Therapeutic Use Of Antimicrobials Research Articles

How Should Clinicians Navigate Interprofessional Tension in Their Roles as Antimicrobial Stewards?

Pharmacists and physicians play key roles in antimicrobial stewardship. This commentary on a case describes these health professionals' need to collaborate to optimize therapeutic use of antimicrobials in clinical settings. Prescription preauthorization is one antimicrobial stewardship strategy that can meet with some physicians' frustration and generate conflict between pharmacists and prescribing physicians, particularly when pharmacists make alternative treatment recommendations. This commentary considers interprofessional tension concerning prescription preauthorization and suggests strategies for navigating such conflict.

A survey of antimicrobial use practices on veal farms in the United States.

Neonatal veal calves are highly susceptible to bacterial diseases. Occasional sub-optimal early-life care and long-distance transportation result in high disease burden and antimicrobial treatment incidence. Nonetheless, judicious use of antimicrobials is necessary to mitigate the animal and human health impacts of antimicrobial resistance. The objective of this cross-sectional study was to use a clinical vignette-based survey approach to evaluate the potential for reduced group or individual therapeutic antimicrobial use. The survey included items probing the adherence to veterinary-written protocols, antimicrobial use (AMU) at the calf- and group-level, and the treatment actions to case vignettes of calf diarrhoea, pneumonia, and navel infection. The survey was mailed to all veal calf producers within two U.S. production companies (n = 32 producers in Company 1; n = 70 producers in Company 2) in February and December 2019, respectively. The overall survey response rate was 36% (21/59). Although 95% of producers reported having veterinary-written treatment protocols for diarrhoea, pneumonia, and navel infection, veal producers infrequently (<50% of the time) referenced these protocols. Veal producers were primarily trained for disease identification and treatment by observing other personnel "on-the-job" (81%). Veal producers reported a high incidence of calf diarrhoea relative to pneumonia and naval infection, a lower percentage (≤40%) of diarrhoea cases being treated individually with antimicrobials. Using clinical vignettes, our results suggest that AMU decisions among veal producers depend on the severity of clinical signs for diarrhoea and pneumonia, while navel infections are often treated with antimicrobials regardless of sign severity. Nearly two-thirds of veal producers reported treating uncomplicated cases of diarrhoea (watery stool with normal body temperature, activity, and appetite), more than previously reported from dairy producers (37.1%). Findings from this survey suggest that calf producer-focused training to guide antimicrobial treatment decisions and improve producer adherence to veterinary-written treatment protocols may have important impacts on judicious antimicrobial use.

2022 AAFP/AAHA Antimicrobial Stewardship Guidelines.

2022 AAFP/AAHA Antimicrobial Stewardship Guidelines.

Factors associated with antimicrobial use in pig and veal calf farms in the Netherlands: A multi-method longitudinal data analysis

Minimizing antimicrobial use (AMU) in livestock is needed to control antimicrobial resistance (AMR). In the Netherlands, the livestock sector reduced AMU by almost 70 % since 2009, but this reduction stagnated in recent years. With only therapeutic AMU allowed, it is clear that besides socio-economic and behavioral factors, also the farm technical characteristics influence the conditions under which farmers need AMU. These characteristics pertain to farm management, including biosecurity, vaccination schemes, nutrition, micro-climate and husbandry practices. Identifying farm-related risk factors for AMU is needed to control AMR in a sustainable and pragmatic way. This need, often concerns the overall contribution of seemingly related (rather than individualized) factors. Here, risk factors for AMU in pig and calf farms were determined using two approaches: a typical risk factor analysis based on generalized estimating equations (GEEs) or hierarchical mixed-effects models and a multiblock partial least-squares regression analysis. These methods were applied to longitudinal data from two previous studies, i.e. a panel study and an intervention study involving 36 multiplier pig farms and 51 veal calf farms in the Netherlands, respectively. The multiblock analysis allowed us to quantify the importance of each factor and their respective block (i.e. farm management domain). For pigs, factors related to internal biosecurity had the highest impact on AMU, while for calves, these were mainly related to micro-climate. Structural characteristics, such as farm size and production type, followed in importance for both sectors. While both methods provided similar outcomes, the multiblock approach provided further insights by grouping and comparing factors believed to be inter-related.

