A case report of acute renal failure caused by anti-brucellosis treatment.

RATIONALE: Rifampicin, as a main chemotherapy drug treating brucellosis, is widely used in clinical practice. Rifampicin-associated ARF is not rare, especially in those rifampicin re-exposure patients. However, this was rare complication of severe renal involvement due to multiple factors including rifampicin, nephrotoxic gentamicin, and contrast medium, and few studies have reported it. PATIENT CONCERNS: A 59-year-old male presented to our hospital with acute renal failure (ARF) caused by anti-brucellosis treatment with rifampicin (675 mg/day), gentamicin (320 mg/day), and doxycycline (200 mg/day). He had a contrast-enhanced CT of the upper abdomen before the onset of. After stopping rifampicin and undergoing integrated therapy, the patient's renal function gradually recovered. DIAGNOSES: Considering that the patient had a history of using rifampicin for pulmonary tuberculosis in the past, based on the examination results, the patient was diagnosed with rifampicin-associated ARF. INTERVENTIONS: Symptomatic treatment such as hemodialysis, and anti-brucella treatment with doxycycline and moxifloxacin were given. OUTCOMES: The patient had significant anuric and polyuric periods and acute tubular necrosis is considered. After treatment, his renal function and urine volume returned to normal, and Brucella melitensis was not isolated from blood cultures. LESSONS: The case reveals that severe renal involvement due to multiple factors including rifampicin, nephrotoxic gentamicin, and contrast medium. Misdiagnosis and mistreatment can deteriorate the patient's condition. Renal function should be closely monitored in the susceptible patients. Early recognition can provide appropriate therapy to patients. If unexplained renal failure during the use of rifampicin, especially in those rifampicin re-exposure patients, rifampicin-associated ARF should be considered.

The Nephroprotective Effect of Zizyphus lotus L. (Desf.) Fruits in a Gentamicin-Induced Acute Kidney Injury Model in Rats: A Biochemical and Histopathological Investigation.

Zizyphus lotus L. (Desf.) (Z. lotus) is a medicinal plant largely distributed all over the Mediterranean basin and is traditionally used by Moroccan people to treat many illnesses, including kidney failure. The nephrotoxicity of gentamicin (GM) has been well documented in humans and animals, although the preventive strategies against it remain to be studied. In this investigation, we explore whether the extract of Zizyphus lotus L. (Desf.) Fruit (ZLF) exhibits a protective effect against renal damage produced by GM. Indeed, twenty-four Wistar rats were separated into four equal groups of six each (♂/♀ = 1). The control group was treated orally with distilled water (10 mL/kg); the GM treated group received distilled water (10 mL/kg) and an intraperitoneal injection of GM (80 mg/kg) 3 h after; and the treated groups received ZLF extract orally at the doses 200 or 400 mg/kg and injected intraperitoneally with the GM. All treatments were given daily for 14 days. At the end of the experiment, the biochemical parameters and the histological observation related the kidney function was explored. ZLF treatment has significantly attenuated the nephrotoxicity induced by the GM. This effect was indicated by its capacity to decrease significantly the serum creatinine, uric acid, urea, alkaline phosphatase, gamma-glutamyl-transpeptidase, albumin, calcium, sodium amounts, water intake, urinary volume, and relative kidney weight. In addition, this effect was also shown by the increase in the creatinine clearance, urinary creatinine, uric acid, and urea levels, weight gain, compared to the rats treated only with the GM. The hemostasis of oxidants/antioxidants has been significantly improved with the treatment of ZLF extract, which was shown by a significant reduction in malondialdehydes levels. Histopathological analysis of renal tissue was correlated with biochemical observation. Chemical analysis by HPLC-DAD showed that the aqueous extract of ZLF is rich in phenolic compounds such as 3-hydroxycinnamic acid, catechin, ferulic acid, gallic acid, hydroxytyrosol, naringenin, p- coumaric Acid, quercetin, rutin, and vanillic acid. In conclusion, ZLF extract improved the nephrotoxicity induced by GM, through the improvement of the biochemical and histological parameters and thus validates its ethnomedicinal use.

Identification of a series of hair-cell MET channel blockers that protect against aminoglycoside-induced ototoxicity.

