Dr Nguyen Xuan Bich Huyen
Respiratory Specialist and Head of Sleep Disorders
Community Health Care Center (CHAC)
Vietnam

Prior to the emergence of the COVID-19 pandemic, lower respiratory tract infections, such as community-acquired pneumonia (CAP), were already recognised as leading causes of morbidity and mortality on a global scale.¹ These infections were associated with a hospitalisation rate typically ranging between 30% and 50%.² Notably, the COVID-19 pandemic has caused significant shifts in the epidemiological patterns of other respiratory tract viruses, thereby affecting the landscape of CAP and complicating its management.³

Dr Nguyen Xuan Bich Huyen, based in Vietnam, provide insights into the current landscape of CAP diagnosis and treatment in the post-COVID-19 era, with a particular focus on the crucial role of fluoroquinolones such as levofloxacin.

Q1: How has the landscape of diagnosing and treating CAP evolved since the COVID-19 pandemic, and what specific clinical challenges have emerged as a result?
In the pre-COVID-19 era, adults with CAP commonly presented with infections attributed to rhinovirus, influenza and Streptococcus pneumonia.^4–7 However, the COVID-19 pandemic has introduced a challenge in differentiating between bacterial and viral causes of CAP. Therefore, empirical antibacterials are administered to all patients suspected of having CAP and COVID-19 coinfection. Stratification of patients is typically based on the presence or absence of comorbidities. For patients with comorbidities, monotherapy with a respiratory fluoroquinolone is considered a viable treatment option.

Q2: In the context of the COVID-19 pandemic, what difficulties have healthcare providers faced when distinguishing between respiratory infections like COVID-19 and CAP, and how has this affected treatment decision-making?
Unlike typical viral respiratory tract infections that predominantly impact the upper respiratory tract, COVID-19 displays a distinctive characteristic by significantly affecting the lower respiratory tract. This unique clinical manifestation leads to symptom similarities in symptoms between COVID-19 and bacterial pneumonia. To address this diagnostic dilemma, a comprehensive testing approach is employed for individuals presenting with symptoms of respiratory tract infection during the pandemic. This includes viral antigen testing, sputum and blood cultures and assessment of inflammatory markers before initiating treatment.

Furthermore, considering the overlap in relevant bacterial pathogens in patients with both COVID-19 coinfection and CAP, there is a tendency for empirical antibiotic recommendations to be consistent. This implies that similar bacterial pathogens are implicated in both conditions. Combination therapy is usually administered in these clinical scenarios.

Procalcitonin (PCT), a biomarker, has emerged as a valuable tool in distinguishing between viral and bacterial infections by exhibiting elevated levels in response to bacterial infections.⁸ A recent study has also highlighted the potential advantages of incorporating PCT into a hospital-based public health protocol aimed at reducing resource overutilisation and combating antimicrobial resistance.⁹ Clinicians may adhere to existing lower respiratory tract infection guidelines for the use of PCT to initiate and de-escalate antibiotics in the context of COVID-19 infection, although further research is needed to establish specific blood level cut-offs.⁹

Q3: How has the role of fluoroquinolones, such as levofloxacin, evolved in the treatment of CAP over the years, both before and after the COVID-19 pandemic?
The management landscape of CAP continues to be a significant global health concern, marked by substantial morbidity and mortality. The appropriate selection of empirical treatment for CAP patients is critical, aiming to ensure comprehensive coverage against causative pathogens, including resistant strains. Respiratory fluoroquinolones, such as levofloxacin, have emerged as crucial players in this scenario. They stand out as a class of antimicrobials with high efficacy against the pathogens most commonly associated with CAP, including macrolide-resistant and penicillin-resistant pneumococci, H. influenzae, Legionella spp. and various atypical pathogens.

The role of fluoroquinolones, notably levofloxacin, in the treatment of CAP has evolved significantly, particularly during the COVID-19 pandemic. A retrospective study focused on COVID-19 patients, indicated that levofloxacin, with its broad-spectrum antimicrobial properties and immunomodulatory effects, could serve as a beneficial adjunct treatment.^{10, 11} In the comparative analysis, superior outcomes in high-resolution computed tomography (HRCT) chest severity scores were observed with adjunct levofloxacin compared with azithromycin, although the antibiotics were comparable in terms of respiratory morbidity.¹⁰

Q4: With the increasing challenge of antibiotic resistance, what is the current status of levofloxacin’s effectiveness and safety in treating CAP in the post-pandemic era?
Numerous studies have shown that in patients with CAP, levofloxacin monotherapy may be associated with improved clinical outcomes as compared with conventional treatment, including a faster resolution of pneumonia symptoms and shorter hospital stay.^{12, 13} The pharmacokinetic profile of levofloxacin contributes to its therapeutic efficacy. The substantial lung penetration capacity and high oral bioavailability of levofloxacin underscore its effectiveness in addressing challenges posed by antibiotic resistance in the treatment landscape of CAP. A distinct advantage of levofloxacin lies in its low resistance potential which may be attributed to infrequency of spontaneous mutations associated with fluoroquinolone resistance.

