DOCSLIB.ORG

Developing Animal Models for Polymicrobial Diseases

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Developing Animal Models for Polymicrobial Diseases REVIEWS DEVELOPING ANIMAL MODELS FOR POLYMICROBIAL DISEASES Lauren O. Bakaletz Polymicrobial diseases involve two or more microorganisms that act synergistically, or in succession, to mediate complex disease processes. Although polymicrobial diseases in animals and humans can be caused by similar organisms, these disease are often also caused by organisms from different kingdoms, genera, species, strains, substrains and even by phenotypic variants of a single species. Animal models are often required to understand the mechanisms of pathogenesis, and to develop therapies and prevention regimes. However, reproducing polymicrobial diseases of humans in animal hosts presents significant challenges. There is now compelling evidence that many infectious also have important advantages over in vitro methods, diseases of humans (FIG. 1) and animals (TABLE 1) are including the presence of organized organ systems, an caused by more than one microorganism. The mixed intact immune system and, in inbred mice, specific microbial nature of these diseases has been recognized genetic backgrounds, and the availability of many since the early 1920s but there has been renewed interest reagents for characterizing the immune response to in this topic since the 1980s1,signalled by the publication sequential or co-infecting microorganisms. The availabil- of four important reviews (REFS 2–5) from 1982 to the pre- ity of mice with specific genetic backgrounds can have a sent date. Polymicrobial diseases (see BOX 1 for nomen- pivotal role in understanding the mechanisms of patho- clature) can be caused by the synergistic or sequential genesis of polymicrobial diseases, as exemplified by stud- action of infectious agents from either the same or dif- ies on septic peritonitis11–17,periodontal disease18 and ferent kingdoms, genera, species, strains or substrains, or Lyme arthritis19,20.Understanding the molecular mecha- by different phenotypic variants of a single species6. nisms underlying polymicrobial diseases of veterinary Polymicrobial diseases share underlying mechanisms of importance has also been facilitated by the use of animal pathogenesis, such as common predisposing factors models. These veterinary systems are useful examples for (BOX 2),but each disease has unique aspects. Although those researchers attempting to develop animal models the molecular mechanisms of some polymicrobial infec- of complex human diseases. tions are known, other polymicrobial diseases are not So far, most animal models for human polymicro- well understood. Owing to their complexity, the study of bial diseases are rodents, usually mice, but also rats, Center for Microbial polymicrobial infections requires a multidisciplinary gerbils, cotton rats and chinchillas. Other animal Pathogenesis, Columbus approach and specific in vitro methodologies and ani- models include non-human primates, which are use- Children’s Research mal models. The development of assay systems and ful for modelling diseases that are caused by microor- Institute, Department of treatment and prevention regimes is needed. ganisms with a restricted host range. For most human Pediatrics, The Ohio State University College of Multiple diverse in vitro systems have been used to viral co-infections of clinical importance, good ani- Medicine & Public Health, study polymicrobial diseases (BOX 3).Although in vitro mal models and culture systems are lacking and are 700 Children’s Drive, methods are crucial for understanding polymicrobial urgently required. Columbus, Ohio 43205- diseases, rigorous, reproducible and relevant animal This review provides an overview of the pathogenesis 2696, USA. models of human diseases are essential for the prevention of selected polymicrobial diseases, the molecular basis for e-mail: BakaletL@ 7–10 pediatrics.ohio-state.edu and treatment of these co-infections .All animal mod- some of these co-infections and describes animal models doi:10.1038/nrmicro928 els of human diseases have inherent limitations but they that have been developed to mimic these diseases. 