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

'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

Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins.

Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR S Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the blaCTX-M-15 extended-spectrum β-lactamase, and carrying the qnrS fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited high sequence identity to plasmids found in other enteric bacteria isolated from widely distributed geographic locations. This study highlights three concerning problems: the receding antibiotic arsenal for typhoid treatment, the ability of S Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid, and the ability of XDR clones to spread globally.IMPORTANCE Typhoid fever is a severe disease caused by the Gram-negative bacterium Salmonella enterica serovar Typhi. Antibiotic-resistant S Typhi strains have become increasingly common. Here, we report the first large-scale emergence and spread of a novel extensively drug-resistant (XDR) S Typhi clone in Sindh, Pakistan. The XDR S Typhi is resistant to the majority of drugs available for the treatment of typhoid fever. This study highlights the evolving threat of antibiotic resistance in S Typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases. We genetically characterized the XDR S Typhi to investigate the phylogenetic relationship between these isolates and a global collection of S Typhi isolates and to identify multiple genes linked to antibiotic resistance. This S Typhi clone harbored a promiscuous antibiotic resistance plasmid previously identified in other enteric bacteria. The increasing antibiotic resistance in S Typhi observed here adds urgency to the need for typhoid prevention measures

Safety and immunogenicity of three doses of an eleven-valent diphtheria toxoid and tetanus protein – conjugated pneumococcal vaccine in Filipino infants

BACKGROUND: An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduction in pneumococcal disease burden than the currently available 7-valent vaccine formulation in many countries. METHODS: In total, 50 infants were enrolled to this open, uncontrolled study, which evaluated the safety and immunogenicity of an aluminium adjuvanted 11-valent mixed-carrier diphtheria toxoid or tetanus protein-conjugated vaccine (11-PncTD) when administered in three doses at 6, 10 and 14 weeks of age simultaneously with DTwP//PRP-T and OPV vaccines in Filipino infants. RESULTS: The rates of local reactions between the two injection sites, those associated with the 11-PncTD vaccine and those with the DTwP//PRP-T were almost of equal frequency for all three vaccine doses except for induration, which was significantly more common in the DTP//PRP-T injection site. Fever was present in 39%, 22% and 21% of infants following each of the three doses. Antibody responses were determined by an enzyme immunoassay method before the first vaccination and after the three doses. The vaccine elicited a significant anti-pneumococcal polysaccharide antibody response against all serotypes included in the vaccine, except for type 14, for which the pre-vaccination geometric mean antibody concentration (GMC) was high (1.61 μg/ml). The GMCs one month after the vaccination series ranged from 1.1 micrograms/ml for type 6B to 23.4 μg/ml for type 4. CONCLUSION: The 11-PncTD vaccine is safe, well-tolerated and immunogenic. The effectiveness of the non-adjuvanted formulation of the vaccine in preventing pneumonia is currently being evaluated in the Philippines

Characterising B cell numbers and memory B cells in HIV infected and uninfected Malawian adults

BACKGROUND: Untreated human immunodeficiency virus (HIV) disease disrupts B cell populations causing reduced memory and reduced naïve resting B cells leading to increases in specific co-infections and impaired responses to vaccines. To what extent antiretroviral treatment reverses these changes in an African population is uncertain. METHODS: A cross-sectional study was performed. We recruited HIV-uninfected and HIV-infected Malawian adults both on and off antiretroviral therapy attending the Queen Elizabeth Central hospital in Malawi. Using flow cytometry, we enumerated B cells and characterized memory B cells and compared these measurements by the different recruitment groups. RESULTS: Overall 64 participants were recruited - 20 HIV uninfected (HIV-), 30 HIV infected ART naïve (HIV+N) and 14 HIV-infected ART treated (HIV+T). ART treatment had been taken for a median of 33 months (Range 12-60 months). Compared to HIV- the HIV+N adults had low absolute number of naïve resting B cells (111 vs. 180 cells/μl p = 0.008); reduced memory B cells (27 vs. 51 cells/μl p = 0.0008). The HIV+T adults had B-cell numbers similar to HIV- except for memory B cells that remained significantly lower (30 vs. 51 cells/μl p = 0.02). In the HIV+N group we did not find an association between CD4 count and B cell numbers. CONCLUSIONS: HIV infected Malawian adults have abnormal B-cell numbers. Individuals treated with ART show a return to normal in B-cell numbers but a persistent deficit in the memory subset is noted. This has important implications for long term susceptibility to co-infections and should be evaluated further in a larger cohort study

