Search Results (149)

Background: Invasive pneumococcal disease (IPD) is predominantly caused by Streptococcus pneumoniae and is associated with high mortality. This vaccine-preventable disease has been a significant public health concern, particularly among children < 5 years and adults > 50 years in India. Pneumococcal vaccines help prevent pneumococcal infections caused by certain strains of S. pneumoniae, but diagnostic challenges in India hinder disease management. Methods: The objective of this expert panel discussion is to deliberate upon the pathogenesis and epidemiology of S. pneumoniae in India, techniques for overcoming the diagnostic challenges in the isolation and detection of S. pneumoniae, and to explore opportunities for partnerships between clinicians and microbiologists to bridge gaps. A non-systematic, targeted literature search was conducted to identify studies supporting key themes of expert panel discussion. Eight microbiologists, one infectious disease, one pediatrics and neonatology, and one respiratory medicine specialist from different parts of India participated in the discussion. Results: The panelists reiterated that while culture is the gold standard, multiplex real-time polymerase chain reaction and BioFire^® FilmArray^® technology have been the most common diagnostic methods for the detection of S. pneumoniae in India, especially in tier 1 cities. Conclusions: This article elucidates the challenges faced by microbiologists and clinicians in isolating and detecting the pathogen, and proposes solutions to determine the true burden of pneumococcal disease in India. This information could further inform public health policy and vaccination strategies. Full article

Co-infection between influenza and Streptococcus pneumoniae is an important public health concern, since influenza can increase susceptibility to secondary bacterial invasion and enhance bacterial transmission. We develop and analyze a compartmental model of influenza–pneumococcal co-infection with eleven epidemiological compartments, incorporating imperfect vaccination, quarantine, and a three-stage pneumococcal progression from colonization to invasive disease. We establish the positivity and boundedness of solutions, determine the equilibria, and derive, via the next-generation matrix method, the sub-model reproduction numbers $R_0^I$ and $R_0^P$ together with the composite threshold $R_0=max\{R_0^I,R_0^P\}$. Each single infection undergoes a forward bifurcation: the disease-free equilibrium is locally asymptotically stable when the corresponding reproduction number is below unity, and a unique endemic equilibrium—globally asymptotically stable in the pneumococcal sub-model, established by a Goh–Volterra Lyapunov function—emerges above it. When both thresholds exceed unity, the two infections compete for the shared susceptible pool and undergo competitive exclusion: one infection persists while the other, together with the co-infected class, is eliminated. We show that the outcome is governed not by the disease-free reproduction numbers but by the invasion reproduction numbers evaluated at the single-infection boundary equilibria, so that even equal disease-free thresholds do not yield coexistence. Numerical simulations confirm the analytical results and quantify the effect of quarantine and vaccination, providing a framework for assessing control of interacting respiratory infections. Full article

Background/Objectives: Invasive pneumococcal disease (IPD) remains associated with substantial mortality. We evaluated whether routinely available baseline variables were associated with 65-day all-cause mortality among adults hospitalized with IPD. Methods: We conducted a retrospective cohort study of 195 adults hospitalized with IPD. The primary endpoint was 65-day all-cause mortality, with hospital admission as the time origin and administrative censoring at day 65. Logistic regression and Cox proportional hazards models were fitted with a prespecified adjustment set that included age, sex, invasive mechanical ventilation, procalcitonin, and pH. Results: Overall, 42 patients died during follow-up. Non-survivors had lower admission pH, higher procalcitonin concentrations, and more frequent invasive mechanical ventilation. In the adjusted logistic model, lower pH showed a directionally consistent but non-significant association with mortality (OR per 0.05-unit decrease, 1.45; 95% CI, 0.96–2.20; p = 0.080). In the adjusted Cox model, lower pH was associated with a higher mortality hazard (HR per 0.05-unit decrease, 1.31; 95% CI, 1.03–1.65; p = 0.026). When lower pH was correctly oriented as the risk marker, its AUC was 0.729. The apparent AUC of the multivariable model was 0.831, and the bootstrap optimism-corrected AUC was 0.785. Conclusions: In adults hospitalized with IPD, lower admission pH, higher procalcitonin levels, and invasive mechanical ventilation were associated with worse outcomes. Lower pH showed the most consistent prognostic signal, particularly in time-to-event analysis, but estimates were imprecise and should be interpreted as exploratory. These findings support the potential bedside value of early acid–base assessment for risk stratification in IPD. Full article

