Burden, Richard P.

Finch, Roger G. A.

Harding, Ian

Holliday, manda P.

Innes, Andrew

Morgan, Anthony G.

Shaw, P. Nicholas

Wale, Martin C. J.

Ad Hoc Advisory Committee on Peritonitis Management.

Bonati M.

Guay D. R. P.

Neville L. O.

Patton K. R.

Traina G. L.

Wale M. C. J.

Wilcox M. H.

Crossref

Pharmacokinetic behavior of intraperitoneal teicoplanin during treatment of peritonitis complicating continuous ambulatory peritoneal dialysis

University of Queensland eSpace

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug. 1996, p. 1971–1972 Vol. 40, No. 8
0066-4804/96/$04.0010
Copyright q 1996, American Society for Microbiology
Pharmacokinetic Behavior of Intraperitoneal Teicoplanin during Treatment of
Peritonitis Complicating Continuous Ambulatory Peritoneal Dialysis
Continuous ambulatory peritoneal dialysis (CAPD) is an
established alternative to hemodialysis for the treatment of
end stage renal disease. However, catheter-related infections
and peritonitis remain serious disadvantages. The incidence of
peritonitis is about one episode per patient per year (9) but has
been declining with improved administration systems.
Coagulase-negative staphylococci (CNS) and Staphylococcus
aureus account for 50 to 80% of peritonitis episodes (9). Cur-
rent treatment recommendations advise vancomycin plus in-
traperitoneal ceftazidime or an aminoglycoside as initial em-
piric therapy (1). Vancomycin is usually given at doses of 15 to
25 mg/liter per bag, sometimes with an intravenous loading
dose.
Teicoplanin is a glycopeptide antibiotic with a spectrum of
activity similar to that of vancomycin. To date, limited clinical
and pharmacokinetic studies of treating CAPD peritonitis have
been conducted (2, 3, 5). Following Ethics Committee ap-
proval, we have studied the pharmacokinetic behavior of teico-
planin at 20 mg/liter per bag, administered over a 10-day pe-
riod in 16 patients with clinical and laboratory evidence of
peritonitis. Exclusion criteria were age of ,18 years, allergy to
the study medication, pregnancy or lactation, peritoneal leu-
kocyte count of ,100 ml, effective antibiotic therapy within the
previous 48 h, or refusal to give written informed consent.
Teicoplanin at 20 mg/liter and aztreonam at 250 mg/liter per
dialysis bag were administered at each exchange (four per day)
and continued for up to 10 days, or for 5 days after the dialy-
sate cleared; aztreonam was stopped on the basis of microbi-
ologic culture and sensitivity data.
Samples of early-morning serum and dialysate (7- to 10-h
dwell time) were collected and assayed for teicoplanin on days
1, 3, 5, 7, 10, and 20 by a microbiologic assay (6), which was
unaffected by the presence of aztreonam. Dialysate drug levels
ranged from 4.5 to 6.0 mg/ml during the dosing period and
decreased to ,1 mg/ml by day 20 (Fig. 1). In contrast, the
serum drug levels increased to a maximum of ca. 9 mg/ml by
day 10 of the study and decreased to ca. 5 mg/ml 10 days after
stopping of teicoplanin. A two-compartment model was fitted
to the serum drug concentration data by using nonlinear re-
gression analysis (PCNONLIN), and this indicated the total
clearance (CLtot) to be 0.0025 (standard deviation [SD],
0.0009) liters/h/kg of body weight, the terminal half-life to be
508 (SD, 193) h by using a mean dose of 1.56 mg of teicoplanin
per kg per day, and the volume of distribution of the control
compartment (Vc) to be 0.48 liters/kg. These data are in keep-
ing with previously published single-dose data (4, 7). An at-
tempt to fit a three-compartment model was made, but no
advantage was gained.
The regimen adopted for this study was chosen in order to
simplify previous dosage recommendations which adopted a
deescalating dosage regimen over a 3-week period (5). The
observed maximum concentration of drug in serum (Cmax)
exceeded the MIC for all target gram-positive pathogens. Con-
cerns about drug accumulation were not observed; by day 10,
concentrations were well within plasma drug levels achieved by
intravenous administration. The washout time (Fig. 1) indi-
cates continued inhibitory dialysate drug concentrations for
several days after stopping of treatment. The therapeutic re-
sponse to this regimen for teicoplanin has also confirmed clin-
ical and microbiologic efficacy (8).
REFERENCES
1. Ad Hoc Advisory Committee on Peritonitis Management. 1993. Peritoneal
dialysis-related peritonitis treatment recommendations: 1993 update. Perit.
Dial. Int. 13:14–28.
2. Bonati, M., G. L. Traina, M. G. Gentile, G. Fellin, R. Rosina, et al. 1988.
Pharmacokinetics of teicoplanin in patients with chronic renal failure on
continuous ambulatory peritoneal dialysis. Br. J. Clin. Pharmacol. 25:761–765.
3. Bowley, J. A., S. J. Pickering, A. J. Scantlebury, P. Ackrill, and D. M. Jones.
1988. Intraperitoneal teicoplanin in the treatment of peritonitis associated
with continuous ambulatory peritoneal dialysis. J. Antimicrob. Chemother.
21(Suppl. A):133–138.
4. Guay, D. R. P., W. M. Awni, C. E. Halstenson, M. T. Kenny, W. F. Keane, and
G. R. Matzke. 1989. Teicoplanin pharmacokinetics in patients undergoing
continuous ambulatory peritoneal dialysis after intraperitoneal and intrave-
nous dosing. Antimicrob. Agents Chemother. 33:2012–2015.
5. Neville, L. O., R. Baillod, D. Grady, W. Brumfitt, and J. M. T. Hamilton-
Miller. 1987. Teicoplanin in patients with chronic renal failure on dialysis:
microbiological and pharmacokinetic aspects. Int. J. Clin. Pharmacol. Res.
VII:485–490.
6. Patton, K. R., A. Beg, D. Felmingham, G. L. Ridgway, and R. N. Gruneberg.
1987. Determination of teicoplanin in serum using a bioassay technique.
FIG. 1. Mean (6 SD) (error bars) serum and dialysate teicoplanin concentra-
tions (micrograms per milliliter). The dosage was 20 mg/liter intraperitoneally per
exchange.
1971
 o
n
 O
ctober 21, 2015 by University of Queensland Library
http://aac.asm
.org/
D
ow
nloaded from
 
