Neomycin Group Research Articles

Efficacy and Safety of Oral Neomycin for the Decolonization of Carbapenem-Resistant Enterobacterales: An Open-Label Randomized Controlled Trial.

Patients with carbapenem-resistant Enterobacterales (CRE) in the gastrointestinal (GI) tract are at risk for subsequent infections and transmission, necessitating contact precautions. Neomycin has shown in vitro activity against CRE in 66-85% of isolates. This study evaluated the efficacy and safety of neomycin for CRE decolonization. In this open-label randomized controlled trial, stool/rectal swab samples from high-risk patients were collected and tested for CRE colonization in the GI tract. Patients who had CRE and met eligible criteria were divided into a neomycin group (n = 26; treated with 4.2 g/day neomycin for 5 days) and a control group (n = 26). CRE detection in stool/rectal swabs was performed on days 7 ± 2 and 14 ± 2. The two groups' baseline characteristics were similar. CRE presence on day 7 ± 2 was significantly lower in the neomycin group (46.2%) than in the control group (80.8%, p = 0.01). Efficacy of neomycin (4.2 g/day for 5 days) for CRE decolonization was 42.8-53.8% by day 7. By day 14 ± 2, the CRE rate in the neomycin group had risen to align with the control group's rate (73.1% vs. 61.5%, p = 0.56). The neomycin group experienced mild, temporary, gastrointestinal side-effects. Neomycin effectively reduced CRE colonization on day 7 ± 2, but its impact waned by day 14 ± 2. This suggests that neomycin dosage was too low and the duration of treatment was too short for lasting CRE decolonization.

Distinct Changes in Microbiota-Mediated Intestinal Metabolites and Immune Responses Induced by Different Antibiotics.

The cocktails of antibiotics are utilized to study the functions of microbiota. There have been studies on the alteration of not only the microbiota composition but also the host's metabolism or immunity. However, the bacterial species associated with these altered physiologic markers are still unclear. Therefore, we supplied mice with drinking water containing ampicillin (AMP), vancomycin (VAN), neomycin (NEO), or metronidazole (MET) to observe the effect of each antibiotic on helper T cells and inflammation-related gene expression and metabolism, including amino acid metabolism and changes in gut microbiota. We observed major changes in gut microbiota in mice treated with AMP and VAN, respectively, immediately after administration. The abundance of the genera Parabacteroides and Akkermansia increased in the AMP and VAN groups, while Prevotella almost disappeared from both groups. The compositional changes in intestinal metabolites in the AMP and VAN groups were more distinct than those in the NEO and MET groups, which was similar to the microbiome results. In particular, the most distinct changes were observed in amino acid related metabolism in AMP and VAN groups; the amounts of phenylalanine and tyrosine were increased in the AMP group while those were decreased in the VAN group. The changed amounts of intestinal amino acids in each of the AMP and VAN groups were correlated with increases in the abundance of the genera Parabacteroides and Akkermansia in the AMP and VAN groups, respectively. The most distinctive changes in intestinal gene expression were observed in the ileum, especially the expression Th17-related genes such as rorgt, il17a, and il17f, which decreased dramatically in the guts of most of the antibiotic-treated groups. These changes were also associated with a significant decrease in Prevotella in both the AMP and VAN groups. Taken together, these findings indicate that changes in gut microbiota as well as host physiology, including host metabolism and immunity, differ depending on the types of antibiotics, and the antibiotic-induced gut microbiota alteration has a correlation with host physiology such as host metabolic or immunological status. Thus, the immune and metabolic status of the host should be taken into account when administering antibiotics.