Off label use of human approved drugs in treatment of dogs in the Republic of Serbia.

Since drug companies are driven by the need to produce profit they are unwilling to make large investments in the development of new drugs if there is no market large enough to justify such investment. For this reason, veterinarians face a major obstacle - the veterinary drug market is not very profitable, which sometimes leads to not having a licensed drug available for treatment in veterinary practice. In this case, the cascade procedure allows veterinarians to, under certain circumstances, prescribe human approved drugs. The aim of our study was to analyze the pattern of human approved drugs prescription for 150 medical records of dogs participating in the survey. The results show that antimicrobial agents were the most commonly prescribed drugs for animals (50%) of all human approved drugs, and beta-lactams (38.6%) were the most widely used antibiotic classes. The most common general conditions for therapeutic use of antimicrobials in this study were digestive, skin and respiratory disorders. Our study shows that the frequency of bacterial culture, susceptibility testing and cytology was very low. Even though the off-label use of human approved drugs in animal practice is regulated by law, the results of this study indicate the need for more specific strategies and guidelines for such use. This may represent a potential for improvement by raising veterinarians' awareness toward more prudent use of human drugs.

Effects of prophylactic and therapeutic antimicrobial uses in small-scale chicken flocks.

SummaryAntimicrobials are extensively used both prophylactically and therapeutically in poultry production. Despite this, there are little data on the effect of antimicrobial use (AMU) on disease incidence rate and per cent mortality. We investigated the relationships between AMU and disease and between AMU and mortality using data from a large (n = 322 flocks) cohort of small‐scale chicken flocks in the Mekong Delta, Vietnam, that were followed longitudinally from day old to slaughter (5,566 observation weeks). We developed a parameterized algorithm to emulate a randomized control trial from observational data by categorizing the observation weeks into ‘non‐AMU’, ‘prophylactic AMU’ and ‘therapeutic AMU’. To evaluate the prophylactic AMU effect, we compared the frequencies of clinical signs in ‘non‐AMU’ and ‘prophylactic AMU’ periods. To analyse therapeutic AMU, we compared weekly per cent mortality between the weeks of disease episodes before and after AMU. Analyses were stratified by clinical signs (4) and antimicrobial classes (13). Prophylactic AMU never reduced the probability of disease, and some antimicrobial classes such as lincosamides, amphenicols and penicillins increased the risk. The risk of diarrhoea consistently increased with prophylactic AMU. Therapeutic AMU often had an effect on mortality, but the pattern was inconsistent across the combinations of antimicrobial classes and clinical signs with 14/29 decreasing and 11/29 increasing the per cent weekly mortality. Lincosamides, methenamines and cephalosporins were the only three antimicrobial classes that always decreased the mortality when used therapeutically. Results were robust respective to the parameters values of the weeks categorization algorithm. This information should help support policy efforts and interventions aiming at reducing AMU in animal production.

Even therapeutic antimicrobial use in animal husbandry may generate environmental hazards to human health.

The potential negative impact for human health of veterinary use of antimicrobials in prophylaxis, metaphylaxis and growth promotion in animal husbandry was first established in the 1960s and 1970s. Determination of the molecular structure of antimicrobial resistance plasmids at that time explained the ability of antimicrobial resistance genes to disseminate among bacterial populations and elucidated the reasons for the negative effects of antimicrobials used in food animals for human health. In this issue of Environmental Microbiology, Liu et al. (2016) show that even therapeutic use of antimicrobials in dairy calves has an appreciable environmental microbiological footprint. We discuss the negative implications of this footprint for human health and the possibility they may lead to calls for increased regulation of veterinary antimicrobial use in terrestrial and aquatic environments.

