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Topic:Pathogens

Pathogens are microorganisms, such as bacteria, viruses, fungi, and parasites, that can cause disease in horses. These microorganisms interact with the equine immune system, often leading to a range of health issues that can affect individual horses or entire populations. Pathogens can be transmitted through various routes, including direct contact, vectors, or environmental exposure. Common equine pathogens include Streptococcus equi, Equine Herpesvirus, and Strongylus vulgaris. Understanding the interactions between equine hosts and pathogens is essential for disease prevention, management, and treatment. This page compiles peer-reviewed research studies and scholarly articles that explore the identification, transmission, and impact of pathogens on equine health.
Minimum inhibitory concentrations of equine Corynebacterium pseudotuberculosis isolates (1996-2012).
Journal of veterinary internal medicine    January 14, 2015   Volume 29, Issue 1 327-332 doi: 10.1111/jvim.12534
Rhodes DM, Magdesian KG, Byrne BA, Kass PH, Edman J, Spier SJ.Few studies report the minimum inhibitory concentrations for antimicrobials against equine Corynebacterium pseudotuberculosis isolates. Objective: To evaluate trends in the in vitro activities of 20 antimicrobials against equine Corynebacterium pseudotuberculosis isolates from 1996 to 2012 and to determine if a relationship exists between the minimum inhibitory concentration (MIC) and location of the abscess. Methods: Corynebacterium pseudotuberculosis isolates from 196 horses with naturally occurring disease. Methods: Retrospective and cross-sectional design. Medical records were reviewed to ...
Seasonal changes of diagnostic potential in the detection of Anoplocephala perfoliata equine infections in the climate of Central Europe.
Parasitology research    December 25, 2014   Volume 114, Issue 2 767-772 doi: 10.1007/s00436-014-4279-9
Tomczuk K, Kostro K, Grzybek M, Szczepaniak K, Studzińska M, Demkowska-Kutrzepa M, Roczeń-Karczmarz M.For this study, 724 gastrointestinal tracts of slaughter horses were investigated to determine the prevalence, intensity of Anoplocephala perfoliata and tapeworm development stages over the second, third and fourth quarter of 2012 and the first quarter of 2013. For each positive horse, faecal samples were collected from the rectum or small colon for coproscopic examinations. The samples were analysed using dedicated modified sedimentation-flotation methods. In total, 52 horses were infected with A. perfoliata in the course of the study, with an overall prevalence of 7.2 %. The prevalence chang...
MDR ST2179-CTX-M-15 Escherichia coli co-producing RmtD and AAC(6′)-Ib-cr in a horse with extraintestinal infection, Brazil.
The Journal of antimicrobial chemotherapy    December 23, 2014   Volume 70, Issue 4 1263-1265 doi: 10.1093/jac/dku520
Leigue L, Warth JF, Melo LC, Silva KC, Moura RA, Barbato L, Silva LC, Santos AC, Silva RM, Lincopan N.No abstract available
Equine pancreatic disease: a review and characterization of the lesions of four cases (2005-2014). Newman SJ.Equine pancreatic disease is considered rare, and successful treatment is limited. Additionally, antemortem diagnosis of equine pancreatitis is difficult because of the lack of definitive diagnostic tests. Although a paucity of information exists on this entity in the horse, pancreatic disease has typically been shown to be secondary to other gastrointestinal, hepatic, and endocrine conditions. No predisposition based on age, sex, or breed appears to exist, but several conditions predispose a horse to pancreatitis, including grain overload, endocrine disease, and parasite migration. A retrospe...
Re-emergence of a genetic outlier strain of equine arteritis virus: Impact on phylogeny.
Virus research    December 17, 2014   Volume 202 144-150 doi: 10.1016/j.virusres.2014.12.009
Steinbach F, Westcott DG, McGowan SL, Grierson SS, Frossard JP, Choudhury B.Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory and reproductive disease of equids, which is notifiable in some countries including the Great Britain (GB) and to the OIE. Herein, we present the case of a persistently infected stallion and the phylogenetic tracing of the virus strain isolated. Discussing EAV occurrence and phylogenetic analysis we review features, which may aid to harmonise and enhance the classification of EAV.
Draft Genome Sequence of Taylorella equigenitalis Strain MCE529, Isolated from a Belgian Warmblood Horse.
