Review Article Actinomycosis : An Update Moniruddin ABM1, Begum H2, Nahar K3

Abstract: Endocaditis8, Pericarditis12, Pneumonia (Community Acquired1 or Nosocomia15), Lung absecess5, Actinomycosis is a very rare disease caused usually by one Bronchiectasis5, Empyema Thoracis12 etc when caused by of a group of oppurtunistic otherwise harmless commensals these organisms remain undiagnosed or if not properly that may be complicated by one or more of another group of treated would endanger the life of the patient. There are co-pathogens. Because of its rarity, there is a chance of significant morbidities as well. missing its diagnosis & proper treatment leading to substantial morbidity & mortality. Maltreated patients are Aetiology at risk of developing life threatening complications. This The causative organisms are non-motile, non-spore forming, article is intended to review the present status of aetiology, non-acid fast, Gram positive pleomorphic, anaerobic-to- pathology, clinical features, complications & management microaerophilic filamentous bacterial rods3. The most of actinomycosis. common ones are1 Actinomyces israeli, Actinomyces gerencseriae, Actinomyces naeslundii, Actinomyces Keywords odontolyticus, Actinomyces viscosus, Actinomyces Actinomyces israeli, Actinomyces gerencseriae, Actinomyces turicensis, Actinomyces meyeri, Propionibacterium naeslundii, Actinomyces odontolyticus, Actinomyces propionicus. In addition to these microorganisms, almost all viscosus, Actinomyces turicensis, Actinomyces meyeri, actinomycotic lesions contain so-called companion bacteria. Propionibacterium propionicus, Peptostreptococcus, The most important of these bacteria is Actinobacillus Actinobacillus actinomycetemcomitans, Prevotella, actinomycetemcomitans, followed by Peptostreptococcus, Fusobacterium, Bacteroides, Staphylococcus, Streptococcus, Prevotella, Fusobacterium, Bacteroides, Staphylococcus, Enterobacteriaceae, actinomycetes. and Streptococcus species, and Enterobacteriaceae, depending on the location of actinomycotic lesions. These Introduction: companion bacteria appear to magnify the low pathogenic Actinomycosis was once a common & ultimately fatal potential of actinomycetes2. disease1. Now the number has declined since the Actinomycosis can affect people of all ages, but the introduction of antimicrobial agents. The outlook of patients majority of cases are reported in young to middle-aged suffering from this infection has improved remarkably. Few adults (aged 20-50 yrs)2. No racial predilection exists. For physicians see many cases. As patients no longer commonly unknown reasons, men are affected more commonly than present advanced disease, actinomycosis has become a more women, with the exception of pelvic actinomycosis11. The diagnostic challenge2. Actinomycosis is a subacute-to- reported male-to-female ratio2 is 3:1. chronic bacterial infection characterized by contiguous spread, suppurative and granulomatous inflammation, and Actinomycosis occurs worldwide, with likely higher formation of multiple abscesses and sinus tracts that may prevalence rates in areas with low socioeconomic status and discharge ‘sulfur granules’3. As a disease process, the poor dental hygiene. causative organism can primarily or secondarily invade History gum, jaw4, neck, pleura, lungs5, liver6, kidney7, appendix7, caecum7, skin1, heart8, meninges9 etc. Even bones like Bollinger first reported the yellow granules in jaw masses of mandible, ribs & vertebra (causing osteomyelitis)10 are not cattle in 1877. In 1878, Israel described the first human immune to its invasion. The most common clinical forms of case. In 1879, Hartz first observed the microscopic actinomycosis are cervicofacial (ie, lumpy jaw), thoracic, appearance of granules of actinomyces infection1. and abdominal1. In women, pelvic actinomycosis is documented11. Epidural abscesses9, Meningitis9, Frequency Actinomycosis is a rare infection; Its exact incidence is not 1. ABM Moniruddin MBBS, FCPS(S) Consultant, Surgery, General Hospital, Narayanganj. known in Bangladesh. During the 1970s, the reported 2. Hamida Begum MBBS, FCPS annual incidence in the Cleveland area of the United States Assistant Professor, Department of Obstetrics and Gynaecology was 1 case per 300,0002. Improved dental hygiene and Bangabandhu Sheikh Mujib Medical University, Dhaka widespread use of antibiotics for various infections probably 3. Khairun Nahar MBBS, FCPS Assistant Professor, Department of Obstetrics and Gynaecology have contributed to the declining incidence of this disease1. Bangabandhu Sheikh Mujib Medical University, Dhaka