Antimicrobial resistance (AMR) and virulence have traditionally been viewed as competing traits in bacterial evolution due to fitness costs. However, Streptococcus pneumoniae has emerged as a paradigm of successful coevolution, with multidrug-resistant clones simultaneously maintaining or enhancing pathogenic potential. This review examines the molecular mechanisms, epidemiological patterns, and clinical consequences of the convergence between AMR and virulence in Streptococcus pneumoniae. Resistance to β-lactams is driven by mosaic penicillin-binding protein genes (pbp1a, pbp2b, pbp2x), while macrolide resistance is mediated primarily by the erm(B) gene (MLS phenotype) and mef(A/E)–msr(D) genes encoding an efflux system. These determinants are frequently co-localized on integrative and conjugative elements, ICEs, (e.g., Tn916 family) within successful clonal complexes such as CC271/320 and lineages including ST320 and GPSC10. Contrary to the classical fitness cost hypothesis, compensatory epistasis, capsular recombination, metabolic adaptations, and intra-serotype phenotypic variation enable certain clones to combine high-level resistance to β-lactams, macrolides, and tetracyclines with enhanced colonization, biofilm formation, immune evasion, and invasive capacity. Post-pneumococcal conjugate vaccine (PCV) surveillance reveals the persistence and expansion of these high-risk lineages, contributing to treatment-refractory invasive pneumococcal disease (IPD), increased morbidity, and mortality. Although PCVs have reduced vaccine-type resistant strains in some settings, serotype replacement and emerging metabolic genotypes continue to drive adaptation. This review highlights the need for integrated genomic surveillance, novel therapeutics (e.g., omadacycline, lefamulin, endolysins), monoclonal antibodies, and next-generation vaccines targeting both resistance and conserved virulence determinants. A multifaceted strategy combining antimicrobial stewardship, strengthened surveillance, and innovative interventions is essential to curb the evolving threat of resistant and virulent S. pneumoniae. Full article

Background/Objectives: Following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Oman, this study aimed to characterize the genomic epidemiology, serotype distribution, and antimicrobial resistance (AMR) of Streptococcus pneumoniae causing invasive pneumococcal disease (IPD). Methods: All IPD isolates collected through national laboratory-based surveillance between 2018 and 2021 were analyzed using Whole-Genome Sequencing (WGS). Bioinformatics tools determined serotypes, multilocus sequence types (MLSTs), and Global Pneumococcal Sequence Clusters (GPSCs). Clinical correlates and predictors of mortality were assessed via multivariate logistic regression. Results: A total of 129 IPD isolates were included. Serotype 3 (11.6%) was the most prevalent, followed by 23B and 9N (10.8% each), and 8 (8.5%). PCV13 serotypes accounted for only 26.4% of isolates, while PCV20 coverage reached 59.7%. Significant clonal diversity was observed, with GPSC12 (Serotype 3) and GPSC699 (Serotype 9N/13) being prominent lineages. Multidrug resistance (MDR) was identified in 36.4% of isolates, primarily driven by GPSC6 and GPSC699. The case fatality rate was 23.0%. Advanced age (≥65 years) and clinical presentation with bacteremia were significant independent predictors of death, whereas bacterial genotype and AMR status were not. Conclusions: The findings demonstrate significant serotype replacement in Oman after the introduction of PCV13. The high prevalence of non-vaccine serotypes and emerging MDR clones justifies the transition to higher-valency vaccines like PCV20. Sustained genomic surveillance remains essential to monitor the evolving landscape of invasive pneumococcal lineages. Full article

