•These guidelines provide recommendations for the diagnosis and management of bacterial urinary tract infections in dogs and cats.•Sporadic bacterial cystitis, recurrent bacterial cystitis, ...pyelonephritis, bacterial prostatitis, and subclinical bacteriuria are addressed.•Issues pertaining to urinary catheters, medical dissolution of uroliths and prophylaxis for urological procedures are discussed.
Urinary tract disease is a common clinical presentation in dogs and cats, and a common reason for antimicrobial prescription. This document is a revision and expansion on the 2011 Antimicrobial Use Guidelines for Treatment of Urinary Tract Disease in Dogs and Cats, providing recommendations for diagnosis and management of sporadic bacterial cystitis, recurrent bacterial cystitis, pyelonephritis, bacterial prostatitis, and subclinical bacteriuria. Issues pertaining to urinary catheters, medical dissolution of uroliths and prophylaxis for urological procedures are also addressed.
Combined use of various antimicrobial peptides (AMPs) with enzymes that hydrolyze the signaling molecules of the resistance mechanism of various microorganisms, quorum sensing (QS), to obtain ...effective antimicrobials is one of the leading approaches in solving the antimicrobial resistance problem. Our study investigates the lactoferrin-derived AMPs, lactoferricin (Lfcin), lactoferampin and Lf(1-11), as potential partners for combination with enzymes hydrolyzing lactone-containing QS molecules, the hexahistidine-containing organophosphorus hydrolase (His
-OPH) and penicillin acylase, to obtain effective antimicrobial agents with a scope of practical application. The possibility of the effective combination of selected AMPs and enzymes was first investigated in silico using molecular docking method. Based on the computationally obtained results, His
-OPH/Lfcin combination was selected as the most suitable for further research. The study of physical-chemical characteristics of His
-OPH/Lfcin combination revealed the stabilization of enzymatic activity. A notable increase in the catalytic efficiency of action of His
-OPH in combination with Lfcin in the hydrolysis of paraoxon,
-(3-oxo-dodecanoyl)-homoserine lactone and zearalenone used as substrates was established. Antimicrobial efficiency of His
-OPH/Lfcin combination was determined against various microorganisms (bacteria and yeasts) and its improvement was observed as compared to AMP without enzyme. Thus, our findings demonstrate that His
-OPH/Lfcin combination is a promising antimicrobial agent for practical application.
Antimicrobial resistance (AMR) remains an important global public health issue with antimicrobial misuse and overuse being one of the main drivers. The Global Point Prevalence Survey (G-PPS) of ...Antimicrobial Consumption and Resistance assesses the prevalence and the quality of antimicrobial prescriptions across hospitals globally. G-PPS was carried out at 17 hospitals across Ghana, Uganda, Zambia and Tanzania. The overall prevalence of antimicrobial use was 50% (30–57%), with most antibiotics prescribed belonging to the WHO ‘Access’ and ‘Watch’ categories. No ‘Reserve’ category of antibiotics was prescribed across the study sites while antimicrobials belonging to the ‘Not Recommended’ group were prescribed infrequently. Antimicrobials were most often prescribed for prophylaxis for obstetric or gynaecological surgery, making up between 12 and 18% of total prescriptions across all countries. The most prescribed therapeutic subgroup of antimicrobials was ‘Antibacterials for systemic use’. As a result of the programme, PPS data are now readily available for the first time in the hospitals, strengthening the global commitment to improved antimicrobial surveillance. Antimicrobial stewardship interventions developed included the formation of AMS committees, the provision of training and the preparation of new AMS guidelines. Other common interventions included the presentation of findings to clinicians for increased awareness, and the promotion of a multi-disciplinary approach to successful AMS programmes. Repeat PPS would be necessary to continually monitor the impact of interventions implemented. Broader participation is also encouraged to strengthen the evidence base.
