Nocardia brasiliensis infection causes skin abscesses around the eyes: A case-report and review of literature

Abstract

Nocardia species are widely distributed in environments such as soil. Nocardia brasiliensis is the primary pathogen responsible for primary cutaneous nocardiosis. The clinical manifestations of this disease are often non-specific, making it prone to misdiagnosis. This article reports a case involving a 42-year-old immunocompetent female patient who presented with a right periorbital skin abscess accompanied by cervical lymphadenitis, without a clear history of trauma or insect bite. Empirical antibacterial therapy proved ineffective. The infection was definitively diagnosed as Nocardia brasiliensis by secretion culture (antimicrobial susceptibility testing indicated sensitivity to co-trimoxazole). Based on the susceptibility results, treatment was adjusted to oral trimethoprim-sulfamethoxazole (SMZ-TMP), supplemented by local debridement and drainage. Following significant symptomatic improvement, the patient was discharged and continued with sequential oral SMZ-TMP therapy for two months. Combined with a literature review, this case highlights that: For immunocompetent hosts presenting with progressive periorbital or facial abscesses accompanied by lymphadenitis and lacking typical predisposing factors, cutaneous nocardiosis (particularly infection by N. brasiliensis) should be highly suspected. Early implementation of etiological culture and antimicrobial susceptibility testing is crucial for definitive diagnosis and guiding precise treatment (based on SMZ-TMP), with the prognosis typically being favorable.

Introduction

Nocardia species are opportunistic pathogens found in the environment, with Nocardia brasiliensis serving as the primary causative agent of primary cutaneous nocardiosis, accounting for approximately 80% of cases [1], [2]. Primary cutaneous infection is often associated with local trauma followed by exposure to contaminated sources, but it can also occur in individuals without identifiable predisposing factors [3], [4], [5], [6]. The disease exhibits diverse clinical manifestations (e.g., abscesses, ulcers, cellulitis) that are non-specific. Combined with the lengthy turnaround time and technical demands of pathogen culture, this frequently leads to misdiagnosis or delayed diagnosis [7], [8], [9], [10]. Notably, although cutaneous nocardiosis is relatively uncommon, it possesses significant invasive potential. The pathogen can spread via lymphatic channels or hematogenously, involving deep tissues and lymph nodes, and even posing a threat to ocular and central nervous system structures [7], [9], [11], [12].

The periorbital region represents a site of particular concern due to its anatomical location. Cutaneous nocardiosis in this area carries an increased risk of rapid progression. Abscess formation and local inflammation not only impair function but also heighten the danger of spread into the orbit and intracranial cavity [11], [13]. Furthermore, while immunocompromised status is a well-established risk factor, N. brasiliensis infection can also occur in individuals without underlying immunodeficienc [14], [15], [16], [17]. The exact mechanisms underlying infection in immunocompetent hosts and whether it signifies an unrecognized immune abnormality warrant further investigation [3], [6]. Clinicians should maintain a high index of suspicion for nocardial infection when encountering progressive periorbital abscesses in immunocompetent hosts lacking a typical history of trauma or insect bites.

We report a case of a 42-year-old immunocompetent woman with no history of trauma or insect bites who developed a rapidly progressive right periorbital skin abscess By integrating this case with a review of the literature, we aim to: (1) highlight the distinctive clinical features of periorbital cutaneous nocardiosis complicated by necrotizing cervical lymphadenitis in an immunocompetent host without traditional predisposing factors (trauma, insect bite, or immunodeficiency), which constitutes the primary novelty of this report; (2) provide a detailed description of the diagnostic pathway and therapeutic management of this unique clinical presentation, including the role of imaging in assessing dissemination risk; and (3) emphasize the critical importance of early etiological diagnosis (including culture-based and molecular methods) and susceptibility-guided targeted therapy (with TMP-SMX as the cornerstone) to enhance clinical vigilance and improve management strategies for such distinctive presentations.

Case report

History

A 42-year-old female was admitted on November 15, 2024, presenting with "progressive redness, swelling, pain, and ulceration of the right eyelid for 5 days." Five days prior to admission, the patient developed localized redness, swelling, and pain of the right eyelid without identifiable triggers. The following day, she incidentally noted swelling of the right cervical lymph nodes. She was afebrile. She sought care at a local hospital where empirical antibacterial therapy (specific agents unknown) was initiated. After 3 days of treatment, her symptoms showed no improvement. Two days before admission, the right eyelid redness and swelling increased in area, pain intensified, she developed difficulty opening the eye (blepharoptosis), and skin ulceration with purulent discharge appeared. Concurrently, the right cervical lymphadenopathy progressively worsened and became markedly tender. She remained afebrile and denied headache. She was subsequently transferred to our hospital for further management. Her past medical history was unremarkable, with no history of insect bites, trauma, underlying diseases, or chronic medication use.

