Effect of Peritoneal Dialysis on Serum Levels of Tobramycin and Clindamycin

Malacoff, Robert F.; Finkelstein, Frederic O.; Andriole, Vincent T.

doi:10.1128/aac.8.5.574

Cited by 37 publications

(7 citation statements)

References 18 publications

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“…An infected patient attained therapeutic perito neal fluid and serum levels from the intraperitoneal administration of C-PO4 during the exudative phase. The serum levels are comparable to those achieved with intra venous administration of C-PO4 [3][4][5][6], The infecting organism was not sensitive to clindamycin so his antibi otic was changed. Therefore, no evaluation was made of C-PO4 bioactivity in the postexudative phase of his infec tion.…”

Section: Discussionsupporting

confidence: 50%

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Incomplete Activation of Intraperitoneal Clindamycin Phosphate during Peritoneal Dialysis

Golper¹,

Sewell²,

Fisher³

et al. 1984

Am J Nephrol

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Clindamycin phosphate (C-PO₄) must be hydrolyzed to the active antibiotic, but whether this occurs within the peritoneal cavity during peritoneal dialysis is unknown. Therapeutic peritoneal levels are difficult to achieve after intravenous administration, so direct intraperitoneal instillation is preferred in treating dialysis-associated peritonitis. Therefore, the activation of C-PO₄ in peritoneal dialysate was investigated. Fresh and ‘uremic’ peritoneal dialysates of 1.5 and 4.25% dextrose concentrations at pHs of 5.1 and 7.4 did not activate C-PO₄. Clindamycin hydrochloride in this same fluid was active, ruling out uremic deactivators. A patient with peritonitis was treated with intraperitoneal C-PO₄, and therapeutic ( > 5 μg/ml) serum and peritoneal levels were achieved. Infected (exudative) peritoneal dialysate drained from another patient with peritonitis activated C-PO₄ in vitro. Commercial alkaline phosphatase added to uremic dialysate also activated C-PO₄in vitro. C-PO₄ was instilled into the peritoneal cavities of 10 noninfected patients. Exposure to the peritoneal membrane at two concentrations resulted in a 3% activation of C-PO₄. From these observations it is clear that C-PO₄ is only partially activated intraperitoneally. Uremia or uremic products in the dialysate do not deactivate the antibiotic. Exudative material (bacteria, white blood cells and proteins) in infected dialysate contribute to activation of C-PO₄. The peritoneal membrane further assists in activation. We recommend that C-P0₄ be administered at a concentration of 167 mg/l of dialysate to ensure therapeutic peritoneal levels of the active antibiotic, especially after the exudative phase clears.

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Section: Discussionsupporting

confidence: 50%

“…Malacojf et al [4] administered 600 mg of C-PO4 intravenously to 3 noninfected patients undergoing peri toneal dialysis treatments [4]. During the 1st h when the serum concentration ranged from 10 to 15 pg/ml, the mean dialysate concentration was 1.8 pg/ml.…”

Section: Discussionmentioning

confidence: 99%

Incomplete Activation of Intraperitoneal Clindamycin Phosphate during Peritoneal Dialysis

Golper¹,

Sewell²,

Fisher³

et al. 1984

Am J Nephrol

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“…Tobramycin removal by peritoneal dialysis has ranged in various studies from 23 to 69%o and 16.5 to 26% after intermittent and continuous ambulatory peritoneal dialysis, respectively (3,6,8,11,14,16), but was not removed by activated charcoal in our study. However, the results obtained in our normal subjects cannot be compared with those found in patients with renal failure.…”

Section: * Corresponding Authormentioning

confidence: 72%

Effect of oral activated charcoal on tobramycin clearance

Davis

Koup

Roon

et al. 1988

Antimicrob Agents Chemother

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To evaluate the effect of activated charcoal on aminoglycoside pharmacokinetics, six healthy volunteers received tobramycin intravenously with and without multiple oral doses of activated charcoal. Activated charcoal did not have a statistically significant effect on any pharmacokinetic parameter. We conclude that activated charcoal does not enhance tobramycin clearance in subjects with normal renal function when concentrations in serum are within the therapeutic range.

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“…The half-life of cefamandole in patient 1, calculated from antibiotic concentrations at 1, 2, 3, 4, 5, and 6 h, was 8. function (creatinine, 0.8 to 1.7 mg/100 ml; creatinine clearances, 31 to 123 ml/min), Shemonsky et al (11) observed that doses of 6 to 11 mg/kg (comparable to a dose of 500 mg) given by intramuscular injection resulted in a mean peak serum concentration of 13.7 + 3 ug/ml at 1.5 h and '1.0 ,g/ml at 6 h. In the same study, with doses in the 11-to 17-mg/kg range (approximating the 1-g intramuscular dose used in the present study), the mean peak serum concentrations were observed to be 31.0 + 17. 8 ,ug/ml at 0.5 h and 1.7 ± 0.7 u.g/ml 6 h after cefamandole administration. The calculated half-life in their study ranged from 49 to 129 min.…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics of Cefamandole in Patients Undergoing Hemodialysis and Peritoneal Dialysis

Ahern

Finkelstein

Andriole

1976

Antimicrob Agents Chemother

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The pharmacokinetics of cefamandole nafate, a new parenteral cephalosporin derivative, were evaluated in 11 patients with chronic renal failure (creatinine clearance less than 5 ml/min), including five patients during hemodialysis, four patients during routine peritoneal dialysis, and two patients during the interdialytic period. Peak serum levels of cefamandole were comparable to those observed in patients with normal renal function. Clearance of the drug during the interdialytic period and during hemodialysis and peritoneal dialysis was minimal, with a resultant significant prolongation of serum half-life. The nondialyzability of cefamandole is in contrast with reported studies of cephalothin, where significant reduction of the serum half-life was achieved during hemodialysis but not peritoneal dialysis. The concentration of cefamandole in the peritoneal dialysate after parenteral administration was observed to be bactericidal for many gram-negative pathogens and, with the exception of Streptococcus faecalis , most gram-positive organisms found in bacterial peritonitis in patients with severe renal failure. The present data suggest that if stable bactericidal serum levels of cefamandole are to be maintained during hemodialysis and peritoneal dialysis, a parenteral loading dose must be administered followed by one-half the loading dose every half-life.

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Effect of Peritoneal Dialysis on Serum Levels of Tobramycin and Clindamycin

Cited by 37 publications

References 18 publications

Incomplete Activation of Intraperitoneal Clindamycin Phosphate during Peritoneal Dialysis

Incomplete Activation of Intraperitoneal Clindamycin Phosphate during Peritoneal Dialysis

Effect of oral activated charcoal on tobramycin clearance

Pharmacokinetics of Cefamandole in Patients Undergoing Hemodialysis and Peritoneal Dialysis

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