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Despite the scientific advancements, organophosphate (OP) poisoning continues to be a major threat to humans, accounting for nearly one million poisoning cases every year leading to at least 20,000 deaths worldwide. Oximes represent the most important class in medicinal chemistry, renowned for their widespread applications as OP antidotes, drugs and intermediates for the synthesis of several pharmacological derivatives. Common oxime based reactivators or nerve antidotes include pralidoxime, obidoxime, HI-6, trimedoxime and methoxime, among which pralidoxime is the only FDA-approved drug. Cephalosporins are β-lactam based antibiotics and serve as widely acclaimed tools in fighting bacterial infections. Oxime based cephalosporins have emerged as an important class of drugs with improved efficacy and a broad spectrum of anti-microbial activity against Gram-positive and Gram-negative pathogens. Among the several oxime based derivatives, cefuroxime, ceftizoxime, cefpodoxime and cefmenoxime are the FDA approved oxime-based antibiotics. Given the pharmacological significance of oximes, in the present paper, we put together all the FDA-approved oximes and discuss their mechanism of action, pharmacokinetics and synthesis.

To describe the occurrence of carbapenem resistance among multidrug-resistant (MDR) Escherichia coli and Klebsiella pneumoniae isolated from clinical specimens in Accra using phenotypic and genotypic methods. The study was cross-sectional, involving 144 clinical MDR E. coli and K. pneumoniae isolates recovered from the Central Laboratory of the Korle Bu Teaching Hospital (KBTH). The isolates were re-cultured bacteriologically, identified using standard biochemical tests, and subjected to antibiotic susceptibility testing using the Kirby-Bauer method. Carbapenem resistance was determined based on imipenem, meropenem, and ertapenem zones of inhibition, as well as minimum inhibitory concentrations (MICs). Carbapenemase production was determined phenotypically by modified Hodge test (MHT) and modified carbapenem inactivation method (mCIM), and genotypically with multiplex PCR targeting the blaKPC, blaIMP, blaNDM, blaVIM, and blaOXA-48 genes. Of the 144 MDR isolates, 69.4% were E. coli, and 30.6% were K. pneumoniae. The distribution of antimicrobial resistance rates among them was ampicillin (97.2%), cefuroxime (93.1%), sulfamethoxazole-trimethoprim (86.8%), tetracycline (85.4%), cefotaxime and cefpodoxime (77.1% each), amoxicillin-clavulanate (75%), ceftriaxone (73.6%), ciprofloxacin (70.8%), levofloxacin (66.0%), cefepime (65.3%), ceftazidime (64.6%), gentamicin (48.6), piperacillin-tazobactam (40.3%), cefoxitin (14.6%), amikacin (13.9%), ertapenem and meropenem (5.6% each), and imipenem (2.8%). In total, 5.6% (8/144) of them were carbapenem-resistant (carbapenem MIC range = 0.094-32.0 μg/ml), with 75% (6/8) of these testing positive by the phenotypic tests and 62.5% (5/8) by the genotypic test (of which 80% [4/5] carried blaOXA-48 and 20% (1/5) blaNDM). The blaVIM, blaIMP, and blaKPC genes were not detected. Although the rates of antibiotic resistance among the isolates were high, the prevalence of carbapenemase producers was low. The finding of blaOXA-48 and blaNDM warrants upscaling of antimicrobial resistance surveillance programmes and fortification of infection prevention and control programmes in the country.

Purpose In diabetes, multi-organ level dysfunction arising from metabolic complications is reported to influence the pharmacokinetics (PK) profile of many drugs. Hence, the present study was planned in rats to evaluate the effect of diabetes on the PK profile of cefpodoxime, a widely prescribed oral antibiotic. Method PK profile of cefpodoxime was assessed after oral administration of cefpodoxime proxetil (10 and 20 mg/kg) and intravenous ( i.v ) administration of cefpodoxime sodium (10 mg/kg) in normal and streptozotocin induced diabetic rats. To evaluate the impact of diabetes on oral absorption and serum protein binding, in situ intestinal permeability and in vitro serum protein binding studies were performed for cefpodoxime using Single Pass Intestinal Perfusion model (SPIP) and ultracentrifugation technique, respectively. Result In diabetic rats, there was significant ( p < 0.01 ) decrease in maximum concentration (C max ) and area under the curve (AUC) of cefpodoxime by both oral and intravenous route, which was attributed to augmented clearance of cefpodoxime. There was no change in the time to achieve C max (T max ) suggesting no alteration in oral absorption which was further confirmed through unaltered intestinal permeability in diabetic rats. The protein binding in diabetic rats also remained unchanged, indicating no influence of protein binding on elevated clearance. Conclusion The plasma exposure of cefpodoxime, a renally eliminated drug was significantly lowered in diabetic rats due to enhanced glomerular filtration. However, this observation needs to be confirmed through well controlled clinical trials.

