Co-administration Of Gentamicin Research Articles

The Protective Effects of Different Types of Yemeni Honey on Hepatorenal Toxicity Induced by Gentamicin on Guinea Pigs

Aim: This study aimed to investigate the antioxidant properties of different types of Yemeni honey in reducing hepatotoxicity and nephrotoxicity caused by gentamicin in the female guinea pigs. Method and Results: The administration of Osaimi sider honey, Athel honey, Dam Al-Akhawain honey, Salam honey (5 mg/kg orally), Gentamicin (80 mg/kg i.p.), gentamicin+Osaimi sider honey, gentamicin+ Athel honey, gentamicin+ Dam Al-Akhawain honey, and gentamicin+ Salam honey for 7days caused a significant increase in the levels of AST and ALT, and also caused a significant decrease in the levels of total protein and albumin in gentamicin treated groups together with significant elevation in levels of urea and no significant increase in the level of creatinine. However, co-administration of gentamicin with different types of Yemeni honey used in this study ameliorated the harmful effects of gentamicin in most of the tested parameters. Different types of Yemeni honey used in this study have a protective effect on the histological changes of liver and kidney tissues induced either by gentamicin administration. Conclusion: The present study concluded that the use of antioxidants (Yemeni Honey) showed a highly significant protective effect on the functions and tissue of the liver and kidney when they were used as co-treatment. The effects of honey that were found in our experiment are due to the presence of many antioxidant compounds such as flavonoids, ascorbic acid, tocopherols, catalase, and phenolic compounds, that work together to provide a synergistic antioxidant effect, scavenging and eliminating free radicals. But the protective effect of the treatment with sider honey and Dam Al-Akhawain honey had a greater protective effect on the liver and the treatment with Dam Al-Akhawain honey and Athel honey had a greater protective effect on the kidney which was almost similar to the control.

Sex Difference in Gentamicin-induced Nephrotoxicity: Influence of L-arginine in Rat Model.

Background:L-arginine is an important precursor for the formation of nitric oxide (NO). According to previous studies, NO function is related to gender. Likewise, chronic renal diseases have lower prevalence in female. Gentamicin (GM) is an aminoglycoside antibiotic. According to some studies, males are more sensitive to GM renal nephrotoxicity. This study attempts to find protective effects of L-arginine on GM nephrotoxicity in male and female rats.Methods:Male and female rats were divided into eight groups: Rats were randomly assigned to 8 groups each including both male and female rats. The first and second groups received vehicle (saline), the third and fourth groups received gentamicin (80 mg/kg), the fifth and sixth groups received L-arginine (150 mg/kg), and finally, seventh and eighth groups received gentamicin+ L- arginine. Next, 9 days after administering drugs, blood samples were collected from the heart. After making sacrifices, the level of blood urea, creatinine (Cr), nitrite, and malondialdehyde (MDA) was measured in serums. Likewise, nitrite and MDA were measured in the homogenized kidney tissue.Results:GM significantly increased serum level of urea and Cr in male and female rats (P < 0.05). However, co-administration of GM + L-arginine significantly did not decrease urea and Cr level in male rats, whereas, in female rats, they significantly reduced (P < 0.05). In response to GM, renal MDA level increased in male and female rats (P < 0.05), and in the presence of GM + L-arginine, the level of MDA significantly decreased in both genders (P < 0.05).Conclusions:L-arginine demonstrated some protective effects in female rats but did not protect against GM nephrotoxicity in male rats for unknown reasons, probably related to the effects of sex hormones which needs further studies to be confirmed.

Topographic and quantitative evaluation of gentamicin-induced damage to peripheral innervation of mouse cochleae

