BACKGROUND:Streptococcus pneumoniae remains a leading cause of bacterial meningitis worldwide. Although pneumococcal conjugate vaccines (PCVs) have markedly reduced vaccine serotypes (VTs) invasive pneumococcal disease, the emergence of non-vaccine serotypes (NVTs) has become an increasing concern. Data describing the clinical and microbiological characteristics of pneumococcal meningitis after the introduction of PCV13 remain limited. METHODS:We conducted a retrospective study of culture-confirmed pneumococcal meningitis at Chang Gung Memorial Hospital, Taiwan, from 2009 to 2025. Clinical characteristics, antimicrobial susceptibility profiles, outcomes, and serotype distributions were reviewed and compared between pediatric and adult patients with pneumococcal meningitis. RESULTS:A total of 23 patients with pneumococcal meningitis were identified between 2009 and 2025, including 11 pediatric and 12 adult patients. In children, the mean age was 4.8 years. Majority of the isolates are NVTs (35B, 23 A, and 15B). Two patients had meningitis caused by VTs; however, neither of them received PCV13. Clinical characteristics at admission included fever, productive cough, headache, and decreased consciousness (mean Glasgow Coma Scale:11). Susceptibility to antibiotics were similar, with most of the isolates being resistant to penicillin and ceftriaxone but susceptible to vancomycin. The in-hospital mortality rate was 18% (2/11). Most survivors suffered from complications, including empyema and multiple infarctions following vasculitis. In adults, the mean age was 48.6 years old, and majority of the serotypes were NVTs. Most had comorbidities, and the complications following meningitis were diverse. Overall, 37.5% of the patients (6/16) had meningitis attributed to VTs; all were non-immunized and occurred before 2015. CONCLUSIONS:This study demonstrated a clear serotype replacement pattern in pneumococcal meningitis in Taiwan following PCV13 implementation in children. The emergence of multidrug-resistant NVTs underscores the importance of continuous surveillance and supports the use of higher-valency pneumococcal conjugate vaccines.
BACKGROUND:This study delineated the evolving epidemiology of pneumococcal disease in Taiwan, focusing on emerging serotypes, antimicrobial susceptibility, and genotypes before and after the pandemic. METHODS:Culture-confirmed pneumococcal disease (CCPD) was analyzed across four Chang Gung Memorial Hospitals in Taiwan in 2019∼2024. Serotypes, multi-locus sequence types, and penicillin and ceftriaxone susceptibility of pneumococcal isolates were determined. RESULTS:The incidence of CCPD dropped from 16.09 in 2019 to 5.39 in 2021, followed by a rise to 9.04 in 2024, per 100,000 population. Invasive pneumococcal disease (IPD) accounted for 13.0% (126/969) of CCPD. The most common serotypes for CCPD were 23A (28.4%), 15A (14.2%), 19A (9.5%), and 15B/C (8.7%). Serotype coverage was 24.8% for PCV13, 36.4% for PCV20, and 78.2% for PCV21. Non-PCV13 serotypes contributed to approximately three fourths of CCPD. Penicillin non-susceptibility of non-PCV13 serotypes (59.7%) surpassed that of the PCV13 serotypes (45.7%) in 2024. Penicillin and ceftriaxone non-susceptibility of the isolates from children was higher than that from adults, and such non-susceptibility was more common in isolates from sputum than that from blood. Clonal complex 166 has been emerging as the predominant lineage (27.8%, 269/969), primarily composed of serotypes 23A (85.5%, 230/269) and 11A (6.7%, 18/269). CONCLUSIONS:The study shows continuously escalating penicillin and ceftriaxone resistance among pneumococcal isolates after the pandemic. Lower β-lactam susceptibility in pediatric upper respiratory tract isolates and adult sputum isolates appear to be derived from the serotype shift for CCPD.