Globally, increasing acquired antimicrobial resistance among pathogenic bacteria presents an urgent challenge to human and animal health. As a result, significant efforts, such as the One Health ...Initiative, are underway to curtail and optimize the use of critically important antimicrobials for human medicine in all applications, including food animal production. This review discusses the rationale behind multiple and competing “critically important antimicrobial” lists and their contexts as created by international, regional, and national organizations; identifies discrepancies among these lists; and describes issues surrounding risk management recommendations that have been made by regulatory organizations on the use of antibiotics in food animal production. A more harmonized approach to defining criticality in its various contexts (e.g., for human versus animal health, enteric diseases versus other systemic infections, and direct versus indirect selection of resistance) is needed in order to identify shared contextual features, aid in their translation into risk management, and identify the best ways to maintain the health of food animals, all while keeping in mind the wider risks of antimicrobial resistance, environmental impacts, and animal welfare considerations.
Most of the antibiotics sold for animal use in the US are either not considered medically important by the FDA (e.g., ionophores) or else are not included in the list of critically important antimicrobials for human medicine by the WHO (e.g., tetracyclines). Most of the highest priority critically important antimicrobials (HPCIA) have relatively low sales volumes (e.g., fluoroquinolones and cephalosporins), the exception to this being the macrolide class.
Pharmacists are key partners in antimicrobial stewardship efforts, yet their degree of education on and attitudes toward this topic during training are not well documented. An electronic survey ...measuring knowledge and attitudes regarding antimicrobial use and resistance was administered to graduating pharmacy students at 12 US schools of pharmacy. Of 1445 pharmacy students, 579 (40%) completed the survey. The vast majority (94%) believed that strong knowledge of antimicrobials was important for their pharmacy careers, and 89% desired more education on appropriate antimicrobial use. Most students (84%) considered their pharmacy education regarding antimicrobials useful or very useful, but there was significant variability on perceptions of preparation for most antimicrobial stewardship activities according to the students' school. The mean number of correct answers on a section of 11 knowledge questions was 5.8 (standard deviation 2.0; P value for score between schools <.001). On multivariable linear regression analysis, significant predictors of a higher knowledge score were pharmacy school attended, planned postgraduate training, completion of a clinical rotation in infectious diseases, perception of pharmacy school education as useful, use of resources to answer the knowledge questions, and use of Infectious Diseases Society of America guidelines and smartphone applications as frequent resources for learning about antimicrobials. Pharmacy students perceive antimicrobial stewardship to be an important healthcare issue and desire more education on the subject. Student perceptions of antimicrobial coursework and actual antimicrobial knowledge scores significantly varied by the school of pharmacy attended. Sharing of best practices among institutions may enhance the preparation of future pharmacists to contribute to effective antimicrobial stewardship.
Abstract
Background
Infections caused by antibiotic-resistant bacteria, including carbapenem-resistant Enterobacteriaceae, have increased in frequency, resulting in significant patient morbidity and ...mortality. The Infectious Diseases Society of America continues to propose legislative, regulatory, and funding solutions to address this escalating crisis. This report updates the status of development and approval of systemic antibiotics in the United States as of late 2018.
Methods
We performed a review of the published literature and on-line clinical trials registry at www.clinicaltrials.gov to identify new systemically acting orally and/or intravenously administered antibiotic drug candidates in the development pipeline, as well as agents approved by the US Food and Drug Administration since 2012.
Results
Since our 2013 pipeline status report, the number of new antibiotics annually approved for marketing in the United States has reversed its previous decline, likely influenced by new financial incentives and increased regulatory flexibility. Although our survey demonstrates progress in development of new antibacterial drugs that target infections caused by resistant bacterial pathogens, the majority of recently approved agents have been modifications of existing chemical classes of antibiotics, rather than new chemical classes. Furthermore, larger pharmaceutical companies continue to abandon the field, and smaller companies face financial difficulties as a consequence.
Conclusions
Unfortunately, if 20 × ’20 is achieved due to efforts embarked upon in decades past, it could mark the apex of antibiotic drug development for years to come. Without increased regulatory, governmental, industry, and scientific support and collaboration, durable solutions to the clinical, regulatory, and economic problems posed by bacterial multidrug resistance will not be found.
Benefits and risks of antimicrobial drugs, used in food-producing animals, continue to be complex and controversial issues. This review comprehensively presents the benefits of antimicrobials drugs ...regarding control of animal diseases, protection of public health, enhancement of animal production, improvement of environment, and effects of the drugs on biogas production and public health associated with antimicrobial resistance. The positive and negative impacts, due to ban issue of antimicrobial agents used in food-producing animals, are also included in the discussion. As a double-edged sword, use of these drugs in food-animals persists as a great challenge.