Drugs Exp. Clin. Res. 13:547–550.
7. Traina, G. L., M. G. Gentile, G. Fellin, R. Rosina, L. Cavenaghi, et al. 1986.
Pharmacokinetics of teicoplanin in patients on continuous ambulatory peri-
toneal dialysis. Eur. J. Pharmacol. 31:501–504.
8. Wale, M. C. J., R. G. Finch, A. G. Morgan, R. P. Burden, and A. Holliday.
1992. A prospective randomised trial of teicoplanin plus aztreonam versus
cefuroxime in CAPD peritonitis. Int. J. Antimicrob. Agents 1:S7–S14.
9. Wilcox, M. H., R. G. Finch, R. P. Burden, and A. G. Morgan. 1991. Peritonitis
complicating continuous ambulatory peritoneal dialysis in Nottingham: 1983–
1988. J. Med. Microbiol. 34:137–141.
Roger G. Finch
Amanda P. Holliday
Department of Microbial Diseases
Andrew Innes
Richard P. Burden
Anthony G. Morgan
Department of Renal Medicine
Nottingham City Hospital
Nottingham NG5 1PB, United Kingdom
P. Nicholas Shaw
Department of Pharmaceutical Sciences
School of Pharmacy
University of Nottingham
University Park
Nottingham NG7 2RD, United Kingdom
Ian Harding
Thackelay’s Research Consultancy
Horton
Devizes SN10 3NB, United Kingdom
Martin C. J. Wale
Public Health Laboratory
Laboratory and Pathology Block
General Hospital
Tremona Rd.
Southampton SO9 4XY, United Kingdom
1972 LETTERS TO THE EDITOR ANTIMICROB. AGENTS CHEMOTHER.
 o
n
 O
ctober 21, 2015 by University of Queensland Library
http://aac.asm
.org/
D
ow
nloaded from
 


http://espace.library.uq.edu.au/view/UQ:225488/UQ225488_OA.pdf

Pharmacokinetic behavior of intraperitoneal teicoplanin during treatment of peritonitis complicating continuous ambulatory peritoneal dialysis

Abstract

Similar works

Full text

Available Versions

Crossref

University of Queensland eSpace