Two pneumococcal conjugate vaccines, PCV15 and PCV20, were licensed in June 2021. PCV15 includes two additional serotypes (22F, 33F) beyond those in PCV13, while PCV20 adds seven more (8, 10A, 11A, 12F, 15B, 22F, 33F), covering approximately 30% of invasive pneumococcal disease (IPD) cases in adults. In June 2023, the US CDC's Advisory Committee on Immunization Practices (ACIP) recommended either PCV15 or PCV20 for all children aged < 5 years and children aged 2‒18 years with risk conditions. In June 2024, the FDA approved PCV21 for adults ≥ 18 years. In October 2024, ACIP recommended either PCV20 or PCV21 alone or PCV15 with PPSV23 for adults ≥ 50 years or 19-49 years with risk conditions. These advancements highlight the evolving landscape of pneumococcal vaccination. This review examines the molecular epidemiology of pneumococcal infections, advancements in diagnostic methods, and the anticipated public health impact of these vaccines in reducing pneumococcal disease burden.
As certain vaccine serotypes are still circulating within the community during the PCV13 era, we aimed to delineate the clinical features and assess the immunity following breakthrough infections in children. 101 PCVs-vaccinated children < 18 years with culture confirmed PCV13 serotype breakthrough infection (25/101, invasive pneumococcal disease [IPD]) was identified in Taiwan in 2015–2019. Immunoglobulin G (IgG) antibody levels, IgM+ memory B cells (MBCs), and isotype-switched immunoglobulin (sIg+) MBC specific to serotypes 3, 14, 19 A were assessed prior to and one month after an additional PCV13 booster in 9 patients. A cohort of 89 previously vaccinated, healthy children were enrolled as controls. The majority (88
The publisher regrets Tables were missing from the Supplementary Material available for this article. The Tables have been uploaded as Supplementary Material and are available online via https://doi.org/10.1016/j.jinf.2022.04.022.
Objectives The multi-center clinical microbiological study in Taiwan aimed to evaluate the impact of childhood PCV13 immunization on pneumococcal disease, and the magnitude of serotype replacement in invasive and non-invasive pneumococcal disease among all age groups. Methods The study of culture-confirmed pneumococcal disease (CCPD) was conducted at four hospitals across Taiwan in 2015-2018. Pneumococcal pneumonia was defined as clinical diagnosis with positive sputum or bronchoalveolar lavage culture. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing for penicillin and ceftriaxone were performed. Results A total of 1413 CCPD cases were identified. Invasive pneumococcal disease (IPD) accounted for 13.4% (190/1413) of CCPD. PCV7-type CCPD incidence declined among all age groups between 2015 and 2018. In adults aged 50-64 years, PCV7-type pneumococcal pneumonia incidence in 2018 was 72% lower than that in 2015, and all pneumococcal pneumonia incidence was 35% lower than that in 2015. In children, CCPD incidence was higher in 2018 than in 2015 (IRR 1.75 for age < 5 years, IRR 1.56 for age 5-17 years). Incidence of CCPD caused by non-PCV13-types, mainly 15A and 23A, increased significantly in those younger than 50 years. Serotypes 19A and 19F constituted the largest clonal complex, CC236/320 (n = 280, 19.8%). The rates of penicillin and ceftriaxone non-susceptibility were higher in PCV13-type isolates. Conclusions Childhood PCV13 immunization exerted an indirect protection to vaccine serotype clinically defined non-bacteremic pneumococcal pneumonia among adults, especially those between 50 and 64 years of age. Emerging non-PCV13 serotypes mainly caused non-invasive mucosal disease among children.
