Infection and Drug Resistance Dovepress open access to scientific and medical research Open AccessPDF Full Text ArticleCompressor Free Version REVIEW Actinomycosis: etiology, clinical features, diagnosis, treatment, and management Florent Valour1–3 Abstract: Actinomycosis is a rare chronic disease caused by Actinomyces spp., anaerobic Agathe Sénéchal1,2 Gram-positive bacteria that normally colonize the human mouth and digestive and genital tracts. Céline Dupieux2–4 Physicians must be aware of typical clinical presentations (such as cervicofacial actinomyco- Judith Karsenty1,2 sis following dental focus of infection, pelvic actinomycosis in women with an intrauterine Sébastien Lustig2,5 device, and pulmonary actinomycosis in smokers with poor dental hygiene), but also that Pierre Breton2,6 actinomycosis may mimic the malignancy process in various anatomical sites. Bacterial cultures and pathology are the cornerstone of diagnosis, but particular conditions are required Arnaud Gleizal2,7 in order to get the correct diagnosis. Prolonged bacterial cultures in anaerobic conditions are Loïc Boussel2,8,9 necessary to identify the bacterium and typical microscopic findings include necrosis with 2–4 Frédéric Laurent yellowish sulfur granules and filamentous Gram-positive fungal-like pathogens. Patients 1 Evelyne Braun with actinomycosis require prolonged (6- to 12-month) high doses (to facilitate the drug 1–3 Christian Chidiac penetration in abscess and in infected tissues) of penicillin G or amoxicillin, but the dura- 1–3 Florence Ader tion of antimicrobial therapy could probably be shortened to 3 months in patients in whom Tristan Ferry1–3 optimal surgical resection of infected tissues has been performed. Preventive measures, 1Service des Maladies Infectieuses et such as reduction of alcohol abuse and improvement of dental hygiene, may limit occur- Tropicales, Hospices Civils de Lyon, rence of pulmonary, cervicofacial, and central nervous system actinomycosis. In women, Groupement Hospitalier Nord, Lyon, France; 2Université Claude Bernard Lyon 1, Lyon, intrauterine devices must be changed every 5 years in order to limit the occurrence of pelvic France; 3Centre International de Recherche actinomycosis. en Infectiologie, CIRI, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, Keywords: Actinomyces spp., sulfur granule, osteomyelitis, lumpy jaw syndrome France; 4Laboratoire de Bactériologie, Centre de Biologie du Nord, Hospices Civils de Lyon, Groupement Hospitalier Nord, Lyon, France; 5Chirurgie Orthopédique, Hospices Civils Introduction de Lyon, Groupement Hospitalier Nord, Actinomycosis is an infrequent invasive bacterial disease that has been rec- Lyon, France; 6Stomatologie et Chirurgie Maxillo-faciale, Hospices Civils de Lyon, ognized for over a century. Actinomyces spp. are filamentous Gram-positive Groupement Hospitalier Sud, Lyon, France; bacilli, mainly belonging to the human commensal flora of the oropharynx, 7Chirurgie Maxillo-faciale, Hospices Civils de Lyon, Groupement Hospitalier Nord, Lyon, gastrointestinal tract, and urogenital tract. To date, multiple different clinical France; 8Radiologie, Hospices Civils de Lyon, Groupement Hospitalier Nord, Lyon, France; features of actinomycosis have been described, as various anatomical sites (such 9Creatis, CNRS UMR 5220, INSERM U1044, as face, bone and joint, respiratory tract, genitourinary tract, digestive tract, Université Lyon 1, INSA Lyon, Lyon, France central nervous system, skin, and soft tissue structures) can be affected. Of note, in any site, actinomycosis frequently mimics malignancy, tuberculosis, or Correspondence: Tristan Ferry Service de Maladies Infectieuses nocardiosis, as it spreads continuously and progressively, and often forms a cold et Tropicales, Hospices Civils abscess.1–3 de Lyon – Hôpital de la Croix-Rousse, 103, Grande-Rue de la Croix-Rousse, In this review, we aim to describe: 1) the overview of the different species of 69317 Lyon cedex 04, France Actinomyces; 2) their involvement in different clinical features with illustrative cases; Tel +33 4 7207 2481 and 3) key elements for the diagnosis, ie, bacterial cultures and pathology; and 4) current Fax +33 4 7207 1750 Email [email protected] and emerging treatment options. submit your manuscript | www.dovepress.com Infection and Drug Resistance 2014:7 183–197 183 Dovepress © 2014 Valour et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) http://dx.doi.org/10.2147/IDR.S39601 License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Valour et al