Ototoxicity induced by aminoglycoside antibiotics appears to occur both in hair cells (HCs) and the cochlear nerves that innervate them. Although HC loss can be easily quantified, neuronal lesions are difficult to quantify because two types of afferent dendrites and two types of efferent axons are tangled beneath the hair cells. In the present study, ototoxicity was induced by gentamicin in combination with the diuretic agent furosemide. Neuronal lesions were quantified in cochlear whole-mount preparations combined with microsections across the habenular perforate (HP) openings to achieve a clear picture of the topographic relationship between neuronal damage and HC loss. Multiple immunostaining methods were employed to differentiate the two types of afferent dendrites and two types of efferent axons. The results show that co-administration of gentamicin and furosemide resulted in a typical dynamic pattern of HC loss that spread from the basal turn to the outer hair cells to the apex and inner hair cells, depending on the dose and survival time after drug administration. Lesions of the innervation appeared to occur at two stages. At the early stage (2–4 days), the loss of labeling of the two types of afferent dendrites was more obvious than the loss of labeled efferent axons. At the late stage (2–4 weeks), the loss of labeled efferent axons was more rapid. In the high-dose gentamicin group, the loss of outer HCs was congruent with afferent dendrite loss at the early stage and efferent axon loss at the late stage. In the low-dose gentamicin group, the loss of labeling for cochlear innervation was more severe and widespread. Thus, we hypothesize that the gentamicin-induced damage to cochlear innervation occurs independently of hair cell loss.

Histopathological study of the combination of metformin and garlic juice for the attenuation of gentamicin renal toxicity in rats.

Introduction: Tubular toxicity is one of the most important side effects of aminoglycoside antibiotics, especially gentamicin.Objectives: We histopathologically studied the effect of garlic extract and metformin co-administration, in attenuation of genetamicin induced tubular toxicity in rats. Materials and Methods: In this study seventy rats were divided into seven equal groups and except group 1 (control) were injected 100 mg/kg/day gentamicin (GM) intraperitoneally (i.p.) for 10 days. Other than GM, group III received 20 mg/kg garlic (i.p.), group IV metformin (MF) (100 mg/kg, orally), group V a combination of MF with garlic juice (100 and 20 mg/kg/day, respectively) and group VI a combination of MF and garlic juice (50 and 10 mg/kg/day, respectively) for following 10 days. Group VII received a combination of MF and garlic juice (100 and 20 mg/kg, respectively) along with GM. Animals were sacrificed on the 20th day of the experiment and the kidneys were removed for histological examinations. Results: GM induced nephrotoxicity and garlic or MF alone and a combination of both with high doses (not low doses) significantly abolished the kidney tubular injury induced by GM. In addition, co-administration of GM, MF and garlic (group 7) prevented the GM- induced tissue damage more than the groups in which MF and garlic were injected 10 days post GM administration. Conclusion: Garlic extract and Metformin, alone or in a combination, might be safely used to ameliorate GM induced tubular toxicity.

Cochlear Cell Death Induced Via Cisplatin or Gentamycin in Combination with Furosemide in Rodents

Ototoxic models of animal represent an elemental tool in basic otological research. In the present study, using guinea pigs we compared cochlear lesions mediated via cisplatin applied in terms of two regimens: consecutive application alone and in combination with furosemide. The influences of furosemide alone were also assessed; it was observed to result in temporary hearing loss and reversible damage to the stria vascularis. Consecutive administration of cisplatin alone tended to be disadvantageous because it bred progressive body weight loss and higher mortality compared with the combined regimen, which utilized a smaller cisplatin dose. The combined regimen brought about remarkable hair cell loss without corresponding lesion of spiral ganglion neurons. This difference suggests that the co-administered regimen did not mimic the damage to cochlear neuronal innervation caused by clinical application of cisplatin. In the meantime, we spread this method to the ototoxic model build in mice. Coadministration of gentamicin and furosemide caused marked hair cell loss as well as less mortality compared with consecutive application of gentamicin in mice. Due to different pharmacokinetics between cisplatin in guinea pigs and gentamicin in mice, the injection regimens of co-administration of furosemide - cisplatin in guinea pigs and gentamicin – furosemide in mice were varied. Overall, the methods of co-administration of cisplatin/gentacimin and furosemide in rodents facilitate ototoxic model build.

Prevention of hepatic and renal toxicity with bradykinin potentiating factor (BPF) isolated from Egyptian scorpion venom (Buthus occitanus) in gentamicin treated rats

