Pharmacologic contraception methods for people with cystic fibrosis: A practical review for clinicians.

Over the last several decades, substantial treatment advances have improved the quality of life and median predicted survival in people with cystic fibrosis (PwCF). It is critical for CF clinicians to begin to discuss health considerations related to an aging and overall healthier CF population. Such considerations include family planning, reproductive health, and contraception. CF care teams are trusted sources of medical information and therefore often have initial discussions related to contraception for PwCF. The purpose of this article is to review the available pharmacologic contraceptive methods, with a specific focus on the benefits and risks that may be more relevant to PwCF.

Review of Tobramycin Dosing in Pediatric Patients With Cystic Fibrosis.

OBJECTIVE: An institution's tobramycin pharmacokinetics (PK) database was reviewed to evaluate the efficacy and safety of empiric tobramycin dosing and monitoring strategies used in pediatric patients with cystic fibrosis (CF). The relationship between patient age and tobramycin dosing needed to achieve the area under the curve (AUC) goal was investigated. METHODS: Retrospective chart review was performed for patients who received tobramycin during a CF exacerbation from 2009 to 2019 who received PK monitoring by pediatric pharmacists. Tobramycin dosing needed to achieve an AUC of 100 mg·hr/L was calculated for each patient. Serum creatinine and concomitant nephrotoxin use were collected as surrogate nephrotoxicity endpoints to evaluate safety. RESULTS: Goal AUC (100 ± 15 mg·hr/L) was achieved based on initial or repeat PK calculations in 43.5% (95% CI, 37.7-49.3) of 85 unique patients across 326 encounters. Patients with calculated recommended doses of 9.5 to 11.9 mg/kg every 24 hours empirically achieved goal AUC in 77% (78/101) of encounters. The odds of achieving goal AUC were 56% higher for children aged 10 vs 5 years (OR = 1.56; 95% CI, 1.04-2.34; p = 0.033) and 32% higher for children aged 15 vs 10 years (OR = 1.32; 95% CI, 1.07-1.61; p = 0.008). Overall rates of acute kidney injury and concomitant nephrotoxin use were 10.8% (95% CI, 6.2-15.5) and 80.7% (95% CI, 74.3-87.1), respectively. CONCLUSIONS: Desired AUC was achieved by 43.5% of pediatric patients with CF using tobramycin 10 mg/kg every 24 hours. Older patient age was associated with higher initial AUC attainment and fewer dose modifications. Younger children may require higher weight-based dosing to meet AUC goals.

A Review of Extended and Continuous Infusion Beta-Lactams in Pediatric Patients.

Intravenous beta-lactam antibiotics are the most prescribed antibiotic class in US hospitalized patients of all ages; therefore, optimizing their dosing is crucial. Bactericidal killing is best predicted by the time in which beta-lactam drug concentrations are maintained above the organism's minimum inhibitory concentration (MIC), rather than achievement of a high peak concentration. As such, administration of beta-lactam antibiotics via extended or continuous infusions over a minimum of 3 hours, rather than standard infusions over approximately 30 minutes, has been associated with improved achievement of pharmacodynamic targets and improved clinical outcomes in adult medical literature. This review summarizes the pediatric medical literature. Applicable studies include pharmacodynamic models, case series, retrospective analyses, and prospective studies on the use of extended infusion and continuous infusion penicillins, cephalosporins, carbapenems, and monobactams in neonates, infants, children, and adolescents. Specialized patient populations with unique pharmacokinetics and high-risk infections (neonates, critically ill, febrile neutropenia, cystic fibrosis) are also reviewed. While more studies are needed to confirm prospective clinical outcomes, the current body of evidence suggests extended and continuous infusions of beta-lactam antibiotics are well tolerated in children and improve achievement of pharmacokineticpharmacodynamic targets with similar or superior clinical outcomes, particularly in infections associated with high MICs.

Rapid Infliximab Biosimilar Infusion in Children With Inflammatory Bowel Disease.

OBJECTIVES: Compare prevalence of infusion reaction (IR) between infliximab (IFX) and infliximab biosimilar (IFX-abda) at standard and rapid rates and measure the impact on health care cost in children with inflammatory bowel disease (IBD). METHODS: Records of subjects receiving IFX and IFX-abda were reviewed over a 21-month period. Demographics and IRs were recorded. Cost analysis utilized average wholesale pricing, infusion duration, nursing time, and infusion center throughput. RESULTS: Fifty-six subjects received 498 infusions. Sixteen subjects received both IFX and IFX-abda. Thirteen IRs occurred for an overall prevalence of 2.6%. One outlier subject accounted for 8 of 13 (62%) of IRs. Data were analyzed with and without the outlier. Standard rate infusion of both IFX and IFX-abda was associated with increased risk of IR compared with rapid rate but only reached significance for IFX when calculated with the outlier removed. Risk of IR was not statistically significant between IFX and IFX-abda for both standard and rapid rates. IFX-abda saved an average of $2,611 per infusion. Rapid infusion saved 70 minutes of infusion time, 20 minutes of estimated nursing time per infusion, and decreased infusion center appointment length by as much as 2 hours per infusion. CONCLUSIONS: Rapid IFX-abda appears safe without increased IRs and decreases cost.

Evaluation of the safety of cefepime prolonged infusions in pediatric patients with cystic fibrosis.

OBJECTIVE: Pediatric cystic fibrosis (CF) patients possess unique pharmacokinetics and may benefit from prolonged beta-lactam infusions to optimize pharmacodynamics. This study compared adverse drug event (ADE) rates with cefepime prolonged (PI) and standard infusions (SI). METHODS: This retrospective study included pediatric patients treated with cefepime for CF exacerbations between 2009 and 2019. One encounter per patient was analyzed with prioritization of SI encounters given sample size limitations. Baseline lab abnormalities, seizure disorders, and bleeding were exclusion criteria. The primary outcome was a composite safety endpoint (acute kidney injury [AKI], hepatotoxicity, hematologic toxicity, neurotoxicity, and hypersensitivity). RESULTS: Of 188 patients, 135 received PI and 53 received SI. Baseline characteristics were similar between groups. More PI patients used CF transmembrane conductance regulator (CFTR) modulators (25% vs. 0%, p < 0.01) or had antibiotic allergies (62% vs. 38%, p = 0.02). Difference in rates of composite safety endpoint was not statistically significant between PI and SI (21 [15.6%] vs. 6 [11.3%] p = 0.46) nor was incidence of AKI (16 [11.8%] vs. 6 [11.3%], p = 0.92). Other ADEs were rarely observed. Length of stay (12.2 vs. 10.1 days, p = 0.06), change in discharge ppFEV1 from admission (13 vs. 12, p = 0.91) or from baseline (-4 vs. -6.5, p = 0.33), and time to next exacerbation (249.7 vs. 192.5 days, p = 0.93) were similar. CONCLUSIONS: No difference in risk of ADEs including AKI was seen with cefepime PI in pediatric CF patients. Clinical outcomes were not significantly different between groups, but sample size may have limited comparison. PI cefepime may be considered in pediatric CF patients to optimize pharmacodynamics.