PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-15 (15)
 

Clipboard (0)
None

Select a Filter Below

Journals
Authors
more »
Year of Publication
Document Types
1.  Time-restricted feeding schedules modify temporal variation of gentamicin experimental nephrotoxicity. 
The effect of timing of gentamicin dosing relative to food access periods was evaluated in experimental animals. Female Sprague-Dawley rats were treated for 4 and 10 days with gentamicin (40 mg/kg of body weight/day) intraperitoneally at either 0700, 1300, 1900, or 0100 h according to three food presentation schedules: food was available from 0800 to 1600 h in the first group, from 1600 to 0000 h in the second group, and from 0000 to 0800 h in the last group. Animals were thus subjected to a restricted feeding period. Results indicate that time-restricted feeding schedules displace the peak and the trough of gentamicin-induced renal toxicity, as evaluated by changes in the inhibition of sphingomyelinase activity, cellular regeneration (incorporation of [3H]thymidine into DNA of renal cortex), and blood urea nitrogen and serum creatinine levels, as well as histopathological lesions observed after 10 days of treatment. In fact, the toxicity was minimal when gentamicin was injected during the feeding period, while the maximal toxicity was found when gentamicin was administered during the fasting period. It is concluded that the feeding period can modulate aminoglycoside nephrotoxicity. The time of dosing of gentamicin relative to the time of feeding seems to be a more important modulator of gentamicin nephrotoxicity than the light-dark cycle.
PMCID: PMC163942  PMID: 9210668
2.  Attenuation of gentamicin-induced nephrotoxicity in rats by fleroxacin. 
The effect of fleroxacin on gentamicin-induced nephrotoxicity was evaluated with female Sprague-Dawley rats. Animals were injected during 4 or 10 days with saline (NaCl; 0.9%), gentamicin alone at doses of 10 and 40 mg/kg of body weight/12 h (subcutaneously), fleroxacin alone at a dose of 25 mg/kg/12 h (intraperitoneally), or the combination gentamicin-fleroxacin in the same regimen. Gentamicin induced a dose- and time-dependent renal toxicity as evaluated by gentamicin cortical levels, sphingomyelinase activity in the renal cortex, histopathologic and morphometric analysis, blood urea nitrogen and serum creatinine levels, and cellular regeneration ([3H]thymidine incorporation into DNA of cortical cells). The extent of these changes was significantly reduced when gentamicin was given in combination with fleroxacin. Although the mechanisms by which fleroxacin reduces the nephrotoxic potential of gentamicin are unknown, we propose that the fleroxacin-gentamicin combination enhances exocytosis activity in proximal tubular cells, as suggested by the higher excretion of urinary enzymes and lower cortical levels of gentamicin observed in animals treated with the combination fleroxacin-gentamicin compared with those treated with gentamicin alone. The protective effect of fleroxacin on gentamicin nephrotoxicity should be investigated further.
PMCID: PMC163893  PMID: 9174177
3.  Temporal variation in nephrotoxicity of low doses of isepamicin in rats. 
The temporal variation in the nephrotoxicity of low doses of isepamicin was studied in male Sprague-Dawley rats treated with a single daily intraperitoneal injection of saline (NaCl, 0.9%) or isepamicin (80 mg/kg of body weight) at either 0800, 1400, 2000, or 0200 h for 4 and 10 days. On day 10, the cellular regeneration (incorporation of [3H] thymidine into DNA of renal cortex) and cortical accumulation of isepamicin were significantly higher in animals treated at 1400 h than at 0200 h (P < 0.01). Immunogold labeling studies showed that isepamicin was essentially localized in the lysosomes of proximal tubular cells in all treated groups, but the density of the gold particles over the lysosomes was higher in animals treated at 1400 than at 0200 h. The results of the present study show that the renal toxicity of isepamicin was maximal at 1400 h (midlight period) and minimal at 0200 h (middark period).