552 | JULY 2004 | VOLUME 2 www.nature.com/reviews/micro REVIEWS Central nervous Table 1 | Examples of polymicrobial diseases system Sinuses • Multiple sclerosis* Host Infection or disease • Sinusitis • Alzheimer's disease* Cattle Bovine respiratory disease complex (BRDC), bovine gastroenteritis Ear Oral cavity Sheep Ovine conjunctivitis, ovine foot rot, chronic • Dental caries • Otitis media non-progressive pneumonia • Periodontitis • Adenotonsillitis Pigs Porcine atrophic rhinitis, porcine Respiratory tract gastroenteritis, porcine respiratory disease • Otitis media complex (PRDC) Heart • Pneumonia Poultry Poult enteritis mortality syndrome, • Stenotic artery • Pertussis disease infectious coryza • Atherosclerosis* • Kawasaki disease* Lung • Carotid coronary* • Cystic fibrosis • Pertussis the BVDV biotypes and can result in severe respiratory, • Chronic obstructive enteric or reproductive disease. The severity of the dis- pulmonary disease Gastrointestinal tract ease depends on the relative virulence of the viral strain, • Peritontitis physical and environmental stresses, and co-infection • Gastroenteritis Liver with another pathogen. • Hepatitis • Sarcoidosis* Bladder Porcine co-viral diseases. Porcine reproductive and respi- ratory syndrome (PRRS) results from infection with the Genitourinary tract • UTIs PRRS virus (PRRSV) followed by infection with a bacte- • Vaginitis rial or viral co-pathogen. Co-infecting viruses include • Inflammatory bowel porcine coronavirus, swine influenza virus22–24 and disease* pseudorabies virus25.Different plaque variants of PRRSV can also co-infect a porcine host26.Porcine post-weaning Skin and skeletal systems multisystemic wasting syndrome (PMWS) is due to • Necrotizing fasciitis • Group A streptococcal co-infection of pigs with porcine circovirus 2 (PCV-2) infection and porcine parvovirus (PPV)27,28. PCV-2 and PPV are • Lyme disease • Abscess thought to enter the host through tonsillar macrophages • Osteomyelitis and viraemia results within 3 days of infection. PCV-2 • Sarcoidosis* and PPV can replicate in circulating peripheral mono- cytes and contribute to both cell-associated viraemia and viral distribution throughout lymphoid tissues28. Hepatitis virus co-infection. Human co-infections with multiple hepatotropic viruses from the hepatitis virus group are well documented. Co-infection with multiple hepatitis viruses is possible owing to their similar routes of transmission and ability to chronically infect the host. Figure 1 | Human polymicrobial diseases. Polymicrobial diseases and suspected polymicrobial Hepatitis A virus (HAV) co-infection of individuals that diseases (indicated by an asterisk) are listed in the anatomical niche in which the disease are chronically infected with hepatitis B virus (HBV) pathology is mainly observed. and/or hepatitis C virus (HCV) results in a disease of increased severity and risk of death. Moreover, Viral co-infections HBV–HCV co-infection occurs in 10–15% of HBV Infections involving bovine viral diarrhoea virus. In cat- patients, and hepatitis G virus (HGV)–HCV co-infec- tle, infections with bovine viral diarrhoea virus (BVDV) tion occurs in 10–20% of individuals with chronic HCV can be clinically asymptomatic or can cause severe infection; however, HBV–hepatitis D virus (HDV) co- symptoms. The outcome depends on whether the pri- infection occurs only in the setting of co-infecting HBV. mary infection occurred in utero or after birth21 and VIRAL INTERFERENCE, in which replication of one virus is whether the primary infection was with a cytopathic or suppressed by another virus, is an intriguing aspect of non-cytopathic biotype of BVDV.Milder, congenital triple HBV–HCV–HDV infection — HDV can suppress persistent infection follows foetal infection with non- both HBV and HCV replication29.In a retrospective cytopathic BVDV. Death, or culling from the herd study of patients with hepatitis virus co-infections, HDV within 1 year of birth after failure to thrive, is common; was dominant by RT-PCR detection of HDV RNA in however some persistently infected calves seem healthy triple co-infections, but in dual co-infections there were at birth and survive for several years. Mucosal disease alternating dominant roles for either HBV or HCV. follows congenital persistent infection and is due to co- Multiple hepatotropic viral infections are associated with infection with cytopathic and non-cytopathic BVDV in reduced HCV replication but increased pathology. VIRAL INTERFERENCE One virus suppresses the utero. Conversely, acute bovine diarrhoeal disease is Patients with dual or triple co-infections have more replication of another. induced by primary post-natal infection with either of severe liver disease pathologies than patients that are NATURE REVIEWS | MICROBIOLOGY VOLUME 2 | JULY 2004 | 553 REVIEWS Co-infection with HIV and herpes simplex virus. In Box 1 | Nomenclature of polymicrobial diseases 1994, Kaposi’s sarcoma-associated herpesvirus For diseases and infections that involve two or more microorganisms, several terms are used (KSAV), also known as human herpesvirus type 8 in the literature, often interchangeably, and include: polymicrobial diseases, complex (HHSV-8), was isolated. KSAV is found in all clinical diseases, complicated infections, co-infections, concurrent infection, polybacterial diseases, variants of Kaposi’s sarcoma and is also associated dual infections, mixed infections, synergistic infections, superinfections and secondary with
Load more

Recommended publications