Purpose Antimicrobial resistance of nontyphoidal Salmonella (NTS) is a threat to public health worldwide. Methods A study on longitudinally collected NTS isolates from a medical center in Taiwan from 2011 to 2019 was undertaken. The multidrug resistance (MDR) and extensively drug resistance (XDR) phenotypes were determined according to internationally used definitions. Molecular serotyping was performed on the resistant NTS. Results Notably 16.1% (870/5412) of the isolates were MDR, while XDR accounted for 2.1% (111/5412). Both MDR and XDR NTS have increased significantly from 2011 to 2019, especially from 2015 to 2017 (MDR from 9.6% in 2015 to 23.1% 2017; XDR from 1.4% in 2016 to 4.7% in 2017). S. Anatum was the commonest NTS serotype expressing MDR and XDR, in 256/559 (45.8%) and 81/111 (73.0%) of the isolates, respectively, followed by S. Typhimurium and S. Goldcoast. Children < 18 years old contributed to 69.0% of all MDR cases and 64.0% of all XDR cases; majority of them aged less than 5 years. Conclusions Increasing MDR and XDR NTS is a threat to public health. MDR and XDR NTS usually caused gastroenteritis in children < 5 years old. Multiple NTS serotypes expressing MDR and XDR indicate multiple food vehicles involved in the transmission. Proper food hygiene practice should never be over-reinforced.
Background/purpose: Salmonella Panama was considered an invasive non-typhoidal Salmonella (iNTS) serovar. Comprehensive clinical, microbiological, and genomic studies on S. Panama are scarce. We aimed to characterize the clinical and microbiological characteristics of S. Panama infection. Virulence mechanism of S. Panama and other iNTS serovars were also examined. Methods: Based on data from the longitudinal surveillance system for Salmonella deployed in Taiwan since 2004, a case-control study was undertaken to evaluate clinical characteristics of S. Panama infection during an outbreak in 2015-2016. Cellular experiments were conducted to compare pathogenicity of S. Panama and other iNTS with S. Typhimurium. Results: Most patients (41/44, 93.2%) infected by S. Panama were <5 years old (median, 1.3 years). The case-control study showed that 28 out of the 41 (68.3%) manifested as bacteremia, compared to S. Typhimurium (11.1%). Patients infected by S. Panama had longer durations of fever (P Z 0.005) and hospitalization (P < 0.001). Genomic analyses split the isolates into three clades: two clones caused the outbreak, whereas another one accounted for the sporadic infections before 2015. Cellular experiments revealed that S. Panama and other iNTS serovars showed higher monolayer penetration and intracellular survival within macrophages, compared to S. Typhimurium.Conclusion: This study confirmed that S. Panama is a clinically invasive serovar. Different iNTS serovars express common virulence phenotypes, but they may acquire invasiveness through distinct expression or combinations of virulence genes. Copyright 2021, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Significant reduction in the incidence rates of both vaccine and non-vaccine serotype invasive pneumococcal disease among children and adults during the COVID-19 pandemic were observed after the implementation of non-pharmaceutical interventionshttps://bit.ly/36CAute
An ongoing outbreak of multidrug-resistant Salmonella enterica serovar Anatum began in Taiwan in 2015. Pork and poultry were identified as vehicles for transmission. Contaminated meat contributed to the high rate of infections among children. Nearly identical Salmonella Anatum strains have been identified in the United Kingdom, the United States, and the Philippines.