Antibiotic treatment targeting gram negative bacteria prevents neratinib-induced diarrhea in rats

BackgroundNeratinib is a pan-ErbB tyrosine kinase inhibitor used for extended adjuvant treatment of HER2-positive breast cancer. Diarrhea is the main adverse event associated with neratinib treatment. We aimed here to determine whether antibiotic-induced gut microbial shifts altered development of neratinib-induced diarrhea. MethodsFemale Albino Wistar rats (total n = 44) were given antibiotics (vancomycin, neomycin, or a cocktail of vancomycin, neomycin and ampicillin) in drinking water for four weeks, and then treated daily with neratinib (50 mg/kg) for 28 days. Diarrhea, along with markers of gastrointestinal damage and microbial alterations were measured by histopathology and 16S sequencing, respectively. ResultsRats treated with vancomycin or neomycin had significantly lower levels of diarrhea than rats treated with neratinib alone. In the distal ileum, neratinib was associated with a statistically significant increase in histological damage in all treatment groups expect the antibiotic cocktail. Key features included villous blunting and fusion and some inflammatory infiltrate. Differences in microbial composition at necropsy in vehicle control, neratinib and neratinib + neomycin groups, were characterized by a neratinib-induced increase in gram-negative bacteria that was reversed by neomycin. Neomycin shifted bacterial composition so that Blautia become the dominant genus. ConclusionsNarrow spectrum antibiotics reduced neratinib-induced diarrhea. This suggests that the microbiome may play a key role in the development and prolongation of diarrhea following neratinib treatment, although further research is required to understand the key bacteria and mechanisms by which they reduce diarrhea, as well as how this may impact presentation of diarrhea in clinical cohorts.

Comparative Antibiotic and Probiotic Effects on Antimicrobial Sensitivity of Escherichia coli Isolates and Performance of Broiler Chickens

The study evaluated the growth performance, haematology, serum biochemistry, intestinal microbial count, and antimicrobial resistance profile of Escherichia coli (E. coli) from broiler chicks fed diets supplemented with antibiotics (neomycin, and oxytetracycline), and probiotic (Saccharomyces cerevisiae). One hundred and twenty Abor acre broiler chicks randomly alloted to four treatment groups (30 birds/group; 10 birds/replicate) were used in the 49 days study. Group one (G 1, control) were fed basal diet while G 2, 3, and 4 received basal diet containing S. cerevisiae (0.80g/kg; 108cfu/g), neomycin (0.50g/kg) and oxytetracycline (0.30g/kg), respectively. Results showed significant treatment effects on body weight, feed intake, linear body values, some haematological indices, intestinal, caecal and combined caecal and intestinal bacteria counts, diameter of E. coli inhibition zone, and mortality. Body weight and feed intake were significantly higher in the supplemented groups. Intestinal bacterial count was highest in neomycin and control groups (5.29 ± 0.01 and 5.22 ± 0.02 Log10 cfu/ml, respectively) while S. cerevisiae and neomycin groups yielded the highest caecal, and combined caecal and intestinal bacterial counts. Eimeria Oocyst count did not differ significantly between groups. Escherichia coli from antibiotic fed groups had reduced sensitivity or were resistant to the antibiotics. It was concluded that subtherapeutic use of antibiotics as growth promoters in broiler chickens caused the development of antibiotic resistance, and therefore, should be avoided.

THE EFFECT OF 10 % LIDOCAINE SPRAYED TO NASAL PACKS ON PAIN AFTER ELECTIVE SEPTOPLASTY.

Aim To study analgesic effect of lidocaine10 % sprayed to 10 cm х 10 cm gauze swabs with neomycin and bacitracin ointment nasal packing using visual analog scale (VAS) in postoperative period for patients underwent septoplasty operation. Materials and methods 100 patients aged between 17 and 50 years and divided into two equal groups. Group L lidocaine 10% was sprayed to gauze swabs with neomycin and bacitracin ointment nasal packing and group S control group 0.9% NaCl applied to same nasal packing. Postoperatively, VAS scale, side effects and analgesic requirements were recorded. Results There were no differences between the number of female and male patients. Postoperative pain was less in group L than group S, there was a statistically significant difference between L group and S group (p <0.05). The patient in the S group needs more rescue drug. L group had significantly better pain score versus S group at all intervals (2, 6, 12, 18, and 24) postoperative period. Conclusion Lidocaine 10% sprayed to 10 cm х 10 cm gauze swabs with neomycin and bacitracin ointment nasal pack provide better analgesic effect and reduced needs to analgesic requirement after septoplasty surgery.

