Infection in Acute Leukemia Patients Receiving Oral Nonabsorbable Antibiotics

This study was concerned with the effect of Cetomacrogol (polyethylene glycol 1000 monocetyl ether), a nonionic surfactant, on the absorption of gentamicin and amikacin from the gastrointestinal tract of rats. A 200-mg dose of Cetomacrogol coadministered orally with 10 mg of gentamicin resulted in a mean peak gentamicin blood concentration of 14.1 ,ug/ml, compared with 67.8 ,ug/ml when the same gentamicin dose was administered intramuscularly. The area under the curve after administration of the oral mixture was 23% of that after the intramuscular dose. The rectal administration of the mixture resulted in a mean peak gentamicin blood level of 8.2 jug/ml, compared to 16.5 ,Ag/ml when the mixture was administered orally. A 50-mg dose of amikacin coadministered orally with 200 mg of Cetomacrogol resulted in a mean peak amikacin blood level of 13.3 yg/ ml, compared to 310 tLg/ml when this amikacin dose was administered intramuscularly. Cetomacrogol augments the intestinal absorption of gentamicin and amikacin in rats. If the toxicity of the combination in humans is limited, the combination may be potentially clinically useful.As a class, the aminoglycosides are poorly absorbed from the gastrointestinal tract, and because of this they must be administered parenterally. This limits therapeutic application of these agents to hospital or clinic settings. In an effort to circumvent this liability, a study has been made of the effects of a nonionic surfactant, Cetomacrogol, on absorption of gentamicin and amikacin after administration by mouth and by rectum to rats. This approach rested upon previous results demonstrating that various nonionic surfactants enhance the intestinal absorption of heparin, cephalothin, and cephaloridine in rats (5) and in dogs (6), and upon our recent observations that Cetomacrogol enhances the oral and rectal absorption of insulin in rats (2).The objectives of the present study were: (i) to examine the influence of the dose of Cetomacrogol on absorption of gentamicin after oral administration; (ii) to compare the blood levels of gentamicin and amikacin attained after oral administration of each drug along with the optimal dose of Cetomacrogol with those achieved when the same doses of these aminoglycosides were administered intramuscularly; and (iii) to compare the blood levels of gentamicin attained after oral and rectal administration in combination with Cetomacrogol.Cetomacrogol was specifically chosen because of its low toxicity in rats (E. Toitou, M. Donbrow, and E. Rubinstein, J. Pharm. Pharmacol., in press) and because of our previous experience with this agent (2). The results of these studies and their possible therapeutic implication are presented.(This work was presented in part at the 11th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, Mass., October 1979

Section: Discussionmentioning

confidence: 99%

Increase of the intestinal absorption of gentamicin and amikacin by a nonionic surfactant

Rubinstein¹,

Rubinstein²,

Toitou³

et al. 1981

“…A major problem with the G+N regimen is the lack of patient compliance because of nausea, vomiting, and unpleasant taste. This compliance problem is of significant concern because the patients who discontinue the antibiotics while still granulocytopenic are at risk of rapid regrowth in the alimentary tract by gentamicin-resistant P. aeruginosa (2) or by facultatively anaerobic potential pathogens with subsequent infection (8). Therefore the total elimination ofthe intestinal flora is best reserved for a protected environment, e.g., laminar air flow room.…”

Section: Discussionmentioning

confidence: 99%

“…It has been our opinion that infections are reduced when these prophylactic drug combinations are used outside of laminar air flow reverse isolation (8,10); however, patients taking oral nonabsorbable antibiotics often acquire, become colonized with, and subsequently become infected with organisms resistant to these antibiotics (2). This would be expected in view of the microbial vacuum created; however, it might be possible to suppress the potentially pathogenic aerobic flora without suppressing the anaerobic flora and thus to allow for the preservation of the colonization resistance afforded by the anaerobes in the gastrointestinal tract.…”

mentioning

confidence: 99%

Selective suppression of alimentary tract microbial flora as prophylaxis during granulocytopenia

Hargadon¹,

Young²,

Schimpff³

et al. 1981

Oral nonabsorbable antibiotics have been used to suppress the rectal flora in granulocytopenic patients. Problems with these therapies, i.e., compliance, acquisition of undesirable flora, and cost, motivated the search for an alternative therapy which would increase compliance and effectively reduce the Enterobacteriaceae without creating a microbiol vacuum. Trimethoprim-sulfamethoxazole was found to be easily taken, to suppress the Enterobacteriaceae, and to maintain the anaerobic rectal flora for biological stability of the rectal ecosystem. However, concurrent use of parenteral antibiotics profoundly influenced rectal flora and temporarily destroyed the colonization resistance afforded by the anaerobes.

“…Elimination of microorganisms in this region can result in a reduction in the infection frequency in granulocytopenic patients. This can be done by oral administration of nonabsorbable antibiotics, such as gentamicin and vancomycin (resulting in total decontamination) (3,7,11,15,17,18,22,25,26,30,39). However, this procedure eradicates both the aerobic organisms and the anaerobic organisms in the gut flora (4,22).…”

mentioning

confidence: 99%

Bacteriological aspects of selective decontamination of the digestive tract as a method of infection prevention in granulocytopenic patients

Vries-Hospers¹,

Sleijfer²,

Mulder³

et al. 1981

We describe the bacteriological results of a controlled clinical trial of selective decontamination of the digestive tract as a method of infection prevention in granulocytopenic patients. Selective elimination of Enterobacteriaceae and Pseudomonadaceae species was accomplished by the oral administration of nalidixic acid, co-trimoxazole, or polymyxin. Yeasts were eliminated selectively by amphotericin B or nystatin treatment. The drugs used in this study were chosen because of their capacities to selectively eliminate gram-negative rods and yeast without affecting the anaerobic part of the gut flora which is responsible for colonization resistance. Compared with the control group, the selectively decontaminated patients had significantly fewer (P less than 0.0005) gram-negative rods or yeasts or both in their throat swab cultures and in their feces. This reduction may explain the clinical effectiveness of selective decontamination.