Fluoroquinolone use associated with unplanned discontinuation in PJIs
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The use of fluoroquinolones was associated with significantly higher unplanned drug discontinuation and more adverse events among patients with prosthetic joint infections, according to a study published in Clinical Infectious Diseases.
“Fluoroquinolones have been a popular antibiotic choice among bone and joint infections due to high bioavailability, coverage of typical organisms and convenient dosing,” Nicholas J. Vollmer, PharmD, a PGY2 critical care pharmacy resident at the Mayo Clinic in Rochester, Minnesota, told Healio. “That said, the FDA releasing concerning warnings, coupled with increasing rates of resistance, have led many clinicians to be increasingly wary of their use. As fluoroquinolones are currently a guideline-recommended antibiotic for prosthetic joint infections, we were interested in seeing how many patients were able to tolerate their long courses due to their numerous adverse events and warnings.”
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Vollmer and colleagues assessed 156 adult patients 64 of whom had total hip arthroplasty (THA) and 92 who had total knee arthroplasty (TKA) infections who were treated for staphylococcal periprosthetic joint infections with debridement, antibiotics and implant retention between Jan. 1, 2007, and Nov. 21, 2019.
According to the study, the primary outcome was rate of unplanned drug discontinuation and secondary outcomes included incidence of severe adverse events, unplanned rifamycin discontinuation, mean time to unplanned regimen discontinuation, and all-cause mortality.
The study showed that unplanned drug discontinuation occurred in 35.6% (32 of 90) patients who received fluoroquinolones and 3% (2 of 66) of patients in the nonfluoroquinolone group. Additionally, the rate of unplanned discontinuation of fluoroquinolones regimens as
compared with that of nonfluoroquinolone regimens was 27.5% vs. 4.2% (P = .021) in THA infections and 42% vs. 2.4% (P < .001) in TKA infections. The researchers also found that there was no significant difference in severe adverse events between fluoroquinolone and nonfluoroquinolone regimens in both THA and TKA infections. The overall rate of nonsevere adverse events among those in the fluoroquinolones regimen compared with that of nonfluoroquinolone regimens was 43.3% vs. 6.1% (P < .001), they reported.
“While we pointed out that fluoroquinolones do have a much higher incidence of adverse events and unplanned discontinuation, I don't believe that we should avoid them altogether,” Vollmer said. “I think they still serve a place in the right patient with the right follow-up and monitoring. Programs such as complex outpatient antimicrobial therapy (COpAT) may be ideal for patients receiving fluoroquinolones as they will have routine follow-up where their concerns and adverse events can be closely monitored and addressed.”
In a related editorial, Monica V. Mahoney, PharmD, clinical pharmacy coordinator for infectious diseases, and Kyleen E. Swords, DNP, a nurse practitioner — both at Beth Israel Deaconess Medical Center in Boston — described the relationship between quinolone antibiotics and infectious disease clinicians as “it’s complicated.”
Mahoney and Swords explained the decade-long timeline of the FDA adding box warnings for fluoroquinolones.
“The combination of these warnings and collateral damage has led some institutions to completely remove fluoroquinolones from their formulary medications,” they wrote. “Alternatively, at the opposite end of the stewardship spectrum, there [are] increasing data and clinician comfort regarding the use of oral antibiotics to treat infections historically managed with IV antibiotics.”
They cited the POET trial which “demonstrated that transitioning to oral therapy is effective in endocarditis therapy” and noted that “oral step-down therapy, usually fluoroquinolones, in gram-negative bloodstream infections is also effective.” They wrote that the OVIVA trial “showed similar outcomes with oral therapy in bone and joint infections.”
Based on the complicated history and data available, they said the benefits and risks associated with fluoroquinolone therapy must be balanced and monitored closely.
“Rather than shunning an entire class of antibiotics, perhaps a moderate approach of carefully selecting patients for oral fluoroquinolone therapy with formalized COpAT follow-up at predetermined time intervals could mitigate the risks while maximizing the benefits,” Mahoney and Swords concluded.
References:
Mahoney MV, Swords KE. Clin Infect Dis. 2021;doi:10.1093/cid/ciab150.
Vollmer NJ, et al. Clin Infect Dis. 2021;doi:10.1093/cid/ciab145.
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