Dr NguyễnHứa Quang
Head of Respiratory Department, Da Nang Hospital
Da Nang City, Vietnam

The 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) clinical guidelines on the diagnosis and treatment of community-acquired pneumonia (CAP) provide conditional recommendations for macrolide monotherapy in the treatment of outpatients with CAP based on resistance levels.¹ For the standard empiric therapy of patients with severe CAP, the guidelines recommend a combination of β-lactam/macrolide in favour of β-lactam/fluoroquinolone.

Dr NguyễnHứa Quang – Head of Respiratory Department at the Da Nang Hospital – shares his experience on the management of patients with CAP caused by macrolide-resistant respiratory pathogens.

Q1: What is the prevalence of macrolide-resistant CAP pathogens in Vietnam?

Surveys carried out in Vietnam have shown that Streptococcus pneumoniae and Haemophilus influenzae are common causes of CAP in adults. S. pneumoniae accounts for 30% of CAP. Other causative pathogens include Moraxella catarrhalis, Gram-negative bacteria including Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa; Staphylococus aureus are also observed at a lower rate compared with other causative pathogens. The detection rate of atypical pathogens is about 30%, with Mycoplasma pneumoniae being the most common (81.4%).

Resistance rates of S. pneumoniae and H. influenzae to macrolides are very high in Vietnam. According to the Survey of Antibiotic Resistance (SOAR) study, S. pneumoniae resistance to macrolides was 96% to 97%; about 31% of H. influenzae were resistant to azithromycin due to high minimum inhibitory concentration (MIC).

Q2: How are patients with CAP caused by macrolide-resistant pathogens managed? How has the updated 2019 ATS/IDSA clinical guidelines influenced treatment decisions for this group of patients?

S. pneumoniae have demonstrated a high resistance rate not only to macrolides but also to β-lactams. In Vietnam, resistance rates for S. pneumoniae to macrolides was more than 90%. Moreover, more than 60% of S. pneumoniae strains that caused CAP are penicillin-resistant S. pneumoniae (PRSP). Thus, in our department, respiratory quinolones such as levofloxacin and moxifloxacin are preferred over β-lactams plus macrolides in the treatment of patients with CAP. This practice is also in accordance to the ATS/IDSA clinical guidelines.

Q3: Is levofloxacin typically used as a monotherapy or combination therapy for patients with CAP (e.g., patients with comorbidities, those with non-severe CAP, mild-to-moderate CAP, and severe CAP)?

Levofloxacin is used as a monotherapy or combination therapy for patients with CAP depending on the patient’s condition. Monotherapy levofloxacin is used in the majority of CAP cases owing to the high resistance rates of S. pneumoniae and H. influenzae to macrolides, penicillin as well as β-lactams.

In Vietnam, levofloxacin and moxifloxacin are recommended for the treatment of CAP outpatients with comorbidities including chronic heart, lung, liver or renal diseases, diabetes mellitus, alcoholism, malignancy, and asplenia as well as for patients who have recently used antibiotics. Monotherapy with respiratory quinolone is also indicated for mild-to-moderate inpatients with CAP.

For inpatients with severe CAP who are admitted to the intensive care unit (ICU), especially patients suspected to be infected with P. aeruginosa, levofloxacin or ciprofloxacin plus an anti-pseudomonal β-lactam are recommended.

Q4: What is the role of high dose, short course levofloxacin (750 mg for 5 days) in the management of respiratory tract infections (RTI) in Vietnam?

As mentioned earlier, PRSP is a major cause of CAP in Vietnam. As such, levofloxacin plays an important role in the management of patients with RTI. Levofloxacin is recommended for mild or moderate CAP and moderate exacerbation of chronic obstructive pulmonary disease (COPD) as monotherapy.

Q5: What are the advantages of using this regimen (in terms of efficacy and safety)? Are there any differences in using this regimen compared with the conventional dosing regimen?

Levofloxacin is a fluoroquinolone with a broad spectrum of activity against Gram-positive and Gram-negative bacteria as well as atypical respiratory pathogens. It is active against both penicillin-susceptible and penicillin-resistant S. pneumoniae. It has high oral bioavailability and a long half-life. Levofloxacin is a concentration-dependent bactericidal agent and its therapeutic effect is linked to the area under the curve/minimum inhibitory concentration (AUC/MIC) and maximum concentration to MIC ratio (Cmax/MIC). Thus, high-dose levofloxacin has greater therapeutic efficacy compared with the conventional dose.

In my opinion, the high dose, short course levofloxacin regimen is well tolerated with a similar side effect profile to the conventional regimen for the treatment of patients with respiratory infection. This high dose, short course regimen is also convenient for patients as the duration of treatment can be shortened. In addition, the short course contributes to the reduction of mutation-mediated antibiotic resistance.

Q6: Are other fluoroquinolones being prescribed for the treatment of patients with CAP?

Levofloxacin and moxifloxacin are fluoroquinolones that are prescribed for the treatment of patients with CAP in my department. We prefer using levofloxacin over moxifloxacin for the treatment of patients in whom the causative pathogens cannot be determined (i.e., over 50% of CAP). We also use levofloxacin for the treatment of patients with severe CAP and suspected to be infected with P. aeruginosa.

References:

1. Metlay JP, et al. Am J Respir Crit Care Med 2019;200:e45-e67.
2. Van PH, et al. J Antimicrob Chemother 2016; 71(Suppl 1):i93-i102.