483 Phenotype and Antibiotic Response in Patients With Elevated Baseline Hydrogen Breath Test Results: A Large Scale Database Analysis

INTRODUCTION: Breath testing (BT) is a non-invasive method used for diagnosis of small intestinal bacterial overgrowth (SIBO). Elevated baseline hydrogen breath test results, defined as no excessive methane and elevated hydrogen production >20 part per million (ppm), is an uncommon but important pattern in breath testing. This result has been difficult to understand in clinical settings. Multiple interpretations are used including an abnormal result suggesting SIBO or attributing to poor compliance with the diet for the test. Large-scale studies are lacking to explore the clinical characteristics of these patients and potential response to treatment regimens. METHODS: We reviewed a database of 14,847 consecutive lactulose breath tests performed between November 2005 and October 2013 at a single institution. All subjects underwent a low fermentation diet on the day prior to the test and fasted for at least 8 hours overnight. Compliance to diet and fasting was confirmed prior to testing. Breath tests with an elevated baseline hydrogen result (>20 ppm) were identified. A retrospective chart review was performed to retrieve patient characteristics including age, gender, BMI, symptoms, and medications. Furthermore, the response to and type of antibiotic treatment was assessed. RESULTS: A cohort of 107 patients with elevated baseline hydrogen BT was identified. Basic demographics showed females comprising 72%, mean age 40.3 (std dev 19.3) and mean BMI = 24.2 kg/m2 (std dev 5.7). The most common symptoms experienced included abdominal pain (84%), bloating/distention (87%), fecal urgency (82%) and flatulence (80%) (Table 1). Regarding medications relevant to SIBO, patients used PPI (31%), chronic narcotics (21%), probiotics (5%) and antidiarrheals (10%). In patients who were treated with antibiotics after an elevated baseline hydrogen result (n = 22), 55% responded to antibiotics. Response rates in the rifaximin alone group (n = 11) and rifaximin plus neomycin group (n = 4) were 73% and 25% respectively (P < 0.01) CONCLUSION: In the largest cohort of patients with elevated baseline hydrogen breath tests analyzed to date, the most common gastrointestinal symptoms were abdominal bloating, pain, and urgency. Response to rifaximin alone appeared better than rifaximin/neomycin however small sample sizes were analyzed. An elevated baseline hydrogen breath test can occur despite full compliance with diet and fasting prior to the test. Further prospective controlled studies are needed to validate these findings

Antibiotic Abuse Induced Histopathological and Neurobehavioral Disorders in Mice.

Introduction:Antibiotic abuse is a common phenomenon in Egypt as medications are prescribed without supervision. It is suggested that the excess use of antibiotics modifies the gut microbiota and plays a role in the development of neurological and psychiatric disorders.Objective:The aim of the present study was to use bulb-c mice as models for curam (amoxicillin /clavulanic acid) abuse compared to the locally acting neomycin model, then restoring the probiotic balance to look at the possible effects on the animal brains.Methods:The results showed early excitable brains demonstrated by S100b immunohistochemistry in both cortexes and hippocampuses of neomycin-treated mice. Staining with PAS stain showed no suggested neurodegenerative changes. Treatment with probiotics improved the S100b immunohistochemistry profile of the curam group partially but failed to overcome the neuroinflammatory reaction detected by hematoxylin and eosin stain. Curam was possibly blamed for the systemic effects.Results:The neurobehavioral tests showed delayed impairment in the open field test for the curam group and impaired new object recognition for the neomycin group. These tests were applied by video recording. The neurobehavioral decline developed 14 days after the end of the 3-week antibiotic course. Unfortunately, curam abuse induced animal fatalities.Conclusion:Antibiotic abuse has a neurotoxic effect that works by both local and more prominent systemic mechanisms. It can be said that antibiotic abuse is a cofactor behind the rise of neuropsychiatric diseases in Egypt.