PMCID: PMC163205  PMID: 8851618
4.  L-651,392, a potent leukotriene inhibitor, controls inflammatory process in Escherichia coli pyelonephritis. 
In this study, the relationship between leukotrienes, peritubular cell infiltration with polymorphonuclear cells (PMNs) and renal tubular damage was investigated in a rat model of acute ascending pyelonephritis. Infection was induced by the injection of 10(5) CFU of Escherichia coli into the bladder and occlusion of the left ureter for 24 h. Treatment of infected animals was started 24 h after the induction of pyelonephritis with either hydrocortisone (25 mg/kg of body weight per day), the leukotriene inhibitor L-651,392 (10 mg/kg/day), or the vehicle of L-651,392 and was maintained for 5 days. At the end of treatment, the animals were killed, serum was collected, and both kidneys were removed for colony counts and histopathology. Renal function was evaluated by the measurement of blood urea nitrogen levels and creatinine clearance. The numbers of PMNs and mononuclear cells (MNs) in the cortex and medulla were recorded for all groups on plastic sections done from the left kidney. Infection alone (vehicle of L-651,392) resulted in intensive interstitial infiltration and a severe tubular destruction in the cortex. Treatment with hydrocortisone did not prevent PMN migration and tissue damage. By contrast, treatment with L-651,392 resulted in a significant reduction in PMNs (P < 0.001 in comparisons with all other groups) and greater preservation of the tubular structure despite identical bacterial counts than in the group receiving hydrocortisone. We conclude that L-651,392 prevents inflammatory cells from reaching the site of infection and protects the kidney from tubular damage associated with inflammation during pyelonephritis. Inhibitors of leukotrienes should be further investigated for their potential benefit as adjuvants to antibiotherapy in the treatment of pyelonephritis.
Images
PMCID: PMC284592  PMID: 7979288
5.  Daptomycin may attenuate experimental tobramycin nephrotoxicity by electrostatic complexation to tobramycin. 
The lipopeptidic antibiotic daptomycin is reported to reduce experimental tobramycin nephrotoxicity (D. Beauchamp, M. Pellerin, P. Gourde, M. Pettigrew and M. G. Bergeron, Antimicrob. Agents Chemother. 34:139-147, 1990; C. A. Wood, H. C. Finkbeiner, S. J. Kohlhepp, P. W. Kohnen, and D. C. Gilbert, Antimicrob. Agents Chemother. 33:1280-1285, 1989). In an attempt to explain these results, the in vivo and in vitro interactions between daptomycin and tobramycin were studied. Tobramycin alone and preincubated with negatively charged phospholipid bilayers (liposomes) was dialyzed against increasing concentrations of daptomycin in buffer at pH 5.4. A significant drop in the concentration of tobramycin was observed when daptomycin was added to the opposite half cells. Furthermore, daptomycin induced a concentration-dependent release of lipid-bound tobramycin. Gold labeling experiments showed that daptomycin could be incorporated into phospholipid layers. Female Sprague-Dawley rats were treated with daptomycin alone, with tobramycin alone, or with the combination over 2 to 10 days. Levels of daptomycin and tobramycin in serum were similar in all groups. The levels of tobramycin in the renal cortex increased significantly with time and, on day 10, reached values of 654 +/- 122 and 844 +/- 298 micrograms/g of tissue (mean +/- standard deviation; not significant) in animals treated with tobramycin and the combination of daptomycin-tobramycin, respectively. No significant difference was observed in the levels of tobramycin in the kidneys between animals treated with tobramycin or the daptomycin-tobramycin combination at any time. By contrast, daptomycin levels were significantly higher in the renal cortexes of animals treated with daptomycin-tobramycin in comparison with those in the renal cortexes of animals treated with daptomycin alone on days 6,8, and 10 (P < 0.01). For immunogold labeling studies, animals were killed 4 h after a single injection of daptomycin alone or daptomycin in combination with tobramycin. Daptomycin was found throughout the matrixes of the lysosomes of proximal tubular cells of animals treated with daptomycin alone. In animals treated with the combination of daptomycin and tobramycin, daptomycin was associated with intralysosomal myeloid bodies. Our results suggest that daptomycin might attenuate experimental aminoglycoside nephrotoxicity by interacting with the aminoglycoside, perhaps electrostatically, and thereby protecting intracellular targets of toxicity.
