Dr Susan Shin-Jung Lee, MD, PhD

Associate Professor, National Yang Ming University, Taipei, Taiwan.

Chief, Division of Infectious Diseases, Department of Internal Medicine;

Chief, Division of Microbiology, Department of Pathology and Laboratory,

Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

In 2016, pneumonia was listed as the third leading cause of death in Taiwan – moving up one rank from the previous year – with approximately 12,000 deaths in 2016, of which 90% were those aged 65 or above.¹

While the Taiwan Centers for Disease Control continues to strengthen its preventive measures for influenza and pneumonia through vaccination,¹ the Infectious Diseases Society of Taiwan (IDST) has been periodically updating the Guidelines on Antimicrobial Therapy of Pneumonia in Taiwan to serve as an accessible reference for physicians in managing patients with pneumonia.² The first version was established and issued in 1999, with subsequent revisions in 2001 and 2007, in conjunction with the Taiwan Society of Chest and Critical Care Medicine (TSCCM).

Dr Susan Shin-Jung Lee – expert in infectious diseases – provides an overview of pneumonia in Taiwan and discusses the latest updates in the 2018 Taiwan pneumonia guidelines.

Q1. Despite the availability of effective vaccines and potent antimicrobials, pneumonia remains one of the leading cause of deaths in Taiwan. Describe the unique aetiology and epidemiology profile of pneumonia in the country.

In Taiwan, the microbiologic diagnosis of pneumonia can be confirmed in up to 75% of cases with extensive diagnostic tools.³ The five most significant pathogens for community-acquired pneumonia (CAP) remain Streptococcus  pneumoniae (23–26 %), Mycoplasma pneumoniae (14–20%), Chlamydophila pneumoniae (8–1 3%), Haemophilus  influenzae (5–9%), and Klebsiella  pneumoniae (5–7%).³ Age plays an important role in the distribution of pathogens in CAP.  In patients more than 60 years old, S. pneumoniae is a predominant pathogen of CAP with a prevalence of 28.7%, while M. pneumoniae accounts for 19% of CAP in patients younger than 44 years of age.  K. pneumoniae is a major cause of CAP in patients in the middle age range. Additionally, K. pneumoniae and P. aeruginosa are significant pathogens in patients in patients with high disease severity – such as a high pneumonia severity index (PSI) or respiratory failure requiring mechanical ventilation.^3,4

Worldwide, the five most common pathogens causing hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are Staphylococcus aureus, Pseudomonas species, Acinetobacter species, Escherichia species and Klebsiella species – causing nearly 80% of all episodes.  S. aureus ranks first as the causative pathogen of HAP and VAP in the United States (36.3%) and in Europe (23%); however, in Taiwan, S. aureus ranks the fourth place, accounting for only 8% of HAP and VAP. P. aeruginosa is the most common pathogen in Taiwan, followed by K. pneumoniae, Acinetobacter baumannii, S. aureus, Enterobacter species, S. maltophilia, and Escherichia coli.^3,4

Unusual pathogens of pneumonia in Taiwan include Mycobacterium tuberculosis, which accounts for 1% of CAP, and Burkholderia pseudomallei, which occurs sporadically in Southern Taiwan, especially after heavy rains. ^3,4

In children, S.pneumoniae remains a major pathogen of CAP, accounting for up to 41% – reported in a study done during 2010-2013. The national pneumococcal childhood immunisation program (with the 13-valent, pneumococcal conjugate vaccine, PCV) began in 2015 in Taiwan, and we expect to see the impact of vaccination on the aetiology of CAP in the future, with a shift towards a viral aetiology – based on the experiences in other countries with a universal PCV program.^3,4

Q2. The 2007 Guidelines on Antimicrobial Therapy of Pneumonia in Taiwan featured the addition of new antimicrobial agents, dosage recommendation of parenteral agents, and new classification of pneumonia.² In the 11 years that have elapsed since the last revision, what were the considerations for re-evaluating the guidelines?

Since the last revision, there has been a new body of evidence on the treatment of pneumonia, and many new drugs have become available since then. Several international guidelines on pneumonia have been revised in the recent years, including the United Kingdom (2014),⁵ United States (2016),⁶ China (2016),⁷ South Africa (2017)⁸ and Europe (2017)⁹ – to name a few. Therefore, there was an urgency to re-evaluate and revise the Taiwan guidelines to meet contemporary clinical practice needs.

Q3. What are the major differences between the 2007 and 2018 version?

