- Structural analysis of a novel N-carbamoyl-d-amino acid amidohydrolase from a Brazilian Bradyrhizobium japonicum strain: In silico insights by molecular modelling, docking and molecular dynamics. [Journal Article]
- JMJ Mol Graph Model 2018 Oct 09; 86:35-42
- In this work we performed several in silico analyses to describe the relevant structural aspects of an enzyme N-Carbamoyl-d-amino acid amidohydrolase (d-NCAase) encoded on the genome of the Brazilian...
In this work we performed several in silico analyses to describe the relevant structural aspects of an enzyme N-Carbamoyl-d-amino acid amidohydrolase (d-NCAase) encoded on the genome of the Brazilian strain CPAC 15 (=SEMIA 5079) of Bradyrhizobium japonicum, a nonpathogenic species belonging to the order Rhizobiales. d-NCAase has wide applications particularly in the pharmaceutical industry, since it catalyzes the production of d-amino acids such as D-p-hydroxyphenylglycine (D-HPG), an intermediate in the synthesis of β-lactam antibiotics. We applied a homology modelling approach and 50 ns of molecular dynamics simulations to predict the structure and the intersubunit interactions of this novel d-NCAase. Also, in order to evaluate the substrate binding site, the model was subjected to 50 ns of molecular dynamics simulations in the presence of N-Carbamoyl-d-p-hydroxyphenylglycine (Cp-HPG) (a d-NCAase canonical substrate) and water-protein/water-substrate interactions analyses were performed. Overall, the structural analysis and the molecular dynamics simulations suggest that d-NCAase of B. japonicum CPAC-15 has a homodimeric structure in solution. Here, we also examined the substrate specificity of the catalytic site of our model and the interactions with water molecules into the active binding site were comprehensively discussed. Also, these simulations showed that the amino acids Lys123, His125, Pro127, Cys172, Asp174 and Arg176 are responsible for recognition of ligand in the active binding site through several chemical associations, such as hydrogen bonds and hydrophobic interactions. Our results show a favourable environment for a reaction of hydrolysis that transforms N-Carbamoyl-d-p-hydroxyphenylglycine (Cp-HPG) into the active compound D-p-hydroxyphenylglycine (D-HPG). This work envisage the use of d-NCAase from the Brazilian Bradyrhizobium japonicum strain CPAC-15 (=SEMIA 5079) for the industrial production of D-HPG, an important intermediate for semi-synthesis of β-lactam antibiotics such as penicillins, cephalosporins and amoxicillin.
- Salmonella enterica isolates from Western Australian rangeland goats remain susceptible to critically important antimicrobials. [Journal Article]
- SRSci Rep 2018 Oct 17; 8(1):15326
- This study investigated faecal carriage and antimicrobial resistance (AMR) of Salmonella enterica recovered from rangeland goats. Faecal samples (n = 400) were collected at slaughter from four consig...
This study investigated faecal carriage and antimicrobial resistance (AMR) of Salmonella enterica recovered from rangeland goats. Faecal samples (n = 400) were collected at slaughter from four consignments of goats (n = 100 samples per consignment), each from one of four localities in Western Australia. Carriage of Salmonella spp. was detected in 106 samples (26.5%; 95% CI 22.4-31.0%). The rate of faecal carriage for each consignment ranged between 23-30%. PCR assays targeting the STM2755 and STM4497 genes revealed 84.9% (90/106) of the isolates were of serovar Typhimurium. Salmonella Chester (11/106, 10.4%) and S. Saintpaul (5/106, 4.7%) were characterised at invA and ompF genes. Antimicrobial susceptibility testing demonstrated that 84.0% of isolates were susceptible to all tested (n = 13) antimicrobials. Resistance was identified to azithromycin (14.2%), tetracycline (10.4%), ampicillin (5.7%), amoxicillin-clavulanate and cefoxitin (3.8%), trimethoprim/sulfamethoxazole (1.9%), gentamicin and streptomycin (0.9%). No isolate was resistant to four or more antimicrobials, or to critically important antimicrobials such as fluoroquinolones and extended spectrum cephalosporins. This is the first study reporting AMR in Salmonella isolates from Australian rangeland goats. The rate of detection of AMR was very low, some resistance to low-importance drugs was present in the Salmonella population, despite the absence of active selection pressure.
- The Pregnant Patient: Managing Common Acute Medical Problems. [Journal Article]
- AFAm Fam Physician 2018 Nov 01; 98(9):595-602
- Women often see their primary care physicians for common acute conditions during pregnancy. These conditions may be caused by pregnancy (obstetric problems) or worsened by pregnancy (obstetrically ag...
