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Background: Pathophysiological changes often result in altered pharmacokinetics of ciprofloxacin in critically ill patients. Although ciprofloxacin clearance (CLCIP) substantially depends on kidney function in healthy volunteers, its relationship to measured creatinine clearance (CLCRM) is weak in critically ill patients.Objectives: To assess the need for dose reductions in isolated or combined kidney and liver dysfunction in critically ill patients and to re-evaluate relationships between kidney parameters, demographics and ciprofloxacin pharmacokinetics.Methods: A population pharmacokinetic model was developed based on 444 ciprofloxacin serum concentrations from 15 critically ill patients with severe infections. CLCIP relationships to parameters reflecting hepatic function, CLCRM, Cockcroft-Gault creatinine clearance (CLCRCG), serum creatinine, sex, weight and age were explored. A simulation study was conducted to integrate knowledge from the new and previously published models.Results: Total bilirubin was identified as a hepatic parameter with a clear relationship to CLCIP. A significant relationship between CLCIP and CLCRCG could be attributed to age and sex only. CLCIP was not associated with CLCRM. The predicted risk of potential overexposure (AUC > 250 mg·h/L) was low even with 1200 mg/day ciprofloxacin daily for patients with reduced CLCRCG (<30 mL/min: risk of 0.7%), while the risk was remarkably higher in elderly female patients with elevated bilirubin (risk of about 20% for 65-year-old women with total bilirubin of 4 mg/dL).Conclusions: Bilirubin, age and sex should be considered to assess the need for dose reductions. For MICs ≤0.25 mg/L, it might be appropriate to reduce the dose to 400 mg/day for elderly female subjects with high bilirubin. [ABSTRACT FROM AUTHOR]

Objectives: Insufficient linezolid levels, which are associated with a poorer outcome, are often observed in ICU patients who receive standard dosing. Although strategies to overcome these insufficient levels have been discussed, appropriate alternative dosing regimens remain to be identified.Methods: Various infusion regimens (1200-3600 mg/day; q6h, q8h, q12h and continuous) were simulated in 67 000 ICU patients. The probability of attaining pharmacodynamic targets ( T >MIC ≥85%, AUC/MIC ≥100, cumulative fraction of response for Staphylococcus aureus and Enterococcus spp., PTA for an MIC of 0.5-4 mg/L) as well as the avoidance of toxic concentrations and concentrations constantly below the MIC (lack of antibiotic effect) or inside a mutant selection window (resistance development) were evaluated.Results: Best target attainment according to T >MIC was observed for continuous infusions, followed by q6h, q8h and q12h. A substantially reduced target attainment was observed in patients with acute respiratory distress syndrome (ARDS). In patients without ARDS, 1200 mg/day was insufficient irrespective of the regimen, while a dose of 1400 mg/day administered q6h or by continuous infusions provided an acceptable target attainment (e.g. cumulative fraction of response with regards to T >MIC  ≥93%). Higher rates of potentially toxic trough concentrations (28% versus 12%) and concentrations constantly inside the mutant selection window (15% versus <0.1%) were observed with continuous infusions compared with q6h infusions (1400 mg/day, patients without ARDS).Conclusions: Irrespective of the regimen, 1200 mg/day linezolid might be insufficient for the treatment of ICU patients. Patients without ARDS might particularly benefit from q6h infusions with increased daily doses (e.g. 1400 mg/day). [ABSTRACT FROM AUTHOR]

The article presents a case study of a patient with septic shock and multiple organ failure, characterized by excessive inflammatory responses. An initial laparotomy showed an ischaemic bowel with peritonitis, and the patient was given intravenous meropenem and segmental resection of the jejunum and colon. The patient was given with linezolid and meropenem. The case demonstrated the effect of cytokine adsorber treatment on antibiotic concentrations.