Dr Vo Thi Kim Phuong
Medical Director
Hanh Phuc Hospital, Vietnam

In 2019, the American Thoracic Society and the Infectious Diseases Society of America jointly published guidelines for the management of immunocompetent adults with community-acquired pneumonia (CAP).¹ The guidelines recommended that treatment decisions should be based on the severity of the pneumonia, treatment setting (inpatient or outpatient), and the presence of comorbidities or risk factors for drug-resistant pathogens.¹

Dr Vo Thi Kim Phuong shares her clinical experience of the management of CAP in patients with and without comorbidities, and the role of levofloxacin in optimizing the treatment of CAP.

Q1: The etiology of CAP may be complex and differ between patients, and additional complexity stems from the presence of comorbidities. What are the key differences in treatment strategies for CAP when comparing patients with comorbidities and patients without comorbidities?

CAP is a common infectious disease encountered in clinical practice. The etiology is diverse, with causative bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Legionella pneumophila, Chlamydia pneumoniae, Mycoplasma pneumoniae and aerobic Gram-negative bacteria.¹ Some of the risk factors that may determine the severity of CAP include the presence of comorbidities such as pulmonary cystic fibrosis and chronic obstructive pulmonary disease (COPD), alcohol abuse and the presence of Gram-negative pneumonia. The treatment strategy will need to be different for patients with or without comorbidities. For patients with comorbidities, in addition to choosing antibiotics that cover atypical pathogens with good penetration into lung parenchyma, the antibiotic therapy should include agents with antipseudomonal activity. Levofloxacin is often chosen for the treatment of CAP, and can be used alone or in combination, based on its broad-spectrum activity against several causative pathogens of CAP, and because it may have a synergistic effect with other antibiotics. In patients that are suspected to have  Staphylococcus aureus infection, levofloxacin therapy can be combined with vancomycin, teicoplanin or linezolid.

Q2: What are the disease and patient factors that should be considered when deciding to use levofloxacin as treatment for CAP, whether as adjunct therapy with other antimicrobials or as first-line empirical treatment?

CAP is usually treated empirically. The treatment regimen recommended for CAP patients is one that is effective in providing coverage for Streptococcus pneumoniae and other atypical bacteria. Levofloxacin is a broad-spectrum antibacterial agent with activity against a range of Gram-positive and Gram-negative bacteria, especially atypical bacteria of the respiratory tract. Monotherapy with a fluoroquinolone, also known as a “respiratory quinolone”, such as levofloxacin, can be prescribed as an alternative to combination therapy with a third-generation cephalosporin plus a macrolide.¹ In patients with comorbidities, levofloxacin is the recommended choice for combination therapy with a beta-lactam to increase treatment effectiveness and antibiotics coverage.

In addition to being recommended for CAP, hospital-acquired pneumonia (HAP) and ventilator-associate pneumonia (VAP), levofloxacin is also recommended as a first-line empirical treatment or in combination with other antibiotics for the treatment of urinary tract infection.²

Q3: In your clinical experience, is the high-dose, short course levofloxacin regimen beneficial for CAP patients with comorbidities and those without comorbidities? What are your considerations when prescribing this regimen?

The American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) CAP guidelines recommend monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily) for outpatient adults with comorbidities such as chronic heart, lung, liver or renal disease, diabetes mellitus, alcoholism, malignancy or asplenia.¹ For inpatient adults with non-severe CAP without risk factors for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa, the ATS/IDSA CAP guideline recommend empiric monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily).¹

Based on my clinical experience, high-dose levofloxacin 750mg being used alone or in combination therapy demonstrates favourable efficacy, convenience, ease-of-use and cost-ffectiveness in patients with CAP, with or without comorbidities. In our current practice, we are prescribing levofloxacin 750 mg once daily for 7 days for patients with CAP. For severe disease, the treatment duration can be 10–14 days. During the course of the therapy, continuous re-assessment of disease progression and adequate antibiotic therapy is important. For prescription of high-dose, short course levofloxacin to patients, clinicians should consider factors such as the patient’s medical history, comorbidities and the clinical context. Patients with multiple co-morbidities and immunocompromised patients should receive close monitoring.

Q4: Levofloxacin should be used with caution in patients with history of convulsive diseases, patients with severe nephropathy, patients aged 75 years and above, and those taking non-steroidal anti-inflammatory drugs (NSAIDs).³ How can the risk of adverse events be monitored and managed in the outpatient setting, and what are your recommended approaches?

We have been prescribing levofloxacin for a long time and have found that levofloxacin is a relatively safe antibiotic when recommendations are followed, and patients are carefully monitored. For patients with a history of convulsions, severe renal failure and who are over 75 years old, levofloxacin should not be prescribed in outpatient settings, but only in inpatient settings with an appropriate dose adjustment for renal function, and patients should be closely monitored for side effects. Consciousness disturbance and increased convulsions are some of the side effects that we encounter in our clinical practice. In young, physically active patients, as well as in elderly patients using corticosteroids, the risk of tendonitis and possible rupture of tendons should be kept in mind.⁴ Therefore, we need to be aware of the side effects and advise family members to monitor patients when they are treated as outpatients.

References

1. Metlay JP, et al. Am J Respir Crit Care Med. 2019;200(7):e45–e67.
2. Cao D, et al. Front Pharmacol. 2021;12:658095.
3. Yamaguchi H, et al. Chemotherapy. 2007;53(2):85–103.
4. Kim GK. J Clin Aesthet Dermatol. 2010; 3(4): 49–54.