The present investigation report the effect of a bradykinin-potentiating factor (BPF) on gentamicin-induced oxidative stress in rat liver and kidney. BPF is a peptide fraction isolated from the venom of the Egyptian scorpion (Buthus occitanus) has been demonstrated to have antioxidant, free radical scavenger and anti-inflammatory effects. Thirty male Rattus norvegicus (130–150g) were included and divided into three equal groups as follows: Group I (control), group II was (ip) injected with gentamicin alone (80mg/kg/day) for 15days, group III was given (ip) injection of BPF (1mg/kg/day) one hour prior to gentamicin treatment for 15days with the same dose of gentamicin as group II. Both organs were subjected to histopathological analysis with the light microscope. The activities of alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphatase (ALP) in serum were measured as indicators of the liver function. As parameters of the kidney function, creatinine, uric acid and urea concentrations were determined. Also, malondialdehyde (MDA), reduced glutathione (GSH), super oxide dismutase (SOD) and catalase (CAT) were determined in both tissues. Gentamicin caused a significant decrease or inhibition in the activities of GSH, SOD, and CAT, with significant increase in the level of MDA, ALT, AST, ALP, as well as creatinine, uric acid and urea concentrations in versus to control groups in both liver and kidney. Co-administration of gentamicin and BPF significantly increased the activity of GSH, SOD, and CAT, with significant decrease in the level of MDA and maintained serum (ALT); (AST); (ALP), creatinine, uric acid and urea concentrations as the same level as control group. Moreover, administration of gentamicin resulted in damage to liver and kidney structures. Administration of BPF before gentamicin exposure prevented severe alterations of biochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with BPF significantly attenuated the physiological and histopathological alterations induced by gentamicin. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs dysfunctions and diseases.

Erythropoietin ameliorates genetamicin-induced renal toxicity: A biochemical and histopathological study

Investigations have attempted to modify the outcome of tubular injury by either ameliorating renal tubular damage or promoting tubular regeneration in the case of acute tubular necrosis. We investigated the protective effect of Eprex an erythropoietin analogue on tubular injury induced by gentamicin (GM). Forty male Wistar rats were randomly divided into four groups. In group 1,rats were served as a sham group. In group 2, rats were injected intraperitoneally with 100 mg/kg of GM for 10 consecutive days (positive control group) and then were sacrificed. In group 3, rats received GM for 10 days then Eprex 100U/kg was injected intraperitoneally for the next 10 days and then they were sacrificed at the day 20th. In group 4 rats were injected a combination of GM (80 mg/kg) and Eprex 100U/kg intraperitoneally for 10 days and then were sacrificed. The results indicated that, Eprex prevented the increase in serum creatinine (Cr) and blood urea nitrogen (BUN). The effect of Eprex on damage score, showed that co-administration of GM and Eprex (group 3 and 4) reduced the kidney tissue damage compared to positive control group (P<0.05). This result indicat that Eprex potentially can reduce or prevent the kidney tissue damage. Ameliorative effect of Eprex when the drug was given in combination with GM and also when the drug was applied after GM-induced tubular damage, revealed the renoprotective potency of Eprex. Eprex is a promising drug to prevent or attenuate tubular damage induced by GM or other nephrotoxic agents which act through the same mechanisms as gentamicin.

Interaction between gentamicin and mycophenolate mofetil in experimentally induced pyelonephritis

Acute pyelonephritis (APN) is an inflammatory disease that leads to kidney malfunction. The objective of this investigation was to evaluate the impact of gentamicin (GEN) and ceftriaxone (CEF) alone and in combination with mycophenolate mofetil (MMF) on experimentally induced APN. Forty two Wistar male rats were assigned into seven groups +APN, APN +GEN, APN+CEF, APN+MMF, APN+GEN+MMF and APN+CEF+MMF. APN was induced by injecting E. coli in the left kidney. The control and +APN groups were treated with normal saline while the other APN groups received GEN, CEF, or MMF alone and/or in combination for 2 weeks. The elevated total white blood cells count and increased level of creatinine and blood urea nitrogen (BUN) in +APN groups returned to normal levels following 14 days treatment with GEN and CEF. Co-administration of GEN with MMF could not recover the APN-induced changes and resulted in a significant (P < 0.05) elevation of creatinine and BUN levels. Histopathological studies supported the biochemical findings as GEN and CEF alone could partly restore the APN-induced degeneration and leukocytic infiltration; however, the combination therapy of GEN plus MMF failed to reduce the APN-induced damages. The antibacterial susceptibility test demonstrated that the strain of E. coli used in this study was susceptible to GEN and CEF and the combination therapy did not change the antibacterial potency. These findings suggest that co-administration of GEN with MMF in APN may enhance kidney damage and the adverse effects of combination therapeutic regimen could be related partly to incompatibility of these compounds.