The role of levofloxacin in treating CAP in the post-pandemic era is a subject of interest amidst the COVID-19 pandemic. The American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) guidelines recommend empirical antibiotic coverage for bacterial pathogens in CAP patients, including those with confirmed COVID-19 pneumonia.¹⁴ The relevant bacterial pathogens for COVID-19 patients are considered similar to those in previous CAP cases, and thus recommendations include the use of respiratory fluoroquinolones like levofloxacin.¹⁴

The safety profile of levofloxacin has been established before the COVID-19 pandemic, and evidence indicates that it is generally well-tolerated.^{15, 16} Adverse events reported include nausea, vomiting, diarrhoea and dizziness, with a comparable incidence noted between different dosages.¹⁵ Photosensitivity reactions and potential QT interval prolongation have also been observed.¹⁵ Tendon effects, including ruptures, may occur, particularly in elderly patients or in those concurrently receiving corticosteroids.¹⁵ Blood glucose monitoring is recommended for diabetic patients using hypoglycaemic agents simultaneously with levofloxacin.¹⁵

While the safety of levofloxacin has been established in pre-COVID-19 contexts, it is crucial to acknowledge the need for ongoing research on its safety in the setting of the COVID-19 pandemic. Monitoring for potential interactions and adverse events will assist in promoting the safe and effective use of levofloxacin in treating CAP during the post-pandemic era.

Q5: When it comes to transitioning from intravenous to oral therapy with levofloxacin for CAP, what specific strategies do you recommend to ensure sufficient antibiotic coverage is maintained? What, if any, are the key differences in efficacy and safety profiles of intravenous versus oral levofloxacin that must be considered when initiating the transition?
Intravenous (IV) medications typically guarantee 100% bioavailability, a parameter not always paralleled by oral antibiotics. To be effective, oral antibiotics must achieve serum bactericidal activity almost comparable to that of its IV counterpart. As mentioned previously, levofloxacin is a frontline option for the treatment of CAP. In numerous studies, IV/oral levofloxacin 500 mg once daily have demonstrated clinical success rate of over 90%, further supporting its role in CAP management.^{17, 18} Levofloxacin, characterised by favourable bioavailability exceeding >90%, makes it suitable for oral switch therapy.

Approximately 40–60% of hospitalised patients with CAP are eligible for switch therapy over 2–4-day treatment period.^18–21 This process necessitates continuous monitoring of white blood cell (WBC) count and vital signs, before the transition from IV to oral therapy takes place.¹⁸

References

1. GBD 2015 LRI Collaborators. Lancet Infect Dis 2017;17:1133–1161.
2. Steppuhn H, et al. J Health Monit 2017;2:3–35.
3. Nowak MD, et al. J Med Virol 2020;92:1699–1700.
4. Serigstad S, et al. BMC Infect Dis 2022;22:763.
5. Tang HJ, et al. Antibiotics (Basel) 2022;11:315.
6. Erdahl L & Ballester M. Citing websites: Community-Acquired Pneumonia in the Era of COVID-19. Available from: https://www.reliasmedia.com/articles/149264-community-acquired-pneumonia-in-the-era-of-covid-19. Accessed 2 January 2024.
7. Regunath H, Oba Y. Citing websites: Community-Acquired Pneumonia. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430749/. Accessed 2 January 2024.
8. Gautam S, et al. Thorax 2020;75:974–981.
9. Massey B, et al. J Public Health Emerg 2023;7:11.
10. Embaby DL, et al. J Pulm Respir Med 2022;12:615.
11. Karampela I & Dalamaga M. Arch Med Res 2020;51:741–742.
12. Carratalá J, et al. Clin Microbiol Infect 2006;12 Suppl 3:2–11.
13. Ball P, et al. Curr Ther Res Clin Exp 2003;64:646–661.
14. Metlay JP & Waterer GW. Ann Intern Med 2020;173:304–305.
15. Noreddin AM & Elkhatib WF. Expert Rev Anti Infect Ther 2010;8:505–14.
16. Karwat KJ, et al. Adv Respir Med 2006:74;77–79.
17. Furlanut M, et al. J Antimicrob Chemother 2003;51:101–6.
18. Mazumder SA. Citing websites: Intravenous-to-Oral Switch Therapy. Available from: https://emedicine.medscape.com/article/237521-overview?form=fpf. Accessed 4 December 2023.
19. Cyriac JM & James E. J Pharmacol Pharmacother 2014;5:83–7.
20. Fish DN & Chow AT. Clin Pharmacokinet 1997;32:101–19.
21. Ramirez JA, et al. BMC Infect Dis 2012;12:159.