Are fluoroquinolones safe? These panelists discuss current indications for this class of antibiotics, concerns over emerging black box warnings as well as keys to patient education and appropriate, safe prescribing.
In what circumstances might you employ the fluoroquinolone class of antibiotics for infected wounds?
Kazu Suzuki, DPM, CWS relates that when he suspects a wound infection due to Pseudomonas, specifically when there is green discharge or that distinct fishy smell, more often than not, an oral fluoroquinolone is an appropriate antibiotic choice. He still advocates for wound culture to help ensure appropriate treatment of the right organism when starting oral antibiotics.
Warren Joseph, DPM, FIDSA stresses the importance of the appropriate use of this class of antibiotics, citing a link to increased rates of gram positive and gram negative resistance, and adverse effects.
“That being said, if one uses (fluoroquinolones) correctly, they are broad spectrum, effective and can be an appropriate selection in the treatment of infected wounds,” says Dr. Joseph.
After one has obtained culture results, Dr. Joseph advocates for employment of definitive, directed, narrower spectrum therapy, known in antimicrobial stewardship terms as “de-escalation therapy.”
“(Given) their extremely broad spectrum, fluoroquinolones are rarely the best definitive therapy,” explains Dr. Joseph. “They may be appropriate if properly obtained cultures show mixed flora including gram negatives such as Pseudomonas aeruginosa, for which the fluoroquinolone continues to be an oral drug of choice.”
Robert Smith, DPM, MSc, RPh, CPed, CPRS says that he initially uses the Sanford Guide to Antimicrobial Therapy as a reference for empiric therapy after ascertaining the patient’s medication allergies, medical history (including checking for diabetes, hypertension, cardiac disease, collagen disorders and pregnancy), and age. He additionally relates that fluoroquinolones can be of use in some cases of certain bite wounds, as an alternative in infected extremity trauma wounds and in diabetic foot wounds, especially in cases of osteomyelitis with extensive local inflammation and systemic toxicity. More recently, Dr. Smith points to emerging literature supporting the use of nanotechnology and moxifloxacin-impregnated films in wound healing.1
Have Food and Drug Administration (FDA) warnings about this class of drugs changed your usage algorithm? There was a 2019 warning about aortic rupture/dissection and a 2018 warning about glucose homeostasis in addition to previous warnings about tendinopathy and tendon rupture.2
“I don't think these warnings changed my usage at all as there are really no good oral alternatives to fluoroquinolones when I want to treat gram negative organisms in the outpatient and ambulatory setting,” says Dr. Suzuki. He relates that he often combines a fluoroquinolone with oral doxycycline to cover gram positive bacteria while adding levofloxacin 500 mg once to twice daily to cover gram negative infections. For patients on dialysis, Dr. Suzuki also instructs them to take 500 mg of levofloxacin after hemodialysis or every other day for most patients undergoing dialysis three times weekly.
Sharing a historical perspective on the evolution of fluoroquinolone antibiotics, Dr. Joseph notes that the marketing of early quinolones over 25 years ago included promotion as drugs that “did it all” and that their broad spectrum lessened the need for other antibiotics or even cultures. Dr. Joseph says this “dangerous line of thinking” led to overprescription that he believes continues to this very day.
Dr. Joseph says reports of serious adverse effects of certain fluoroquinolones began to emerge soon after the drug class became available, resulting in the removal of ofloxacin (psychiatric disturbances), trovafloxacin (hepatic issues and possible deaths), temafloxacin, gemifloxacin and grepafloxacin from the market. Dr. Joseph shares that in 2008, tendinopathy and tendon rupture became “black box” warnings associated with fluoroquinolone antibiotics, and this warning has widened to include peripheral neuropathy and worsening symptoms of myasthenia gravis.2
He adds that there are also label “warnings and precautions” for mental health disturbances, hypoglycemia and, most recently, an increased risk for rupture of an aortic aneurysm in certain patients.
Dr. Smith agrees that the warnings and evidence associated with fluoroquinolones have indeed changed his prescribing algorithm. Having authored articles on “black box” drug warnings and drug prescribing safety, he implores providers to be vigilant in continually reviewing for new warnings associated with medications they prescribe.
“Podiatric physicians have an ethical obligation to prescribe responsibly and cautiously to diminish and minimize the growth of adverse effects from medications,” adds Dr. Smith.
What clinical steps do you feel podiatrists can take to use this class of antibiotics most safely and appropriately in wound care patients?
Dr. Suzuki thinks history taking and close monitoring is the key to prescribing fluroquinolones, or any other antibiotics.
“Although it is not life-threatening like an aortic rupture, Achilles tendon rupture is common enough that I have seen a few cases concomitant with fluoroquinolone use,” says Dr. Suzuki. “As an Achilles tendon rupture can certainly be very debilitating physically, it may be a good idea to warn the patient taking a fluoroquinolone for a skin infection to stay away from ballistic movement, such as running, jumping, or pick-up basketball games on weekends.”
Dr. Joseph stresses that the most important step podiatrists can take it to only use antibiotics for infected wounds as there is no evidence that prophylactic treatment has any effect and is contrary to evidence-based treatment guidelines. Pursuant to antibiotic stewardship principles, he advocates for using the narrowest spectrum antibiotic possible for the suspected (empiric) or cultured (definitive) organisms for the shortest possible period of time.
“If a fluoroquinolone is considered the correct choice and prescribed, then the provider should educate the patient on all of the potential adverse effects and particularly the black box warning,” explains Dr. Joseph. “One should also advise the patient to contact the prescriber or his or her primary care provider as soon as any side effects are noted.”
When considering the prescribing of medications with FDA black box warnings, Dr. Smith says podiatric physicians need to ask themselves two important questions:
- Do equally effective and safer alternative medications exist?
- Does the potential benefit of the drug with the black box warning outweigh the safety concern?
In the case of fluoroquinolones, Dr. Smith says potential adverse effects, including aortic rupture and dissection, must be routine considerations in a risk-benefit assessment.
Dr. Smith shares that when one looks at published literature and practice management survey data, the clinical data supports that quinolone prescribing is decreasing among podiatric physicians. He attributes this to multiple factors, including awareness of potential adverse drug reactions and black box warnings.
Dr. Joseph is a Diplomate of the American Board of Podiatric Medicine. A Fellow of the Infectious Diseases Society of America, Dr. Joseph frequently lectures on lower extremity infectious diseases. He is currently in practice in Philadelphia, Pa. and Cottonwood, Ariz.
Dr. Smith is the Chair of the Podiatric Medicine Academy, which is part of the National Academies of Practice. He is in private practice in Ormond Beach, Fla.
Dr. Suzuki is the Medical Director of the Apex Wound Care Clinic in Los Angeles. He is also a member of the attending staff of Cedars-Sinai Medical Center in Los Angeles. He can be reached at Kazu.Suzuki@cshs.org.
- Lee EJ, Huh BK, Kim SN, et al. Application of materials as medical devices with localized drug delivery capabilities for enhanced wound repair. Prog Mater Sci. 2017;89:392-410.
- Sakoulas G. Adverse effects of fluoroquinolones: where do we stand? NEJM Journal Watch. Available at: https://www.jwatch.org/na48248/2019/02/13/adverse-effects-fluoroquinolones-where-do-we-stand . Published February 13, 2019. Accessed July 1, 2020.