Background The global incidence of foodborne infections and antibiotic resistance is recently increased and considered of public health concern. Currently, scarcely information is available on foodborne infections and ESBL associated with poultry and beef meat in Egypt. Methods In total, 180 chicken and beef meat samples as well as internal organs were collected from different districts in northern Egypt. The samples were investigated for the prevalence and antibiotic resistance of Salmonella enterica serovars and Escherichia coli . All isolates were investigated for harbouring class 1 and class 2 integrons. Results Out of 180 investigated samples 15 S. enterica (8.3%) and 21 E. coli (11.7%) were isolated and identified. S. enterica isolates were typed as 9 S. Typhimurium (60.0%), 3 S. Paratyphi A (20.0%), 2 S . Enteritidis (13.3%) and 1 S. Kentucky (6.7%). Twenty-one E. coli isolates were serotyped into O1, O18, O20, O78, O103, O119, O126, O145, O146 and O158. The phenotypic antibiotic resistance profiles of S. enterica serovars to ampicillin, cefotaxime, cefpodoxime, trimethoprim/sulphamethoxazole and tetracycline were 86.7, 80.0, 60.0, 53.3 and 40.0%, respectively. Isolated E. coli were resistant to tetracycline (80.9%), ampicillin (71.4%), streptomycin, trimethoprim/sulphamethoxazole (61.9% for each) and cefotaxime (33.3%). The dissemination of genes coding for ESBL and AmpC β-lactamase in S. enterica isolates included bla CTX-M (73.3%), bla TEM (73.3%) and bla CMY (13.3%). In E. coli isolates bla TEM , bla CTX-M and bla OXA were identified in 52.4, 42.9 and 14.3%, respectively. The plasmid-mediated quinolone resistance genes identified in S. enterica were qnr A (33.3%), qnr B (20.0%) and qnr S (6.7%) while qnr A and qnr B were detected in 33.3% of E. coli isolates. Class 1 integron was detected in 13.3% of S. enterica and in 14.3% of E. coli isolates. Class 2 integron as well as the colistin resistance gene mcr -1 was not found in any of E. coli or S. enterica isolates. Conclusions This study showed high prevalence of S. enterica and E. coli as foodborne pathogens in raw chicken and beef meat in Nile Delta, Egypt. The emergence of antimicrobial resistance in S. enterica and E. coli isolates is of public health concern in Egypt. Molecular biological investigation elucidated the presence of genes associated with antibiotic resistance as well as class 1 integron in S. enterica and E. coli .

Background Strengthening global surveillance for antimicrobial resistance (AMR) is critical. Our study focused on antibiotic prescribing errors (APE) in a psychiatric hospital, a possible cause for AMR. Data sets are essential, especially in negligent settings such as psychiatric hospitals. Methods An observational study was conducted at the psychiatric hospital St. Josef AMEOS, Oberhausen, Germany (Jan. 2023-2024) and approved by the ethics committee. The therapeutic protocols (TP) of all patients were collected. The frequency, location, responsible person (RP), type and reason of each APE were analyzed according to the EQUIP methodology. In addition, a clinical pharmacology specialist evaluated possible side effects and effects on the psychopathology of the patient using the FDA database drugs.com. Results Of 6805 TP, 130 included APE (51.5%male: 49.5%female, duration of antibiotic therapy: 5 ± 1.2 days, length of stay: 7.3 ± 2.4 days). 3 APE had serious side effects due to allergic reaction. 20 APE were isolated in the addiction clinic. RP were residents. 121 APE were dose-related, only 9 APE were due to writing failures. The frequency of APE according to substance was: amoxicillin (n = 42), amoxicillin/clavulanic acid (n = 31), cefuroxime (n = 28), cefpodoxime (n = 21), ciprofloxacin (n = 7), meropenem (n = 1). Pharmacological evaluation revealed an interaction between valproic acid and meropenem, and raised the adverse effect profile of ciprofloxacin administration. A drug specific algorithm was developed for the prevention of possible APE - AMR. Conclusions Although the incidence of APE in psychiatric setting is low, it remains an important issue of potential allergic reaction and AMR. Psychiatric settings need to evaluate their APE and take action on this public health issue. Key messages • Research concerning antibiotic prescribing errors is an important issue for psychiatric hospitals and has impact on public health and society. • Algorithms are important intervention to reduce antimicrobial resistance:

