Fluoroquinolones for the Management of Skin and Soft Tissue Infections

13 June, 2023

Dr Jakrapan Jirasiritham
Head of Gastrointestinal and General Surgery Unit
Department of Surgery, Faculty of Medicine
Ramathibodi Hospital, Mahidol University
Bangkok, Thailand

Bacterial infections affecting the skin and the underlying soft tissues require timely and appropriate treatment.¹Fluoroquinolones have demonstrated effectiveness in treating such bacterial infections, and current guidelines recommend that fluoroquinolones be reserved for moderate to severe skin and soft tissue infections (SSTIs) caused by Gram-negative bacteria, and for cases where patients are unable to tolerate other antibiotics.²

Dr. Jakrapan Jirasititham from Thailand provides his insights on the use of fluoroquinolones for SSTIs, including considerations for patient selection, optimal dosing regimens, and strategies for minimising the risk of adverse effects.

Q1: What are the main risk factors for contracting SSTIs in Thailand, and do these risk factors differ from other countries?

The main risk factors for SSTIs in Thailand are similar to those observed in other countries. These risk factors include trauma or injury, an immunocompromised host, cardiovascular disease, obesity, intravenous drug use (IVDU), chronic skin disease, and poor hygiene.³ Among these factors, the most prominent one in Thailand is the combination of trauma or injury with compromised immunity. It is worth noting that cases of IVDU are relatively uncommon in the context of SSTIs in Thailand.

Q2: What are the current guidelines for the prevention of SSTIs in Thailand? How do these guidelines compare to international guidelines for preventing SSTIs?

At present, there are no official local guidelines for the prevention or management of SSTIs in our region. As such, we adopt international guidelines, such as the 2018 World Society of Emergency Surgery (WSES) and the Surgical Infection Society Europe (SIS-E) consensus conference recommendations for the management of SSTIs or the Surgical Infection Society’s 2020 Updated Guidelines on the Management of Complicated, as the basis for our approach to the management of SSTIs.^{4, 5}

Q3: How do different patient populations (e.g. immunocompromised patients) affect the choice of antibiotic regimen for the treatment of SSTIs?

The selection of antibiotics for the empirical treatment of SSTIs varies depending on the patient population. Prior to initiating treatment, it is crucial to accurately diagnose and categorise the SSTI as either complicated or uncomplicated.⁶In the case of complicated SSTIs, further identification of necrotising or non-necrotising subtypes is necessary before determining the appropriate choice of antibiotics.⁶

Another important factor to consider is whether the patient has a community-acquired or hospital-acquired infection.⁶ Additionally, if available, the antibiogram data from each hospital or region can provide valuable insights for selecting the most effective antibiotics tailored to local antimicrobial resistance patterns.⁷ These considerations contribute to the precise and individualised selection of antibiotics for the management of SSTIs.

Q4: When is it appropriate to prescribe fluoroquinolones for SSTIs? Can you discuss the latest research or developments in the use of fluoroquinolones for SSTIs?

The role of fluoroquinolones in the treatment of SSTIs has been well-established and has garnered support from major infection guidelines. Particularly notable are the third and fourth generation fluoroquinolones, owing to their broad-spectrum activity, covering Gram-positive bacteria, including anaerobes (fourth generation), and their exceptional ability to penetrate the skin and soft tissues.⁸

According to the 2018 WSES/SIS-E consensus paper, fluoroquinolones are recommended for the treatment of both uncomplicated and non-necrotising complicated SSTIs in regions with a low incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection.⁴ This recommendation is based on the favourable characteristics of fluoroquinolones described above.

Q5: What is the rationale for using once-daily, high-dose (750 mg) levofloxacin in the treatment of complicated SSTIs? Please provide an overview of the evidence supporting this regimen.

High-dose levofloxacin is the recommended treatment option for non-necrotising complicated SSTIs owing to its broad spectrum of activity against Gram-positive aerobes, Gram-negative aerobes, and Pseudomonas spp. These microorganisms are commonly associated with skin/subcutaneous abscesses, burn wounds, bite wounds, and pressure ulcers. Levofloxacin also exhibits greater penetration into the skin and soft tissues compared to linezolid, doxycycline, tigecycline, or azithromycin.⁹

In some cases, the addition of anti-MRSA agents or anti-anaerobic agents may be necessary to provide comprehensive empiric or targeted treatment. In Thailand, levofloxacin is effectively utilised owing to the relatively low prevalence of resistant strains, particularly when compared to Western countries. Additionally, the low incidence of MRSA pathogens makes levofloxacin suitable for monotherapy. While severe cases often necessitate treatment initiation with parenteral levofloxacin and a later switch to oral therapy, non-severe or uncomplicated SSTIs can be managed solely with oral levofloxacin.

Supporting evidence for this regimen stems from a large multicenter, open label, randomised trial published in Clinical Infectious Disease in 2002, which compared high-dose levofloxacin (750 mg, intravenous/oral) with ticarcillin-clavulanate (TC; 3.1 g intravenous every 4 to 6 hours) alone or followed by amoxicillin-clavulanate (AC; 875 mg every 12 hours).¹⁰ In the clinically evaluable population, the success rates were 84% for levofloxacin group and 80% for TC/AC group, with no statistically significant difference observed between the groups.¹⁰ This finding highlighted that a once-daily dose of 750 mg levofloxacin is at least as effective as TC/AC for the treatment of complicated SSTIs.

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