Bone and Skin/Subcutaneous Tissue Concentrations of Cefiderocol During Treatment of Extensively Drug-Resistant Pseudomonas aeruginosa.

Pyoderma gangrenosum is a rare dermatologic disorder that disrupts the skin barrier, requiring immunosuppressive therapy. We successfully used cefiderocol for the treatment of an extensively drug-resistant Pseudomonas aeruginosa bacteremia, and presumed osteomyelitis in a patient with severe pyoderma gangrenosum and associated immunosuppressive therapy while being medically optimized for skin grafting. We obtained bone and skin/subcutaneous tissue while the patient was on cefiderocol under an institutional review board-approved biologic waste recovery protocol. Cefiderocol concentrations in bone and skin/subcutaneous tissue were 13.9 and 35.9 mcg/g, respectively. The patient recovered from bacteremia and underwent autografting without further complications. Cefiderocol at approved dosing of 2 g IV (3-hour infusion) every 8 hours resulted in bone and skin/subcutaneous tissue concentrations adequate to treat extensively drug-resistant Gram-negative bacteria that remain susceptible to cefiderocol.

Augmented Renal Function in Burn Patients: Occurrence and Discordance With Commonly Used Methods to Assess Renal Function.

Augmented renal clearance (ARC) is defined by supraphysiologic renal function and is associated with drug failure due to subtherapeutic drug exposure. Burn patients are cited as being at high risk for ARC, yet rates of ARC have not been well described. This retrospective study described the prevalence and incidence of ARC, and compared 12-hour urine collection values (CrCl-12) vs. common estimates of renal function in assessed patients at an American Burn Association-verified burn center. All thermally injured burn patients with a CrCl-12 result were included. ARC was defined as a CrCl-12 >130 ml/min. Cockcroft-Gault, modification of diet in renal disease (MDRD), and CKD-EPI-2021 estimates were calculated. Over 13 months, 163 CrCl-12 results were collected in 68 patients at a median of 9 days from admission with an average value of 160 ml/min. The median total body surface area (total body surface area [TBSA]%) was 17.25%. ARC prevalence was 70.6% with an incidence of 66.3% in all CrCl-12 assessments. Those with ARC were less likely to have heart failure, P = .007. Age, TBSA%, and trauma were not different between those with or without ARC. ARC incidences in those with TBSAs of ≥20%, <20%, or <10%, were 70.5%, 58.6%, and 76.7%, respectively. Agreement of Cockcroft-Gault, MDRD, and CKD-EPI-2021 to CrCl-12 was moderate to weak and frequently failed to identify ARC. ARC is common in burn patients, regardless of TBSA%. Widely accepted estimations of renal function may be incorrect resulting in under-dosing of medications. Additional research is required to identify burn patients at greatest risk for ARC and subsequent dosing strategies to maintain pharmacologic efficacy without unduetoxicity.