Proton pump inhibitor therapy does not increase serum endotoxin activity in patients with cirrhosis

Proton pump inhibitors (PPIs) are frequently prescribed in patients with cirrhosis, but this therapy entails potential complications. We aimed to investigate the influence of PPI use on intestinal permeability in patients with cirrhosis. We recruited 228 patients with cirrhosis and divided them into four groups. Group (Gp)1 comprised patients receiving a PPI with concurrent neomycin (NEO) (PPI-NEO group, n = 14 [6.1%]), Gp2 and Gp3 comprised those receiving either PPI or NEO (PPI group, n = 91 [39.9%]; and NEO group, n = 11 [4.4%]), and Gp4 comprised those receiving neither of these medications (control group; n = 112 [49.1%]). We assessed the intestinal permeability by measuring endotoxin activity (EA) using a luminol chemiluminescence method. Endotoxin activity levels were significantly higher in patients with Child B cirrhosis than in those with Child A cirrhosis, but we found no significant differences in EA levels between patients with Child C cirrhosis and those with either Child A or B cirrhosis. We observed no significant differences in EA levels among groups 1-4. Patients without antibiotic exposure (n = 203), comprising 91 patients on PPI therapy (Gp2) and 112 no-PPI-therapy controls (Gp4), were subdivided according to Child-Pugh (CP) classification. We found no significant differences in EA levels between Gp2 and Gp4 in either CP class. Our results suggest that PPI usage does not have a significant impact on serum levels of gut-derived endotoxins, which are already elevated because of the increased intestinal permeability in patients with cirrhosis.

A Comparative Study on Efficacy of Polymyxin B, Neomycin and Polymyxin B, Neomycin, Hydrocortisone in the Treatment of Otitis Externa at Nepal Medical College and Teaching Hospital, Kathmandu

IntroductionAcute otitis externa (AOE) is a common but preventable ear condition. Tenderness with movement of the tragus or pinna is a classic feature of otitis Externa. Polymyxin B, neomycin, hydrocortisone preparations are the choice for first-line therapy when the tympanic membrane is intact. This study atiempted to compare the efficacy of polymyxin B, neomycin and polymyxin B, neomycin, hydrocortisone in the treatment of otitis Externa.ObjectiveTo compare the efficacy of polymyxin B, neomycin and polymyxin B, neomycin, hydrocortisone in the treatment of otitis Externa.MethodologyTo evaluate the efficacy of polymyxin B, neomycin and polymyxin B, neomycin, hydrocortisone in the treatment of otitis Externa, a hospital based, randomized, prospective study was conducted in Nepal Medical College and Teaching Hospital (NMCTH), Atiarkhel, Kathmandu from August 2012 to May 2014. 70 outpatients suffering from otitis Externa who met the inclusion and exclusion criteria were included. Patients were randomized into group A and group B with lotiery system. Odd number patients were included in group A and even number patients in group B. Group A patients received pack soaked with ribbon gauge in polymyxin B, neomycin ointment and Group B patients received pack soaked with ribbon gauge in polymyxin B, neomycin, hydrocortisone ointment. The patients were called for follow up after 48 hours and 96 hours to assess the improvement on the basis of tragal and circumduction tenderness either present or absent (present 1 or absent 2). A decrease in the clinical signs and symptoms (i.e. tragal and circumduc_on tenderness) was noted. Absence of pain was considered as clinically cured.ResultsIn comparison to polymyxin B, neomycin group, hydrocortisone group exhibited statistically significant effectiveness after 48 hours of treatment (p<0.05), but in cure rates after 96 hours, no statistical significant difference was observed between two groups (p>0.05).ConclusionPolymyxin B, neomycin, hydrocortisone group showed higher and faster cure rates than polymyxin B, neomycin group in the treatment of otitis Externa at 48 hours follow up. Birat Journal of Health SciencesVol.2/No.1/Issue 2/ Jan - April 2017, Page: 162-167

