Health management with reduced antibiotic use - the U.S. experience

Since World War II the use of antimicrobial products associated with food animal production has increased. Antimicrobials along with evolving production practices have significantly increased throughput, animal welfare, and improved health. Concerns surrounding the growing significance of emerging and in some cases rapidly disseminating antibiotic (antimicrobial) resistant bacterial pathogens among human and livestock populations has stimulated a reassessment of this application. The negative publicity has led many consumers and activist groups to believe that protein derived from food animals grown in the absence of those drugs is safer than products derived from the conventionally reared. There is a general fear that antimicrobial usage in agriculture threatens the sustainability of human therapeutic agents and the public wellbeing. The issue has gradually emerged from "fringe group paranoia" to mainstream - finally impacting consumer choices. Antimicrobial resistance concerns have stimulated a significant reaction by the US animal agriculture industry. Numerous pig production entities, large and small, have attempted to create additional pork product value by developing niche marketing opportunities. Thus far most of the subtherapeutic in-feed antimicrobial reduction has been voluntary in the US. Two production areas have developed where reduced usage occurs. First is the growth of antibiotic free production (ABF) and second is an increased use of treatment levels which avoids subtherapeutic criticism. The bulk of this article is directed at new production practices, pig health management, disease elimination, and biosecurity efforts that result from early industry attempts at reduced or excluded antimicrobial pig production. Raising antimicrobial (antibiotic) free (ABF) pork from birth is challenging for a variety of reasons. Some of these challenges can be cost effectively dealt with while others are difficult if not impossible to control in modern production environments. Healthy pig production is essential for sustainable ABF operations.     

Routine prophylactic antibiotic use in the management of snakebite

Background  

Routine antibiotic prophylaxis following snakebite is not recommended but evidence suggests that it may be common practice in Zimbabwe. This study set out to determine and describe the extent of this practice at Parirenyatwa Hospital, a large teaching hospital in Zimbabwe     

Delayed uterine fluid clearance and reduced uterine perfusion in bitches with endometrial hyperplasia and clinical management with postmating antibiotic

In many species a transient uterine inflammatory response follows mating and is proposed to remove excess spermatozoa, bacteria, and other contaminants from the uterus. Similar events have been documented in the bitch involving increased uterine contractions, polymorphonuclear neutrophil influx and uterine artery vasodilation. Some healthy bitches with endometrial hyperplasia have increased numbers of uterine luminal polymorphonuclear neutrophils after mating and reduced fertility; it is purported that this represents a presumed postmating endometritis. This study used B-mode and Doppler ultrasonography at the time of mating to measure uterine contractions, clearance of ejaculated fluid, and uterine artery velocity in normal bitches and those with endometrial hyperplasia. Mating resulted in an increase in the number of uterine contractions, although fewer mating-induced contractions were noted in bitches with endometrial hyperplasia. Interestingly, uterine fluid cleared significantly more slowly after mating from the bitches with endometrial hyperplasia than the normal bitches (P = 0.01). In a further study, Doppler ultrasonography showed that in normal bitches there was a significant increase in uterine artery blood velocity (P = 0.04) and a decrease in the resistance index after mating (P = 0.04), indicating vasodilation. In bitches with endometrial hyperplasia the baseline resistance index was significantly higher than normal bitches (P = 0.05), and furthermore, although there was a significant decrease in resistance index after mating, in the bitches with endometrial hyperplasia this was of a smaller magnitude that in normal bitches. These findings indicate lower baseline uterine perfusion, and a blunted vasodilation response to mating in bitches with endometrial hyperplasia. Short-duration postmating administration of systemic antibiotic increased pregnancy rates in bitches with endometrial hyperplasia (P < 0.01). Litter sizes in bitches with endometrial hyperplasia were lower than those of normal bitches both before and after treatment with postmating antibiotic (P = 0.04 and < 0.01, respectively). Mating-induced endometritis in bitches with endometrial hyperplasia appears to affect fertility by reducing the uterine vasodilatory response to mating and delaying clearance of uterine fluid as a result of decreased uterine contractions but the effect can be ameliorated in part by the postmating administration of antibiotic.     