Physical examination on admission

Vital signs were stable, afebrile. The right eyelid exhibited significant erythema and edema. A central skin ulceration was present, with yellowish-white purulent discharge. Palpebral fissure narrowing was evident due to swelling (Fig. 1: Pre-treatment appearance). Right maxillofacial skin showed erythema and swelling. Scattered erythematous patches were noted on the right neck skin. Multiple enlarged lymph nodes were palpable in the right cervical region. The largest measured approximately 2 cm× 1.5 cm, demonstrating firm consistency, restricted mobility, and marked tenderness (rated 3 +). No other superficial lymphadenopathy was detected. Cardiopulmonary and abdominal examinations revealed no abnormalities.

Fig. 1.

Pre-treatment appearance.

Diagnostic investigations

Laboratory findings

Inflammatory Markers: C-reactive protein (CRP) 29.83 mg/L; White blood cell count (WBC) 14.55 × 10⁹/L, Neutrophil count (NEUT) 12.47 × 10⁹/L, Neutrophil percentage (NEUT%) 85.7%. Lymphocyte Subsets: Absolute lymphocyte count 1464 cells/μL, Total T cells (CD3 +) 1118 cells/μL, B cells (CD19 +) 242 cells/μL, CD4 + T cells 614 cells/μL, CD8 + T cells 322 cells/μL, Natural Killer (NK) cells 92 cells/μL. Wound Secretion: Acid-fast stain: Negative. Other Tests: Liver and renal function tests, electrolytes, procalcitonin, coagulation profile, cardiac markers, urinalysis, stool analysis, and blood cultures: All results were within normal limits.

Imaging studies

Orbital CT Scan (Plain + Contrast-enhanced + 3D Reconstruction): Revealed marked swelling and thickening of the soft tissues involving the right eyelid and periorbital region. Post-contrast images showed pronounced heterogeneous enhancement interspersed with multiple small non-enhancing hypodense areas, consistent with infection and multiple small abscess formations (Fig. 2: Axial contrast-enhanced CT).

Fig. 2.

Axial contrast-enhanced CT.

Neck CT Scan (Plain + Contrast-enhanced + 3D Reconstruction): Demonstrated soft tissue swelling in the right submandibular and cervical regions. Multiple enlarged lymph nodes were noted in the right deep and superficial cervical chains, some appearing confluent. The largest node, located in right level II (inferior to the parotid gland), measured approximately 1.8 cm × 1.5 cm. This node exhibited peripheral rim enhancement with a central non-enhancing necrotic core on post-contrast images (Fig. 3: Coronal contrast-enhanced CT), findings compatible with suppurative lymphadenitis.

Fig. 3.

Coronal contrast-enhanced CT.

Clinical course and management

Initial Treatment (Commencing November 15): A diagnosis of bacterial skin and soft tissue infection with abscess formation and lymphadenitis was considered. Empirical intravenous cefmetazole (dose, e.g., 1 g every 8 h) was initiated. Concurrently, local wound debridement and abscess incision and drainage were performed.

Microbiological Diagnosis and Therapeutic Adjustment: On hospital day 6 (November 21), pus culture results identified Nocardia brasiliensis (see Culture and Microbiological Identification above for detailed microbiologic findings). Antimicrobial susceptibility testing confirmed susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX), linezolid, and moxifloxacin (see Antimicrobial Susceptibility Testing above). Cefmetazole was discontinued immediately, and oral TMP-SMX therapy (trimethoprim 160 mg / sulfamethoxazole 800 mg every 12 h) was commenced.brasiliensis. Antimicrobial susceptibility testing confirmed susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX), linezolid, and moxifloxacin. Cefmetazole was discontinued immediately, and oral TMP-SMX therapy (specific dosing, e.g., trimethoprim 160 mg / sulfamethoxazole 800 mg every 12 h) was commenced.

Culture and Microbiological Identification: Pus specimens were inoculated onto blood agar, chocolate agar, and Sabouraud dextrose agar and incubated at 35°C under aerobic conditions with 5% CO₂. After 48–72 h of incubation, small, white, dry-appearing colonies with a chalky surface and characteristic musty odor were observed on blood agar. The colonies developed a more rugose, cerebriform appearance and a yellowish-white pigment with prolonged incubation. Gram staining of the colonies revealed branching, beaded, Gram-positive filamentous bacilli, consistent with Nocardia morphology.

