Rev Soc Bras Med Trop 51(1):7-13, January-February, 2018 doi: 10.1590/0037-8682-0215-2017 Review Article Actinomycosis, a lurking threat: a report of 11 cases and literature review Catarina Oliveira Paulo[1], Sofia Jordão[1], João Correia-Pinto[2], Fernando Ferreira[3] and Isabel Neves[1] [1]. Infectious Diseases Unit, Medical Department, Hospital Pedro Hispano - Matosinhos Local Health Unit, Matosinhos, Portugal. [2]. Department of Anatomical Pathology, Hospital Pedro Hispano - Matosinhos Local Health Unit, Matosinhos, Portugal. [3]. Department of General Surgery, Hospital Pedro Hispano - Matosinhos Local Health Unit, Matosinhos, Portugal. Abstract Actinomycosis remains characteristically uncommon, but is still an important cause of morbidity. Its clinical presentation is usually indolent and chronic as slow growing masses that can evolve into fistulae, and for that reason are frequently underdiagnosed. Actinomyces spp is often disregarded clinically and is classified as a colonizing microorganism. In this review of literature, we concomitantly present 11 cases of actinomycosis with different localizations, diagnosed at a tertiary hospital between 2009 and 2016. We outline the findings of at least one factor of immunosuppression in > 90% of the reported cases. Keywords: Actinomycosis. Immunosuppression. Infection. Underdiagnosis. INTRODUCTION There are multiple possible focalizations, the most frequently described being oro-cervicofacial (55%) and abdominal- Actinomycosis is uncommon, indolent, and chronic, and is pelvic (20%). The abdomino-pelvic focalization is frequently caused by the microorganism Actinomyces spp. Its incidence associated with a past history of perforated appendicitis12,13 has diminished globally due to improved oral hygiene and or with the prolonged use of an intrauterine device (IUD)14,15. the development of antibiotics. Actinomycosis is frequently underdiagnosed because of its clinical and imagiological In 15% of cases, the location is thoracic, including intra- 16 mimicry of other infectious diseases (e.g. nocardiosis, thoracic organs and the thoracic wall . Cases of musculoskeletal tuberculosis) and malignancies1,2. actinomycosis, such as that of the long bones are rare, and are typically described as chronic sclerotic or spherical Due to its filamentous morphology, this gram-positive osteomyelitis17,18. Such infections originate from infected anaerobe was previously classified as a fungus. Presently it is adjacent tissues or, less frequently, following hematogenous considered as a member of the order Actinomycetales (grouped dissemination. Infections of the urogenital tract19, eye20-22, skin, with nocardias, streptomyces, and micobacterias), and is a and disseminated disease23,24 focalized in the central nervous part of the oral, gastrointestinal and urogenital commensal system (CNS)25 are rare; a case of chronic lymphadenitis flora3-6,. Actinomyces is known for its ability to evolve into has also been reported26. Only vertical transmission has been invasive masses with or without fistulous tracts when there are reported, and two cases of neonatal sepsis have been described: minor breaches in tissue integrity (e.g. trauma, radiotherapy, one caused by A. neuii and the other (species unidentified) with inflammatory perforation)7,8. uterine cerclage as the identifiable risk factor27,28. The most common pathogenic species is Actinomyces israelii. There seems to be a relationship between development of Occasionally Actinomyces naeslundii, Actinomyces odontolyticus, infection and an immunosuppression risk factor underlining it, as Actinomyces viscosus, Actinomyces meyeri (most frequent agent it has been described in patients with human immunodeficiency of disseminated disease), and rarely Actinomyces neuii (these virus (HIV) infection, leukemia, solid organ malignancies, last two species are typically non filamentous)9,10 among others11, and others29-33. Based on the localization of the infection, its have been found as the etiological agents. extension, time of evolution, and basal status of the patient, the disease may manifest in multiple forms, and may present with fever, asthenia, and progressive loss of sense of well-being. The biochemical profile is non-specific and varies with the Corresponding author: Dra. Catarina Oliveira Paulo. clinical manifestation of the disease, though anemia, elevated e-mail: [email protected] reactive C protein (RCP) and/or changes in the sedimentation Received 20 August 2017 Accepted 28 December 2017 rate (SR), and mild leucocytosis are common. Radiological 7 Paulo CO et al. - Actinomycosis: 11 cases and literature review findings might include presence of masses, cold abscesses, or vegetative ulcerated mass with a circumferential cervical