Both direct and indirect (herd) effects against PD were considered. Effectiveness of PCV13 was extrapolated from observed PCV7 data, using assumptions of serotype prevalence and PCV13 protection against the 6 serotypes not in PCV7. To simulate 2009–2010 H1N1, autopsy data were used to estimate the overall proportion of flu deaths with bacterial coinfections. By assuming that increased risk of death during the pandemic occurred among those with comorbidity (using obesity as proxy) and bacterial coinfections primarily due to S. pneumoniae or S. aureus, we estimated the proportion co-infected among all (fatal and non-fatal) flu cases (7.6% co-infected with any organism; 2.2% with S. pneumoniae). PD incidence, mortality, and total healthcare costs were evaluated over a 1-year horizon. Results: In a normal flu season, compared to PCV7, PCV13 is expected to prevent an additional 13,400 invasive PD (IPD) cases, 399,000 pneumonia cases, and 2,900 deaths, leading to cost savings of $472 M. In a pandemic similar to 2009–2010 H1N1, PCV13 would prevent 22,800 IPD cases, 872,000 pneumonia cases, and 3,700 deaths, resulting in cost savings of$1.0 B compared to PCV7. Conclusions: In a flu pandemic similar to the 2009–2010 H1N1, protection against the 6 additional serotypes in PCV13 would likely be effective in preventing pandemic-related PD cases, mortality, and associated costs

Maternal Influenza Immunization and Reduced Likelihood of Prematurity and Small for Gestational Age Births: A Retrospective Cohort Study

In an analysis of surveillance data from the state of Georgia (US), Saad Omer and colleagues show an association between receipt of influenza vaccination among pregnant women and reduced risk of premature births

Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data

Background: Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%. Methods: This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant. Results: Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged ≤59 months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program. Conclusions: Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort

Imputing direct and indirect vaccine effectiveness of childhood pneumococcal conjugate vaccine against invasive disease by surveying temporal changes in nasopharyngeal pneumococcal colonization

The limited capabilities in most low-middle income countries to study the benefit of pneumococcal conjugate vaccine (PCV) against invasive pneumococcal disease (IPD), calls for alternate strategies to assess this. We used a mathematical model, to predict the direct and indirect effectiveness of PCV by analyzing serotype specific colonization prevalence and IPD incidence prior to and following childhood PCV immunization in South Africa. We analyzed IPD incidence from 2005-2012 and colonization studies undertaken in HIV-uninfected and HIV-infected child-mother dyads from 2007-2009 (pre-PCV era), in 2010 (7-valent PCV era) and 2012 (13-valent PCV era). We compared the model-predicted to observed changes in IPD incidence, stratified by HIV-status in children >3 months to 5 years and also in women aged >18-45 years. We observed reductions in vaccine-serotype colonization and IPD due to vaccine serotypes among children and women after PCV introduction. Using the changes in vaccine-serotype colonization data, the model-predicted changes in vaccine-serotype IPD incidence rates were similar to the observed changes in PCV-unvaccinated children and adults, but not among children <24 months. Surveillance of colonization prior and following PCV use can be used to impute PCVs' indirect associations in unvaccinated age groups, including in high HIV-prevalence settings