  • LYME DISEASE Other Names: Borrelia Burgdorferi
    LYME DISEASE Other names: Borrelia burgdorferi CAUSE Lyme disease is caused by a spirochete bacteria (Borrelia burgdorferi) that is transmitted through the bite from an infected arthropod vector, the black-legged or deer tick Ixodes( scapularis). SIGNIFICANCE Lyme disease can infect people and some species of domestic animals (cats, dogs, horses, and cattle) causing mild to severe illness. Although wildlife can be infected by the bacteria, it typically does not cause illness in them. TRANSMISSION The bacteria has been observed in the blood of a number of wildlife species including several bird species but rarely appears to cause illness in these species. White-footed mice, eastern chipmunks, and shrews serve as the primary natural reservoirs for Lyme disease in eastern and central parts of North America. Other species appear to have low competencies as reservoirs for the bacteria. The transmission of Lyme disease is relatively convoluted due to the complex life cycle of the black-legged tick. This tick has multiple developmental stages and requires three hosts during its life cycle. The life cycle begins with the eggs of the ticks that are laid in the spring and from which larval ticks emerge. Larval ticks do not initially carryBorrelia burgdorferi, the bacteria must be acquired from their hosts they feed upon that are carriers of the bacteria. Through the summer the larval ticks feed on the blood of their first host, typically small mammals and birds. It is at this point where ticks may first acquireBorrelia burgdorferi. In the fall the larval ticks develop into nymphs and hibernate through the winter.
    [Show full text]
  • Redalyc.Establishment of a Pathogenicity Index for One-Day-Old
    Revista Brasileira de Ciência Avícola ISSN: 1516-635X [email protected] Fundação APINCO de Ciência e Tecnologia Avícolas Brasil Pilatti, RM; Furian, TQ; Lima, DA; Finkler, F; Brito, BG; Salle, CTP; Moraes, HLS Establishment of a Pathogenicity Index for One-day-old Broilers to Pasteurella multocida Strains Isolated from Clinical Cases in Poultry and Swine Revista Brasileira de Ciência Avícola, vol. 18, núm. 2, abril-junio, 2016, pp. 255-260 Fundação APINCO de Ciência e Tecnologia Avícolas Campinas, Brasil Available in: http://www.redalyc.org/articulo.oa?id=179746750008 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative Brazilian Journal of Poultry Science Revista Brasileira de Ciência Avícola Establishment of a Pathogenicity Index for One-day- ISSN 1516-635X May - Jun 2016 / v.18 / n.2 / 255-260 old Broilers to Pasteurella multocida Strains Isolated http://dx.doi.org/10.1590/1806-9061-2015-0089 from Clinical Cases in Poultry and Swine Author(s) ABSTracT Pilatti RMI Although Pasteurella multocida is a member of the respiratory Furian TQI microbiota, under some circumstances, it is a primary agent of diseases Lima DAI , such as fowl cholera (FC), that cause significant economic losses. Finkler FII Brito BGII Experimental inoculations can be employed to evaluate the pathogenicity Salle CTPI of strains, but the results are usually subjective and knowledge on the Moraes HLSI pathogenesis of this agent is still limited.
    [Show full text]
  • ﺑﺴﻢ اﷲ اﻟﺮﺣﻤﻦ اﻟﺮﺣﻴﻢ Molecular Characterization Of
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by KhartoumSpace ﺑﺴﻢ اﷲ اﻟﺮﺣﻤﻦ اﻟﺮﺣﻴﻢ Molecular Characterization of Pasteurella multocida Vaccine Strains By: Hajir Badawi Mohammed Ahmed B.V.M Khartoum University (2006) Supervisor: Dr. Awad A. Ibrahim A dissertation submitted to the University of Khartoum in partial fulfillment of the requirements for the degree of M. Sc. in Microbiology Department of Microbiology, Faculty of Veterinary Medicine, University of Khartoum June, 2010 Dedication To my mother Father Brother, sister and friends With great love Acknowledgments First and foremost, I would like to thank my Merciful Allah, the most beneficent for giving me strength and health to accomplish this work. Then I would like to deeply thank my supervisor Dr. Awad A. Ibrahim for his advice, continuous encouragement and patience throughout the period of this work. My gratitude is also extended to prof. Mawia M. Mukhtar and for Dr. Manal Gamal El-dein, Institute of Endemic Disease. My thanks extend to members of Department of Microbiology Faculty of Veterinary Medicine for unlimited assistant and for staff of Central Laboratory Soba. I am grateful to my family for their continuous support and standing beside me all times. My thanks also extended to all whom I didn’t mention by name and to the forbearance of my friends, and colleagues who helped me. Finally I am indebted to all those who helped me so much to make this work a success. Abstract The present study was carried out to study the national haemorrhagic septicaemia vaccine strains at their molecular level.