Major differences between the 2007 and 2018 guideline include: 1) the use of Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology in developing the guideline; 2) the inclusion of healthcare-associated pneumonia (HCAP) – due to the different epidemiology of pneumonia seen in this category of patients in Taiwan; and 3) recommendations for treatment for paediatric pneumonia.³

Q4. How are the Guidelines on Antimicrobial Therapy of Pneumonia in Taiwan different from the Infectious Diseases Society of America (IDSA) and European guidelines?

The guidelines on Antimicrobial Therapy of Pneumonia in Taiwan was developed in view of the local epidemiology, and antimicrobial agents currently available in Taiwan. As such, we retained the category of HCAP – which was further stratified by the risk of multidrug-resistant organisms (MDRO), and subcategorised into nursing home-acquired pneumonia (NHAP) and hemodialysis-associated pneumonia (HDAP).³ Recommendations were referred to treatment of CAP and HAP based on this risk.

Q5. While the 2016 IDSA guidelines removed healthcare-associated pneumonia (HCAP) as a distinct entity in the classification of pneumonia, the European guidelines do not cover HCAP management due to its similar aetiology to that of CAP.^9,10 What is your take on this? Should HCAP be covered in the management of pneumonia in the Taiwan guidelines?

HCAP is defined as a distinct category in the 2018 Taiwan guidelines.^3,4 In contrast to the situation in Europe, where the aetiology of HCAP was found to be similar to CAP – this is not the case in Taiwan.⁹ Taiwan has a unique medical system, in which long-term care facilities include respiratory care wards (RCW), and caring for chronically ventilated patients and hemodialysis (HD) clinics are fully reimbursed by Taiwan’s universal national health insurance (NHI).^3,4 Frequent patient transfers between these long-term care facilities and the hospitals increase the risk for infections with MDRO. Ambulatory patients in nursing homes constitute a low risk for MDRO infection, and patients under maintenance hemodialysis (HD) in community HD centers or in hospitals have a moderate risk.

As mentioned earlier, the recommendations for treatment of HCAP outlined in the 2018 Taiwan pneumonia guidelines refer to the CAP and HAP treatment regimens based on stratification for risk of MDRO infections.^3,4

Q6. Fluoroquinolones are effective antimicrobial therapy in the treatment of pneumonia. What is the role of levofloxacin for empirical HAP/VAP treatment in Taiwan?   

Fluoroquinolones remains an effective antimicrobial agent in the treatment of pneumonia. Levofloxacin is recommended as an alternative empiric monotherapy in hospitalised patients with CAP and as combination therapy for those with severe CAP.^3,4 It is also recommended as an alternative choice for non-hospitalised patients with CAP of low severity, but with comorbidities or history of antibiotic use in the past 3 months.^3,4

In HAP/VAP, levofloxacin is recommended as an empiric monotherapy in hemodynamically stable patients with low risk of MDRO infection, and as combination therapy in hemodynamically unstable patients and/or those with high risk of MDRO infection.^3,4

References

1. Ministry of Health and Welfare. Pneumonia listed as 3^rd highest national cause of death in 2016, Taiwan CDC urges severe illness high-risk groups to strengthen protective measures for influenza and Streptococcus pneumoniae infection to reduce the risk of death. Available at: https://www.mohw.gov.tw/cp-3425-33849-2.html. Accessed 8 November 2018.
2. Infectious Diseases Society of Taiwan, et al. J Microbiol Immunol Infect 2007;40:279-283.
3. Chou CC, et al. Recommendations and guidelines for the treatment of pneumonia in Taiwan. J Microbiol Immunol Infect 2019 Feb; 52(1):172-199. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30612923. Accessed 31 May 2019.
4. The Infectious Diseases Society of Taiwan. Taiwan Guidelines for the Management of Pneumonia (Traditional Chinese version). Available at: https://pneumonia.idtaiwanguideline.org/. Accessed 25 January 2019.
5. National Institute for Health and Care Excellence. Pneumonia in adults: Diagnosis and management. Available at: https://www.nice.org.uk/guidance/cg191/chapter/1-recommendations. Accessed 25 January 2019.
6. Kalil AC, et al. Clin Infect Dis 2016;63:e61-e111.
7. Cao B, et al. Clin Respir J 2018;12:1320-1360.
8. Boyles TH, et al. J Thorac Dis 2017;9:1469-1502.
9. Torres A, et al. Eur Respir J 2017;50: 1700582.
10. Healio Infectious Diseases News. Guidelines for managing community-acquired pneumonia n need of re-evaluation. Available at: https://www.healio.com/infectious-disease/respiratory-infections/news/print/infectious-disease-news/%7B645ca03e-a867-4969-b4f4-ef824b221497%7D/guidelines-for-managing-community-acquired-pneumonia-in-need-of-re-evaluation. Accessed 8 November 2018.