Reconsidering fluoroquinolone for skin, soft tissue and bone infections

28 July, 2020

Professor Terapong Tantawichien

Professor, Division of Infectious Diseases,

Department of Medicine, Faculty of Medicine,

Chulalongkorn University, Thailand

In the 2014 Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections, the Infectious Diseases Society of America (IDSA) recommends the use of a fluoroquinolone (e.g., ciprofloxacin and levofloxacin) in combination with metronidazole for surgical site infections and polymicrobial necrotising fasciitis while ciprofloxacin, levofloxacin or moxifloxacin monotherapy can be used for purulent bite wounds and abscesses.¹ In low-risk patients with suspected or confirmed skin and soft tissue infections (SSTIs), the combination of ciprofloxacin or levofloxacin with amoxicillin-clavulanate is preferred during the initial episodes of fever and neutropenia.

Meanwhile, the 2015 IDSA practice guidelines also recommends the use of levofloxacin as parenteral antimicrobial treatment for patients with osteomyelitis.²

Professor Terapong Tantawichien, infectious disease expert at Chulalongkorn University, shares his experience on the use of fluoroquinolone for the treatment of SSTIs and bone infections.

Q1. What are the most commonly seen SSTIs in Thailand? How are these patients being treated?

In Thailand, the most commonly seen SSTIs are community acquired cellulitis and skin abscess caused by Streptococci, methicillin-sensitive Staphylococcus aureus and Gram-negative pathogens. These SSTIs can cause serious complications in elderly patients, those with comorbidities such as diabetes and cirrhosis, as well as in patients who are immunocompromised and those who use steroids.

Fortunately, antibiotic resistance is not a concern in most pathogens that cause community-acquired SSTIs. As such, these patients are typically treated with cloxacillin, second or third generation cephalosporins with or without metronidazole or beta-lactamase inhibitors such as amoxicillin/clavulanic acid and ampicillin/sulbactam.

Contrarily, antibiotic resistance is an increasing challenge in the treatment of nosocomial SSTIs such as surgical site infections, bedsores and burn wound infections. Common causative pathogens of nosocomial SSTIs include methicillin-resistant S. aureus, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. The antibiotics of choice differs depending on the situation of antibiotic resistance in each hospital in the country. For instance, in hospitals with serious nosocomial SSTIs, an increasing usage of carbapenems or antipseudomonal beta-lactamase inhibitors with or without vancomycin has been observed.

Q2. What is your opinion on the use of levofloxacin in SSTIs? Are other fluoroquinolones being prescribed?

Levofloxacin is known for its excellent oral bioavailability and broad-spectrum activity against aerobic and anaerobic pathogens of community-acquired bacterial SSTIs. Levofloxacin has also demonstrated good penetration profiles.

In my opinion, levofloxacin should be prescribed for treatment of SSTIs in patients with penicillin allergy; SSTIs in patients with mixed Gram-negative/Gram-positive infections; and SSTIs with bone and joint involvement. In addition, due to the good oral bioavailability of levofloxacin, it can be used in switch therapy – from intravenous antibiotics to oral antibiotics – in early discharge programmes.

Q3. Fluoroquinolones have shown good tissue penetration;³ but there are only few data concerning their penetration into bone tissue.⁴ What is your experience in using levofloxacin for the treatment of osteomyelitis?

Theoretically, fluoroquinolones have shown good bone penetration. Hence, fluoroquinolones such as ciprofloxacin is the treatment choice for many orthopaedists and infectious disease specialists.

In addition to having bactericidal activity against the common pathogens that cause community-acquired SSTIs in Thailand, infectious disease specialists here also use levofloxacin for the treatment of bone and joint infections such as in patients with penicillin allergy; mycobacterial infection; and mixed or unknown community-acquired infections including uncomplicated diabetic foot infection and animal bite infection involving bone and joint. Levofloxacin is also used in combination with other antibiotics for synergistic effects.

Q4. The emergence of EBSL-producing pathogens and methicillin-resistant Staphylococcus aureus (MRSA) is one of the challenges faced in the treatment of SSTIs.⁵What are some treatment strategies to resolve this? How do fluoroquinolones play a role and does sitafloxacin, in particular, have a role?

Although the incidence of antibiotic-resistant infections has been increasing in Thailand, SSTIs caused by MRSA or ESBL-producing Enterobacteriaceae in our practice are less commonly seen. The most commonly seen SSTIs are complicated diabetic foot infections and nosocomial SSTIs – particularly in the burn units, dialysis units and intensive care units within the hospital. In such cases, majority of patients are given parenteral antibiotics active against MRSA (e.g., vancomycin and linezolid) and multidrug-resistant (MDR) Gram-negative bacteria (e.g., antipseudomonal beta-lactamase inhibitors, imipenem and meropenem). Ciprofloxacin or newer fluoroquinolones are used as a combination therapy for MDR SSTIs due to their synergistic effects.

Besides, in Thailand, sitafloxacin is active against common community-acquired pathogens including ESBL-producing Enterobacteriaceae, thus used for the treatment of SSTIs caused by multiple organisms – particularly in uncomplicated diabetic foot infections or in mild-to-moderate infections. Sitafloxacin is also used as a monotherapy in these cases – taking into consideration patients’ compliance with a single agent.

In my experience, the use of oral sitafloxacin in SSTIs caused by ESBL-producing Enterobacteriaceae (e.g., complicated diabetic foot infections and surgical site infections) can shorten the course of parenteral broad-spectrum antibiotic therapy, i.e. switching from intravenous to oral antibiotic for ambulatory care.