Genome announcements    November 26, 2014   Volume 2, Issue 6 doi: 10.1128/genomeA.01214-14
Hébert L, Touzain F, de Boisséson C, Breuil MF, Duquesne F, Laugier C, Blanchard Y, Petry S.Taylorella equigenitalis is the causative agent of contagious equine metritis (CEM), a sexually transmitted infection of horses. We herein report the genome sequence of T. equigenitalis strain MCE529, isolated in 2009 from the urethral fossa of a 15-year-old Belgian Warmblood horse in France.
In contrast to other species, α-Galactosylceramide (α-GalCer) is not an immunostimulatory NKT cell agonist in horses.
Developmental and comparative immunology    November 10, 2014   Volume 49, Issue 1 49-58 doi: 10.1016/j.dci.2014.11.005
Dossa RG, Alperin DC, Garzon D, Mealey RH, Brown WC, Jervis PJ, Besra GS, Cox LR, Hines SA.α-GalCer is a potent immunomodulatory molecule that is presented to NKT cells via the CD1 antigen-presenting system. We hypothesized that when used as an adjuvant α-GalCer would induce protective immune responses against Rhodococcus equi, an important pathogen of young horses. Here we demonstrate that the equine CD1d molecule shares most features found in CD1d from other species and has a suitable lipid-binding groove for presenting glycolipids to NKT cells. However, equine CTL stimulated with α-GalCer failed to kill cells infected with R. equi, and α-GalCer did not increase killing by C...
Equine protozoal myeloencephalitis.
The Veterinary clinics of North America. Equine practice    November 6, 2014   Volume 30, Issue 3 659-675 doi: 10.1016/j.cveq.2014.08.012
Howe DK, MacKay RJ, Reed SM.Equine protozoal myeloencephalitis (EPM) can be caused by either of 2 related protozoan parasites, Sarcocystis neurona and Neospora hughesi, although S. neurona is the most frequent etiologic pathogen. Horses are commonly infected, but clinical disease occurs infrequently; the factors influencing disease occurrence are not well understood. Risk factors for the development of EPM include the presence of opossums and prior stressful health-related events. Attempts to reproduce EPM experimentally have reliably induced antibody responses in challenged horses but have not consistently produced acut...
Predominance of Leptospira interrogans serovar Bratislava DNA in vaginal fluid of mares suggests sexual transmission of leptospirosis.
Animal reproduction science    October 28, 2014   Volume 151, Issue 3-4 275-279 doi: 10.1016/j.anireprosci.2014.10.019
Hamond C, Martins G, Bremont S, Medeiros MA, Bourhy P, Lilenbaum W.The purpose of the present study was to detect the presence of DNA of pathogenic Leptospira sp. in vaginal fluids of mares regarding a possible role of the sexual transmission. A total of 134 breeding mares from four troops were studied and sampling was conducted from vaginal fluids and urine for culture and PCR; and blood for serology. From the 134 serum samples tested, 59 (44%) were seroreactive, and serovar Bratislava was the most frequent (54.2%). None positive culture was obtained, but leptospiral DNA was detected by PCR (lipL32 gene) in 45 (33.5%) urine samples and 43 (32%) vaginal fluid...
Occurrence of Treponema DNA in equine hoof canker and normal hoof tissue.
Equine veterinary journal    October 9, 2014   Volume 47, Issue 5 627-630 doi: 10.1111/evj.12327
Sykora S, Brandt S.Equine hoof canker is a chronic pododermatitis of still unknown aetiology. Recent findings reported for 3 canker-bearing individuals are suggestive for Treponema spp. having a role in disease pathogenesis. Objective: Based on this hypothesised association, we assessed a larger number of DNA samples from hooves with canker and normal hooves for the presence of treponemal DNA. Methods: Retrospective survey of archived material. Methods: The study involved 71 archival, PCR-compatible DNA extractions purified from 59 canker samples obtained from 26 equine cases and from 12 hoof biopsies taken from...
Antiviral activity of a Bacillus sp. P34 peptide against pathogenic viruses of domestic animals.
Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]    October 9, 2014   Volume 45, Issue 3 1089-1094 doi: 10.1590/s1517-83822014000300043
Scopel e Silva D, de Castro CC, da Silva e Silva F, Sant'anna V, Vargas GD, de Lima M, Fischer G, Brandelli A, da Motta Ade S, Hübner Sde O.P34 is an antimicrobial peptide produced by a Bacillus sp. strain isolated from the intestinal contents of a fish in the Brazilian Amazon basin with reported antibacterial activity. The aim of this work was to evaluate the peptide P34 for its in vitro antiviral properties against canine adenovirus type 2 (CAV-2), canine coronavirus (CCoV), canine distemper virus (CDV), canine parvovirus type 2 (CPV-2), equine arteritis virus (EAV), equine influenza virus (EIV), feline calicivirus (FCV) and feline herpesvirus type 1 (FHV-1). The results showed that the peptide P34 exhibited antiviral activity a...
Impact of equine herpesvirus type 1 (EHV-1) infection on the migration of monocytic cells through equine nasal mucosa.
Comparative immunology, microbiology and infectious diseases    October 8, 2014   Volume 37, Issue 5-6 321-329 doi: 10.1016/j.cimid.2014.09.004
Baghi HB, Nauwynck HJ.The mucosal surfaces are important sites of entry for a majority of pathogens, and viruses in particular. The migration of antigen presenting cells (APCs) from the apical side of the mucosal epithelium to the lymph node is a key event in the development of mucosal immunity during viral infections. However, the mechanism by which viruses utilize the transmigration of these cells to invade the mucosa is largely unexplored. Here, we establish an ex vivo explant model of monocytic cell transmigration across the nasal mucosal epithelium and lamina propria. Equine nasal mucosal CD172a(+) cells (nmCD...
Detection of modified-live equine intranasal vaccine pathogens in adult horses using quantitative PCR.
The Veterinary record    October 1, 2014   Volume 175, Issue 20 510 doi: 10.1136/vr.102592
Harms C, Mapes S, Akana N, Coatti Rocha D, Pusterla N.No abstract available
Pathology of gastric lesions in donkeys: A preliminary study.
Equine veterinary journal    September 29, 2014   Volume 47, Issue 6 684-688 doi: 10.1111/evj.12336
Al-Mokaddem AK, Ahmed KA, Doghaim RE.Donkeys (Equus africanus asinus) are important working animals, particularly in countries where the majority of the population lives below the poverty line. Gastric ulceration has been shown to be common in British donkeys but donkeys from other parts of the world have not been as extensively researched. Objective: This study was performed as a preliminary overview of the severity and distribution of gastric lesions in mature donkeys and to document which parasites were present. Methods: Descriptive study of pathological findings. Methods: Stomachs of 35 mature draught donkeys were examined gr...
Effect of breeding activity on the microflora of the external genitalia and in the semen of stallions, and the relationship between micro-organisms on the skin and on the external genitalia.
Reproduction in domestic animals = Zuchthygiene    September 15, 2014   Volume 49, Issue 6 926-933 doi: 10.1111/rda.12403
Guimarães T, Miranda C, Pinto M, Silva E, Damásio L, Costa AL, Correia MJ, Duarte JC, Cosinha C, Lopes G, Thompson G, Rocha A.A possible role of breeding activities in the composition of the microbial population in stallions' external genitalia (EG) and the relationship between micro-organisms colonizing the skin of the abdomen and the ones colonizing the EG have not been studied. In experiment 1, EG microbiological samples were collected from 41 stallions used for both natural cover and semen collection (BST) and from 18 non-breeding stallions (NBST). A higher (p < 0.05) frequency of isolation of potentially pathogenic species was found for BST. Age did not influence number of micro-organism species isolated both in...
Immunogenicity of an electron beam inactivated Rhodococcus equi vaccine in neonatal foals.
PloS one    August 25, 2014   Volume 9, Issue 8 e105367 doi: 10.1371/journal.pone.0105367
Bordin AI, Pillai SD, Brake C, Bagley KB, Bourquin JR, Coleman M, Oliveira FN, Mwangi W, McMurray DN, Love CC, Felippe MJ, Cohen ND.Rhodococcus equi is an important pathogen of foals that causes severe pneumonia. To date, there is no licensed vaccine effective against R. equi pneumonia of foals. The objectives of our study were to develop an electron beam (eBeam) inactivated vaccine against R. equi and evaluate its immunogenicity. A dose of eBeam irradiation that inactivated replication of R. equi while maintaining outer cell wall integrity was identified. Enteral administration of eBeam inactivated R. equi increased interferon-γ production by peripheral blood mononuclear cells in response to stimulation with virulent R. ...
