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Background/Aim:Gentamicin is an aminoglycoside antibiotic that can cause nephrotoxicity by damaging the kidneys due to high relative blood flow. In this study, the protective and therapeutic effects of CoQ10and vitamin E on GM-induced nephrotoxicity were investigated. Methods:Fifty Wistar Albino rats were used as live material in this study, which were randomly divided into 5 groups of 10 animals. These groups, and the treatment they received, were as follows: a) control group: Physiological saline (i.p) for 8 days, b) GM group: Gentamycin 80 mg/kg/day/i.p for 8 days, c) GM+CoQ10 group: Gentamycin 80 mg/kg/day/i.p+ CoQ10 10 mg/kg/day/ i.p for 8 days, d) GM+ Vit E group: Gentamycin 80 mg/kg/day/i.p+ Vit E 250 mg/kg /day/ip administrated for 8 days, and e) GM+CoQ10+Vit E group: Gentamycin 80 mg/kg/day/ip + CoQ10 10 mg/kg/day/ip + Vitamin E 250 mg/kg /day/ip for 8 days. Following the test period, urea, creatinine, K, Na, Cl, retinol, vitamin D, and vitamin E levels of the subjects were measured in plasma, while MDA, GSH, AOPP, nitrite, nitrates, CAT, SOD, and GPx activities were measured in kidney tissues. Results:A severe nephrotoxic effect of GM administration in rats were detected as part of this study. The administration of CoQ10and vitamin E, alone or in combination, was not sufficient to repair the kidney damage at the histopathological level. However, the renal tissue enzyme levels, along with other related to oxidative stress and plasma biochemical parameter analyses, were found to have improved greatly with the administration of vitamin E. Conclusion:CoQ10and vitamin E can be suggested as supplementary agents to gentamicin treatment to prevent cell degeneration in the kidney and ensure healing

Bone infections are a serious problem to cure, as systemic administration of antibiotics is not very effective due to poor bone vascularization. Therefore, many drug delivery systems are investigated to solve this problem. One of the potential solutions is the delivery of antibiotics from poly(L-actide-co-glycolide) (PLGA) nanoparticles suspended in the gellan gum injectable hydrogel. However, the loading capacity and release kinetics of the system based on hydrophilic drugs (e.g., gentamycin) and hydrophobic polymers (e.g., PLGA) may not always be satisfying. To solve this problem, we decided to use hydrophobized gentamycin obtained by ion-pairing with dioctyl sulfosuccinate sodium salt (AOT). Herein, we present a comparison of the PLGA nanoparticles loaded with hydrophobic or hydrophilic gentamycin and suspended in the hydrogel in terms of physicochemical properties, drug loading capacity, release profiles, cytocompatibility, and antibacterial properties. The results showed that hydrophobic gentamycin may be combined in different formulations with the hydrophilic one and is superior in terms of encapsulation efficiency, drug loading, release, and antibacterial efficacy with no negative effect on the NPs morphology or hydrogel features. However, the cytocompatibility of hydrophobic gentamycin might be lower, consequently more extensive study on its biological properties should be provided to evaluate a safe dose.

Background: Sea cucumbers have number of one of a pharmacological effects counting anticancer, anticoagulant, anti-inflammatory, antioxidant, and wound healing. Biological properties and therapeutic benefits of Sea cucumbers can be connected to the presence of a wide cluster of bioactive compounds particularly triterpene glycosides (saponins). Aims: The present study aimed to explore the hepatoprotective and nephroprotective activity of Sea cucumbers-saponin (Sc-S) on gentamicin-induced hepatorenal toxicity in rats. Main methods: Eighteen male Wistar rats were divided into three groups, control, gentamycin, and gentamycin+ Sc-S. The hepatorenal toxicity model was induced by gentamycin (80 mg/kg, i.p) for 8 days. Results: The Sc-S group showed a reduction in the concentrations of urea, uric acid, creatinine, MDA and the activities of AST, ALT, and ALP. While it caused a general increase in the levels of CAT and GSH. Microscopic examination appeared a clear enhancement in liver and kidney histology of Sc-S group. Conclusion: The antioxidant activity of Sc-S is the main mechanism for the protection of the liver and kidney against gentamicin toxicity.

Background Gentamicin (GM) is a low-cost, low-resistance antibiotic commonly used to treat gram-negative bacterial diseases. Cisplatin (Csp) is a platinum-derived anti-neoplastic agent. This experiment aimed to identify the early signs of gentamicin and cisplatin-induced nephrotoxicity in rats. Thirty Wistar rats were divided into three groups of 10: a control group, which received no treatment; a gentamicin group administered by a dose of (100 mg/kg, IP) for 7 consecutive days, and a cisplatin group was administered intraperitoneal in a dose of (1.5 mg/kg body weight) repeated twice a week for 3 weeks. Results Both experimental groups exhibited increased levels of creatinine, urea, and uric acid, with the cisplatin-treated group showing higher levels than the gentamicin group. Experimental groups also exhibited significantly increased Malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) with more pronounced effects in the cisplatin-treated group. Further, both experimental groups exhibited significant up-regulation of Tumor Necrosis Factor α (TNF-α), caspase-3, and Bax and down regulation of Bcl-2. Conclusion These findings confirm the use of necrotic, apoptotic genes as early biomarkers in the detection of tubular kidney damage. Further, cisplatin was shown to have a greater nephrotoxic effect than gentamicin; therefore, its use should be constrained accordingly when co-administered with gentamicin.