Images
PMCID: PMC284536  PMID: 8031040
6.  Ceftriaxone protects against tobramycin nephrotoxicity. 
The effect of ceftriaxone on tobramycin-induced nephrotoxicity was investigated. Female Sprague-Dawley rats were treated during 4 and 10 days with saline (NaCl, 0.9%), ceftriaxone at a dose of 100 mg/kg of body weight/12 h subcutaneously, tobramycin at doses of 40 and 60 mg/kg/12 h intraperitoneally, or the combination ceftriaxone-tobramycin. Creatinine levels in serum were significantly higher in animals treated with tobramycin alone given at 60 mg/kg/12 h during 10 days, compared with control animals (P < 0.01) or animals receiving the combination tobramycin-ceftriaxone (P < 0.01). After 10 days of treatment, ceftriaxone did not accumulate in renal tissue but did reduce the renal intracortical accumulation of tobramycin (P < 0.05). Tobramycin given alone at either 40 or 60 mg/kg/12 h induced a significant inhibition of sphingomyelinase activity compared with control animals (P < 0.05). However, this enzyme activity was significantly less inhibited when tobramycin was injected in combination with ceftriaxone (P < 0.05). Ceftriaxone alone had no effect on the activity of this enzyme. The [3H]thymidine incorporation into the DNA of renal cortex was also significantly lower in animals treated with tobramycin-ceftriaxone compared with animals receiving tobramycin alone (P < 0.05). The 24-h urinary excretion of beta-galactosidase was significantly reduced in animals treated with the combination tobramycin-ceftriaxone compared with the administration of tobramycin alone at 40 and 60 mg/kg/12 h after 5 and 10 days (P < 0.05). Histologically, ceftriazone induced very few cellular alterations and reduced considerably the presence of typical signs of tobramycin nephrotoxicity. This investigation demonstrated that ceftriaxone protects animals against tobramycin-induced nephrotoxicity.
PMCID: PMC284537  PMID: 8031041
7.  Subcellular distribution of daptomycin given alone or with tobramycin in renal proximal tubular cells. 
Previous studies in experimental animals showed that daptomycin, a lipopeptide antibiotic, protects against aminoglycoside nephrotoxicity (C. A. Wood, H. C. Finkbeiner, S. J. Kohlhepp, P. W. Kohnen, and D. N. Gilbert, Antimicrob. Agents Chemother. 33:1280-1285, 1989; D. Beauchamp, M. Pellerin, P. Gourde, M. Pettigrew, and M. G. Bergeron, Antimicrob. Agents Chemother. 34:139-147, 1990). In order to better understand the mechanism involved in this protective effect, the subcellular distribution of daptomycin was investigated in the proximal tubular cells of animals treated with daptomycin alone or in combination with tobramycin. A first group of female Sprague-Dawley rats received a single intravenous injection of daptomycin at a dose of 100 mg/kg of body weight and were killed at 10 min, 1 h, or 24 h after the injection. Other groups of rats were treated during 10 days with saline (NaCl, 0.9%), tobramycin at dosages of 20 mg/kg/12 h, daptomycin at dosages of 10 mg/kg/12 h, or the combination tobramycin-daptomycin at the same dosages. At the time of sacrifice, the renal cortex of the right kidney of each animal was dissected, and small blocks of tissue were fixed, dehydrated, and embedded in Araldite 502 epoxy resin. The subcellular distribution of daptomycin and tobramycin was determined on ultrathin sections by immunogold labeling. Ten minutes after the injection of daptomycin alone, gold particles were seen over the brush border membrane and on the membranes of the endocytic vacuoles of proximal tubular cells. One hour after the injection, a similar distribution was seen and numerous gold particles were found over the lysosomes of proximal tubular cells. The results suggest that daptomycin might protect against aminoglycoside nephrotoxicity by interfering with the interaction between the aminoglycoside and phospholipids inside the lysosomes of proximal tubular cells.
Images
PMCID: PMC284424  PMID: 8192441
8.  Modification in penicillin-binding proteins during in vivo development of genetic competence of Haemophilus influenzae is associated with a rapid change in the physiological state of cells. 
Infection and Immunity  1992;60(10):4024-4031.
By using whole-cell labeling assay with 125I-penicillin V, we observed a reduction in the binding of the radiolabeled beta-lactam to four or five penicillin-binding proteins (PBPs) in Haemophilus influenzae cells cultivated under specific conditions. PBPs 3A, 3B, 4, and 6 were altered after the growth of bacteria in diffusion chambers implanted in the peritoneal cavity of rats. PBP 2 was also modified when cells were cultivated in human cerebrospinal fluids. Because this observation may have important consequences on the efficacy of beta-lactams during antibiotic therapy, we characterized the physiological state of bacteria cultivated in animals in the hope of explaining how such important changes in cell properties develop in vivo. Since the development of natural genetic competence occurs at the stationary phase of growth in H. influenzae, we used a DNA transformation assay to evaluate the physiological state of bacteria grown in diffusion chambers implanted in rats. Chromosomal DNA isolated from an antibiotic-resistant donor strain was mixed with bacteria in diffusion chambers. At different times during a 5-h incubation period, recipient bacteria were collected from the chambers, CFU were determined by plate counting, and antibiotic-resistant transformants were isolated on selective plates. Genetic competence rapidly developed in cells grown in rats, and the frequency of transformation by test DNA was elevated. Electron microscopy revealed an irregular cell shape and blebs at the surface of bacteria cultivated in animals and in cerebrospinal fluids. In an attempt to induce a similar physiological state in vitro, we supplemented broth cultures with cyclic AMP or synchronized cultures by a nutritional upshift. No changes in PBPs were observed with supplemental cyclic AMP or during a single cell cycle. Finally, a reduction in the affinity of PBPs for 125I-penicillin V identical to that observed in bacteria grown in rats was observed in cells isolated from the stationary phase of growth in vitro. These results clearly indicate that H. influenzae cells grown in animals undergo a rapid change to a physiological state similar to that found in late-stationary-phase cultures in vitro. This observation indicates that the rational design of future and improved antibiotic therapy of H. influenzae infections should consider cell properties of slow-growing or latent bacteria.
