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Streptococcus pneumoniae is a major cause of meningitis in under developed countries with low vaccination rates and high antibiotic resistance. This study aimed to analyze 83 suspected meningitis patients in Karachi for the detection of S. pneumoniae followed by its whole genome sequencing and Pan Genome analysis. Out of the 83 samples collected, 33 samples with altered physical (turbidity), cytological (white blood cell count) and biochemical (total protein and total glucose concentrations) parameters indicated potential meningitis cases, while these parameters were within normal healthy ranges in remaining 50 samples. Latex particle agglutination (LPA) was performed on the 33 samples, revealing 20 positive cases of bacterial meningitis. The PCR and culturing methods revealed 5 S. pneumoniae isolates. Antibiotic susceptibility tests showed that one S. pneumoniae strain was resistant to erythromycin, levofloxacin, and tetracycline. Whole-genome sequencing of this resistant strain was performed and S. pneumoniae was confirmed with MLST analysis, while it had > 2.3 Mb genome and a single repUS43 plasmid. In CARD analysis, the strain had tet(M), ermB, RlmA(II), patB, pmrA, and patA ARGs, which could provide resistance against tetracycline, macrolide, fluoroquinolone, and glycopeptide antibiotics. Phylogenetic analysis revealed that the isolate was closely related to strains from Hungary and the USA. Pan-genome analysis with 144 genome assemblies from NCBI database showed that 1101 non-redundant core genes were shared between all strains. This study gives valuable understanding into the prevalence and characterization of meningitis-causing bacteria in Karachi, Pakistan  with prime focus on multi-drug resistant S. pneumoniae., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The clinical implication of extended-spectrum cephalosporin (ESC) resistance has been unclear in patients with Streptococcus pneumoniae meningitis (SPM). We collected the clinical data of 120 patients with SPM in 12 hospitals of the Republic of Korea. The clinical characteristics and outcomes of 23 ESC-nonsusceptible SPM episodes were compared to those of 97 ESC-susceptible episodes. Hospital acquisition, presence of other foci of pneumococcal infection, septic shock at initial presentation, or concomitant bacteremia were more commonly observed in ESC-nonsusceptible than ESC-susceptible SPM. Empiric antimicrobial therapy with vancomycin and ESC combination was very common in both groups. Although there was a tendency towards higher early fatality in ESC-nonsusceptible SPM (3-day mortality; 17.4 % vs. 4.4 %, p = 0.05), in-hospital mortality (26.1 % vs. 20.9 %, p = 0.59) and median length of hospital stay (20 days vs. 24 days, p = 0.34) did not differ between ESC-nonsusceptible and ESC-susceptible SPM.

Streptococcus pneumoniae causes considerable global paediatric morbidity and mortality, despite the availability of safe and effective pneumococcal conjugate vaccines (PCVs). To justify the introduction of PCVs, accurate information on the burden of disease is required. Here, we present an appraisal of the pneumococcal epidemiological situation in 11 Central European countries. The data are based on study findings presented at the 12th Central European Vaccine Advisory Group (CEVAG) meeting, held on 21-22 May 2010 in Sofia, Bulgaria, and a literature review of the PubMed database using the search terms 'pneumococcal' or 'Streptococcus pneumoniae', in combination with 'otitis media', 'pneumonia', 'meningitis' or 'bacteraemia/sepsis', and '[Central European country name]'. The incidence of pneumococcal disease appears to be lower in Central Europe than previously reported for Europe as a whole, with the highest risk in infants aged 0-2 years. The fatality rates in the under fives from invasive infections are up to 40%. A paucity of comprehensive country-specific data on pneumococcal disease burden arises from the lack of homogenous surveillance programmes. Standardised, active surveillance systems are required for the accurate evaluation of the pneumococcal disease burden in the region. Only then can the need for vaccination be addressed.

Presently, several pneumococcal proteins are being evaluated as potential vaccine candidates. Here, we gather novel insights in the immunogenicity of PLY, PsaA, PspA, PspC, NanA, Hyl, PpmA, SlrA, Eno, IgA1-protease, PdBD, BVH-3, SP1003, SP1633, SP1651, SP0189 and SP0376. We developed a multiplex bead-based immunoassay (xMAP(®) Technology, Luminex Corporation) to simultaneously quantify antibodies against these 17 pneumococcal proteins in serum. The median fluorescence intensity (MFI) values obtained for human pooled serum with the multiplex assay were between 82% and 111% (median 94%) of those obtained with the singleplex assays. For IgG, the coefficient of variation (CV) in serum ranged from 2% to 9%, for IgA, the CV ranged from 3% to 14% and for IgM, the CV ranged from 11% to 15%. Using this immunoassay, we showed that anti-pneumococcal antibody levels exhibited extensive inter-individual variability in young children suffering from invasive pneumococcal disease. All proteins, including the proteins with, as yet, unknown function, were immunogenic. In conclusion, the multiplex Streptococcus pneumoniae immunoassay based on proteins is reproducible. This assay can be used to monitor anti-S. pneumoniae antibody responses in a material- and time-saving manner.