Background: Urinary Tract Infection (UTI) is a common infection in children. Prompt diagnosis and appropriate treatment are very important to reduce the morbidity associated with this condition. Objective: To provide an update on the evaluation, diagnosis, and treatment of urinary tract infection in children. Methods: A PubMed search was completed in clinical queries using the key terms “urinary tract infection”, "pyelonephritis" OR "cystitis". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature and the pediatric age group. Patents were searched using the key terms “urinary tract infection” "pyelonephritis" OR "cystitis" from www.google.com/patents, http://espacenet.com, and www.freepatentsonline.com. Results: Escherichia coli accounts for 80 to 90% of UTI in children. The symptoms and signs are nonspecific throughout infancy. Unexplained fever is the most common symptom of UTI during the first two years of life. After the second year of life, symptoms and signs of pyelonephritis include fever, chills, rigor, flank pain, and costovertebral angle tenderness. Lower tract symptoms and signs include suprapubic pain, dysuria, urinary frequency, urgency, cloudy urine, malodorous urine, and suprapubic tenderness. A urinalysis and urine culture should be performed when UTI is suspected. In the work-up of children with UTI, physicians must judiciously utilize imaging studies to minimize exposure of children to radiation. While waiting for the culture results, prompt antibiotic therapy is indicated for symptomatic UTI based on clinical findings and positive urinalysis to eradicate the infection and improve clinical outcome. The choice of antibiotics should take into consideration local data on antibiotic resistance patterns. Recent patents related to the management of UTI are discussed. Conclusion: Currently, a second or third generation cephalosporin and amoxicillin-clavulanate are drugs of choice in the treatment of acute uncomplicated UTI. Parenteral antibiotic therapy is recommended for infants ≤ 2 months and any child who is toxic-looking, hemodynamically unstable, immunocompromised, unable to tolerate oral medication, or not responding to oral medication. A combination of intravenous ampicillin and intravenous/intramuscular gentamycin or a third-generation cephalosporin can be used in those situations. Routine antimicrobial prophylaxis is rarely justified, but continuous antimicrobial prophylaxis should be considered for children with frequent febrile UTI.

The biofilm-associated infections of bones are life-threatening diseases, requiring application of dedicated antibiotics in order to counteract the tissue damage and spread of microorganisms. The in vitro analyses on biofilm formation and susceptibility to antibiotics are frequently carried out using methods that do not reflect conditions at the site of infection. To evaluate the influence of nutrient accessibility on Staphylococcus aureus biofilm development in vitro, a cohesive set of analyses in three different compositional media was performed. Next, the efficacy of four antibiotics used in bone infection treatment, including gentamycin, ciprofloxacin, levofloxacin, and vancomycin, against staphylococcal biofilm, was also assessed. The results show a significant reduction in the ability of biofilm to grow in a medium containing elements occurring in the serum, which also translated into the diversified changes in the efficacy of used antibiotics, compared to the setting in which conventional media were applied. The differences indicate the need for implementation of adequate in vitro models that closely mimic the infection site. The results of the present research may be considered an essential step toward the development of in vitro analyses aiming to accurately indicate the most suitable antibiotic to be applied against biofilm-related infections of bones.

Peroxisome proliferator-activated receptor gamma (PPAR-γ) is ubiquitously expressed in testicular tissue and plays a crucial role in regulating various physiological processes. Pioglitazone (PIO) is one of the PPAR-γ agonists, having anti-oxidant and anti-inflammatory effects. Patients on gentamycin treatment may undergo serious side effects such as testicular damage. To the best of our knowledge, this was the first study to investigate the possible protective anti-inflammatory and anti-apoptotic effects of PIO on gentamycin-induced testicular damage. Fifty adult male Wistar albino rats included in the study as the control group (CTL) received normal saline; a gentamycin-induced testicular damage group (GM) received gentamycin (100 mg/kg); PIO5, PIO10, PIO20 groups received PIO at a dose of 5, 10, and 20 mg/ kg, respectively, for 21 days, and gentamycin was started at day 15 of the experiment for 6 days. The parameters of spermatozoa and histopathological alterations in the testes were significantly improved in the PIO20 group. Moreover, MDA levels, inflammatory mediators, and apoptotic Bax expression were decreased. The activity of glutathione peroxidase, catalase, total antioxidant capacity, and anti-apoptotic Bcl-2 genes expression were increased. It was concluded that PIO20 could protect against gentamycin-induced testicular damage in Wistar rats through its anti-oxidant, anti-inflammatory, and antiapoptotic effects.

Background and Objectives Locacorten Vioform (Novartis UK) is frequently prescribed for otomycosis. Its component, Clioquinol, also has anti-bacterial properties. Up to this point, its ototoxic potential has not been evaluated. Our objective aims to evaluate Locacorten Vioform’s potential ototoxicity when applied directly to the middle ear cavity. Materials and Methods We performed an experimental prospective animal study in our animal research center with 20 Hartley guinea pigs divided into 2 groups. The first group (experimental) was treated with Locacorten Vioform in one ear and with a physiologic saline solution in the other. The second group (positive control) was treated with concentrated gentamycin in one ear and physiologic saline in the other. Auditory brainstem response measurements were obtained before and after three sets of injections. Statistics were analyzed using a variance analysis with repeated measures. The histological state of cochlear outer hair cells was compared between the two groups using scanning electron microscopy. Results Average hearing loss in ears treated with Locacorten Vioform was 32.1 dB, compared with a 2.5 dB average loss in the saline-treated ears. Ears treated with gentamycin lost an average of 33.0 dB. There were clinically and statistically significant differences between the two ears of the guinea pigs in both groups (p

