Recurrent Subcutaneous Abscess Due to Nocardia farcinica in an Immunocompetent Patient: A Case Report

Nocardiosis, an opportunistic infection that is rare in immunocompetent patients, is caused by Nocardia genus.¹ Nocardia species are gram-positive, aerobic actinomycetes found in soil, water, dust, decaying vegetation, and organic matter.² Individuals can be infected most commonly by inhalation of spores and less commonly by direct inoculation. Both routes of infection can occur either in the community or nosocomially.^3-6 Nosocomial Nocardia infections at surgical sites that were transmitted from operating room personnel to patients undergoing open-heart surgery, with a median onset of 28 days postsurgery, have been documented.⁶Nocardia infections are encountered most commonly in immunocompromised patients, including recipients of organ or hematopoietic stem cell transplants, patients with malignancy, and those receiving long-term corticosteroid treatments as well as patients with chronic alcoholism, diabetes mellitus, or human immunodeficiency virus (HIV).^2,3,7,8  Nearly 60% of cases are reported as being associated with immunosuppression.¹

The current antimicrobial treatments in use for nocardiosis are aminoglycosides such as gentamycin and amikacin, trimethoprim/sulfamethoxazole (TMP-SMX), minocycline, and imipenem as well as cephalosporins such as ceftiofur, ceftriaxone, and cephalexin.^3,5,9 Of these treatments, either used alone or in combination, the most effective ones are imipenem, amikacin, cephalexin, and ceftiofur; the least effective ones are gentamycin and TMP-SMX.^5,9

Of the more than 100 species of Nocardia genus, Nocardia farcinica has been isolated at rates of 22% in immunocompromised patients and 45% in immunocompetent patients.⁵N farcinica is of great importance because the infection may spread hematogenously to cause disseminated disease, and this species is intrinsically multidrug-resistant.^5,8 The disease may manifest as cutaneous nocardiosis, pulmonary nocardiosis, central nervous system (CNS) nocardiosis, or disseminated nocardiosis.¹⁰ Cutaneous infection, mostly encountered in immunocompetent patients, may occur primarily via direct inoculation or secondarily as cutaneous involvement of a hematogenously disseminated airborne infection.^1,11 The most commonly used antimicrobial treatments for N farcinica infection are TMP-SMX, amikacin, and imipenem.¹²

The purpose of this case study is to describe a case of cutaneous nocardiosis in an immunocompetent patient.

A 37-year-old White man was admitted to the outpatient clinic with a complaint of redness and swelling in the right forearm. The injury occurred after a grease canister cut the patient’s forearm 3 months prior while he was working in his backyard. A general practitioner treated the patient with daily topical mupirocin applications for a period that was not recalled by the patient, but the purulent drainage remained until the patient presented to the authors’ clinic.

Ethical considerations. The patient provided written informed consent for the use of the photographs.

Patient history and examination. The medical history showed that the patient had no known disease other than Tourette’s syndrome, which was diagnosed at the age of 8 and managed with drug therapy (baclofen 10 mg BID and carbamazepine 200 mg BID) since diagnosis.

On physical examination, a draining fistula between the skin and forearm muscles was seen, and a 5 cm × 5 cm immobile hard mass with tenderness was palpated on the right forearm volar side (Figure 1A). The forearm was edematous, and the patient had a positive Wartenberg sign and loss of power in the opposition movement.

The timeline table presented (Table 1) summarizes the long treatment process for the patient.

Diagnostic focus and assessment. Blood laboratory tests revealed that the patient had an increased erythrocyte sedimentation rate and C-reactive protein with normal leukocyte count, normal liver and kidney function tests, normal blood glucose levels. Enzyme-linked immunosorbent assay testing for hepatitis B, hepatitis C, and HIV was negative.

Ultrasound imaging displayed multiple abscess foci with deep components between the right forearm muscles. Magnetic resonance imaging (MRI) revealed interdependent abscess foci and subacute hematoma focus in the muscle tissues, with the largest being 3 cm in diameter, hyperintense in T1A and hypointense in T2A (Figure 1B).

Microbiologic assessment was performed for the tissue culture obtained during the first surgery. The isolate was found to be a gram-positive rod with short-branched filaments (Figure 2A and B). Colonies were catalase-positive but oxidase-negative. The identification of the isolate was incorrect with API Coryne (bioMérieux, France) due to slow growth rate. Then, the isolate was identified as N farcinica by MALDI-TOF MS (Bruker) with a 1.93 score value. No bacteria were detected on direct microscopic examination of a Gram smear of the specimen. The smear was evaluated again and, after a long examination, gram-positive rods with branched filaments at only 2 microscopic areas were found (Figure 2C). The smear was stained with EZN and examined again, and ARB rod with branched filaments were detected on the same areas. Definitive identification was performed by sequencing the full length of 16S rRNA gene. A gradient test was performed for antimicrobial susceptibility. The bacterial suspension was adjusted to the turbidity of 1.0 McFarland then spread onto Muller-Hinton blood agar plates and incubated for 48 to 72 hours at 35°C. The minimum inhibitory concentration was defined as the value at which the inhibition zone intercepted the scale on the gradient test stripe. Inhibition zone diameters were measured. The antibiotic susceptibility was judged as susceptible, intermediate, or resistant based on CLSI M24-2A (Table 2).¹³

Therapeutic focus and assessment. The patient had several surgeries to drain the multiple abscess foci and debride the necrotic tissues. Multiple sessions of negative pressure wound therapy (NPWT) were used following surgery. During the first surgery, the fistula tract on the volar side of the right forearm that had formed between the skin and forearm muscles was excised; the incision was extended to explore all the muscles that appeared to be involved. Multiple abscess foci spread between the palmaris longus (PL), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), and flexor digitorum profundus (FDP) muscle bodies; musculotendinous junctions were drained; and liquefied necrosis sites were debrided thoroughly (Figure 1C). Wound cultures were obtained, and the wound was closed using NPWT dressing with intermittent saline irrigation. The wound culture results showed N farcinica as the causative agent. Following the antibiogram results (Table 2), the empirical antibiotic therapy consisting of ampicillin/sulbactam (SAM) 1000 mg 2 × 1 was changed to trimethoprim/sulfamethoxazole (TMP-SMX) 400 mg/80 mg 3 × 3 daily intravenously.