This research aimed to improve the solubility and stabilize cefpodoxime proxetil (CP), a class IV drug, by amorphous solid dispersion (ASD) technique. Four formulations were prepared by dispersing amorphous CP in soluplus, polyvinylpyrrolidone (PVP K30), and ethyl cellulose (EC) blends in different compositions and ratios. The optimum formulation was stored in accelerated conditions at 40 °C and 75% relative humidity for six months. The drug's solubility and dissolution rate in different systems were explored. Furthermore, Differential Scanning Calorimetry (DSC), X-ray Powder Diffractometry (PXRD), Fourier Transform Infrared spectroscopy (FTIR), and Field Emission Scanning Electron Microscopy (FESEM) were used to examine the physical state of the drug. The antibacterial activity of the drug was evaluated during the experiment. When mixing CP with soluplus and PVP K30 in a 1:1:1 ratio as ASD, the drug solubility at pH 1.2 enhanced about 28 folds than a pure drug, and the dissolution rate increment was observed. The DSC, FTIR, and PXRD data confirmed the drug is amorphous and miscible with these polymers. FESEM revealed particle size reduction. The antibacterial activity was raised. After storage in the accelerated condition, physical investigations indicated that no recrystallization occurred, and this condition had little effect on in vitro drug dissolution and antibacterial activity. This can be a good indicator of the drug's solubility enhancement and physical stability optimization that will make the possibility of preparing this drug in the future as an oral solid dosage form with the possibility of manufacturing with a drug company due to the promising results.

This study aimed to investigate how the presence of co-morbid conditions influenced antimicrobial usage as presumptive prophylaxis for suspected bacteremia in dogs and cats undergoing dental treatments at primary care veterinary clinics in the United States. In 2020, data was collected from 1076 veterinary clinics across 44 US states. A total of 681,541 general anesthesia dental procedures were conducted on 592,472 dogs and 89,069 cats. This revealed that systemic antimicrobials were administered in 8.8% of dog procedures and 7.8% of cat procedures in the absence of concurrent periodontal disease or extractions. Cefpodoxime, clindamycin, and amoxicillin-clavulanate were the most frequently used antimicrobials in dogs, while cefovecin, amoxicillin-clavulanate, and clindamycin topped the list for cats. Dogs with cardiovascular, hepato-renal, and endocrine co-morbidities, as well as those undergoing concurrent removal of cutaneous or subcutaneous neoplasia, displayed higher antimicrobial use. Similarly, cats with endocrine or hepato-renal disease, retroviral infection (i.e., feline leukemia virus (FeLV), feline immunodeficiency virus (FIV)), and concurrent removal of cutaneous or subcutaneous neoplasia exhibited increased antimicrobial use. Dogs with hepato-renal abnormalities had longer treatment durations compared to those without (10.1 vs. 9.6 days). Conversely, cats with concurrent removal of cutaneous or subcutaneous neoplasia had shorter durations of treatment as compared to those that did not have this procedure performed (8.4 vs 9.2 days). The findings of this study underscore the necessity for further research and collaboration within the veterinary community to develop evidence-based guidelines, promoting responsible antimicrobial use, and advancing the field of veterinary dentistry for enhanced patient outcomes.

[...]the developed method for taste masking CFPD PRXL and preparing orodispersible tablets proved to be simple, cost-effective, and potentially suitablefor industrialapplication. In a previous study, the preparation and evaluation of the DRC was performed using Kyron T-114, a weak acid derivative of methyl acrylic acid cross-linked polymer having a carboxylic acid functional group, which is responsible for its taste masking property for a pharmaceutical suspension; however, its use in tablet formulation was not investigated. [...]the specific objective of this present study was to develop and evaluate an orally disintegrating tablet (ODT) of CFPD PRXL using the optimized DRC that were utilized for suspension formulation (6). Dispersible tab-lets, as defined by the US Food and Drug Administra-tion's (FDA's) Center for Drug Evaluation and Research (CDER), consist of a fine mixture of dry, divided drugs and/or chemicals that, when combined with suitable vehi-cles, yield a tablet (8). The dry powder blend, prepared for compression, underwent evaluation for flow properties and drug content.

