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- Combined effects of two antibiotic contaminants on Microcystis aeruginosa. [JOURNAL ARTICLE]
- J Hazard Mater 2014 Jul 11.:148-155.
Combined toxicity of spiramycin and amoxicillin was tested in Microcystis aeruginosa. The respective 50% effective concentrations (EC50mix) expressed in toxic unit (TU) values were 1.25 and 1.83 for spiramycin and amoxicillin mixed at 1:7 and 1:1, suggesting an antagonistic interaction at the median effect level. Deviations from the prediction of concentration addition (CA) and independent action (IA) models further indicated that combined toxicity of two antibiotics mixed at 1:1 varied from synergism to antagonism with increasing test concentration. Both the EC50mix of 0.86 (in TU value) and the deviation from two models manifested a synergistic interaction between spiramycin and amoxicillin mixed at 7:1. At an environmentally relevant concentration of 800ngL(-1), combined effect of mixed antibiotics on algal growth changed from stimulation to inhibition with the increasing proportion of higher toxic component (spiramycin). Chlorophyll-a content and expression levels of psbA, psaB, and rbcL varied in a similar manner as growth rate, suggesting a correlation between algal growth and photosynthesis under exposure to mixed antibiotics. The stimulation of microcystin-production by mixed antibiotics was related with the elevated expression of mcyB. The mixture of two target antibiotics with low proportion of spiramycin (<50%) could increase the harm of M. aeruginosa to aquatic environments by stimulating algal growth and production and release of microcystin-LR at their current contamination levels.
- Is the standard dose of amoxicillin-clavulanic acid sufficient? [JOURNAL ARTICLE]
- BMC Pharmacol Toxicol 2014 Jul 21; 15(1):38.
The pharmacodynamic (PD) efficacy target of amoxicillin is 40% time above the minimal inhibition concentration (40%T > MIC). Recent studies of other antibiotics have shown that PD-efficacy targets are not always reached. The aim of this study was to evaluate the percentage of hospitalised patients, using amoxicillin/clavulanic acid intravenously (iv), that reach the pharmacodynamic efficacy target 40%T > MIC. Additionally, the association of demographic anthropomorphic and clinical parameters with the pharmacokinetics and pharmacodynamics of amoxicillin were determined.In serum of 57 hospitalised patients amoxicillin concentrations were measured using high performance liquid chromatography. Patients were older than 18 years and most patients had an abdominal infection. The standard amoxicillin/clavulanic acid dose was 4 times a day 1000/200 mg iv. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\Pharm 3.60). A one-compartment open model was used. Individual dosing simulations were performed with MW\Pharm.In our study population, the mean (+/-SD) age was 67 (+/-16) years and the mean clearance corrected for bodyweight was 0.17 (+/-0.07) L/h/kg. Only, 65% of the patients reached the proposed amoxicillin 40%T > MIC with amoxicillin/clavulanic acid for bacterial MICs of 8 mg/L. A computer simulated increase of the standard dose to 6 times daily, increased this percentage to 95%. In this small study group 40%T > MIC was not associated with clinical or microbiological cure.A substantial proportion of the hospitalised patients did not reach the 40%T > MIC with the standard dose amoxicillin/clavulanic acid for a bacterial MIC of 8 mg/L. Therefore, we suggest increasing the standard dose of amoxicillin/clavulanic acid to 6 times a day in patients with severe Enterobacteriaceae infections.Trial registration: Trial registration number: NTR1725 16th march 2009.
- Increased Release Time of Antibiotics from Bone Allografts through a Novel Biodegradable Coating. [Journal Article]
- Biomed Res Int 2014.:459867.
The use of bone allografts is contraindicated in septic revision surgery due to the high risk of graft reinfection. Antibiotic release from the graft may solve the problem and these combinations can theoretically be used for prevention or even therapy of infection. The present study investigated whether amoxicillin, ciprofloxacin, and vancomycin alone or in combination with chitosan or alginate are suitable for short-term or long-term bone coating. Human bone allografts were prepared from femoral head and lyophilized. Antibiotic coating was achieved by incubating the grafts in antibiotic solution and freeze-drying again. Two biopolymers chitosan and alginate were used for creating sustained-release implantable coatings and the drug release profile was characterized in vitro by spectrophotometry. Using lyophilization with or without chitosan only resulted in short-term release that lasted up to 48 hours. Alginate coating enabled a sustained release that lasted for 8 days with amoxicillin, 28 days with ciprofloxacin coating, and 50 days with vancomycin coating. Using only implantable biodegradable allograft and polymers, a sustained release of antibiotics was achieved with ciprofloxacin and vancomycin for several weeks. Since the calculated daily release of the antibiotic was lower than the recommended IV dose, the calcium alginate coated bone graft can support endoprosthesis revision surgery.
- Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. [Journal Article, Review]
- Infect Drug Resist 2014.:183-97.
Actinomycosis is a rare chronic disease caused by Actinomyces spp., anaerobic Gram-positive bacteria that normally colonize the human mouth and digestive and genital tracts. Physicians must be aware of typical clinical presentations (such as cervicofacial actinomycosis following dental focus of infection, pelvic actinomycosis in women with an intrauterine device, and pulmonary actinomycosis in smokers with poor dental hygiene), but also that actinomycosis may mimic the malignancy process in various anatomical sites. Bacterial cultures and pathology are the cornerstone of diagnosis, but particular conditions are required in order to get the correct diagnosis. Prolonged bacterial cultures in anaerobic conditions are necessary to identify the bacterium and typical microscopic findings include necrosis with yellowish sulfur granules and filamentous Gram-positive fungal-like pathogens. Patients with actinomycosis require prolonged (6- to 12-month) high doses (to facilitate the drug penetration in abscess and in infected tissues) of penicillin G or amoxicillin, but the duration of antimicrobial therapy could probably be shortened to 3 months in patients in whom optimal surgical resection of infected tissues has been performed. Preventive measures, such as reduction of alcohol abuse and improvement of dental hygiene, may limit occurrence of pulmonary, cervicofacial, and central nervous system actinomycosis. In women, intrauterine devices must be changed every 5 years in order to limit the occurrence of pelvic actinomycosis.
- Targeted adsorption of molecules in the colon with the novel adsorbent-based medicinal product, DAV132: a proof of concept study in healthy subjects. [JOURNAL ARTICLE]
- J Clin Pharmacol 2014 Jul 8.
During antibiotic treatments, active residuals reaching the colon profoundly affect the bacterial flora resulting in the emergence of resistance. To prevent these effects, we developed an enteric-coated formulated activated-charcoal based product, DAV132, meant to deliver its adsorbent to the ileum and neutralize antibiotic residues in the proximal colon. In a randomized, control, crossover study, the plasma pharmacokinetics of the probe drugs amoxicillin (500 mg) absorbed in the proximal intestine, and sulfapyridine (25 mg) metabolized from sulfasalazine in the cecum and rapidly absorbed, were compared after a single administration in 18 healthy subjects who had received DAV132, uncoated formulated activated charcoal (FAC) or water 16 and 8 hours before, concomitantly with the probe drugs, and 8 hours thereafter. The AUC0-96 h of amoxicillin was reduced by more than 70% when it was taken with FAC, but bioequivalent when it was taken with water or DAV132. By contrast, the AUC0-96 h of sulfapyridine was reduced by more than 90% when administered with either FAC or DAV132 in comparison with water. The results show that DAV132 can selectively adsorb drug compounds in the proximal colon, without interfering with drug absorption in the proximal small intestine, thereby constituting a proof of concept that DAV132 actually functions in humans.
- PPCPs removal by aerobic granular sludge membrane bioreactor. [JOURNAL ARTICLE]
- Appl Microbiol Biotechnol 2014 Jul 20.
An aerobic granular sludge membrane bioreactor (GMBR) was applied to the treatment of pharmaceutical and personal care products (PPCPs) wastewater. The influence of granular sludge on five antibiotic and antiphlogistic PPCPs wastewater and the removal effect of methyl alcohol and conventional organic matter were investigated while constantly reducing the density of inflow organic matter. The results showed that the sludge granulation process in the system was rapid but unstable, and that the system exhibits a dissolution-reunion dynamic equilibrium. The reactor demonstrated varying removal effects of PPCPs on different objects. The use of a GMBR was more effective for the removal of prednisolone, naproxen, and ibuprofen; the first two drugs were lower the average removal rate of which reached 98.46 and 84.02 %, respectively; whereas the average removal rate of ibuprofen was 63.32 %. By contrast, the GMBR has an insignificant degradation effect on antibiotics such as amoxicillin, indicating that such antibiotic medicine is not easily degraded by microorganisms, which plays different roles in system operation. Because of the different chemical structures and characteristics of drugs that result in various degradation behavior. During the GMBR granulation process, the value of mixed liquor volatility suspended solids (MLVSS) gradually increases from 1.5 to 4.1 g/L during the GMBR granulation process, and the removal rate of CODCr reaches up to 87.98 %. After reducing the density of organic matter is reduced, the removal rates of NH3-N and TP both reach more than 90 %, respectively. Moreover, the proposed technique is considerably effective in the removal of methanol.