Characterisation of nasal Staphylococcus delphini and Staphylococcus pseudintermedius isolates from healthy donkeys in Tunisia.
Equine veterinary journal    August 14, 2014   Volume 47, Issue 4 463-466 doi: 10.1111/evj.12305
Gharsa H, Slama KB, Gómez-Sanz E, Gómez P, Klibi N, Zarazaga M, Boudabous A, Torres C.Staphylococcus intermedius group (SIG) bacteria can colonise the nares of some animals but are also emerging pathogens in humans and animals. Objective: To analyse SIG nasal carriage in healthy donkeys destined for food consumption in Tunisia and to characterise recovered isolates. Methods: Nasal swabs from 100 healthy donkeys were tested for SIG recovery, and isolates were identified by biochemical and molecular methods. Antimicrobial susceptibility of isolates was tested and detection of antimicrobial resistance and virulence genes was performed. Isolates were typed at the clonal level by mu...
Administration of commercial Rhodococcus equi specific hyperimmune plasma results in variable amounts of IgG against pathogenic bacteria in foals.
The Veterinary record    August 12, 2014   Volume 175, Issue 19 485 doi: 10.1136/vr.102594
Sanz MG, Oliveira AF, Page A, Horohov DW.Rhodococcus equi is the most common cause of pneumonia in young foals. A vaccine is not available and the use of R equi-specific hyperimmune plasma (HIP) is common. Despite its widespread use, the efficacy of HIP in preventing disease remains controversial. The objectives of this study were (1) to evaluate the virulence associate protein A (VapA)-specific IgG and IgG subclasses in commercially available R equi HIP and (2) to evaluate serum VapA-specific IgG and IgG subclasses in foals following administration of commercial R equi HIP. Three different lots from four commercial R equi HIP were s...
Infection of equine monocyte-derived macrophages with an attenuated equine infectious anemia virus (EIAV) strain induces a strong resistance to the infection by a virulent EIAV strain.
Veterinary research    August 9, 2014   Volume 45, Issue 1 82 doi: 10.1186/s13567-014-0082-y
Ma J, Wang SS, Lin YZ, Liu HF, Liu Q, Wei HM, Wang XF, Wang YH, Du C, Kong XG, Zhou JH, Wang X.The Chinese attenuated equine infectious anemia virus (EIAV) vaccine has successfully protected millions of equine animals from EIA disease in China. Given that the induction of immune protection results from the interactions between viruses and hosts, a better understanding of the characteristics of vaccine strain infection and host responses would be useful for elucidating the mechanism of the induction of immune protection by the Chinese attenuated EIAV strain. In this study, we demonstrate in equine monocyte-derived macrophages (eMDM) that EIAVFDDV13, a Chinese attenuated EIAV strain, indu...
Bacteriostatic effect of equine pure platelet-rich plasma and other blood products against methicillin-sensitive Staphylococcus aureus. An in vitro study.
Veterinary and comparative orthopaedics and traumatology : V.C.O.T    August 4, 2014   Volume 27, Issue 5 372-378 doi: 10.3415/VCOT-14-04-0054
López C, Carmona JU, Giraldo CE, Alvarez ME.1) To evaluate the bacteriostatic in vitro effect of pure platelet-rich plasma (P-PRP), pure platelet-rich gel (P-PRG), leukocyte-poor gel (LPG), platelet-poor plasma (PPP), and heat inactivated plasma (IP) against methicillin-sensitive Staphylococcus aureus (MSSA) over a period of 24 hours. 2) To determine the degradation of platelet factor-4 (PF-4), transforming growth factor beta 1 (TGF-β1), and platelet-derived growth factor isoform BB (PDGF-BB) in these equine blood components. 3) To establish correlations between platelet and leukocyte counts, PF-4 concentrations, and MSSA growth. Metho...
Evaluation of regional limb perfusion with chloramphenicol using the saphenous or cephalic vein in standing horses.