Background: Urinary tract infections (UTIs) is a common medical problem that affects all age groups but with significant morbidity in females because of the nature of their anatomy and physiology. This study was aimed to identify the common causative organisms of UTI and their antimicrobial susceptibility pattern among female students in Babcock University. Methods: A cross-sectional study, in which 200 female participants with symptoms of UTI were recruited. Mid-stream urine was collected from them and processed using the standard microbiological procedures. Antimicrobial susceptibility testing was performed on isolates from the samples with significant bacteriuria. Sociodemographic and risk factors were obtained using standard questionnaires, and statistical analysis was performed using SPSS version 23.0. Results: UTIs were confirmed in 14.5% (29/200) participants. Of the pathogens isolated, Escherichia coli was predominant 30.6% (11/36). Most of the pathogens isolated were susceptible to ofloxacin and gentamicin, while ceftriaxone had the least susceptibility (18.2%). The majority of the participants, 165 (82.5%) though symptomatic, did not have bacteriuria. The participants aged 15–20 years were mostly infected [24 (13.4%)]. No significant association was found between the sociodemographic factors and UTI. Conclusion: The prevalence of UTI from this study was 14.5%. E. coli was the predominant bacteria pathogen isolated, and ofloxacin and gentamycin were the most active antibiotics on susceptibility pattern. The majority of the patients though symptomatic, had no pathogens isolated from their urine. Therefore, caution should be applied on the use of antibiotics when managing UTI based on symptoms alone, to prevent antibiotic resistance

Ceftriaxone remains a first-line treatment for patients infected by Neisseria gonorrhoeae in most settings. We investigated the possible spread of a ceftriaxone-resistant FC428 N. gonorrhoeae clone in Japan after recent isolation of similar strains in Denmark (GK124) and Canada (47707). We report 2 instances of the FC428 clone in Australia in heterosexual men traveling from Asia. Our bioinformatic analyses included core single-nucleotide variation phylogeny and in silico molecular typing; phylogenetic analysis showed close genetic relatedness among all 5 isolates. Results showed multilocus sequence type 1903; N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) 233; and harboring of mosaic penA allele encoding alterations A311V and T483S (penA-60.001), associated with ceftriaxone resistance. Our results provide further evidence of international transmission of ceftriaxone-resistant N. gonorrhoeae. We recommend increasing awareness of international spread of this drug-resistant strain, strengthening surveillance to include identifying treatment failures and contacts, and strengthening international sharing of data.

BACKGROUND: The rising number of primary joint replacements worldwide is causing an increase of endoprosthetic revision surgery due bacterial infection. Revision surgery using non-cemented implants seems beneficial for the long-term outcome, and the use of antibiotic-impregnated bone grafts might control the infection and provide agood support for the implant. In this study, we evaluated the release of antibiotics from fresh-frozen and lyophilized allogeneic bone grafts. METHODS: Heat-treated, lyophilized and fresh frozen cryopreserved bone chips were impregnated with gentamicin sulphate, gentamicin palmitate and vancomycin, and calcium carbonate/calcium sulphate treated with antibiotics. The efficacy of each preparation was measured by drug release tests and bacterial susceptibility using B.subtilis, S.aureus and methicillin-resistant Staphylococcus aureus. RESULTS: The release of gentamicin from lyophilized bone was similar to the release rate from fresh frozen bone during the entire experiment. This might be related to the similar porosity and microstructure of the bone chips. The release of gentamicin from lyophilized and fresh frozen bone was high on the first and second days, then decreased and stayed at alow rate until the end of the second week. CONCLUSION: Depending on the surgical strategy, either polymethylmethacrylate or allogeneic bone are able to deliver sufficient concentrations of gentamicin to achieve bacterial inhibition within 2 weeks after surgery. In the case of uncemented revision of joint replacements, allogeneic bone can deliver therapeutic doses of gentamicin and peak levels immediately and afortnight after implantation.

Lactobacillus (L. casei) Zhang is a koumiss-originated probiotic strain, which was used as a model in a long-term antibiotics-driven evolution experiment to reveal bacterial evolutionary dynamics; and we isolated gentamycin-resistant L. casei Zhang descendents. To decipher the gentamycin resistance mechanism, here we cultivated the parental L. casei Zhang and its descendent cells in an antibiotics-containing environment to compare their global protein expression profiles using the iTRAQ-based proteomic approach. A total of 72 proteins were significantly up-regulated (>2.0-fold, P < 0.05), whilst 32 proteins were significantly down-regulated