Genotypic-phenotypic discrepancies between antibiotic resistance characteristics of Escherichia coli isolates from calves in management settings with high and low antibiotic use

We hypothesized that bacterial populations growing in the absence of antibiotics will accumulate more resistance gene mutations than bacterial populations growing in the presence of antibiotics. If this is so, the prevalence of dysfunctional resistance genes (resistance pseudogenes) could provide a measure of the level of antibiotic exposure present in a given environment. As a proof-of-concept test, we assayed field strains of Escherichia coli for their resistance genotypes using a resistance gene microarray and further characterized isolates that had resistance phenotype-genotype discrepancies. We found a small but significant association between the prevalence of isolates with resistance pseudogenes and the lower antibiotic use environment of a beef cow-calf operation versus a higher antibiotic use dairy calf ranch (Fisher's exact test, P = 0.044). Other significant findings include a very strong association between the dairy calf ranch isolates and phenotypes unexplained by well-known resistance genes (Fisher's exact test, P < 0.0001). Two novel resistance genes were discovered in E. coli isolates from the dairy calf ranch, one associated with resistance to aminoglycosides and one associated with resistance to trimethoprim. In addition, isolates resistant to expanded-spectrum cephalosporins but negative for bla(CMY-2) had mutations in the promoter regions of the chromosomal E. coli ampC gene consistent with reported overexpression of native AmpC beta-lactamase. Similar mutations in hospital E. coli isolates have been reported worldwide. Prevalence or rates of E. coli ampC promoter mutations may be used as a marker for high expanded-spectrum cephalosporin use environments.     

Incorporation of a chiral gem-disubstituted nitrogen heterocycle yields an oxazolidinone antibiotic with reduced mitochondrial toxicity

gem-Disubstituted N-heterocycles are rarely found in drugs, despite their potential to improve the drug-like properties of small molecule pharmaceuticals. Linezolid, a morpholine heterocycle-containing oxazolidinone antibiotic, exhibits significant side effects associated with human mitochondrial protein synthesis inhibition. We synthesized a gem-disubstituted linezolid analogue that when compared to linezolid, maintains comparable (albeit slightly diminished) activity against bacteria, comparable in vitro physicochemical properties, and a decrease in undesired mitochondrial protein synthesis (MPS) inhibition. This research contributes to the structure-activity-relationship data surrounding oxazolidinone MPS inhibition, and may inspire investigations into the utility of gem-disubstituted N-heterocycles in medicinal chemistry.     

Characterization of Renibacterium salmoninarum with reduced susceptibility to macrolide antibiotics by a standardized antibiotic susceptibility test

Three cohorts of juvenile and subadult Chinook salmon Oncorhynchus tshawytscha received multiple treatments with macrolide antibiotics for bacterial kidney disease (BKD) during rearing in a captive broodstock program. A total of 77 mortalities among the cohorts were screened for Renibacterium salmoninarum, the etiologic agent of BKD, by agar culture from kidney, and isolates from 7 fish were suitable for growth testing in the presence of macrolide antibiotics. The minimum inhibitory concentration (MIC) of erythromycin and azithromycin was determined by a modification of the standardized broth assay using defined medium. The American Type Culture Collection (ATCC) type strain 33209 exhibited a MIC of 0.008 microg m(-1) to either erythromycin or azithromycin. Isolates from 3 fish displayed MICs identical to the MICs for the ATCC type strain 33209. In contrast, isolates from 4 fish exhibited higher MICs, ranging between 0.125 and 0.250 microg ml(-1) for erythromycin and between 0.016 and 0.031 microg ml(-1) for azithromycin. Sequence analysis of the mutational hotspots for macrolide resistance in the 23S rDNA gene and the open reading frames of ribosomal proteins L4 and L22 found identical sequences among all isolates, indicating that the phenotype was not due to mutations associated with the drug-binding site of 23S rRNA. These results are the first report of R. salmoninarum with reduced susceptibility to macrolide antibiotics isolated from fish receiving multiple antibiotic treatments.     

Seasonal response of nutrients to reduced phosphorus loading in 12 Danish lakes

1. Concentrations of phosphorus, nitrogen and silica and alkalinity were monitored in eight shallow and four deep Danish lakes for 13 years following a phosphorus loading reduction. The aim was to elucidate the seasonal changes in nutrient concentrations during recovery. Samples were taken biweekly during summer and monthly during winter. 2. Overall, the most substantive changes in lake water concentrations were seen in the early phase of recovery. However, phosphorus continued to decline during summer as long as 10 years after the loading reduction, indicating a significant, albeit slow, decline in internal loading. 3. Shallow and deep lakes responded differently to reduced loading. In shallow lakes the internal phosphorus release declined significantly in spring, early summer and autumn, and only non‐significantly so in July and August. In contrast, in deep lakes the largest reduction occurred from May to August. This difference may reflect the much stronger benthic pelagic‐coupling and the lack of stratification in shallow lakes. 4. Nitrogen only showed minor changes during the recovery period, while alkalinity increased in late summer, probably conditioned by the reduced primary production, as also indicated by the lower pH. Silica tended to decline in winter and spring during the study period, probably reflecting a reduced release of silica from the sediment because of enhanced uptake by benthic diatoms following the improved water transparency. 5. These results clearly indicate that internal loading of phosphorus can delay lake recovery for many years after phosphorus loading reduction, and that lake morphometry (i.e. deep versus shallow basins) influences the patterns of change in nutrient concentrations on both a seasonal and interannual basis.     