Complicated community-acquired pneumonia (cCAP) remains a major cause of morbidity in children. Although pneumococcal conjugate vaccines (PCVs) have reduced invasive disease, severe complications such as empyema and lung abscess persist. A retrospective analysis was conducted on 69 children treated at the University Children’s Hospital Belgrade between 2019 and 2024. Data included demographic characteristics, pneumococcal vaccination status, and radiologically confirmed complications. Patients were classified by residence and vaccination status. Statistical analysis included chi-square (χ²) tests, odds ratios (ORs) with 95% confidence intervals, and multivariable logistic regression. Pleuropneumonia and pleural effusion were the most frequent complications, while empyema and lung abscess were the most severe. Both occurred significantly more often in unvaccinated children (p = 0.0054 and p = 0.0027). Multivariable analysis confirmed vaccination as an independent protective factor against empyema (adjusted OR = 0.19, 95% CI 0.06–0.61). No significant regional differences were observed after accounting for vaccination status. Vaccination showed a strong protective effect against empyema and lung abscess (OR = 0.24 and 0.04, respectively). Unvaccinated children had significantly longer hospital stays, indicating a more severe clinical course. Prolonged hospitalization was associated with intensified antibiotic therapy, reflecting underlying disease severity. Lack of pneumococcal vaccination is strongly associated with severe complications in children with cCAP. Maintaining high PCV coverage remains essential, alongside early recognition and timely management of pleural disease. Full article

Background: Streptococcus pneumoniae may asymptomatically colonize the human nasopharynx and remains a leading cause of invasive and noninvasive disease in children, accounting for an estimated 294,000 global deaths in those aged under five years. Nationally representative serotype data from Indonesia remain limited despite national PCV13 rollout in 2022. This study aims to evaluate the distribution of Streptococcus pneumoniae serotypes and estimate the coverage of pneumococcal conjugate vaccines (PCVs) among children aged 0–18 years in Indonesia. Methods: Systematic search of PubMed, Scopus, ScienceDirect, Google Scholar, and Paediatrica Indonesiana (to December 2025) for observational studies (PROSPERO CRD420251239935). The extracted data included the study period, setting, population, specimen type, serotypes, sample size, and nasopharyngeal carriage. Pooled serotype prevalence is calculated; vaccine coverage estimated for pneumococcal conjugate vaccines containing 10 (PCV10), 13 (PCV13), 15 (PCV15), and 20 (PCV20) serotypes assuming vaccine-type priority in multicolonization. Risk of bias assessed using the Joanna Briggs Institute’s checklist for prevalence studies. Results: Nineteen studies across 13 regions of Indonesia involving children aged 0–18 years included. Nasopharyngeal carriage ranged from 21.0% to 87.6% in healthy children and 9.2% to 73% in children with illnesses. The most common serotypes were 19F, 23F, 6B, 14, 19A, and 34. Non-typeable isolates accounted for more than 20% of all isolates in several studies. The pooled coverage for PCV10, PCV13, PCV15, and PCV20 was 40.3%, 50.2%, 50.8%, and 57.0% respectively. Low-moderate RoB (63% low). Conclusions: The dominant serotypes largely included in PCV13. Active surveillance is required to monitor serotype shifts and ensure the long-term effectiveness of the national vaccination program. Full article

Background: Workplace-related outbreaks of invasive pneumococcal disease (IPD) have been increasingly reported among shipyard workers, yet their epidemiological and clinical features remain incompletely characterized. This systematic review and meta-analysis aimed to synthesize available evidence on IPD outbreaks in shipyard settings. Methods: A systematic search of PubMed/MEDLINE, Scopus, EMBASE, and medRxiv was conducted up to March 2026. Observational studies reporting IPD outbreaks in shipyards were included. Pooled incidence rates and clinical outcomes were estimated using random-effects models, with heterogeneity assessed by I² statistics. Risk of bias was evaluated using the Newcastle–Ottawa Scale. Results: Eight studies describing six outbreaks across four European countries (France, Norway, Northern Ireland, Finland; 2015–2025) were included, encompassing 131 cases among 35,623 workers. The pooled incidence was 368.9 cases per 100,000 workers with an attack rate of 2.36 per 1000 person-months for total cases, compared to 200.49 cases per 100,000 workers (95%CI 103.54–387.85) and 1.10 cases per 1000 person-months (95% CI 0.17–2.03) for laboratory confirmed cases, with considerable heterogeneity across studies. Most cases occurred in men (97.7%), with the median age ranging from 39 to 48 years. Hospitalizations occurred in 79.1% of cases, intensive care unit admission in 13.7%, and the case fatality ratio was 0.8%. Serotype 4 accounted for 67.2% of characterized isolates. Occupational exposures and shared accommodation may have contributed to transmission, although this could not be formally assessed. Conclusions: IPD outbreaks in shipyard settings are characterized by high incidence but relatively favorable outcomes, likely reflecting workforce demographics. However, considerable heterogeneity and methodological limitations across studies constrain the interpretation of pooled estimates. Preventive strategies, including vaccination and workplace-targeted interventions, should be considered as plausible public health measures, with a proactive role for occupational health services. Full article

