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- Ferrate(VI) oxidation of β-lactam antibiotics: reaction kinetics, antibacterial activity changes, and transformation products. [JOURNAL ARTICLE]
- Environ Sci Technol 2014 Jul 29.
Oxidation of β-lactam antibiotics by aqueous ferrate(VI) was investigated to determine reaction kinetics, reaction sites, antibacterial activity changes, and products. Apparent second-order rate constants (kapp) were determined in the pH range 6 - 9.5 for the reaction of ferrate(VI) with penicillins (amoxicillin, ampicillin, cloxacillin, and penicillin G), a cephalosporin (cephalexin), and several model compounds. Ferrate(VI) shows an appreciable reactivity toward the selected β-lactams (kapp for pH 7 = 110-770 M(-1) s(-1)). The pH-dependent kapp could be well explained by considering species-specific reactions between ferrate(VI) and the β-lactams (with reactions occurring at thioether, amine, and/or phenol groups). Based on the kinetic results, the thioether is the main reaction site for cloxacillin and penicillin G. In addition to the thioether, the amine is a reaction site for ampicillin and cephalexin, and amine and phenol are reaction sites for amoxicillin. HPLC/MS analysis showed that the thioether of β-lactams was transformed to stereoisomeric (R)- and (S)-sulfoxides and then to a sulfone. Quantitative microbiological assay of ferrate(VI)-treated β-lactam solutions indicated that transformation products resulting from the oxidation of cephalexin exhibited diminished, but non-negligible residual activity (i.e., ≥24% as potent as the parent compound). For the other β-lactams, the transformation products showed much lower (<5%) antibacterial potencies compared to the parent compounds. Overall, ferrate(VI) oxidation appears to be effective as a means of lowering the antibacterial activities of β-lactams, though alternative approaches may be necessary to achieve complete elimination of cephalosporin activities.
- Comparison of 7-day triple, 10-day sequential and 7-day concomitant therapies for Helicobacter pylori infection - a randomized controlled trial. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2014 Jul 28.
With rising prevalence of antimicrobial resistance, the failure rate of the standard triple therapy for H pylori infection is increasing. Sequential therapy and concomitant therapy have been recommended to replace standard triple therapy for H pylori eradication in regions with high clarithromycin resistance. The aim of this prospective, randomized, controlled study was to simultaneously assess the efficacies of 10-day sequential and 7-day concomitant therapies versus 7-day standard triple therapy for treating H pylori infection.Consecutive H pylori-infected subjects were randomly assigned to a 7-day standard triple therapy (pantoprazole, clarithromycin, and amoxicillin for 7 days), 10-day sequential therapy (pantoprazole and amoxicillin for 5 days, followed by pantoprazole, clarithromycin and metronidazole for a further 5 days) or 7-day quadruple therapy (pantoprazole, clarithromycin, amoxicillin and metronidazole for 7 days). H pylori status was confirmed 6 weeks after therapy.307 H pylori-infected participants were randomized to receive triple (n = 103), sequential (n = 102) or concomitant (n = 102) therapies. Eradication rates by intention-to-treat analysis in the three treatment groups were 81.6% (95% confidence interval (CI), 74.1 - 89.0%), 89.2% (95% CI, 83.2 - 95.2%) and 94.1% (95% CI, 89.5 - 98.7%). 7-day concomitant therapy had a higher eradication rate than 7-day triple therapy (Difference: 12.5%; 95% CI, 3.7 - 21.3%). There were no significant differences in eradication rates between sequential and standard triple therapies. All the three treatments exhibited similar frequencies of adverse events (8.7%, 8.8% and 13.7%, respectively) and drug compliance (99.0%, 98.0% and 100.0%, respectively).7-day concomitant therapy is superior to 7-day standard triple therapy for H pylori eradication. Additionally, it is less complex than 10-day sequential therapy for not changing drugs halfway through the treatment course.
- Biofilm formation in Haemophilus parasuis: relationship with antibiotic resistance, serotype and genetic typing. [JOURNAL ARTICLE]
- Res Vet Sci 2014 May 10.