The surveillance of serotypes causing invasive pneumococcal disease (IPD) provides further insight into the pathogenesis of pneumococcal disease and is important in order to track vaccine impact. Although the Quellung reaction has been accepted as the standard method for serotyping, prior antibiotic use causes a gap in studies based on bacterial culture. A total of 31 cerebrospinal fluid (CSF) samples found to be positive for Streptococcus pneumoniae by polymerase chain reaction (PCR) targeting the ply gene during an active surveillance were tested in a Bio-Plex multiplex antigen detection assay capable of detecting 14 serotypes/groups (1, 3, 4, 5, 6A, 6B, 7F/A, 8, 9V, 14, 18, 19A, 19F, and 23F). Twenty-seven CSF samples could be serotyped. The most common serotypes were serotypes 5 (n = 7), 19F (n = 5), 1 (n = 3), and 23F (n = 3). Theoretical coverage rates by the heptavalent (PCV7), 10-valent (PCV10), and 13-valent (PCV13) pneumococcal conjugate vaccines for bacterial meningitis were 48.1, 85.2, and 92.3%, respectively, for all age groups and 71.4, 85.7, and 100.0%, respectively, for those under 2 years of age. We propose that antigen detection assay used in conjunction with a PCR assay can be effectively applied in CSF samples to detect the pneumococcal serotypes, especially when the patient may have already been treated and, therefore, the cultures would be negative.

The purpose of this study was to determine the prevalence of acquired antimicrobial resistance in Streptococcus pneumoniae isolated from nasopharyngeal swabs and blood and cerebrospinal fluid (CSF) specimens of 3,028 children hospitalized with signs or symptoms of pneumonia, sepsis, or meningitis in rural Philippines between 1994 and 2000. Pneumococci were identified using standard methods, serotyped, and their susceptibility to oxacillin, erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole was determined using the disk diffusion method. Penicillin minimum inhibitory concentrations (MICs) of the oxacillin-resistant isolates were further tested. The clonality of the penicillin-nonsusceptible (PNSP) isolates was analyzed using pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Altogether 1,048 isolates were analyzed, of which 35 were invasive and 1,013 nasopharyngeal isolates. None was resistant, but 22 (2.1%) were intermediately resistant to penicillin, 4 (0.2%) were resistant to chloramphenicol, 3 (0.2%) to erythromycin, 39 (3.7%) to tetracycline, and 4 (0.2%) to trimethoprim/sulfamethoxazole. Twelve of the 22 PNSP isolates were of serotype 14 and of sequence type 63. These included the two invasive PNSP isolates. PFGE profiling further identified three separate clusters among the sequence of type 63, serotype 14 (ST63(14)) isolates. Antimicrobial resistance in both invasive and nasopharyngeal pneumococcal pediatric isolates in rural Philippines is rare. In spite of this remote setting, the PNSP isolates of the serotype 14 clusters were of ST63 type, which has been described previously on other continents.

Meropenem is a carbapenem antibiotic that is highly active against the pathogens causing meningitis. Results with meropenem in the experimental rabbit model of penumococcal meningitis have been controversial, and the possible role of renal dehydropeptidase I in meropenem efficacy has been suggested. The aim of this study was to determine the efficacy of meropenem in two meningitis models and the possible influence of the animal model over results. Two strains of Streptococcus pneumoniae with different susceptibility to beta-lactams have been used in a guinea pig model and the classical rabbit meningitis model. Meropenem was bactericidal at 6 h in the guinea pig model against both strains with a reduction of >4 log ufc/ml. In the rabbit model it was bactericidal at 6 h against the susceptible strain, but against the resistant 3/8 therapeutical failures were recorded at 6 h, being bactericidal at 24 h. In conclusion, meropenem has shown bactericidal activity in both experimental models. This work emphasises the importance of an adequate election of the animal model for the appropriate development of studies of antimicrobial efficacy. We believe that guinea pig should be considered the best choice among laboratory animal species when assessing meropenem efficacy.