SEROVARS AND ANTIMICROBIAL RESISTANCE OF Salmonella spp. ISOLATED FROM TURKEY AND BROILER CARCASSES IN SOUTHERN BRAZIL BETWEEN 2004 AND 2006.

Salmonella spp. causes diseases in fowls, when species-specific serovars (Salmonella Pullorum and S.Gallinarum) are present in flocks, and public health problems, when non-typhoid serovars are isolated, as well as possible bacterial resistance induced by the preventive and therapeutic use of antimicrobials in animal production. This study describes the serovars and bacterial resistance of 280Salmonella spp. strains isolated from turkey and broiler carcasses in Southern Brazil between 2004 and 2006. SalmonellaEnteritidis was the most prevalent serovar (55.7%), followed by Heidelberg (5.0%), Agona (4.3%), Bredeney (3.9%), Hadar (3.2%), and Typhimurium (2.9%). Tennessee and S. Enterica subspecies enterica(O: 4.5) were isolated only in turkeys, and Hadar (18.6%) was the most prevalent serovar in this species. Antimicrobial susceptibility tests were performed in 178 isolates (43 from turkeys and 135 from broilers). All isolates were sensitive to amoxicillin + clavulanic acid, polymyxin B, ciprofloxacin, and norfloxacin, and were resistant to bacitracin and penicillin. Broiler carcass isolates showed resistance to nalidixic acid (48.9%), nitrofurantoin (34.3%), neomycin (9.6%), tetracycline (5.2%), and kanamycin (8.9%); and turkey carcass isolates were resistant to nalidixic acid (62.8%), tetracycline (34.9%), and neomycin (30.2%), with a significant difference in turkeys when compared to broiler carcass isolates. These results indicate the need for judicious use of antimicrobials in livestock production, given that the serovars identified are potential causes of food poisoning.

ACVIMConsensus Statement on Therapeutic Antimicrobial Use in Animals and Antimicrobial Resistance

The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.

Reduction of veterinary antimicrobial use in the Netherlands. The Dutch success model.

Use of antimicrobials in animals poses a potential risk for public health as it contributes to the selection and spread of antimicrobial resistance. Although knowledge of the negative consequences of extensive antimicrobial use in humans and animals accumulated over the decades, total therapeutic antimicrobial use in farm animals in the Netherlands doubled between 1990 and 2007. A series of facts and events formed a window of opportunity to reduce antimicrobial use in farm animals. The recent discovery of significant reservoirs of antimicrobial-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase-producing bacteria (ESBL) in farm animals, with potential public health implications, combined with an increasing lack of confidence of the public in intensive livestock industries, and discrepancy between the very low antimicrobial use in humans and high use in animals, resulted in intensive collaboration between the government, veterinary professional organizations and important stakeholders within the livestock sector. A combination of compulsory and voluntary actions with clear reduction goals resulted in a 56% reduction in antimicrobial use in farm animals in the Netherlands between 2007 and 2012 and aims at accomplishing a 70% reduction target in 2015. This article describes and analyses the processes and actions behind this transition from an abundant antimicrobial use in farm animals towards a more prudent application of antimicrobials in farm animals in the Netherlands.

Multifocal abscesses due to multiresistant Escherichia coli after transrectal ultrasound‐guided prostate biopsy

We report an unusual case of multidrug-resistant Escherichia coli bacteraemia causing multifocal abscesses, septic arthritis, lumbar discitis and osteomyelitis after transrectal ultrasound-guided prostate biopsy, requiring restricted antibiotics and surgical debridement. This case highlights the importance of risk assessment, prophylactic and therapeutic antimicrobial use, and urology infectious diseases collaboration to improve clinical outcomes after such procedures.

