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2 Actinomyces species: Clinical aspects and diagnostic possibilities Willem Manson Prof. dr. John Degener, dr. Willem Manson University Medical Center Groningen UMCG

3 AIM OF THIS PRESENTATION, to gain knowledge of: the clinical importance of Actinomyces spp. Clinical pitfalls. Basic bacteriological properties of Actinomyces spp. Methods of isolation and identification. Recent taxonomic changes. Antimicrobial susceptibility and therapeutc options.

4 A 41 year old man complains since some weeks of fever, malaise and weight loss Since 2 days pain in the left chest Moderately ill, dyspnea Temp 38 C, Friction rub. BSE 67 mm L 15.5 X thorax: infiltrate left CTscan: diminished perfusion DIAGNOSIS: lung embolism

5 Intravenous heparin was administered and after 10 days the patient was discharged Symptoms of malaise, weight loss and periods of fever persisted BSE 127 mm, L 19.0, T 37.5 Sputum cultures didn t reveal any pathogenic microorganism. ZN negative Gram stain pleural fluid: L+++, no micro-organisms, culture neg No diagnosis was made and the patient was discharged again

6 Clinical condition deteriorated and 15 weeks after the first admission the patient was admitted for the third time. Because of a suspicion of a malignancy a thoracotomy was performed. PATHOLOGY: a inflammatory infiltrate neutrophils. Clusters of branched bacteria. No malignacy Microbiology: Gram L +++, sporadic branched Gram positive rods Culture: Actinomyces species

7 Treatment with i.v.penicillin G for 2 months followed by oral doxycyclin for 6 months At follow-up 12 months after starting therapy the patient was in a good condition without pulmonary complaints. It was noted however that his dental status was poor and he was advised to visit his dentist for sanitation.

8 Actinomycosis presenting as carcinoma. Hinnie J, Jaques BC, Bell E, Hansell DT, Milroy R. Pulmonary actinomycosis resembling an anterior mediastinal tumor Sato T, Takada N,Dobashi Y, Suzuki M, Ouchi M,Abe Y Cervical actinomycosis. A rare differential diagnosis of parotid tumor Lang-Roth R, Schippers C, Eckel HE. Abdominal actinomycosis presenting as a malignant tumor--report of a case and review of the literature Molnar T, Nagy A, Ligeti E, Gyulai C, Marton J, Nagy F. Endobronchial actinomycosis simulating endobronchial tuberculosis: a case report. Lee SH, Shim JJ, Kang EY, Lee SY, Jo JY, In KH, Yoo SH, Kang KH. Abdominal actinomycosis misdiagnosed as a secondary bladder tumor: a case report. Kawahara M, Kawahara K, Goto T, Yamamoto S, Fuchinoue S, Matsumoto T

9 ACTINOMYCES / NOCARDIA Bacteria that masquerade as fungi or cancer C. Sullivan, S. Chapman. Proc.Am. Thorac. Soc : Order Actinomycetales: Aerobic: Nocardia, Gordona,Tsukamurella,Streptomyces, Rhodococcus, Corynebacteria Anaerobic: Actinomyces,Arachnia,Rothia, Bifidobacterium

10 ACTINOMYCOSE 1877 infections in cattle (Bollinger) 1878 Actinomyces was found during an obduction (Israel) 1879 oral-cervicofacial abscess (Ponflick) 1891 isolation of Actinomyces by Israel & Wolf 1898 Actinomyces israelii

11 Deep Actinomyces infections are rare 1 : CERVICOFACIAL 60% ABDOMINAL 20% THORACAL 15% OTHERS 5%

12 CERVICAL ACTINOMYCOSIS

13 ACTINOMYCOSE OF THE LUNG

14 ACTINOMYCOSE OF THE LUNG

15 SECTION OF LESION IN THE LONG, CAUSED BY ACTINOMYCES

16 Brain abscess due to a combined Actinomyces- Actinobacillus actinomycetemcomitans infection. Zijlstra EE, Swart GR, Godfroy FJM, DegenerJE. J. Infection :83-87.