To identify small molecules that shield mammalian sensory hair cells from the ototoxic side effects of aminoglycoside antibiotics, 10,240 compounds were initially screened in zebrafish larvae, selecting for those that protected lateral-line hair cells against neomycin and gentamicin. When the 64 hits from this screen were retested in mouse cochlear cultures, 8 protected outer hair cells (OHCs) from gentamicin in vitro without causing hair-bundle damage. These 8 hits shared structural features and blocked, to varying degrees, the OHC's mechano-electrical transducer (MET) channel, a route of aminoglycoside entry into hair cells. Further characterization of one of the strongest MET channel blockers, UoS-7692, revealed it additionally protected against kanamycin and tobramycin and did not abrogate the bactericidal activity of gentamicin. UoS-7692 behaved, like the aminoglycosides, as a permeant blocker of the MET channel; significantly reduced gentamicin-Texas red loading into OHCs; and preserved lateral-line function in neomycin-treated zebrafish. Transtympanic injection of UoS-7692 protected mouse OHCs from furosemide/kanamycin exposure in vivo and partially preserved hearing. The results confirmed the hair-cell MET channel as a viable target for the identification of compounds that protect the cochlea from aminoglycosides and provide a series of hit compounds that will inform the design of future otoprotectants.

Nephroprotective effects of Datura metel extract in gentamicin induced mice model: biochemical and histological evidences.

Datura metel is traditionally used as a remedy for renal toxicity. However, the nephroprotection has not been scientifically validated yet. To evaluate the nephroprotective like effect of methanolic extract of D. metel in gentamicin induced mice model, mice of either sex were divided into groups. One group received normal saline as negative control. The 2nd group received gentamicin 100mg/kg for 8 days as positive control, 3rd group received 50mg/kg silymarin as standard, while the reaming groups received 100, 200 and 300 mg/kg of MEDM and gentamicin 100mg/kg, for 8 days. The blood and urine samples were collected on 9th day, animals were then dissected and whole kidneys were removed and preserved in formalin for later histological examinations. The level of serum creatinine, blood urea nitrogen, urine creatinine and urine urea were significantly (P<0.05) elevated and the renal MDA level was also elevated significantly (P<0.05) by gentamicin in mice. After the treatment of test animals with MEDM, the elevated level of serum and urine biomarkers by gentamicin were reversed by MEDM. The nephroprotective effect was found in dose dependent manner. As the MEDM significantly protected the nephrotoxicity via its antioxidant effect. The findings of our study thus proved the scientific background for the nephroprotective effect of MEDM.

Nephroprotective Effect of Moringa Oleifera Seed Oil on Gentamicin-Induced Nephrotoxicity in Rats: Biochemical Evaluation of Antioxidant, Anti-inflammatory, and Antiapoptotic Pathways.

Objective: Gentamicin is an efficacious aminoglycoside antibiotic widely used to treat life-threatening Gram-negative bacteria infections. However, its specific non-targeted induction of nephrotoxicity is a worrying clinical challenge. The study explored the nephroprotective effect of Moringa oleifera seed oil (MOO) against gentamicin-induced oxidative nephrotoxicity, pro-inflammation, and apoptosis in male Wistar rats.Method: Twenty-four rats divided into 4 groups (n = 6) were administered MOO (5 ml/kg) for 16 days and/or gentamicin (100 mg/kg bw/d, ip) injected from day 11 to day 16. The renal antioxidant enzyme activities reduced glutathione, lipid peroxidation, and serum renal markers. Urea and creatinine levels were estimated. The renal expression of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) were determined. Renal levels of inducible nitric oxide synthase (iNOS), nuclear factor-ĸB (NF-ĸB), and caspase-3 were determined to detect possible mechanism of inflammation and apoptosis with histology.Results: MOO prominently reduced serum creatinine and urea levels with amelioration of histopathological abrasions induced by gentamicin (GM). It significantly depressed oxidative stress through lowering of renal malondialdehyde (MDA) and elevation of renal superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and reduced glutathione (GSH) level. MOO restored renal content of IL-1ß, IL-6, TNF-α, and NO, coupled with the mechanistic downregulation of NF-ĸB, iNOS, and caspase-3 activities. The histopathological alterations were ameliorated by MOO.Conclusions: MOO possesses marked nephroprotective effect against GM-induced renal damage via modulating oxidative stress, inflammation, and apoptosis in Wistar rats.

