ABSTRACT
OBJECTIVE: Review the efficacy and safety of an updated empiric vancomycin dosing protocol in a neonatal intensive care unit (NICU). METHODS: Retrospective chart review including neonates with postmenstrual age (PMA) less than 40 weeks without renal dysfunction who received vancomycin per protocol at a single institution's NICU before and after implementation of an updated dosing protocol. The primary outcome is the proportion of initial therapeutic troughs. Secondary outcomes include average trough, achievement of a therapeutic trough, number of days before attainment of a therapeutic trough, and proportion of acute kidney injury (AKI) during therapy. RESULTS: The 2 groups were similar in gestational age, race, birth weight, PMA, and weight at time of vancomycin initiation. The post-implementation group had a higher proportion of initial therapeutic troughs (33.0% vs 55.1%) and a lower proportion of a subtherapeutic (58.7% vs 43.8%) and supratherapeutic (8.3% vs 1.1%) initial troughs (p = 0.002). The median trough was not different (9.20 vs 10.50 mg/L; p = 0.092). There was no difference in the proportions of achieving a therapeutic trough throughout therapy (69% vs 76%; p = 0.235); however, the post-implementation group achieved a therapeutic trough 1 day earlier (3 vs 2 days; p < 0.001). There was no difference in proportions of AKI developing between the pre-implementation vs post-implementation groups (10.1% vs 5.6%; p = 0.251). CONCLUSIONS: Implementation of an updated vancomycin dosing protocol yielded a higher percentage of initial therapeutic vancomycin troughs and patients reached the therapeutic range 1 day earlier without increasing the proportion of AKI.
ABSTRACT
The development of modulator therapy has, for the first time, allowed direct targeting of the underlying cause of cystic fibrosis (CF), the cystic fibrosis transmembrane conductance regulator (CFTR). Patients treated with CFTR modulators have improvement in lung function and decreased rates of pulmonary exacerbations. In 2019, elexacaftor/tezacaftor/ivacaftor was approved for use in the United States, opening these therapies to 90% of patients with CF. Intolerable adverse drug reactions to CFTR modulators results in discontinuation of therapy, which can be devastating to our patients. We describe our approach to two cases, not previously reported, of rash to elexacaftor/tezacaftor/ivacaftor in patients with a previous history of cutaneous adverse reactions to dual modulator therapy that had been addressed by desensitization. Case 1 was able to tolerate elexacaftor/tezacaftor/ivacaftor after desensitization to the triple combination therapy, while in Case 2 tolerance was obtained by treating through the reaction. The loss of tolerance in these patients was unexpected, and may be a common finding in patients with history of cutaneous adverse reactions to these drugs. We hope reporting our experience, including our desensitization protocol, may benefit CF patients for whom these drug reactions may be limiting access to powerful disease altering therapies.