Characteristics of antibiotic use in children

In antibiotic therapy of children bacteriological findings should be considered. The choice of antibiotic doses depends on the drug pharmacokinetics and damaging effect, the state of the excretory organs and some other factors. Antibiotic elimination in children during the postnatal period is limited: there is a relationship between the gestation term and intensity of drug elimination. Antibiotics penetrate through the placental barrier. They are detected in the mother milk. The damaging effect of antibiotics in many respects depends on their properties, dosage and administration route. Children are more sensitive to the direct toxic action of antibiotics as compared to adults. Development of dysbacteriosis in children is frequent. Allergic reactions with diverse clinical signs are possible in children. Combined antibiotic therapy with observation of definite requirements is more efficient. Still, because of the antibiotic damaging effect monotherapy is more preferable in all possible cases.     

Habitat use and behaviour of European hedgehogErinaceus europaeus in a Danish rural area

HedgehogsErinaceus europaeus Linnaeus, 1758 were radio-tagged and monitored during the summer of 2001 in a Danish rural area with the objective of quantifying home ranges, nightly distances travelled, habitat use, activity patterns, day-nesting habits, and body-weight changes of the five males and five females being recorded. Males had larger home-range sizes and travelled longer nightly distances than females. The two most common habitat types within the home ranges of the hedgehogs were deciduous forest and arable land, whereas the two most frequently used habitat types were deciduous forest and grassland. No differences between the sexes were found in the proportions of different habitat types within the home ranges or in habitat use. Non-random habitat use was found; forested areas and edge habitats seemed preferred to open areas. The most frequently used day-nesting habitat was deciduous forest. Foraging was by far the most time-consuming nightly activity for both sexes. Males lost weight during the study period (May–July), whereas females gained weight. A peak in the frequency of sexual behaviour was found from late-June to mid-July. The high level of male ranging activity and the weight loss of males are interpreted as a consequence of the promiscuous mating system of hedgehogs.     

Water quality management in the River Gudenaa,a Danish lake-stream-estuary system

Waste water purification has been established to some extent throughout the 3,260 km² catchment area of the River Gudenaa water system during the last 20 years. Biological treatment and phosphorus removal are now undertaken in almost all towns, and organic matter and phosphorus loading from fishponds and farms has been reduced. The pollution abatement strategy employed has been to coordinate and differentiate waste water treatment so as to maximise the environmental benefit/cost ratio. The time lag between implementing an abatement measure and observing an improvement in water quality varies considerably depending on the nature and cultural history of the water bodies involved and the processes occurring during the passage of water between them.Nutrient transformation and retention within water bodies of the Gudenaa system is of great importance for nutrient loading of the downstream lakes and of the estuary (Randers Fjord), and even for the Danish Belt sea. When loading is reduced retention changes, but to a different extent in different water bodies.     

Health care experiences of people with dementia and their caregivers: a meta-ethnographic analysis of qualitative studies

Background:

Understanding the health care experience of people with dementia and their caregivers is becoming increasingly important given the growing number of affected individuals. We conducted a systematic review of qualitative studies that examined aspects of the health care experience of people with dementia and their caregivers to better understand ways to improve care for this population.

Methods:

We searched the electronic databases MEDLINE, Embase, PsychINFO and CINAHL to identify relevant articles. We extracted key study characteristics and methods from the included studies. We also extracted direct quotes from the primary studies, along with the interpretations provided by authors of the studies. We used meta-ethnography to synthesize the extracted information into an overall framework. We evaluated the quality of the primary studies using the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist.

Results:

In total, 46 studies met our inclusion criteria; these involved 1866 people with dementia and their caregivers. We identified 5 major themes: seeking a diagnosis; accessing supports and services; addressing information needs; disease management; and communication and attitudes of health care providers. We conceptualized the health care experience as progressing through phases of seeking understanding and information, identifying the problem, role transitions following diagnosis and living with change.

Interpretation:

The health care experience of people with dementia and their caregivers is a complex and dynamic process, which could be improved for many people. Understanding these experiences provides insight into potential gaps in existing health services. Modifying existing services or implementing new models of care to address these gaps may lead to improved outcomes for people with dementia and their caregivers.The global prevalence of Alzheimer disease and related dementias is estimated to be 36 million people and is expected to double in the next 20 years.¹ Several recent strategies for providing care to patients with dementia have highlighted the importance of coordinated health care services for this growing population.^2–5 Gaps in the quality of care for people with dementia have been identified,^6–8 and improving their quality of care and health care experience has been identified as a priority area.^2–5Incorporating the health care experience of patients and caregivers in health service planning is important to ensure that their needs are met and that person-centred care is provided.⁹ The health care experience of people with dementia and their caregivers provides valuable information about preferences for services and service delivery.¹⁰ Matching available services to patient treatment preferences leads to improved patient outcomes^11,12 and satisfaction without increasing costs.¹³ Qualitative research is ideally suited to exploring the experiences and perspectives of patients and caregivers and has been used to examine these experiences for other conditions.¹⁴ We performed a systematic review and meta-ethnographic synthesis of qualitative studies exploring the health care experience of people with dementia and their caregivers in primary care settings, and we propose a conceptual framework for understanding and improving these health care experiences.     