Enhanced mitochondrial membrane potential and ATP synthesis by photobiomodulation increases viability of the auditory cell line after gentamicin-induced intrinsic apoptosis.

Photobiomodulation (PBM) has been suggested to have a therapeutic effect on irreversible hearing loss induced by aminoglycosides, including gentamicin (GM). However, its intracellular mechanism(s) in GM-induced ototoxicity remain poorly understood. In the present study, we investigated the effect of PBM in GM-induced ototoxicity in auditory cells. We tried to characterize the downstream process by PBM, and the process that triggered the increased cell viability of auditory cells. As a result, the effects of PBM against GM-induced ototoxicity by increasing ATP levels and mitochondrial membrane potential was confirmed. These results suggest a theory to explain the therapeutic effects and support the use of PBM for aminoglycoside-induced hearing loss.

The protective role of estrogen and its receptors in gentamicin-induced acute kidney injury in rats.

AIM: Investigating the impact of 17ß-Estradiol/estrogen receptors in gentamicin-induced nephrotoxicity. MAIN METHODS: Three weeks post-ovariectomy or sham surgery for the Wistar albino female rats, thirty sham rats were randomly grouped (n = 6), received either vehicle or gentamicin; the estrogen receptors down regulator (fulvestrant); gentamicin plus fulvestrant; gentamicin plus the phytoestrogen (genistein). Forty-eight ovariectomized rats were randomly grouped (n = 6), treated with either vehicle or gentamicin; fulvestrant; gentamicin plus fulvestrant; genistein; gentamicin plus genistein; estradiol benzoate; gentamicin plus estradiol benzoate. Just post-treatment termination, the traditional kidney injury biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers (serum Kidney injury molecule -1, cystatin C, lactate dehydrogenase and, gamma-glutamyl transferase) were determined. Bovine serum albumin labeled with fluorescence isothiocyanate assessed megalin expression/endocytic functionality in the proximal tubules epithelial cells (PTECs). The immunohistochemical investigation for the same-sectioned slides of PTECs assessed the correlation between estrogen receptors α and megalin receptors expression. Histopathological examination of PTECs and subjective scoring system graded the damage markers. KEY FINDINGS: Estrogen receptor α expression was markedly dimensioned post-ovariectomy, co-localized and inversely correlated to megalin expression. Serum levels of the novel biomarkers were directly proportional to megalin expression in the PTECs and inversely correlated with estrogen receptor α expression. The injury was exaggerated in ovariectomized and intact rats received fulvestrant. Supplementation with estrogen or genistein ameliorated this injury. SIGNIFICANCE: Estrogen/estrogen receptors have a protective impact on gentamicin-induced acute kidney injury. Estrogen receptors antagonist exacerbate the injury, and oppositely, estrogens or phytoestrogens improve it.

Gentamicin as Empirical Treatment in Hemodialysis Patients: Safety, Pharmacokinetics, and Pharmacodynamics.

The aim of this study was to describe the safety profile and pharmacokinetic/pharmacodynamic parameters in end-stage renal disease patients who received gentamicin as empirical treatment in catheter-related bacteremia when they showed infection signs, regardless of the timing of the next HD. Patients received gentamicin 3 mg/kg before blood culture extraction when they showed infection signs and regardless of the timing of next hemodialysis session. Serum concentrations were collected after the gentamicin administration (peak level) and before the next HD (trough level). Toxicities and adverse drug events were registered. The main pharmacokinetic/pharmacodynamic goal for Gram-negative infections was peak:minimum inhibitory concentration (MIC) ≥10. Sixteen patients were included. Nephrotoxicity was not assessed in this population, and no ototoxicity was found. According to microbial isolation and gentamicin susceptibility, the value of peak:MIC was 5.4 ± 2.0. The administration of gentamicin in these conditions was safe. Estimated pharmacokinetic values were consistent with previous studies and appropriate according to peak:MIC goal for Gram-negative organisms with MIC ≤1 mg/L.

Protective effect of date extract on rat nephrotoxicity induced by gentamicin, clinical, histological and antioxidant evidences.