Abstract Introduction/Objective Acinetobacter baumannii is a multi-drug resistant gram-negative bacterium often isolated in water and soil. A challenge in both human and veterinary nosocomial infections, Acinetobacter is adaptable, forming biofilms and carbapenem resistance (CRAB). As an opportunistic infection, Acinetobacter is an emerging pathogen especially in immunocompromised individuals which include marginalized housing insecure populations. Anchorage dedicates large areas for urban park environments providing high impact of human and moose wildlife interaction. Previous studies link zoonotic transmission of bacteria through direct fecal contact or water contamination. The significant number of vulnerable unsheltered individuals in Anchorage using public green belts presents a potential risk for Acinetobacter baumannii colonization. Methods/Case Report To assess environmental Acinetobacter exposure from urban wildlife, we ground collected 150 moose fecal samples between 2019-2022. Samples were placed into support medium, cultured onto MacConkey agar and incubated at 37C. Biochemical identification and antibiotic susceptibility testing were performed using MicroScan™ (Beckman/Coulter Brea, CA) conventional panels with antimicrobial interpretation along clinical laboratory standards (CLSI). Results (if a Case Study enter NA) Acinetobacter baumannii was isolated in moose feces, with proportion of positive samples increasing annually: 7.5% (2019), 12.5% (2020), and 14.2% (2021). Antimicrobial analysis found 100% of samples resistant to cefpodoxime, cefazolin, ceftriaxone, cefuroxime, ampicillin, and ampicillin-sulbactam, with 72% resistant to ertapenem and imipenem. Aztreonam resistance was 22%, cefepime 17%, with only 5% resistant to ciprofloxacin. Conclusion The increasing colonization of moose feces with multi-drug resistant Acinetobacter baumannii potentially poses a significant public health risk in Anchorage, Alaska. With moose inhabiting areas used by the vulnerable homeless and outdoor enthusiasts, there exists a high risk for exposure potential towards opportunistic infection, and colonization. The multi-drug resistance pattern on observed on several of A. baumannii isolates suggests the possibility of CRAB. As one of the five pathogens listed as an urgent threat by the CDC, it is imperative to study potential sources of carbapenem resistant A. baumannii, including environmental exposure. Finding moose fecal samples positive for A. baumannii indicates a need for continued surveillance and risk assessment for community acquired infection.

The exposure-response relationship of anti-infective agents at the site of infection is currently being re-examined. Epithelial lining fluid (ELF) has been suggested as the site (compartment) of antimicrobial activity against lung infections caused by extracellular pathogens. There have been an extensive number of studies conducted during the past 20 years to determine drug penetration into ELF and to compare plasma and ELF concentrations of anti-infective agents. The majority of these studies estimated ELF drug concentrations by the method of urea dilution and involved either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Antibacterial agents such as macrolides, ketolides, newer fluoroquinolones and oxazolidinones have ELF to plasma concentration ratios of >1. In comparison, β-lactams, aminoglycosides and glycopeptides have ELF to plasma concentration ratios of ≤1. Potential explanations (e.g. drug transporters, overestimation of the ELF volume, lysis of cells) for why these differences in ELF penetration occur among antibacterial classes need further investigation. The relationship between ELF concentrations and clinical outcomes has been under-studied. In vitro pharmacodynamic models, using simulated ELF and plasma concentrations, have been used to examine the eradication rates of resistant and susceptible pathogens and to explain why selected anti-infective agents (e.g. those with ELF to plasma concentration ratios of >1) are less likely to be associated with clinical treatment failures. Population pharmacokinetic modelling and Monte Carlo simulations have recently been used and permit ELF and plasma concentrations to be evaluated with regard to achievement of target attainment rates. These mathematical modelling techniques have also allowed further examination of drug doses and differences in the time courses of ELF and plasma concentrations as potential explanations for clinical and microbiological effects seen in clinical trials. Further studies are warranted in patients with lower respiratory tract infections to confirm and explore the relationships between ELF concentrations, clinical and microbiological outcomes, and pharmacodynamic parameters.