Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gentamicin-induced nephrotoxicosis developed in a mature Holstein cow without evidence of preexisting renal disease. Factors possibly predisposing to the nephrotoxicosis included coadministration of a nonsteroidal anti-inflammatory drug and severe gram-negative bacterial sepsis. The cow recovered after prolonged hospitalization.
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PMID:Gentamicin-induced nephrotoxicosis in a cow. 336 80

Gentamicin is a commonly used antibiotic in the treatment of gram-negative infections including septicemia and pyelonephritis. Bacterial endotoxin is liberated during antibiotic therapy and may lead to endotoxemic shock. Steroids such as hydrocortisone are generally recommended in the treatment of endotoxemic shock. There are very limited data on the influence of endotoxin or corticosteroids on the pharmacology of antibiotics, especially aminoglycosides, which are nephrotoxic. We studied the influence of both Escherichia coli endotoxin and hydrocortisone succinate on the renal uptake of gentamicin in rats. Animals were injected intravenously with endotoxin (0.25 mg/kg) and/or hydrocortisone (25 mg/kg) plus gentamicin (10 mg/kg). Gentamicin levels in the serum and renal parenchyma as well as renal function and histology were evaluated. Both endotoxin and hydrocortisone given alone increased the concentration of gentamicin in the renal cortex (P less than 0.05). Normal values in serum were observed in all groups at most time intervals. When administered together, endotoxin and hydrocortisone did not potentiate each other. The combination of endotoxin and hydrocortisone gave significantly higher levels of gentamicin than endotoxin or hydrocortisone alone when endotoxin was injected 3 h before hydrocortisone (P less than 0.05). Blood pressure and cardiac frequency were normal when gentamicin was given. Endotoxin alone slightly decreased the glomerular filtration rate, and hydrocortisone alone slightly modified renal plasma flow. The combination of both drugs did not significantly affect renal function. No histological lesion was noted on light microscopy in animals receiving endotoxin. Competitive or synergistic activity of endotoxin, gentamicin, and hydrocortisone at the cellular level, especially on membranes or lysosomes, might explain in part our observation on the renal uptake of gentamicin. By increasing the total amount of drug within the kidney, endotoxin and hydrocortisone might increase the risk of nephrotoxicity associated with aminoglycosides.
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PMID:Influence of hydrocortisone succinate on intrarenal accumulation of gentamicin in endotoxemic rats. 343 28

Serum gentamicin concentrations were measured and pharmacokinetic values were calculated for 12 equine patients receiving parenteral gentamicin therapy. Horses were selected for monitoring of gentamicin pharmacokinetics if they met several criteria of high risk for gentamicin-induced toxicosis. Two blood samples were obtained, one immediately before gentamicin dosing and one at 1 hour after dosing. Gentamicin serum concentrations were analyzed and dosage adjustments were made on the basis of calculated one-compartment pharmacokinetic values. Nine of the 12 horses required dosage adjustment to optimize therapeutic concentrations. Even for horses for which there was no evidence of decreased renal function, variation in the disposition of gentamicin was substantial. Because of the larger volume of distribution in foals, an initial dosage of 3 mg/kg every 12 hours was found to best approximate target concentrations. Therefore, published standard dosages were a poor means of achieving desired peak and trough concentrations in many animals. Seemingly, for optimal treatment of horses with sepsis, gentamicin dosage adjustments based on the patient's pharmacokinetic values is required.
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PMID:Pharmacokinetic adjustment of gentamicin dosing in horses with sepsis. 377 40

Assessment of the glomerular filtration rate (GFR) in the newborn is often imprecise because of difficulties in urine collection and because the plasma creatinine level, the traditional marker of renal function, is influenced by many factors in this age group. Gentamicin is given to most preterm infants for suspected or proved sepsis. This drug is eliminated almost entirely by the kidney and its rate of elimination parallels the GFR. We calculated gentamicin pharmacokinetic parameters (t1/2, volume of distribution, and clearance) from three consecutive concentration-time points (trough, peak, and next trough levels) in 38 newborn infants. Creatinine clearance was measured by the conventional method. Both t1/2 (r = 0.74; P less than 0.001) and gentamicin clearance (r = 0.77; P less than 0.001) correlated well with measured creatinine clearance. There was no correlation between these variables and urine output. Gentamicin elimination t1/2 and clearance are useful indices of GFR in the newborn infant and can be easily calculated during routine therapeutic drug monitoring.
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PMID:A simple method for the estimation of glomerular filtration rate by gentamicin pharmacokinetics during routine drug monitoring in the newborn. 406 69

Gentamicin and tobramycin have been compared in vitro and as single-drug therapy in patients with a serious infection caused by gram-negative rods. In vitro, a slight advantage of tobramycin over gentamicin has been found against Pseudomonas aeruginosa. Cross-resistance between gentamicin and tobramycin has been observed for gentamicin-resistant strains of P. aeruginosa and Providence but was not always present. The clinical effectiveness of gentamicin and tobramycin was similar: 14 (45.1%) out of the 31 patients in each series responded favorably. The clinical results were much better in urinary tract infections (66% of favorable responses) than in wound infections, pulmonary infections, septicemia, and meningitis (26% of favorable responses). The frequency of adverse reactions encountered in the present series was similar for both drugs.
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PMID:Comparative clinical study of tobramycin and gentamicin. 459 59