We report an episode of bacterial meningitis in a 45 year-old woman, who was treated with infliximab for Wegener's granulomatosis. This patient presented with the classic clinical presentation of acute meningitis: the triad of fever, neck stiffness, and an altered mental state that appeared 6 months after the infliximab initiation. A computed tomographic (CT) scan of the head showed cerebral edema and Streptococcus pneumoniae was isolated from blood and CSF cultures. Prompt diagnosis and early treatment improved the outcome of this patient.

Since pneumococcal meningitis continues to have high mortality and morbidity, and may be under-reported to national surveillance systems, the present study was conducted to assess the incidence, features, and outcomes of microbiologically confirmed cases of pneumococcal meningitis in North Yorkshire, England, between 1997 and 2002. The review revealed 50 cases, which accounted for an incidence of 1.1. per 100,000 per year. The incidence was markedly seasonal, with 76% of cases occurring in the winter months. Mortality was 28%, and 28% of the survivors suffered long-term sequelae. A high Glasgow Coma Score on hospital admission was significantly associated with survival. There were 12 children in the study, aged 2 months to 2 years, and none of them would have been classified as candidates for conjugate pneumococcal vaccination according to UK recommendations.

Using Streptococcus pneumoniae as an example, the ability of multilocus sequence typing (MLST) to characterise isolates directly from cerebrospinal fluid (CSF) was investigated. A nested multiplex polymerase chain reaction method that amplifies the seven housekeeping gene fragments used for pneumococcal MLST was applied to 30 CSF samples from suspected cases of bacterial meningitis. The fragments were amplified from all 14 samples from which Streptococcus pneumoniae was cultured, and, after direct sequencing, the allelic profiles obtained from ten of the samples corresponded to those of clones previously associated with invasive pneumococcal disease. MLST could also predict the penicillin susceptibility and serotype of the CSF isolates.

In a rabbit model of meningitis caused by a pneumococcus highly resistant to penicillin (MIC, 4 microg/ml), meropenem, a broad-spectrum carbapenem, was bactericidal (-0.48+/-0.14 deltalog10 cfu/ml h) and slightly superior to ceftriaxone (-0.34+/-0.23 deltalog10 cfu/ml x h) and vancomycin (-0.39+/-0.19 deltalog10 cfu/ml x h). Although the combination of vancomycin with ceftriaxone was significantly more active than ceftriaxone alone (-0.55+/-0.19 deltalog10 cfu/ml x h), only an insignificant gain was observed by the addition of vancomycin to meropenem (-0.55+/-0.28 deltalog10 cfu/ml x h).

The molecular epidemiological characteristics of pneumococcal meningitis in children were studied. Pneumococcal isolates were characterized by serotyping and two genotyping methods, BOX fingerprinting and restriction fragment end labeling, to evaluate whether clonal strains were present within the serotypes or serogroups. During a 17-year period, 68 children admitted to the Sophia Children's Hospital were diagnosed with meningitis due to Streptococcus pneumoniae. Pneumococcal isolates from 44 patients were still available for analysis. All strains were susceptible to penicillin. Serotypes/ serogroups 14, 19, 6, and 18 represented 56% of all isolates. The results of the molecular typing methods demonstrate the absence of clonal relatedness between isolates from patients with pneumococcal meningitis.

Mortality rates of pneumococcal meningitis ranges from 13-60% in different parts of the world. Reports of pneumococci with multiple antibiotic resistance add urgency to the need for developing means of primary prevention. A 14-valent pneumococcal vaccine was licensed in 1977, and a 23-valent pneumococcal vaccine in 1983. In the present work 131 strains of pneumococci isolated from meningitis cases in Egypt were identified and serotyped by Quellung reaction. The most frequently isolated serotype was serotype 1 (32%). Serotypes 6A, 9L, 12A, 19A and 29 were next in prevalence. The age groups 0-18 years were the most frequently affected groups (79%) and over 18 years of age were only 21% of total cases. A vaccine formulation is suggested to have a coverage rate against pneumococcal meningitis cases of 79.3% and 89.3% of a proposed 14-valent vaccine and 23-valent vaccine versus to coverage rate of 48% and 54% of 14-valent and 23-valent International vaccines respectively. According to the age distribution of cases and the isolated serotypes a vaccination could be recommended during the first two years of age in order to protect the most frequently infected groups.