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Pathology recent or remote bowel surgery (eg, perforated acute appendicitis, perforated colonic diverticulitis following Actinomycetes are prominent among the normal flora of the trauma to the abdomen) or ingestion of foreign bodies (eg, oral cavity but less prominent in the lower gastrointestinal chicken or fish bones), during which actinomycetes is tract and female genital tract. As these microorganisms are introduced into the deep tissues. The ileocecal region is not virulent, they require a break in the integrity of the involved most frequently and the disease presents mucous membranes and the presence of devitalized tissue to classically as a slowly growing tumor. Diagnosis is usually invade deeper body structures and cause human illness. established postoperatively, following exploratory Furthermore, actinomycosis generally is a polymicrobial laparotomy for a suspected malignancy. Involvement of any infection, with isolates numbering as many as 5-10 bacterial abdominal organ, including the abdominal wall, can occur species2. Establishment of human infection may require the by direct spread, with eventual formation of draining presence of such companion bacteria, which participate in sinuses. Actinomycosis of the pelvis most commonly occurs the production of infection by elaborating a toxin or enzyme by the ascending route from the uterus in association with or by inhibiting host defenses. These companion bacteria intrauterine contraceptive devices (IUCDs). In such cases, appear to act as copathogens that enhance the relatively low an IUCD has been in place for an average of 8 years. invasiveness of actinomycetes. Specifically, they may be responsible for the early manifestations of the infection and Complications for treatment failures. Once infection is established, the host Osteomyelitis of the mandible, ribs, and vertebrae, CNS mounts an intense inflammatory response (ie, suppurative, granulomatous), and fibrosis may develop subsequently. disease, including brain abscess, chronic meningitis, Infection typically spreads contiguously, frequently ignoring actinomycetoma, cranial, epidural, and subdural infection, tissue planes and invading surrounding tissues or organs. and spinal epidural infection, Hepatic actinomycosis, Renal Ultimately, the infection produces draining sinus tracts. actinomycosis, Endocaditis8, Pericarditis12, Pneumonia Hematogenous dissemination7 to distant organs may occur (Community Acquired1 or Nosocomial5), Lung absecess5, in any stage of the infection, whereas lymphatic Bronchiectasis5, Empyema Thoracis12 etc. In addition to its dissemination is unusual. serious nature of organ involvement, it can complicate other operations or situations like hip prosthesis infection13, septic Cervicofacial actinomycosis arthritis14, endodontic infection15, IUD infection16, pos- Cervicofacial actinomycosis is the most common operative viscous endophthalmitis17, etc. Opportunistic manifestation, comprising 50-70% of reported cases. actinomycotic infection has been reported in Infection typically occurs following oral surgery or in osteoradionecrosis18 in patients having head & neck cancer. patients with poor dental hygiene2. This form of Disseminated actinomycosis19 by Actinomyces meyeri & actinomycosis is characterized in the initial stages by soft- and Actinobacillus actinomycetemcomitans has also been tissue swelling of the perimandibular area. Direct spread reported. into the adjacent tissues occurs over