Effect of hydrogen peroxide on the lateral line hair cell regeneration of zebrafish

Objective:To investigate effect of hydrogen peroxide (H₂O₂) in the lateral line hair cell growth and regeneration after damage on zebrafish. Method:Select 5 dpf zebrafish, each group of 10, randomly divided into A control group: the system of water culture. B H₂O₂ group: 10 μmol/L, 20 μmol/L H₂O₂ solution to replace three times a day. C neomycin group: treatment with system water after 1 h culture by 200 μmol/L neomycin. D neomycin + H₂O₂ group: 20 μmol/L H₂O₂ solution to replace three times a day after 200 μmol/L neomycin treatment for 1 h. E cisplatin group: treatment with system water after 3 h culture by 1 000 μmol/L cisplatin. F cisplatin + H₂O₂ group: 20 μmol/L H₂O₂ solution to replace three times a day after 1 000 μmol/L cisplatin treatment for 3 h. Each group in H₂O₂ treatment for 0 h, 24 h, 48 h was marked their hair cells by immunofluorescence method and count the P1, P7, P8 neuromasts under the fluorescence microscope. Repeat 3 times. Result:The number of hair cells on P1, P7, P8 three neuramasts among 5 to 7 dpf zebrafish were 9.364±0.901(n=11),9.645±0.598(n=15),9.922±0.862(n=13), no obvious difference (P>0.05); 10μmol/L, 20μmol/L H₂O₂ treated zebrafish for 48 h, the numbers were 11.540±0.741,11.905±0.607,compaired with the control group(10.841±0.389), P<0.05; neomycin+ H₂O₂ 48 h and neomycin 48 h respectively were 10.600±0.689,8.767±0.603, P<0.01; cisplatin+ H₂O₂ 48 h and cisplatin 48 h were 5.967±1.086,5.633±1.548, P>0.05. Conclusion:20 μmol/L H₂O₂ promotes the development of lateral line hair cells of zebrafish; H₂O₂ promotes the regeneration of the lateral line hair cells after injury of neomycin, but not cisplatin.

The minimum peptides of IGF-1 and substance P protect vestibular hair cells against neomycin ototoxicity

Conclusions: Our data indicate that SSSR and SSSR + FGLM-NH2 protect sensory hair cells against neomycin-induced death in the vestibular epithelium. In addition, the results show that SSSR and FGLM-NH2 can be used as protective molecules against aminoglycoside ototoxicity. Objectives: This study investigated the role of the peptides SSSR and SSSR + FGLM-NH2 in mammalian vestibular hair cell death induced by aminoglycoside. Methods: Cultured utricles from mature CBA/N mice were used in this study. The cultured utricles were assigned to five groups (control group, neomycin group, neomycin + SSSR group, neomycin + FGLM-NH2 group, and neomycin + SSSR + FGLM-NH2 group). Aat 24 h after exposure to neomycin, the hair cells were labeled immunohistochemically, and the rate of survival of vestibular hair cells was evaluated using a fluorescence microscope. Results: The rate of survival of vestibular hair cells was significantly higher in the neomycin + SSSR and neomycin + SSSR + FGLM-NH2 groups than in the neomycin group. The results suggest that SSSR could protect hair cells against aminoglycoside ototoxicity.

Coenzyme Q10 protects hair cells against aminoglycoside.

It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10) is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group). In the neomycin group, utricles were cultured with neomycin (1 mM) to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30–0.3 µM). Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.