Biofilms are surface-associated microbial communities, which are encased in self-synthesized extracellular environment. Biofilm formation may trigger drug resistance and inflammation, resulting in persistent infections. Haemophilus parasuis is the etiological agent of a systemic disease, Glässer's disease, characterized by fibrinous polyserositis, arthritis and meningitis in pigs. The purpose of this study was to examine the correlation between biofilm and antibiotic resistance among the clinical isolates of H. parasuis. In the present study, we tested biofilm-forming ability of 110 H. parasuis isolates from various farms using polystyrene microtiter plate assays. Seventy-three isolates of H. parasuis (66.4%) showed biofilm formation and most of them performed weak biofilm-forming ability (38/73). All isolates were tested for antimicrobial susceptibility to 18 antimicrobial agents by the broth microdilution method. H. parasuis isolates showed very high resistance (>90%) to sulfanilamide, nalidixic acid, and trimethoprim. Resistance to eight antibiotics such as penicillin (41.1% vs 8.1%), ampicillin (31.5% vs 8.1%), amoxicillin (28.8% vs 5.4%), gentamicin (46.6% vs 24.3%), cefazolin (19.2% vs 2.7%), doxycycline (19.2% vs 8.1%), cefotaxime (11% vs 2.7%), and cefaclor (13.7% vs 5.4%) was comparatively higher among biofilm producers than non-biofilm producers. Pulsed-field gel electrophoresis (PFGE) analyses could distinguish various isolates. Our data indicated that H. parasuis field isolates were able to form biofilms in vitro. In addition, biofilm positive strains had positive correlation with resistance to β-lactams antibiotics. Thus, biofilm formation may play important roles during H. parasuis infections.
- Epidural abscess caused by Veillonella parvula: Case report and review of the literature. [JOURNAL ARTICLE]
- J Microbiol Immunol Infect 2014 Jul 25.
Veillonella parvula, an anaerobic, Gram-negative coccus is part of the normal flora of the oral, gastrointestinal, respiratory, and genitourinary tracts in humans and animals. We herein present a case of epidural abscess caused by V. parvula in a 68-year-old man with sinus squamous cell carcinoma who presented with a 3-week history of low back pain. Blood and pus cultures were positive for Veillonella spp. After sequencing of the 16S ribosomal DNA, the pathogen was identified as V. parvula. Surgical debridement was performed following which the patient received intravenous administration of amoxicillin/clavulanate. To our knowledge, there are only seven reported cases of spinal infection caused by Veillonella spp. and these are reviewed here.
- Nitrofurantoin retains antimicrobial activity against multidrug-resistant urinary Escherichia coli from US outpatients. [JOURNAL ARTICLE]
- J Antimicrob Chemother 2014 Jul 25.
To examine the prevalence of multidrug-resistant (MDR) urinary Escherichia coli among US outpatients and to assess the antimicrobial activity of oral antibiotics commonly used to treat urinary tract infections (UTIs) against MDR isolates.Antimicrobial susceptibility testing data from outpatient urine cultures in The Surveillance Network (TSN) Database USA were analysed. Six antimicrobial agents from six separate drug classes were included: ampicillin, cefalotin, ciprofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole and amoxicillin/clavulanate. Isolates were categorized as resistant to one, two, three, four, five and six agents and compared for the years 2001 and 2010. Phenotypes of MDR isolates were assessed to determine antimicrobial activity of recommended therapy for UTIs.Prevalence of MDR E. coli increased from 9.1% in 2001 (n = 29 198) to 17.0% in 2010 (n = 32 742) (P < 0.0001). In isolates that demonstrated resistance to three, four or five antimicrobial agents in 2010, resistance to nitrofurantoin was observed in only 2.1%, 7.5% and 24.1% of isolates, respectively. Conversely, widespread resistance was observed for trimethoprim/sulfamethoxazole (62.6%, 88.6% and 97.9% for isolates resistant to three, four and five agents, respectively) and ciprofloxacin (48.9%, 84.3% and 98.2% for isolates resistant to three, four and five agents, respectively).Because of its consistent antimicrobial activity against MDR E. coli, nitrofurantoin remains a reliable first-line agent for the empirical treatment of acute uncomplicated cystitis.