Journal of veterinary pharmacology and therapeutics    July 30, 2014   Volume 38, Issue 1 35-40 doi: 10.1111/jvp.12140
Kelmer G, Tatz AJ, Famini S, Bdolah-Abram T, Soback S, Britzi M.Regional limb perfusion (RLP) significantly decreases morbidity and mortality associated with distal limb injuries in horses. There is an urgent need for finding additional effective antimicrobial drugs for use in RLP. In this study, we tested the pharmacokinetics (PK) of chloramphenicol in RLP. Eight horses participated in the study, which was approved by the University Animal Care and Use Committee. The cephalic and the saphenous veins were used to perfuse the limbs. Synovial samples were collected from the metacarpo/metatarsophalangeal (MCP/MTP) joint. The Friedman Test was applied for asse...
Multiresistant extended-spectrum β-lactamase-producing Enterobacteriaceae from humans, companion animals and horses in central Hesse, Germany.
BMC microbiology    July 12, 2014   Volume 14 187 doi: 10.1186/1471-2180-14-187
Schmiedel J, Falgenhauer L, Domann E, Bauerfeind R, Prenger-Berninghoff E, Imirzalioglu C, Chakraborty T.Multiresistant Gram-negative bacteria producing extended-spectrum β-lactamases (ESBLs) are an emerging problem in human and veterinary medicine. This study focused on comparative molecular characterization of β-lactamase and ESBL-producing Enterobacteriaceae isolates from central Hesse in Germany. Isolates originated from humans, companion animals (dogs and cats) and horses. Results: In this study 153 (83.6%) of the human isolates (n = 183) and 163 (91.6%) of the animal isolates (n = 178) were confirmed as ESBL producers by PCR and subsequent sequencing of the PCR amplicons. Predomin...
Rapid detection of equine influenza virus H3N8 subtype by insulated isothermal RT-PCR (iiRT-PCR) assay using the POCKIT™ Nucleic Acid Analyzer.
Journal of virological methods    June 30, 2014   Volume 207 66-72 doi: 10.1016/j.jviromet.2014.06.016
Balasuriya UB, Lee PY, Tiwari A, Skillman A, Nam B, Chambers TM, Tsai YL, Ma LJ, Yang PC, Chang HF, Wang HT.Equine influenza (EI) is an acute, highly contagious viral respiratory disease of equids. Currently, equine influenza virus (EIV) subtype H3N8 continues to be the most important respiratory pathogen of horses in many countries around the world. The need to achieve a rapid diagnosis and to implement effective quarantine and movement restrictions is critical in controlling the spread of EIV. In this study, a novel, inexpensive and user-friendly assay based on an insulated isothermal RT-PCR (iiRT-PCR) method on the POCKIT™, a field-deployable device, was described and validated for point-of-nee...
Clonal spread of highly successful ST15-CTX-M-15 Klebsiella pneumoniae in companion animals and horses.
The Journal of antimicrobial chemotherapy    June 27, 2014   Volume 69, Issue 10 2676-2680 doi: 10.1093/jac/dku217
Ewers C, Stamm I, Pfeifer Y, Wieler LH, Kopp PA, Schønning K, Prenger-Berninghoff E, Scheufen S, Stolle I, Günther S, Bethe A.To investigate the clinical relevance and molecular epidemiology of extended-spectrum β-lactamase (ESBL)-producing Klebsiella species in animals. Methods: Antimicrobial susceptibilities and presence of ESBLs were examined among Klebsiella spp. (n = 1519) from clinical samples (>1200 senders from Germany and other European countries) mainly from companion animals and horses from October 2008 to March 2010. Multilocus sequence typing (MLST) and PFGE were performed including human isolates for comparative purposes. Results: The overall ESBL rate was 8% for Klebsiella pneumoniae subsp. pne...
Full genome sequences of zebra-borne equine herpesvirus type 1 isolated from zebra, onager and Thomson’s gazelle.
The Journal of veterinary medical science    June 11, 2014   Volume 76, Issue 9 1309-1312 doi: 10.1292/jvms.14-0183
Guo X, Izume S, Okada A, Ohya K, Kimura T, Fukushi H.A strain of equine herpesvirus type 1 (EHV-1) was isolated from zebra. This strain, called "zebra-borne EHV-1", was also isolated from an onager and a gazelle in zoological gardens in U.S.A. The full genome sequences of the 3 strains were determined. They shared 99% identities with each other, while they shared 98% and 95% identities with the horse derived EHV-1 and equine herpesvirus type 9, respectively. Sequence data indicated that the EHV-1 isolated from a polar bear in Germany is one of the zebra-borne EHV-1 and not a recombinant virus. These results indicated that zebra-borne EHV-1 is a ...