Background: Streptococcus pneumoniae, also referred to as pneumococcus, is of immense public health significance. In particular, it causes severe invasive diseases among children. This has led to the recommendation of anti-pneumococcal prophylaxis, including the administration of penicillin and pneumococcal conjugate vaccines (PCVs), which have become available in about 90% of the countries in sub-Saharan Africa. Nonetheless, breakthrough disease still occurs. Also, PCVs can cause a shift in the distribution of pneumococcal serotypes, usually towards non-vaccine types. However, in many sub-Saharan African countries where PCVs have been introduced, there are hardly any comprehensive post-vaccination surveillance data on pneumococcus. Aim: To describe the post-vaccination epidemiology of invasive pneumococcal disease (IPD) in Ghana, including the prevalence, serotype distribution and antibiotic resistance. Methods: The study was cross-sectional and involved 14,597 patients recruited at the Korle Bu Teaching Hospital, Greater Accra Regional Hospital, Princess Marie Louise Children’s Hospital, Ho Regional Hospital, Eastern Regional Hospital, and Zonal Public Health and Reference Laboratory, Tamale. Specimens of cerebrospinal fluid (obtained by lumbar puncture) and blood were collected routinely from meningitis patients, while blood specimens were taken from pneumonia patients. These were cultured for S. pneumoniae following standard microbiological methods and subjected to antimicrobial susceptibility testing. The isolates were serotyped by the pneumotest latex agglutination kit, and the results confirmed by Quellung reaction, using serotype-specific antisera. Results: The overall prevalence of IPD was 0.66% (n = 97), varying across syndromes: bloodstream infections (0.53%, n = 38), meningitis (2.45%, n = 43), and pneumonia (0.28%, n = 16). The majority of the cases (56.70%, n = 55) occurred in the 11–20-year-old group. Ten pneumococcal serotypes were identified, with Serotype 1 being predominant (58.76%), followed by Serotypes 23B (11.34%), 33F (9.28%), and 12F (8.24%). Vaccine serotypes accounted for 81.44% of the isolates, while 18.56% were non-vaccine serotypes (23A, 23B, and 38). Antimicrobial resistance was highest against sulphamethoxazole-trimethoprim (52%), ampicillin (51%), and penicillin (46%). No resistance was observed against ciprofloxacin, levofloxacin, and vancomycin. The multidrug resistance proportion was 42.3% (n = 41). Conclusions: Even in the post-vaccination era, vaccine-type IPD remains a significant public health issue in Ghana. The observed serotype distribution and antimicrobial resistance patterns warrant sustained surveillance, more adaptive vaccination policies, and rigorous antibiotic stewardship to effectively mitigate IPD burden. Full article

Background/Objectives: Infection from Streptococcus pneumoniae can lead to serious complications, such as meningitis and pneumonia, in children under 2 years of age, older adults, and immunocompromised populations. Conjugate vaccines against the pathogen have been licensed for the prevention of invasive pneumococcal disease. Conjugate vaccine development is an involved process demanding extensive characterization of both the polysaccharide (PS) and protein (Pr) moieties in complex structures. One powerful tool in our analytical tool kit that can shed light on various analytical attributes of conjugate vaccines, such as molecular weight and composition and conjugation efficiency, is the size-exclusion chromatography-multi-angle light scattering detector (SEC-MALS) technique. Herein, we demonstrate the applicability of the SEC-MALS approach for pneumococcal conjugate vaccine product characterization. Methods: Capsular polysaccharides for serotypes (STs) 1, 3, 5, 10 A, 18 C, 24 F, and 33 F conjugated to rCRM197 carrier protein were chosen for this study. Results: The technique was very straightforward, with a high degree of accuracy (>90% based on standards) and repeatability (<2% RSD) for conjugate molar mass measurements. In addition, leveraging the capability of SEC-MALS for compositional analysis, we were able to get detailed information on the molecular assembly and conformation of the conjugates and further tweak the conjugation process to yield conjugates of a desired molar mass. Conclusions: Thus, this study highlights the usefulness of the SEC-MALS technique for in-depth conjugate vaccine biophysical characterization, which is critical for achieving optimal product attributes, driving manufacturing consistency and vaccine potency. Full article