In this study, it was aimed to investigate the effect of the date extract (Phoenix dactylifera) on certain biochemical parameters and total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index in nephrotoxicity induced by gentamicin. The rats used in the study were randomly selected and divided into 4 groups, each consisting of 8 rats: control group, date extract (DE) group, gentamicin (GEN) group, gentamicin+date extract (GEN+DE) group. Blood samples and kidney tissues were taken 24 hours after eight days of trial. Urea, Creatinine, BUN, Na, Cl and K analyzes on the serum samples were carried out in auto analyzer. One of the kidney tissues was examined histopathologically. The supernatant, which was obtained by homogenizing the other kidney tissue was used in TAS and TOS analyzes. OSI was calculated using the formula. Urea, Creatinine, and BUN levels were higher in the GEN group, when compared to the other groups (p<0.001), while Na (p<0.05), Cl and K levels (p<0.001) were lower than those of the other groups. When the control group and the GEN group were compared, it was observed that the level of TAS decreased in the renal tissue and the level of TAS increased in the GEN+DE group. It was determined that TOS (p<0.01) and OSI (p<0.001) levels increased in the GEN group and renal TOS and OSI levels decreased in the GEN+DE group when compared to the GEN group. In conclusion, when the histopathological changes in kidney tissue with antioxidant and oxidant status in nephrotoxicity with gentamicin are examined, it can be said that date extract with gentamicin attenuates nephrotoxicity caused by gentamicin and date extract protects the kidney.

Nephroprotective properties of the methanol stem extract of Abrus precatorius on gentamicin-induced renal damage in rats.

Background The use of plants for the treatment and prevention of diseases in man and his animals has led to a renewed scientific interest in the use of medicinal plants for therapeutic purposes. The nephroprotective properties of methanol stem bark extract of Abrus precatorius against gentamicin-induced renal damage in rats was evaluated in this study. Methods Thirty male Wistar rats were divided into five equal groups. Group A was the negative control group while B was the positive control group which received gentamicin 100 mg/kg intra-peritoneally for 6 days. Group C were pretreated with 100 mg/kg extract for the 3 days and then concurrently with gentamicin 100 mg/kg for 3 days and group D were pretreated with 200 mg/kg extract for 3 days and then concurrently with gentamicin 100 mg/kg for 3 days. Group E received gentamicin intraperitoneally for 6 days followed by administration of 200 mg/kg of the extract for 3 days. Blood samples, kidneys and kidney homogenates were collected for haematological, biochemical, histopathological and immunohistochemical analysis. Results The results showed that no significant haematological changes were noted. The groups treated with extract exhibited significant increase in body weight gain. While group B significantly exhibited focal areas of inflammation, fatty degeneration, congestion of vessels, tubular necrosis and glomerular atrophy, the lesions were mild with the treated groups. Treated groups exhibited a dose dependent significant decrease in serum creatinine, urea, XO, NO and Myeloperoxidase, AOPP, Protein carbonyl, H2O2 generated and MDA levels when compared with group B. There were significant dose dependent improvements in SOD, GST, GSH, Protein thiol, and non-protein thiol levels in the treated groups when compared with group B. In immunohistochemistry, Group B exhibited over expression of CRP and NF-κB levels, and marked reduction in expression of Bcl-2 while the reverse was seen in the groups treated with methanol extracts of Abrus precatorius. Conclusion The methanol extract of Abrus precatorius plays a vital role against gentamicin induced renal damage by reducing levels of renal markers of oxidative stress, inflammation and apoptosis, enhancing enzymatic and non enzymatic renal antioxidant system, alongside an increase in Bcl-2 and a decrease in NF-κB and CRP expressions.

In vitro evaluation of biomarkers of nephrotoxicity through gene expression using gentamicin.

Acute renal failure is one of the most frequent effects observed after taking medicine. Such situations have been tardily discovered, given that existing methods for assessing toxicity are not predictive. In this light, the present work evaluated the effects of gentamicin, a form of nephrotoxic drug, on HK-2 and HEK-293 cells. By using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and flow cytometry, both cells demonstrated that cytotoxicity occurs in a dose-dependent manner through the processes of apoptosis and cell necrosis. Gene expression analysis showed a relative increase of expression for genes related to cell processes and classic biomarkers, such as TP53, CASP3, CASP8, CASP9, ICAM-1, EXOC3, KIM-1, and CST3. A decrease in expression for genes BCL2L1 and EGF was observed. This study, therefore, indicates that, when the methods are used together, gene expression analysis is able to evaluate the nephrotoxic potential of a substance.