Effect of probiotic on haematogical paramaters of diseased fish (Cirrihinus mrigal)

Epizootic ulcerative syndrome (EUS) is a dreadful disease of several aquatic animals including mrigal (Cirrhinus mrigala Ham.). Prevention of the disease with the help of chemical compo-unds may prove harmful for the fish as well as the end consumer. Now-a-days the use of pro-biotics has become firmly established due to their beneficial effects at the nutritional as well as therapeutic levels. Therefore, research efforts have been concentrated on optimizing production with eco-friendly alternatives to the therapeutic use of antimicrobials. Commercially available probiotics were used for controlling this disease in mrigal in the present study. The effect of probiotic on four haemotogical parameters viz. amount of haemoglobin (Hb), hemocrit / pac-ked cell volume (PCV), total erythrocyte count (TEC), and total leucocytes count (TLC) were studied over a period of eight weeks. The level of these parameters decreased significantly in the blood of fish treated with pathogenic bacteria. The fish administrated with probiotics showed significant increase in the hematological parameters thus contributing towards overall health of the fish.

Antimicrobial Stewardship and Surveillance: Great Expectations

Nosocomial infections are a major cause of morbidity in the critically injured. The frequent use of antimicrobials in the critically ill has compounded problem of multidrug resistance organisms. Although nosocomial infections have become an important public health issue in all areas of hospital care, those arising in the Intensive Care Unit (ICU) have become especially problematic with a dramatic increase in resistant organisms. The emergence of multi-drug resistant organisms necessitates new drugs and interventions to combat this serious threat. “A nil antibiotic era” is approaching as the pipeline for new antimicrobials has run dry. Management of sepsis requires accurate empiric cover without antimicrobial overuse- a goal that may be achieved by microbiological surveillance and antimicrobial stewardship. A number of interventions to control bacterial resistance have been advocated. Unfortunately class restriction of specific agents and antibiotic cycling has had little effect and with time has demonstrated an increase in resistance to alternative drugs. The two most effective strategies are strict infection control measures and optimizing both prophylactic and therapeutic antimicrobial use by surveillance, establishing a protocol, education and stewardship. An effective empiric protocol is vital based on knowledge of local microbiologic patterns and defining risk factors which indicate when de-escalation may be warranted.

The Importance of Sample Size in the Determination of a Flock-Level Antimicrobial Resistance Profile forEscherichia coliin Broilers

Determining herd- or flock-specific antimicrobial resistance profiles is important to guide therapeutic use of antimicrobials and to assess risk factors for the development and spread of antimicrobial resistance. As such, it is of utmost importance to optimize the sampling strategy for the determination of herd-specific antimicrobial resistance profiles. However, the multitude of prevalences measured at the same time as well as the presence of variation both at the level of the animal and the bacterial population of concern make it impossible to use conventional sample size determination methods. In this article, the use of bootstrapping techniques for sample size determination was explored. In particular, one-stage and two-stage bootstrap samplings were used to determine the optimal number of animals and the optimal number of isolates within one animal. Results show that focus should be on the number of animals sampled rather than on the number of isolates tested within one animal.

The role of infection in the pathogenesis of vaso-occlusive crisis in patients with sickle cell disease.

Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive crisis (VOC). Patients with SCD have impaired immunity and are thus predispose to infections. The vast majority of SCD patients live in underdeveloped nations with high prevalence and transmission rates of infections. This makes the SCD patients prone to infections, which frequently precipitate VOC. We reviewed the role of infection in the pathogenesis of VOC, taking into consideration all potential mechanisms from previous studies and hypothetical perspectives. The potential mechanisms through which infections may lead to VOC involve several pathological changes including pneumonitis, pyrexia, acute phase reaction, hypercoagulability, neutrophilia, eosinophilia, thrombocytosis, bronchospasm, red cell cytopathic and membrane changes, auto-antibodies mediated red cell agglutination and opsonization, diarrhoea and vomiting, which may act singly or in concert to cause red cell sickling. These changes can induce sickling directly or indirectly through their adverse effects on Hb oxygenation and polymerization, hydration, blood viscosity, red cell metabolism, procoagulant activation, intercellular adherence and aggregation, culminating in VOC. There is therefore the need to ameliorate the burden of infection on SCD through immunization, prophylactic and therapeutic use of antimicrobials, barrier protection and vector control in communities with high prevalence of SCD.

