Clinical trial NCT04367974: Clinical Pharmacokinetic Study of Ceftazidime and Cefazolin
Official title: Clinical Pharmacokinetic Study of Ceftazidime and Cefazolin in Treating CAPD-related Peritonitis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: CAPD-related Peritonitis
Lead sponsor: Fifth Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2020-04-29
Enrollment: 20
Sex: ALL
Minimum age (years): 15
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: CAPD-related peritonitis patients who accord with the inclusion Criteria and without the exclusion Criteria.

Brief summary: Peritoneal dialysis-related peritonitis is a common complication of peritoneal dialysis, which is the main cause of transfer from peritoneal dialysis to hemodialysis. Guidelines for International Society for peritoneal dialysis（ISPD）published in 2016 recommend that timely and adequate use of antibiotics is the most important part of treatment. Empiric treatment should be initiated as soon as possible after obtaining microbiological specimens，then adjust the antibiotics according to culture results and drug sensitivity of bacteria. Intraperitoneal antibiotic can ensure antibiotic concentrations at the local sites of the infection are maximized，however, in patients with renal failure, the investigators should pay attention to the nephrotoxicity caused by the reduction of renal excretion，being guided by Pharmacokinetic/ Pharmacodynamic Principle on antibiotic can develop dosing recommendations to optimize antibiotic efficacy and minimize toxicity. In this study, the investigators aim to detect the concentration of ceftazidime and cefazolin in CAPD patients，so as to analyze the pharmacokinetics parameters and evaluate the rationality of the treatment.

Detailed description: The dose of cefazolin and Ceftazidime co-administered were 20 mg /kg，they were given intraperitoneal twice daily in the first bag and the fourth bag for 5 days，and given 1g once daily in the fourth bag for 9 days. Total treatment duration was 2 weeks.

At least 1-mL serum and 5-mL dialysate samples were collected at 1, 2, 4, 6, 10, 14 days after complete instillation of the first dialysis bag containing antibiotic into the peritoneal cavity. The samples were then centrifuged at 3,000 rpm, all study samples were stored frozen (-80℃) within 1 hour after collection.

Eligibility criteria: Inclusion Criteria:

Maintained on continuous ambulatory PD (CAPD) for at least 1 month,all patients received 4 exchanges per day with dialysate volumes of 2 L per exchange.

1. The diagnostic criteria for CAPD-related peritonitis are as follows:

   The dialysate fluid appears cloudy and accord with the following peritonitis diagnostic criteria: (with the following two can be diagnosed) A. Clinical manifestations of peritoneics, such as abdominal pain and/or turbid flow of fluid from peritoneal dialysis; B. Perital dialysis discharge of liquid pathogen culture positive. C. The white blood cell count of perital dialysis outflow liquid were more than 0. 1 x 10 x 9/L, and the percentage of polymorphic nucleocells is more than 50% (peritoneal dialysis fluid remains in the abdominal cavity for at least 2 hours for more than 2 hours);
2. No urine (less than 100ml per 24h).
3. Age range form 15 years old to 70 years old, gender is not limited;
4. Understand and agree to this clinical trial study.

Exclusion Criteria:

1. With a clear history of cephalosporine drug allergy or hypersensitivity;
2. Received antibiotic treatment within 1 week prior to entering the study;
3. Pregnant and lactating women;
4. Sepsis;
5. Patients with celiac malignancy;
6. The patient is unable to cooperate or unwilling to accept the test.

Primary outcomes:
measure: concentration of ceftazidime and cefazolin
timeFrame: 2 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Zhuhai
country: China
facility: the fifth affiliated hospital of SUN YAT-SEN university
state: Guangdong
Study officials:
References:
citation: Li PK, Szeto CC, Piraino B, de Arteaga J, Fan S, Figueiredo AE, Fish DN, Goffin E, Kim YL, Salzer W, Struijk DG, Teitelbaum I, Johnson DW. ISPD Peritonitis Recommendations: 2016 Update on Prevention and Treatment. Perit Dial Int. 2016 Sep 10;36(5):481-508. doi: 10.3747/pdi.2016.00078. Epub 2016 Jun 9. No abstract available.
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citation: Cardone KE, Grabe DW, Zasowski EJ, Lodise TP. Reevaluation of ceftazidime dosing recommendations in patients on continuous ambulatory peritoneal dialysis. Antimicrob Agents Chemother. 2014;58(1):19-26. doi: 10.1128/AAC.00873-13. Epub 2013 Oct 14.
citation: Tosukhowong T, Eiam-Ong S, Thamutok K, Wittayalertpanya S, Na Ayudhya DP. Pharmacokinetics of intraperitoneal cefazolin and gentamicin in empiric therapy of peritonitis in continuous ambulatory peritoneal dialysis patients. Perit Dial Int. 2001 Nov-Dec;21(6):587-94.
citation: Booranalertpaisarn V, Eiam-Ong S, Wittayalertpanya S, Kanjanabutr T, Na Ayudhya DP. Pharmacokinetics of ceftazidime in CAPD-related peritonitis. Perit Dial Int. 2003 Nov-Dec;23(6):574-9.
citation: Grabe DW, Bailie GR, Eisele G, Frye RF. Pharmacokinetics of intermittent intraperitoneal ceftazidime. Am J Kidney Dis. 1999 Jan;33(1):111-7. doi: 10.1016/s0272-6386(99)70265-9.