A brief introduction to equine influenza and equine influenza viruses.
Methods in molecular biology (Clifton, N.J.)    June 6, 2014   Volume 1161 365-370 doi: 10.1007/978-1-4939-0758-8_31
Chambers TM.Equine influenza virus (EIV) is a common respiratory pathogen of horses and other equids in most parts of the world. EIV are Type A influenza viruses and two subtypes are known: H3N8 and H7N7. Both are believed to have evolved from avian influenza virus ancestors. The H3N8 subtype circulates widely, but the H7N7 subtype is thought to be extinct. The clinical disease in horses, caused by either subtype, is an upper respiratory infection of varying severity depending upon the immune status of the individual animal. It is not normally life-threatening in itself except in very young foals; however...
Coagulopathies in horses.
The Veterinary clinics of North America. Equine practice    June 4, 2014   Volume 30, Issue 2 437-ix doi: 10.1016/j.cveq.2014.04.002
Epstein KL.Although primary coagulopathies are rare in horses, changes in coagulation and fibrinolysis are commonly associated with inflammatory diseases. A clear understanding of the pathophysiology of normal and abnormal hemostasis is required to be able to choose and interpret diagnostic tests evaluating coagulation and fibrinolysis. After diagnosis, treatment of the underlying disease must occur regardless of whether clinical manifestations (excessive bleeding or thrombosis) of the coagulopathy are present or not. Specific treatment may be initiated if there are clinical signs of coagulopathy.
Development of a loop-mediated isothermal amplification method for detecting Streptococcus equi subsp. zooepidemicus and analysis of its use with three simple methods of extracting DNA from equine respiratory tract specimens.
The Journal of veterinary medical science    May 28, 2014   Volume 76, Issue 9 1271-1275 doi: 10.1292/jvms.14-0140
Kinoshita Y, Niwa H, Katayama Y.Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is a dominant pathogenic bacterium in equine pneumonia. We developed a specific loop-mediated isothermal amplification (LAMP) method, which targets the gene encoding sorbitol-6-phosphate 2-dehydrogenase (sorD), for detecting S. zooepidemicus and examined the clinical efficacies of its use in combination with each of 3 DNA extraction methods easily used by veterinary practitioners, namely the Loopamp PURE DNA Extraction Kit, InstaGene Matrix and a conventional boiling method. The LAMP method plus the Loopamp PURE DNA Extraction Kit gave...
Prevalence and species of ticks on horses in central Oklahoma.
Journal of medical entomology    May 23, 2014   Volume 50, Issue 6 1330-1333 doi: 10.1603/me13117
Duell JR, Carmichael R, Herrin BH, Holbrook TC, Talley J, Little SE.Ticks are common on horses, but there is a dearth of contemporary data on infestation prevalence, predominant species, and tick-borne disease agents important in this host. To determine the species of ticks most common on horses and the prevalence of equine exposure to and infection with tick-borne disease agents, ticks and blood samples were collected from 73 horses during May, June, and July of 2010. Adult ticks were identified to species, and antibodies to Ehrlichia spp., Anaplasma spp., and Borrelia burgdorferi were identified using indirect fluorescence antibody assay, a commercial point-...
In vitro susceptibility of equine-obtained isolates of Corynebacterium pseudotuberculosis to gallium maltolate and 20 other antimicrobial agents.
Journal of clinical microbiology    May 14, 2014   Volume 52, Issue 7 2684-2685 doi: 10.1128/JCM.01252-14
Norman TE, Batista M, Lawhon SD, Zhang S, Kuskie KR, Swinford AK, Bernstein LR, Cohen ND.This study's objective was to determine the in vitro antimicrobial activities of gallium maltolate (GaM) and 20 other antimicrobial agents against clinical equine isolates of Corynebacterium pseudotuberculosis. The growth of cultured isolates was not inhibited by any concentration of GaM. MIC data revealed susceptibility to commonly used antimicrobials.
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