Antibiotic treatment of constipation-predominant irritable bowel syndrome.

The antibiotic rifaximin is used to treat non-constipated irritable bowel syndrome (IBS). Methane production is associated with constipation and its severity in constipation-predominant IBS (C-IBS). A previous retrospective study suggested that rifaximin and neomycin was superior to neomycin alone in improving symptoms in methane-positive subjects. To determine the effectiveness of neomycin alone or with rifaximin in improving symptoms in methane-positive C-IBS subjects. A double-blind, randomized, placebo-controlled trial was performed from 2010 to 2013 at three tertiary care centers. Subjects aged 18-65 with C-IBS (Rome II criteria) and breath methane (>3ppm) meeting the inclusion and exclusion criteria were recruited. Subjects completed a baseline symptom questionnaire rating the severity of abdominal and bowel symptoms on a visual analog scale and were randomized to receive neomycin and placebo or neomycin and rifaximin for 14 days. Symptom severity was assessed by weekly questionnaire for 2weeks of therapy and 4 additional weeks of follow-up. Thirty-one subjects (16 neomycin and placebo, 15 neomycin and rifaximin) were included in the intention-to-treat analysis. Constipation severity was significantly lower in the neomycin and rifaximin group (28.6±30.8) compared to neomycin alone (61.2±24.1) (P=0.0042), with greater improvement in constipation (P=0.007), straining (P=0.017) and bloating (P=0.020), but not abdominal pain. In the neomycin and rifaximin group, subjects with methane <3ppm after treatment reported significantly lower constipation severity (30.5±21.8) than subjects with persistent methane (67.2±32.1) (P=0.020). Rifaximin plus neomycin is superior to neomycin alone in improving multiple C-IBS symptoms. This effect is predicted by a reduction in breath methane.

Effect of the Antibiotic Neomycin on the Toxicity of the Glycoside Vicine in Rats

Vicine is hydrolyzed by microflora to highly reactive free radical generating compound divicine which causes mortality and other adverse effects. This study in the rats established the effect of a broad spectrum and poorly absorbed antibiotic, neomycin sulfate on the toxicity of vicine. The results showed extremely decrease in mortality rate in the group pretreated with neomycin. Hemoglobin (Hb) concentration, hematocrit (Hct) value, and red blood cells (RBCs) count were significantly decreased after injection of vicine and the improvement of these values in the group pretreated with neomycin. The same results were observed in white blood cells (WBCs). The results showed a significant decrease in glucose level and returned to normal in group pretreated with neomycin. Glutathione (GSH) was significantly decreased in the vicine group and returned to normal value in the group pretreated with neomycin. Lipid peroxide (TBARs) was significantly increased in the group treated with vicine and neomycin pretreated group decreased to the normal level. Glucose-6-phosphate dehydrogenase (G6-PD) activity was significantly decreased and returned to normal level in rats pretreated with neomycin. Serum protein and globulin were significantly decreased but serum albumin showed insignificant decrease in vicine and neomycin groups compared to control. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly decreased in the vicine group. The group pretreated with neomycin showed significantly increased activities of AST and ALT compared with vicine group. In conclusion, neomycin pretreatment of rats injected with glycoside vicine decreased to a great extent of its toxic and mortality effects and is useful in favism and hemolytic anemia.

