Gentamicin Group Research Articles

The role of deferoxamine in the prevention of gentamicin ototoxicity: a histological and audiological study in guinea pigs

Conclusion. The addition of deferoxamine to gentamicin seems to confer partial functional and histological protection to the cochlea. Objective. Aminoglycosides are known ototoxic agents. The toxicity occurs via an activation process involving the formation of an iron–gentamicin complex with free radical production. Iron chelation will supposedly limit this toxic effect. This study aimed to determine the possible cochleoprotective role of deferoxamine on the ototoxic effect of gentamicin. Materials and methods. Sixty healthy active guinea pigs, weighing 400–600 g, with an average age of 6 months were used. They were divided into three groups. Group 1 received intramuscular gentamicin 8 mg/kg/day, group 2 received gentamicin 8 mg/kg/day and deferoxamine 150 mg/kg twice daily for 19 days and group 3 served as a control. All animals had a baseline measurement of distortion product autoacoustic emissions. At the end of 33 days they were submitted to another measurement and then the animals were sacrificed and their cochleas were examined histologically by light and transmission electron microscopy.Results. In group 1 the mean amplitude post-injection ranged from 5.83 dB at 1001 Hz to 22.33 dB at 6348 Hz. In the deferoxamine + gentamicin group the mean amplitude post-injection ranged from 5.10 dB at 1001 Hz, to 24.45 dB at 6348 Hz. This was statistically significant. At 4004, 5042 and 6348 Hz group 2 showed less histological damage than group 1.

Effect of sevoflurane anesthesia on the severity of renal histopathologic changes in rabbits pretreated with gentamicin: A controlled, investigator-blinded, experimental study

Background: Inorganic fluoride and compound A are potential nephrotoxic products of sevoflurane, a halogenated inhalational general-anesthetic drug. Objective: The aim of this study was to microscopically examine the effect of sevoflurane on the severity of renal histopathologic changes in rabbits pretreated with gentamicin. Methods: In this controlled, investigator-blinded, experimental study at the Firat University School of Medicine, Elazig, Turkey, male New Zealand white rabbits (age range, 6–8 months; weight range, 2600–3400 g) were randomly divided into 4 groups of equal size. The gentamicin group received IM gentamicin 10 mg/kg · d −1 for 10 days. Rabbits in the sevoflurane group received pH-balanced saline solution at a volume of 10 mg/kg · d −1 for 10 days, equivalent to the volume of gentamicin administered to the gentamicin group. On day 11, anesthesia was induced with 8% sevoflurane in 50% oxygen and air using a suitable facemask. When a sufficient depth of anesthesia (loss of eyelash reflex and tolerance to tail-clamp stimuli) was reached (without a muscle relaxant), the rabbits were intubated (3-mm ID) and allowed to breathe spontaneously. End-tidal or end expiratory concentration of sevoflurane was then decreased to 4% and the rabbits were anesthetized at a flow rate of 4 L/min for 4 hours. The rabbits in the gentamicin + sevoflurane group were treated with IM gentamicin at a dosage of 10 mg/kg · d −1 for 10 days. On day 11, they were exposed to sevoflurane, as described for the sevoflurane group. The control group received IM pH-balanced saline solution for the duration of the study. Twenty-four hours after treatment completion, all rabbits were euthanized and kidney tissue samples were obtained. Histopathologic examinations were then carried out using light microscopy. Changes in renal histopathology were based on the percentage of acute tubular necrosis (ATN) and judged on a scale from none to severe. Results: Forty male New Zealand white rabbits (mean [SD] age, 7 [0.49] months; mean [SD] weight, 2900 [150] g) were divided into 4 groups of 10 rabbits each. Proximal renal tubule cell injury in the form of ATN (the mean score) was significantly greater in the 3 treatment groups than in the control group (all, P < 0.001), especially at the corticomedullary junction. In the 3 treatment groups, the most severe renal damage observed was rated as mild (10%–25%). More rabbits in the gentamicin + sevoflurane group had mild renal damage (7) than in the gentamicin group (4) or the sevoflurane group (4), but the between-group differences were not statistically significant. Conclusion: In this experimental study of the effects of sevoflurane on the severity of renal histopathologic changes, a higher percentage of rabbits were observed to have greater renal damage in the gentamicin + sevoflurane group than the other groups. However, between-group differences did not reach statistical significance.

