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Background: Patients with cystic fibrosis (CF) experience recurrent bacterial pulmonary exacerbations. Management of these infections is increasingly challenging due to decreased antimicrobial susceptibility to beta-lactam antibiotics. The pharmacokinetics of these agents are inadequately characterized in patients with CF., Methods: One hundred fifty-five pediatric and adult participants with CF receiving cefepime (n=82), meropenem (n=42), or piperacillin-tazobactam (n=31) were enrolled. Opportunistic blood samples were obtained during hospitalization. Population PK analysis was conducted using nonlinear mixed-effects modeling. Clinical and demographic characteristics were evaluated as potential covariates. Monte Carlo simulations were performed to evaluate probability of target attainment (PTA) for different dosing regimens., Results: Estimated creatinine clearance, and total or lean body weight, affected the pharmacokinetics of cefepime and meropenem. No covariates were identified for piperacillin and tazobactam. In the cefepime group, a 3-h infusion achieved higher PTA than a 0.5-h infusion for all participants. Estimated breakpoints (the respective minimum inhibitory concentration (MIC) up to which ≥90% of patients are predicted to reach a PK/PD target) were two- to four-fold higher in pediatric participants receiving a 3-h vs. 0.5-h infusion. In the meropenem group, increased creatinine clearance led to reduced PTA. In the piperacillin-tazobactam group, total daily dose and mode of administration were principal drivers of PTA., Conclusions: Standard dosing regimens fail to achieve specific MIC targets in patients with CF. Therefore, clinicians should incorporate local antibiograms and PK models to determine optimal dosing. Further PK optimization to account for interindividual differences could be achieved by real-time beta-lactam therapeutic drug monitoring., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Hypophosphatemia is common in critically ill patients and has been associated with generalized muscle weakness, ventilatory failure and myocardial dysfunction. Continuous renal replacement therapy causes phosphate depletion, particularly with prolonged and intensive therapy. In a prospective observational cohort of critically ill patients with acute kidney injury (AKI), we examined the incidence of hypophosphatemia during dialysis, associated risk factors and its relationship with prolonged respiratory failure and 28-day mortality., Methods: This is a single-center prospective observational study. Included in the study were 321 patients with AKI on continuous dialysis as initial treatment modality., Results: Four per cent of the patients had a phosphate level <2 mg/dL at initiation and 27% during dialysis. Low baseline phosphate was associated with older age, female gender, parenteral nutrition, vasopressor support, low calcium, and high urea, bilirubin and creatinine, whereas hypophosphatemia during dialysis correlated with the ischemic acute tubular necrosis etiology of renal failure, intensive dose and longer therapy. Serum phosphate decline during dialysis was associated with higher incidence of prolonged respiratory failure requiring tracheostomy [odds ratio (OR) = 1.81; 95% confidence interval (CI) = 1.07-3.08], but not 28-day mortality (OR = 1.16; 95% CI = 0.76-1.77) in multivariable analysis., Conclusions: Hypophosphatemia occurs frequently during dialysis, particularly with long and intensive treatment. Decline in serum phosphate levels during dialysis is associated with higher incidence of prolonged respiratory failure requiring tracheostomy, but not 28-day mortality.