A Monte Carlo Analysis of Peritoneal Antimicrobial Pharmacokinetics

Peritonitis is the leading cause of transfer from peritoneal dialysis (PD) to hemodialysis (HD). It is also the leading cause of hospitalization of PD patients. The usual treatment of peritonitis for automated PD (APD) patients consists of antibiotics given once daily in the long dwell. However, the once-daily antibiotic dosing recommendations are based primarily on studies with continuous ambulatory PD (CAPD) regimens. Published studies on antibiotic dosing in APD are very limited. We will review the scant literature on this topic. It is possible that extrapolating once-daily dosing from CAPD to APD may lead to underdosing. There is a need for further pharmacokinetic studies of antibiotic dosing in APD.

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“…The levels were < 5 x MIC for 75% – 100% of the time. The same was true with intermittent dosing of cefazolin (33).…”

Section: Third Generation Cephalosporins Specifically Ceftazidimementioning

confidence: 84%

“…Table 3 shows the limited data on the use of third- generation cephlosporins in APD. Of the 4 papers listed, 1 was simulated data (Monte Carlo) (33). The Monte Carlo analysis demonstrated the inability of intermittent dosing with ceftazidime to achieve an IP antibiotic level of > 5 x MIC.…”

Section: Third Generation Cephalosporins Specifically Ceftazidimementioning

confidence: 99%

Review of Antibiotic Dosing with Peritonitis in APD

Mancini

Piraino

2019

Perit Dial Int

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“…To date, multiple pharmacokinetic (PK) studies of intraperitoneal (i.p.) ceftazidime have been conducted and have recommended a range of dosing schemes with various antibiotic dwell times, weight-based versus fixed doses, dosing amounts, continuous versus intermittent dosing, and differing frequencies of administration (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). On the basis of data from these studies, the current guideline for peritoneal-dialysis-related infections suggests using 1 or 1.5 g of ceftazidime administered via the i.p.…”

mentioning

confidence: 99%

Reevaluation of Ceftazidime Dosing Recommendations in Patients on Continuous Ambulatory Peritoneal Dialysis

Cardone

Grabe

Zasowski

et al. 2014

Antimicrob Agents Chemother

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cWhile intraperitoneal (i.p.) ceftazidime is commonly used to treat continuous ambulatory peritoneal dialysis (CAPD)-related infections, the ability of i.p. regimens to achieve critical pharmacodynamic targets in both blood and dialysate has not been reported. To understand the pharmacodynamic profile of ceftazidime during CAPD, data were obtained from a single-dose pharmacokinetic (PK) i.p. ceftazidime study that included 10 CAPD patients who received i.p. ceftazidime at 15 mg/kg of body weight. The probability of target attainment (concentrations maintained above the MIC for >60% of the dosing interval [60% T > MIC]) was determined for six simulated regimens. A 3-compartment model with each dialysis dwell modeled as a separate differential equation was fit to ceftazidime concentrations using BigNPAG. Embedded with the final PK model, serum and dialysate concentration-time profiles of ceftazidime at 1, 1.5, and 2 g i.p. every 24 h (q24h) to q48h were simulated using ADAPT 5. The mean population pharmacokinetic parameters were as follows: apparent volume of the central compartment (V c ), 7.57 liter; apparent volume of the peritoneal cavity (Vpd), 2.44 liter; clearance from the central compartment (CL), 0.379 liter/h; intercompartmental transfer rate constants (first order) between the central and peripheral compartments (k 12 and k 21 ), 4.66 and 4.88 h ؊1 , respectively; and intercompartmental transfer rate constants (first order) between the central and peritoneal compartments (k 13 and k 31 ), 0.111 and 0.227 h ؊1 , respectively. In serum, the probability of target attainment for MICs of <8 mg/liter exceeded 90% for 1.5 to 2 g i.p. q24h to q48h. However, no tested regimen provided adequate dialysate exposure at MICs of >8 mg/liter on day 1 without the use of a 3-g loading dose (post hoc analysis). On day 2, 1.5 to 2 g i.p. q24h or 2 g i.p. q48h provided adequate exposure in the peritoneal cavity. These results should be validated in the presence of infection. Ceftazidime i.p. at 1.5 or 2 g q24h to q48h is recommended for nonperitoneal infections. For peritonitis, a 3-g load with maintenance dosing of 1 to 2 g i.p. q24h or 2 g i.p. q48h is recommended.

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