Images
PMCID: PMC257432  PMID: 1328054
9.  Effect of beta-lactams on peptidoglycan metabolism of Haemophilus influenzae grown in animals. 
Antimicrobial Agents and Chemotherapy  1992;36(10):2147-2155.
We have examined bacterial determinants that influence beta-lactam activity in Haemophilus influenzae cells cultivated in a system that reproduces in vivo growth conditions. Bacteria grown in diffusion chambers were recovered from the peritoneal cavities of rats, and their cell properties were compared with those of bacteria grown in broth cultures by various tests performed in vitro. The rate of peptidoglycan synthesis was measured as the incorporation of [14C]alanine into cell wall material in the presence of chloramphenicol. The total incorporation of [14C]alanine into peptidoglycan was markedly increased in cells grown in rats prior to the assay but was efficiently reduced by the beta-lactams. The extent of cross-linking was lower in the peptidoglycan of in vivo-grown bacteria, as estimated by sodium dodecyl sulfate- to trichloroacetic acid-insoluble radioactive cell wall material ratios. A whole-cell labeling assay with 125I-penicillin was used to characterize the penicillin-binding proteins (PBPs). Four PBPs showed a striking reduction in the binding of the labeled penicillin in cells grown in rats. Such changes resembled the PBP alterations seen in beta-lactamase-negative clinical strains that were resistant to the beta-lactams. Although ampicillin and moxalactam showed delayed inhibitory activities in vitro for cells collected from rats, cells recovered from beta-lactam-treated rats showed evidence of antibiotic effectiveness (binding of the beta-lactams to PBPs in vivo and altered morphology), and the killing of cells exposed to antibiotics in broth or in peritoneal fluid was equally good. Finally, the frequencies of spontaneous resistance or tolerance to ampicillin or moxalactam were estimated, and there was no significant difference for in vitro- or in vivo-grown cells. These data demonstrated that the cultivation of H. influenzae in animals created changes in PBPs and the overall peptidoglycan metabolism. Such alterations did not impair the bactericidal activities of the beta-lactams, although they resulted in delayed bacterial inhibition, a phenomenon that may have important consequences in antibiotherapy.
Images
PMCID: PMC245469  PMID: 1444294
10.  Subcellular localization of tobramycin and vancomycin given alone and in combination in proximal tubular cells, determined by immunogold labeling. 
Antimicrobial Agents and Chemotherapy  1992;36(10):2204-2210.
The subcellular localization of tobramycin and vancomycin in the renal cortices of rats was determined with ultrathin sections by immunogold labeling. Four groups of four rats each were treated for 10 days with saline (NaCl, 0.9%), tobramycin at dosages of 20 mg/kg of body weight per 12 h intraperitoneally, vancomycin at dosages of 25 mg/kg/12 h subcutaneously, or the combination tobramycin-vancomycin. On day 11, the animals were killed, and cubes of renal cortex were fixed overnight in phosphate-buffered glutaraldehyde (0.5%), dehydrated in ethanol, and embedded in Araldite 502 resin. Ultrathin sections were made and incubated with sheep antitobramycin antibody followed by protein A-gold (15-nm diameter) complex or rabbit antivancomycin antibody followed by gold (30-nm diameter)-labeled goat anti-rabbit antibody. For the double labeling, incubations were made on opposite sides of the grid. Tobramycin was detected over the lysosomes of proximal tubular cells, but the labeling was concentrated into small areas in the matrix of the lysosomes. Vancomycin was seen over the lysosomes of proximal tubular cells and was distributed uniformly throughout the matrix of the lysosomes. In rats treated with tobramycin-vancomycin, both drugs were still detected in lysosomes of proximal tubular cells. It is concluded that tobramycin and vancomycin accumulate in lysosomes of proximal tubular cells throughout 10 days of treatment and that vancomycin has no effect on the subcellular distribution of tobramycin.