BACKGROUND:Zoonotic Salmonella enterica serovar Choleraesuis (S. Choleraesuis), causing paratyphoid in pigs and bacteremia in humans, commonly carry a virulence plasmid and sometimes a separate antimicrobial-resistant plasmid or merging together. This study aimed to analyze the likely mechanism of how to form a virulence-resistance chimera of plasmid in S. Choleraesuis.METHODS:Whole plasmid sequence of pOU7519 in S. Choleraesuis strain OU7519 was determined using shotgun cloning and sequencing. Sequence annotation and comparison were performed to determine the sequence responsible for the formation of a chimeric virulence-resistance pOU7519. Other chimeric plasmids among the collected strains of S. Choleraesuis were also confirmed.RESULTS:The sequence of pOU719, 127,212 bp long, was identified to be a chimera of the virulence plasmid pSCV50 and a multidrug-resistant plasmid pSC138 that have been found in S. Choleraesuis strain SC-B67. The pOU7519 is a conjugative plasmid carrying various mobile DNAs, including prophages, insertion sequences, integrons and transposons, especially a Tn6088-like transposon. By dissecting the junction site of the pSCV50-pSC138 chimera in pOU7519, defective sequences at integrase gene scv50 (int) and its attachment site (att) were found, and that likely resulted in a stable chimera plasmid due to the failure of excision from the pSCV50-pSC138 chimera. Similar structure of chimera was also found in other large plasmids.CONCLUSION:The deletion of both the int and att sties could likely block chimera excision, and result in an irreversible, stable pSCV50-pSC138 chimera. The emergence of conjugative virulence and antimicrobial-resistant plasmids in S. Choleraesuis could pose a threat to health public.
Background: The epidemiology of nontyphoidal Salmonella (NTS) resistant to ciprofloxacin or ceftriaxone and its impact on patients’ clinical course are rarely reported. Methods: Children with culture-proven salmonellosis treated in a medical center in northern Taiwan in 2017 were enrolled. To trace the source of Salmonella, Salmonella isolated from food samples were collected from markets. Antimicrobial susceptibility and serotypes were determined. Results: Among the 453 isolates, 122 (26.9%) were highly antimicrobial-resistant, as defined by resistance to ciprofloxacin or ceftriaxone or both. The most prevalent highly resistant serotype was S. Anatum (66, 54.1%). Salmonella was detected in 94.1%, 66.7%, and 8.6% of examined pork, chicken, and vegetables examined, respectively. S. Anatum (6, 21.4%) and S. Derby (6, 21.4%) were the major serotypes isolated. Majority of the S. Anatum (5, 83.3%) were highly antimicrobial-resistant. More patients infected by highly resistant Salmonella required carbapenem treatment (OR = 23.5, 95% confidence interval [CI] 2.8–192.7, P < 0.001). Patients with ceftriaxone-resistant NTS infections had a significantly longer hospital stay than others (P < 0.001). Totally, 34 (7.5%) presented with invasive diseases (31 bacteremia, 1 intestinal perforation, 1 toxic megacolon and 1 septic arthritis). Risk factors for invasive disease included prolonged fever for ≧5 days and infection occurring in warmer season from May to October. The rise of ambient temperature in northern Taiwan was associated with increasing Salmonella infections. Conclusions: Retail meats were the main source of highly antimicrobial-resistant NTS in northern Taiwan. Highly antimicrobial resistance significantly impacted the clinical course and treatment of children with NTS infection.
In 500 children aged ≤10 years after 13-valent pneumococcal conjugate vaccine (PCV)13 immunisation in different schedules, serotypes 19A-specific and 19F-specific immunoglobulin G (IgG) were predicted to persist above 0.35 µg/mL for ≥10 years in all groups, likely due to PCV13-induced memory with natural boosting from residual diseases and colonisation. Generally, serotype-specific IgG could persist above 0.35 µg/mL longer (≥5 years) in the catch-up group than in the 2+1 and 3+1 immunisation groups. 14.5% of the carriage isolates belonged to PCV13 serotypes; statistical analysis revealed that a high serum IgG level (>10.96 µg/mL) will be required to eliminate the point-prevalence nasopharyngeal carriage of serotype 19A.