time, along with development of fistulas (sinus tracts) that discharge purulent Clinical Features material containing yellow (ie, sulfur) granules. Invasion of 1. History taking20 the cranium or the bloodstream may occur if the disease is left untreated. For Cervicofacial actinomycosis (ie, lumpy jaw): History of dental manipulation or trauma to the mouth, poor oral Thoracic actinomycosis hygiene, dental caries, or periodontal disease; local tissue Thoracic actinomycosis accounts for 15-20% of cases. damage caused by neoplasm or radiation treatment, or of Aspiration of oropharyngeal secretions containing painless or occasionally painful soft-tissue swelling actinomycetes is the usual mechanism of infection. involving the submandibular or perimandibular region; over Occasionally, thoracic actinomycosis may result from the time, multiple sinuses drain pus containing sulfur granules; introduction of organisms via esophageal perforation, by tendency to remit and recur, or of reddish or bluish direct spread from an actinomycotic process of the neck or discoloration of the skin overlying the lesion or of chewing abdomen, or via hematogenous spread from a distant lesion. difficulties (ie, with involvement of mastication muscles) Thoracic actinomycosis3 commonly presents as a pulmonary For Thoracic acinomycosis: History of aspiration (Risk infiltrate or mass, which, if left untreated, can spread to factors include seizure disorder, alcoholisms, and poor involve the pleura, pericardium, and chest wall, ultimately dental hygiene), or of dry or productive cough, occasionally leading to the formation of sinuses that discharge sulfur blood-streaked sputum, shortness of breath, chest pain, or of granules. fever, weight loss, fatigue, anorexia. Actinomycosis of the abdomen and pelvis For Abdominal actinomycosis: History of abdominal Actinomycosis of the abdomen7 and pelvis accounts for 10- surgery, perforated viscus, mesenteric vascular 20% of reported cases. Typically, patients have a history of insufficiency, or ingestion of foreign bodies (eg, fish or

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chicken bones), or of Nonspecific symptoms: The most isolation of the infecting organism from a clinical specimen common nonspecific symptoms are low-grade fever, weight or from sulfur granules is necessary for definitive diagnosis loss, fatigue, or of change in bowel habits, or of vague in most cases. abdominal discomfort, or of nausea, or of vomiting, or of a. Acceptable specimen material is obtained from draining sensation of a mass. sinuses, deep needle aspirate, or biopsy specimens; swabs, For Pelvic actinomycosis: History of IUCD, or of lower sputum, and urine specimens are unacceptable or abdominal discomfort, abnormal vaginal bleeding or inappropriate. discharge. b. Prompt transport of the specimens to the microbiology 2. Physical findings20: laboratory is necessary for optimal isolation of actinomycetes, preferably in an anaerobic transport device. For Cervicofacial actinomycosi: Tender or nontender woody hard multiple nodular lesions, usually located at the angle c. A Gram-stained smear of the specimen may demonstrate of the jaw, multiple abscesses, and multiple sinuses that the presence of beaded, branched, gram-positive open onto the cheek or submandibular area, sulfur granules filamentous rods, suggesting the diagnosis of in the exudate, typical absence of lymphadenopathy, woth actinomycosis. or without trismus & fever. d. Cultures should be placed immediately under anaerobic For Thoracic actinomycosis: Fever, cachexia, abnormal conditions and incubated for 48 hours or longer; the breath sounds, cough (dry or productive of purulent isolation and definitive identification of actinomycetes may sputum), hemoptysis, sinus tracts with drainage from the require 2-3 weeks. chest wall (ie, pleurocutaneous fistula) e. Nucleic acid probes and polymerase chain reaction (PCR) For Abdominal actinomycosis: Scar (s) from antecedent methods are being developed for more rapid and more abdominal surgery, low-grade fever and cachexia (variably accurate identification. present), mass most often located in the right lower f. Antimicrobial susceptibility testing is not indicated in the quadrant, less frequently in the left lower quadrant; mass management of actinomycosis, partly because of their typically firm-to-hard in consistency, nontender, often fixed predictable antibiogram. to underlying tissue, sinus tracts with drainage from either the abdominal wall (ie, peritoneocutaneous fistula) or the (b) The preliminary diagnosis of actinomycosis also can be perianal region made by examining sulfur granules20. Granules should be crushed between 2 slides, stained with 1% methylene-blue For Pelvic actinomycosis: Pelvic mass, menometrorrhagia, solution, and examined microscopically for features other manifestations, as in abdominal actinomycosis. characteristic of actinomycetes. Differential Diagnoses (c) Serologic diagnosis: Current serologic tests have no role Abdominal abscess, Lung cancer, Adnexal tumours, Non- in diagnosing actinomycosis. Hodgkin’s Lymphoma, Appendicitis, Small & Large Papanicolaou test11,17: intestinal malignancy,Blastomycosis, Nocardiasis, Brain abscess, Epidural abscess, Pelvic Inflammatory Disease, a. The relationship between a Papanicolaou test that is Aspiration pneumonia, Bacterial pneumonia, Fungal positive for actinomycetelike organisms and the eventual pneumonia, Crohn’s disease, Diverticulitis, Tuberculosis, development of pelvic actinomycosis is unclear. Lung abscess, Liver abscess, Uterine cancer, Any b. The prevalence of smears positive for Actinomyces abdominal mass1,2,20 organisms in women who use IUCDs is approximately 7%.5 Laboratory Studies c. Because of the lack of sensitivity and specificity and low (A) CBC count: Anemia and mild leukocytosis are positive predictive value, the prognostic significance of common2. detecting Actinomyces organisms is minimal in the absence of concomitant symptoms.5 (B) Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are often elevated2. Imaging Studies: Chest X-ray & CT Scan (C) Chemistry results usually are normal, with the exception A chest radiograph20 may reveal a poorly defined mass or of a frequently elevated alkaline phosphatase level in pneumonitis or cavitary lesion, with or without pleural hepatic actinomycosis20. involvement. Hilar adenopathy is uncommon. The presence of a masslike lesion that extends across fissures or pleura, (D) Organism cultures21 invades into the adjacent chest wall or thoracic vertebrae, or (a) Because actinomycosis is difficult to diagnose based on causes local destruction of the ribs or sternum suggests the typical clinical features, direct identification and/or thoracic actinomycosis.

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CT scanning22 (irrespective of the anatomic area of wk, then switch to PO (penicillin VK) for 6-12 mo] involvement) usually reveals an infiltrative mass with focal administered over a prolonged period (6 months to 1 year) areas of decreased attenuation that enhance with contrast. is the cornerstone of therapy for actinomycosis. Success This infiltrative mass tends to invade surrounding tissues. with shorter courses of therapy (<6 mo) has been reported, Surrounding lymphadenopathy is uncommon. especially in cervicofacial actinomycosis. Ultimately, the treatment duration should be tailored to the individual Sometimes Colonoscopy, CT scans are combinedly patient based on clinical and radiographic response. Patients required for diagnosis22 should be monitored more closely if shorter treatment FNAC & Open biopsy durations are considered. CT scan or ultrasound-guided fine-needle aspiration and/or The risk of actinomycetes developing penicillin resistance biopsy3,20,22 have been used successfully to obtain clinical appears to be minimal. Lack of a clinical response to material for diagnosis of actinomycosis. penicillin usually indicates the presence of resistant companion bacteria, which may require modification of the Surgery24 (eg, thoracotomy with open lung biopsy, exploratory antibiotic regimen (ie, addition