NOVEL INSIGHTS INTO PHARMACOKINETICS OF INTRAPERITONEAL AZTREONAM AND MEROPENEM DURING AUTOMATED PERITONEAL DIALYSIS

OBJECTIVES
Peritoneal-dialysis-associated-peritonitis (PDAP) is a serious complication of automated-peritoneal-dialysis (APD), regarding mortality and morbidity.(1)  Current ISPD guidelines recommend intraperitoneal (IP) antibiotics like aztreonam and meropenem as a potential second-line therapy in PDAP treatment. However, data on pharmacokinetics (PK) and optimal dosing of these antibiotics during APD remain limited. (2)
This study aims to evaluate and optimize the PK profile of aztreonam and meropenem in APD patients by administering them during the first short dwell of the cycler therapy, rather than the long dwell.

METHODS
For each antibiotic, six adult, non-infected patients were enrolled. The antibiotics were administered exclusively via the heating bag during cycler therapy, followed by an antibiotic-free dwell solution after the completion of APD to facilitate back-diffusion from the serum into the peritoneal cavity. Dialysate and serum samples were collected and analysed using high-performance liquid chromatography coupled to a mass spectrometer (HPLC-MS). Pharmacokinetic calculations were conducted consecutively.

RESULTS
The time during which the antibiotic concentrations remained above the minimum inhibitory concentration (t>MIC), based on the expected bacterial spectrum, was the primary outcome measure, with a target of 60%. For aztreonam 2g, the mean serum values were: t>4mg/L: 94.58% (SD ± 4.82), t>8mg/L: 72.11% (SD ± 19.86) (Figure A*). In the dialysate, the mean values were: t>4mg/L: 71.49% (SD ± 21.84), t>8mg/L: 42.21% (SD ± 9.66) (Figure B*). For meropenem 1g, the mean serum values were: t>2mg/L 81.58 % (SD ± 17.86), t>8mg/L: 22.41% (SD ± 22.6) (Figure C*). In the dialysate, the mean values were: t>2mg/L 96.62% (SD ± 7.9), t>8mg/L: 41.46% (SD ± 13.28) (Figure D*).

CONCLUSIONS
This study proposes an alternative treatment strategy for PDAP in APD patients, highlighting its potential to achieve highly effective serum and IP aztreonam and meropenem concentrations. Further studies are required to optimize the drug dosage for this route of administration.


REFERENCES
1.Recent Peritonitis Associates with Mortality among Patients Treated with Peritoneal Dialysis; Boudville, Neil; Kemp, Anna; Clayton, Philip; Lim, Wai; Badve, Sunil V.; Johnson, David W. et al.; Journal of the American Society of Nephrology 2012;23(8): 1398-1405: DOI: 10.1681/ASN.2011121135
2.ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment. Peritoneal Dialysis International; Li, Philip Kam-Tao; Chow, Kai Ming; Cho, Yeoungjee; Fan, Stanley; Figueiredo, Ana E.; Harris, Tess et al.; 2022;42(2):110-53. DOI: https://doi.org/10.1177/0896860822108586 (accessed 2022/07/14)

*figures not include in KRIS-abstract