17 Actinomycosis of 54 years' duration Clin. Infect Dis 1998: 27: years old man was wounded at the 6th of june 1944 at the hand. After some weeks a purulent discharge appeared with yellow-white granula Actinomyces israelii Treatment with courses of erythromycin, oral penicillins, tetracyclines and clindamycin all gave only temporarily resolution of symptoms The disease persisted for 54 years

18 ACTINOMYCETES: Heterogeneous group Gram pos. mo Grampositive rods, often branched Sulphur granula (facultative) anaerobe mo molar like aspect Motility: - catalase - ( excl. A.viscosus en A.neuii) indole -

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22 Actinomyces Sulphur granules- purulent discharge originating from Actinomyces infection

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25 Actinomyces Grows slowly in culture- should be observed for up to 21 days Selective medium- MMBA Molar tooth colonies

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27 SELECTIVE MEDIA: ISOLATION - IDENTIFICATION Cadmium Fluoride Acriflavin Tellurite agar Mupirocin Metronidazole Blood Agar (MMBA) (Columbia agar with 128 mg/l mupirocin en 2.5 mg/l metronidazole) Colony morphology GLC PHENOTYPIC SEQUENCE (16s RNA) Malditof 97% correct id

28 Online Lecture Library Slide withheld at request of author

29 Online Lecture Library Slide withheld at request of author

30 ACTINOMYCES ( presently 42 species, 2 subsp) A. israelii A. naeslundii A. viscosus A. odontolyticus A. georgiae A. meyeri A. gerencseriae A. graevenitzii A. europaeus A. neuii A. radinga A. turicensis A. cardiffensis A. houstonensis A. hongkongensis A. funkei

31 taxonomic changes among Actinomyces and closely related genera from human sources Year current name previous or source taxonomic position 1994 A. neuii supsp anitratus CDC gr 1 coryneform abscess, blood 1994 A. neuii subsp neuii CDC gr 1 like coryneform abscess, blood 1995 A. radingae A. pyogenes - like polymicrobial 1995 A. turicensis A. pyogenes - like polymocrobial 1995 A. europaeus new abscess 1997 A. graevenitzii new resp.tract 2000 A. radicidentis new oral cavity 2000 A. urogenitalis new urogenital 2001 A. funkii new blood 1997 Actinobaculum schaalii new blood 1997 Arcanobacterium bernardiae A. bernardiae abscess, blood 1998 Arcanobacterium pyogenes A. pyogenes polymicrobial Sarkonen, et al. J.Clin. Microbiol(2001)

32 Online Lecture Library Slide withheld at request of author

33 Phenotypic identification of Actinomyces, obsolete?

34 IDENTIFICATION OF ACTINOMYCES BY AMPLIFIED 16S RIBOSOMAAL DNA Val Hall et al. J.Clin. Microbiol 39: 3555 (2001) 475 clinical Actinomyces isolates 331 (70%) Actinomyces species 44(9%) no Actinomyces 113 A. meyeri : 21 A. meyeri 63 A. turicensis 7 other Actinomycetes 22 not identified

35 SUSCEPTIBILITY OF ACTINOMYCES All Actinomyces spp are susceptible to penicillins, cefalosporins, linezolid Most of the Actinomyces spp are resistant against ciprofloxacin A. turicensis is less susceptible to tetracycline A. europaeus is less susceptible to erythromycin and clindamycin Smith et al. J. Antimicrobiol. Chemother. (2005)

36 SURGIGAL THERAPY ANTIBIOTIC THERAPY THERAPY FOR ACTINOMYCOSIS ME i.v. Penicillin G 2 6 weeks 6 (3) 12 months oral therapy Alternatives 1: Alternatives 2: clindamycin, erythromycin, doxycycline ceftriaxone, imipenem

37 Medical management of pulmonary actinomycosis: data from 49 consecutive cases, co-morbidity 70% 46 patients iv antibiotics 21.5 days 43 patients oral antibiotics 115 days (penicillins, doxycyclin, macrolide) 16 patients side effects 5 patients lost for follow up 41 patients follow-up for 27 months 35 patients were cured (85%) 6 recurrence duration of AB treatment 5/6 recurrence treatment < 3 month (p<0.001 compared with 35 patients with uneventful follow-up) Kolditz et al. (JAC : ) Pulmonary actinomycosis with adequate antibiotic treatment has an excellent prognosis

38 OPTIMAL DURATION OF IV AND ORAL ANTIBIOTICS IN THE TREATMENT OF THORACIC ACTINOMYCOSIS n= 28 IV antibiotc PO antibiotic days days Surgical (n=13) 8 (3 17) 150 (0 534) Medical (n= 15) 2 (0 18) 167 (76-412) No disease recurrence with a short treatment regimen Choi et al. Chest (2005)

39 Volume: 37, Issue: 1, Pages: Human Pathology (2006)

40 Online Lecture Library Slide withheld at request of author

41 Online Lecture Library Slide withheld at request of author

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