of an agent that is active laparotomy) may be required for diagnostic purposes. against these copathogens). Histologic Findings Alternative to Penicillins if the patient is hypersensitive to Actinomycosis is characterized by mixed suppurative and penicillin or the causative oganisms are resistant to granulomatous inflammatory reactions, connective-tissue Penicillin are Ceftriaxone (Adult: 2 g IV/IM q12-24h; not proliferation, and the presence of sulfur granules1,2,20. to exceed 4 g/d), Imipenem/Cilastin (Adult: 500 mg- 1000mg IV q8h; not to exceed 4 g/d), Clindamycin (Adult: 600 mg IV q8h, or 150 - 300 mg PO q8h), Amoxycillin/Clavulanic acid (Adult: 500 mg PO q8h, or 875 mg PO q12h), Doxycycline (Adult: 100 mg PO/IV q12h), Tetracycline, Lincomycin, Macrolides (erythromycin, Carbomycin, Spiramycin, Oleandomycin) Ð all these are effective. But the sensitivity should be checked Fig. A- Actinomycosis in Endometrial tissue in the laboratory3. Recalcitrant actinomycosis sometimes need treatment with ciprifloxacin23. Antibiotics that possess The sulfur granules are nearly pathognomonic for no activity against Actinomyces species1 include actinomycosis, although similar findings have been reported metronidazole, aminoglycosides, aztreonam, co-trimoxazole with infections caused by Nocardia brasiliensis, (TMP-SMX), penicillinase-resistant penicillins (eg, Streptomyces madurae, and Staphylococcus aureus methicillin, nafcillin, oxacillin, cloxacillin), and cephalexin. presenting as botryomycosis. The granules are The data concerning the fluoroquinolones (ciprofloxacin, approximately 0.1-1 mm in diameter and may be seen with levofloxacin, moxifloxacin) are limited; however, treatment the naked eye as yellowish particles. success has been cited in case reports Microscopically, the granules manifest a cauliflower like Surgical treatment: shape at low magnification; at higher magnification (X100), when the particle has been pressed between slide and cover Attempts are made to cure actinomycosis, including slip, a clump of filamentous actinomycete microcolonies extensive disease, with aggressive antimicrobial therapy surrounded by polymorphonuclear neutrophils (PMNs) can alone initially. Surgery is indicated to take a biopsy be observed. Gram stain renders these microcolonies visible specimen, to drain abscesses, to extirpate (wide exicision) a as gram-positive, intertwined branching filaments, with fibrotic sinus tract (not responsive to conservative radially arranged, peripheral hyphae. Coexisting with them trearment) or a recalcitrant fistula tract, to decompress or are the companion bacteria, which are gram-positive and remove a intra-cranial or intraspinal Space Occupying gram-negative cocci and rods. Lesion, to remove severely damaged segment of lung or Treatment liver, relieving obstruction (eg, when actinomycotic lesions compress the ureter)20, & to repair a defect, or to rule out a Medical treatment: Bronchogenic carcinoma etc24. 1,2,20 In most cases of actinomycosis, antimicrobial therapy is Probenecid can increase effects; coadministration of the only treatment required, although surgery can be tetracyclines can decrease effects adjunctive in selected cases. Penicillin G is the drug of choice for treating infections caused by actinomycetes. Follow-up High-dose penicillin [Adult:Penicillin G - 12-24 million U/d Follow up should be adequate & meticulous to have a IV by continuous infusion or in divided doses q4h for 1-2 complete cure of the disease1,2,20.

