Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “gentamicin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1998

Gentamicin dosage intervals in neonates: longer dosage interval--less toxicity.

OBJECTIVES: The aim of this study was to determine the incidence of toxic trough serum gentamicin levels in neonates in the first week of life, with different dosage intervals. METHODS: This was a retrospective study of neonates born between 01.07.95 and 31.12.95, who received gentamicin. Data were collected on birth weight, gestation, gentamicin dose, the trough level of gentamicin, serum creatinine and urine output. A trough serum gentamicin level of > or =1.5 mg/L was considered toxic. RESULTS: One hundred and seventy infants met the study criteria. All 21 infants in group one (24-29 weeks) received gentamicin with a dosage interval of 24 h. Sixteen (76%) infants had toxic trough serum gentamicin levels. In group two (30-34 weeks) 8 infants had gentamicin q12hly and all (100%) had toxic trough serum gentamicin levels. Fourteen infants had gentamicin every 18 h and 13 (93%) had toxic trough serum gentamicin levels. Sixty-one infants had gentamicin q24hly and 25 (41%) had toxic trough serum gentamicin levels. The differences in proportions with toxic levels were statistically significant. In group three (> or =35 weeks) 29 infants had gentamicin q12hly and 25 (86%) had toxic trough serum gentamicin levels. Six infants had gentamicin every 18 h and 2 (33%) had toxic trough serum gentamicin levels. Thirty-one infants had gentamicin q24hly and 4 (13%) had toxic trough serum gentamicin levels. The differences in proportions comparing infants having gentamicin q12hly with those having it q24hly were statistically significant. CONCLUSIONS: A starting gentamicin dosage interval of 12 h in infants of any gestational age, or a starting dosage interval of 24 h for infants of less than 30 weeks gestational age, leads to most having toxic trough serum gentamicin levels. In infants of 30 weeks gestational age or greater, most have safe non-toxic trough serum gentamicin levels if started on a dosage interval of 24 h.

Drug Administration Schedule↗
PubMed1979

Renal tubular transport of gentamicin in the rat.

The renal handling of gentamicin in the rat was examined by clearance, microinjection, and renal cortical-slice techniques. The steady-state renal clearance of 14C-gentamicin, when corrected for the 7.5% binding to plasma protein, was not significantly different from that of 3H-inulin. At the end of the renal clearance experiments, the cortical concentration of gentamicin was 93 +/- 7 microgram/g of tissue (N = 7), a concentration threefold greater than that of the medulla and 20-fold greater than that of serum. Absorption of 3H-gentamicin along the proximal convoluted tubule and loop of Henle was demonstrated by the tubular microinjection technique. No reabsorption of 3H-gentamicin was detected beyond the early distal convoluted tubule. The tubular absorption of 3H-gentamicin was load dependent. Fractional absorption of 3H-gentamicin averaged 30.1 +/- 2.7% when the dose of 3H-gentamicin injected into early proximal tubular convolutions averaged 132 +/- 17 pg. It was decreased to 13.6 +/- 2.6% when the microinjected dose of gentamicin was increased to 1996 +/- 388 pg. No evidence of transtubular absorption of 3H-gentamicin was detected during the microinjection experiments. Microperfusion of pertubular capillaries failed to demonstrate urinary precession of 3H-gentamicin over 14C-inulin, a finding which argues against a rapid transtubular secretory flux of gentamicin. Significant uptake of gentamicin was demonstrated by renal cortical slices incubated in medium containing 14C-gentamicin. The accumulation of 14C-gentamicin by renal cortical slices was not inhibited by probenecid or N1-methylnicotinamide but was inhibited by netilmicin and tobramycin. These data support the conclusion that the renal accumulation of gentamicin reflects transport of gentamicin across both the apical and basolateral membranes of proximal tubular epithelium.

Animals↗
PubMed1983

Aztreonam, cefoperazone, and gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis in rabbits.

The effectiveness of aztreonam, cefoperazone, and gentamicin alone and in combination was evaluated in Enterobacter aerogenes endocarditis in rabbits. The minimal inhibitory concentration/minimal bactericidal concentration ratios for E. aerogenes were as follows: aztreonam, 0.4/0.4 microgram/ml; cefoperazone, 0.8/0.8 microgram/ml; and gentamicin, 3.1/3.1 micrograms/ml. With an inoculum of 10(9) organisms per ml, aztreonam and cefoperazone were equivalent in reducing titers of E. aerogenes in broth, and both drugs demonstrated an increased rate of reduction when gentamicin was added; gentamicin alone was least effective. E. aerogenes endocarditis in rabbits was treated intramuscularly with aztreonam (60 mg/kg) every 6 h, with cefoperazone (60 mg/kg) every 6 h, with gentamicin (1.7 mg/kg) every 8 h, and with aztreonam plus gentamicin or cefoperazone plus gentamicin for 5 and 10 days, respectively. All of the therapeutic regimens were effective in reducing vegetation titers as compared with untreated controls. Aztreonam plus gentamicin was more effective than either aztreonam or gentamicin alone. Cefoperazone plus gentamicin was more effective than cefoperazone alone but was not more effective than gentamicin alone. Neither aztreonam and cefoperazone nor aztreonam and gentamicin differed significantly, but gentamicin was significantly more effective than cefoperazone. Aztreonam plus gentamicin did not differ significantly in effectiveness from cefoperazone plus gentamicin. Aztreonam gave a peak level of about 135 micrograms/ml and a half-life of 0.7 h. Cefoperazone gave a peak level of about 155 micrograms/ml and a half-life of 1.1 h. Gentamicin gave a peak level of 7.4 micrograms/ml and a half-life of 1.3 h.

