Dr Tu Chih-Yen
Professor and Chair, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital
Chair of Internal Oncology of China Medical University Hospital Cancer Center
Director of Taiwan Society of Pulmonary and Critical Care Medicine

The selection of antibiotics for the treatment of pneumonia is a critical decision that is regularly encountered by healthcare professionals (HCPs). One key factor for consideration is whether to select an innovator or generic drug. While innovator drugs are often perceived as more reliable and potent, generic alternatives offer potential cost savings.¹ Awareness of the comparative efficacy and safety profiles of these treatment options is crucial for HCPs when making informed decisions and may impact patient outcomes.

Dr Tu Chih-Yen from Taiwan shares his experiences and evidence-based perspectives on the clinical effectiveness of innovator versus generic antibiotics for optimising the treatment of pneumonia.

Q1: What are the key differences between innovator and generic antibiotics in terms of their clinical effectiveness in treating pneumonia?
Based on the findings from the paper published in the Journal of Global Antimicrobial Resistance in 2023, the rates of resistance against innovator levofloxacin were observed to be significantly lower compared to its generic counterpart.² Furthermore, innovator levofloxacin demonstrated a more favourable response compared to generic levofloxacin with regard to treating common pathogens in community-acquired pneumonia (CAP), such as methicillin-sensitive Staphylococcus aureus (MSSA), Streptococcus, Escherichia coli and Klebsiella pneumoniae. It is worth noting that, in Taiwan, the spectrum of pathogens encountered in CAP predominantly include Streptococcus, while Klebsiella pneumoniae is a common pathogen in patients with diabetes mellitus (DM) or liver cirrhosis.³

Q2: Can you discuss the safety profiles of innovator and generic antibiotics for the treatment of pneumonia? Are there any notable differences or considerations in terms of adverse effects or potential risks?
The common side effects of levofloxacin, both innovator and generic, include dizziness, nausea, headache, gastrointestinal (GI) disturbance and QTc prolongation. However, the incidence of adverse effects leading to discontinuation with innovator levofloxacin 750 mg is
relatively low (less than 2%).⁴ Based on clinical experience, some patients who were switched from intravenous (IV) innovator levofloxacin to oral generic levofloxacin experienced GI discomfort and headaches. Additionally, patients using IV innovator levofloxacin did not experience QTc prolongation. These findings suggest that there may be some differences in the safety profiles of innovator and generic antibiotics for the treatment of pneumonia. However, it is important to consider individual patient factors and potential drug interactions when selecting the appropriate antibiotic.

Q3: Are there any specific subtypes or strains of pneumonia where the choice between innovator and generic antibiotics becomes more critical?
There is no specific evidence indicating that certain subtypes or strains of pneumonia require a more critical choice between innovator and generic antibiotics. Based on my clinical experience, the choice between innovator and generic antibiotics should be made on a case-by-case basis, taking into consideration factors such as the causative pathogen, patient characteristics and any potential drug interactions or contraindications. In the absence of specific evidence to dictate the choice between innovator and generic antibiotics, it is essential for HCPs to rely on guidelines and recommendations from reputable sources. For example, the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) provide guidelines for the management of CAP, which include recommendations for antibiotic selection based on the severity of illness, risk factors for specific pathogens and local resistance patterns.⁵

In my opinion, for patients with moderate-to-severe CAP, it is crucial to select adequate and effective antibiotics. Therefore, selecting innovator levofloxacin rather than generic levofloxacin for the treatment of pneumonia in these patients is reasonable.

Q4: Can you share your insights or experiences regarding patient acceptance or adherence to treatment when it comes to innovator or generic antibiotics (e.g., fluoroquinolones) for pneumonia?
Pneumonia remains a significant cause of mortality in Taiwan, with an annual death toll of approximately 10,000 individuals in 2022.⁶ Insights derived from studies conducted in the United States and Denmark, published in Nature Communications and Journal of Antimicrobial Chemotherapy, shed light on the impact of introducing generic antibiotics, including fluoroquinolones, into clinical practice.^{7, 8} The introduction of generic antibiotics, including fluoroquinolones, has been associated with an increase in their consumption rates. This surge in usage has, in turn, led to a rise in resistance rates among Escherichia coli strains. These findings underscore the complex relationship between antibiotic availability and utilisation and the development of antimicrobial resistance.

An additional clinical observation is that patients may have a higher likelihood of experiencing side effects when transitioning from innovator levofloxacin to generic levofloxacin. This shift is of clinical significance, as it can potentially influence patients’ adherence to their prescribed treatment regimens.

In my experience, patient acceptance and adherence to treatment can vary depending on various factors. Some patients may prefer innovator medications owing to its perceived higher quality or efficacy, while others may prioritise cost savings with generic antibiotics. It is important for HCPs to provide guidance on the choice between innovator and generic antibiotics and likely outcomes.

Q5: How do you communicate with patients about the choice between innovator and generic antibiotics for pneumonia treatment?
When communicating with patients about the choice between innovator and generic antibiotics for pneumonia treatment, I engage in shared decision-making (SDM). While there is little evidence regarding the optimal patient communication strategies when selecting between innovator and generic antibiotics for pneumonia treatment, the concept of SDM is widely recognised and recommended by clinical practice guidelines. For example, the Institute for Patient- and Family-Centered Care emphasises the importance of involving patients in decision making and tailoring treatment plans to their individual needs and preferences.⁹

In my practice, the available antibiotic options are discussed with the patient, including the benefits and potential risks of both innovator and generic antibiotics. In Taiwan, the cost of antibiotics is covered by the health insurance system. Therefore, patients often choose innovator levofloxacin over generic levofloxacin for their pneumonia treatment.

References

1. Cotia A, et al. Antibiotics (Basel) 2023;12:935.
2. Ma P, et al. J Glob Antimicrob Resist 2023;33:120 –
3. Lin YT, et al. BMC Infect Dis 2010;10:307.
4. Citing websites: Levaquin. Available from: https://www.rxlist.com/levaquin-drug.htm. Accessed 10 Oct 2023.
5. Metlay JP, et al. Am J Respir Crit Care Med 2019;200:e45–
6. Citing websites: Number of deaths from pneumonia in Taiwan in 2022, by age group. Available from: https://www.statista.com/statistics/944267/taiwan-number-of-deaths-from-pneumonia-by-age-group/. Accessed 2 Oct 2023.
7. Kållberg C, et al. Nat Commun 2021;12:2937.
8. Jensen US, et al. J Antimicrob Chemother 2010;65:1286–
9. Hsu C, et al. BMC Fam Pract 2019;20:35.