Pharmacokinetics of culture-directed antibiotics for the treatment of peritonitis in automated peritoneal dialysis: A systematic narrative review

Abstract

The objectives of this study were to provide a summary of the pharmacokinetic data of some intraperitoneal (IP) antibiotics that could be used for both empirical and culture-directed therapy, as per the ISPD recommendations, and examine factors to consider when using IP antibiotics for the management of automated peritoneal dialysis (APD)-associated peritonitis. A literature search of PubMed, EMBASE, Scopus, MEDLINE and Google Scholar for articles published between 1998 and 2020 was conducted. To be eligible, articles had to describe the use of antibiotics via the IP route in adult patients ≥18 years old on APD in the context of pharmacokinetic studies or case reports/series. Articles describing the use of IP antibiotics that had been recently reviewed (cefazolin, vancomycin, gentamicin and ceftazidime) or administered for non-APD-associated peritonitis were excluded. A total of 1119 articles were identified, of which 983 abstracts were screened. Seventy-three full-text articles were assessed for eligibility. Eight records were included in the final study. Three reports had pharmacokinetic data in patients on APD without peritonitis. Each of cefepime 15 mg/kg IP, meropenem 0.5 g IP and fosfomycin 4 g IP given in single doses achieved drug plasma concentrations above the minimum inhibitory concentration for treating the susceptible organisms. The remaining five records were case series or reports in patients on APD with peritonitis. While pharmacokinetic data support intermittent cefepime 15 mg/kg IP daily, only meropenem 0.5 g IP and fosfomycin 4 g IP are likely to be effective if given in APD exchanges with dwell times of 15 h. Higher doses may be required in APD with shorter dwell times. Information on therapeutic efficacy was derived from case reports/series in individual patients and without therapeutic drug monitoring. Until more pharmacokinetic data are available on these antibiotics, it would be prudent to shift patients who develop peritonitis on APD to continuous ambulatory peritoneal dialysis, where pharmacokinetic information is more readily available.

Practice variations in antibiotic administration for the management of peritonitis in patients on automated peritoneal dialysis in Australia and New Zealand

“…Several studies 15 –17 have demonstrated that frequent and rapid exchanges in APD are likely to result in greater peritoneal drug clearance, and extrapolation of antibiotics dosing from CAPD to APD may result in significant under-dosing. 1 Furthermore, our recent systematic review 4 concluded that the limited available PK data for IP antibiotics in APD might not be valid in patients receiving variable APD regimens. It highlighted that patient-related factors, particularly the presence of residual kidney function and different stages of the peritoneal inflammation during peritonitis episodes, could also affect the PK of IP antibiotics.…”

“…Antibiotic dosing recommendations are primarily based on pharmacokinetic (PK) studies in patients on continuous ambulatory peritoneal dialysis (CAPD), 2 while data on automated peritoneal dialysis (APD) remain scarce. 3,4 Although the ISPD recommendations have raised concerns over the potential under-dosing of antibiotics in patients on APD, no specific recommendations were made to treat peritonitis in this group of patients. Substantial variations in the outcomes of peritonitis have been reported within Australia 5 ; this may be related in part to the variability in practice on how peritonitis is treated in patients on APD.…”

Transcriptomics Changes in the Peritoneum of Mice with Lipopolysaccharide-Induced Peritonitis

“…As a clinical challenge that often causes organ damage and death, LPS-induced peritonitis is associated with factors such as peritoneal dialysis, sepsis, and pathogenic microbial infections [ 2 , 3 , 4 ]. Although some encouraging progress has been achieved, its mechanism of action is still not fully elucidated [ 1 ].…”

“…Although a series of treatment progressions have been achieved, the mortality rate caused by peritonitis and its complications is still rising [ 1 ]. Based on the cause of its occurrence, peritonitis can be divided into aseptic peritonitis, bacterial peritonitis, peritoneal dialysis-related peritonitis, and LPS (lipopolysaccharide, LPS)-induced peritonitis [ 2 , 3 , 4 ].…”

Reply to: Inconsistencies in 2022 ISPD peritonitis guidelines

“…Of the published pharmacokinetic studies in patients on APD, they were mostly conducted in patients without peritonitis (except vancomycin and amikacin). 5,6 Regarding antibiotic dosing recommendation in Table 5, the footnote ‘supplemental doses may be needed for APD patients’ applied to the table in general. 2 For some medications like vancomycin, we have provided specific additional information for APD.…”