Modified Acid-Fast Staining: A modified Kinyoun acid-fast stain (using 1% sulfuric acid as decolorizer) was performed on the cultured isolate and demonstrated partially acid-fast branching filamentous bacilli, a finding characteristic of Nocardia species and useful for rapid presumptive identification. A standard acid-fast stain (Ziehl-Neelsen) performed directly on wound secretion was negative; however, the modified staining method on cultured colonies yielded positive results, highlighting the importance of using appropriate staining techniques for Nocardia detection.

Species Identification: Species-level identification was accomplished by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS; Bruker Biotyper), which identified the isolate as Nocardia brasiliensis with a high confidence score (>2.0). Molecular confirmation by 16S rRNA gene sequencing was not performed due to the unavailability of this technique at our center, which represents a limitation of this study. However, MALDI-TOF MS has demonstrated reliable performance for Nocardia species identification in recent studies, with updated spectral databases achieving identification rates exceeding 90% for clinically relevant Nocardia species.

Antimicrobial Susceptibility Testing: Antimicrobial susceptibility testing was performed using the broth microdilution method according to Clinical and Laboratory Standards Institute (CLSI) M24 guidelines. The isolate was susceptible to trimethoprim-sulfamethoxazole (TMP-SMX; MIC ≤ 0.25/4.75 μg/mL), linezolid (MIC 2 μg/mL), and moxifloxacin (MIC 0.5 μg/mL), and resistant to cefmetazole, confirming the rationale for the therapeutic switch.

Treatment Response: Following the switch to TMP-SMX, significant clinical improvement was observed. Right eyelid erythema, edema, pain, and purulent discharge markedly diminished, and blepharoptosis resolved. Cervical lymph node enlargement and tenderness also subsided substantially.

Discharge and Follow-up: Clinical symptoms had largely resolved, and the right eyelid ulceration site showed crusting and healing (Fig. 4: Post-treatment appearance). The patient was discharged on November 27, 2024. She was instructed to continue oral TMP-SMX (same dosage) as an outpatient, with a planned total treatment duration of 3 months (including inpatient therapy). Follow-up at 2 months post-discharge revealed no local signs of inflammation recurrence, no palpable lymphadenopathy, normalized inflammatory markers, and good tolerance to therapy.

Fig. 4.

Post-treatment appearance.

Discussion

This case illustrates primary periorbital cutaneous nocardiosis caused by Nocardia brasiliensis in an immunocompetent host with no underlying immunodeficiency and no identifiable history of trauma or insect bites, complicated by significant cervical lymphadenitis. Its rapidly progressive course and occurrence within this uncommon context underscore the critical importance of recognizing such distinctive presentations to avert misdiagnosis and therapeutic delays. We discuss the core features of this case in conjunction with the relevant literature.

Differential diagnosis

The initial differential diagnosis for this patient's rapidly progressive periorbital lesion with cervical lymphadenitis included several entities: (1) severe bacterial skin and soft tissue infection (cellulitis/abscess) caused by common pyogens such as Staphylococcus aureus or Streptococcus pyogenes—this was the leading initial impression and prompted empirical cefmetazole therapy; (2) atypical mycobacterial infection, given the subacute progression and lymph node involvement; (3) sporotrichosis or other deep fungal infections, which can present with lymphocutaneous spread; (4) cat-scratch disease (Bartonella henselae), which frequently manifests with regional lymphadenopathy; and (5) actinomycosis, which shares morphologic features with nocardiosis on Gram stain.

Several clinical features prompted consideration of a non-typical pathogen and ultimately led to the diagnosis of nocardiosis. First, the complete lack of response to 3 days of empirical antibacterial therapy and continued lack of improvement after initiation of cefmetazole—an agent with no reliable activity against Nocardia species—was a crucial early clue. Second, the presence of necrotizing lymphadenitis on CT imaging (peripheral rim enhancement with central necrosis) suggested an invasive, potentially lymphotropic pathogen rather than a common pyogenic bacterium. Third, the patient's immunocompetent status and absence of identifiable predisposing factors (trauma, insect bite, underlying disease) argued against typical severe bacterial infection and heightened suspicion for an opportunistic or unusual pathogen. These features, in aggregate, warranted pursuing culture-based diagnosis and consideration of Nocardia as a potential etiology.

