Antimicrobial susceptibility trends for invasive pneumococcal disease in the post-vaccine era: Insights from Taiwan

28 November, 2023

Professor Lee Chen-Hsiang
Division of Infectious Diseases,
Chang Gung Memorial Hospital,
Taiwan

The pneumococcus vaccination has played a pivotal role in reducing the burden of invasive pneumococcal disease (IPD) in adults. However, the emergence of new patterns of antimicrobial resistance may present a significant challenge in the effective management of this infectious condition.¹ Understanding the antimicrobial susceptibility patterns in adult IPD is crucial for guiding appropriate treatment decisions and ensuring optimal patient outcomes.

Professor Lee Chen-Hsiang, from Taiwan, discusses the effects of vaccination on antimicrobial susceptibility profiles of pneumococcal strains and the strategies that may be employed to address antimicrobial resistance in the management of adult IPD.

Q1: Which adult pneumococcal vaccine is most commonly used in Taiwan? What has been the impact, if any, of widespread uptake of pneumococcus vaccination in adults on the epidemiology and virulence of pneumococcal strains in Taiwan?
In Taiwan, the Advisory Committee on Immunization Practices currently recommends the 13-valent pneumococcal conjugate vaccine (PCV13) for vaccination of children. For adults, both the PCV13 and 23-valent pneumococcal polysaccharide vaccine (PPV23) are available options to prevent pneumococcal diseases including IPD. Notably, the national immunisation program implemented since 2015 for PCV13 in Taiwanese children has yielded significant positive outcomes. Recent studies have indicated a decrease in the incidence of culture-confirmed pneumococcal diseases caused by vaccine serotypes, encompassing mucosal diseases in children and non-bacteraemic pneumococcal pneumonia in adults.^1,2 Furthermore, there is a noticeable decline in the incidence of vaccine-type IPD across all age groups, underscoring the substantial impact of widespread PCV13 uptake on pneumococcal disease epidemiology in Taiwan. ^{1, 2}

Q2: What are the emerging trends or changes in the antimicrobial resistance patterns of pneumococcal strains following the introduction of the pneumococcus vaccination program?
According to the Clinical and Laboratory Standards Institute criteria, the prevalence of penicillin-non-susceptible Streptococcus pneumoniae isolated from 252 nonduplicate strains collected from patients admitted to 16 hospitals in Taiwan between 2017 and 2019 declined from 43.6% to 17.2% for non-meningitis cases.³ However, for meningitis cases, the prevalence of penicillin-non-susceptible S. pneumoniae remained high, with 90.1% reported in 2017 and 82.8% in 2019. Ceftriaxone non-susceptible S. pneumoniae rates also remained high at 64.4% in 2017 and 62.5% in 2019 for meningitis cases. Almost all isolates were susceptible to vancomycin (100%) and linezolid (99.6%). Notably, the susceptibility to levofloxacin and moxifloxacin were reported to have remained consistently high between 2017 and 2019, ranging from 94.1% to 96.9% for levofloxacin and 95.0% to 96.9% for moxifloxacin.³

Q3: What is your decision-making process for selecting antimicrobial agents for the treatment of adult IPD, considering recent antimicrobial susceptibility patterns of pneumococcal strains?
The primary challenge in selecting antimicrobial agents for adult IPD treatment is considering recent susceptibility patterns of pneumococcal strains. Penicillin remains consistently effective for non-meningitis pneumococcal diseases. However, when addressing pneumococcal meningitis empirically, caution is warranted against the use of ceftriaxone monotherapy owing to rising ceftriaxone-non-susceptibility rates.

The average non-susceptibility rates for moxifloxacin and levofloxacin are 4.2% and 6.7%, respectively. Notably, there is a relatively higher prevalence of levofloxacin non-susceptibility (11.4%) among elderly patients, which is likely linked to prior fluoroquinolone (FQ) exposure.³ Overall, resistance to FQs in S. pneumoniae remains low in Taiwan. The judicious use of antibiotics and ongoing microbial susceptibility monitoring is crucial to mitigate the burden of antimicrobial resistance in the context of adult IPD treatment.

Q4: What is your preferred first-line antimicrobial treatment for IPD, and which guidelines or evidence form the basis of your approach?
The empiric antibiotic therapy for IPD requires consideration of recent pneumococcal susceptibility patterns. In this context, clinicians in Taiwan draw upon established guidelines for management of community-acquired pneumonia (CAP), such as the Taiwan pneumonia guidelines.⁴ Notably, scientific literature strongly supports the use of levofloxacin for both empiric antibiotic therapy and definitive treatment for IPD.

Q5: What clinical strategies may be employed to prevent growing antimicrobial resistance in pneumococcal strains, to better reserve options for IPD in the future?
A recent study has revealed that vaccination with PCV13 is linked to a 10.0% reduction in hospitalised pneumonia and a 9.4% reduction in hospitalised lower respiratory tract infections when compared to unvaccinated adults.⁵ These findings provide strong evidence that PCV13 vaccination for older adults could offer significant public health benefits, including a reduction in exacerbations of chronic diseases.

Following the successful implementation of PCV13, a significant decrease in pneumococcal antibiotic resistance was demonstrated in Taiwan. However, several years post-PCV13 implementation, antibiotic resistance has been on the rise in certain bacterial strains owing to the emergence of resistant non-vaccine serotypes.^1–3 This evolving landscape necessitates proactivity to address anticipated changes, such as serotype replacement and increasing antibiotic resistance. In light of the upcoming next-generation PCVs, the need to implement clinical strategies aimed at mitigating antibiotic resistance in pneumococcal strains is paramount. These efforts, such as prudent use of antibiotics, are crucial to preserve the efficacy of available antimicrobial options for the future management of IPD.

References