The patient underwent 5 NPWT sessions with intermittent saline irrigation, with the dressing changed every 2 days. No abscess foci were seen on the follow-up MRI. The patient was discharged with TMP-SMX 800/160 mg 2 ×  2 orally, and a 1 cm × 2 cm superficial wound left to heal by secondary intention and managed with chlorhexidine xeroform gauze dressings.

Seven (7) weeks after discharge, the patient was referred to the outpatient clinic with a complaint of purulent drainage on his forearm, and the wound culture was once again positive for N farcinica (Figure 1D). The MRI revealed inflammation and volume loss in PL, FDS, and FCU muscles; an 8 mm × 8 mm × 40 mm abscess foci in the FCU muscle; and granulation tissue formation limited to the superficial to deep fascia with intact tendons and deep muscles. Surgery was scheduled and, during this procedure, drainage and irrigation of the abscess foci in the muscle were performed and wound tissue cultures were obtained. These cultures were negative. The patient underwent follow-up for 10 days with chlorhexidine xeroform gauze dressings, and a third surgery with debridement of necrotic subcutaneous tissues was performed. Tissue cultures obtained during this surgery were also negative. Following 23 days of topical wound care chlorhexidine xeroform dressings, sufficient granulation tissue had developed to schedule the fourth surgical procedure. The 4 cm × 5 cm defect in the volar forearm was covered with a full-thickness skin graft. Full graft take was achieved, and the patient was discharged with a treatment plan of 6-months TMP-SMX oral antibiotics.                                                    

One and a half month after this discharge, the patient presented again with sensitivity and pain in the forearm. MRI revealed a 15 mm × 27 mm abscess focus in the subcutaneous tissue localized distal to the old abscess foci in the right forearm, and inflammatory processes were found in the surrounding tissues. To exclude immunosuppression, immunological markers were requested and an immunology consultation was performed. The results suggested chronic inflammation, not immunosuppression. The patient had low C3 and C4 levels with normal erythrocyte sedimentation rate (11 mm/hr) and C-reactive protein (4 mg/L).

His total T to B lymphocyte ratio was normal, indicating that he was immunocompetent, and increased monocyte and granulocyte ratios suggested that the wound was in the inflammatory phase of healing. The report also showed a lowered CD4/CD8 ratio of 1.14 due to increased CD8 T lymphocytes as well as natural killer, natural killer T, and gamma delta T cells. The greater than 1 ratio of CD4/CD8 ratio also indicated a normal immune status. The results showed that the patient was not immunosuppressed and had chronic N farcinica  infection.

The patient underwent a fifth surgical procedure to drain abscess foci and the wound was closed with sutures. At the same time, he received amikacin 2 × 1000 mg and imipenem 2 × 1000 mg intravenously for 10 days. He was discharged with TMP-SMX 800/160 2 × 2 mg tablets daily for 1 month. The treatment was ceased as the clinical symptoms resolved and the control ultrasound was found to be free of abcess foci while revealing only scar tissue.

Summary. This patient underwent treatment for nearly 7 months, in addition to the 3 months before admission. He underwent 5 surgeries, 1 of which  was for wound closure. During this long treatment process, the patient’s Tourette syndrome worsened from time to time, probably due to the stress of returning to the hospital and the infection. Drug therapies were changed to aripiprazole 10 mg 2 × 1,  and the condidion showed improvement. The persistent nature of N farcinica infection also affected the patient’s psychological status negatively and pychiatric support without medication was provided. The patient was free of physical symptoms after 15 days of ceasing antibiotic treatment.

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,⁹N 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.^1,3,16-18N 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.

The authors presented a cutaneous nocardiosis case in an immunocompetent patient who presented with  a draining fistula between the skin and forearm muscles and a 5 cm × 5 cm immobile hard mass with tenderness on the right forearm. N farcinica infection should be considered if the patient has a history of skin injury and if the infection has a long inoculation time, even when the patient is immunocompetent. Treatment should include serial debridements and proper wound care as well as culture-specific antibiotic treatment for at least 6 months. The psychological status of the patient should also be taken into consideration because of the stress of the long treatment process. N farcinica infections can be fatal when dissemination occurs and every precaution should be taken to limit and cure the infection.

The authors thank Emin Bulut, MD, Sisli Etfal Training and Research Hospital, Department of Medical Microbiology, for identification verification; and Professor Barış Otlu, Inonu University, Faculty of Medicine, Department of Medical Microbiology, for definitive identification of the isolate.

Dr. Acuner is an assistant professor, Zonguldak Bülent Ecevit University, Faculty of Medicine, Department of Plastic, Reconstructive and Aesthetic Surgery, and Dr. Cömert is a professor, Zonguldak Bülent Ecevit University, Faculty of Medicine, Department of Medical Microbiology. Address all correspondence to: Burçin Acuner, MD, FEBOPRAS, Zonguldak Bülent Ecevit University, Faculty of Medicine, Department of Plastic, Reconstructive and Aesthetic Surgery, İbn-i Sina Campus, Esenköy, Kozlu 67600 Zonguldak Turkey; tel: +905304662201; fax: +903722610155; email: burcinyalaz@yahoo.com.