Biological Aspects of the Interaction Between Gentamicin and Carbenicillin

The in vitro antimicrobial activity of O-demethylfortimicin A (ODMF), a derivative of fortimicin A, was compared with those of fortimicin A and gentamicin against a spectrum of 256 organisms. All three antibiotics were active in low concentrations against all strains of Enterobacteriaceae, Acinetobacter sp., and Staphylococcus aureus, with ODMF most active against Proteus mirabilis, indole-positive Proteus, and Providencia and gentamicin most active against other species. Activity of each of the antibiotics against group D streptococci was poor. The overall activity of ODMF was superior to that of fortimicin A for all groups of organisms examined and was most pronounced, approximately three-fold, against strains of Pseudomonas aeruginosa. Both ODMF and fortimicin A were resistant to the action of several aminoglycoside-inactivating enzymes, with the exception of 3-N-acetyltransferase-I. ODMF and fortimicin A showed similar rapid bactericidal effects at multiples of the minimum inhibitory concentration and equivalent synergistic activity against enterococci when combined with penicillin G. The combination of carbenicillin with ODMF, fortimicin A, or gentamicin was synergistic for approximately 80% of the P. aeruginosa strains tested. Inactivation of ODMF and fortimicin A when combined with carbenicillin in vitro was minimal or absent, whereas gentamicin was substantially inactivated under similar conditions. ODMF, fortimicin A, and gentamicin exhibited protective activity in mice infected with Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, S. aureus, or P. aeruginosa. Gentamicin was the most active, followed by ODMF and fortimicin A. The superior in vitro activity of ODMF compared with fortimicin A against P. aeruginosa was confirmed in vivo.

Section: Fig 1 Comparative Bactericidal Activity Ofmentioning

confidence: 94%

Comparative antimicrobial activity of O-demethylfortimicin A, a derivative of fortimicin A

Girolami¹,

Stamm²

1980

“…However, in vitro studies have demonstrated that at high concentrations penicillins such as carbenicillin and ticarcillin can inactivate aminoglycosides (2,5,10,11,13). Evidence suggests that the inactivation mechanism involves the nucleophilic opening of the penicillin beta-lactam ring, which then combines with an amino group of the aminoglycoside, resulting in the formation of a biologically inactive amide (3,16). The rate of in vitro inactivation is dependent upon temperature, time, the composition of the medium, and the concentration of the betalactam (11,13,14,16).…”

mentioning

confidence: 99%

“…Evidence suggests that the inactivation mechanism involves the nucleophilic opening of the penicillin beta-lactam ring, which then combines with an amino group of the aminoglycoside, resulting in the formation of a biologically inactive amide (3,16). The rate of in vitro inactivation is dependent upon temperature, time, the composition of the medium, and the concentration of the betalactam (11,13,14,16). Aminoglycoside inactivation also can occur in vivo when excretion of both drugs is delayed, as in patients with renal insufficiency (5,6,14).…”

mentioning

confidence: 99%

Stability of gentamicin, tobramycin, and amikacin in combination with four beta-lactam antibiotics

Glew¹,

Pavuk²

1983

The stability of the aminoglycosides gentamicin, tobramycin, and amikacin stored in combination with carbenicillin, piperacillin, cefotaxime, and moxalactam was evaluated at four temperatures (25, 4, -8, and -70 degrees C) over a 3-week period. Amikacin was the most stable of the aminoglycosides and demonstrated no loss of activity when stored with either carbenicillin or piperacillin. Gentamicin and tobramycin were inactivated by carbenicillin and piperacillin at 25 and 4 degrees C, with aminoglycoside activity declining substantially after 8 to 48 h of storage; virtually no loss of gentamicin or tobramycin activity occurred with storage at -8 or -70 degrees C. Cefotaxime and moxalactam produced no degradation of any of the three aminoglycosides.

“…It has been reported that gentamicin is biologically and immunologically inactivated by incubation with carbenicillin in vitro (11,18,19). Therefore, experiments were designed to determine whether tobramycin, measured by radioimmunoassay, would decrease in immunoreactivity after incubation with carbenicillin or other antibiotics containing the 18-lactam ring.…”

Section: Resultsmentioning

confidence: 99%

Radioimmunoassay of Iodinated Tobramycin

Broughton

Strong²,

Pickering³

et al. 1976

A radioimmunoassay for tobramycin was developed using antisera from rabbits injected with a tobramycin-bovine serum albumin conjugate. The antibody had a relatively high affinity for 125 I-labeled tobramycin (1.6 × 10 9 liters/mol), thus indicating little interference in immunoreactivity by iodination. The radioimmunoassay was highly specific, and only minor cross-reaction occurred with other aminoglycoside antibiotics. The radioimmunoassay was also more sensitive than previously published tobramycin assays (minimum sensitivity, 280 pg), and there was a significant correlation ( P < 0.05) with both the radioenzymatic and microbiological assays.