Pharmacokinetics of anti-infective agents during CytoSorb hemoadsorption

Cytokine hemoadsorption might be beneficial in patients with sepsis. However, its effect on anti-infective agents' disposition remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham extracorporeal circuit (controls) and to drug combinations (3 cases and 3 controls for each combination). Hemoadsorption was performed with CytoSorb (CytoSorbents Corporation, USA). We evaluated 17 drugs (clindamycin, fluconazole, linezolid, meropenem, piperacillin, anidulafungin, ganciclovir, clarithromycin, posaconazole, teicoplanin, tobramycin, ceftriaxone, ciprofloxacin, metronidazole, liposomal amphotericin B, flucloxacillin and cefepime). Repeated blood sampling from the extracorporeal circulation (adsorber inlet/outlet, sham circuit) was performed over six hours following administration. Total clearance and adsorber-specific clearance were computed. Hemoadsorption was associated with increased clearance of all study drugs, except ganciclovir. Its impact on total body clearance was considered as moderate for fluconazole (282%) and linezolid (115%), mild for liposomal amphotericin B (75%), posaconazole (32%) and teicoplanine (31%) and negligible for all other drugs. Hemoadsorber clearance declined over time, with even delayed desorption for beta-lactams. It was moderately correlated with drug's lipophilicity (p = 0.01; r2 = 0.43). Hemoadsorption with CytoSorb appears to increase to a clinically significant extent the clearance of five among 17 tested anti-infectives. Studies in human patients are required to confirm the need for dosage adjustment of these agents.

A novel dosing strategy of ceftolozane/tazobactam in a patient receiving intermittent hemodialysis

We describe a case of a 54 years old male receiving intermittent hemodialysis (iHD) who was found to have P. aeruginosa bacteremia secondary to osteomyelitis of the calcaneus bone. The patient was clinically cured without recurrence using a ceftolozane/tazobactam (CTZ) dosing strategy of 100/50mg every 8 hours (standard dosing) and 1000/500mg thrice weekly following iHD. Utilizing a susceptibility breakpoint of ≤ 4 µg/ml for P. aeruginosa, the T>MIC for standard dosing and the 1000/500mg thrice weekly following iHD regimen were calculated to be 92.7% and 94.1%, respectively. Ceftolozane total body clearance for the standard q 8 h dosing and the 1000/500mg thrice weekly following iHD regimen were calculated to be 0.196 L/h and 0.199 L/h, respectively. To our knowledge, this is the first report to illustrate the administration of CTZ at a dose of 1000/500mg thrice weekly following iHD.

Pharmacokinetics of Anti-Infective Agents During CytoSorb Hemoadsorption: An Experimental Study

Background: Cytokine hemoadsorption might be effective in patients with sepsis. However, its effect on anti-infective agents' pharmacokinetics remains largely unknown. We sought to determine the influence of hemoadsorption on the pharmacokinetics of common anti-infective agents. Methods: This is an interventional experimental study, conducted in 24 healthy pigs. Animals were randomly allocated to either hemoadsorption (cases) or sham procedure (controls) and to a drug combination (3 cases and 3 controls for each combination). Hemoadsorption was performed with CytoSorb® (CytoSorbents Corporation, USA). We evaluated 17 drugs (clindamycin, fluconazole, linezolid, meropenem, piperacillin, anidulafungin, ganciclovir, clarithromycin, posaconazole, teicoplanin, tobramycin, ceftriaxone, ciprofloxacin, metronidazole, liposomal amphotericin B, flucloxacillin and cefepime). Repeated blood sampling from the extracorporeal circulation (adsorber inlet/outlet, sham circulation) were performed within six hours of administration. Total clearance and adsorber-specific clearances were computed at each time point.Results: Hemoadsorption was associated with increased clearance of all study drugs, except for ganciclovir. Its impact on total body clearance was major for fluconazole (+282%), linezolid (+115%) and amphotericin B (+75%). It was minor for posaconazole (+32%), teicoplanin (+31%), anidulafungin (+23%), piperacillin (+19%), flucloxacillin (+16%), metronidazole (+16%) and ciprofloxacin (+15%) and insignificant (<10%) for all other drugs. Hemoadsorber clearance declined over time with even delayed desorption for beta-lactams. It was moderately correlated with drug's lipophilicity (p=0.01; r2=0.43). Conclusions: Hemoadsorption with CytoSorb® has limited effect on the pharmacokinetics of most tested anti-infective drugs but appears to increase fluconazole, linezolid and liposomal amphotericin B clearance. Studies in humans with sepsis are required to confirm these findings.

Pharmacokinetics of cefquinome in goats after intramuscular administration alone and with meloxicam

Background: Nonsteroidal anti-inflammatory drugs and antibiotics are commonly prescribed together. We aimed to study the kinetic profile of cefquinome (2 mg/kg b.wt.) following intramuscular administration of it alone and co-administered with meloxicam (0.2 mg/kg b.wt.) in goats.Methods: Five Egyptian Baladi goats, each goat was injected intramuscularly at the dose rate of 2 mg/kg b.wt. Cefquinome into the deep gluteal muscle of hindquarter alone and then after fifteen days washout period, these animals also injected intramuscularly at the dose rate of 2 mg/kg b.wt. Cefquinome preceded with meloxicam at the dose rate of 0.2 mg/kg b.wt. The serum concentrations of cefquinome were detected by high performance liquid chromatography, two compartment model.Results: Following a single dose intramuscular administration of cefquinome alone, peak plasma concentration (1.71±0.0189 μg/ml) was obtained at 1.59±0.0038 h. The absorption half-life (t1/2ab), total body clearance (Cltot), elimination half-life (t1/2el) and area under curve (area under concentration (AUC(0-inf)) of cefquinome were 0.4±0.0028 h, 0.068±0.78 l/h/kg, 9.21±0.178h and 29.36±0.78 µg.h.ml-1, respectively. Following a single dose intramuscular co-administration of cefquinome and meloxicam, peak plasma concentration (1.60±0.0124 μg/ml) was obtained at 1.49±0.0092 h. The absorption half-life (t1/2ab), total body clearance (Cltot), elimination half-life (t1/2el) and area under curve (AUC(0-inf)) of cefquinome were 0.396±0.006 h, 0.094±0.25 l/h/kg, 6.5±0.221 h and 21.38±0.696 µg/h/ml, respectively. Non significant alters were reported in the parameters following co-administration of Cefquinome with meloxicam.Conclusions: From our results, may be concluded that intramuscular administration of meloxicam may be successfully co-administrated with cefquinome for combating bacterial infections with an inflammatory condition in goats without any antagonistic effect.