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Prophylaxis: 10. Rothschild B, Naples V, Barbian L.ÊBone manifestations of actinomycosis.ÊAnn Diagn Maintenance of good oral hygiene and adequate regular Pathol.Ê2006;10 :24-27.Ê dental care are important. Patients and physicians alike should be aware of the increased risk of infection associated 11. Lippes J.ÊPelvic actinomycosis: a review and with insertion of IUCD2,11,16,20. preliminary look at prevalence.ÊAm J Obstet Gynecol.Ê1999;180 :265-9.Ê Prognosis 12. Litwin KA, Jadbabaie F, Villanueva M.ÊCase of The availability of antibiotics has greatly improved the pleuropericardial disease caused by Actinomyces prognosis for all forms of actinomycosis1. At present, cure odontolyticus that resulted in cardiac tamponade.ÊClin rates are high and neither deformity nor death is common. Infect Dis.Ê1999;29 :219-20.Ê When actinomycosis is diagnosed early and treated with 13. Wust J, Steiger U, Vuong H, Zbinden R.ÊInfection of a appropriate antibiotic therapy, the prognosis is excellent. hip prosthesis by Actinomyces naeslundii.ÊJ Clin The more advanced and complicated actinomycotic forms Microbiol.Ê2000;38 :929-30. require aggressive antibiotic and surgical therapy for optimal outcome; however, deaths can occur despite such 14. Lequerre T, Nouvellon M, Kraznowska K.ÊSeptic therapy20,24. arthritis due to Actinomyces naeslundii: report of a case.ÊJoint Bone Spine.Ê2002;69 :499-501.Ê Conclusion: 15. T, Baumgartner JC.ÊOccurrence of Actinomyces in As it is an endogenous disease, there is no risk of person to infections of endodontic origin.ÊJ Endod.Ê2003;29 :549- person transmission. This is an important message for 52.Ê health personnels & patient attendants e.g. relatives. To 16. Soria-Aledo V, Flores-Pastor B, Carrasco-Prats minimize delays in diagnosis, actinomycosis should be M.ÊAbdominopelvic actinomycosis: a serious considered in the differential diagnoses of any inflammatory complication in intrauterine device users.ÊActa Obstet lesion of subacute or long-term nature. Gynecol Scand.Ê2004;83 :863-5. References: 17. Scarano FJ, Ruddat MS, Robinson A.ÊActinomyces viscosus postoperative endophthalmitis.ÊDiagn 1. DavidÊJ.ÊM.ÊHaldane. Community Acquired Pneumonia. Microbiol Infect Dis.Ê1999;34 :115-7.Ê In: Springer US. Medicine 2007. 53:827-840. 2. Weese WC, Smith IM.ÊA study of 57 cases of 18. Curi MM, Dib LL, Kowalski LP.ÊOpportunistic actinomycosis over a 36-year period. A diagnostic actinomycosis in osteoradionecrosis of the jaws in ''failure''with good prognosis after treatment.ÊArch patients affected by head and neck cancer: incidence Intern Med.Ê1975; 135 :1562-8.Ê and clinical significance.ÊOral Oncol.Ê2000;36 :294-9.Ê 3. De Montpreville VT, Nashashibi N, Dulmet 19. Kuijper EJ, Wiggerts HO, Jonker GJ.ÊDisseminated EM.ÊActinomycosis and other bronchopulmonary actinomycosis due to Actinomyces meyeri and infections with bacterial granules.ÊAnn Diagn Actinobacillus actinomycetemcomitans. Scand J Infect Pathol.Ê1999;3 :67-74.Ê Dis.Ê1992;24 :667-72. 4. LernerPI: The lumpy jaw. Cervicofacial actinomycosis. 20. Schaal KP, Lee HJ.ÊActinomycete infections in humans- Infect Dis Clin North Am 1988;2:203. -a review.ÊGene. 15Ê1992;115 :201-11. 5. Court C.A, Garrard C.S. 1992. Nosocomial pneumonia 21. Smith AJ, Hall V, Thakker B, Gemmell in the intensive care unit Ð mechanism & significance. CG.ÊAntimicrobial susceptibility testing of Actinomyces Thorax 47: 465-473. species with 12 antimicrobial agents.ÊJ Antimicrob 6. Felekouras E, Menenakos C, Griniatsos J, et al.ÊLiver Chemother.ÊÊ2005;56 :407-9. resection in cases of isolated hepatic actinomycosis: 22. Kim JC, Ahn BY, Kim HC.ÊEfficiency of combined case report and review of the literature.ÊScand J Infect colonoscopy and computed tomography for diagnosis of Dis.Ê2004;36 :535-8. colonic actinomycosis: a retrospective evaluation of 7. Cintron JR, Del Pino A, Duarte B, Wood D.ÊAbdominal eight consecutive patients.ÊInt J Colorectal Dis.Ê2000;15 actinomycosis.ÊDis Colon Rectum.ÊJanÊ1996;39 :105-8.Ê :236-42.Ê 8. Huang KL, Beutler SM, Wang C.ÊEndocarditis due to 23. Macfarlane DJ, Tucker LG, Kemp RJ.ÊTreatment of Actinomyces meyeri.ÊClin Infect Dis.Ê1998;27 :909-10. recalcitrant actinomycosis with ciprofloxacin.ÊJ 9. Yung BC, Cheng JC, Chan TT, et al.ÊAggressive Infect.Ê1993;27:177-80.Ê thoracic actinomycosis complicated by vertebral 24. Endo S, Murayama F, Yamaguchi T.ÊSurgical osteomyelitis and epidural abscess leading to spinal considerations for pulmonary actinomycosis.ÊAnn cord compression.ÊSpine.Ê2000;25 :745-8 Thorac Surg.Ê2002;74:185-90.

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