Effect of methionine on hepatotoxicity due to co-administration of gentamicin and indomethacin in rats

Synchronous administration of gentamicin and indomethacin is, sometimes, a necessity. However, the effect of this treatment on the liver and the possible effect of methionine on their hepatotoxicity have not been studied well. This study was performed on 42 male Sprague Dawley rats to elucidate the effect of combined treatment with gentamicin and indomethacin and the potential effect of methionine on their hepatotoxicity. Rats were divided into six equal groups randomly and were injected with normal saline, gentamicin, indomethacin, gentamicin and indomethacin, methionine, and a combination of three above-mentioned treatments for 14 days. Twenty-four hours after the last injection, blood samples were taken for measuring AST and ALT. Histopathologic and biochemical evaluations have shown severe hyperemia in the indomethacin group but no significant changes in AST or ALT. Gentamicin-administered rats have shown mild hyperemia, capillarization of sinusoids, deformed and acidophilic hepatocytes, and apoptosis and infiltration of mononuclear cells in the parenchyma and portal area. These changes were associated with elevated levels of AST and ALT. Co-administration of gentamicin and indomethacin has resulted in the development of various lesions in liver structure and enhanced concentrations of AST and ALT, while administration of methionine with the two other agents ameliorated these changes as evidenced by a mild hyperemia observed in hepatic tissue and no significant changes in AST and ALT. Methionine-treated rats, as rats injected by normal saline, have shown no pathologic lesion and no liver enzyme activity augmentation. The obtained results revealed that gentamicin may aggravate indomethacin hepatotoxicity, and methionine managed to ameliorate this effect.

Mechanisms of rapid sensory hair-cell death following co-administration of gentamicin and ethacrynic acid

Concurrent administration of a high dose of gentamicin (GM; 125 mg/kg IM) and ethacrynic acid (EA; 40 mg/kg IV) results in rapid destruction of virtually all cochlear hair cells; however, the cell death signaling pathways underlying this rapid form of hair-cell degeneration are unclear. To elucidate the mechanisms underlying GM/EA-mediated cell death, several key cell death markers were assessed in the chinchilla cochlea during the early stages of degeneration. In the middle and basal turns of the cochlea, massive hair-cell loss including destruction of the stereocilia and cuticular plate occurred 12 h after GM/EA treatment. Condensation and fragmentation of outer hair-cell nuclei, morphological features of apoptosis, were first observed 5–6 h post-treatment in the basal turn of the cochlea. Metabolic function, reflected by succinate dehydrogenase histochemistry and mitochondrial staining, decreased significantly in the basal turn 4 h following GM/EA treatment; these early changes were accompanied by the release of cytochrome c from the mitochondria into the cytosol and intense expression of initiator caspase-9 and effector caspase-3. GM/EA failed to induce expression of extrinsic initiator caspase-8. These results suggest that the rapid loss of hair cells following GM/EA treatment involves cell death pathways mediated by mitochondrial dysfunction leading to the release of cytochrome c, activation of initiator caspase-9 and effector caspase-3.

Poly-l-aspartic Acid Enhances and Prolongs Gentamicin-mediated Suppression of the CFTR-G542X Mutation in a Cystic Fibrosis Mouse Model

Aminoglycosides such as gentamicin have the ability to suppress translation termination at premature stop mutations, leading to a partial restoration of protein expression and function. This observation led to studies showing that this approach may provide a viable treatment for patients with genetic diseases such as cystic fibrosis that are caused by premature stop mutations. Although aminoglycoside treatment is sometimes associated with harmful side effects, several studies have shown that the co-administration of polyanions such as poly-L-aspartic acid (PAA) can both reduce toxicity and increase the intracellular aminoglycoside concentration. In the current study we examined how the co-administration of gentamicin with PAA influenced the readthrough of premature stop codons in cultured cells and a cystic fibrosis mouse model. Using a dual luciferase readthrough reporter system in cultured cells, we found that the co-administration of gentamicin with PAA increased readthrough 20-40% relative to cells treated with the same concentration of gentamicin alone. Using a Cftr-/- hCFTR-G542X mouse model, we found that PAA also increased the in vivo nonsense suppression induced by gentamicin. Following the withdrawal of gentamicin, PAA significantly prolonged the time interval during which readthrough could be detected, as shown by short circuit current measurements and immunofluorescence. Because the use of gentamicin to suppress disease-causing nonsense mutations will require their long term administration, the ability of PAA to reduce toxicity and increase both the level and duration of readthrough has important implications for this promising therapeutic approach.