Animals↗
PubMed2005

The influence of ultrasound on the release of gentamicin from antibiotic-loaded acrylic beads and bone cements.

Gentamicin-loaded acrylic beads are loosely placed in infected bone cavities, whereas gentamicin-loaded acrylic bone cement is used as a mechanical filler in bone to anchor prosthetic components. Both drug delivery systems are used to decrease infection rates by gentamicin release. The objective of this study is to investigate the effects of pulsed ultrasound on gentamicin release from both materials. Gentamicin release from gentamicin-loaded beads (Septopal) and from three commercially-available brands of gentamicin-loaded bone cement (CMW 1, Palacos R-G, and Palamed G) was measured after 18 h of exposure in PBS to an ultrasonic field of 46.5 kHz in a 1:3 duty cycle with an average acoustic intensity of 167 mW/cm(2). Samples not exposed to ultrasound were used as controls. Pulsed ultrasound significantly enhanced gentamicin release from gentamicin-loaded beads, whereas gentamicin release from the gentamicin-loaded bone cements was not significantly enhanced. Mercury intrusion porosimetry revealed an increased distribution of pores between 0.1 and 0.01 microm in beads after gentamicin release, while in bone cements no increase in the number of pores was found. Increased gentamicin release in beads due to ultrasound may be explained by micro-streaming in a porous structure, whereas the absence of changes in pore structure after gentamicin release in bone cement is concurrent with the lack of an enhanced release of the antibiotic by ultrasound. As an effective treatment of infections requires high local concentrations of antibiotic, increased gentamicin release due to ultrasound may be of clinical significance, especially since ultrasound has been demonstrated to increase bacterial killing by antibiotics.

Anti-Bacterial Agents↗
PubMed1992

Gentamicin clearance during continuous arteriovenous hemodiafiltration.

OBJECTIVE: To investigate the feasibility of predicting gentamicin dosing requirements during continuous arteriovenous hemodiafiltration (CAVHD). DESIGN: Prospective study. SETTING: General intensive therapy unit in a university teaching hospital. PATIENTS: Five adult patients with acute renal failure in whom both dialytic and gentamicin therapy were indicated. MEASUREMENTS AND MAIN RESULTS: CAVHD clearance and total body clearance of gentamicin were estimated from serial gentamicin concentrations in the blood and the combined ultrafiltrate and dialysate. Results (mean +/- SD) were: CAVHD clearance of gentamicin 5.2 +/- 1.8 mL/min; total body clearance of gentamicin 20.5 +/- 6.9 mL/min; ultrafiltrate flow rate 7.0 +/- 2.4 mL/min (420 +/- 146 mL/hr). CAVHD clearance of gentamicin was small and represented approximately 25% of total body clearance of gentamicin, although significant interpatient variation existed in these measurements and in the proportion of total gentamicin clearance attributable to CAVHD. CAVHD clearance of gentamicin was related to the ultrafiltrate flow rate (r2 = .81). CONCLUSIONS: CAVHD clearance of gentamicin may be predicted for variable ultrafiltrate flow rates. However, due to its minor and variable contribution to total body clearance of gentamicin, prediction of gentamicin dosing requirements based on estimates of CAVHD clearance of gentamicin would be precluded and close monitoring of circulating gentamicin concentrations during CAVHD is necessary.

Acute Kidney Injury↗
PubMed2002

Comparison of two gentamicin dosing schedules in very low birth weight infants.

