Interactions between aminoglycoside antibiotics and carbenicillin or ticarcillin

Piperacillin inactivation of the aminoglycosides isepamicin and gentamicin in 12 chronic hemodialysis patients was assessed. Six subjects each received isepamicin (7.5 mg/kg of body weight) or gentamicin (2 mg/kg) alone and in combination with piperacillin (4 g every 12 h for four doses). Isepamicin and gentamicin concentrations in plasma and urine were monitored over 48 h after each dose and analyzed by highperformance liquid chromatography and fluorescence polarization immunoassay, respectively. The pharmacokinetics of isepamicin were not significantly altered during combination treatment with piperacillin. piperacillin (3.56 0.38 ml/min) increased significantly compared with that of gentamicin (2.03 0.50 ml/min) given alone. The results of this study suggest that no additional dosage adjustment of isepamicin during concomitant therapy with piperacillin in hemodialysis patients is necessary. However, this does not preclude the need for appropriately ex vivo-handled specimens for monitoring isepamicin concentrations in plasma to ensure therapeutic efficacy and prevent toxicity. Furthermore, additional dosage adjustments may be necessary when gentamicin is used concomitantly with piperacillin, on the basis of the significant in vivo inactivation that takes place in end-stage renal disease patients.

Section: Materuils and Methodsmentioning

confidence: 99%

Section: Materuils and Methodsmentioning

confidence: 99%

Effect of concomitant administration of piperacillin on the dispositions of isepamicin and gentamicin in patients with end-stage renal disease

Halstenson

Wong

Herman

et al. 1992

“…Chemical inactivation of 1-lactam and aminoglycoside antibiotics occurs in vitro (18). Phamacokinetic interactions between these two classes of antibiotics have been reported in patients with normal and impaired renal functions (3,10,11,14,19,25). Since cefepime, as a 3-lactam, could be used in such a combination therapy, it was deemed * Corresponding author.…”

mentioning

confidence: 99%

Lack of pharmacokinetic interaction between cefepime and amikacin in humans

Barbhaiya

Knupp

Pfeffer

et al. 1992

The interaction potential between cefepime and amikacin was investigated in a steady-state pharmacokinetic study in 16 healthy male subjects. Eight subjects (group A) received a first course of 2,000 mg of cefepime; this was followed by a second course of 2,000 mg of cefepime with 300 mg of amikacin and a third course of 2,000 mg of cefepime. Eight other subjects (group B) received a first course of 300 mg of amikacin, a second course of 300 mg of amikacin with 2,000 mg of cefepime, and a third course of 300 mg of amikacin. Each course consisted of four consecutive doses administered every 8 h as 30-min intravenous infusions. Serial plasma and urine samples, which were collected after administration of the fourth dose of each course, were assayed for cefepime and/or amikacin by validated high-performance liquid chromatographic assays. Trough levels of cefepime and amikacin indicated that these antibiotics attained a steady state prior to administration of the fourth dose of each course. Key pharmacokinetic parameters for each antibiotic were determined by noncompartmental methods. The peak concentrations of cefepime and amikacin in plasma when the drugs were given alone were about 160 and 27 ,g/ml, respectively. Levels of each antibiotic in plasma declined, with an apparent half-life of approximately 2.2 h. Urinary recovery of cefepime and amikacin accounted for more than 85% of the administered dose of each antibiotic. Mean renal clearances for cefepime and amikacin ranged from 79 to 95 ml/min and suggested that glomerular filtration is the primary excretion mechanism. The results of the statistical analyses indicated that the pharmacokinetic parameters of cefepime following the concurrent administration of amikacin and following the discontinuation of the amikacin therapy were not significantly altered. Similarly, the pharmacokinetic parameters of amikacin following the concurrent administration of cefepime and following the discontinuation of the cefepime therapy were not significantly altered. Cefepime and amikacin can be coadministered to patients with normal renal function by using the standard recommended dosing regimens.Cefepime (BMY-28142) is a new parenteral cephalosporin with significant potential advantages over other new cephalosporins and nontraditional ,3-lactam antibiotics with respect to its antimicrobial spectrum of activity (12,15). In addition, cefepime appears to have a low affinity for chromosomally derived P-lactamases (23). Clinical experience indicates that cefepime is safe and well tolerated when single or multiple (every 8 or 12 h) doses of 250 to 2,000 mg are given by the intravenous (4, 5) or intramuscular (9) routes of administration. The pharmacokinetics of this cephalosporin are linear (4, 5, 9). Over 80% of the administered dose of cefepime is recovered in urine in an unchanged form (4, 5, 7-9).In the most severely infected patients, empiric therapy consists of the administration of antibacterial therapy before pathogen identification. The standard approach has been to use an ant...