Effect of Nystatin on Guinea Pigs’ Inner Ear

Nystatin is a topical antifungal agent. Its wide spectrum of action and low cost make it a treatment of choice. Though it is safe for external ear use, no study has proven its safety in cases of tympanic membrane perforation (TMP). We aim to test the safety of Nystatin when applied directly to the middle ear of a Guinea Pig model. We performed an experimental study with 18 Hartley Guinea Pigs that were divided into two groups. All tympanic membranes were perforated at the beginning of the study. Exposing one group to Nystatin and the other to the ototoxic Neomycin, we compared results of auditory brainstem response testing at three intervals. Each animals' contralateral ear was used as a negative control. At the end, we performed a histological analysis of the animals' cochleae using a scanning electron microscope (SEM). Average hearing loss in the Nystatin group was 13.0dB which was similar to the results obtained in the negative control group (13.1dB). Average hearing loss in the Neomycin group was 39.3dB, which represents a statistically significant difference (P<0.001). SEM evaluation revealed intact cochlear hair cell architecture in the Nystatin and normal saline groups, whereas significant hair cell losses were noted in the Neomycin group was noted. Nystatin does not cause hearing impairment or cochlear hair cell damage when exposed directly to the middle ear of a Guinea Pig model. It is therefore a safe treatment option for otomycosis with presence of TMP.

A Combination of Rifaximin and Neomycin Is Most Effective in Treating Irritable Bowel Syndrome Patients With Methane on Lactulose Breath Test

There is a growing interest in methane and its association with constipation in functional bowel disease. Neomycin-based treatment of methane-positive subjects has resulted in improvement of constipation. Rifaximin, although superior for the treatment of irritable bowel syndrome compared with other antibiotics, seems less effective in methane-positive subjects. In this study, we evaluate 3 different antibiotic treatments in patients who have a methane-positive breath test: rifaximin only, neomycin only, and the combination of neomycin and rifaximin. A retrospective chart review was conducted on patients with methane on their lactulose breath test (> or =3 ppm of methane) who received one of the following antibiotic treatments: 500 mg b.i.d. for 10 days of neomycin alone, 400 mg t.i.d. for 10 days of rifaximin alone, or a combination of both rifaximin and neomycin for 10 days. All patients must have received antibiotic treatment after their initial consultation at the medical center and, in addition, had at least 1 follow-up to evaluate the effects of the treatment. After inclusion/exclusion criteria were met, all charts were evaluated to determine if the subject was a responder to the antibiotic therapy. This included clinical symptom improvement and eradication of methane on their breath test. Of the subjects receiving the treatment of rifaximin and neomycin (n=27), 85% had a clinical response, compared with 63% of subjects in the neomycin only group (n=8) (P=0.15) and 56% of subjects in the rifaximin only group (n=39) (P=0.01). When comparing the neomycin group with the rifaximin group, the difference was nonsignificant. When evaluating methane eradication results, 87% of subjects taking the rifaximin and neomycin combination eradicated the methane on their breath test. This is compared with 33% of subjects in the neomycin group that eradicated the methane (P=0.001), and only 28% of subjects in the rifaximin group (P=0.001). Of the patients who did not eliminate the methane with only rifaximin treatment, 66% of those who subsequently used the rifaximin and neomycin treatment were able to normalize their breath test. The combination of rifaximin and neomycin is more effective in treating methane-producing subjects-in both clinical response and methane elimination.

Thermodynamics and Kinetics of Association of Antibiotics with the Aminoglycoside Acetyltransferase (3)-IIIb, a Resistance-Causing Enzyme

The thermodynamic and kinetic properties of interactions of antibiotics with the aminoglycoside acetyltransferase (3)-IIIb (AAC) are determined with several experimental methods. These data represent the first such characterization of an enzyme that modifies the 2-deoxystreptamine ring common to all aminoglycoside antibiotics. Antibiotic substrates for AAC include kanamycin A, kanamycin B, tobramycin, sisomicin, neomycin B, paromomycin, lividomycin A, and ribostamycin. Kinetic studies show that kanamycin group aminoglycosides have higher k(cat) values than members of the neomycin group. Only small aminoglycosides without intraring constraints show substrate inhibition. Isothermal titration calorimetry (ITC) and fluorescence measurements are consistent with a molecular size-dependent stoichiometry where binding stoichiometries are 1.5-2.0 for small antibiotics and 1.0 for larger. Antibiotic-enzyme interaction occurs with a favorable enthalpy (DeltaH < 0) and a compensating unfavorable entropy (TDeltaS < 0). The presence of coenzyme A significantly increases the affinity of the antibiotic for AAC. However, the thermodynamic properties of its ternary complexes distinguish this enzyme from other aminoglycoside-modifying enzymes (AGMEs). Unlike other AGMEs, the enthalpy of binding becomes more favored by 1.7-10.0-fold in the presence of the cosubstrate CoASH, while the entropy becomes 2.0-22.5-fold less favored. The overall free energy change is still only 1.0-1.9 kcal/mol from binary to ternary for all antibiotics tested, which is similar to those for other aminoglycoside-modifying enzymes. A computationally derived homology model provides structural support for these conclusions and further indicates that AAC is likely a member of the GCN5-related acetyltransferase family of proteins.