Introduction. Today, it is well established that almost 80% of all infectious diseases are caused by microorganisms that exist in the form of biofilms. Microorganisms in the biofilms acquire signs of increased resistance to antibiotics, disinfectants and other aggressive environmental factors, complicate the course of infectious diseases and play an important role in their chronicity. Formation of biofilms by hospital strains of bacteria poses a serious threat to the practical medicine. Enterococci, foremost Enterococcus faecium and Enterococcus faecalis, are the third most common cause of hospital infections, most of which involve the use of permanent medical equipment. Internal hospital infections gain particular importance in intensive care units and in surgical hospitals, since the formation of biofilms is the cause of severe catheter and fan associated infections, sepsis, pneumonia and endocarditis. It should be noted that ineffective antibiotic therapy of infections, accompanied by the formation of biofilms, also leads to significant economic losses. The aim of the work was to study the effects of gentamicin and gentamicin in combination with a penetrator on the processes of enterococci biofilm formation. Materials and methods. The objects of the study included 3 strains of bacteria genus Enterococcus, obtained from the bacteria museum of the Mechnikov Institute of Microbiology and Immunology National Academy of Medical Sciences of Ukraine: E. faecalis ATCC 29212, E. faecalis ІМІ (Х) 49 р, E. faecium ІМІ (Х) 80. The biofilms modelling was performed in 4-section polystyrene Petri dishes. To study the influence of compounds on biofilm formation, a photometric method was used. The optical density (OD) of eluates from enterococci biofilms, stained with crystal violet, was measured with the SF-56L spectrophotometer at a wavelength of 590 nm. Statistical processing of the obtained data was carried out by means of nonparametric statistical methods using Microsoft Excel 2007 and STATISTICA 6.0 programs. The validity of the differences between the two related samples was assessed by the Wilcoxon test and the Sign test. The effect of the compound was evaluated using biofilm inhibition index (BII), which was calculated according to the formula: [(OD positive control - OD tested) / OD positive control] × 100%. Reduction of the OD value by more than 25% in the experiment relative to OD positive control was considered as a positive effect. Results and discussions. Analysis of the results allowed to conclude that gentamicin at concentration of 8 mcg/ml is capable of preventing the formation of biofilms taken in experiments with enterococci. Further increase in the concentration of gentamicin to 64 mcg/ml did not lead to an increase in its activity relative to biofilm formation. When applying gentamicin at concentrations of 8 mcg/ml, 16 mcg/ml, 32 mcg/ml and 64 mcg/ml, the index of inhibition equaled 53,8%, 56,6%, 49,9% and 49,6% respectively. A higher inhibitory effect of gentamicin was identified for the formation of E. faecium biofilms than for E. faecalis ones. Thus, when applying gentamicin at concentrations of 8 mcg/ml, 16 mcg/ml, 32 mcg/ml and 64 mcg/ml for E. faecalis biofilm formation, the inhibition index was equal to 45,5 %, 46,7 %, 49,6 % and 48,5 %, for E. faecium – 54,8 %, 53,5 %, 65,3 % and 60,2 % respectively. One way of facilitating the transportation of biocides through the extracellular matrix of biofilms to the target of action may be the use of so-called penetrators. Polyethylene glycol was used as a penetrator (PNT) in our studies. Inhibition index analysis showed a statistically significant increase in the suppressing effect of the combination of gentamicin and PNT on the enterococci biofilm formation compared to the effect of gentamicin without PNT (рE. faecium compared to E. faecalis. Thus, the results obtained suggest that polyethylene glycol can increase the penetration of gentamicin through the biofilm glycocalyx. Conclusion. Gentamicin at concentrations of 8 mcg/ml, 16 mcg/ml, 32 mcg/ml and 64 mcg/ml shows an inhibitory effect on enterococci biofilm formation (inhibition index varied from 49,6 % to 56,6 %). Inhibitory effect of gentamicin at concentrations of 8 mcg/ml, 16 mcg/ml, 32 mcg/ml and 64 mcg/ml on enterococci biofilm formation is enhanced under the influence of polyethylene glycol (inhibition index – from 73,5 % to 78,2 %).

Methicillin-resistant Staphylococcus aureu s (MRSA) mulai dijumpai pada penderita dermatitis atopik (DA) derajat sedang hingga berat dan bersifat multiresisten terhadap antibiotik topikal. Gentamisin telah digunakan secara luas, sedangkan mupirosin merupakan pilihan utama eradikasi MRSA. Penelitian ini bertujuan untuk mengetahui kolonisasi MRSA pada penderita DA dan sensitivitasnya terhadap mupirosin dibandingkan dengan gentamisin di Poliklinik Departemen Ilmu Kesehatan Kulit dan Kelamin Rumah Sakit Umum Pusat Dr. Hasan Sadikin Bandung. Survei potong lintang analitik dilakukan selama 19 September–31 Oktober 2011 terhadap 22 penderita DA derajat sedang hingga berat sesuai dengan Scoring Atopic Dermatitis objektif dan 22 individu sehat. Seluruh subjek dilakukan pemeriksaan apusan kulit untuk deteksi MRSA dan uji sensitivitas terhadap mupirosin dan gentamisin. Pada kedua kelompok masing-masing didapatkan 10 laki-laki dan 12 perempuan. Pada kelompok penderita DA didapatkan DA derajat sedang (10/22) dan berat (12/22), dengan lesi akut (14/22) dan kronik (8/22). Pertumbuhan S. aureus didapatkan pada 17/22 penderita DA dengan sensitivitas terhadap mupirosin 14/17 dan gentamisin 11/17 penderita. Pada individu sehat tidak didapatkan pertumbuhan koloni S. aureus. Galur MRSA ditemukan pada 3/17 penderita DA dan dianggap berbeda secara bermakna bila dibandingkan dengan individu sehat (p

Background/Aims: The aminolycoside Gentamicin is a widely used antibiotic, applied in equine medicine. Despite its clinical use, concerns remain regarding the potential toxic side-effects, such as nephrotoxicity. Early detection of renal damage is critical in preclinical drug development. This study was aimed to determine whether kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be early indicators in the assessment of Gentamycin-induced nephrotoxicity. Methods: In our study, a model of Gentamicin-induced nephrotoxicity in male Sprague Dawley rats treated for up to 7 days at 50 or 100mg/kg/day was used to monitor the expressions of novel biomarkers of renal toxicity during the progression of acute kidney injury (AKI). Additionally, biomarkers were assessed in human kidney proximal epithelial cells (HK-2) treated with Gentamicin for 2, 6, 12, 24, 36 or 48h in vitro. Results: Repeated administration of Gentamicin to rats for 1, 3, or 7 days resulted in a dose- and time-dependent increase in the expression of KIM-1 and NGAL. The expressions of the two biomarkers changed prior to renal tubule damage and increases in serum creatinine (SCr) and blood urea nitrogen (BUN) levels, suggesting their usefulness for predicting Gentamicin-induced acute kidney injury (AKI) in vivo. Conclusions: In contrast, no significant increase in the expression of the biomarker genes and proteins were evident in HK-2 cells after treated by Gentamycin for up to 48h, suggesting that they may not be suitable endpoints for sensitive detection of nephrotoxic effects in vitro.