Potential action of Rumex vesicarius (L.) against potassium dichromate and gentamicin induced nephrotoxicity in experimental rats.

To determine the ameliorative potential of the active fraction from different extracts of Rumex vesicarius against potassium dichromate and gentamicin induced nephrotoxicity in experimental rats and its possible mechanism of action. Both sex wistar rats were divided into 6 groups (n=6/group) were fed with a control, potassium dichromate and gentamicin supplemented with different extracts at the doses of 200 and 400mg/kg respectively. Oral administration of EERV offered a significant (p<0.01 and p<0.001) dose dependent protection against PD and GN induced nephrotoxicity. Potassium dichromate and gentamicin nephrotoxicity assessed in terms of body weight, kidney weight, creatinine, urea, uric acid, BUN, albumin and total protein. Thus the present study revealed that EERV phytochemical constituents play an important role in protection against kidney damage.

Nephrotoxic effects of Valeriana wallichii.

Aminoglycosides are the commonly used antibiotics against Gram negative bacteria. Their clinical applications are limited due to nephrotoxic side effects. Therefore, the current study was undertaken in an attempt to increase the use of these drugs without causing nephrotoxicity by exploring the nephroprotective effects of a medicinal plant with high flavonoid contents and strong antioxidant properties, namely Valeriana wallichii. A daily dose of 200mg/kg of the extract derived from V. wallichii was employed for a period of three weeks. The results obtained revealed that co-therapy of extract with gentamicin protected some changes in renal functions; however, failed to provide a complete protection as assessed by biochemical, physiological and histological parameters. It can be concluded from the current findings that V. wallichii failed to deliver protective effects against gentamicin induced renal damage in spite of strong flavonoid contents and antioxidant properties.

Brainstem auditory evoked responses in 37 dogs with otitis media before and after topical therapy.

OBJECTIVES: The objective of this study was to determine whether intra-aural administration of aqueous solutions of marbofloxacin, gentamicin, tobramycin and ticarcillin (used off-licence) was associated with changes in hearing as measured by brainstem auditory evoked responses. MATERIALS AND METHODS: Dogs diagnosed with otitis media (n=37) underwent brainstem auditory evoked response testing and then were treated for their ear disease. First, the external ear canal and middle ear were flushed with sterile saline followed by EDTA tris with 0·15% chlorhexidine. Then, a combination of aqueous antibiotic mixed with an aqueous solution of EDTA tris was instilled into the middle ear. Follow-up examinations were undertaken for each dog, and treatment was continued until there were no detected infectious organisms or inflammatory infiltrate. Brainstem auditory evoked response testing was repeated after resolution of the infection and discontinuation of therapy. RESULTS: Brainstem auditory evoked responses in dogs treated with aqueous solutions of marbofloxacin or gentamicin remained unchanged or improved after therapy of otitis media but were impaired in dogs treated with ticarcillin or tobramycin. CLINICAL SIGNIFICANCE: If off-licence use of topical antibiotics is deemed necessary in cases of otitis media, aqueous solutions of marbofloxacin and gentamicin appear to be less ototoxic than aqueous solutions of ticarcillin or tobramycin.

Treatment of peripheral vestibular dysfunction using photobiomodulation.

Gentamicin, which is still used in modern medicine, is a known vestibular toxic agent, and various degrees of balance problems have been observed after exposure to this pharmacologic agent. Photobiomodulation is a candidate therapy for vertigo due to its ability to reach deep inner ear organs such as the cochlea. Previous reports have suggested that photobiomodulation can improve hearing and cochlea function. However, few studies have examined the effect of photobiomodulation on balance dysfunction. We used a rat model to mimic human vestibulopathy resulting from gentamicin treatment and evaluated the effect of photobiomodulation on vestibular toxicity. Slow harmonic acceleration (SHA) rotating platform testing was used for functional evaluation and both qualitative and quantitative epifluorescence analyses of cupula histopathology were performed. Animals were divided into gentamicin only and gentamicin plus laser treatment groups. Laser treatment was applied to one ear, and function and histopathology were evaluated in both ears. Decreased function was observed in both ears after gentamicin treatment, demonstrated by low gain and no SHA asymmetry. Laser treatment minimized the damage resulting from gentamicin treatment as shown by SHA asymmetry and recovered gain in the treated ear. Histology results reflected the functional results, showing increased hair cell density and epifluorescence intensity in laser-treated cupulae.