- Preliminary Evaluation of Probiotic Properties of Lactobacillus Strains Isolated from Sardinian Dairy Products. [JOURNAL ARTICLE]
- Biomed Res Int 2014.:286390.
Twenty-three Lactobacillus strains of dairy origin were evaluated for some functional properties relevant to their use as probiotics. A preliminary subtractive screening based on the abilities to inhibit the growth of microbial pathogens and hydrolyze conjugated bile salts was applied, and six strains were selected for further characterization including survival under gastrointestinal environmental conditions, adhesion to gut epithelial tissue, enzymatic activity, and some safety properties. All selected strains maintained elevated cell numbers under conditions simulating passage through the human gastrointestinal tract, well comparable to the values obtained for the probiotic strain Lactobacillus rhamnosus GG, and were able to adhere to Caco-2 cells to various extents (from 3 to 20%). All strains exhibited high aminopeptidase, and absent or very low proteolytic and strong β-galactosidase activities; none was found to be haemolytic or to produce biogenic amines and all were susceptible to tetracycline, chloramphenicol, erythromycin, ampicillin, and amoxicillin/clavulanic acid. Our results indicate that the Lactobacillus strains analyzed could be considered appropriate probiotic candidates, due to resistance to GIT simulated conditions, antimicrobial activity, adhesion to Caco-2 cell-line, and absence of undesirable properties. They could be used as adjunct cultures for contributing to the quality and health related functional properties of dairy products.
- Easily missed, potentially fatal complication in an extremely preterm infant. [Journal Article]
- BMJ Case Rep 2014.
A baby girl was delivered by emergency caesarean section at 23+6 weeks gestation weighing 440 g. Apgar scores were 1, 3 and 4 at 1, 5 and 10 min, respectively. She was intubated and transferred to the neonatal intensive care unit. Umbilical arterial and venous lines and an orogastric tube (OGT) were inserted. On day 4 of life the OGT appeared to be outside of the gastrointestinal tract on X-ray. Feeds were held and contrast oesophagography confirmed suspicion of an oesophageal perforation. She was treated with intravenous metronidazole, gentamycin and amoxicillin and placed nil by mouth for 10 days. Resolution of the perforation was confirmed on repeat contrast study (day 10) and feeds were restarted with no further complications.
- Detection of antibiotics in goat's milk: effect of detergents on the response of microbial inhibitor tests. [Journal Article]
- J Dairy Res 2014 Aug; 81(3):372-7.
The aim of the study was to evaluate the interference of acid and alkaline detergents employed in the cleaning of milking equipment of caprine dairy farms on the performance of microbial tests used in antibiotic control (BRT MRL, Delvotest MCS, and Eclipse 100). Eight concentrations of commercial detergents, five acid (0-0·25%) and five alkaline (0-1%) were add to antimicrobial-free goat's milk to evaluate the detergent effect on the response of microbial inhibitor tests. To evaluate the effect of detergents on the detection capability of microbial tests two detergents at 0·5 ml/l (one acid and one basic) and eight concentrations of four β-lactam antibiotics (ampicillin, amoxicillin, cloxacillin and benzylpenicillin) were used. Milk without detergents was used as control. The spiked samples were analysed twelve times by three microbial tests. The results showed that the presence of acid detergents did not affect the response of microbial tests for any of the concentrations tested. However, at concentrations equal to or greater than 2 ml/l alkaline detergents positive results were found in microbial tests (16·7-100%). The detection limits of the screening tests for penicillins were not modified substantially by the presence of detergents. In general, the presence of acid and alkaline detergents in goat's milk did not produce a great interference in the microbial tests, only high concentrations of detergents could cause non-compliant results, but these concentrations are difficult to find in practice if proper cleaning procedures are applied in goat dairy farms.
- 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.