“…Amikacin's stability against inactivation has been shown previously (5,6,8,13,15). We further demonstrated that heparin at a concentration as high as 100 U/ml did not interfere with the determination of isepamicin levels by automated FPI immunoassay when compared with 0.5% EDTA as an anticoagulant control.…”

Section: Discussionmentioning

confidence: 89%

Comparative inactivation of isepamicin, amikacin, and gentamicin by nine beta-lactams and two beta-lactamase inhibitors, cilastatin and heparin

Walterspiel¹,

Feldman²,

Van³

et al. 1991

This study was undertaken to compare the susceptibility to inactivation of isepamicin with amikacin and gentamicin when. exposed to different beta-lactams, ,I-lactamase inhibitors, and heparin. The aminoglycosides (5; 10, 20, and 50 ,g/ml) were incubated in human serum with ampicillin, azlocillin, aztreonam, carbenicillin, ceftazidime, piperacillin, and ticarcillin (100 and 600 ,ug/ml) and with clavulanate, cilastatin, 1:1 imipenemcilastatin? oxacilin, and sulbactam (20 and 120 ,ug/ml) for 48 h at 37°C. Aminoglycoside concentrations were measured by fluorescence polarization immunoassay (FPI) after 0, 8, and 48 h of incubation and by radial difibsion bipassay after 48 h of incubation. Each of the three aminoglycosides was also added to whole blood tontaihing either hebarin (100 U/ml) or 0.5% EDTA as a control and assayed after 6 h by FPI. The degree of inactivation of isepamicin by the beta-lactams was significantly less than that by amikacin (P < 0.003) and gentamAicih,(P < O.0.X2) when determined by bioassay. Piperacillin, carbenicillin, and azlocillin produced the greatest amount of inactivation, and cilastatin and oxacillin produced the least. A similar pattern was observed when the degree of inactivation ywvs measured by FPI. A significant difference in the degree of inactivation was noted between isepanticin and gentamicin (P < 0.003 at 8 h and P < 0.006 at 48 h) but not between isepamicin and amikacin (P> Q.7 at 8h and P > 0.08 at 48 h). Aminoglycoside determinations by FPI were not influenced by the,pirestnce of heparin. In summary, isepamicin was found to be at least as stable as amikacin against inactivration by beta-lactam compounds and Il-lactamase inhibitors. Heparin (100 U/ml) did not influence aminoglycoside determinations by FPL Aminoglycoside antibiotics interact with beta-lactam compounds and heparinr (11,12,14). The mechanism for the interaction with beta-lactams is thought to consist of a nuc1 ophilic opening of the beta-lactam ring by an amino group, leading to formation of. an amide, with loss of biological activity of both (2). Heparin in contrast binds by ionic ijiteraction only, a process that is reversible by dilution (12). The concentrations of heparin that are used therapeutically are too low for this to occur in vivo, but sufficient concentrations can be reached in blood collection tubes (12).The inactivation of aminoglycosides by beta-lactam antibiotics is clinically relevant for patients with renal failure, in whom beta-lactams can accumulate to high concentrations and inactivate an aminoglycoside given concomitantly (4,11,16). Loss of the aminoglycoside due to in vitro inactivation can also occur when specimens containing both compounds are processed after delay (14). Tissue culture media frequently contain both types of antibiotics, and inactivation can limit the time for storage and exchange of media.Isepamicin is an aminoglycoside with increased stability against enzymatic degradation and low oto-and nephrotoxicity (9). Its sensitivity to inactivation by beta-lactam compounds ...