Incidence of invasive pneumococcal disease caused by antimicrobial-resistant Streptococcus pneumoniae types not included in pneumococcal conjugate vaccines has increased, including a penicillin- and meropenem-resistant serotype 15A-ST63 clone in Japan. During 2013–2017, we collected 206 invasive pneumococcal isolates in Taiwan for penicillin and meropenem susceptibility testing. We found serotypes 15B/C-ST83 and 15A-ST63 were the most prevalent penicillin- and meropenem-resistant clones. A transformation study confirmed that penicillin-binding protein (PBP) 2b was the primary meropenem resistance determinant, and PBP1a was essential for high-level resistance. The rate of serotype 15B/C-ST83 increased during the study. All 15B/C-ST83 isolates showed an ermB macrolide resistance genotype. Prediction analysis of recombination sites revealed 12 recombination regions in 15B/C-ST83 compared with the S. pneumoniae Spain23F-ST81 genome. Pneumococcal clones rapidly recombine to acquire survival advantages and undergo local expansion under the selective pressure exerted by vaccines and antimicrobial drugs. The spread of 15B/C-ST83 is alarming for countries with high antimicrobial pressure.
BACKGROUND:Carriage of methicillin-resistant Staphylococcus aureus (MRSA) is associated with its transmission. International travels and massive gatherings may accelerate such transmission. MRSA carriage was surveyed among the attendees of two international medical conferences held in Taipei in 2010.METHODS:A total of 209 attendees from 23 countries were recruited. Nasal specimens were collected from each volunteer and subjected to polymerase chain reaction (PCR) detection for MRSA. Molecular analysis, including pulsed-field gel electrophoresis, multilocus sequence typing (MLST), typing of staphylococcal cassette chromosome mec (SCCmec) and staphylococcal protein A (spa) genes, and detection of Panton-Valentine leukocidin (PVL) and sasX genes, was performed.RESULTS:MRSA carriage was detected in 10 (4.8%) attendees from Vietnam (3/8, 37.5%), Korea (2/6, 33.3%), Japan (2/41, 4.9%), Philippines (2/52, 3.8%), and Bangladesh (1/4, 25.0%). The proportion of MRSA colonizers was significantly higher in the local hospital group compared to those from the other groups (3/17 vs. 7/192, p < 0.05). Six MRSA isolates were available for molecular analysis. They all carried a type IV SCCmec gene. Five pulsotypes were identified; four genotypes, respectively, were identified by MLST and spa typing. None of the isolates carried either PVL or sasX genes. None of common molecular characteristics was shared by isolates from different countries. Most of these isolates were local endemic community clone in each country.CONCLUSIONS:As healthcare workers, a certain proportion of international medical conference attendees harbored MRSA in their nares, mostly local endemic community clones in each country, which has the potential of spread among attendees.
The study aimed to investigate the impact of 13-valent pneumococcal conjugate vaccine (PCV13) immunization on the overall pneumococcal disease in children in Taiwan by surveillance of culture-confirmed pneumococcal disease (CCPD). This study was conducted in a medical center from 2012 to 2016. Clinical isolates of Streptococcus pneumoniae were prospectively collected from pediatric patients. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing were performed. A total of 473 patients with CCPD, including 58 with invasive pneumococcal disease (IPD), were identified. The incidence of CCPD per 10,000 admissions decreased from 71.7 in 2012 to 27.0 in 2016. The proportion of additional PCV13 serotypes significantly decreased from 52.0% in 2012 to 21.7% in 2015 but increased slightly to 26.7% because of serotype 19A in 2016 (P < 0.0001). The proportion of non-vaccine serotypes (NVTs) increased significantly from 18.4% in 2012 to 66.7% in 2016, but the increase of the incidence of CCPD caused by NVTs was not considered significant (P = 0.0885). Genotyping identified predominant clones, ST63(15A), ST83(15B), and ST166/338(23A), for major NVTs. The penicillin non-susceptibility of PCV13 serotypes was significantly higher than that of NVTs (P < 0.0001). Surveillance of CCPD appears superior to IPD alone for evaluation of the overall impact of pneumococcal immunization. Serotype replacement occurred quickly after the use of PCV13, while the incidence of NVT infection did not show a significant increase in children over the years. The gradual introduction of PCV13 into national immunization program is effective in reducing overall pneumococcal disease in children. (C) 2019 Elsevier Ltd. All rights reserved.