Background/Aims: Motility is a feature of many pathogens that contributes to the migration and dispersion of the infectious agent. Whether gentamycin has a post-antibiotic effect (PAE) on the swarming and swimming motility of Escherichia coli (E. coli) remains unknown. In this study, we aimed to examine whether short-term pretreatment of sub-inhibitory concentrations of gentamycin alter motility of E. coli and the mechanisms involved therein. Methods: After exposure to sub-inhibitory concentrations (0.8 μg/ml) of gentamicin, the swarming and swimming motility of E. coli was tested in semi-solid media. Real-time PCR was used to detect the gene expression of succinate dehydrogenase (SDH). The production of SDH and fumarate by E. coli pretreated with or without gentamycin was measured. Fumarate was added to swarming agar to determine whether fumarate could restore the swarming motility of E. coli. Results: After pretreatment of E. coli with sub-inhibitory concentrations of gentamycin, swarming motility was repressed in the absence of growth inhibition. The expression of all four subunits of SDH was down-regulated, and the intracellular concentration of SDH and fumarate, produced by E. coli, were both decreased. Supplementary fumarate could restore the swarming motility inhibited by gentamycin. A selective inhibitor of SDH (propanedioic acid) could strongly repress the swarming motility. Conclusion: Sub-inhibitory concentrations of gentamycin inhibits the swarming motility of E. coli. This effect is mediated by a reduction in cellular fumarate caused by down-regulation of SDH. Gentamycin may be advantageous for treatment of E. coli infections.

The infant gut microbiota undergoes dramatic changes during the first 2 years of life. The acquisition and development of this population can be influenced by numerous factors, and antibiotic treatment has been suggested as one of the most significant. Despite this, however, there have been relatively few studies which have investigated the short-term recovery of the infant gut microbiota following antibiotic treatment. The aim of this study was to use high-throughput sequencing (employing both 16S rRNA and rpoB -specific primers) and quantitative PCR to compare the gut microbiota of nine infants who underwent parenteral antibiotic treatment with ampicillin and gentamicin (within 48 h of birth), 4 and 8 weeks after the conclusion of treatment, relative to that of nine matched healthy controls. The investigation revealed that the gut microbiota of the antibiotic-treated infants had significantly higher proportions of Proteobacteria ( P = 0.0049) and significantly lower proportions of Actinobacteria ( P = 0.00001) (and the associated genus Bifidobacterium [ P = 0.0132]) as well as the genus Lactobacillus ( P = 0.0182) than the untreated controls 4 weeks after the cessation of treatment. By week 8, the Proteobacteria levels remained significantly higher in the treated infants ( P = 0.0049), but the Actinobacteria , Bifidobacterium , and Lactobacillus levels had recovered and were similar to those in the control samples. Despite this recovery of total Bifidobacterium numbers, rpoB -targeted pyrosequencing revealed that the number of different Bifidobacterium species present in the antibiotic-treated infants was reduced. It is thus apparent that the combined use of ampicillin and gentamicin in early life can have significant effects on the evolution of the infant gut microbiota, the long-term health implications of which remain unknown.

Introduction: Antibiotic prophylaxis is defined as the use of antimicrobials in the absence of symptoms of infection, with the aim of preventing or reducing the incidence of infection after surgery. We analyzed the incidence of surgical wound infection in patients in whom a protection of hemoprophylaxis conducted using cefazolin and gentamicin, and determine the frequency of surgical wound infection in patients in whom there was a deviation in the implementation of hemoprophylaxis protection.Methods: This retrospective-prospective study included 100 patients surgically treated at the The Department of Orthopedics and Traumatology, University Clinical Center in Tuzla from December 2007 to February 2010, which examined the incidence of surgical wound infection after surgical treatment of fractures or degenerative changes in the hip, thigh and lower leg fractures.Results: In the first group, in patients who were treated with cefazolin were detected in 2 cases (5.7%) while the length of hemoprophylaxis was 7 days, patients who were treated with cefazolin and gentamicin were detected in 1 case (2.8%) and duration hemoprophylaxis was 7 days. In another control group tah was found 9 cases of wound infection (30%), and hemoprophylaxis duration was 10 days.Conclusion: The combination of cefazolin and gentamycin for a period of 5 days significantly reduces the incidence of infection and significantly shortened the time of antibiotics in group that is respected application protocol in accordance with international recommendation.

Inguinal hernia repair is a clean surgical procedure and surgical site infection (SSI) rate is generally below 2%. Antibiotic prophylaxis is not routinely recommended, but it may be a good choice for institutions with high rates of wound infection (>5%). Typical prophylaxis is the intravenous application of first or second-generation cephalosporins before the skin incision. However, SSI rate remains more than 2% in many centers in spite of intravenous antibiotic prophylaxis. Even a 1% SSI rate may be unacceptable for the surgeons who specifically deal with hernia surgery. A hernia center targets to be a center of excellence not only in respect of recurrence rate but also for other postoperative outcomes, therefore a further measure is required for an excellent result regarding infection control. Topical gentamycin application in combination with preoperative single-dose intravenous antibiotic may be a useful to obtain this perfect outcome. Data about this subject are not complete and high-grade evidence has not been cumulated yet. Prospective randomized controlled trials can make our knowledge more solid about this subject and help the surgeons who seek perfect outcome regarding infection control in inguinal hernia surgery.

