Stability of ceftolozane and tazobactam in different peritoneal dialysis solutions

Abstract

Background:

Peritonitis is a common and serious complication of peritoneal dialysis (PD). PD-associated peritonitis (PDAP) caused by Pseudomonas is usually resistant to most antibiotics, resulting in high failure rates. Ceftolozane/tazobactam (C/T) has been shown to be effective in treating urinary tract and intra-abdominal infections caused by beta-lactam resistant Pseudomonas and other gram-negative bacteria. Given its favourable adverse effects profile, it has a potential role in the treatment of PDAP caused by Pseudomonas species resistant to other antibiotics. Intraperitoneal administration of antibiotics admixed with PD solutions for the treatment of PDAP is associated with superior outcomes. However, there is a lack of published data on the stability of C/T in PD solutions. Therefore, this study investigated the physical and chemical stability of C/T in commonly used PD solutions at different temperatures.

Methods:

A total of 27 PD bags (3 PD bags for each type of PD solution including Dianeal®, Extraneal®, Balance® and Physioneal® PD bags) containing C/T were prepared and stored at 25°C for 6 h, followed by 4°C for 168 h and then 37°C for 12 h. An aliquot from each PD bag was withdrawn, and the concentration of C/T before (0 h) and after predefined time points was determined using a stability-indicating high-performance liquid chromatography assay. Samples were also assessed for pH, colour change and particulate matter immediately after preparation and on each day of analysis.

Results:

C/T retained more than 97% of their initial concentration when stored at 25°C for 6 h followed by storage at 4°C for 168 h and then at 37°C for 12 h. Particle formation was not detected at any time under the tested storage conditions. The pH and colour remained essentially unchanged throughout the study.

Conclusions:

These results provide a platform for clinical studies to determine the safety and therapeutic efficacy of intraperitoneal C/T for the treatment of PDAP caused by resistant Pseudomonas species.

Keywords

Ceftolozane chromatography peritoneal dialysis peritonitis tazobactam

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References

Brown

Simpson

Kerssens

, et al. Peritoneal dialysis-associated peritonitis rates and outcomes in a national cohort are not improving in the post-millennium (2000–2007). Perit Dial Int 2011; 31(6): 639–650.

Mudge

Boudville

Brown

, et al. Peritoneal dialysis practice in Australia and New Zealand: a call to sustain the action. Nephrology 2016; 21(7): 535–546.

Ghali

Bannister

Brown

, et al. Microbiology and outcomes of peritonitis in Australian peritoneal dialysis patients. Perit Dial Int 2011; 31(6): 651–662.

Mehrotra

Singh

. Peritoneal dialysis-associated peritonitis with simultaneous exit-site infection. Clin J Am Soc Nephrol 2013; 8(1): 126–130.

Mujais

. Microbiology and outcomes of peritonitis in North America. Kidney Int Suppl 2006; 70(103): S55–S62.

Szeto

Chow

Leung

, et al. Clinical course of peritonitis due to Pseudomonas species complicating peritoneal dialysis: a review of 104 cases. Kidney Int 2001; 59(6): 2309–2315.

PK-T

Szeto

Piraino

, et al. ISPD peritonitis recommendations: 2016 update on prevention and treatment. Perit Dial Int 2016; 36(5): 481–508.

Barretti

Doles

Pinotti

, et al. Efficacy of antibiotic therapy for peritoneal dialysis-associated peritonitis: a proportional meta-analysis. BMC Infect Dis 2014; 14(1): 445.

Gupta

Muralidharan

Gokulnath , et al. Epidemiology of culture isolates from peritoneal dialysis peritonitis patients in southern India using an automated blood culture system to culture peritoneal dialysate. Nephrology 2011; 16(1): 63–67.

10.

Nichols

de Jonge

BLM

Kazmierczak

, et al. In vitro susceptibility of global surveillance isolates of Pseudomonas aeruginosa to ceftazidime-avibactam. Antimicrob Agents Chemother 2016; 60(8): 4743–4749.

11.

Zhanel

Chung

Adam

, et al. Ceftolozane/tazobactam: a novel cephalosporin/beta-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs 2014; 74(1): 31–51.

12.

Seifert

Korber-Irrgang

Kresken

. In-vitro activity of ceftolozane/tazobactam against pseudomonas aeruginosa and Enterobacteriaceae isolates recovered from hospitalized patients in Germany. Int J Antimicrob Agents 2018; 51(2): 227–234.

13.

US Food and Drug Administration. FDA Approval Label for Zerbaxa, http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206829lbl.pdf (2014, accessed 14 May 2019).

14.

Kandel

Zaidi

STR

Wanandy

, et al. Stability of ceftazidime and heparin in four different types of peritoneal dialysis solutions. Perit Dial Int 2018; 38(1): 49–56.

15.

Tissel

. Avoiding common flaws in stability and compatibility studies of injectable drugs. Am J Hosp Pharm 1983; 40(7): 1159–1160.

16.

Siva

Hawley

McDonald

, et al. Pseudomonas peritonitis in Australia: predictors, treatment and outcomes in 191 cases. Clin J Am Soc Nephrol 2009; 4(5): 957–964.

17.

Gallagher

Satlin

Elabor

, et al. Ceftolozane-tazobactam for the treatment of multidrug-resistant Pseudomonas aeruginosa infections: a multicenter study. Open Forum Infect Dis 2018; 5(11): ofy280.

18.

Haidar

Philips

Shields

, et al. Ceftolozane-tazobactam for the treatment of multidrug resistant Pseudomonas aeruginosa infections: clinical effectiveness and evolution of resistance. Clin Infect Dis 2017; 65(1): 110–120.

19.

Ballinger

Palmer

Wiggins

, et al. Treatment for peritoneal dialysis-associated peritonitis. Cochrane Database Syst Rev 2014; 4: CD005284.

20.

de Vin

Rutherford

Faict

. Intraperitoneal administration of drugs in peritoneal dialysis patients: a review of compatibility and guidance for clinical use. Perit Dial Int 2009; 29(1): 5–15.