Dr Sombat Leelasupasri, MD, PhD

Infectious disease consultant, Phyathai II Hospital, Thailand

Sitafloxacin, a fluoroquinolone, is a newer generation wide-spectrum antibiotic that has been shown to be active against Gram-positive and -negative bacteria, including those that have developed resistance to other antibiotics.^2-4 It is indicated for the treatment of various bacterial infections, including respiratory and urinary tract infections.² In addition, sitafloxacin was also demonstrated to be effective against antimicrobial resistant bacteria including the strains resistant to other fluoroquinolones.^2,5-7

This interview session features Dr Sombat Leelasupasri, an infectious disease consultant at the Phyathai II Hospital, in a discussion on the role of sitafloxacin in the combatting the rise of drug-resistant infections.

Q1. What is the current epidemiology of bacterial infections in Thailand? Based on your clinical experience, what is the estimated percentage of infections caused by antimicrobial resistant pathogens in your centre? What are the challenges you encounter in the management of antimicrobial resistant infections?

A1: In Thailand, antimicrobial resistant infections caused by Gram-negative bacilli are more prevalent compared with those caused by Gram-positive cocci. One of the major concerns in Thailand is the development of resistance against the last-line antibiotics, such as carbapenem. In 2018, the National Antimicrobial Resistance Surveillance Center, Thailand (NARST) has reported that about 55.5% of Acinetobacter baumannii and 20% of Pseudomonas aeruginosa isolated in Thailand were carbapenem-resistant.⁸ Among Enterobacteriaceae, less than 5% of Escherichia coli and 10% of Klebsiella pneumoniae isolates were also found to be carbapenem-resistant.⁸ Meanwhile, the NARST also reported that extended spectrum beta-lactamases (ESBL) -producing bacteria consist of 46% and 48% of E. coli and K. pneumoniae isolates, respectively.⁸ In the Phyathai II Hospital, the prevalence of carbapenem-resistant Enterobacteriaceae and carbapenem-resistant A. baumannii (CRAB) were found to be less than 5% and 50–60%, respectively. The most challenging case of antimicrobial resistance is ventilator-associated pneumonia (VAP) caused by CRAB.

Q2. Sitafloxacin is a newer generation of fluoroquinolone that may be used for the treatment of bacterial infections.² What are the criteria for sitafloxacin use? Based on your experience, what is the clinical efficacy of sitafloxacin in your patients?

A2: Based on my clinical experience, sitafloxacin may be used for Gram-negative infections, especially for complicated urinary tract and lower respiratory tract infections. It may also be considered in combination with metronidazole in intra-abdominal infections caused by ESBL-producing bacteria. In my opinion, due to high rate of sitafloxacin susceptibility, sitafloxacin 100 mg twice daily should be considered as an adjunctive therapy to the treatment with colistin and carbapenem in patients with VAP. The dose consideration is based on minimum inhibitory concentration (MIC) breakpoint of ≤2 mcg/ml, used in studies in Thailand.^9,10 The dose is maintained if the sensitivity result shows intermediate resistance, or reduced to 50 mg twice daily if the bacteria were susceptible to sitafloxacin (MIC <1 mcg/ml). Because of higher MIC₉₀ distribution of sitafloxacin against Gram-negative bacilli isolated from Thai patients, compared with those of Japanese patients,^9-11 I prefer 100 mg twice daily administration for empirical treatment. Based on my experience, sitafloxacin is efficacious especially in urinary tract infection (UTI); more than 90% of UTI cases under my care show improvement with sitafloxacin.

Q3. A few strains of bacteria, such as E. coli, have also reportedly developed resistance against fluoroquinolones.¹² How frequent do you encounter fluoroquinolone-resistant cases in your clinical practice? Would sitafloxacin have a role in managing these cases?

A3: A study showed that fluoroquinolone-resistant bacteria were isolated in 51% of urine samples collected from Thai patients, which was comparable to that reported for other Asia Pacific countries.¹³ Based on my clinical experience, sitafloxacin may be considered in these cases especially in UTIs. However, it should also depend on the sensitivity test result.

Q4. Sitafloxacin use has been associated with a few side effects, such as gastrointestinal and hepatic function disorders.¹⁴ How common are these side effects and how are they addressed in clinical practice?

A4: Based on my clinical experience, side effects related to the use of sitafloxacin are uncommon. Only a few complaints of stomach discomfort, somnolence and non-restorative sleep were reported by my patients. One case of dysglycaemia was found in a diabetic patient. However, there was no reported case of transaminitis, haematological side effects or prolonged QT interval. In case of side effects, dose adjustment or treatment withdrawal will be considered depending on the goal of treatment, patient’s tolerability and availability of alternative drugs. In case of prolonged QT, the Thailand Food and Drug Administration and the manufacturer must be notified.

References

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3. Huang YS, et al. J Microbiol Immunol Infect 2015;48:545-551.
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5. Rodjun V, et al. Open Forum Infect Dis 2018;5(Suppl 1):S718–S719.
6. Malaisri C, et al. J Infect Chemother 2017;23:556-562.
7. Manosuthi W, Wiboonchutikul S. Springerplus 2016;5:410.
8. National Antimicrobial Resistance Surveillance Center, Thailand. Antimicrobial Resistance 2000-2019. Available at: http://narst.dmsc.moph.go.th/. Accessed 18 October 2019.
9. Tiengrim S, et al. J Med Assoc Thai 2012;95:S6-17.
10. Leechawengwongs M, et al. Antimicrob Agents Chemother 2017;62(1).
11. Amano A, et al. Jpn J Antibiot 2010;63:411-430.
12. Spellberg B. J Infect Dis 2015;212:1853-1855.
13. Polwichai P, et al. J Med Assoc Thai 2009;92:S59-67.
14. Matsumoto T, et al. Jpn J Antibiot 2011;64:319-337.