    [Show full text]
  • BD-CS-057, REV 0 | AUGUST 2017 | Page 1
    EXPLIFY RESPIRATORY PATHOGENS BY NEXT GENERATION SEQUENCING Limitations Negative results do not rule out viral, bacterial, or fungal infections. Targeted, PCR-based tests are generally more sensitive and are preferred when specific pathogens are suspected, especially for DNA viruses (Adenovirus, CMV, HHV6, HSV, and VZV), mycobacteria, and fungi. The analytical sensitivity of this test depends on the cellularity of the sample and the concentration of all microbes present. Analytical sensitivity is assessed using Internal Controls that are added to each sample. Sequencing data for Internal Controls is quantified. Samples with Internal Control values below the validated minimum may have reduced analytical sensitivity or contain inhibitors and are reported as ‘Reduced Analytical Sensitivity’. Additional respiratory pathogens to those reported cannot be excluded in samples with ‘Reduced Analytical Sensitivity’. Due to the complexity of next generation sequencing methodologies, there may be a risk of false-positive results. Contamination with organisms from the upper respiratory tract during specimen collection can also occur. The detection of viral, bacterial, and fungal nucleic acid does not imply organisms causing invasive infection. Results from this test need to be interpreted in conjunction with the clinical history, results of other laboratory tests, epidemiologic information, and other available data. Confirmation of positive results by an alternate method may be indicated in select cases. Validated Organisms BACTERIA Achromobacter
    [Show full text]
  • Pasteurella Multocida Isolated from Cattle
    Journal of Applied Pharmaceutical Science Vol. 3 (04), pp. 106-110, April, 2013 Available online at http://www.japsonline.com DOI: 10.7324/JAPS.2013.3419 ISSN 2231-3354 Antibiotic Susceptibility and Molecular Analysis of Bacterial Pathogen Pasteurella Multocida Isolated from Cattle Azmat Jabeen, Mahrukh Khattak, Shahzad Munir*, Qaiser Jamal, Mubashir Hussain Department of Microbiology, Kohat University of Science and Technology, Kohat, Khyber Pakhtunkhwa, Pakistan. ARTICLE INFO ABSTRACT Article history: Pasteurella multocida is a Gram negative, non motile and coccobacillus bacterium. It has 5 strains i.e. A, B, D, Received on: 01/02/2013 E and F and 16 serotypes (1-16). In present study, we analyzed Pasteurella multocida B: 2 strains, responsible Revised on: 19/02/2013 for Hemorrhagic Septicemia (HS) in cattle, on morphological/microbial, biochemical, molecular level and to Accepted on: 15/03/2013 check the antibiotic sensitivity of the Pasteurella multocida. Microbial analysis showed that while grown on Available online: 27/04/2013 Brain Heart Infusion agar plates and Blood Agar Base Medium, grayish lustrous colonies of Pasteurella multocida were observed. Gram staining showed that Pasteurella multocida are gram negative. Microscopic Key words: observations revealed it to be coccobacillus and it was non- motile. Identification was conducted by Pasteurella multocida, conventional biochemical tests and percentage identification of Analytical Profile Index was 96 %. Antibiotic Hemorrhagic Septicemia, sensitivity with different antibiotics was checked by disk diffusion method and was found resistant to Analytical Profile Index, Augmentin, Amoxicillin and Aztreonam and was more susceptible to Ceftiofur. On molecular level its DNA Antibiotic sensitivity. was extracted and was run with marker having range from 0.5 – 10 kb.