Kiwifruit ameliorates gentamicin induced histological and histochemical alterations in the kidney of albino mice.

Gentamicin is an antibiotic used worldwide for treating Gram-negative bacterial infections. Gentamicin causes nephrotoxicity in up to 25% of therapeutic cases owing to increased production of free radicals. Kiwifruit are nutrient-dense fruits that have proven effective for ameliorating many pathological conditions caused by oxidative stress. We investigated the possible prophylactic and therapeutic effects of kiwifruit on the changes in renal histology and histochemistry caused by gentamicin. Intramuscular injection of mice with gentamicin for 10 consecutive days was nephrotoxic as indicated by epithelial vacuolization, glomerular atrophy and tubular necrosis. Necrotic tubule cells lost most of their polysaccharides and structural proteins. Co-administration of kiwifruit with gentamicin prevented nephrotoxic changes to a modest degree. When administered subsequent to gentamicin intoxication, kiwifruit ameliorated significantly the histological and histochemical alterations caused by gentamicin. Our findings support the use of kiwifruit in cases of acute renal injury due to gentamicin.

Ototoxicity associated with topical administration of diclofenac sodium as an otic drop: An experimental animal study.

OBJECTIVES: The aim of the study is to evaluate the ototoxicity of topical diclofenac sodium in comparison to positive and negative controls prior to the investigation of analgesic and anti-inflammatory efficacy of the agent in otic administration. METHODS: Twenty four ears of 12 guinea pigs were included in the study. Wide myringotomy was performed on all tympanic membranes under general anesthesia and auditory brainstem responses (ABR) were evaluated. The subjects were separated into four groups, two groups received diclofenac sodium at low and high doses, positive controls received gentamicin and negative controls received isotonic sodium chloride topically for 14 days and ABRs were reevaluated. RESULTS: No significant difference were observed between the pre and post-treatment click response, 1 kHz and 8 kHz response threshold levels after isotonic sodium chloride administration. All threshold levels were elevated in the positive control group. In the low and high dose diclofenac sodium groups, click response, 1 kHz and 8 kHz response threshold levels were significantly higher compared to the baseline values. Pre and post-treatment mean threshold level changes were not significantly different between the low and high dose diclofenac sodium groups. Pre and post-treatment mean threshold level changes in the gentamicin group were not significantly different from low or high dose diclofenac sodium groups. CONCLUSION: Diclofenac sodium, considered as an analgesic and anti-inflammatory otic preparation, is shown to be as ototoxic as gentamicin in chronic use which may lead to loss of hearing especially when used topically in chronic otitis cases with tympanic membrane damage.

Protective role of intratympanic nigella sativa oil against gentamicin induced hearing loss.

OBJECTIVE: Aminoglycosides, used to combat with life-threatening infections, have a substantial risk of hearing loss. Nigella sativa is an annual herbaceous plant and used for treatment of many diseases for ages. We aimed to investigate the protective role of intratympanic nigella sativa oil against gentamicin induced hearing loss in an animal model. METHODS AND MATERIALS: Twenty eight guinea pigs were randomly divided into four groups: i-control, ii- Intratympanic nigella sativa oil (IT-NSO), iii- Intraperitoneal gentamicin (IP-G) and iv- Intraperitoneal gentamicin and intratympanic nigella sativa oil (IP-G + IT-NSO). Preoperative and postoperative hearing thresholds were determined with auditory brainstem response with click and 8 kHz tone-burst stimuli. Histological analysis of the cochlea specimens were performed under light microscope. Semiquantitative grading of the histological findings was carried out and compared between the groups. RESULTS: Highest posttreatment hearing thresholds were detected in IP-G group. Posttreatment mean hearing threshold of the IP-G group with click stimulus was significantly higher than the IP-G + IT-NSO group (p = 0.004). whereas the difference was not significant with 8 kHz tone-burst stimulus (p = 0.137). Both IP-G and IP-G + IT-NSO groups had significantly higher hearing thresholds compared to control and IT-NSO groups (p > 0.05). Histological examination of the control and IT-NSO groups demonstrated normal appearance of cochlear nerve, stria vascularis and organ of Corti. IP-G group showed the most severe histological alterations including hydropic and vacuolar degenerations, hair cell damage and deformation of the basilar mambrane. Histological evidence of damage was significantly reduced in IP-G + IT-NSO group compared to IP-G group. CONCLUSION: Addition of intratympanic NSO to systemic gentamicin was demonstrated to have beneficial effects in hearing thresholds which was supported by histological findings.