Comparative effects of selective and non-selective nitric oxide synthase inhibition in gentamicin-induced rat nephrotoxicity

Different nitric oxide synthase (NOS) isoforms are found in the kidney. Some studies provided evidences that increased endothelial NOS (eNOS) activity leads to restoration of renal function after injury, but activation of inducible NOS (iNOS) aggravates renal failure. In the present study, the beneficial effects of selective iNOS blockade in gentamicin (GM) induced nephrotoxicity have been investigated. Four groups of rats were studied. Untreated control rats received saline. In GM group, GM was injected (IV, 4 mg kg(-1)). In GM + L-NAME group rats received L-NAME (N-omega-L-arginine methyl ester, a non-selective NOS inhibitor) simultaneously with GM (IV, 30 mg kg(-1)). Additional doses of L-NAME were administered 2 and 4 h after GM (IP, 30 mg kg(-1)). In GM + L-NIL group rats were treated by N-imino-ethyl lysine (L-NIL, a selective iNOS inhibitor). First dose (IV, 3 mg kg(-1)) administrated simultaneously with GM. Next doses (IP, 3 mg kg(-1)) were administered 2 and 4 h after GM. In all groups, serum and urine creatinine levels were measured. Creatinine clearance was calculated and considered as an estimation of glomerular filtration rate (GFR). Urine N-acetyl-b-D-glucose aminidase (NAG) activities were also determined. After experiments, kidney sections were histologically studied. Selective iNOS inhibition by L-NIL prevented the GM-induced decrease in GFR and increase in creatinine levels, while complete non-selective NOS inhibition by L-NAME aggravated the GFR reduction, elevation of creatinine levels and enzyme release (P < 0.05). Histological studies showed that GM-treated kidneys had evidences of tubular damages and these damages were less evident by the administration of L-NIL. In conclusion, selective inhibition of iNOS may prevent GM-induced nephrotoxicity, whereas non-selective inhibition of NOS aggravates it.

Comparison of Low-Dose Gentamicin With Minocycline as Catheter Lock Solutions in the Prevention of Catheter-Related Bacteremia

Catheter-restricted antibiotic lock solutions were found to be effective in the prevention of catheter-related bacteremia (CRB), but insufficient data are available about the ideal agent and dose. We hypothesized that a low concentration of gentamicin would be as effective as the high doses studied in the past. In this prospective, open-labeled, randomized, clinical trial of patients on long-term hemodialysis therapy, patients were randomly assigned to administration of an antibiotic lock solution of gentamicin/citrate (4 mg/mL), minocycline/EDTA, or the control solution of heparin. Patients were followed up until the study end point of CRB was reached or a censoring event occurred. Interim data analysis was performed after 6 months to assess data safety; efficacy was noted and the study was terminated early. Sixty-two patients were enrolled into the study, evenly distributed in 3 arms, with data from 1 patient excluded from analysis. Seven of 20 patients in the heparin group (4.0 events/1,000 catheter days), 1 of 21 patients in the minocycline group (0.4 events/1,000 catheter days), and none of 20 patients in the gentamicin group developed bacteremia. Results were statistically significant by using 2-tailed Fisher exact test; heparin versus gentamicin, P = 0.008, and heparin versus minocycline, P = 0.020. Antibiotic lock solutions are superior to the standard heparin lock alone in the prevention of CRBs, and low-dose gentamicin solution has efficacy similar to that of greater concentrations used in previous studies.

Increased Expression of Heat Shock Protein 72 Protects Renal Proximal Tubular Cells from Gentamicin-induced Injury

The nephrotoxicity of gentamicin (GM) has been widely recognized. Heat shock protein 72 (HSP72) has been reported to be a cytoprotectant. However, its cytoprotective effect against GM induced kidney injury has not yet been studied. In this study, we investigated the cytoprotective effect of HSP72 on GM-induced nephrotoxicity in vitro. Human Kidney tubular cell line, HK-2 cells were divided into four groups: control group, GM group (cells incubated with GM only), heat shock (HS) group (cells incubated at 43℃ for 30 min), and GM plus HS group, respectively. Lactate dehydrogenanse (LDH) release increased time-dependently from 24 hr to 96 hr compared to the data of cells treated with GM only. Results of NAG activities, superoxide dismutase (SOD) activities and malondialdehyde (MDA) content were similar to that of the LDH release. The amount of HSP72 positive cells increased significartly at 72 hr after cells were treated with GM only. Both HSP72 protein and gene expression increased significantly at 72 hr when cells were treated with GM. On the other hand, HS induced HSP72 expression markedly. Pretreatment of HS inhibited HK-2 cells from GM-induced injury. It could reduce LDH release and NAG activity. HS also increased SOD activity, and decreased MDA content when cells were damaged by GM. These findings suggested that HS may protect kidney cells from GM-induced injury. Pre-induction of HSP72 may provide therapeutic strategies for nephrotoxicity induced by GM.