Ethanolic extract from Hemidesmus indicus (Linn) displays otoprotectant activities on organotypic cultures without interfering on gentamicin uptake

The ethanolic extract from Hemidesmus indicus (Linn) (Apocynaceae) ( Hie) was studied for its otoprotective effects in ex vivo rat organotypic model of gentamicin (GM) toxicity. In organ of Corti organotypic cultures (OC), GM can induce a fast dose-dependent apoptosis of hair cells (HC), both external and internal. We found that, after coadministration of GM and Hie to organotypic cultures, the extract was able to significantly counteract this toxic effect on HC, at the concentration of 25 and 50 μg/ml. Interestingly, at these concentrations the extract was present in the cell medium at a concentration 1.6- and 3.3-fold lower than GM, suggesting its otoprotective activity could not merely due to an aspecific inhibition of GM entry. To support this hypothesis, we evaluated the amount of GM present in organotypic cultures after the coadministration of 1.5 mg/ml GM and Hie, and found no significant reduction of GM uptake in the presence of 100 μg/ml Hie. These data suggest the otoprotective action of Hie derives from specific inhibition of the apoptotic routine induced by GM treatment.

Serum Bactericidal Activities of High-Dose Daptomycin with and without Coadministration of Gentamicin against Isolates of Staphylococcus aureus and Enterococcus species

The purpose of this experiment was to evaluate the pharmacokinetics and serum bactericidal titers (SBTs) of daptomycin alone and in combination with gentamicin against strains of Staphylococcus aureus and enterococci to determine if there might be any benefit to the addition of the aminoglycoside. A multiple-dose, randomized crossover study was performed in 11 healthy volunteers to evaluate the steady-state pharmacokinetic profile of 6 mg/kg of body weight daptomycin once daily with or without 1 mg/kg gentamicin every 8 h. SBTs were determined against clinical isolates of nosocomial (MRSA 494) and community-acquired (CA-MRSA 44) methicillin-resistant S. aureus, vancomycin-susceptible Enterococcus faecalis (VSEF 49452), vancomycin-resistant Enterococcus faecium (VREF 80), and quality control strains of methicillin-susceptible S. aureus (ATCC 29213) and vancomycin-susceptible E. faecalis (ATCC 29212). Enhancement of bactericidal activity was evaluated by calculating and comparing the areas under the bactericidal curve (AUBC) for each dosing regimen against each isolate. The area under the concentration-time curve from 0 to 24 h and clearance for daptomycin alone were 645 +/- 91 microg.h/ml and 9.47 +/- 1.4 mg/h/kg, respectively, compared with 642 +/- 69 microg.h/ml and 9.45 +/- 1.0 mg/h/kg for daptomycin plus gentamicin. Daptomycin alone displayed sustained bactericidal activity against five of the six isolates over the entire 24-h dosing interval; bactericidal activity was maintained for 8 h against VREF 80. Mean AUBCs for daptomycin alone ranged from 935 to 1,263 and 36 to 238 against staphylococcal and enterococcal isolates, respectively, compared with 902 to 972 and 34 to 213 against staphylococci and enterococci when coadministered with gentamicin. The results of this study suggest that the addition of gentamicin does not alter the pharmacokinetic profile or enhance the bactericidal activity of daptomycin against staphylococcal or enterococcal isolates.

Time course of efferent fiber and spiral ganglion cell degeneration following complete hair cell loss in the chinchilla