Women often see their primary care physicians for common acute conditions during pregnancy. These conditions may be caused by pregnancy (obstetric problems) or worsened by pregnancy (obstetrically aggravated problems), or they may require special consideration during pregnancy because of maternal or fetal risks (nonobstetric problems). Primary care physicians should know the differential diagnosis for common conditions during pregnancy and recognize the important findings of obstetric and urgent nonobstetric problems. The family physician can evaluate and treat most nonobstetric problems, although obstetric problems require referral to a primary maternity care clinician. A tiered approach, including routinely looking for all-cause red flag symptoms and signs, while remaining aware of estimated gestational age, allows for high-quality care and shared decision making between the family physician and the pregnant patient. When treating common causes of nausea and epigastric pain/gastroesophageal reflux, lifestyle modifications are considered the safest and first-choice therapy, followed by well-established low-risk therapies, such as vitamin B6 (pyridoxine) and doxylamine for nausea, and antacids not containing salicylates (found in bismuth combination products) for gastroesophageal reflux. Other common conditions during pregnancy are best treated with low-risk therapies, such as using antihistamines or topical steroids for rashes, first-generation cephalosporins or amoxicillin for cystitis, and physical therapy and acetaminophen for low back pain and headaches.
- Dynamics of antimicrobial resistance of Helicobacter pylori isolates in the Smolensk region of Russian Federation. [Journal Article]
- HHelicobacter 2018 Oct 16; :e12545
- CONCLUSIONS: H. pylori resistance to clarithromycin remained low in the Smolensk region of Russian Federation between 2009 and 2017. Resistance to levofloxacin and metronidazole increased between 2009 and 2017.
- Electrochemical dewatering for the removal of hazardous species from sludge. [Journal Article]
- JEJ Environ Manage 2018 Oct 11
- This work focuses on the evaluation of the electrochemical dewatering of sludge polluted with model hazardous species. To do this, two sludge samples taken from the outlet of the anaerobic digesters ...
This work focuses on the evaluation of the electrochemical dewatering of sludge polluted with model hazardous species. To do this, two sludge samples taken from the outlet of the anaerobic digesters of the municipal Wastewater Treatment Facility of Ciudad Real were polluted with herbicide clopyralid (CP) and with antibiotics amoxicillin (AMX) and ampicillin (AMP), respectively. These sludge samples underwent first dewatering by press filtration and then, the dewatering continued by the application of an electrochemically assisted driven process with increasing electric fields (1.0, 2.0 and 3.0 V cm-1). Results demonstrate that the electrochemically-assisted process can help to exhaust the pollutant adsorbed onto the sludge and attain a supplemental removal (up to 15%) of water in both cases. This is a highly important result, because it can help to develop technologies for sludge treatment that avoid the diffusion of hazardous pollution during the land application of the sludge. No reactivity of the pollutants was observed during the tests.
- Efficacy of standard triple therapy versus Levofloxacin based alternate therapy against Helicobacter pylori infection. [Journal Article]
- JPJ Pak Med Assoc 2018; 68(9):1295-1299
- CONCLUSIONS: Effectiveness of both standard triple therapy and alternate triple therapy were found satisfactory to be used for treatment in our region. Levofloxacin based alternate therapy is safer to the patients. It can be used in conditions where adverse effects caused by standard therapy are unbearable.
- Distribution of hydrophilic and lipophilic antibacterial drugs in skim milk, cream, and casein. [Journal Article]
- JDJ Dairy Sci 2018 Oct 10
- This study determined the distribution of drugs to different milk fractions according to their physicochemical properties. Hydrophilic drugs tend to concentrate in skim milk, whereas lipophilic drugs...