- Amoxicillin-associated interference in an HPLC-EC assay for urinary fractionated metanephrines: potential pitfall in pheochromocytoma biochemical diagnosis. [JOURNAL ARTICLE]
- Clin Biochem 2014 Jul 16.
Ojective Measurement of urinary fractionated metanephrines represents a first-line test for the biochemical diagnosis of pheochromocytoma. The high performance liquid chromatography coupled to electrochemical detection (HPLC-EC) assays used in the routine clinical laboratory can be subjected to analytical interferences by the presence of drugs or their metabolites. In this paper we describe interference on urinary normetanephrine (uNMN) caused by amoxicillin. Design and methods Two pediatric patients suspected of pheochromocytoma had very high uNMN levels (2543 and 4227μg/g Cr respectively; upper reference value: 339μg/g Cr). Amoxicillin interference was assessed by comparison for co-elution with uNMN and by LC-MS/MS analysis.After amoxicillin interference was suspected and the therapy was stopped uNMN levels returned to normal (149 and 214μg/g Cr respectively). Chromatograms obtained by HPLC-EC clearly showed that amoxicillin co-elutes with uNMN. Patients' uNMN levels measured by LC-MS/MS were in the normal range.Amoxicillin is responsible for analytical interference on HPLC-EC assay for uNMN. This finding can be of help in distinguishing true- positive from false-positive results in the course of a biochemical diagnosis for pheochromocytoma.
- Epidemiology and pattern of antibiotic resistance in Helicobacter pylori: Scenario from Saudi Arabia. [JOURNAL ARTICLE]
- Saudi J Gastroenterol 2014 July-August; 20(4):212-218.
Helicobacter pylori is recognized as a major cause of gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoma. Infection with this gram-negative microaerophile has been treated using combination of antibiotics and proton pump inhibitors for different gastrointestinal diseases. The most commonly used treatment is triple therapy which consists of administration of a proton pump inhibitor, clarithromycin, and amoxicillin. Many factors contribute to treatment failure, but one of the main reasons is development of bacterial antibiotic resistance. The percent prevalence of antibiotic resistance varies among different countries; it appears to be partly determined by the geographic factors and its ability to undergo frequent homologous recombination. The aim of this paper is to review the prevalence of H. pylori infection, association of clinical outcomes with H. pylori genotypes, and current status of antibiotic resistance in H. pylori in Saudi Arabia. It also discusses the different alternative approaches for the treatment of H. pylori using antibiotics. In addition, association of antibiotic resistance with H. pylori virulent genotypes in Saudi population and its underlying resistance mechanism will also be discussed.
- Centipeda periodontii in human periodontitis. [JOURNAL ARTICLE]
- Odontology 2014 Jul 19.
This study assessed the subgingival occurrence of the flagellated, Gram-negative, anaerobic rod Centipeda periodontii in chronic periodontitis and periodontal health/gingivitis with species-specific nucleic acid probes, and evaluated the in vitro resistance of subgingival isolates to therapeutic levels of amoxicillin, metronidazole, and doxycycline. Subgingival plaque biofilm specimens from 307 adults with chronic periodontitis, and 48 adults with periodontal health/localized gingivitis, were evaluated with digoxigenin-labeled, whole-chromosomal, DNA probes to C. periodontii ATCC 35019 possessing a 10(4) cell detection threshold. Fifty-two C. periodontii subgingival culture isolates were assessed on antibiotic-supplemented enriched Brucella blood agar for in vitro resistance to either amoxicillin at 2 µg/ml, metronidazole at 4 µg/ml, or doxycycline at 2 µg/ml. A significantly greater subgingival occurrence of C. periodontii was found in chronic periodontitis subjects as compared to individuals with periodontal health/gingivitis (13.4 vs. 0 %, P < 0.003), although high subgingival counts of the organism (≥10(6) cells) were rarely detected (1.3 % of chronic periodontitis subjects). In vitro resistance was not found to amoxicillin or metronidazole, and to doxycycline in only 2 (3.9 %) of the 52 C. periodontii clinical isolates studied. These findings indicate that C. periodontii is not a major constituent of the subgingival microbiome in chronic periodontitis or periodontal health/gingivitis. The potential contribution of C. periodontii to periodontal breakdown in the few chronic periodontitis subjects who yielded high subgingival levels of the organism remains to be delineated. C. periodontii clinical isolates were susceptible in vitro to therapeutic concentrations of three antibiotics frequently used in treatment of human periodontitis.
- Making Sense of Cephalosporin and Amoxicillin/Clavulanate Susceptibility Testing for Uropathogens. [LETTER]
- Clin Infect Dis 2014 Jul 16.