Antimicrobial resistance (AMR) is a high priority across countries as it increases morbidity, mortality and costs. Concerns with AMR have resulted in multiple initiatives internationally, nationally ...and regionally to enhance appropriate antibiotic utilization across sectors to reduce AMR, with the overuse of antibiotics exacerbated by the COVID-19 pandemic. Effectively tackling AMR is crucial for all countries. Principally a narrative review of ongoing activities across sectors was undertaken to improve antimicrobial use and address issues with vaccines including COVID-19. Point prevalence surveys have been successful in hospitals to identify areas for quality improvement programs, principally centering on antimicrobial stewardship programs. These include reducing prolonged antibiotic use to prevent surgical site infections. Multiple activities centering on education have been successful in reducing inappropriate prescribing and dispensing of antimicrobials in ambulatory care for essentially viral infections such as acute respiratory infections. It is imperative to develop new quality indicators for ambulatory care given current concerns, and instigate programs with clear public health messaging to reduce misinformation, essential for pandemics. Regular access to effective treatments is needed to reduce resistance to treatments for HIV, malaria and tuberculosis. Key stakeholder groups can instigate multiple initiatives to reduce AMR. These need to be followed up.
Peptides have important biological functions. However, their susceptibility to proteolysis limits their applications. We demonstrated here for the first time, that poly(2‐oxazoline) (POX) can work as ...a functional mimic of peptides. POX‐based glycine pseudopeptides, a host defense peptide mimic, had potent activities against methicillin‐resistant S. aureus, which causes formidable infections. The POX mimic showed potent activity against persisters that are highly resistant to antibiotics. S. aureus did not develop resistance to POX owning to the reactive oxygen species related antimicrobial mechanism. POX‐treated S. aureus is sensitive to common antibiotics, demonstrating no observable antimicrobial pressure or cross‐resistance in using antimicrobial POX. This study highlights POX as a new type of functional mimic of peptides and opens new avenues in designing and exploring peptide mimetics for biological functions and applications.
Poly(2‐oxazoline) (POX) was employed to access a new class of functional peptide mimics, using the host defense peptide as a model. These mimics have potent in vitro and in vivo activities against methicillin‐resistant Staphylococcus aureus (MRSA) while alleviating antibiotic resistance and killing antibiotic‐tolerant MRSA persisters. ROS=reactive oxygen species.
Currently, more antimicrobial drug candidates are urgently needed to combat the rise in drug-resistance among pathogenic microbes. A new antimicrobial peptide, MP1102, a variant of NZ2114, was ...designed, evaluated, and overexpressed in Pichia pastoris. The total secreted protein in cultures reached 695 mg/l, and the concentration of the recombinant MP1102 (rMP1102) was 292 mg/l. rMP1102 was purified from the fermentation supernatant by one-step cation exchange chromatography to obtain a yield of 197.1 mg/l with 96.4 % purity. rMP1102 exhibited potent activity against Gram-positive bacteria, and its minimum inhibitory concentrations (MICs) for four Staphyloccocus aureus (S. aureus) strains ranged from 0.028 to 0.11 μM, and it had stronger activity (MIC = 0.04 to 0.23 μM) to 20 clinical isolates of MRSA (cMRSA) than rNZ2114 (MIC = 0.11 to 0.90 μM). rMP1102 was shown to kill over 99.9 % of tested S. aureus cells within 6 h when treated at one, two, and four times its MIC and over 90 % of S. aureus cells within 12 h at concentrations of 5, 10, and 20 mg/kg in a mouse thigh infection model. The higher sensitivity of MRSA to MP1102 than to its parental peptide, NZ2114, indicated by this initial pharmacodynamic analysis suggests a possible difference in the killing mechanism of these two molecules. rMP1102 caused less than 0.05 % hemolytic activity at 128 μg/ml and exhibited good thermostability from 20 to 80 °C, with its highest activity being observed at pH 8.0. These results suggest that this yeast expression system is feasible for large-scale production, and rMP1102 exerted stronger activity against S. aureus than NZ2114 via a different mechanism and exhibited potential as a new antimicrobial agent for S. aureus, especially MRSA infections.
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