Oral Administration of Antibiotics in Peritoneal Dialysis Patients with Peritonitis Safe and Effective

Globally, particularly in developing countries, the use of peritoneal dialysis is growing rapidly. In the past 12 years, the number of peritoneal dialysis patients in developing countries has increased 2.5-fold. A major barrier to peritoneal dialysis use is peritonitis related to the modality; peritonitis adversely affects technique and patient survival, and increases the financial burden on patients and healthcare systems.

The 2010 and 2016 International Society of Peritoneal Dialysis (ISPD) guidelines for management of peritonitis call for empirical antibiotics to cover both Gram-positive and Gram-negative organisms, preferably administered intraperitoneally. However, according to Rong Xu, MD, and colleagues, intraperitoneal administration outside the hospital setting is difficult, particularly for elderly and diabetic patients who may have impaired visual acuity, dexterity, and cognitive function. Intraperitoneal administration also increases treatment time. Concerns such as these are particularly important in patients of lower socioeconomic status, including a large segment of peritoneal dialysis populations in both developed and developing countries.

Oral administration of antibiotics may a substitute or complementary therapy for peritoneal dialysis­–related peritonitis. Because of their rapid and substantial absorption in the guy and the achievement of therapeutic concentrations in plasma and dialysate, fluoroquinolones are most often cited for use in patients with peritoneal–related peritonitis. Oral monotherapy with quinolones reportedly cures on 40% to 78% of episodes of peritonitis; the rate could reach 73% to 94% when combined with cefazolin or vancomycin.

The researchers conducted a pilot study to compare the complete cure rate and primary or secondary treatment failure rate of oral quinolones plus intra-peritoneal vancomycin (treatment group) with those of patients receiving conventional intraperitoneal vancomycin plus ceftazidime (control group). The study aimed to test the hypothesis that combination therapy of intraperitoneal vancomycin and oral moxifloxacin would result in a complete cure rate and primary or secondary treatment failure rates comparable to those of conventional intraperitoneal vancomycin plus ceftazidime. Results were reported in the American Journal of Kidney Diseases [2017;70(1):30-37].

The single-center study was conducted at the Peking University First Hospital, Beijing, China. There were 207 episodes of peritonitis at the center from November 1, 2102, through March 11, 2016 (0.23 episodes per patient-year). Of those 207, 127 were excluded (45 did not meet inclusion criteria, 47 declined to participate, and 35 were excluded for other reasons). The remaining 80 episodes were included in the analysis. The 80 patients were randomly assigned in a 1:1 ratio to receive either intraperitoneal vancomycin, 1 g, every 5 days plus oral moxifloxacin, 400 mg, every day (treatment group, n=40) or intraperitoneal vancomycin, 1 g, every 5 days plus intraperitoneal ceftazidime, 1 g, every day (control group, n=40). There were no differences in demographics, clinical parameters, or outcomes between patients with included and excluded episodes.

Baseline demographic, clinical, and laboratory characteristics were also similar between the two study groups. Microbiologic spectra of peritonitis episodes were also similar between the two groups: proportions of Gram-positive bacteria were 77% in the treatment group and 73% in the control group; proportions of Gram-negative bacteria were 19% in the treatment group and 23% in the control group. Culture-negative rates were 23% in the treatment group and 25% in the control group, and there was one episode of fungal peritonitis in each group.

In the treatment group the complete cure rate was 78% versus 80% in the control group (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.30-2.52; P=.8). In the treatment group, there were three relapse episodes; there was one in the control group (OR, 2.62; 95% CI, 0.63-10.95; P=.2). During the study period, four patients in the treatment group (one recurrent, one repeat, one other type, and one from whom effluent was not sent for bacterial culturing) and two patients in the control (one repeat and one other type) had successive episodes of peritonitis.

There were no statistically significant differences between the two groups in primary treatment failure rates (33% in the treatment group vs 20% in the control group; OR, 1.93; 95% CI, 0.70-5.34; P=.2) or in secondary treatment failure rates (10% vs 13%, respectively; OR, 0.78; 95% CI, 0.19-3.14; P=.7). Six patients in each group transferred to hemodialysis. There were two deaths related to peritonitis: one in the treatment group due to gastrointestinal hemorrhage and one in the control group due to sepsis. In the three months following completion of peritonitis therapy, there were no deaths in either group.

Mild nausea after oral moxifloxacin was reported by one patient in the treatment group; following adjustment of time of administration, the nausea disappeared. A mild rash that resolved following treatment with oral antiallergy drugs was reported by one patient in the control group. There were no other reports of adverse events in either group.

The researchers cited some limitations to the study, including the small study size that limited statistical power for discerning small differences in efficacy and harms between the two study groups; the low eligibility ratio; and the high rate (71%) of episodes that were first episodes of peritonitis.

In conclusion, the researchers said, “This pilot study suggests that intraperitoneal vancomycin plus oral moxifloxacin is a safe, well-tolerated, and effective treatment that potentially could be used as a first-line empirical treatment regimen for peritoneal dialysis–related peritonitis. Patients appeared to adhere well to the treatment regimen, which would reduce medical expenses compared to daily intraperitoneal antibiotic administration. These results support implementation of a randomized, multicenter, controlled study with a larger sample size.”

Takeaway Points

  1. Researchers conducted a pilot study to compared complete cure rate of oral quinolones plus intraperitoneal vancomycin with conventional intraperitoneal vancomycin plus ceftazidime to treat peritoneal dialysis patients who develop peritonitis.
  2. The treatment group (n=40) received intraperitoneal vancomycin, 1 g, every 5 days plus oral moxifloxacin, 400 mg, every day; the control group (n=40) received intraperitoneal vancomycin, 1 g, every 5 days plus intraperitoneal ceftazidime, 1 g, every day.
  3. Complete resolution of peritonitis was achieved in 78% of cases in the treatment group and 80% of cases in the control group (odds ratio, 0.86; 95% confidence interval, 0.30-2.52).