    [Show full text]
  • Canine Lyme Borrelia
    Canine Lyme Borrelia Borrelia burgdorferi bacteria are the cause of Lyme disease in humans and animals. They can be visualized by darkfild microscopy as "corkscrew-shaped" motile spirochetes (400 x). Inset: The black-legged tick, lxodes scapularis (deer tick), may carry and transmit Borrelia burgdorferi to humans and animals during feeding, and thus transmit Lyme disease. Samples: Blood EDTA-blood as is, purple-top tubes or EDTA-blood preserved in sample buffer (preferred) Body fluids Preserved in sample buffer Notes: Send all samples at room temperature, preferably preserved in sample buffer MD Submission Form Interpretation of PCR Results: High Positive Borrelia spp. infection (interpretation must be correlated to (> 500 copies/ml swab) clinical symptoms) Low Positive (<500 copies/ml swab) Negative Borrelia spp. not detected Lyme Borreliosis Lyme disease is caused by spirochete bacteria of a subgroup of Borrelia species, called Borrelia burgdorferi sensu lato. Only one species, B. burgdorferi sensu stricto, is known to be present in the USA, while at least four pathogenic species, B. burgdorferi sensu stricto, B. afzelii, B. garinii, B. japonica have been isolated in Europe and Asia (Aguero- Rosenfeld et al., 2005). B. burgdorferi sensu lato organisms are corkscrew-shaped, motile, microaerophilic bacteria of the order Spirochaetales. Hard-shelled ticks of the genus Ixodes transmit B. burgdorferi by attaching and feeding on various mammalian, avian, and reptilian hosts. In the northeastern states of the US Ixodes scapularis, the black-legged deer tick, is the predominant vector, while at the west coast Lyme borreliosis is maintained by a transmission cycle which involves two tick species, I.
    [Show full text]
  • Studies on Oral Colonization of Periodontopathogenic Bacterium
    Studies on oral colonization of periodontopathogenic bacterium Eikenella corrodens 㸦ṑ࿘⑓ཎᛶ⣽⳦ (LNHQHOODFRUURGHQV ࡢཱྀ⭍ෆᐃ╔࡟㛵ࡍࡿ◊✲㸧 㻌 㻌 FARIHA JASIN MANSUR 2017 㻌 㻌 DEDICATED TO MY BELOVED PARENTS CONTENTS CONTENTS…………………………………………………………. 1 LIST OF ABBREVIATIONS ……………………………………. 2 CHAPTER 1: GENERAL INTRODUCTION …………………………………... 4 CHAPTER 2 .………………………………………………………. 11 2.1 ABSTRACT ……………………………………………………. 12 2.2 INTRODUCTION ……………………………………………... 13 2.3 MATERIALS AND METHODS ……………………………… 16 2.4 RESULTS AND DISCUSSION ……………………………….. 21 CHAPTER 3 ………………………………………………………... 31 3.1 ABSTRACT …………………………………………………….. 32 3.2 INTRODUCTION ……………………………………………… 33 3.3 MATERIALS AND METHODS ………………………………. 35 3.4 RESULTS AND DISCUSSION ………………………………... 38 CHAPTER 4: GENERAL CONCLUSION ………………………………………... 44 SUMMARY ………………………………………………………….. 50 JAPANESE SUMMARY ……………………………………………. 52 ACKNOWLEDGEMENTS …………………………………………. 54 REFERENCES ……………………………………………………….. 56 LIST OF PUBLICATIONS ………………………………………….. 65 㻝㻌 㻌 LIST OF ABBREVIATIONS CE Cell envelope GalNAc㻌㻌㻌㻌㻌㻌 N-acetyl-D-galactosamine g Gram g/L Gram/litre HA㻌㻌㻌㻌㻌㻌㻌㻌 Hemagglutination ∆hlyA hlyA-deficient strain H hour IL Interleukin IPTG Isopropyl β-D-1-thiogalactopyranoside LB㻌 㻌 㻌 㻌 Luria broth M Molar mM Milimolar min Minute mL Mililitre mg/mL Milligram/mililitre NaCl Sodium chloride ORF Open reading frame PBS Phosphate-buffered saline㻌 PCR Polymerase chain reaction pH㻌㻌 㻌 㻌㻌㻌㻌㻌㻌㻌Potential of hydrogen SDS–PAGE Sodium dodecyl sulfate polyacrylamide gel electrophoresis TSB Tryptic soy broth 㻞㻌 㻌 μL Microlitre μM Micromolar
    [Show full text]
  • Investigation of the Lipoproteome of the Lyme Disease Bacterium
    INVESTIGATION OF THE LIPOPROTEOME OF THE LYME DISEASE BACTERIUM BORRELIA BURGDORFERI BY Alexander S. Dowdell Submitted to the graduate degree program in Microbiology, Molecular Genetics & Immunology and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. _____________________________ Wolfram R. Zückert, Ph.D., Chairperson _____________________________ Indranil Biswas, Ph.D. _____________________________ Mark Fisher, Ph.D. _____________________________ Joe Lutkenhaus, Ph.D. _____________________________ Michael Parmely, Ph.D. Date Defended: April 27th, 2017 The dissertation committee for Alexander S. Dowdell certifies that this is