Images
PMCID: PMC245477  PMID: 1444301
11.  Molecular basis of the non-beta-lactamase-mediated resistance to beta-lactam antibiotics in strains of Haemophilus influenzae isolated in Canada. 
A study recently conducted across Canada showed that 64 of 2,503 clinical isolates of Haemophilus influenzae were resistant to beta-lactams without production of a beta-lactamase (L. D. Tremblay, J. L'Ecuyer, P. Provencher, M. G. Bergeron, and Canadian Study Group, Can. Med. Assoc. J. 143:895-900, 1990). The beta-lactamase-negative strains formed three distinct groups, with ampicillin MICs of 0.5 to 1, 2 to 4, and greater than or equal to 8 micrograms/ml for groups I, II, and III, respectively. We have investigated the mechanisms of resistance for eight strains originating from different infections and geographic areas. These strains were representative of groups I to III. Five strains were nontypeable, two were type B, and one was non-B. Chromosomal DNA extracted from each strain was used to transform the laboratory strain Rd. Transformants were selected on beta-lactam-containing plates and showed the same level of resistance to ampicillin as the donor strains. Differences in outer membrane proteins, porins, and lipopolysaccharide profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) did not change with resistance. Functional analyses of purified porins in artificial lipid bilayer experiments did not explain resistance. Peptidoglycan synthesis was measured by incorporation of [14C]alanine into trichloroacetic acid-insoluble cell wall material in the presence of chloramphenicol. The growth rate and the rate of peptidoglycan synthesis observed for the transformants of the isogenic set did not correlate with resistance. Whole-cell labeling with 125I-penicillin revealed modifications in penicillin-binding proteins (PBPs) among the transformants. In particular, PBPs 3A and 3B (65 and 63 kDa, respectively) showed a decrease in affinity for beta-lactams in all transformants (groups I, II, and III) and correlated with an increased MIC except in the transformant of group III, which showed higher levels of resistance. Partial purification and proteolytic digestion of 125I-penicillin-labeled PBP 3B led to two types of CnBr peptide profiles on SDS-PAGE, the profiles of the transformed strains from groups I and II being different from those of the control group and group III. Finally, electron microscopy revealed a distinct cell filamentation for the group III transformants. These data clearly indicate that changes in PBPs are a common mechanism that results in a significant level of non-beta-lactamase-mediated beta-lactam resistance in H. influenzae despite serotype, origin of isolation, or geographic distribution.
Images
PMCID: PMC191612  PMID: 1510447
12.  Subcellular distribution of gentamicin in proximal tubular cells, determined by immunogold labeling. 
Antimicrobial Agents and Chemotherapy  1991;35(11):2173-2179.
The subcellular distribution of gentamicin in rat renal proximal tubular cells was evaluated by immunogold labeling. The distribution of the drug was monitored from 10 min to 10 days following single (40 mg/kg of body weight) and multiple (5 and 20 mg/kg/12 h) injections of gentamicin. Animals were killed on day 11, and cubes of renal cortex tissue were fixed overnight in cold phosphate-buffered glutaraldehyde (0.5%), dehydrated in ethanol, and embedded in Araldite 502 epoxy resin. Ultrathin sections were made and incubated with sheep antigentamicin and then with protein A-gold (15 nm) complex. At 10 min after a single injection, the labeling was found over the brush border membrane and over the membranes of endocytic apical vesicles of proximal tubular cells. After 1 h, a similar distribution was observed and the labeling was also seen over small lysosomes located close to the brush border membrane. At 24 h, gold particles were found over large lysosomes of proximal tubular cells. Following 10 days of treatment, lysosomes of proximal tubular cells were densely labeled with gold particles. The labeling was distributed uniformly over the lysosomes, although a lower density of labeling was observed over the myeloid bodies inside the lysosomes. Necrotic proximal tubular cells showed labeling over intact lysosomes and also in the cytoplasms of the cells, in the mitochondria, and in the nucleoli. The various control experiments demonstrated the high specificity of these results. The present immunocytochemical study better documents the subcellular disposition of gentamicin in proximal tubular cells, as previously evaluated by subcellular fractionation and autoradiography. This technique will be useful for better understanding the relationship between drug disposition and drug-induced toxicity.
