Trends in antimicrobial resistance and serotype distribution of blood and cerebrospinal fluid isolates of streptococcus pneumoniae in South Africa, 1991–1998

AbstractObjective: Since 1979, the South African Institute for Medical Research (SAIMR) has served as the national reference center for pneumococcal serotyping and monitoring of antibiotic resistance trends. This study documents trends in antimicrobial resistance in pneumococci isolated from blood or cerebrospinal fluid (CSF) between 1991 and 1998 in South Africa.Methods: Pneumococcal isolates (n = 7406) from either blood or CSF were sent to the SAIMR reference laboratory for serotyping. The isolates were evaluated for resistance to penicillin, chloramphenicol, tetracycline, erythromycin, clindamycin, and rifampicin.Results: Resistance to one or more antibiotics increased significantly from 19% in 1991 to 1994 to 25% in 1995 to 1998 in all ages, and in children from 32% to 38% (P < 10−6). Although penicillin resistance did not increase in children (28.1% vs. 28.9%), penicillin resistance in all ages increased from 9.6% to 18.0%. Significant increases in resistance to chloramphenicol, tetracycline, erythromycin, and rifampicin also were seen in both groups. Multiple resistance increased significantly, from 2.2% to 3.8%. The proportion of isolates with intermediate or high-level penicillin resistance remained constant during the surveillance period. Erythromycin resistance, predominantly expressed as simultaneous resistance to erythromycin and clindamycin, increased from 1.6% to 2.6%. The percentage of erythromycin-resistant isolates that were resistance to erythromycin alone increased from 10.6% to 28.7%, suggesting the emergence of mefE-mediated resistance. In children 2 years of age and younger, although serogroup 6 remained the most common, there were significant increases in serogroups 19, 18, and 13. The percentage of the total invasive pneumococcal disease in this population that is caused by serogroups found in the nonavalent pneumococcal conjugate vaccine (serogroups 1, 4, 5, 613, 9V, 14, 18C, 19F, 23F) increased from 72% to 91%.Conclusions: Antibiotic resistance in the pneumococcus is increasing in South Africa, although the proportion of strains with high-level penicillin resistance has not increased. New conjugate vaccines may not only decrease the burden of all pneumococcal disease but, in addition, lower the incidence of antibiotic-resistant disease in South Africa

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

The Battle against Emerging Antibiotic Resistance: Should Fluoroquinolones Be Used to Treat Children?

Inappropriate use of antibiotic drugs in humans and animals has led to widespread resistance among microbial pathogens. Resistance is the phenotypic expression corresponding to genetic changes caused by either mutation or acquisition of new genetic information. In some cases, multidrug resistance occurs. Streptococcus pneumoniae is one of the most important respiratory pathogens, playing a major role in both upper and lower respiratory tract infections. Pneumococcal resistance to antimicrobials may be acquired by means of horizontal transfer followed by homologous recombination of genetic material from the normal flora of the human oral cavity or by means of mutation. Resistance to penicillins and macrolides has been increasing for some time, but, recently, fluoroquinolone resistance has become an issue as well. We are concerned that, if fluoroquinolones are approved for use in children, their widespread use will result in rapid emergence of pneumococcal resistance, because children are more often colonized in the nasopharynx with high-density populations of pneumococci than are adult

Increased Nasopharyngeal Density and Concurrent Carriage of Streptococcus Pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis Are Associated with Pneumonia in Febrile Children.

We assessed nasopharyngeal (NP) carriage of five pathogens in febrile children with and without acute respiratory infection (ARI) of the upper (URTI) or lower tract, attending health facilities in Tanzania. NP swabs collected from children (N = 960) aged 2 months to 10 years, and with a temperature ≥38°C, were utilized to quantify bacterial density of S. pneumoniae (Sp), H. influenzae (Hi), M. catarrhalis (Mc), S. aureus (Sa), and N. meningitidis (Nm). We determined associations between presence of individual species, densities, or concurrent carriage of all species combination with respiratory diseases including clinical pneumonia, pneumonia with normal chest radiography (CXR) and endpoint pneumonia. Individual carriage, and NP density, of Sp, Hi, or Mc, but not Sa, or Nm, was significantly associated with febrile ARI and clinical pneumonia when compared to febrile non-ARI episodes. Density was also significantly increased in severe pneumonia when compared to mild URTI (Sp, p<0.002; Hi p<0.001; Mc, p = 0.014). Accordingly, concurrent carriage of Sp+, Hi+, and Mc+, in the absence of Sa- and Nm-, was significantly more prevalent in children with ARI (p = 0.03), or clinical pneumonia (p<0.001) than non-ARI, and in children with clinical pneumonia (p = 0.0007) than URTI. Furthermore, Sp+, Hi+, and Mc+ differentiated children with pneumonia with normal CXR, or endpoint pneumonia, from those with URTI, and non-ARI cases. Concurrent NP carriage of Sp, Hi, and Mc was a predictor of clinical pneumonia and identified children with pneumonia with normal CXR and endpoint pneumonia from those with febrile URTI, or non-ARI episodes

Impact of Experimental Human Pneumococcal Carriage on Nasopharyngeal Bacterial Densities in Healthy Adults

Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study’s sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute

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

Cohort Profile: The Study of Respiratory Pathogens in Andean Children

We investigated respiratory pathogens in a prospective cohort study of young children living in the Peruvian Andes. In the study we assessed viral respiratory infections among young children, and explored interactions of viruses with common respiratory bacteria, especially Streptococcus pneumoniae. Through weekly household visits, data were collected on the signs and symptoms of acute respiratory illness (ARI), nasal samples were collected to test for viruses during episodes of ARI, and nasopharyngeal samples were collected on a monthly basis to monitor bacterial colonisation. We also collected data on vaccination coverage, patterns of social mixing, geographic information, and environmental and socio-demographic variables. Understanding the interaction of respiratory viruses with bacteria and its impact on the burden and severity of ARIs in rural areas of developing countries is critical to designing strategies for preventing such infections. Investigators interested in more details about this study or in accessing these resources should contact Dr. Carlos G. Grijalva at Vanderbilt University ([email protected]

Nasopharyngeal pneumococcal density is associated with viral activity but not with use of improved stoves among young Andean children

Indoor smoke exposure is common in developing countries and may influence nasopharyngeal (NP) pneumococcal colonization density and risk of acute respiratory illness. We compared colonization density among Andean children living in households previously enrolled in a randomized controlled trial of a home intervention package including improved stoves to reduce smoke, kitchen sinks, and water disinfection.; We enrolled 260 children aged &lt;3 years and made weekly household visits to assess for acute respiratory illness (ARI) and collect nasal swabs for respiratory virus polymerase chain reaction (PCR) testing during ARI. At monthly intervals, NP swabs were collected to determine pneumococcal colonization density through quantitative lytA PCR. We used linear quantile mixed-effects models to compare median log-transformed colonization densities among children in households randomized to the control (n = 129) versus intervention (n = 131) in sequential time points, accounting for random effects of multiple="multiple" samples from individual children. Other covariates included age, sex, month, antibiotic exposure, and timing of sample collection relative to ARI with and without viral detection.; Age and sociodemographic characteristics were similar between groups. Although no differences were observed in densities between groups, colonization density varied significantly over time in both groups, with highest densities coinciding with spring months. Time during and after virus-associated ARI was also associated with higher pneumococcal colonization density than time remote from ARIs.; A home intervention package, including improved stoves, was not associated with changes in pneumococcal densities in young Andean children. However, increasing pneumococcal density was observed with spring season and viral-associated ARIs