Dovepress Overview of the different high because of previous antibiotic therapy, inhibition of species of Actinomyces bacteria Actinomyces growth by concomitant and/or contaminant that causePDF actinomycosis Compressor Free Version microorganisms, inadequate culture conditions, or inadequate Bacteria of the genus Actinomyces belong to the Actinobacteria short-term incubation.16 Because of the microaerophilic or phylum and Actinomycetales order and are related to other genera strict anaerobic character of Actinomyces, strict anaerobic such as Corynebacterium, Mycobacterium, Nocardia, and processing (rapid transport to the laboratory and/or transport Propionibacterium. Besides Actinomyces, Propionibacterium in an anaerobic transport medium) and anaerobic growth propionicum (formerly Arachnia propionica), has often conditions should be used for primary isolation. The most been reported as an agent of actinomycosis-like infections.2,4 appropriate clinical specimens are tissue from surgical biopsy More than 30 species of Actinomyces have been described. or pus; swabs must be avoided. Finally, clinicians should Actinomyces israelii is the most prevalent species isolated indicate suspicion for actinomycosis to the microbiologist in human infections and is found in most clinical forms of to ensure that prolonged culture on appropriate media and actinomycosis.1–3,5,6 Actinomyces viscosus and Actinomyces in an appropriate atmosphere is performed. Moreover, the meyeri are also often reported in typical actinomycosis, identification of Actinomyces in mucosa, where these bacteria although they are less common,6,7 and A. meyeri is considered are normal inhabitants, is of little significance in the absence to have a great propensity for dissemination. Some species, of sulfur granules (see “Pathology of actinomycosis”) or a including Actinomyces naeslundii, Actinomyces odontolyticus, typical clinical syndrome, highlighting the importance of Actinomyces gerencseriae (formerly A. israelii serotype 2), microbiological investigations in combination with histologic Actinomyces neuii, Actinomyces turicensis, and Actinomyces analysis. radingae, have been associated with particular clinical A Gram stain of the specimen is usually more sensitive syndromes.8–11 Thus, A. israelii and A. gerencseriae are than culture, especially if the patient had received antibiotics. responsible for about 70% of orocervicofacial infections.5 Actinomyces are non-spore-forming Gram-positive rods. Hematogenous dissemination of actinomycosis is extremely Except for A. meyeri, which is small and nonbranching, all rare and has mainly been associated with A. meyeri, A. israelii, the other species are branching filamentous rods. and A. odontolyticus.12 Of note, most of the Actinomyces spp. Growth of Actinomyces is slow; it appears within at least are present in polymicrobial flora. Therefore Actinomyces 5 days and may take up to 15–20 days. Thus, incubation of are often isolated with other normal commensals, such as at least 10 days is required before conclusion of a negative Aggregatibacter actinomycetemcomitans, Eikenella corrodens, culture. Most Actinomyces spp. are facultative anaerobes, Capnocytophaga, fusobacteria, Bacteroides, staphylococci, but some relevant species (such as A. meyeri), are strictly streptococci, or Enterobacteriaceae, depending on the site of anaerobic, so cultures must be incubated in an anaerobic infection.4 As such, it is difficult to discriminate colonization atmosphere. Actinomyces can be cultured on chocolate of mucosa-contaminating samples and infection due to blood agar media at 37°C. Other enriched media can be Actinomyces except when the culture is pure and associated used for Actinomyces isolation: brain heart infusion broth with the presence of polynuclear neutrophils. On the other and Brucella Blood Agar with hemin and vitamin K1. The hand, Actinomyces infections could be polymicrobial use of semi-selective media (such as phenylethyl alcohol or and associated with other bacteria, named “companion mupirocin-metronidazole blood agar) may increase isolation microbes”, which contribute to initiation and development rates by inhibiting overgrowth of concomitant organisms.17 of infection by inhibiting host defenses or reducing oxygen Actinomyces can be initially suspected by colony morphology tension.3 The multimicrobial nature of infection is well and biochemical profiling. For example, A. israelii forms described in animal models and in human cervicofacial a “molar tooth” colony on agar and grows as