Background: Systemic lupus erythematosus (SLE) may present with heterogeneous clinical manifestations in pediatric patients. Although infections are a major cause of morbidity and mortality in SLE, severe bacterial infections rarely represent the presenting clinical event leading to diagnosis. Case description: We report the case of a 13-year-old boy diagnosed with SLE with Sjögren’s syndrome overlap who presented with pneumococcal sepsis. The patient was admitted with high-grade fever and facial swelling, and blood cultures grew Streptococcus pneumoniae. Although an initial clinical response to antibiotic therapy was observed, fever subsequently recurred, accompanied by persistent systemic symptoms and progressive laboratory abnormalities. Further investigations revealed hematologic abnormalities, serosal involvement, renal disease, and a characteristic autoantibody profile. The patient fulfilled the 2019 ACR/EULAR classification criteria for SLE after comprehensive autoimmune evaluation. The overlap with Sjögren’s syndrome was supported by the autoantibody profile and imaging findings involving the parotid glands. Following treatment with intravenous methylprednisolone pulses, oral prednisone, hydroxychloroquine, and mycophenolate mofetil, the patient showed rapid clinical improvement and sustained remission. Conclusions: This case highlights that severe invasive bacterial infection may occasionally be the clinical circumstance that leads to the diagnosis of pediatric systemic lupus erythematosus. Persistent systemic inflammation or evolving multisystem involvement despite appropriate antimicrobial therapy should prompt consideration of an underlying autoimmune disease, even in patients without a prior history of immune dysfunction. Full article

Background/Objectives: Streptococcus pneumoniae remains a major cause of morbidity and mortality in Egypt, yet pneumococcal conjugate vaccines (PCVs) are not included in the national immunization program. Recent commitments to domestic vaccine manufacturing and temporary Gavi support create a timely decision context for policymakers to assess whether PCV introduction is cost-effective, affordable, and sustainable within Egypt’s health financing constraints. This study evaluates the cost-effectiveness, budget impact, and return on investment (ROI) of PCV introduction in Egypt. Methods: A deterministic, age-structured dynamic transmission model was developed to estimate the health and economic outcomes of PCV introduction over a 20-year horizon from a healthcare payer perspective. The analysis was conducted in line with the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) guidelines. The model captures direct and indirect effects across all age groups and includes pneumonia, meningitis, non-pneumonia non-meningitis invasive disease, and acute otitis media. Scenarios assessed immediate versus delayed introduction, alternative PCV10-to-PCV13 pathways, and domestic manufacturing price assumptions. Outcomes included deaths averted, incremental cost-effectiveness ratios (ICERs) relative to GDP per capita, budget impact, and ROI using the value of statistical life. Results: Immediate PCV13 introduction was projected to avert 139,451 deaths across all age groups over 20 years, with an ICER of 523.31 USD per DALY averted equal to 0.16 × GDP per capita. The total budget impact was USD 124.9 million per year without Gavi support and USD 120.9 million with support, yielding an ROI of 23.1. Delaying the introduction substantially reduced health gains and economic returns. Pathways involving initial PCV10 introduction followed by transition to PCV13 achieved similar health outcomes with a lower budget impact and higher ROI. Conclusions: PCV introduction in Egypt represents a high-value investment. Immediate introduction maximizes health and economic benefits, while delayed introduction entails substantial opportunity costs. Alternative PCV10-to-PCV13 pathways offer a more affordable route with a similar long-term impact. Full article

