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Multidrug-resistant gram-negative bacterial infections have emerged as a major threat in hospitalized patients. Treatment options are often inadequate and, as a result, these infections are associated with high mortality. A cephalosporin and a novel synthetic non-β-lactam, β-lactamase inhibitor, ceftazidime-avibactam, is approved for the treatment of serious infections caused by resistant gram-negative bacteria. This article reviews the spectrum of activity, clinical pharmacology, pharmacodynamic and pharmacokinetic properties, clinical efficacy and tolerability, and dosing and administration of ceftazidime-avibactam.
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An in-house database of 520 compounds was docked against Entamoeba histolytica thioredoxin reductase (EhTrR), a promising target for the treatment of amoebiasis. Amongst these, some metronidazole (MTZ)-triazole hybrids were ranked high, with docking scores from -10.23 to -7.56. Studies of the binding orientations and conformations show that the head groups of MTZ-triazole hybrids interact with the arginine residues within the binding pocket of EhTrR, making it clear that such is the optimal and most reliable orientation for this class of compounds. The top-ten MTZ-triazole hybrids were then selected for evaluation of their activity against the HM1:IMSS strain of amoeba. The most active compound, 2-pyridyl-(1,2,3-triazolyl)metronidazole 10, with an IC50 value of 8.4 nM, was significantly more active than the standard drug MTZ alone. Docking studies revealed that compound 10 may act as an EhTrR inhibitor with activity in the nanomolar range and satisfactory ADME properties; it is a suitable candidate to be carried forward as a potential lead in the discovery of drugs to combat amoebiasis.
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Information was collected over an initial six-week period from 175 general dental practitioners on their current antibiotic prescribing practices. The information collected was the antibiotic prescribed including dose, frequency and duration, the clinically presenting signs and conditions, the medical history (if for prophylaxis), and any other reasons for prescribing. This was compared to the practitioners' antibiotic prescribing for a further six-week period following an audit, which included an educational component and the issuing of guidelines.
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A study of the predominant microflora in active sites of noma (cancrum oris) lesions was carried out in eight noma patients 3-15 years of age in Sokoto State in northwestern Nigeria. Paper point sampling and conventional anaerobic microbiologic techniques were used. Fusobacterium necrophorum was recovered from 87.5% of the noma lesions. Oral microorganisms included Prevotella intermedia, alpha-hemolytic streptococci, and Actinomyces spp. which were isolated from 75.0%, 50.0%, and 37.5% of the patients, respectively. Peptostreptococcus micros, Veillonella parvula, Staphylococcus aureus, and Pseudomonas spp. were each recovered from one lesion. The F. necrophorum and P. intermedia isolates were tested for antibiotic sensitivity to clindamycin, tetracycline, metronidazole, and penicillin using the E-test, and all strains were observed to be sensitive to all of the antibiotics tested with the exception of one strain of P. intermedia, which showed resistance to penicillin. The first reported isolation from human noma lesions of F. necrophorum, a pathogen primarily associated with animal diseases, may have important etiologic and animal transmission implications.
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The association of outlying peripheral neuropathy and inflammatory bowel disease is a rare fact leaving aside factors like the deficit of intestinal absorption of vitamins or the neurotoxicity of drugs employed for the treatment of the inflammatory bowel disease. We presented a series of four patients with this association, to whom a retrospective study was carried out. In all cases polineuropathy followed a course parallel to the inflammatory bowel disease, being acute and reversible in two cases. The polyneuropathy could be attributed to a deficit of vitamin B12 in one case and to metronidazole neurotoxicity in the other; in the remaining two cases the polineuropathy was chronic and no etiological factor could be found except for the own activity of the inflammatory bowel disease. We think that the neuropathy can represent a rare extraintestinal manifestation of the illness with a common autoimmune pathogenic mechanism. In one of our cases, the nerve biopsy demonstrated an axonal neuropathy with an alteration of the epineural vessels which showed a healed aspect.
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Postoperative clinical healing was similar in the 3 groups. There were no statistically significant differences between the 2 experimental groups in any parameters. Statistically significant differences were observed for AEJE, NCH, NBH, and NCTH in experimental groups when compared with the controls. Statistically significantly greater NCH, NBH, and NCTH were seen in the experimental groups than the controls and control defects showed longer AEJE than the experimental defects.
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We present a case of Clostridium difficile associated colitis in a 10-year-old girl; following 2 consecutive courses of oral antibiotics she developed severe diarrhea and a hip effusion. This is the fourth published pediatric case of C. difficile associated reactive arthritis. C. difficile toxins A and B were isolated from stool culture. She made a full recovery following metronidazole therapy.
The one-step spray-drying method was applied in the preparation of liposomes containing drug and cyclodextrin (CD). Spray-dried lecithin liposomes, entrapping metronidazole or verapamil alone or together with hydroxypropyl-beta-cyclodextrin (HP beta CD), were characterized for morphology, size distribution, and drug entrapment efficiency. The main factor influencing the liposomal size was the volume of aqueous medium used for hydration of the spray-dried product. No differences in size or entrapment between liposomes prepared by immediate hydration of dried powder or by hydration after 1 year of powder storage at 4 degrees C were observed. All liposomes were tested for their serum stability. The most stable liposomes (still retaining about 10% of the originally entrapped drug even after 24 hr incubation with serum) were liposomes prepared by the direct spray-drying of the mixture of lipid, drug, and HP beta CD.
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H. pylori-positive patients (n=228) were randomized to receive one of the 1-week regimens: lansoprazole 30 mg, clarithromycin 500 mg and amoxicillin 1 g (LAC), or lansoprazole 30 mg, clarithromycin 500 mg and metronidazole 500 mg (LMC), each given twice daily. H. pylori status was assessed by 13C-urea breath test and culture at diagnosis and by 13C-urea breath test 6 weeks after therapy. Antibiotic susceptibility was determined by E-test (n=98).
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Twenty pulpally involved non-vital carious human primary mandibular second molars with furcal abscess were randomly allocated into two groups to evaluate the efficacy of metronidazole gel (3% w/v) and metronidazole solution (0.5% w/v) against E. faecalis. Subjects in the first experimental group were subjected to treatment with metronidazole gel (3% w/v) and subjects in the second experimental group were treated with metronidazole solution (0.5% w/v). Two microbial samples (pre-operative and post-operative samples) were obtained from the root canals of each subject from both the groups; sub cultured and efficacy of both the groups were evaluated.
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The H. pylori eradication rates with concomitant therapy were higher than sequential therapy in both intention-to-treat (96.4% versus 81.4%, p = 0.012) and per-protocol (100% versus 85.4%, p = 0.006) analysis. The adverse effects in both groups were similarly mild. In the patients who received sequential therapy, clarithromycin resistance was significantly associated with eradication failure (p = 0.02). There were no significant differences in the antibiotic-resistant rates to amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin between the patients with and without T2DM.