Microbiological Evaluation of Bb-K 8, a New Semisynthetic Aminoglycoside

108

The in vitro susceptibility to BB-K8, butirosin, gentamicin, sisomicin, and tobramycin of seven groups of clinically significant gram-negative bacilli and Staphylococcus aureus was assessed by using the International Collaborative Study-World Health Organization criteria. The activity of gentamicin, sisomicin, and tobramycin generally paralleled each other. Sisomicin was the most potent compound by weight and usually demonstrated the most rapid rate of killing. BB-K8 and butirosin were less potent, but higher serum levels may be achieved with these agents. BB-K8 generally showed the greatest ratio between achieveable mean peak serum levels and concentrations needed to inhibit [Formula: see text] of each group of organisms tested. Additionally, BB-K8 was active against six of seven highly gentamicin-resistant strains. All of these antibiotics showed diminished activity at pH 6.4 but only gentamicin and sisomicin showed occasionally enhanced activity at pH 8.4.

Section: Resultssupporting

confidence: 82%

Section: Resultssupporting

confidence: 79%

Activity of Five Aminoglycoside Antibiotics In Vitro Against Gram-Negative Bacilli and Staphylococcus aureus

Young

Hewitt

1973

108

“…Studies were performed in six patients undergoing a 4-h hemodialysis using two Cordis-Dow model no. 4 hollow fiber kidneys. Blood flow during dialysis was approximately 200 ml/min, and dialysate flow was 500 ml/min.…”

Section: Methodsmentioning

confidence: 99%

“…Amikacin is a new aminoglycoside antibiotic with an antibacterial spectrum comparable to gentamicin and tobramycin (3,4). Since aminoglycosides are excreted mainly through the kidney and not metabolized in the body, their toxic effects are increased in renal failure.…”

mentioning

confidence: 99%

Effect of Renal Failure and Dialysis on the Serum Concentration of the Aminoglycoside Amikacin

Madhavan

Yaremchuk²,

Levin³

et al. 1976

Serum and dialysate levels of amikacin were determined at appropriate intervals after a 300-mg intravenous dose as a continuous infusion in six patients with end-stage renal failure undergoing hemodialysis and in three patients on peritoneal dialysis. The mean serum half-life of amikacin was 3.75 h during (or after) hemodialysis and 29 h during (or after) peritoneal dialysis. Although not on hemodialysis in the same six patients, the serum half-life was 28 h. The results indicate that the maintenance dose of amikacin should be markedly decreased in patients with severe renal failure even ifthey are treated with peritoneal dialysis, and that serial serum antibiotic concentrations are essential to prevent cumulative toxicity of the drug.Amikacin is a new aminoglycoside antibiotic with an antibacterial spectrum comparable to gentamicin and tobramycin (3, 4). Since aminoglycosides are excreted mainly through the kidney and not metabolized in the body, their toxic effects are increased in renal failure. However, these antibiotics may be the only available agents to treat life-threatening infections. It, therefore, is important to know how renal failure and renal dialysis effect the pharmacology of amikacin. We accordingly determined the serum concentration, half-life, and dialysate concentration of amikacin in patients with renal failure who were being dialyzed, and the results are the subject of this report.MATERIALS AND METHODS Patient selection. Studies were performed in six patients undergoing a 4-h hemodialysis using two Cordis-Dow model no. 4 hollow fiber kidneys. Blood flow during dialysis was approximately 200 ml/min, and dialysate flow was 500 ml/min. Three patients who were being treated with peritoneal dialysis using Impersol solution run at 2 liters/h for 48 h were studied. The patients had stable creatinine clearance values below 10 mg/min.Patients with congestive heart failure, concurrent hepatic disease, and acute blood loss were excluded from this study. The age, sex, body weight, serum creatinine, total protein, and serum albumin levels in six patients with end-stage renal disease on hemodialysis are summarized in Table 1. All patients were evaluated before and 1 week after amikacin administration for adverse effects, and no changes were found in the histories and physical examinations, blood count, urinalysis, bilirubin, serum glutamic oxalacetic transaminase, alkaline phosphatase, serum protein, serum albumin, creatinine, blood urea nitrogen, and serum electrolytes.Collection of specimens. Patients on hemodialysis. A single dose of 300 mg of amikacin was administered intravenously (i.v.) over a period of 60 min starting 75 min before the onset of dialysis. Blood samples were drawn at the beginning of dialysis and thereafter at 5, 30, 90, 210, and 270 min and 12 and 24 h. The dialysate was collected and pooled. Volumes were measured, and a 20-ml sample was taken for antibiotic assay and then frozen immediately. The same dose of amikacin was given 10 to 14 days later to the same six patients on a day...

“…Continued efforts to elucidate the mechanism of antibiotic resistance among bacteria may serve to direct appropriate chemical modifications of antibiotics, thereby changing their susceptibility to inactivating enzymes. The development of BB-K8 (amikacin) exemplifies the favorable experience that molecular modifications may have in rendering antibiotics resistant to enzymatic destruction (13). This continued effort, coupled with appropriate restraint with antibiotics and surveillance of changing patterns of antibiotic resistance, may allow for the continued availability of effective antimicrobial agents.…”

Section: Resultsmentioning

confidence: 99%

Phosphorylation of Kanamycin, Lividomycin A, and Butirosin B by Providencia stuartii

Marengo

Chenoweth

Overturf

et al. 1974

The isolation of Providencia stuartii resistant to multiple aminoglycoside antibiotics prompted an investigation into the mechanism of their resistance. Crude enzyme extracts of a strain of P. stuartii inactivated kanamycin, lividomycin A, and butirosin B in the presence of adenosine 5′-triphosphate (ATP), as measured by a microbiological assay. The occurrence of inhibitory concentrations of 500 μg or greater per ml against kanamycin, lividomycin A, and butirosin B, coupled with the inactivation of these antibiotics in the presence of ATP, suggested enzymatic phosphorylation. This was documented by the transfer of the γ-phosphate of [γ- 32 P]ATP. In contrast, the inability to inactivate gentamicin or tobramycin by the crude enzyme extracts in the presence of ATP suggests another enzymatic mechanism of resistance for these antibiotics, such as adenylation or acetylation. Of importance is the fact that amikacin, a semisynthetic analogue of kanamycin A which is resistant to inactivation by most resistance transfer factor enzymes, was found to inhibit the growth of P. stuartii at low concentrations.