Cloxacillin versus vancomycin for presumed late-onset sepsis in the Neonatal Intensive Care Unit and the impact upon outcome of coagulase negative staphylococcal bacteremia: a retrospective cohort study

BackgroundCoagulase negative staphylococcus (CONS) is the main cause of late-onset sepsis in Neonatal Intensive Care Units (NICU). Although CONS rarely causes fulminant sepsis, vancomycin is frequently used as empiric therapy. Indiscriminate use of vancomycin has been linked to the emergence of vancomycin resistant organisms. The objective of this study was to compare duration of CONS sepsis and mortality before and after implementation of a policy of selective vancomycin use and compare use of vancomycin between the 2 time periods.MethodsA retrospective study was conducted of infants ≥4 days old, experiencing signs of sepsis with a first positive blood culture for CONS, during two 12-month periods. Late-onset sepsis was treated empirically with vancomycin and gentamicin during period 1, and cloxacillin and gentamicin during period 2. The confidence interval method was used to assess non-inferiority of the outcomes between the two study groups.ResultsThere were 45 episodes of CONS sepsis during period 1 and 37 during period 2. Duration of sepsis was similar between periods (hazard ratio of 1.00, 95%CI: 0.64, 1.57). One death during period 2 was possibly related to CONS sepsis versus none in period 1. Vancomycin was used in 97.8% of episodes in period 1 versus 81.1% of episodes in period 2.ConclusionAlthough we failed to show non-inferiority of duration of sepsis in the cloxacillin and gentamicin group compared to the vancomycin and gentamicin group, duration of sepsis was clinically similar. Restricting vancomycin for confirmed cases of CONS sepsis resistant to oxacillin appears effective and safe, and significantly reduces vancomycin use in the NICU.

GENTAMICIN IMPROVES HEMODYNAMICS IN OVINE SEPTIC SHOCK AFTER SMOKE INHALATION INJURY

Previously, our group developed an ovine model of hyperdynamic sepsis associated with acute lung injury. In this study, we sought to modify this sepsis model by the administration of gentamicin to more closely simulate the symptoms observed in human sepsis in the intensive care unit. In a prospective, controlled, randomized laboratory experiment, 18 female sheep were surgically prepared for chronic study. After a tracheotomy had been performed, the sheep were randomized into sham, control, and gentamicin groups (n = 6 each). Sham animals were surgically prepared for the study but were neither injured nor treated. Control and gentamicin animals received 48 breaths of cotton smoke (<40 degrees C) followed by the instillation (via a bronchoscope) of live Pseudomonas aeruginosa (2-5 x 10(11) colony-forming units) bacteria into the lung. All sheep were mechanically ventilated with 100% O2 for the duration of the 24-h experimental period. Gentamicin (2 mg/kg) was administered at 6, 12, and 18 h after injury. The animals were resuscitated with lactated Ringer's solution to maintain filling pressures and hematocrit on a constant level. Cardiopulmonary variables were stable in sham animals, but in the control group, cardiac index increased significantly after 24 h versus baseline (BL, 5.1 +/- 0.4 L.min(-1).m(-2) vs. 24 h, 7.3 +/- 0.7 L.min(-1).m(-2); P < 0.05); this was associated with a significant drop in mean arterial pressure (BL, 95 +/- 3 mmHg vs. 24 h, 65 +/- 4 mmHg, P < 0.05) and systemic vascular resistance index (BL, 1410 +/- 118 dynes s.cm.m vs. 24 h, 598 +/- 101 dynes s.cm.m, P < 0.05). Treatment with gentamicin stabilized cardiac index (BL, 5.0 +/- 0.4 L.min(-1).m(-2) vs. 24 h, 4.7 +/- 0.4 L.min(-1).m(-2)) and attenuated the decrease in mean arterial pressure (BL, 99 +/- 3 mmHg vs. 24 h, 84 +/- 4 mmHg) and systemic vascular resistance index (BL, 1573 +/- 173 dynes s.cm.m vs. 24 h, 1263 +/- 187 dynes s.cm.m). In addition, the fluid requirement in the gentamicin group was significantly lower than in the control group. Pulmonary function remained stable in sham animals, but the PaO2/FiO2 ratio and shunt fraction deteriorated similarly in the control and the gentamicin groups. Because gentamicin improved hemodynamic variables and reduced the fluid requirement in this ovine model, we believe that this modified sepsis model might provide a clinically relevant and useful new approach for future studies focusing on hemodynamic variables and outcome.

Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats

A potential therapeutic approach to protect or reverse gentamicin-induced oxidative stress and nephrotoxicity would have more importance for clinical consequences. Therefore, the present study was designed to investigate the possible protective effects of lycopene against gentamicin-induced renal damage in rats. Male Sprague-Dawley rats were divided into four groups of six rats in each one; first group served as control. The other groups were treated intraperitoneally with gentamicin alone (100 mg kg −1 per day) for six successive days, gentamicin for 6 days following 10 days of orally lycopene (4 mg kg −1 per day) pre-treatment and 6-days of simultaneous lycopene and gentamicin. Biochemical and histopathological examinations were utilized for evaluation of the oxidative stress and renal nephrotoxicity. Creatinine, urea, Na + and K + levels in plasma and malondialdehyde (MDA), reduced glutathione (GSH) levels and glutathione peroxidase (GSH-Px) and catalase (CAT) activities were determined in kidney tissue. Administration of gentamicin to rats induced a marked renal failure, characterized by a significant increase in plasma creatinine and urea concentrations. The animals treated with gentamicin alone showed a significantly higher kidney MDA and lower GSH-Px and CAT activities but unaffected GSH concentrations when compared with the control group. Pre-treatment with lycopene produced amelioration in biochemical indices of nephrotoxicity in plasma. However, little changes were observed in the kidney MDA and GSH levels and GSH-Px and CAT activities when compared with the gentamicin treated group. The histological structures of the renal proximal tubules showed similar patterns. On the other hand, administration of simultaneous lycopene to rats produced amelioration in MDA and GSH levels and GSH-Px and CAT activities when compared with gentamicin group. In addition, simultaneous lycopene was found to reduce the degree of kidney tissue damage in histopathological findings. These results indicate that specially simultaneous treatment of lycopene might have produced amelioration in biochemical indices and oxidative stress parameters against gentamicin-induced nephrotoxicity, but pre-treatments with lycopene had no beneficial effects on these parameters. It was concluded that lycopene as a novel natural antioxidant might have protective effects against gentamicin-induced nephrotoxicity and oxidative stress in rats.

Nitric Oxide in Gentamicin-induced Acute Tubular Necrosis in Rats

Gentamicin is still widely used in clinical practice in spite of its renal toxicity. The role of nitric oxide (NO) in that process is not completely elucidated. The aim of this study was to investigate the relationship between plasma level of NO and the histopathological changes of kidney in acute tubular necrosis (ATN) induced by gentamicin in rats. Study was carried out in Albino-Wistar rats, both sexes (n=16), average body weight 200-250 g. divided in two equal groups: control and gentamicin group. The control group was injected with 0.9% NaCl i.p. and gentamicin group was injected with gentamicin in the dose of 80 mg/kg/day i.p. in a period of 5 consecutive days. NO plasma level was determined by the production of nitrates and nitrites using classical colorimetrical Griess reaction. Kidney specimens were stained with hematoxylin-eosin (H-E) and Periodic acid-Schiff (PAS) stain. Semiquantitative histological analysis was used for the evaluation of the level of kidney damage. Both, the plasma NO level and the level of kidney damage were statistically higher in rats with gentamicin-induced ATN in comparison to the control group. In spite of that the correlation between plasma NO level and the level of kidney damage was not found. The rise of plasma level NO in gentamicin induced ATN in rats could possibly indicate on the role of NO in renal damage caused by gentamicin.