In 66 newborn infants (AGA) suffering from septicemia concentration time courses of gentamicin, ampicillin and cefotaxim were determined to perform and an individual drug monitoring. Gentamicin was analysed from capillar blood samples using EMIT, Ampicillin and Cefotaxim by HPLC-technique. Volumes of distribution, apparent elimination half lives, maximum -, minimum and steady state concentrations were calculated using digital iteration programs. Based on a fixed dose regimen the kinetic parameters of gentamicin were extremely variable. To achieve a median steady state concentration of 3 micrograms/ml gentamicin in serum corrections from -17% to +110% of the foregoing dose were necessary. With 100 mg/kg ampicillin or cefotaxim per day sufficient concentrations in serum were reached. But in some patients a dosage of 5-7 mg/kg/d of gentamicin is too low, while others show concentrations near to the toxic levels. By a combination of gentamicin plus ampicillin pharmacokinetic parameters are not influenced; while if gentamicin is combined with cefotaxim the apparent elimination halflife of gentamicin (beta-slope) is significantly reduced. Therefore an individual drug monitoring of drugs with a small therapeutic range, for example gentamicin, is necessary to optimize therapeutic results.
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PMID:[Pharmacokinetics of combined antibiotic therapy in the newborn infant]. 630 79

Gentamicin and ampicillin were dissolved in an L-amino acid solution especially prepared for newborn infants and infused intravenously over 24 h in 7 babies with serious neonatal surgical problems. Serum concentrations of the antibiotics were maintained rather constant and well above the minimal inhibitory concentration for most bacterial strains. One very sick newborn infant died with overwhelming Klebsiella pneumoniae septicemia. No signs of renal toxicity or ototoxicity were found. The serum amino acids remained within the normal range, except in 1 child with cytomegalovirus infection and liver insufficiency.
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PMID:Administration of gentamicin and ampicillin by continuous intravenous infusion to newborn infants during parenteral nutrition. 680 53

The heat sensitivity of the murine jejunum from C3H/HeJ mice and its capacity to develop thermotolerance were measured. Exteriorized loops of murine jejunum were heated in water baths at temperatures of 43-46 degrees C for various times. Animal mortality was used to calculate the median lethal dose by day 7 (LD50/7) in minutes as a function of temperature. The LD50/7 value was independent of the length of the intestinal loop, the presence of serum in the heating medium, prior starvation of animals, and fluid replacement post heating. The time-temperature plot for the LD50/7 values had an exponential slope constant of -0.71 degrees C-1, similar to that for other normal tissues. A heat treatment of 5 minutes at 45 degrees C increased the LD50/7 (total time at 45 degrees C) from 5.9 minutes to 13.0 and 15.6 minutes for 1- and 3-day fractionation intervals, respectively. Death after intestinal heating was associated with septicemia and reached a peak on days 2 and 3 post hyperthermia. Gentamicin (0.1 mg/mouse/day) increased the LD50/7 at 45 degrees C from 5.9 to 9.6; however, septicemia was still noted in dying, gentamicin-treated mice. Additional antibiotics did not further increase the LD50/7. Heat fractionation with gentamicin increased the LD50/7 (total time at 45 degrees C) to 23.0 and 12.5 minutes at 45 degrees C for 1- and 3-day intervals, respectively. These data suggest that thermotolerance plays a significant role in the intestinal heat response, but that the heat damage to intestinal barriers against bacterial septicemia may be superimposed on the cellular damage to the crypt-villus system.
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PMID:Thermotolerance in the murine jejunum. 695 68

Aminoglycosides remain the cornerstone of prophylaxis and therapy against the majority of aerobic gram-negative organisms responsible for serious sepsis in the hospital. Gentamicin, tobramycin, amikacin are all equally efficacious against susceptible organisms and differ only in their patterns of resistance and pharmacokinetic profiles. The ototoxic and nephrotoxic potential of gentamicin, tobramycin, and amikacin is comparable. Amikacin appears to be preferred for general use at present because of its low resistance potential and superior pharmacokinetic profile (high and predictable serum peaks, wide toxic-therapeutic ratio, high "kill ratio," and q 12 h dosing). In spite of the introduction of the third generation cephalosporins, which are highly active against a variety of aerobic gram-negative organisms, the aminoglycosides will continue to play an important role in the treatment of gram-negative infections. Indeed, the expected usefulness of aminoglycosides may be prolonged by the introduction of the third generation cephalosporins since these drugs will probably be used in combination with aminoglycosides to extend spectrum and to take advantage of possible synergy.
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PMID:The aminoglycosides. 703 38

The effects of orally administered gentamicin and colistin on stool bacterial flora and overall antibiotic sensitivity patterns were evaluated in 100 newborns at risk for neonatal necrotizing enterocolitis. Gentamicin (2.5 mg/kg q6h) and colistin (1 mg/kg q6h) were administered to randomly selected groups of 50 newborns for 3 wk after birth during an 11-month study period. Stools were collected on days 1, 11, and 21 and cultures were grown under aerobic conditions on three different media. Staph. epidermidis was the most common predominant organism in both antibiotic groups, whereas E. coli and Klebsiella were the most common Gram-negative bacteria isolated. Seventeen % of these Gram-negative species were resistant to colistin and 9% to gentamicin, with a gradual increase occurring during the 3-wk period. On the basis of 980 positive cultures from all sites in babies in the nursery during the 11-month study, E. coli sensitivity to kanamycin and gentamicin ranged between 92% and 100% except for one month midway through the study when sensitivity to kanamycin was at 80% and then returned to the 92-100% range. Klebsiella sensitivity to both aminoglycosides remained greater than 95% throughout. The incidence of neonatal sepsis remained consistent at seven to nine per 1000 live births during the study. One baby of 50 in the gentamicin group developed necrotizing enterocolitis at 5 wk of age; 0/50 in the colistin group had necrotizing enterocolitis (not significant).
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PMID:Effects of oral antibiotics on stool flora and overall sensitivity patterns in an intensive care nursery. 705 Aug 68


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