Ethacrynic acid (EA) is known to interact with aminoglycoside antibiotics such as gentamicin (GM). In the chinchilla, co-administration of GM and EA can produce hair cell lesions ranging from a small loss of outer hair cells (OHCs) in the base of the cochlea to complete destruction of all hair cells, depending on dosing parameters. Although hair cell loss has been characterized, little is known about the fate of efferent fibers or spiral ganglion neurons (SGNs) in this model. To study the time course of efferent fiber and SGN loss, chinchillas were injected with GM (125 mg/kg IM) followed immediately by EA (40 mg/kg IV). Estimates of efferent fiber loss and density changes were made after 3 days or 1, 2, 3, or 4 weeks of survival. Estimates of SGN loss and density changes were made after 15 days or 1, 2, 4, or 6 months of survival. Cochlear function was rapidly abolished and all cochlear hair cells were missing within 24 h after treatment. Inner hair cells (IHCs) in the middle turn of the cochlea died earlier than cells in the apex or base, and OHCs in Rows 1 and 2 died earlier than OHCs in Row 3. Degeneration of efferent nerve fibers began 3–7 days post-injection, versus 15–30 days for SGNs, and the loss of efferent fibers was essentially complete within 1 month, versus 2–4 months for SGNs. The rapid time course of efferent fiber and SGN loss in the chinchilla may make it a practical model for studying mechanisms of neural loss and survival in the mammalian inner ear.

Supplemental iron exacerbates aminoglycoside ototoxicity in vivo

There is increasing evidence to suggest that free radical generation is central to a variety of pathological processes, including drug toxicity. Studies demonstrating the ability of gentamicin to facilitate the generation of radical species suggest that this process plays an important role in aminoglycoside-induced ototoxicity. Because transition metals, particularly iron, play an important role in the production of free radicals and the generation of reactive oxygen species, we sought to determine whether gentamicin-induced ototoxicity is exacerbated by increases in serum iron levels. To this end, we assessed the effects of supplemental iron administration (2 mg/kg/day and 6 mg/kg/day) on changes in auditory function induced by co-administration of gentamicin (100 mg/kg/day for 30 days). Experiments were carried out on pigmented guinea pigs initially weighing 250–300 g. Changes in cochlear function were characterized as shifts in compound action potential (CAP) thresholds, estimated every third day throughout the treatment period by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results showed that animals receiving iron in combination with gentamicin demonstrated a more rapid and profound elevation in CAP thresholds compared with animals receiving gentamicin alone. This effect occurred in a dose-dependant manner. Animals receiving supplemental iron alone maintained normal CAP thresholds throughout the treatment period. There was no statistically significant difference in serum gentamicin levels between groups receiving gentamicin alone or gentamicin plus iron. These results provide further evidence of the recently reported intrinsic role of iron in aminoglycoside ototoxicity, and highlight a potential risk of aminoglycoside administration in patients with elevated serum iron.

Hormone-dependent enhancement in binding of oto- and nephrotoxic aminoglycoside antibiotics.

Intraperitoneal administration of gentamicin (40 mg/ml) to the guinea pig is known to cause damage of the tissue of the kidneys and auditory organs. By indirect immunohistochemical staining with anti-gentamicin antiserum, those cells with high affinity to gentamicin in the auditory organs and kidneys were the hair cells in the cochlea and the epithelial cells in the renal tubules. The concentrations of gentamicin in the serum and perilymph of the guinea pig with tissue damage were found to be 2 and 0.6 mg/ml at the maximal levels, respectively, by high performance liquid chromatography. The same concentration of gentamicin, 2 mg/ml, also inhibited cell growth and resulted in cell damage of the renal tubule-derived cell lines, JTC-12 and MDCK. Among the antibiotics examined, i.e. streptomycin, gentamicin, fradiomycin and kanamycin, gentamicin showed the strongest effect on growth inhibition of the renal tubule-derived cells, when these cells were cultured in a medium with 5% fetal calf serum. Although the number of JTC-12 cells in the medium without fetal calf serum remained the same for a week, even with the addition of either gentamicin (0.5 mg/ml) or parathyroid hormone (2 mM) the coadministration of gentamicin and parathyroid hormone resulted in a loss of cells due to cellular death, and the amount of gentamicin bound onto the cells cultured with gentamicin plus parathyroid hormone was significantly higher than that with gentamicin alone. These results indicate that the expression of the receptor for gentamicin on the cell surface is greatly enhanced by hormonal stimulation.

Combined activity of metronidazole and gentamicin on Bacteroides fragilis in vivo and in vitro.

A mixed aerobic/anaerobic infection in mice was established by co-injecting Bacteroides fragilis and Escherichia coli into a thigh muscle. Metronidazole administration 6 h after this inoculation resulted in a dose-dependent decrease of Bact. fragilis at 18 h after drug administration. Co-administration of gentamicin with metronidazole resulted in a significant decrease of the numbers of E. coli but did not markedly influence the effect of metronidazole on Bact. fragilis.