Dr Ya-Sung Yang

Attending Physician,

Section of Infectious Diseases,

Tri-Service General Hospital, Taiwan

The emergence of macrolide-resistant pathogens in community-acquired pneumonia (CAP) has been reported worldwide. In Taiwan, there have been an increase of CAP caused by macrolide resistant pathogens.^1,2
Dr Ya-Sung Yang, an attending physician at the Tri-Service General Hospital in Taiwan, provides an epidemiological overview of pneumonia caused by macrolide-resistant Streptococcus pneumoniae and atypical pathogens in Taiwan.

Q1: In a systematic review of Asian studies, Streptococcus pneumoniae and atypical bacteria were commonly identified as causative pathogens for community-acquired pneumonia (CAP).¹ Could you describe the epidemiology profile of these organisms in Taiwan?

In Taiwan, the second edition Guidelines on Antimicrobial Therapy of Pneumonia in Adults, published by the Infectious Diseases Society of Taiwan (IDST), reported the five most significant causative pathogens for CAP to be Streptococcus pneumoniae (23-26%), Mycoplasma pneumoniae (14-20%), Chlamydia pneumoniae (8-13%), Haemophilus influenzae (5-9%) and Klebsiella pneumoniae (5-7%).¹

In CAP patients older than 60 years of age, S. pneumoniae, with a prevalence of 28.7%, is the most common pathogen. M. pneumoniae is prevalent in 19% of CAP patients younger than 44 years of age.¹ In children, a study conducted by the Taiwan Pediatric infectious Disease Alliance (TPIDA) reported S. pneumoniae as the predominant pathogen responsible for 31.6% of children with CAP, followed by M. pneumoniae (22.6%). S. pneumoniae was most prevalent in children aged between 2 and 5 years (34.4%), and M. pneumoniae was most prevalent in children aged more than 5 years (34.3%).³

Q2: What is the local prevalence of macrolide-resistant S. pneumoniae and atypical pathogens in CAP patients?

In a study describing invasive pneumococcal disease (IPD) caused by S. pneumoniae infections in Taiwan, the susceptibility rate of S. pneumoniae to erythromycin was only 10.7%.⁴ However, the mean macrolide resistant rate for M. pneumoniae was 24%, ranging from 19% to 30%, between 2010 and 2017, in a Taiwan study published in 2019.⁵

Q3: The Tigecycline In Vitro Surveillance in Taiwan (TIST) study reported an increase in the incidence of mef(A) and erm(B) genes in azithromycin-resistant S. pneumoniae isolates.⁶ For patients infected with isolates that increase macrolide resistance, how does this change the disease course and clinical outcome?

As macrolide resistance in S. pneumoniae is now a global concern with reports of treatment failure in the literature, monotherapy with macrolides is currently not recommended. ^7,8

However, studies about the relationship between macrolide-resistant S. pneumoniae and clinical outcomes of patients treated with β-lactams are scarce. According to the study by Cilloniz and colleagues on 643 CAP patients, macrolide-resistant pneumococci are common in CAP, however they do not affect the severity of illness.⁹ Macrolides should be considered for use, generally as part of a combination regimen, especially for those with severe CAP and sepsis, for their non-antibiotic effects (anti-inflammatory).¹⁰

Q4: In Taiwan, what is the current susceptibility profile and effective antimicrobial therapy for macrolide-resistant S. pneumoniae and atypical pathogens in CAP?

The susceptibility of S. pneumoniae is 63.3%, 34.0% and 24.7% to ceftriaxone, cefepime and penicillin, respectively. All S. pneumoniae isolates were found to be susceptible to vancomycin, linezolid and ertapenem. In the fluoroquinolone group of antibiotics, 95.3% and 92.7% of S. pneumoniae isolates were susceptible to moxifloxacin and levofloxacin, respectively. For carbapenems, 49.3% and 63.3% of isolates were not susceptible to meropenem and imipenem, respectively.⁴ In conclusion, fluoroquinolone is the recommended choice of antimicrobial therapy; followed by vancomycin, linezolid and ertapenem for macrolide-resistant S. pneumoniae and atypical pathogens in CAP.

Q5: What is your diagnostic and treatment strategy for managing pneumonia caused by macrolide-resistant S. pneumoniae and atypical pathogens?

Firstly, the diagnostic process of CAP is relatively straight forward. Sputum and blood cultures will be collected with atypical pathogen tests for Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella species. Based on the microbiology results and clinical responses of patients, clinicians may adjust antimicrobial treatment accordingly.

Referring to the local resistance rates and antimicrobial coverage for atypical pathogens in CAP, fluoroquinolones would be a simple treatment of choice for both pathogens based on the susceptibility profiles. If there are concerns on treating macrolide-resistant S. pneumoniae, cephalosporines, vancomycin, linezolid and ertapenem would also be considered.

References:

1. Chou CC, et al. J Microbiol Immunol Infect 2019;52(1):172-199.
2. Peto L, et al. Trans R Soc Trop Med Hyg 2014;108:326–337.
3. Chi H et al. J Formos Med Assoc 2020 Jul 15. doi: 10.1016/j.jfma.2020.07.014 [Epub ahead of print]
4. Lee MC, et al. J Microbiol Immunol Infect 2020;S1684-1182(20):30004-30009.
5. Yang TI, et al. J Microbiol Immunol Infect 2019;52(2):329-335.
6. Safari D, et al. BMC Infect Dis 2014;14:704.
7. Lynch JP 3rd, Zhanel GG. Semin Respir Crit Care Med 2009;30(2):210-238.
8. Schroeder MR, Stephens DS. Front Cell Infect Microbiol 2016;6:98.
9. Cilloniz C, et al. Am J Respir Crit Care Med 2015;191(11):1265-1272.
10. Niederman MS. Am J Respir Crit Care Med 2015;191(11):1216-1217.