Adverse drug associated mucocutaneous reactions having a preponderance to occur above 1% include urticaria, angioedema, photosensitivity, fixed drug eruptions and Erythema Multiforme (EM). EM is an acute inflammatory disease of the skin and mucous membranes that causes a variety of skin lesions-hence named ‘multiforme’. The aetiological spectrum of EM is wide and is attributed to infectious agents, drugs and food additives. EM is diagnosed based on stringent clinical findings which are pathognomic as microscopic evaluation carries least significance. We report a case of a 38-year-old male who presented with a complaint of severe oral & cutaneous lesions making him difficult to eat & drink. History revealed the usage of clove to get rid of tooth pain following which he developed ulcers in the mouth which made him to visit a general physician where he was administered gentamycin. Later on oral lesions worsened along with the emergence of dermal lesions. In the present case, based on the patient history, clove was found to be a probable aetiological agent and the condition was further precipitated owing to the administration of gentamycin. The patient was successfully treated with corticosteroids adhering to systemic corticosteroid administrative protocols and no remissions and exacerbations were noticed in a year follow up.

Afin de tenter de déterminer les parts respectives des activités bactérienne et algale, nous avons testé d'une part, l'action d'une substance antibactérienne (la gentamycine), et d'autre part, l'action d'un inhibiteur métabolique des cellules eucaryotes (la cycloheximide) sur des cultures d'algues et de bactéries et sur des échantillons provenant du milieu naturel et soumis à des filtrations différentielles. Les effets de ces inhibiteurs ont été testés au niveau des activités hétérotrophe et photosynthétique globales, mais également au niveau de l'incorporation des marqueurs radioactifs lors de la synthèse des macromolécules et des composés de faible poids moléculaire.Les résultats obtenus laissent apparaître que l'inhibition de l'activité bactérienne par la gentamyclne est significative mais non complète (pourcentage d'inhibition moyen = 67 %). De plus, l'efficacité de la gentamycine augmente avec la durée d'incubation. Par ailleurs, les effets secondaires de la gentamycine sur les activités hétérotrophe et photosynthétique d'une culture de Melosira italica subsp. subarctica sont acceptables seulement pour des incubations de courte durée (< 4 heures).En revanche, l'emploi de la cycloheximide s'est révélé sans aucun effet significatif sur les activités photosynthétique et hérérotrophe de la culture de Melosira, même après 24 h d'incubation.A partir des échantillons prélevés en milieu naturel, l'emploi de la gentamycine a permis de réduire l'interférence bactérienne dans les mesures d'activité hétérotrophe algale. Enfin, nous avons pu constater que la gentamycine modifie l'allocation des marqueurs radioactifs dans les macromolécules., The ability of many planktonic algae to use particulate and/or dissolved organic carbon directly by phagotrophy or osmotrophy in laboratory cultures is well documented (DROOP, 1974; NEILSON and LEWIN, 1974; HELLEBUST and LEWIN, 1977; BIRD and KALFF, 1986). In axenic cultures, numerous microalgae grow in the dark with micromolar concentrations of diverse organic nutrients as their sole sources of carbon and energy (RIVKIN and PUTT, 1987). However, to demonstrate algal heterotrophy in the field, it is necessary to differentiate between bacterial and algal activities. In the course of this study, we tested the effect of an antibacterial substance (gentamycin) and of a metabolic inhibitor of eukaryotic cells (cycloheximide) on algal and bacterial cultures, and also on lake water samples submitted to differential filtration. The effect of these inhibitors was tested both at the overall heterotrophic and photosynthetic activities level and the level of the incorporation of radiolabeled tracers in macromolecules and low molecular weight compounds.Gentamycin was tested on bacteria and on an axenic culture of the diatom Melosira italica subsp. subarctica, the dominant species of the spring phyto-planktonic bloom of many temperate lakes. Bacterial culture was obtained by filtration of a senescent culture of Melosira through a 0.45 µm pore-size membrane. During exponential growth, gentamycin (40 µg.ml-1) was added to different flasks containing 100 ml of culture, 30 mn after gentamycin addition, Na H14CO3 (12µCi/100 ml) was introduced into the flasks. In each case, two replicates were incubated in the light and two in the dark for 0.5, 1, 2, 4, 6, 8, 12 and 24 hours. After incubation, aliquots were collected on a filtration membrane (0.45 µm) and the radioactivity was measured using an LKB liquid scintillation counter to estimate photosynthetic activity. Incorporation of inorganic carbon into macromolecules was measured using the procedure described by LANCELOT and MATHOT (1985), which allows the separation of lipids, polysaccharides, proteins and low molecular weight compounds (e.g. amino acids, organic acids and monosaccharides) by virtue of their relative solubilities in different extraction solvents :- lipids were extracted with a 2/1 (v/v) chloroform-methanol mixture;- low molecular weight compounds were extracted with hot ethanol;- proteins were precipated with TCA at elevated temperature; this also separated them from polysaccharides. Nucleic acids were recovered with the polysaccharides fraction. Results are given as a percentage of total radioactivity. The same method, as that described for photosynthetic incorporation, was used to measure incorporation of glucose 3H (19 nmoles.l-1) and for the allocation of radioactive marker in macromolecules. To assess the effect of cycloheximide, the same procedure as that described for gentamycin was used. However, due to the lack of references, three cycloheximide concentrations were tested = 50, 100 and 150 µg.ml-1, and aliquots were collected on a 0.2 µm pore-size membrane.Field samples were taken in Lake Pavin, an oligomesotrophic French lake, during the sedimentation of Melosira italica subsp. subarctica, the prevailing species of the spring bloom. The effects of gentamycin on photosynthetic and heterotrophic incorporations were tested with the came procedure as that described for cultures. However, radioactivity was measured for different size tractions : 0.2-0.45 µm, 0.45-5 µm and 5-160 µm, after incubations for 0.5, 1, 3, 6, 12 and 24 hours. Phytoplanktonic cells were counted on a Wild M40 inverted microscope and bacterial enumeration was realized in epifluorescence microscopy after staining with acridine orange (HOBBIE el al., 1977).Results show that gentamycin used at 40 µg.ml-1 inhibits significantly but not completely the activity of the bacterial culture (mean inhibition percent = 67 %). Gentamycin efficiency increases with incubation time, the inhibition reaching 81 % after 24 h. At the same time, the secondary effects of gentamycin on heterotrophic and photosynthetic activities of Melosira italica subsp. subarctica in culture were only tolerable with short incubation times (< 4 h), when the percents of inhibition were respectively 13.6 and 12.2%. On the other band, cycloheximide produced no significant effect on photosynthetic and heterotrophic activities of Melosira italica in culture, the percent of inhibition always remaining below 6.5 %.The use of gentamycin in natural samples reduced bacterial interference with algal heterotrophic activily measurements. The percent of inhibition caused by gentamycin was high (< 76 %) In the small-size fraction where the bacterial biomass predominate on the phytoplanktonic one.Lastly, in all samples, we could demonstrate that gentamycin modifies the allocation of inorganic carbon and radioactivity in macromolecules. The incorporation in proteins is significantly reduced essentially to benefit of the incorporation in low molecular weight compounds.