the approved version of the following dissertation: INVESTIGATION OF THE LIPOPROTEOME OF THE LYME DISEASE BACTERIUM BORRELIA BURGDORFERI _____________________________ Wolfram R. Zückert, Ph.D., Chairperson Date Approved: May 4th, 2017 ii Abstract The spirochete bacterium Borrelia burgdorferi is the causative agent of Lyme borreliosis, the top vector-borne disease in the United States. B. burgdorferi is transmitted by hard- bodied Ixodes ticks in an enzootic tick/vertebrate cycle, with human infection occurring in an accidental, “dead-end” fashion. Despite the estimated 300,000 cases that occur each year, no FDA-approved vaccine is available for the prevention of Lyme borreliosis in humans. Development of new prophylaxes is constrained by the limited understanding of the pathobiology of B. burgdorferi, as past investigations have focused intensely on just a handful of identified proteins that play key roles in the tick/vertebrate infection cycle. As such, identification of novel B. burgdorferi virulence factors is needed in order to expedite the discovery of new anti-Lyme therapeutics. The multitude of lipoproteins expressed by the spirochete fall into one such category of virulence factor that merits further study.
    [Show full text]
  • ( Eikenella Corrodens のクオラムセンシングと バイオフィルム形成の関連性に関する研究）
    Studies on the relationship between quorum sensing and biofilm formation of Eikenella corrodens ( Eikenella corrodens のクオラムセンシングと バイオフィルム形成の関連性に関する研究） by MOHAMMAD MINNATUL KARIM Thesis Submitted to the United Graduate School of Agricultural Sciences Tottori University, Japan In partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY (PhD) The United Graduate School of Agricultural Sciences Tottori University, Japan September, 2013 1 DEDICATED TO MY BELOVED PARENTS 2 CONTENTS CONTENTS...............................................................................................ⅰ LIST OF ABBREVIATIONS...................................................................ⅱ GENERAL INTRODUCTION................................................................. 1 OBJECTIVES........................................................................................... 10 CHAPTER 1 ............................................................................................. 11 The Periodontopathogenic Bacterium Eikenella corrodens Produces an Autoinducer-2-Inactivating Enzyme 1.1 ABSTRACT ………………………………………………………… 12 1.2 INTRODUCTION …………………………………………………....13 1.3 MATERIALS AND METHODS ……………………………………..15 1.4 RESULTS …………………………………………………………… 19 1.5 DISCUSSION ………………………………………………………. 22 1.6 FIGURES …………………………………………………………….25 CHAPTER 2 …………………………………………………………… 32 LuxS affects biofilm maturation and detachment of the periodontopathogenic bacterium Eikenella corrodens 2.1 ABSTRACT …………………………………………………………. 33 2.2 INTRODUCTION …………………………………………………....34
    [Show full text]
  • Digestive Tract Infections •Skin & Soft Tissue Infections(SSTI)
    EU Conference: Workshop #6 Macrolide Indications: •Ocular Infections •Stomatologic Infections •Digestive tract Infections •Skin & Soft Tissue Infections(SSTI) Dr. S. Simonian (NL) © CBG-MEB 1 Introduction • Problem statement: – What is the (un-)labelled use of individual macrolides in ocular, stomatologic, GI and SSTI infections? – What is the ultimate list of practical indications in these areas? • Approach: – Review information documented in data sheets & clinical literature. – From current global situation to agreed ----> by reconciliation of clinical experience with regulatory process----> state of the art indications. Focus will be primarily on systemic macrolides. © CBG-MEB 2 General Indications Ocular infections 1 ? Conjunctivitis (neonatal) C. trachomatis 2 ? Blepharitis Staphylococcal Stomatologic infections Eikenella corrodens? ? Periodontal disease3 Streptococci spp. Digestive tract infections HP peptic ulcer H. pylori* CJ Acute enteritis4 C. jejuni Cholecystitis5 SSTI Acne P. acnes Impetigo, erysipelas Streptococci spp. Furuncles, abcesses S. aureus Lyme disease?? B. burgdorferi Bartonella infections in HIV-patients ? Unlabelled use Questionable * In combination with PPI and other ?? antibiotics (eg. amoxicillin) As unlabelled alternative to beta-lactams and tetracyclines in early Lyme disease. As second-line in case tetracyline is inappropriate. © CBG-MEB 3 Indication status: Labelled(!), unlabelled & in research Ery Rox Clar Azit Telit Jos Spir Ocular infections Conjunctivitis(of the newborn) ! Blepharitis ! Trachoma