Procalcitonin Predicts Response to Beta-Lactam Treatment in Hospitalized Children with Community-Acquired Pneumonia

BACKGROUND: Antibiotic treatment of community-acquired pneumonia (CAP) in children remains mostly empirical because clinical and paraclinical findings poorly discriminate the principal causes of CAP. Fast response to beta-lactam treatment can be considered a proxy of pneumococcal aetiology. We aimed to identify the best biological predictor of response to beta-lactam therapy in children hospitalized for CAP. METHODS: A retrospective, single-centre cohort study included all consecutive patients 1 month to 16 years old hospitalized in a teaching hospital in Paris, France, because of CAP empirically treated with a beta-lactam alone from 2003 to 2010. Uni- and multivariate analyses were used to study the ability of routine biological parameters available in the Emergency Department to predict a favourable response to beta-lactam (defined as apyrexia within 48 hours of treatment onset). RESULTS: Among the 125 included patients, 85% (106) showed a favourable response to beta-lactam. In multivariate logistic regression, we found procalcitonin (PCT) the only independent predictor of apyrexia (p = 0.008). The adjusted odds ratio for the decadic logarithm of PCT was 4.3 (95% CI 1.5-12.7). At ≥ 3 ng/mL, PCT had 55.7% sensitivity (45.7-65.3), 78.9% specificity (54.4-93.9), 93.7% positive predictive value (84.5-98.2), 24.2% negative predictive value (14.2-36.7), 2.64 positive likelihood ratio (1.09-6.42) and 0.56 negative likelihood ratio (0.41-0.77). In the 4 children with a PCT level ≥ 3 ng/mL and who showed no response to beta-lactam treatment, secondary pleural effusion had developed in 3, and viral co-infection was documented in 1. CONCLUSIONS: PCT is the best independent biologic predictor of favourable response to beta-lactam therapy in children hospitalized for CAP. Thus, a high PCT level is highly suggestive of pneumococcal aetiology. However, a 3-ng/mL cut-off does not seem compatible with daily medical practice, and additional research is needed to further define the role of PCT in managing CAP in children

Circulating TRAIL Shows a Significant Post-Partum Decline Associated to Stressful Conditions

Background: Since circulating levels of TNF-related apoptosis inducing ligand (TRAIL) may be important in the physiopathology of pregnancy, we tested the hypothesis that TRAIL levels change at delivery in response to stressful conditions. Methods/Principal Findings: We conducted a longitudinal study in a cohort of 73 women examined at week 12, week 16, delivery and in the corresponding cord blood (CB). Serum TRAIL was assessed in relationship with maternal characteristics and to biochemical parameters. TRAIL did not vary between 12 (67.6627.6 pg/ml, means6SD) and 16 (64.0616.2 pg/ml) weeks ’ gestation, while displaying a significant decline after partum (49.3626.4 pg/ml). Using a cut-off decline.20 pg/ml between week 12 and delivery, the subset of women with the higher decline of circulating TRAIL (41.7%) showed the following characteristics: i) nullipara, ii) higher age, iii) operational vaginal delivery or urgent CS, iv) did not receive analgesia during labor, v) induced labor. CB TRAIL was significantly higher (131.6652 pg/ml) with respect to the corresponding maternal TRAIL, and the variables significantly associated with the first quartile of CB TRAIL (,90 pg/ml) were higher prepregnancy BMI, induction of labor and fetal distress. With respect to the biochemical parameters, maternal TRAIL at delivery showed an inverse correlation with C-reactive protein (CRP), total cortisol, glycemia and insulin at bivariate analysis, but only with CRP at multivariate analysis

Public health and economic impact of vaccination with 7-valent pneumococcal vaccine (PCV7) in the context of the annual influenza epidemic and a severe influenza pandemic

Background: Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1) outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. Methods: A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal disease incidence and mortality during a typical influenza season (13/100) and a severe influenza pandemic (30/100). Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd) protection of non-vaccinated persons. Results: The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save$7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd) protection in the unvaccinated. Conclusions: PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection