Conjugate Vaccine Era Research Articles

Epidemiological trends in viral meningitis in England: Prospective national surveillance, 2013–2023

BackgroundIn the conjugate vaccine era, viruses are the most common cause of meningitis. Here, we evaluated epidemiological trends in laboratory-confirmed viral meningitis across all age-groups over an 11-year period in England. MethodsIn England, hospital laboratories routinely report laboratory-confirmed infections electronically to the UK Health Security Agency. Records of positive viral detections in cerebrospinal fluid during 2013-2023 were extracted. Incidence rates with confidence intervals were calculated using mid-year resident population estimates. ResultsThere were 22,114 laboratory-confirmed viral meningitis cases, including 15,299 cases during 2013-19 (pre COVID-19), with a gradual increase in incidence from 3.5/100,00 (95%CI, 3.3-3.6) to 3.9/100,000 (95%CI, 3.6-4.1). During 2020-21 when pandemic restrictions were in place, there were 2,061 cases (1.8/100,000; 1.7 - 1.9), which increased to 4,754 (4.2/100,000; 4.0-4.3) during 2022-23 (post pandemic restrictions).Infants aged <3 months accounted for 39.4% (8,702/22,048) of all cases, with a stable incidence 2013-19 (504/100,000, 95%CI: 491-517), followed by a significant decline during 2020-21 (204/100,000; 188-221) and then an increase during 2022-23 (780/100,000; 749-812), with enteroviruses being the commonest cause (84.9%, 7387/8,702; 424.74/100,000; 95%CI, 415.12-434.51), followed by parechoviruses (9.1%, 792/8702; 45.54/100,000; 95%CI, 42.42-48.82) and herpes simplex virus (4.4%, 380/8702; 21.85/100,000; 95%CI, 19.71-24.16). Pandemic restrictions were associated with significant declines in the incidence of enterovirus (77.7%) and parechoviruses (64% lower), with rebounds after societal restrictions lifted. ConclusionsRates of viral meningitis have returned to pre-pandemic levels since societal restrictions were lifted. The highest incidence of viral meningitis remains in infants aged <3 months and most commonly due to enteroviral infection.

Orbital complications of pediatric acute rhinosinusitis in the pneumococcal conjugate vaccine era

ObjectivesTo evaluate the impact of the pneumococcal conjugate vaccines (PCVs) introduction on the orbital complications of acute rhino-sinusitis (OC-ARS). MethodsA retrospective cohort study of all pediatric patients with OC-ARS during the period 2002–2019. Data included clinical, demographic, laboratory, and microbiology findings. Patients were divided into three groups: before PCV7 introduction (group 1), after PCV7 and before PCV13 (group 2), and after PCV13 (group 3). ResultsOf 265 enrolled patients, 117, 39, and 109 were assigned to groups 1, 2, and 3. During the study period, a significant decrease was recorded in the percentages of patients in Chandler classification severity category 1, with an increase in patients in category 3 (P = 0.011). The yearly incidence of OC-ARS decreased from 12.64 cases per 100,000 population in 2002 to 5.56 per 100,000 in 2008, and 2.99 per 100,000 in 2019 (P < 0.001). Patients aged 0–4 years showed a dramatic decrease from 29 cases per 100,000 population in 2002 to 4.27 per 100,000 in 2019 (P < 0.001). The pathogens retrieved from all cultures performed were Streptococcus pneumoniae (32.5%), non-typeable Haemophilus influenzae (27.5%), Streptococcus Species, (12.5%), and Staphylococcus aureus (20%), with no changes in distribution during the study periods. Surgery was performed in 28 (10.6%) patients. ConclusionsA significant decrease was seen in the overall incidence of OC-ARS, mainly attributable to the decrease in patients aged 0–4 years. An increase was recorded in the severity of the disease following PCVs introduction.

Invasive Pneumococcal Disease Epidemiology and Serotype Replacement After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Ontario, Canada, 2007-2022.

New vaccine products were recently authorized for protection against invasive pneumococcal disease (IPD) in Canada. Our aim was to determine age- and serotype-specific trends in IPD incidence and severity in Canada's largest province, Ontario. We included all confirmed IPD cases reported in Ontario and defined the pre-pneumococcal 13-valent conjugate vaccine (PCV13) era (01/2007 to 12/2010), post-PCV13 era (01/2011 to 12/2019), and coronavirus disease 2019 (COVID-19) pandemic era (01/2020 to 12/2022). We estimated incidence, hospitalization, and case fatality rate (CFR) by age. We grouped IPD cases by vaccine-specific serotypes (PCV13; PCV15-non-PCV13; PCV20-non-PCV13; PCV20-non-PCV15; polysaccharide 23-valent vaccine-non-PCV20; and non-vaccine-preventable [NVP]). We then compared incidence rates by age and serotype group in the pre- and post-PCV13 eras by calculating rate ratios (RRs) and their 95% CIs. Incidence and hospitalizations declined from the pre- to post-PCV13 era in children aged <5 years (RR, 0.7; 95% CI, 0.6-0.8; and RR, 0.8; 95% CI, 0.7-0.9, respectively), but the CFR increased (1.4% to 2.3%). Other age groups saw smaller declines or more stable incidence rates across the years; hospitalizations increased in adults aged 50-64 years (RR, 1.2; 95% CI, 1.1-1.4) and ≥65 years (RR, 1.1; 95% CI, 1.0-1.1). For all ages, IPD cases and hospitalizations attributable to PCV13 serotypes declined, and those attributable to PCV15-non-PCV13, PCV20-non-PCV13, and NVP serotypes increased. IPD incidence declined during the COVID-19 era. IPD incidence and hospitalizations due to PCV13 serotypes decreased after PCV13 introduction but increased for other serotypes. Continued surveillance is required to evaluate changes to pneumococcal vaccination programs and ongoing changes to the distribution of IPD-causing serotypes.

Pediatric Otitis Media in the New Pneumococcal Conjugate Vaccines Era: What's Next?

Pediatric Otitis Media in the New Pneumococcal Conjugate Vaccines Era: What's Next?

Clinical and Microbial Determinants of Upper Respiratory Colonization with Streptococcus pneumoniae and Native Microbiota in People with HIV-1 and Control Adults.

The substantial risk for respiratory and invasive infections with Streptococcus pneumoniae (Spn) among people with HIV-1 (PWH) begins with asymptomatic colonization. The frequency of Spn colonization among U.S. adults with and without HIV-1 infection is not well-characterized in the conjugate vaccine era. We determined Spn colonization frequency by culture and specific lytA gene QPCR and microbiota profile by 16S rRNA gene sequencing in nasopharyngeal (NP) and oropharyngeal (OP) DNA from 138 PWH and 93 control adults and associated clinical characteristics. The frequencies of Spn colonization among PWH and controls did not differ (11.6% vs 8.6%, respectively; p=0.46) using combined results of culture and PCR, independent of vaccination or behavioral risks. PWH showed altered microbiota composition (i.e., beta-diversity. NP: p=0.0028, OP: p=0.0098), decreased alpha-diversity (NP: p=0.024, OP: p=0.0045), and differences in the relative abundance of multiple bacterial taxa. Spn colonization was associated with altered beta-diversity in the NP (p=0.011), but not OP (p=0.21). Despite widespread conjugate vaccine and antiretroviral use, frequencies of Spn colonization among PWH and controls are currently consistent with those reported in the pre-conjugate era. The persistently increased risk of pneumococcal disease despite ART may relate to behavioral and immunologic variables other than colonization.

Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology

The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes. Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology. The cohort included 3002 children (median age 2·4 months); 1101/3002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <6 months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age 6 months to 9 years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis. Bacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis. This study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research.

Molecular characteristics and antimicrobial resistance of invasive pneumococcal isolates from children in the post-13-valent pneumococcal conjugate vaccine era in Shenzhen, China

This study aimed to evaluate the molecular epidemiology and antimicrobial resistance of invasive pneumococcal isolates from children in Shenzhen, China, in the early stage of the pneumococcal 13-valent conjugated vaccine (PCV-13) era from 2018 to 2020. Invasive pneumococcal strains were isolated from hospitalized children with invasive pneumococcal diseases (IPDs) from January 2018 to December 2020. The serotype identification, multilocus sequence typing (MLST), and antibiotic susceptibility tests were performed on all culture-confirmed strains. Sixty-four invasive strains were isolated mainly from blood (70.3%). Prevalent serotypes were 23F (28.1%), 14 (18.8%), 19F (15.6%), 6A/B (14.1%), and 19A (12.5%), with a serotype coverage rate of 96.9% for PCV13. The most common sequence types (STs) were ST876 (17.1%), ST271 (10.9%), and ST320 (7.8%). Half of the strains were grouped in clonal complexes (CCs): CC271 (21.9%), CC876 (20.3%), and CC90 (14.1%). Meningitis isolates showed a higher resistance rate (90.9% and 45.5%) to penicillin and ceftriaxone than the rate (3.8% and 9.4%) of non-meningitis isolates. The resistance rates for penicillin (oral), cefuroxime, and erythromycin were 53.13%, 73.4%, and 96.9%, respectively. The dual ermB and mefA genotype was found in 81.3% of erythromycin-resistant strains. The elevated minimum inhibitory concentration (MIC) of β-lactam antibiotics and dual-genotype macrolide resistance were related mainly to three major serotype-CC combinations: 19F-CC271, 19A-CC271, and 14-CC876. Invasive pneumococcus with elevated MICs of β-lactams and increased dual ermB and mefA genotype macrolide resistance were alarming. Expanded PCV13 vaccination is expected to reduce the burden of paediatric IPD and to combat antibiotic-resistant pneumococcus in Shenzhen.

Prevalence and resistance characteristics of multidrug-resistant Streptococcus pneumoniae isolated from the respiratory tracts of hospitalized children in Shenzhen, China.

PCV13 introduction in China has led to a significant reduction of vaccine serotype Streptococcus pneumoniae. However, non-vaccine serotypes with highly resistance and invasiveness were often reported in the post-pneumococcal conjugate vaccine era and there was regional differences. A total of 669 S. pneumoniae strains were collected from the respiratory tracts of hospitalized children at Shenzhen Children's Hospital in 2021 and 2022. Antimicrobial resistance (AMR) characteristics were assessed through antibiotic susceptibility testing performed with the VITEK 2 compact system. AMR genes and single nucleotide polymorphisms (SNPs) in pbp1a, pbp2b, and pbp2x were identified via analysis of whole genome sequencing data. Statistical examination of the data was conducted employing chi-square and Fisher's exact tests. We found that non-vaccine serotypes strains had accounted for 46.6% of all the pneumococcal isolated strains. The most common non-vaccine serotype is 23A, with a prevalence rate of 8.9%, followed by 15A (6.6%), 6E (5.7%), 34 (3.2%), and 15B (2.9%). The multidrug resistance rates (MDR) of vaccine serotypes were 19F (99.36%), 19A (100%), 23F (98.08%), 6B (100%), and 6C (100%). Meanwhile, the MDR of non-vaccine serotypes were 15B (100.00%), 6E (100%), 15C (100%), 34 (95.24%), and 23A (98.31%). Resistance rates of 6E to more than six antibiotic classes reached 89.47%, which is similar to 19F (83.33%) and 19A (90%). Unique resistance profiles were also identified for non-vaccine serotypes, including significantly higher resistance to chloramphenicol in 6E, 15B, and 15C than in 19F and 19A. Furthermore, through genome sequencing, we revealed strong correlation of cat-TC with chloramphenicol resistance, patA/patB with tetracycline resistance, ermB and pmrA with erythromycin resistance. The introduction of PCV13 into China from 2017 has led to a shift in the dominant composition of pneumococcal strains. There has been a notable rise and spread of multidrug-resistant non-vaccine serotypes among children. Specifically, the non-vaccine serotype 6E, which was not widely reported in China previously, has emerged. To comprehend the resistance mechanisms, it is crucial to further investigate the molecular and genetic characteristics of these non-vaccine serotypes.

Prevalence and Antimicrobial Resistance Patterns of Pathogenic Bacterial Isolates of Hospitalized Sickle Cell Disease Patients Admitted in Our Tertiary Hospital in the Gambia

Background: Sickle Cell Disease (SCD) patients are predisposed to several SCD related complications such as vasocclusive crisis, asplenia, haemolytic crisis and bacterial infection. Despite several other complications encountered by SCD patients during the first few years of life, invasive bacterial infections caused by Streptococcus pneumoniae, Haemophilus influenzae type b, and non-typhi Salmonella species have been reported to be the predominant cause of morbidity and mortality in sickle cell disease patients in many countries (Williams et al. 2009). This is because most SCD patients develop functional asplenism in their early years of life because of repeated episodes of sickling-induced splenic infarction which predisposes them to episodes of infections caused by encapsulated bacteria such as such as Streptococcus Pneumoniae, Haemophilus influenzae type b, and non-typhoidal Salmonella species. The two major prophylactic interventions are vaccination, and daily oral penicillin at least until the fifth year to protect the SCD populations from encapsulated bacterial infections. Aims The aim of this study was to determine the prevalence of invasive bacterial infections and their antimicrobial resistance patterns in SCD patients admitted at the Medical Research Council the Gambia (MRCG) Ward in the era of Pneumococcal Conjugate Vaccine and Haemophilus Influenzae b vaccination in the Gambia. Methods and Results This study was conducted in the clinical laboratory department of MRCG. We retrospectively generated haematological, and blood culture data from our electronic medical records from 2015 to 2022 of SCD patients admitted to MRCG Ward. Of 380 SCD patients, blood culture was requested for 159. Of the 159 admitted SCD, 11 patients had qualified positive blood cultures. Five different types of pathogens were isolated from these positive blood cultures: 4 Staphylococcus aureus, 3 Streptococcus pneumoniae, 2 Salmonella species, 1 Enterococcus species, and 1 Shigella boydii. No episode of bacteremia caused by Haemophilus influenzae type b was identified. The molecular serotyping of the Streptococcus pneumoniae isolates revealed non-vaccine serotypes 10A, 12F and 12F. From our AST result, two of the three Streptococcus pneumoniae were resistant to penicillin antibiotics. The Staphylococcus aureus isolates were penicillin resistant but cefoxitin sensitive, hence no methicillin (oxacillin) resistant Staphylococcus aureus was reported., Generally, the isolated pathogens were all sensitive to chloramphenicol, and vancomycin. Conclusion: Streptococcus pneumoniae and Staphylococcus aureus were the most common cause of bacteremia in these admitted SCD patients. The presence of non-typhoidal Salmonella and Shigella infection coupled with penicillin resistance should be considered during penicillin prophylaxis and empirical treatment regimens for SCD patients and future SCD management policies in the Gambia.

Prevalence of prolonged otitis media with effusion among 2 to 3 years old Cameroonian children in the era of 13-valent pneumococcal conjugate vaccines

ObjectivesThere is data scarcity on the overall effects of pneumococcal conjugate vaccines (PCVs) on otitis media (OM) in low- and middle-income countries. The impact of the 13-valent PCV (PCV13) program on OM was evaluated in Cameroon where infant vaccination was implemented in July 2011 using a 3-dose primary series at 6, 10 and 14 weeks of age. MethodsThrough community-based surveillance, we used a retrospective cohort study design to assess OM prevalence among PCV13-vaccinated children aged 24 to 36 months in 2015. This was compared with a 2013 age-matched cohort of PCV13-unvaccinated children. OM was diagnosed by clinical inspection for chronic suppurative OM (CSOM) and tympanometry for OM with effusion (OME). CSOM was defined as draining of the middle ear with duration of more than 2 weeks and prolonged OME was defined as a flat ‘type B’ tympanogram. PCV13-vaccinated and PCV13-unvaccinated cohorts were compared by calculating prevalence odds ratios for OM and baseline characteristics. ResultsAltogether, 111 OM cases were identified; 42/433 (9.7%) in the PCV13-unvaccinated in 2013 and 69/413 (16.7%) in the PCV13-vaccinated cohort in 2015. In the 2013 baseline survey, 3/433 (0.7%) children were identified with unilateral CSOM compared to 9/413 (2.2%) in the PCV13-vaccinated cohort in 2015. Bilateral prolonged OME was diagnosed in 7/433 (1.6%) PCV13-unvaccinated children and in 12/413 (2.9%) in PCV13-vaccinated children. Proportions of children with unilateral prolonged OME were 31/433 (7.2%) in the PCV13-unvaccinated group compared with 48/413 (11.6%) in the PCV13-vaccinated group. Multivariate logistic regression analysis showed evidence that PCV13-vaccinated children in 2015 had 40% less risk of contracting OM compared to PCV13-unvaccinated children in 2013 (adjusted prevalence odds ratios = 0.60 [95% confidence interval: 0.38 to 0.94], P = 0.025). Additionally, attributable proportion estimates show that, 58% of OM infections among the PCV13-vaccinated group would still have occurred despite PCV13 vaccination. ConclusionOur findings provide significant evidence on the effect of PCV13 in decreasing OM or OME among children in this age group. It also supports justification for government's continuation of PCV13 immunization program in the absence of GAVI's funding. Further research is needed to assess the long-term impact of the PCV13 program on in OM Cameroon.

Genomic analysis of penicillin-binding proteins and recombination events in an emerging amoxicillin- and meropenem-resistant PMEN3 (Spain9V-3, ST156) variant in Taiwan and comparison with global descendants of this lineage.

From 2008 to 2020, the Taiwan National Notifiable Disease Surveillance System database demonstrated that the incidence of non-vaccine serotype 23A invasive pneumococcal disease (IPD) approximately doubled. In this study, 276 non-repetitive pneumococcal clinical isolates were collected from two medical centers in Taiwan between 2019 and 2021. Of these 267 pneumococci, 60 were serotype 23A. Among them, 50 (83%) of serotype 23A isolates belonged to the sequence type (ST) 166 variant of the Spain9V-3 clone. Pneumococcal 23A-ST166 isolates were collected to assess their evolutionary relationships using whole-genome sequencing. All 23A-ST166 isolates were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299, the newly identified PBP2x-299 in Taiwan. Transformation of the pbp1a, pbp2b, and pbp2x alleles into the β-lactam-susceptible R6 strain revealed that PBP2x-299 and PBP2b-11 increased the MIC of ceftriaxone and meropenem by 16-fold, respectively. Prediction analysis of recombination sites in PMEN3 descendants (23A-ST166 in Taiwan, 35B-ST156 in the United States, and 11A-ST838/ST6521 in Europe) showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displayed an evolutionary capacity for global dissemination and persistence, increasing IPD incidence, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases, and contributing to high antibiotic resistance.A clonal shift with a highly β-lactam-resistant non-vaccine serotype 23A, from ST338 to ST166, increased in Taiwan. ST166 is a single-locus variant of the Spain9V-3 clone, which is also called the PMEN3 lineage. All 23A-ST166 isolates, in this study, were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299. PBP2x-299 and PBP2b-11 contributed to the increasing MIC of ceftriaxone and meropenem, respectively. Prediction analysis of recombination sites in PMEN3 descendants showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displays the evolutionary capacity for dissemination, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases and contributing to high antibiotic resistance.

Bacteriological and molecular characterization of temperature- and CO2-dependent Streptococcus pneumoniae serotype 24F ST162 isolated from Japanese children.

Streptococcus pneumoniae serotype 24F is one of the most prevalent non-vaccine serotypes that causes invasive pneumococcal disease (IPD) in many countries, including Japan. This study aimed to analyze the bacteriological and molecular characteristics of serotype 24F sequence type (ST) 162, which has been increasingly isolated from pediatric patients with IPD in Japan recently. The examination of growth conditions, sequencing of genes associated with the CO2 dependence, and antimicrobial susceptibility testing at 35°C under 5% CO2 were performed for 10 isolates obtained from Japanese children with IPD caused by serotype 24F ST162. All isolates failed to grow at 35°C in ambient air; however, they showed growth at 30°C in ambient air and at 35°C under 5% CO2. Sequencing of murF involved in cell wall synthesis indicated that all isolates had a single amino acid substitution, MurFA179V. Additionally, all isolates were sensitive to penicillin G and resistant to trimethoprim-sulfamethoxazole. Furthermore, 25 non-capnophilic strains were obtained from all CO2-dependent isolates, and their murF sequences were compared. Thirteen of the 25 non-capnophilic strains displayed a different amino acid substitution, MurFV179A, whereas the other 12 presented the previously described MurFA179V. This suggests that a proportion of the CO2-dependent phenotype of serotype 24F ST162 may have been conferred by MurFA179V; however, the mechanism for the CO2 dependence of these isolates warrants further investigation. The CO2-dependent serotype 24F ST162 pneumococcal isolates shared common characteristics in terms of growth patterns, molecular basis, and antimicrobial susceptibility; therefore, future epidemiological trends of this clone must be closely monitored. IMPORTANCE We characterized Streptococcus pneumoniae serotype 24F sequence type (ST) 162 isolated from Japanese children with invasive pneumococcal disease (IPD). Owing to its highly invasive nature, serotype 24F is expected to be isolated from clinically significant cases. Serotype 24F ST162 isolates tested in the present study did not grow at 35°C in ambient air. Therefore, antimicrobial susceptibility testing using the broth microdilution method, which is usually conducted in ambient air, cannot be performed, posing a clinical challenge. Clinical practitioners and laboratory personnel should be aware of the epidemiological, bacteriological, and molecular characteristics of serotype 24F ST162. We believe that our findings can help diagnose and treat IPD caused by serotype 24F ST162, a serotype expected to become problematic in the post-13 valent pneumococcal conjugate vaccine era.

Assessing the utilization of antimicrobial agents in pediatric pneumonia during the era of the 13-valent pneumococcal conjugate vaccine: A retrospective, single-center study

Background and purposePneumonia and bronchopneumonia are the most common infectious diseases in children. This study aimed to analyze changes in causative pathogens and antibiotic use for bronchopneumonia or pneumonia after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in children. MethodsThis retrospective study was conducted from 2009 to 2019. Hospitalized children aged 6 months–3 years with a discharge diagnosis of bronchopneumonia or pneumonia were included to analyze changes in the potential mismatch between the diagnosed pathogen and antibiotic use. ResultsThe cohort comprised 1100 patients, including 648 (59%) and 452 (41%) with a discharge diagnosis of bronchopneumonia and pneumonia, respectively. The trend of viral pneumonia increased every year (rs = 0.101, p < 0.05) Antibiotics were administered in 97% patients, with an increasing annual trend in macrolide use (rs = 0.031, p = 0.009). Regarding antibiotic utilization, no significant variations were observed in the days of therapy (DOT) (rs = 0.076, p = 0.208) or length of therapy (LOT) (rs = −0.027, p = 0.534) per patient-year throughout the study duration. Interestingly, the LOT for combined therapy with macrolides and first-line beta-lactams was high (rs = 0.333, p = 0.028). In viral pneumonia treatment, neither the DOT nor LOT exhibited significant variations (rs = −0.006, p = 0.787 and rs = −0.156, p = 0.398). ConclusionAfter the introduction of PCV13 in Taiwan, no decrease in antibiotic use has been observed among children aged 6 months–3 years with a discharge diagnosis of bronchopneumonia and pneumonia.

Biofilm-Forming Bacteria Implicated in Complex Otitis Media in Children in the Post-Heptavalent Pneumococcal Conjugate Vaccine (PCV7) Era.

Background: Chronic media with effusion (COME) and recurrent acute otitis media (RAOM) are closely related clinical entities that affect childhood. The aims of the study were to investigate the microbiological profile of otitis-prone children in the post-PCV7 era and, to examine the biofilm-forming ability in association with clinical history and outcome during a two-year post-operative follow-up. Methods: In this prospective study, pathogens from patients with COME and RAOM were isolated and studied in vitro for their biofilm-forming ability. The minimum inhibitory concentrations (MIC) of both the planktonic and the sessile forms were compared. The outcome of the therapeutic method used in each case and patient history were correlated with the pathogens and their ability to form biofilms. Results: Haemophilus influenzae was the leading pathogen (35% in COME and 40% in RAOM), and Streptococcus pneumoniae ranked second (12% in COME and 24% in RAOM). Polymicrobial infections were identified in 5% of COME and 19% of RAOM cases. Of the isolated otopathogens, 94% were positive for biofilm formation. Conclusions: This is the first Greek research studying biofilm formation in complex otitis media-prone children population in the post-PCV7 era. High rates of polymicrobial infections, along with treatment failure in biofilms, may explain the lack of antimicrobial efficacy in otitis-prone children.

Epidemiology of bacteremia in a pediatric population – A 10-year study

IntroductionWith the widespread introduction of conjugate meningococcal and pneumococcal vaccines, the prevalence and etiology of invasive bacterial infections have changed. We aimed to review all cases of bacteremia in a level II pediatric department over a ten-year period in the post-pneumococcal conjugate vaccine era. MethodsWe reviewed all positive blood cultures (BC) obtained in our department between 2007 and 2016. Results were classified as contaminants, potential pathogens or confirmed pathogens, based on species, number of positive BC in the episode and the patients’ medical history. Demographic and clinical data were collected for patients with identified pathogens. ResultsA total of 638 positive BC were identified (6.6% of total BC); 120 (1.2%) were considered to represent true bacteremia. The most frequently identified microorganism was Streptococcus pneumoniae (29.2%), with a decrease in the number of cases between 2008 and 2015. Staphylococcus aureus was the second most common organism (19.2%) being 21.7% of these methicillin-resistant. Escherichia coli was the most common isolate in children aged less than three months. ConclusionWe found a rate of true bacteremia in children similar to recent studies. Although Streptococcus pneumoniae remains the most common microorganism, its prevalence may be declining. Monitoring microbiological data in children has implications in practice, particularly in local antibiotic prescription.

Changing Trends of Invasive Pneumococcal Disease in the Era of Conjugate Pneumococcal Vaccination in Olmsted County: A Population-Based Study

ObjectiveTo estimate the incidence of invasive pneumococcal disease (IPD) in the pre–13-valent pneumococcal conjugate vaccine (pre-PCV13; 7-valent pneumococcal conjugate vaccine era, 2002-2010) and post-PCV13 (2011-2018) time periods. Patients and MethodsUsing the Rochester Epidemiology Project, we conducted a population-based cohort study of all IPD cases in Olmsted County, Minnesota, from January 1, 2002, to December 31, 2018. ResultsOverall, 187 cases of IPD were identified. The incidence of IPD decreased significantly from 11.1 (95% CI, 9.1 to 13.2) to 5.6 (95% CI, 4.3 to 6.9) per 100,000 person-years when the pre- and post-PCV13 periods (2002-2010 vs 2011-2018) were compared (P<.001). Of the 187 patients with IPD, 112 (59.9%) had previously received at least 1 dose of pneumococcal vaccine. Among the IPD cases in the post-PCV13 period, there was an increase in non-PCV13 serotypes, mainly 11A (from 1.0% [1 of 105] to 6.2% [4 of 64]) and 33F (from 2.9% [3 of 105] to 15.6% [10 of 64]), while PCV13/non–7-valent pneumococcal conjugate vaccine serotypes declined from 38.1% (40 of 105) to 15.6% (10 of 64). At 30 days after an IPD diagnosis, the survival rate was 88.8% (95% CI, 84.4% to 93.4%). ConclusionA marked decline in IPD incidence occurred during the post-PCV13 era. Because of the observed increase in non-PCV13 serotypes, coupled with multiple factors that impact the epidemiology of IPD, ongoing surveillance of patients with IPD, particularly due to non-PCV13 serotypes, is warranted.

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against community-acquired pneumonia in older individuals after the introduction of childhood 13-valent pneumococcal conjugate vaccine: A multicenter hospital-based case-control study in Japan

BackgroundIn the era of childhood pneumococcal conjugate vaccine (PCV) immunization, especially 13-valent pneumococcal conjugate vaccine (PCV13) immunization, serotype replacement of Streptococcus pneumoniae and herd immunity in adults have been reported worldwide. Therefore, continuous evaluation of the effectiveness of the pneumococcal vaccine in adults is crucial because vaccine effectiveness may change owing to these factors. The purpose of this study was to evaluate the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against all-cause pneumonia and pneumococcal pneumonia in older individuals with community-acquired pneumonia (CAP) after the introduction of childhood PCV13 in Japan, a topic that has remained largely unexplored. MethodsWe evaluated pneumococcal vaccine effectiveness in this multicenter, matched case-control study conducted in hospitals and clinics. Cases included patients (aged ≥ 65 years) newly diagnosed with CAP between October 2016 and September 2019. A maximum of five non-pneumonia control patients matched for sex, school grade, date of outpatient visit, and medical institution were selected for each case. Conditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pneumococcal vaccines for the occurrence of all-cause CAP and pneumococcal CAP. ResultsThe analysis included 740 individuals (142 patients and 598 controls). The median age of participants was 75 years (men: 54%). The adjusted OR for pneumococcal vaccination against all-cause CAP was 1.31 (95% CI: 0.84–2.06), while that for PPSV23 vaccination in the previous 5 years was 1.33 (95% CI: 0.85–2.09). The adjusted OR for PPSV23 vaccination in the previous 5 years against pneumococcal CAP was 0.93 (95% CI: 0.35–2.50). ConclusionsThis study was unable to demonstrate the effectiveness of PPSV23 against all-cause and pneumococcal pneumonia after the introduction of childhood PCV13 in Japan. Nonetheless, additional studies are needed to validate these results.

Serious bacterial infections in young children with fever without source after discharge from emergency department: A National Health Insurance database cohort study.

Well-appearing febrile young children discharged from the emergency department (ED) after medical assessment are still at risk for serious bacterial infections (SBI). The incidence of SBI and the effectiveness of laboratory tests in the pneumococcal conjugate vaccine era remain unknown. We conducted a study using Taiwan's National Health Insurance claims data from 2004 to 2014. Children aged 2-24 months discharged from the ED with a diagnosis compatible with fever without source (FWS) were enrolled. The study identified 431,884 children from the ED with FWS. 13.53% of the children had revisits, 8.62% needed hospitalization and 1.57% developed SBI. Younger children had a higher SBI rate, but a lower revisit rate. The revisit rate was 12.22% for children aged 2-6 months, 13.61% for children aged 7-12 months and 13.77% for children aged 13-24 months (p<0.0001). The SBI rate was 4.44% for children aged 2-6 months, 1.85% for children aged 2-6 months and 0.96% for children aged 13-24 months (p<0.0001). Children with hemogram tests, compared to those without, had a higher revisit rate (16.30% vs. 13.15%, p<0.0001), and a higher SBI rate in the children aged 13-24 months (1.30% vs. 0.92%, p<0.0001); furthermore, children with urinalysis had a significantly higher revisit rate (14.42% vs. 13.24%, p<0.0001) and higher SBI rate (2.10% vs. 1.40%, p<0.0001). Children with FWS aged 2-24 months who were discharged from ED after blood test and urinalysis were still at risk for SBI, especially those aged 2-6 months.

Acute Otitis Media in Children-Challenges of Antibiotic Resistance in the Post-Vaccination Era.

Acute otitis media (AOM) is a leading cause of antibiotic prescriptions in children worldwide, even in the era of pneumococcal conjugate vaccines. We aimed to assess the bacterial spectrum of AOM in children and to investigate the antimicrobial resistance profile in culture-positive cases. We performed a retrospective, tympanocentesis-based analysis of antimicrobial resistance patterns in children with AOM hospitalized in “St Mary” Emergency Hospital for Children Iasi, Romania, between January 2013 and December 2021. A total of 147 samples have been assessed, 97 (65.98%) of which had positive cultures, with Streptococcus pneumoniae and Haemophilus influenzae as the most common microorganisms. A worrying proportion, 82.85% (58/70), of the Streptococcus pneumoniae strains were multidrug-resistant. The World Health Organization included Streptococcus pneumoniae and Haemophilus influenzae on the medium priority group due to penicillin non-susceptibility and ampicillin-resistant strains, respectively. Consequently, strategies to address the threats of antimicrobial resistance are needed to reduce the potential negative effects on hospitalization costs.

Genetic characterization of penicillin-binding proteins of nonencapsulated Streptococcus pneumoniae in the postpneumococcal conjugate vaccine era in Japan

ObjectivesNonencapsulated Streptococcus pneumoniae (NESp) is emerging after the introduction of pneumococcal conjugate vaccines (PCVs). This study aimed to elucidate the genetic characteristics of penicillin-binding proteins (PBPs; PBP1a, 2b, and 2x) associated with penicillin nonsusceptibility in emergent NESp. MethodsA total of 71 NESp isolates that were identified in our previous study during the PCV era in Japan (2011–2019) were analyzed for their amino acid sequences of transpeptidase domain in PBP 1a, 2b, and 2x. ResultsOverall, we identified 21 different PBP profiles (1a-2b-2x), all of which represent novel PBP profiles. The dominant PBP profiles were 13-16-ne1 (32.4%, n = 23), ne1-16-ne2 (14.1%, n = 10), and 13-7-ne4 (7.0%, n = 5) (novel PBP type was numbered with “ne” denoting “nonencapsulated”), accounting for 53.5% of all isolates. All isolates with the PBP profiles 13-16-ne1 and 13-7-ne4 and those having PBP1a type-13 and -131, PBP2b type-7, -ne1, and -ne2 showed nonsusceptibility to penicillin. A high degree of genetic diversity was found in PBP2x, with most of them (81.7%) being new types. ConclusionsOur current study identified the 21 novel PBP profiles and remarkable mutations in the PBPs, which may be potentially associated with penicillin nonsusceptibility in NESp.