Gentamicin‐induced nephrotoxicity and protective effect of caffeic acid phenethyl ester in rats

The objective of this study was to investigate the beneficial effects of caffeic acid phenethyl ester (CAPE) on gentamicin (GM)-induced nephrotoxicity in Wistar rats. Twenty-one adult Wistar rats were divided into three groups as follows: control group, GM and GM + CAPE group. Control group rats were injected with 5% ethanol, GM group rats were treated with 100 mg/kg GM and GM + CAPE group were pretreated with 10 mumol/kg CAPE for 2 days, then exposed to GM at the same dose. Drug injections were applied for 12 days. Twenty-four hours after the last injection, rats were killed and kidneys were quickly removed. Tissue malondialdehyde (MDA) measurements and microscopic examination of kidneys were performed. In the GM group, significant increases in MDA levels were observed (P < 0.05). These changes were found to be normalized in the GM + CAPE group. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules were found to be prevented by CAPE pretreatment. In conclusion, CAPE exerted an improvement on GM-induced nephrotoxicity, possibly, at least in part through inhibition of the production of oxygen free radicals that cause lipid peroxidation.

INVITED COMMENTARY

INVITED COMMENTARY

Prophylaxis of sternal wound infections with gentamicin-collagen implant: randomized controlled study in cardiac surgery

Postoperative infections may lead to prolonged hospital stay and increased morbidity, mortality and hospital costs, especially in heart surgery. Finding new means to prevent infections would benefit both the patient and society. The aim of this study was to assess if locally administered gentamicin prevents sternal wound infections in coronary artery bypass (CABG) surgery. We randomized 542 consecutive CABG patients to two groups: those who received gentamicin-collagen implant under their sternum before closure (N=272) and controls (N=270). The subjects received routine intravenous antimicrobial prophylaxis (85% cefuroxime, 14% cefuroxime and vancomycin), and were followed-up for three months. The sternal wound infection rate was 4.0% (11/272) in the gentamicin group and 5.9% (16/270) in the control group. The mediastinitis rates were 1.1 and 1.9%, respectively. This treatment was safe and easy to administer, and no side-effects occurred. No statistically significant difference was demonstrated between infection rates in the two groups. This is the first study on the use of gentamicin-collagen sponge as prophylaxis in cardiac surgery. Our data show that infection was reduced slightly in the gentamicin-collagen group compared with the control group, but the study population was too small to draw conclusions. Further evaluation is needed, and the results may warrant another larger, better-powered study.

Prevention of gentamicin induced ototoxicity by trimetazidine in animal model

To show the efficacy of intra-peritoneally administered trimetazidine to prevent gentamicin ototoxicity, which is still an important cause of profound deafness among children in different parts of the world. Two groups of Swiss albino mice received daily intra-muscular injections of gentamicin for 30 days. One of the groups received trimetazidine intra peritoneally in addition to the gentamicin. Auditory thresholds of the animals were measured by evoked brain stem response at the beginning and the end of the study. Results were compared to the results of the control group, which received intra peritoneal saline injections. Both groups receiving gentamicin injections had significant auditory threshold shifts, but in the group receiving additional trimetazidine, the threshold shift was not statistically significant when compared to control group. Threshold shift in gentamicin group significantly differed from that of the control group (p=0.0001) and gentamicin+trimetazidine group (p=0.0001), on the other hand there was no statistically significant difference between control group and trimetazidine+gentamicin group (p=0.102). Gentamicin ototoxicity can be prevented by intra peritoneal trimetazidine injections in animal model. This treatment modality may be a mode of protection from gentamicin ototoxicity in children.

Topical vancomycin for chronic suppurative otitis media with methicillin-resistant Staphylococcus aureus otorrhoea.

There has been a steady increase in the number of cases of methicillin-resistant Staphylococcus aureus (MRSA) otorrhoea; this is a growing concern. The purpose of this study was to evaluate the efficacy of topical vancomycin treatment in patients with MRSA otorrhoea. Fifty-five patients with MRSA otorrhoea were prospectively enrolled into the study. Thirty-five patients were treated with vancomycin eardrops as outpatients. The concentration of the locally prepared vancomycin solution was 25 mg/ml. The dose of vancomycin was two drops three times daily for 10 days. As a control group, 20 patients were treated with gentamicin 0.3% solution. Data were analysed by the Mann-Whitney U test to compare the efficacy of vancomycin eardrops and gentamicin eardrops. In the vancomycin group, the otorrhoea was significantly reduced in 33 ears (94%); in the gentamicin group, in four ears (20 per cent); this reduction was statistically significant (P < 0.03). The use of topical vancomycin treatment was effective for patients with MRSA otorrhoea refractory to conventional antibiotic treatment.