Neomycin binding preserves extracellular matrix in bioprosthetic heart valves during in vitro cyclic fatigue and storage

Bioprosthetic heart valve (BHV) cusps have a complex architecture consisting of an anisotropic arrangement of collagen, glycosaminoglycans (GAGs) and elastin. Glutaraldehyde (GLUT) is used as a fixative for all clinical BHV implants; however, it only stabilizes the collagen component of the tissue, and other components such as GAGs and elastin are lost from the tissue during processing, storage or after implantation. We have shown previously that the effectiveness of the chemical crosslinking can be increased by incorporating neomycin trisulfate, a hyaluronidase inhibitor, to prevent the enzyme-mediated GAG degradation. In the present study, we optimized carbodiimide-based GAG-targeted chemistry to incorporate neomycin into BHV cusps prior to conventional GLUT crosslinking. This crosslinking leads to enhanced preservation of GAGs during in vitro cyclic fatigue and storage. The neomycin group showed greater GAG retention after both 10 and 50 million accelerated fatigue cycles and after 1 year of storage in GLUT solution. Thus, additional binding of neomycin to the cusps prior to standard GLUT crosslinking could enhance tissue stability and thus heart valve durability.

Neomycin Improves Constipation-Predominant Irritable Bowel Syndrome in a Fashion That Is Dependent on the Presence of Methane Gas: Subanalysis of a Double-Blind Randomized Controlled Study

Recent studies have shown that normalization of the lactulose breath test (LBT) with neomycin leads to a significant reduction in irritable bowel syndrome (IBS) symptoms. This subanalysis was done on the constipation-predominant IBS subgroup of patients (C-IBS) to test the ability of neomycin to improve constipation and its correlation with the elimination of methane on breath test. IBS subjects underwent LBT in a blinded fashion. They were then randomly allocated to neomycin or placebo groups. For the purpose of this analysis, only the C-IBS subjects were identified. They were then evaluated for global improvement, abdominal pain, and constipation severity. The ability of neomycin to eliminate methane and its associated improvement in constipation was also determined. One hundred eleven subjects meeting Rome I criteria for IBS were included in the study. Thirty-nine of these had C-IBS. Of these, 20 received placebo and 19 received neomycin. With neomycin, a global improvement of 36.7+/-7.9% was seen, compared to 5.0+/-3.2% for placebo (P < .001) in the intention-to-treat analysis. Constipation was improved by 32.6+/-9.9% with neomycin compared to 18.7+/-7.2% for placebo (P=.26). Of the original 111 subjects, 12 demonstrated methane on breath test. All 12 of these patients were constipation predominant. In the methane producers receiving neomycin or placebo, improvement in constipation was significantly greater in those receiving neomycin (44.0+/-12.3%) compared to placebo (5.0+/-5.1%) (P < .05). Treatment with neomycin improves constipation in C-IBS. This improvement depends on the presence and elimination of methane on breath test.

Lactulose breath testing, bacterial overgrowth, and IBS: just a lot of hot air?

Lactulose breath testing, bacterial overgrowth, and IBS: just a lot of hot air?