Ein akutes Nierenversagen tritt bei 9 % der hospitalisierten Patienten und bis zu zwei Drit-teln der intensivmedizinisch betreuten Patienten auf. Dadurch werden die Mortalität, die Krankenhausaufenthaltsdauer und gesundheitsökonomischen Kosten erhöht. Das Ziel die-ser Studie war, den Einfluss der Konformität zur den standardisierten Verfahrensanwei-sungen für die Therapie mit Vancomycin, Gentamycin und Tobramycin auf das Auftreten eines akuten Nierenversagens darzustellen. In der klinisch prospektiven Observationsstu-die wurden in zwei separaten Beobachtungszeiträumen 163 erwachsene Patienten erfasst, die länger als 24 Stunden auf einer der drei anästhesiologisch geführten Intensivstationen der Klinik für Anästhesiologie mit Schwerpunkt operative Intensivmedizin der Charité Uni-versitätsmedizin Berlin am Campus Charité Mitte und Campus Virchow-Klinikum aufge-nommen wurden und mit Vancomycin, Gentamicin oder Tobramycin therapiert wurden. Die Gruppeneinteilung in eine Hoch- (HAG) und Niedrigadhärenzgruppe (NAG) erfolgte an-hand eines SOP-Konformitätsrichtwertes von 70 %. Ein akutes Nierenversagen wurde durch die RIFLE-Kriterien klassifiziert. Bezüglich der Basischarakteristika waren die Stu-diengruppen, bis auf einen in der NAG signifikant erhöhten mittleren Aufnahme-APACHE2-Score und eine erniedrigte Häufigkeit von Weichteilinfektionen, homogen. In der LAG (N=75) zeigte sich eine signifikante Erhöhung (p=0,035) der Häufigkeit eines akuten Nie- renversagens mit 36 % gegenüber 21 % in der HAG (N=88). In den univariaten und mul-tivariaten Regressionsanalysen ergab sich die Zugehörigkeit zur NAG als signifikanter Ein-flussfaktor auf die Häufigkeit eines akuten Nierenversagens. Zusammenfassend ist anzunehmen, dass die Qualität der durchgeführten Antibiotikathera-pie mit Vancomycin, Tobramycin und Gentamicin und der Grad der Einhaltung der vorge-gebenen, standardisierten Verfahrensanweisungen wichtige Einflussfaktoren für das Auf-treten eines akuten Nierenversagens darstellen., Objective: Acute kidney failure (AKF) occurs in 9% of hospitalized and in 66% of Intensive Care Unit (ICU) patients. It increases mortality, hospital length of stay, and costs. The aim of this study was to investigate, whether there is an association between adherence to guidelines (standard operating procedures, SOP) for potentially nephrotoxic antibiotics and the occurrence of AKF. Design: Prospective, clinical, non-interventional, observational study Setting: Data collection was performed over a total of 170 days on three ICUs at Charité – Universitaetsmedizin Berlin. Patients: Altogether, 675 patients were included. 163 of them had therapy with vancomycin, gentamicin, or tobramycin; were > 18 years; and treated on ICU for > 24 hours. Pa-tients with an adherence to SOP > 70% were classified into the high adherence group (HAG); patients with an adherence of < than 70 % into the low adherence group (LAG). Definitions: AKF was defined according to RIFLE criteria. Adherence to SOPs was evalu-ated by a retrospective expert audit. Measurements and Main Results: LAG consisted of 75 patients (46%) versus HAG of 88 patients (54%). AKF occurred significantly more in LAG with 36% versus 21% in HAG (p=0,035). Basic characteristics were comparable, except an increased rate of soft tissue infections in LAG. Multivariate analysis revealed an odds ratio of 2, 5- fold for LAG to de-velop AKF compared with HAG (CI 1.038 - 4.437, p=0.039). Conclusion: Low adherence to SOPs was associated with a higher occurrence of AKF.

