CF Patients’ Risk For Ototoxicity Underreported

Las Vegas—The complex needs of patients with cystic fibrosis (CF) who are managed by specialty pharmacies just got a bit more complicated by a new study showing that these patients have a much higher risk for developing aminoglycoside-induced ototoxicity than previously thought.

The researchers are urging centers to monitor patients with CF more closely for aminoglycoside-induced ototoxicity after finding high rates of the complication at their institution.

After implementing a pharmacist-recommended monitoring protocol, physicians increased their use of audiograms in at-risk patients from roughly 25% to nearly 100% and found more than 55% were experiencing aminoglycoside-induced ototoxicity. That is in contrast to the rates of aminoglycoside-induced ototoxicity reported by the Cystic Fibrosis Foundation (CFF): 1.3% among pediatric patients and 2.4% among the overall CF population (on.cff.org/ 3c9Fp6x).

The high rate of ototoxicity found at Children’s Mercy Kansas City after implementation of the algorithm is “extremely interesting” and likely reflects underreporting of the adverse event and low rates of extensive testing and monitoring at many centers, commented Matthew Miller, PharmD, a clinical specialist in infectious diseases and co-chair of antimicrobial stewardship at the University of Colorado Hospital, in Aurora.

“It definitely appears to be a prudent consideration to monitor for ototoxicity for those requiring prolonged or repeated courses of aminoglycosides, including aerosolized routes of administration, and particularly if other risk factors, such as renal impairment or a family history of hearing problems, exist,” Dr. Miller said.

E. Claire Elson, PharmD, a clinical pharmacy specialist in CF and pulmonology, Department of Pharmacy, at Children’s Mercy Kansas City, and her colleagues evaluated their institution’s approach to monitoring patients with CF for this complication by reviewing the medical records of 50 patients with CF treated with IV aminoglycosides and 70 treated with inhaled aminoglycosides between 2014 and 2016. They found that only 25% had undergone an audiogram.

“Most physicians at our institution were aware of the problem of aminoglycoside-induced ototoxicity at that time and were eager for a clinical tool to help them monitor and potentially minimize the impact of this adverse event,” noted Dr. Elson, who presented a study on the topic at the ASHP 2019 Midyear Clinical Meeting (poster 4-061).

To create such a tool, Dr. Elson and her colleagues scoured the published literature and developed an aminoglycoside-induced ototoxicity monitoring algorithm (AIOA). The AIOA specifies monitoring intervals based on the type of aminoglycoside administered, the duration and frequency of treatment, the route of administration, and any patient and family history of hearing problems (Figure).

Pharmacists Take a Lead Role

Pharmacists in the CF clinic and inpatient setting take a lead role in monitoring by identifying patients for ototoxicity screening, tracking exposure to aminoglycosides, and reviewing audiogram results, Dr. Elson said. They also recommend therapeutic drug monitoring, alternative agents when necessary and otoprotective agents for patients with ototoxicity, she explained.

Pharmacist-recommended treatment decisions following a finding of ototoxicity depend on the severity of the adverse event and specific nature of the problem. “If we have alternative agents, we may modify the inhaled/IV antibiotic regimen,” Dr. Elson said. “Otherwise if the ototoxicity is mild and there are no alternative agents, we ensure adequate hydration, appropriate monitoring of therapeutic levels and utilization of otoprotective agents.”

An analysis of 49 patients treated with IV aminoglycosides during a 30-month period after implementation of the AIOA in January 2017 revealed that 98% (48/49) of patients with CF receiving aminoglycosides had at least one audiogram after the protocol was established. Moreover, 56% (27/48) of audiograms uncovered hearing abnormalities, including 12 patients with distortion product otoacoustic emissions abnormalities and 15 with high-frequency hearing loss. Among 33 patients who had multiple audiograms, 45% (15/33) showed significant worsening of ototoxicity over time, Dr. Elson reported.

“I think the most likely explanation as to why our ototoxicity rates are much higher than previously reported in this population is that centers may not have a standard monitoring practice,” Dr. Elson said. “Although it’s possible another reason could be the dosing strategies we use and the risk within our patient population, we’ve evaluated this and determined that we are following standard and guideline-based practice for therapeutic monitoring of aminoglycosides in our population, so I believe this is less likely.”

Dr. Elson said since publicizing her findings, several other CF centers have approached her institution to collaborate and develop a national AIOA. She is also optimistic that the CFF is developing practice guidelines that may include recommendations for audiogram monitoring in this patient population.

Dr. Miller said the researchers’ “very thorough process for monitoring aminoglycoside safety would be worth implementing for those centers that care for a significant population of patients with cystic fibrosis.”

However, the algorithm could be challenging to use in routine practice at centers with low overall aminoglycoside utilization and shorter durations of use, he noted.

“Testing could also be impractical or not possible in patients with critical illness who have received sedation or are mechanically ventilated,” Dr. Miller noted. “Lack of access to the necessary equipment and a noisy or distracting environment may also make it difficult to conduct inpatient audiometry testing.”