Towards a rational antimicrobial testing policy in the laboratory

Antimicrobial policy for prophylactic and therapeutic use of antimicrobials in a tertiary care setting has gained importance. A hospital’s antimicrobial policy as laid down by its hospital infection control team needs to include inputs from the microbiology laboratory, besides the pharmacy and therapeutic committee. Therefore, it is of utmost importance that clinical microbiologists across India follow international guidelines and also take into account local settings, especially detection and presence of resistance enzymes. This article draws a framework for rational antimicrobial testing in our laboratories in tertiary care centers, from the Clinical and Laboratory Standards Institute guidelines. It does not address testing methodologies but suggests ways and means by which antimicrobial susceptibility reporting can be rendered meaningful not only to the treating physician but also to the resistance monitoring epidemiologist. It hopes to initiate some standardization in rational choice of antimicrobial testing in laboratories in the country pertaining to nonfastidious bacteria.

Comparison of Salmonella Serovar Isolation and Antimicrobial Resistance Patterns from Porcine Samples Between 2003 and 2008

Food-borne Salmonella infections can produce symptoms from mild gastroenteritis to severe systemic disease and death, representing an important public health issue in U.S. livestock and livestock products, which have been implicated as frequent sources of Salmonella contamination. Concerns have been raised about the spread of antibiotic resistance in Salmonella strains, particularly those that originate from food animal sources, as a result of prophylactic and therapeutic antimicrobial use in these species. Longitudinal comparisons of Salmonella serovars isolated from porcine tissues submitted to the Iowa State University Veterinary Diagnostic Laboratory in 2003 and 2008 were conducted to evaluate changes in serovar dynamics and antimicrobial resistance. Incidence of recovered group C Salmonella enterica serovar Choleraesuis var. Kunzendorf decreased between 2003 and 2008, while recovery of group B strains Salmonella Typhimurium var. 5-(formerly, Copenhagen), Salmonella Agona, Salmonella Derby, Salmonella Heidelberg, and Salmonella Typhimurium increased. Significant changes in resistance interpretation were seen in Salmonella Derby with regard to spectinomycin and sulfadimethoxine; in Salmonella Heidelberg with regard to florfenicol, spectinomycin, and sulfadimethoxine; and in Salmonella Choleraesuis var. Kunzendorf, Salmonella Typhimurium, Salmonella Typhimurium var. 5-, and Salmonella Agona with regard to spectinomycin. Only 2 of 293 isolates in 2003 and 5 of 395 isolates in 2008 were resistant to enrofloxacin. Utilizing antibiotics approved for use in food animals to evaluate antimicrobial resistance provides more specific information on the selection pressure exerted on Salmonella populations through the use of these drugs.

Role of Antimicrobial Selective Pressure and Secondary Factors on Antimicrobial Resistance Prevalence inEscherichia colifrom Food-Producing Animals in Japan

The use of antimicrobial agents in the veterinary field affects the emergence, prevalence, and dissemination of antimicrobial resistance in bacteria isolated from food-producing animals. To control the emergence, prevalence, and dissemination of antimicrobial resistance, it is necessary to implement appropriate actions based on scientific evidence. In Japan, the Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) was established in 1999 to monitor the antimicrobial susceptibility of foodborne and commensal bacteria from food-producing animals. The JVARM showed that the emergence and prevalence of resistant Escherichia coli were likely linked to the therapeutic antimicrobial use in food-producing animals through not only direct selection of the corresponding resistance but also indirect selections via cross-resistance and coresistance. In addition, relevant factors such as host animals and bacterial properties might affect the occurrence and prevalence of antimicrobial-resistant E. coli under the selective pressure from antimicrobial usage. This paper reviews the trends in antimicrobial resistance in E. coli and consumption of antimicrobials agents in Japan and introduces the relationship between antimicrobial usage and prevalence of antimicrobial-resistant bacteria, from food-producing animals under the JVARM program. In this paper, we will provide the underlying information about the significant factors that can help control antimicrobial resistance in bacteria in veterinary medicine.