The Treatment of Possible Severe Infection in Infants: An Open Randomized Safety Trial of Parenteral Benzylpenicillin and Gentamicin Versus Ceftriaxone in Infants <60 days of Age in Malawi.

BACKGROUND: The World Health Organization recommends benzylpenicillin and gentamicin as antimicrobial treatment for infants with sepsis in low-income settings, and ceftriaxone or cefotaxime as an alternative. In a meta-analysis from 13 low-income settings, Staphylococcus aureus, Klebsiella spp. and Escherichia coli accounted for 55% of infants with sepsis. In a review of bacterial meningitis, resistance to third generation cephalosporins was >50% of all isolates, and 44% of Gram-negative isolates were gentamicin resistant. However, ceftriaxone may cause neonatal jaundice, and gentamicin may cause deafness. Therefore, we compared parenteral benzylpenicillin plus gentamicin with ceftriaxone as first-line treatment, assessing outcome and adverse events. METHODS: This was an open randomized trial carried out in the Queen Elizabeth Central Hospital, Blantyre, Malawi, from 2010 to 2013. Infants <60 days of age with possible severe sepsis received either benzylpenicillin and gentamicin or ceftriaxone. Adverse events and outcomes were recorded until 6 months post discharge. RESULTS: Three-hundred forty-eight infants were included in analyses. Outcome in the benzylpenicillin and gentamicin and ceftriaxone groups was similar; deaths were 13.7% and 16.5% and sequelae were 14.5% and 11.2%, respectively. More infants in the penicillin/gentamicin group required phototherapy: 15% versus 5%, P = 0.03. Thirteen (6%) survivors had bilateral hearing loss. There was no difference between the treatment groups. By 6 months post discharge, 11 more infants had died, and 17 more children were found to have sequelae. CONCLUSIONS: Ceftriaxone and gentamicin are safe for infants in our setting. Infants should receive long-term follow-up as many poor outcomes occurred after hospital discharge.

Protective Effects of Acupuncture Against Gentamicin-Induced Ototoxicity in Rats: Possible Role of Neurotrophin-3.

BACKGROUND The aim of this study was to investigate the protective effects of acupuncture against gentamicin-induced ototoxicity and explore the possible protective role of neurotrophin-3 (NT-3). MATERIAL AND METHODS Twenty-four rats were divided randomly into 4 groups: control group, gentamicin group, neitinggong group, and tinggong group. Rats in the gentamicin, neitinggong, and tinggong groups received intraperitoneal injection of gentamicin (100 mg/kg) for 14 consecutive days. Rats in the neitinggong and tinggong groups further received acupuncture at neitinggong or tinggong acupoints once every 2 days for 20 days. Rats in the control group received intraperitoneal injection of saline. Auditory brainstem response (ABR) was tested in all rats on the day before treatment (day 0), and again on day 14 and day 20 to determine the average threshold value of ABR for each treatment group. The expression of NT-3 in the cochlear nucleus and the inferior colliculus nucleus were detected by immunohistochemical staining. RESULTS The average threshold value of ABR was significantly higher in the gentamicin group as compared with that of the control group on day 14 (P<0.05). On day 20, the average threshold values of ABR in the neitinggong and tinggong groups were significantly lower than that of the gentamicin group (P<0.05). No statistically significant differences in NT-3 expression in the cochlear nucleus were observed among the groups (P>0.05). However, the expression of NT-3 in the inferior colliculus nucleus in both the neitinggong and tinggong groups was significantly higher than that of the gentamicin group (P<0.01). CONCLUSIONS A decrease in NT-3 expression in the inferior colliculus nucleus may contribute to gentamicin-induced ototoxicity in rats. Acupuncture at neitinggong or tinggong acupoints effectively improved hearing, which was attributed partially to the rescue of NT-3 expression in the inferior colliculus nucleus. Therefore, preserving NT-3 expression in the auditory system may be a viable strategy to counteract gentamicin-induced ototoxicity.