Selective vestibular ablation by intratympanic gentamicin in patients with unilateral active ménière's disease: a prospective, double-blind, placebo-controlled, randomized clinical trial

ObjectiveTo establish the efficacy of intratympanic gentamicin treatment in patients with unilateral Ménière's disease.Material and MethodsThis was a prospective, double-blind, randomized clinical trial of intratympanic gentamicin versus intratympanic buffer solution (placebo) in patients with established active Ménière's disease in the affected ear. Outcome measures included the number of vertiginous spells, degree of sensorineural hearing loss, labyrinthine function and labyrinthine asymmetry.ResultsTopical gentamicin provided a significant reduction in the number of vertiginous spells, although a “placebo effect” was also observed. Sensorineural hearing loss did not occur in the gentamicin group, although some deterioration occurred in the placebo group.ConclusionsIntratympanic gentamicin is a safe and efficient treatment for the vertiginous spells associated with Ménière's disease. When applied early in the course of the disease, it may prevent some of the sensorineural hearing deterioration associated with it.

Effect of tempol (4-hydroxy tempo) on gentamicin-induced nephrotoxicity in rats.

We investigated the effects of tempol (4-hydroxy tempo), a membrane-permeable radical scavenger, on gentamicin-induced renal failure in rats. The rats were given gentamicin (100 mg/kg/day, i.p., once a day); and gentamicin (100 mg/kg/day, i.p.) and tempol (3.5, 7 or 14 mg/kg/day, i.p., once a day). At the end of 7 days, the gentamicin group produced the remarkable nephrotoxicity, characterized by a significantly decreased creatinine clearance and increased serum creatinine, blood urea nitrogen (BUN) and daily urine volume when compared with controls. In control the BUN value was 21.2 +/- 0.07 (mg/100 mL); in comparison, it was 96.9 +/- 6.03 in gentamicin group (P < 0.05). Renal histopathologic examination confirmed acute tubular necrosis in this group. In rats treated with gentamicin and tempol a partial improvement in biochemical and histologic parameters was observed. BUN values were 96.9 +/- 6.03 and 36.3 +/- 2.39 in gentamicin, and gentamicin plus tempol (14 mg/kg) treated groups, respectively (P < 0.05). These results suggest that the administration of tempol may have a protective effect on gentamicin-induced nephrotoxicity in rats.

Iontophoresis–gentamicin delivery into the rabbit cornea, using a hydrogel delivery probe

Purpose. To evaluate the efficacy of penetration of gentamicin into the cornea of rabbits using iontophoresis with a hydrogel–gentamicin containing probe. Methods. Eight of 10 groups (groups 3–10) of 6 rabbits (one eye per rabbit), underwent corneal iontophoresis using soft stable hydroxyethyl methacrylate hydrogel discs (80% water content) loaded with gentamicin sulphate which were mounted on an iontophoresis probe. The studied current intensities were 0, 0·1, 0·3 and 0·6 mAmp, and the durations of iontophoresis were 10 and 60 sec. Two control groups received 1·4% topical drops of gentamicin every 5 min for 1 hr (group 1) or sub-conjunctival injection of 10 mg gentamicin (group 2). Following sacrifice, aqueous humour was taken, corneas were excised, and gentamicin concentration was determined in aqueous humour and cornea samples. Results. Post-iontophoresis, the concentration of gentamicin in the corneas ranged from high (88·60±38·64 μg ml −1) to very low (0·10±0·89 μg ml −1). Both the control groups and those rabbits treated with current intensity of 0·1 mAmp or greater obtained therapeutic gentamicin levels in the corneas. Use of iontophoresis for 60 sec or current intensity greater than 0·1 mAmp obtained corneal gentamicin levels not different from sub-conjunctival injection. Application of current intensity of 0·1 mAmp or greater gave corneal gentamicin concentrations comparable to topical application of the drug, except when 0·6 mAmp were used for 60 sec ( p=0·05). Increasing current intensity or duration of iontophoresis significantly increased ( p=0·001 for both) gentamicin penetration into the cornea. Current intensity had more influence (Beta 2=0·40) than duration (Beta 2=0·13) on drug penetration. A significant interaction was found between the duration of iontophoresis and the current intensity. Very small or no concentrations of the drug were discovered in the anterior chambers of rabbits. Conclusions. Iontophoresis using hydrogel–gentamicin probe may deliver therapeutic concentrations of gentamicin into the cornea.