Human kallikrein gene delivery protects against gentamycin-induced nephrotoxicity in rats. The tissue kallikrein-kinin system has been shown to play important roles in cardiovascular and renal function. The aim of this study was to investigate potential protective effects of kallikrein gene delivery in gentamycin-induced nephrotoxicity. Rats were injected subcutaneously with gentamycin daily for 10 to 14 days. Adenovirus, Ad.CMV-cHK carrying the human tissue kallikrein gene or Ad.CMV-LacZ carrying the β-galactosidase gene under the control of the cytomegalovirus promoter, were delivered intravenously on the first day of gentamycin administration. The expression of human tissue kallikrein mRNA was identified in the kidney, aorta, heart and liver and immunoreactive human kallikrein levels were measured in the serum and urine of rats receiving kallikrein gene delivery. Adenovirus-mediated kallikrein gene delivery significantly increased the renal blood flow, glomerular filtration rates, and urine flow while it attenuated renal tubular damage, cellular necrosis, lumenal protein casts and reduced ventricular weight and cardiomyocyte size. Kallikrein gene delivery caused a decrease in blood urea nitrogen levels and increases in urinary kinin and nitrite/nitrate levels. This study shows that kallikrein gene delivery exhibits protection against gentamycin-induced nephrotoxicity, and raises the potential for kallikrein gene therapy to treat drug-induced renal diseases.

Aminoglycosides have the potential to read through stop codons and thus may induce the synthesis of a full-length protein in inherited disorders. The corrective potential of this approach has been documented in patients with cystic fibrosis caused by nonsense mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene.1 Results in treatment of mdx mice with gentamicin, an animal model for Duchenne muscular dystrophy, are conflicting. One study showed an increase in the synthesis of dystrophin,2 which was not confirmed in a subsequent study.3 A clinical trial of gentamicin treatment in patients with Duchenne or Becker muscular dystrophy has observed no changes in muscle strength or increased expression of dystrophin in posttreatment muscle biopsies.4 Here we tested the short-term efficacy of gentamicin in patients with McArdle disease, a rare metabolic myopathy with a defect in the rate-limiting enzyme of glycogen breakdown caused by mutations in the myophosphorylase gene. McArdle …

Background and Objective: Asymptomatic bacteriuria is bacteria in the properly collected urine of a patient, leading to a urinary tract infection with no symptoms. Asymptomatic bacteriuria is a common complication in clinical practice with an increasing prevalence due to increase of age. The present study investigated the prevalence of asymptomatic bacteriuria among pregnant women receiving antenatal care in Ovia North East Local Government Area, Edo State, Nigeria. Materials and Methods: A total of 201 urine samples were collected randomly from pregnant women at Igbinedion University Teaching Hospital, Okha Maternity and Usen General Hospital in in Ovia North East Local Government Area. The bacteria isolation was carried out using the pour plate technique. The bacteria identification was conducted by gram staining and biochemical tests and the antibiotic susceptibility pattern of the bacterial isolates was determined by Kirby-Bauer disc diffusion technique. Results: Eighty-one of the subjects had significant bacteriuria, with a prevalence of 40.3 %. The bacteria isolated in the samples were Streptococcus, Proteus, Klebsiella and Micrococcus species as well as Staphylococcus epidermidis, Escherichia coli and Staphylococcus aureus. Streptococcus spp. occurred more frequently (42.0 %) while S. aureus had the lowest frequency of occurrence (2.5 %) in the samples. The infection was most prevalent among women aged between 28 and 37 years (74.5 %). Pregnant women in their third trimester in this study had the highest prevalence of asymptomatic bacteriuria (55.2 %). Ciprofloxacin was found to be the most effective antibiotic against the urinary isolates. Conclusion: Pregnancy promotes the progression from symptomatic to asymptomatic bacteriuria with its consequences such as pyelonephritis and increased fetal mortality. Therefore, routine culture test should be carried out for all antenatal women to detect asymptomatic bacteriuria and all positive cases should be treated with appropriate antibiotic therapy to prevent any obstetric complications which are associated with pregnancy.

Stem cell differentiation stage factors (SCDSF), taken from Zebrafish embryos during the stage in which totipotent stem cells are differentiating into pluripotent stem cells, have been shown to inhibit proliferation and induce apoptosis in colon tumors. In order to ascertain if these embryonic factors could synergistically/additively interact with 5-Fluorouracil (5-Fu), whole cell-count, flow-cytometry analysis and apoptotic parameters were recorded in human colon cancer cells (Caco2) treated with Zebrafish stem cell differentiation stage factors (SCDSF 3 µg/ml) in association or not with 5-Fu in the sub-pharmacological therapeutic range (0.01 mg/ml). Cell proliferation was significantly reduced by SCDSF, meanwhile SCDSF+5-Fu leads to an almost complete growth-inhibition. SCDSF produces a significant apoptotic effect, meanwhile the association with 5-FU leads to an enhanced additive apoptotic rate at both 24 and 72 hrs. SCDSF alone and in association with 5-Fu trigger both the extrinsic and the intrinsic apoptotic pathways, activating caspase-8, -3 and -7. SCDSF and 5-Fu alone exerted opposite effects on Bax and Bcl-xL proteins, meanwhile SCDSF+5-Fu induced an almost complete suppression of Bcl-xL release and a dramatic increase in the Bax/Bcl-xL ratio. These data suggest that zebrafish embryo factors could improve chemotherapy efficacy by reducing anti-apoptotic proteins involved in drug-resistance processes.