Targeting therapy to minimize antimicrobial use in preweaned calves: Effects on health, growth, and treatment costs

Prophylactic and therapeutic antimicrobial use in food animals is questioned because of the potential for development of resistant bacteria and future inability to use some antimicrobials for human or animal disease. The objectives of this study were to determine the effect of raising preweaned dairy calves without antimicrobials in the milk and minimizing therapeutic antimicrobial treatment on morbidity, mortality, weight gain, and treatment costs. Newborn calves (n = 358) were allocated to 1 of 4 groups, housed outdoors in individual hutches, and monitored for 28 d. Calves in the conventional therapy (CT) group were treated as per dairy protocol with sulfamethoxazole/trimethoprim, spectinomycin, penicillin, and bismuth-pectin for diarrhea. The targeted therapy (TT) group included bismuth-pectin for diarrhea and antimicrobial treatment only in cases of fever or depressed attitude. Within CT and TT groups, calves were equally assigned to receive neomycin and tetracycline in their milk for the first 2 wk of life (AB-milk) or no antimicrobials (NoAB-milk). Daily health evaluations included fecal consistency, respiratory disease, attitude, and hydration status as well as milk and grain consumption. A negative binomial model evaluated the total number of days with diarrhea days in each group. General linear models were used to assess average daily weight gain and grain consumption. Conventionally treated calves had 70% more days with diarrhea than TT calves, and AB-milk calves had 31% more days with diarrhea compared with NoAB-milk calves. The TT calves tended to have a higher average daily gain by 28 d and consumed more grain compared with CT calves. If antimicrobials were used only for diarrhea cases with fever, inappetence, or depression and no in-milk antimicrobials were used, a $10 per calf savings could be realized. Targeting antimicrobial therapy of calf diarrhea cases is prudent not only to save the drugs for future use but also to prevent the potential for antibiotic-associated diarrhea and reduce calf-rearing costs.

Veterinary antibiotics in the aquatic and terrestrial environment

Abstract The fate of antibiotics in the environment, and especially antibiotics used in animal husbandry, is subject to recent studies and the issue of this review. The assumed quantity of antibiotics excreted by animal husbandry adds up to thousands of tonnes per year. Administered medicines, their metabolites or degradation products reach the terrestrial and aquatic environment by the application of manure or slurry to areas used agriculturally, or by pasture-reared animals excreting directly on the land, followed by surface run-off, driftage or leaching in deeper layers of the earth. The scientific interest in antimicrobially active compounds in manure and soil, but also in surface and ground water, has increased during the last decade. On the one side, scientific interest has focused on the behaviour of antibiotics and their fate in the environment, on the other hand, their impact on environmental and other bacteria has become an issue of research. Analytical methods have now been developed appropriately and studies using these new techniques provide accurate data on concentrations of antimicrobial compounds and their residues in different organic matters. Some antibiotics seem to persist a long time in the environment, especially in soil, while others degrade very fast. Not only the fate of these pharmaceuticals but their origin as well is an object of scientific interest. Besides human input via wastewater and other effluents, livestock production has been recognised as a source of contamination. One main concern with regard to the excessive use of antibiotics in livestock production is the potential promotion of resistance and the resulting disadvantages in the therapeutic use of antimicrobials. Since the beginning of antibiotic therapy, more and more resistant bacterial strains have been isolated from environmental sources showing one or multiple resistance. There have been several attempts to use antibiotic resistance patterns in different bacteria as indicators for various sources of faecal pollution. This review gives an overview of the available data on the present use of veterinary antibiotics in agriculture, on the occurrence of antibiotic compounds and resistant bacteria in soil and water and demonstrates the need for further studies.