edema. fistulae, depending on the time-frame and disease progression. Histological examination of the biopsy revealed necrotic tissue Diagnosis is based on characteristic histological and/or with Actinomyces spp. colonies, with no evidence of malignancy microbiological findings (the latter helps in identifying the (Figure 1). Treatment was administered for 2 weeks with species and antimicrobial susceptibility). intravenous penicillin, resulting in resolution of the obstruction and the patient continued the treatment for 12 more months with Histology is characterized by the presence of Gram- oral amoxicillin (500mg every 6 hours), with no recurrence. positive filamentous structures and sulfuric granules. Gomori methenamine-silver and Giemsa stains are commonly used, Case 2. A 34-year-old man with a history of chronic and a rapid direct immunofluorescence method has also been alcohol ingestion was hospitalized with sepsis after a gastric 25 ulcer perforation, and presented with secondary peritonitis. developed to identify a species-specific antibody . Pathogen identification is successful in less than 50% of cases, owing to the Pyroloplasty and vagotomy were performed, and he was treated recent use of antibiotics, overgrowth of other microorganisms, empirically with piperacillin/tazobactam for 7 days. Abdominal and inadequate diagnostic methodology. Gram staining is thus pain and fever were present, despite a favorable initial recovery. considered a more sensitive technique than is culture. Culturing A second exploratory laparotomy was performed, and abscesses Actinomyces requires a selective anaerobe agar maintained in the intestinal loops as well as dispersed intra-abdominal pus at 37ºC, and a growth time of 3 weeks. Swab techniques are were observed, with no evidence of dehiscence of the past surgical procedure. Actinomyces naeslundii was identified reported to be ineffective for culturing this bacterium. In some in the peritoneal fluid, and he was treated with intravenous European reference laboratories, the preferred method for ampicillin (800mg every 8 hours) for 3 weeks (he had received Actinomyces spp. identification is 16s ribosomal ribonucleic a 10-day course of empirical carbapenem previously), resulting acid (rRNA) sequencing25. in analytical and clinical resolution. Oral amoxicillin treatment Antibiotic treatment duration depends on infection at 2g/day was administered for 6 months with no clinical localization and severity, and concomitant surgical excision or intercurrences. IUD removal (in appropriate cases) may be required. Case 3. A 37-year-old obese man with a clinical history Actinomyces spp. is known to be susceptible to penicillins and of perforated appendicitis developed an incisional hernia to other ß-lactams, with the exception of oxacillin, dicloxacillin, shortly after presenting with secondary peritonitis in 2002. The and cephalexin; Actinomyces europaeus and graevenitzii are hernia was surgically approached multiple times, and multiple reported to be resistant to ceftriaxone, and other species with unsuccessful attempts to insert a mesh were made until 2013. intermediate susceptibility to cephalosporins have also been Recurring entero-cutaneous fistulae were detected. described. This anaerobe is also susceptible to doxycycline, In 2010, after another attempt at curing the fistulous tract, a clindamycin, erythromycin and clarithromycin, linezolide, segmental enterectomy was performed, resulting in yet another and tigecicline25,34,35. Aminoglycosides, metronidazole, and recurrence of a fistula in 2011. The fistula was observed to quinolones are not reported to show adequate bactericidal 36 extend through the abdominal wall tissue (12 x 9mm) and activity against Actinomyces spp. Although the organism progress to the adjacent cecum wall. is multisusceptible, in most cases of infection, an initial intravenous treatment with antibiotics for 2 to 6 weeks A final intricate surgical intervention in 2013 was performed (preferably with penicillin G) with subsequent prolonged oral for the correction of a complex hernia, with extensive resection treatment for 6 to 12 month (amoxicillin 2g/day divided in 4 of fibrous adhesions around the abdominal viscera. The old doses) is required25,35. mesh was extracted and sent for microbiological analysis (negative result) and histological examination. Microscopically, Disease prognosis depends on the focalization (worse in Actinomyces spp colonies were identified, and he completed CNS disease), extension of infection, the patient’s baseline 3 weeks of intravenous penicillin followed by amoxicillin at comorbidities, and delay in diagnosis. The current mortality 2g/day for 6 months, with no recurrence of fistulous tracts or 25 rates are reported to vary