The effect of manganese chloride on gentamicin-induced nephrotoxicity in rats

The aim of this study was to investigate the effects of manganese chloride on gentamicin-induced nephrotoxicity in rats. Thirty-six adult Wistar Albino rats were divided into six equal groups. They were injected with gentamicin sulfate (100 mg kg −1 per day i.p.) and manganese chloride (2 or 20 mg kg −1 per day i.p.) and gentamicin together with manganese chloride for 6 days. The animals were killed 24 h after the last injection. Nephrotoxicity was biochemically and histopathologically evaluated. The concentrations of creatinine, urea, sodium and potassium in plasma, malondialdehyde (MDA) and reduced glutathione (GSH) levels, glutathione peroxidase (GSH-Px) and catalase (CAT) activities in kidney tissue were determined. Administration of gentamicin to rats induced a marked renal failure, characterized with a significant increase in plasma creatinine and urea concentrations. A significant increase in kidney MDA and a decrease in GSH concentrations were observed in gentamicin-treated rats. No change was observed in the activities of GSH-Px and CAT in rats treated with gentamicin alone. Administration of the low dose of manganese (Mn 2+) produced amelioration in biochemical indices of nephrotoxicity in plasma and kidney tissue when compared to gentamicin group. The histological signs of renal proximal tubules followed a similar pattern. The high dose of Mn 2+ (20 mg kg −1) caused an opposite effect on nephrotoxicity induced by gentamicin, causing exacerbation in the tubular necrosis. The results suggest that low dose of Mn 2+ may have an antioxidant effect in kidneys of gentamicin administrated rats, but its high doses had no beneficial effect.

The Effect of Treatment with Gum Arabic on Gentamicin Nephrotoxicity in Rats: A Preliminary Study

In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80 mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.

Antimicrobial efficacy testing of moxifloxacin during the peritonitis and abscess formation stages of intra-abdominal sepsis: A controlled trial in the rat model

Background: Moxifloxacin is a fluoroquinolone with a broad range of antimicrobial activity against gram-negative and gram-positive, facultative, and obligately anaerobic bacteria, including certain quinolone-resistant organisms. Objective: Efficacy of moxifloxacin was compared with that of a combination of clindamycin + gentamicin in a rat model of intra-abdominal sepsis, with end points including mortality during the first 2 to 4 days after initiation of sepsis and the incidence of intra-abdominal abscess noted at necropsy. The bacterial challenge was prepared from cecal contents or an enhanced cecal content preparation. Methods: Groups of 20 animals were employed in the first part of the study, which used a cecal content challenge: group 1 served as saline-treated controls; group 2 received moxifloxacin 15 mg once daily; and group 3 received a combination of clindamycin 15 mg TID + gentamicin 2 mg TID. Dosing was determined for all antimicrobial agents based on peak and trough serum levels by prior testing (ie, experiments initiated before this study to determine the appropriate dosage in animals that approximates the levels obtained in humans with the antimicrobial agent under investigation), adjusting doses according to a body surface area/body weight ratio, and comparing these doses and levels with studies in humans. In the second part of the study, moxifloxacin was compared with levofloxacin (both 15 mg once daily) in an enhanced abscess model. Results: The mortality rate was 57.9% in the control group versus 0% in the moxifloxacin group and 5% in the clindamycin + gentamicin group ( P < 0.001 for both treatment groups vs control). The incidence of abscess among survivors was 100% in the control group versus 0% in the moxifloxacin group and 5.3% in the clindamycin + gentamicin group ( P < 0.001 for both vs control). In the Bacteroides fragilis—enhanced abscess model, the incidence of abscess was significantly lower in the moxifloxacin group compared with both the saline-treated controls ( 4 19 [21.1%] vs 5 5 [100%] , respectively; P = 0.003) and the levofloxacin group ( 4 19 [21.1%] vs 11 20 [55%] , respectively; P = 0.042). Conclusions: This study shows that moxifloxacin is as effective as other established therapeutic regimens in reducing the incidence of both mortality and intra-abdominal abscesses in this animal model. In addition, moxifloxacin is extremely effective in preventing abscesses caused by obligate anaerobes, even in an enhanced model for abscess development, and its efficacy is superior to that of levofloxacin.