Dr. Dhitiwat Changpradub
Head of Infectious Disease Division
Department of Internal Medicine
Phramongkutklao Hospital
Thailand

Sitafloxacin is a new generation broad-spectrum fluoroquinolone that has shown good in vitro activity not only against many gram-positive, gram-negative, anaerobic, and atypical pathogens, but also against bacterial strains resistant to other fluoroquinolones.¹ Oral sitafloxacin has demonstrated noninferiority versus other commonly used antibiotics for the treatment of acute bacterial infections, including complicated urinary tract infection/acute pyelonephritis and pneumonia.²

Dr Dhitiwat Changpradub – Head of Infectious Disease Division at the Phramongkutklao Hospital – shares insights into the use of sitafloxacin in his clinical practice.

Q1. In your clinical practice (or in Thailand), what are the indications for sitafloxacin?

Sitafloxacin should be preserved for patients with presumed or proven infection of third-generation cephalosporin-resistant Enterobacterales (3GCRE). For empirical treatment of presumed 3GCRE infection, it should only be prescribed for hemodynamically stable patients due to the limitation of oral drug bioavailability in critically ill patients. For definite treatment, it can be used as a switch regimen from other intravenous antibiotics, after patients are stable and in the absence of a suitable alternative antibiotic. It can also be used in unstable patients with documented infections of multidrug-resistant (MDR) pathogens as an alternative treatment in cases where there are no other susceptible intravenous antibiotics.

Q2. What is the treatment of choice for complicated urinary tract infection and pyelonephritis? What are the considerations when switching treatment to sitafloxacin for acute pyelonephritis?

For complicated upper urinary tract infections, due to the high prevalence of community fluoroquinolone resistance, the treatment of choice is either intravenous third generation cephalosporins (e.g. ceftriaxone) or aminoglycoside (e.g. gentamicin)³. If patients are at risk of 3GCRE infections, carbapenems or piperacillin/tazobactam should be used instead. Switching treatment to sitafloxacin can be done safely if the patient fulfils these criteria: he or she has documented sitafloxacin susceptibility, is haemodynamically stable, and there is no other suitable antibiotic with a narrower spectrum available.

Q3. Sitafloxacin has been shown to penetrate well into the epithelial lining fluid (ELF) in patients with pneumonia.⁴ What is your opinion and experience of using sitafloxacin for patients with pneumonia?

Sitafloxacin can be used effectively in patients with pneumonia in the outpatient setting. However, the spectrum is comparable to levofloxacin, or amoxicillin/clavulanate with macrolides, which are less expensive and are listed in The National List of Essential Medicines (NLEM). Because the common etiologic agents of pneumonia are gram positive or gram negative cocci, these patients may not greatly benefit from the broader spectrum of sitafloxacin in gram negative bacilli. However, it may be used in patients with documented infection of MDR gram negative pathogens, such as A. baumannii, as an alternative treatment, when there are no other susceptible intravenous antibiotics available or when there is a switch from definitive intravenous therapy to oral sitafloxacin in stable pneumonia.

Q4. What are the differences between using sitafloxacin versus other fluoroquinolones and other antibiotics for the treatment of bacterial infections?

The difference between sitafloxacin and other fluoroquinolones is its use against a broader spectrum of gram negative pathogens, especially 3GCRE pathogens. The susceptibility profile of gram positive and atypical pathogens, bioavailability, pharmacokinetics/pharmacodynamics, volume of distribution, and other parameters are comparable to other respiratory fluoroquinolones.⁵

Q5. What is your advice on prescribing sitafloxacin for elderly patients and those with existing comorbid conditions?

Generally, sitafloxacin has a similar safety profile as compared to other fluoroquinolones when treating elderly patients. The elderly should be monitored closely for potential drug interactions and adverse reactions e.g. QT prolongation and CNS excitatory effect.

Q6. Fluoroquinolone use has been associated with serious risk of aortic ruptures or tears as well as other disabling and potentially permanent serious adverse effects.^6,7 What are the precautions when prescribing sitafloxacin? How can these adverse events be managed? 

When any fluoroquinolone is prescribed, patients should be informed and advised to discontinue the medication if any sign of tendinopathy is observed, such as pain and swelling. Adverse events can be managed with the discontinuation of the prescribed drug and switching to other antibiotic regimens, together with surgical consultations for tendon or aortic repair.

References:

1. Keating GM. Drugs 2011;71:731-744.
2. Chen CK, et al. Antibiotics 2020;9:106.
3. Sobel JD, Brown P. Urinary Tract Infections. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 9^th ed. Philadelphia, United States; Elsevier- Health Sciences Division; 2020:962-989.e4.
4. Paiboonvong T, et al. Antimicrob Agents Chemother 2019;63:e00800-e00819.
5. Tanigawara Y, et al. J Infect Chemother 2013;19:858-866.
6. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-increased-risk-ruptures-or-tears-aorta-blood-vessel-fluoroquinolone-antibiotics#:~:text=Health%20care%20professionals%20should%20avoid,syndrome%20and%20Ehlers%2DDanlos%20syndrome%2C. Accessed 27 April 2021.
7. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-advises-restricting-fluoroquinolone-antibiotic-use-certain#:~:text=An%20FDA%20safety%20review%20has,nerves%2C%20and%20central%20nervous%20system. Accessed 27 April 2021.