Effects of reduced oxygen on growth and antibiotic production inStreptomyces clavuligerus

Summary The effects of reduced oxygen on growth and antibiotic production were studied in batch cultures ofStreptomyces clavuligerus in defined media. Antibiotic levels were unaffected by reduced oxygen for the first 50 hours of fermentation. After growth ceased, antibiotic concentrations dropped by a factor of about three under reduced oxygen, while the antibiotic concentration was stable when air was used. This suggests that enzymes for hydrolyzing antibiotics may be regulated by the aeration conditions.     

Modelling batch farrowing management within a farrow-to-finish pig herd: influence of management on contact structure and pig delivery to the slaughterhouse

Pathogen spread within pig host populations can vary depending on within-herd interactions among pigs also called the contact structure. The recommended batch farrowing management, allowing for a fixed-interval mating for groups of sows of equal size, called batches, leads to an all-in/all-out management of pigs in which animals in different batches have no contact. To maintain a profitable pig delivery, producers have to deliver groups of pigs at a given weight, what needs sometimes herd management adaptations. However, producers’ adaptations that avoid delivering pigs below slaughtering weight (out-of-range pigs), result in increasing the contact between animals from different batches. To study the influence of herd management on contact structure and on pig delivery, a stochastic mathematical model representing population dynamics within a farrow-to-finish herd was elaborated. Sixteen management systems were represented combining or not the all-in/all-out management system with producers’ decisions: batch mixing, use of an extra room, suppression of the drying period and sale of post-weaning batches. Two types of contact were considered: via the animals themselves, when batch mixing occurred; and via the room, when decontamination was not complete. The impact of producers’ decisions on contact structure and on pig delivery, differed radically when pig growth was normal and when it was slow (i.e. mean age at slaughtering weight increased by 20%). When pig growth was normal, the all-in/all-out management prevented both contact via the animals and via the room but resulted in 9% of pigs delivered out of range. The use of an extra room or batch mixing decreased this percentage, the latter resulting in very frequent contact between batches via the animals. When pig growth was slow, the all-in/all-out management led to a very high percentage of pigs delivered out of range (almost 80%). The suppression of the drying period at the end of the finishing period and the sale of post-weaning batches induced a significant decrease in this percentage (down to 2% to 20%), the latter allowing to reduce the percentage of batches that made contact via the room (40% instead of 80%). This pig herd model helped to understand the compromise for producers between implementing internal biosecurity or maintaining a profitable pig delivery. Our results show that there was no unique optimal system and that efficient producers’ decisions (for biosecurity and delivery) may differ, depending on pig growth.     

Determination of reduced glutathione in guinea pig and rat tissue by HPLC with electrochemical detection

A method using HPLC with electrochemical detection has been developed for the determination of GSH in tissue. The method is based upon the separation of GSH from other components by cation exchange chromatography coupled with the electrochemical oxidation of GSH to the corresponding disulfide. Detection limits of ca. 5 × 10^?12 moles GSH were established and the method was used to measure GSH content of rat and guinea pig brain, liver and synaptosome preparations.     

Microfungi of a Danish Beech forest Microbiology of a Danish beech forest II

The fungal flora in different parts of a beech forest ecosystem was investigated through a four year period as part of an IBP project. Both colony counts and direct measurements of fungal mycelium indicated that a vast majority of the fungal biomass is concentrated in the upper horizons of the soil, especially in the mull layer. The litter also contained large amounts of fungi when calculated per g dry weight, but still the litter fungi accounted for only a quite small percentage of the total fungal biomass. The fungi growing in direct contact with the living plants, i.e. in the rhizosphere and phylloplane, also accounted for only a few per cent of the total amount of fungi in the ecosystem.
On basis of direct measurements of fungal mycelium the total biomass was estimated to be about 100 g dry wt per m². However, no attempts were made to distinguish between living and dead hyphae, and a large proportion of the observed hyphae may very well be dead or inactive.
Qualitative studies revealed that the upper soil layers not only contained the largest amounts of fungal mycelium, but also by far the highest species diversity. Other parts of the ecosystem, e.g. the phylloplane, were often strongly dominated by one or a few species, whereas soil always contained a large variety of different types.