BACKGROUND: Several dosing schedules for gentamicin have been recommended for very low birth weight infants during the early neonatal period. We conducted a prospective, randomized, controlled trial to compare efficacy and pharmacokinetics of two dosing schedules in preterm neonates. METHODS: Fifty-eight very low birth weight infants (600 to 1500 g), prescribed gentamicin for treatment of suspected sepsis during the first week after birth, were randomized to receive either the new dosing schedule [every 48 h (q48h)] or the existing dosing schedule [every 24 h (q24h)]. Infants in the "q48h" group received gentamicin at 5.0 or 4.5 mg/kg/dose q48h depending on weight group and infants in the "q24h" group received 2.5 or 3.0 mg/kg/dose q24h. Peak and trough serum gentamicin concentrations were monitored. RESULTS: Peak serum gentamicin concentrations after the first dose were significantly higher in the q48h infants than in q24h infants (8.19 +/- 1.3 vs. 6.04 +/- 2.2, P = 0.00001). Ninety percent of all peak serum gentamicin concentrations in the q48h group were in a higher therapeutic range of 6 to 12 microg/ml as compared with 55% of q24h (P = 0.0005). None of the q48h infants had subtherapeutic serum gentamicin concentrations immediately after administration of the first dose as compared with 36% of q24h infants (P < 0.005). Eighteen percent of q24h infants continued to have peak serum gentamicin concentrations in subtherapeutic range even after the third dose at 48 h. Trough serum gentamicin concentrations were significantly lower in q48h infants than in q24h infants. However, 9 of 30 (30%) q48h infants had trough serum gentamicin concentrations of < or = 0.5 microg/ml before the dose at 48 h and 4 of the 9 had serum gentamicin concentrations of <1 microg/ml at 24 h after the first dose. CONCLUSIONS: The q48h dosing schedule of gentamicin given to very low birth weight infants during the first week after birth achieved therapeutic serum gentamicin concentrations and potentially higher peak to MIC ratios for microorganisms in all infants. However, nearly one-third of the infants had extremely low serum gentamicin concentrations before the next dose. A dosing interval of 36 h might be optimal for bactericidal activity and avoid bacterial growth during prolonged periods of extremely low serum gentamicin concentrations; this dosing interval warrants study.

Anti-Bacterial Agents↗
PubMed2006

Loss of the homotypic fusion and vacuole protein sorting or golgi-associated retrograde protein vesicle tethering complexes results in gentamicin sensitivity in the yeast Saccharomyces cerevisiae.

Gentamicin continues to be a primary antibiotic against gram-negative infections. Unfortunately, associated nephro- and ototoxicity limit its use. Our previous mammalian studies showed that gentamicin is trafficked to the endoplasmic reticulum in a retrograde manner and subsequently released into the cytosol. To better dissect the mechanism through which gentamicin induces toxicity, we have chosen to study its toxicity using the simple eukaryote Saccharomyces cerevisiae. A recent screen of the yeast deletion library identified multiple gentamicin-sensitive strains, many of which participate in intracellular trafficking. Our approach was to evaluate gentamicin sensitivity under logarithmic growth conditions. By quantifying growth inhibition in the presence of gentamicin, we determined that several of the sensitive strains were part of the Golgi-associated retrograde protein (GARP) and homotypic fusion and vacuole protein sorting (HOPS) complexes. Further evaluation of their other components showed that the deletion of any GARP member resulted in gentamicin-hypersensitive strains, while the deletion of other HOPS members resulted in less gentamicin sensitivity. Other genes whose deletion resulted in gentamicin hypersensitivity included ZUO1, SAC1, and NHX1. Finally, we utilized a Texas Red gentamicin conjugate to characterize gentamicin uptake and localization in both gentamicin-sensitive and -insensitive strains. These studies were consistent with our mammalian studies, suggesting that gentamicin toxicity in yeast results from alterations to intracellular trafficking pathways. The identification of genes whose absence results in gentamicin toxicity will help target specific pathways and mechanisms that contribute to gentamicin toxicity.

Anti-Bacterial Agents↗
PubMed1976

Nephrotoxicity of cephalosporin-gentamicin combinations in rats.

TO STUDY THE POSSIBILITY THAT CEPHALOSPORINS AUGMENT THE NEPHROTOXICITY OF GENTAMICIN, GROUPS OF RATS WERE GIVEN FOUR HOURLY SUBCUTANEOUS DOSES OF: gentamicin (5 mg/kg), gentamicin plus cephalothin (100 mg/kg), gentamicin plus cefazolin (20 mg/kg), gentamicin plus cefazolin (50 mg/kg), gentamicin plus cephaloridine (50 mg/kg), or saline diluent for 15 days. Periodic measurements were made of urine volume, urine osmolality, urine protein excretion and lysosomal enzymuria, as well as blood urea nitrogen, creatinine clearance, and drug concentrations in renal cortex and medulla. Tissue was examined by light and electron microscopy. Enzymuria and proteinuria increased early in the course of all treatment groups, whereas urine osmolality declined. No distinct patterns of these variables were discernable among the groups. Gentamicin alone, gentamicin plus cephalothin, and gentamicin plus cefazolin (20 mg/kg) caused the same significant fall in glomerular filtrate rate from control values by day 15 (P < 0.05). Gentamicin plus cefazolin (50 mg/kg) and gentamicin plus cephaloridine failed to cause a decline in glomerular filtration rate compared with controls (P > 0.05). Gentamicin concentrations in renal cortex were 5 to 10 times higher than those in medulla in all groups. Cephaloridine and cefazolin (50 mg/kg) also displayed a gradient pattern in renal cortex, whereas cephalothin and cefazolin (20 mg/kg) did not. Cytosegrosomes with myeloid figures were characteristic ultra-structural changes seen in all groups; however, they tended to be smaller with less numerous myeloid bodies in the groups receiving gentamicin plus cephalothin, cefazolin (50 mg/kg), or cephaloridine. Cephalosporins did not augment gentamicin toxicity. High doses of cefazolin and cephaloridine protected kidneys from gentamicin nephrotoxicity. The protection may involve intracellular drug interaction within the renal cortex.

Animals↗