Background: Although pneumococcal conjugate vaccines (PCVs) have substantially reduced invasive pneumococcal disease, the emergence of non-vaccine serotypes and antimicrobial-resistant strains has driven the development of higher-valency vaccines. To support functional immune evaluation of these vaccines, we developed and validated a sixplexed opsonophagocytic killing assay (OPA) covering 24 pneumococcal serotypes. Methods: Eight additional serotypes, beyond the 16 included in the conventional fourplex OPA, were generated through stepwise natural mutation under increasing concentrations of ciprofloxacin or doxycycline. Assay conditions were optimized by evaluating multiple effector-to-target (E:T) ratios and baby rabbit complement (BRC) concentrations to minimize non-specific killing (NSK). Validation assessed (1) specificity using inhibition OPA with homologous and heterologous polysaccharides, (2) accuracy by comparison with the single-serotype OPA (SOPA), and (3) precision across five independent experiments using the coefficient of variation (CV). Results: An E:T ratio of 200:1 combined with 10% BRC consistently maintained NSK below 30% across all assay sets. High serotype specificity was demonstrated by near-complete inhibition following homologous polysaccharide adsorption for all serotypes except serotypes 4 and 8, which exhibited very low opsonic indices. Results from the sixplexed OPA showed strong concordance with SOPA, and overall assay precision was acceptable, with CVs generally below 30% when serotypes with very low opsonic activity were excluded. Conclusions: The sixplexed OPA expands functional antibody assessment from 16 to 24 serotypes within four assay sets, providing an efficient and scalable platform for immunogenicity evaluation of current and next-generation high-valency pneumococcal vaccines. Full article

Background: Vietnam is one of few remaining countries without a pediatric pneumococcal National Immunization Program (NIP). However, four pneumococcal conjugate vaccines (PCVs) are available in Vietnam: 10-, 13-, 15-, and 20-valent PCVs (PCV10, PCV13, PCV15 and PCV20). Given the availability of multiple PCVs, selecting an optimal vaccination strategy is challenging. This paper aims to estimate the vaccination impact of these PCVs, with and without the implementation of a pediatric NIP, to inform decision-makers and healthcare providers. Methods: A Markov model was adapted to evaluate the impact of all vaccines administered under a 3 + 1 schedule (50% vaccine uptake with direct protection assumed only) and a hypothetical scenario including PCVs 2 + 1 in Vietnam’s pediatric NIP (90% uptake with both direct and indirect protection) from a payer’s perspective. For each scenario, we performed stepwise comparisons of each vaccine with the next higher-valent option: PCV13 versus PCV10, PCV15 versus PCV13, and PCV20 versus PCV15. Results: Under the 3 + 1 schedule, PCV13 and PCV20 were cost-effective versus PCV10 and PCV15, respectively. PCV15, however, was not cost-effective versus PCV13, though offering greater health benefit but at a higher total cost. Under the 2 + 1 schedule, PCV13 remained cost-effective over PCV10, while PCV15 was not cost-effective relative to PCV13. PCV20 was dominant over PCV15. Sensitivity analyses demonstrated results consistent with both reference cases. Conclusions: Vaccinating infants in Vietnam through the private market or an NIP with PCV13 or PCV20 was estimated to be more cost-effective or cost saving than strategies based on PCV10 or PCV15, respectively. These findings provide valuable evidence to inform policy decisions. Full article

Background/Objectives: Streptococcus pneumoniae remains a major cause of invasive disease, and antimicrobial resistance is shaped by antibiotic selection and pneumococcal conjugate vaccination. A unified framework is needed to compare proposed mechanisms that maintain coexistence of antibiotic-sensitive and -resistant strains and to interpret post-vaccine resistance trajectories. Methods: We formulated a susceptible–exposed–vaccinated–infectious–recovered (SEVIR) transmission model that tracks antibiotic-sensitive and -resistant pneumococcal infections under vaccination and treatment. The basic reproduction number ($R_0$) was derived using the next-generation matrix method and used to assess local stability of the disease-free equilibrium. Using the same core structure, we evaluated three mechanism-specific extensions: treatment diversity (heterogeneous antibiotic use across host groups), pathogen diversity (serotype/subtype heterogeneity under vaccine targeting), and treatment competition (within-host competition with treatment-induced selection). Results: Treatment diversity generated stable coexistence by creating low-treatment refugia that counterbalanced strong selection in highly treated groups, supporting resistance persistence at moderate population-average treatment. Pathogen diversity reproduced serotype-specific replacement and concentration of resistance within particular subtypes after vaccination. Treatment competition produced nonlinear responses to antibiotic intensity and transient resistance surges. Overall, each mechanism explained a distinct subset of benchmark resistance patterns, suggesting that dominant drivers depend on epidemiological context. Conclusions: Interactions between vaccination, antibiotic pressure, population heterogeneity, pathogen diversity and within-host competition can yield qualitatively different resistance dynamics. Strategies combining high vaccine uptake with targeted antibiotic stewardship are likely required to curb resistance while limiting unintended serotype replacement. Full article