Colistin therapy is associated with the development of nephrotoxicity. We examined the incidence and risk factors of nephrotoxicity associated with colistin dosing. We included adult hospitalized patients who received intravenous (IV) colistin for >72 h between January 2014 and December 2015. The primary endpoint was the incidence of colistin-associated acute kidney injury (AKI). The secondary analyses were predictors of nephrotoxicity, proportions of patients inappropriately dosed with colistin according to the Food and Drug Administration (FDA), European Medicines Agency (EMA), and Garonzik formula and clinical cure rate. We enrolled 198 patients with a mean age of 55.67 ± 19.35 years, 62% were men, and 60% were infected with multidrug-resistant organisms. AKI occurred in 44.4% (95% CI: 37.4–51.7). Multivariable analysis demonstrated that daily colistin dose per body weight (kg) was associated with AKI (OR: 1.57, 95% CI: 1.08–2.30; p = 0.02). Other significant predictors included serum albumin level, body mass index (BMI), and severity of illness. None of the patients received loading doses, however FDA-recommended dosing was achieved in 70.2% and the clinical cure rate was 13%. The incidence of colistin-associated AKI is high. Daily colistin dose, BMI, serum albumin level, and severity of illness are independent predictors of nephrotoxicity.

Purpose: A case of a nortriptyline overdose complicated by delayed ventricular arrhythmias necessitating prolonged sodium bicarbonate infusion is presented, along with a review of tricyclic antidepressant (TCA) toxicology and key concepts for massive overdose management. Summary: A 61-year-old man presented after an intentional nortriptyline overdose with a possible consumption of up to 2500 mg of nortriptyline. Electrocardiogram on presentation demonstrated QRS widening to 240 milliseconds. Despite treatment with a sodium bicarbonate infusion and further narrowing of his QRS interval, his course was complicated by repeated episodes of wide complex tachycardia. Given these episodes, an elevated quantitative serum nortriptyline level of 468 μg/L on hospital day 6 and persistently positive TCA urine screens, the patient was continued on a sodium bicarbonate infusion until hospital day 14. Based on our patient’s quantitative serum nortriptyline levels, we calculated an elimination half-life of 184 hours, 6 days post ingestion as compared to the reported half-life of nortriptyline of 14 to 51 hours. Conclusion: This case demonstrates that at toxic levels of ingestion, routine TCA pharmacokinetics may be unreliable due to delayed absorption, enterohepatic recirculation, large volume of distribution, and saturable kinetics. Therefore, in these cases, pharmacokinetic values derived from routine dosing should not be used to make clinical decisions (such as timing of discontinuation of sodium bicarbonate infusion). We found that urine TCA screens provided similar information to quantitative nortriptyline levels and can be used to guide therapy along the QRS duration.

Purpose The use of a three-drug regimen for the prevention of perinatal transmission of zidovudine- and nevirapine-resistant HIV is described. Summary A 17-year-old Hispanic woman infected with HIV arrived at our clinic for the management of her first pregnancy. The patient was in her second trimester of her pregnancy, had not previously been treated with antiretroviral therapy, and was only taking daily prenatal vitamins at the time of her first clinic visit. Her HIV RNA viral load was 240 copies/mL, and the virus was resistant to both zidovudine and nevirapine. Nelfinavir (compounded suspension), lamivudine, and zidovudine were prescribed for the mother, though she was generally nonadherent to therapy. Nelfinavir, lamivudine, and zidovudine were initiated for the newborn within eight hours of delivery. Six months later, the patient returned to the clinic in the first trimester of her second pregnancy. At this visit, her HIV RNA viral load was 120 copies/mL. After the birth of her second child, the infant received the same regimen received by her firstborn: zidovudine 4 mg/kg orally twice daily for six weeks, lamivudine 2 mg/kg orally twice daily for two weeks, and nelfinavir 55 mg/kg orally twice daily for two weeks. At four months of age, each infant was found to be HIV-negative. Conclusion A prophylactic regimen that included nelfinavir, lamivudine, and zidovudine was used to prevent perinatal transmission of HIV in two neonates. The regimen was well tolerated, and both infants were determined to be HIV-negative at four months of age.