N farcinica has been a known cause of infection in humans since 1975, with an increase in reported cases since then.14 This increase is partly attributed to advances in molecular diagnostic methods, such as 16S rRNA gene sequencing, and partly to the increased number of patients surviving cancer due to improved treatment modalitites.1 Similar to Nocardia infections in general, N farcinica infection is rare in patients who are not immunocompromised because normal functioning T-cell mediated immunity is preventive.15
Clinically, N farcinica is associated with cutaneous and subcutaneous infections more than any other Nocardia species.16 Humans can become infected with N farcinica by inhalation or direct inoculation by contamination of a skin wound, either surgical or traumatic.3,14,17 In a retrospective case report, Shimizu et al18 reported a patient with locally spreading subcutaneous infection in the submandibular region that was suspected to originate from the upper aerodigestive tract or dental plaque.
These skin infections are difficult to treat because this species is known to be multidrug-resistant; therefore, it is advised to perform antibiotic susceptibility testing for clinically efficient treatment.2,19 The antibiotic resistance of Nocardia mostly explains the difficult treatment process of the patient presented here. Despite the carefully planned, susceptibility-test guided antibiotic treatment and thorough debridement, the subcutaneous infection persisted for a long time. This persistence was attributed to the multiple abscess foci in functionally critical tissues, such as tendons and muscles.
N farcinica infection can spread hematogenously to the CNS, skin, kidney, lungs, eyes, bones, and joints.14,20 This spread can be fatal despite early diagnosis and treatment with culture-specific antibiotics, especially in immunocompromised patients.20 In the current patient, even though the treatment process was lengthy, the subcutaneous infection did not spread to other sites. This may be because the patient was not immunocompromised and was receiving continuous antibiotic treatment during the entire period.
In a retrospective case series study, Minero et al1 conducted a review of 37 cases and a review of the literature on 448 cases of nocardiosis. They reported that only 2.9% (13 of 448) of cases were encountered in healthy patients. The remaining patients had underlying medical conditions such as HIV infection, autoimmune disease, chronic lung disease, a history of organ transplantation, or malignancy. The study noted 86.5% cases were community acquired and the remaining were nosocomial infections. Pure cutaneous involvement was reported in 8.1% of cases and none of them was isolated as N farcinica infection. N farcinica was responsible for 24.3% of the total infections and clinically presented as pulmonary, CNS, and disseminated nocardiosis involving multiple cutaneous abscesses. Based on their review, the authors suggested that Nocardia infections seen in immunocompetent patients not involving the CNS should be treated for at least 6 months and followed-up for 1 year to monitor for relapses. Premature cessation of treatment may result in a more serious disseminated disease.21 The patient in the current case report received 6 months of antibiotic treatment and had a relapse in a distal location, which required another surgical intervention.
Tan et al10 reported 134 cases of nocardiosis in 164 patients in their retrospective case series study. In this study, the authors emphasized that although previous studies had stated that pulmonary nocardiosis was most common, they had found that primary cutaneous nocardiosis was more prevalent in their region, with Nocardia brasiliensis as the most common isolated form. Seven (7) cases of N farcinica infections were reported as pulmonary and disseminated nocardiosis, but none of them were cutaneous infections. They reported 2 immunocompetent patients who presented with cellulitis; N flavorosea and N takedensis were isolated in those patients. TMP-SMX, amikacin, meropenem, minocycline, and cefepime were used in combination with surgical therapy as needed.
In a retrospective cross-sectional study, Wang et al7 reported 132 patients with 136 episodes of Nocardia infections, of which the 19 of 138 strains (13.8%) that were isolated were diagnosed as N farcinica. Of these 19 strains, 5 cases were skin or soft tissue abscesses; this suggests a dermal tropism and, when considering other sites like the brain, a propensity to invade deep tissues by N farcinica. In the study by Wang et al, TMP-SMX, linezolid, ceftriaxone, clarithromycin, and tobramycin were used as antibiotic treatment in Nocardiosis based on antibiotic susceptibility tests. The tests of 117 strains revealed that of the types, the isolated 17 N farcinica strains were far less susceptible to ceftriaxone and tobramycin compared with other strains. These were reported to be sensitive to TMP-SMX, amikacin, and linezolid. Based on the the high isolation frequency, invasiveness and low antibiotic susceptibility of the species, the authors concluded that N farcinica is the most pathogenic species of Nocardia genus.
Haussaire et al3 performed a retrospective case series of Nocardia infections in France, including 34 cases. N farcinica was the causative agent in 26.5% of the cases. Cutaneous isolated disease was reported in only 3 patients, all of whom were immunocompetent. Although these patients were reported to be immunocompetent, all of them had high blood pressure and 1 also had diabetes. Of these 3 patients with cutaneous infections, N farcinica was isolated from the patient having high blood pressure and diabetes. The authors reported only TMP-SMX and carbapenem susceptibility, with the latter being higher.
In a retrospective cross-sectional study of 53 Nocardia infections in China by Huang et al,9 N farcinica was the most isolated species (24.5% of cases). The authors reported only 2 cases of superficial skin infections, and the strains were isolated as N farcinica, N terpenica, N cyriacigeorgica, N brasiliensis, and N abscessus. Regarding N farcinica treatment, the antibiotic resistance against TMP-SMX, gentamicin, cefepime, and ceftriaxone was high, and susceptibility to imipenem and amikacin was also high in their series.
Subcutaneous N farcinica infection in immunocompromised patients is well reported in the literature.1,3,16-18 N farcinica infection in non-immunocompromised patients is rare. Schiff et al12 reported a case of late-onset posttraumatic facial subcutaneous abscess and osteomyelitis of the zygomatic bone in an immunocompetent patient. This patient was treated with debridement of necrotic tissues and bone. Antibiotic treatment began with intravenous amikacin 500 mg 2 × 1 for 2 weeks, continued with oral TMP-SMX 2 × 2 tablets, but was discontinued due to intolerance. The regimen was then changed to oral erythromycin 500 mg 4 × 1 and later substituted for intramuscular amikacin 500 mg 2 × 1 for 6 weeks. The abscess healed completely, and no recurrence was observed after 2 years of follow-up. The treatment of the patient of Schiff et al was different from the patient reported here in terms of antibiotics. This can be explained by different antibiotic resistance profiles among the N farcinica species.