This study determined the distribution of drugs to different milk fractions according to their physicochemical properties. Hydrophilic drugs tend to concentrate in skim milk, whereas lipophilic drugs tend to concentrate in cream. The concentration of a drug in casein is related to its degree of binding to milk proteins. Thus, we aimed to determine whether withdrawal time in whole milk differs from that in cream, casein, and skim milk. Amoxicillin and tylosin were selected as prototype hydrophilic and lipophilic drugs, respectively. The study was conducted in vitro and in vivo to determine whether in vitro conditions reflect the distribution of drugs in the different milk fractions in vivo. The in vivo study was conducted using a crossover design on 6 healthy Holstein dairy cattle. First, amoxicillin (i.m., single dose, 14 mg/kg) was administered to cows. Following a 1-wk washout period, tylosin (i.m., single dose, 15 mg/kg) was administered. Concentrations of amoxicillin and tylosin in milk and milk fractions were measured using HPLC-UV. In the in vitro study, 0.04 to 400 μg/g of amoxicillin and 0.05 to 50 μg/g of tylosin were spiked to drug-free milk and the concentrations in milk and milk fractions were measured. In addition, the percentage of total protein in milk and milk fractions was determined. Amoxicillin accumulated more in skim milk than in cream and casein, both in vitro (92%) and in vivo (73%, skim milk-to-whole milk ratio). The distribution of tylosin in whole and skim milk was similar to that of amoxicillin in the in vitro study, in contrast to the accumulation of tylosin in cream seen in vivo. However, the accumulation ratio of tylosin in cream was lower than expected. By either method, tylosin was less concentrated in casein than in skim milk and cream. The percentage of total protein was similar in skim milk and whole milk and higher than in cream. Thus, amoxicillin accumulates less in cream and casein, suggesting that these fractions would pose a lower risk to the consumer. Tylosin was still present at the maximum residue limit (50 μg/kg) 24 h after injection in the casein fraction and 48 h after injection in the cream fraction.
- Significance of the detection of Influenza and other respiratory viruses for Antibiotic Stewardship: The lessons from post-pandemic period. [Journal Article]
- IJInt J Infect Dis 2018 Oct 10
- CONCLUSIONS: Diagnosis of influenza is important for implementation of antimicrobial stewardship programs. Each institution should implement an algorithm for diagnosis and management of URTI. The biomarkers such as CRP and procalcitonin should be used more effectively.
- Maxillary osteomyelitis associated with osteopetrosis: Systematic review. [Review]
- JCJ Craniomaxillofac Surg 2018 Sep 24
- Osteopetrosis is a rare condition which presents increased bone density and deficient bone remodeling. The consequential complications include cranial nerve impairment due compression, bone fractures...
Osteopetrosis is a rare condition which presents increased bone density and deficient bone remodeling. The consequential complications include cranial nerve impairment due compression, bone fractures, and osteomyelitis. Maxillary osteomyelitis is uncommon even in osteopetrosis patients. This is a systematic review of the literature regarding the management and outcomes of maxillary osteomyelitis in patients with autosomal dominant osteopetrosis (ADO) type II. A case of this specific pathology is reported. There are 18 cases of maxillary osteomyelitis associated with ADO type II reported in the literature. The mean age of the patients reported was 33.5 (SD 15.9) years, and the male:female ratio was 1:1. Antibiotic therapy was variable, and amoxicillin with clavulanic acid was the main choice (33.33%). Surgery or sequestrectomy was performed in 88.89% of the studies. Complete healing was achieved in only 44.4% of cases. The treatment protocols remain controversial and often do not lead to complete healing. In the case that we report, complete healing was achieved after prolonged antibiotic therapy, hyperbaric oxygen therapy, and partial resection. In conclusion, the management of maxillary osteomyelitis in ADO type II patients is challenging, and complete resolution of the process is dependent on multiple interventions.
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- Rapid antibiotic susceptibility testing on blood cultures using MALDI-TOF MS. [Journal Article]
- PlosPLoS One 2018; 13(10):e0205603
- Antibiotic resistance is a major public health problem requiring the early optimization of antibiotic prescriptions. Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALD...
Antibiotic resistance is a major public health problem requiring the early optimization of antibiotic prescriptions. Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALDI-TOF MS) has been shown to accurately identify bacteria from positive blood culture. Here, we developed a rapid detection of Escherichia coli resistance to amoxicillin (AMX) and cefotaxime (CTX) from positive blood culture based on MALDI-TOF MS. Potential sparing of broad-spectrum antibiotics was also evaluated. We tested 103 E. coli-positive blood cultures. Blood cultures were subculture 1-hour in antibiotic-free rich liquid media before further incubation with and without AMX for 2.5 h or CTX for 2 h. Protein extracts associated with an internal control were spotted on a MALDI-TOF target and spectra were analyzed with the MBT-ASTRA prototype software (Bruker Daltonik GmbH, Bremen, Germany). Bacterial growth ratio was calculated from the AUC spectra obtained in the presence and absence of the antibiotic and compared to a threshold which classified E. coli as susceptible or resistant. Results were interpreted with MICs determined using agar dilution method as reference technique. MBT-ASTRA recognized 95% and 84% of the AMX- and CTX-susceptible isolates, respectively. Overall, quantitative analysis of mass spectra allows susceptibility testing within 4 hours after the positivity of blood culture with E. coli. At the first report of positive blood culture, MALDI-TOF MS would then provide the prescribers with the bacterial identification and the susceptibility to AMX and CTX, thus limiting the use of broad-spectrum compounds.