    [Show full text]
  • Intrathoracic Infections Due to Eikenella Corrodens
    Thorax: first published as 10.1136/thx.42.9.700 on 1 September 1987. Downloaded from Thorax 1987;42:700-701 Intrathoracic infections due to Eikenella corrodens SHAHROKH JAVAHERI, RICHARD M SMITH, DAVID WILTSE From the Pulmonary Division and Department ofMedicine, Veterans Administration Medical Center, University ofCincinnati College ofMedicine; and the Pulmonary Division, Department ofMedicine, Good Samaritan Hospital, Cincinnati, Ohio, USA Eikenella corrodens, a fastidious facultative anaerobic Gram choscopy showed swelling of the left upper lobe bronchi; all negative bacillus,' is part of the normal human oral flora. specimens were negative for malignant cells. On day 7 a Although it has been implicated as the sole causative agent Gram negative rod was cultured from one of the blood cul- for certain infections, I- its pathogenetic importance ture bottles, and this was identified as E corrodens by mor- remains uncertain. E corrodens has been isolated in respira- phological and biochemical criteria.1 2 The organism was tory tract infections, including pneumonia, abscess, and resistant to clindamycin but sensitive to penicillin. All other empyema, where detailed bacteriological investigations have blood cultures, both aerobic and anaerobic, were negative; been performed, but only in association with other sputum grew normal flora. On day 9 ampicillin was given microbes.2 356 It was recently isolated by transtracheal or and gentamicin and clindamycin were stopped. He then percutaneous aspiration from seven patients with pneu- became afebrile and felt better and his appetite improved. monia or lung abscess,5 but in each case several other Repeated attempts to wean him from intravenous fluid organisms were cultured. The present report shows that E resulted in hypotension.
    [Show full text]
  • Assessing Lyme Disease Relevant Antibiotics Through Gut Bacteroides Panels
    Assessing Lyme Disease Relevant Antibiotics through Gut Bacteroides Panels by Sohum Sheth Abstract: Lyme borreliosis is the most prevalent vector-borne disease in the United States caused by the transmission of bacteria Borrelia burgdorferi harbored by the Ixodus scapularis ticks (Sharma, Brown, Matluck, Hu, & Lewis, 2015). Antibiotics currently used to treat Lyme disease include oral doxycycline, amoxicillin, and ce!riaxone. Although the current treatment is e"ective in most cases, there is need for the development of new antibiotics against Lyme disease, as the treatment does not work in 10-20% of the population for unknown reasons (X. Wu et al., 2018). Use of antibiotics in the treatment of various diseases such as Lyme disease is essential; however, the downside is the development of resistance and possibly deleterious e"ects on the human gut microbiota composition. Like other organs in the body, gut microbiota play an essential role in the health and disease state of the body (Ianiro, Tilg, & Gasbarrini, 2016). Of importance in the microbiome is the genus Bacteroides, which accounts for roughly one-third of gut microbiome composition (H. M. Wexler, 2007). $e purpose of this study is to investigate how antibiotics currently used for the treatment of Lyme disease in%uences the Bacteroides cultures in vitro and compare it with a new antibiotic (antibiotic X) identi&ed in the laboratory to be e"ective against B. burgdorferi. Using microdilution broth assay, minimum inhibitory concentration (MIC) was tested against nine di"erent strains of Bacteroides. Results showed that antibiotic X has a higher MIC against Bacteroides when compared to amoxicillin, ce!riaxone, and doxycycline, making it a promising new drug for further investigation and in vivo studies.
    [Show full text]