Images
PMCID: PMC245355  PMID: 1803988
13.  Prolonged endotoxemia enhances the renal injuries induced by gentamicin in rats. 
The aim of this study was to evaluate the role of chronic endotoxemia in the nephrotoxicity of gentamicin (GM). Saline or Escherichia coli lipopolysaccharide (LPS) was administered to conscious rats by continuous intravenous perfusion (1 mg/kg per day for 7 days) from a subcutaneously implanted osmotic pump. Twenty-four hours after surgery (day zero), treatment with saline or GM (15 mg/kg; intraperitoneally, twice a day) was started for 5 days. Levels of LPS in plasma measured by Limulus amoebocyte lysate activity decreased significantly from days 1 through 8. At days 5 and 8, the cortical concentrations of GM were higher in the LPS-perfused and GM-treated group (LPS plus GM) than they were in the saline-perfused and GM-treated group (saline plus GM) (P less than 0.05). Blood urea nitrogen and serum creatinine remained at normal levels throughout the experiment. A significant increase of cortical tubular cell regeneration was observed in the LPS plus GM animals as compared with regeneration observed in the other groups (saline plus saline, LPS plus saline, and saline plus GM), as measured by [3H]thymidine incorporation into DNA. Moreover, histopathological nephrotoxicity scores showed a synergistic toxic effect between LPS and GM. These results demonstrate that chronic perfusion of low doses of LPS potentiates the nephrotoxicity of GM.
Images
PMCID: PMC171712  PMID: 2360824
14.  Effects of daptomycin and vancomycin on tobramycin nephrotoxicity in rats. 
Daptomycin is a new biosynthetic antibiotic which belongs to a new class of drugs known as lipopeptides. The objective of this study was to evaluate the effects of daptomycin and vancomycin on tobramycin-induced nephrotoxicity. Female Sprague-Dawley rats were treated during 4 and 10 days with either saline (NaCl, 0.9%) or tobramycin at doses of 4 and 40 mg/kg per day (given every 12 h [q12h] intraperitoneally). Each treatment was combined with saline, daptomycin at a dose of 20 mg/kg per day (given q12h subcutaneously), and ancomycin at a dose of 50 mg/kg per day (given q12h subcutaneously). Daptomycin and vancomycin had no effect on the intracortical accumulation of tobramycin. Daptomycin did not accumulate in renal tissue even after 10 days of treatment. Tobramycin given at a dose of 40 mg/kg per day during 10 days induced a significant inhibition of sphingomyelinase activity in the renal cortex (P less than 0.01) and increased cellular regeneration (P less than 0.01), as measured by the incorporation of [3H]thymidine into DNA of the renal cortex. These changes were minimal when daptomycin was combined with tobramycin. Histologically, signs of tobramycin toxicity were also less severe in the presence of daptomycin. The intracortical accumulation of vancomycin was not modified by tobramycin. The sphingomyelinase activity was significantly more inhibited (P less than 0.01) when vancomycin was associated with tobramycin (4 and 40 mg/kg) without affecting the rate of [3H]thymidine incorporation into DNA. Histologically, signs of tobramycin toxicity were not affected by vancomuycin, but the cellular vacuolizations which were also observed in vancomycin-treated animals were still present in the proximal tubular cells of animals that were treated with the combination vancomycin-tobramycin. This study strongly suggests that daptomycin protects animals from tobramycin-induced nephrotoxicity but that vancomycin may enhance the effect of tobramycin. We conclude that daptomycin is safe and protects kidney cells from tobramycin-induced nephrotoxicity.
Images
PMCID: PMC171535  PMID: 2158272
15.  Effect of age on the intracortical accumulation kinetics of gentamicin in rats. 
Antimicrobial Agents and Chemotherapy  1989;33(11):2006-2008.
We have evaluated the influence of age on the intracortical accumulation kinetics of gentamicin in conscious male rats by using a short-term infusion model. Animals were infused with gentamicin over a 6-h period and achieved individual steady-state levels in serum ranging from 0.5 to 12 micrograms/ml. Young rats were about 3 months old, and old rats were about 6 months old. The steady-state elevation of concentrations of gentamicin in serum was associated with a linear increase of the cortical concentrations in both groups. However, the accumulation of gentamicin was lower in the renal cortex of the old rats than in the renal cortex of the young rats. We conclude that the intrarenal uptake of gentamicin is modified during aging. Further studies must be undertaken to better understand the role of age on the mechanism of uptake and the toxicity of aminoglycosides.
PMCID: PMC172804  PMID: 2610510

Results 1-15 (15)