Unique challenges and dissemination risk of periorbital infection

The periorbital region possesses complex anatomy: thin skin, rich lymphatic and venous drainage, and proximity to the orbit and cranial cavity. In this case, the infection progressed rapidly (within 5 days) from eyelid inflammation to abscess formation with regional lymph node involvement (necrotizing lymphadenitis demonstrated on neck CT), emphatically demonstrating the invasive potential of Nocardia brasiliensis. The ability of Nocardia brasiliensis to breach the skin barrier and disseminate via lymphatic channels is attributed to its virulence factors, including cell wall lipid components that facilitate local tissue invasion [18], [19], [20]—as manifested by the necrotizing lymphadenitis observed in this case. Periorbital nocardial infection carries a significant risk of spread into the orbit (e.g., keratitis, necrotizing scleritis [11], [13]) and intracranially (e.g., brain abscess [12]). Although orbital or intracranial extension was ruled out by CT in this case, the presence of marked preseptal soft tissue swelling and necrotic lymphadenitis strongly indicates local invasion and lymphatic spread, necessitating high vigilance for potential occult hematogenous dissemination [9]. Therefore, prompt contrast-enhanced imaging (such as the CT + 3D reconstruction performed here) is crucial to assess the extent of dissemination. Evidence of orbital or intracranial involvement mandates immediate multidisciplinary collaboration involving ophthalmology and neurosurgery to evaluate potential surgical intervention.

Implications of infection in an immunocompetent host without clear precipitating factors

While immunocompromise is a classic risk factor for nocardiosis, this case and others [15], [16], [17] confirm that Nocardia brasiliensis can infect immunocompetent individuals. Comprehensive evaluation for potential immunocompromise was performed: HIV serology was negative; fasting blood glucose and glycated hemoglobin (HbA1c) were within normal limits, excluding diabetes mellitus; there was no history of corticosteroid or other immunosuppressive medication use; and lymphocyte subset analysis yielded results within normal limits, collectively supporting a fundamentally intact immune status. However, it has been suggested that nocardiosis per se may indicate an unrecognized primary immunodeficiency [3], [6]. As more comprehensive immune profiling (e.g., specific pathogen antibody responses, cytokine profiles, genetic screening) was not performed in this case, underlying immune abnormalities cannot be definitively excluded. Clinicians should maintain awareness of this possibility and pursue targeted immune evaluation if warranted. More notably, this case lacked typical inciting events like trauma or insect bites. Aligning with literature reports [3], [6], [14], [17], this suggests Nocardia brasiliensis may exploit minute, unnoticed skin breaches or alternative, undefined environmental exposure routes. This underscores the importance of considering Nocardia infection even in the absence of classic predisposing factors, as intrinsic pathogen virulence may be sufficient to establish disease in immunocompetent hosts.

Diagnostic dilemmas and optimization strategies

Primary cutaneous nocardiosis manifests with non-specific clinical features (e.g., abscess, cellulitis) [21], [22], often mimicking common bacterial infections. The initial lack of response to empirical cefmetazole therapy (typically ineffective against Nocardia) in this case served as a crucial clinical clue suggesting an atypical pathogen, such as Nocardia. Definitive diagnosis relied on pus culture (requiring 6 days) and susceptibility testing. While culture remains the gold standard, its prolonged turnaround time can delay appropriate treatment [23]. Molecular diagnostic techniques, notably next-generation sequencing (NGS), offer advantages in speed and sensitivity [15], [24], [25], [26]. For suspected cases with rapid progression, involvement of critical sites (like the periorbital area), or failure of empirical therapy, early application of NGS should be considered to expedite pathogen identification, although it was not utilized in this instance. For skin lesions, modified acid-fast staining (a potentially useful rapid screen; standard acid-fast stain was negative in this case, but modified staining results were not mentioned) is also a valuable ancillary tool.

Treatment considerations and prognosis

Antibiotic susceptibility among Nocardia brasiliensis isolates exhibits strain-to-strain variation [14], [27], making susceptibility-guided, individualized therapy paramount. The isolate in this case was susceptible to TMP-SMX, linezolid, and moxifloxacin. We selected oral TMP-SMX as the targeted therapy based on several factors: TMP-SMX is the cornerstone of both empirical and directed treatment for cutaneous nocardiosis, with proven efficacy, high oral bioavailability, and favorable cost [7], [9], [10], [14], [27]. Despite the presence of lymphadenitis (indicating local spread), TMP-SMX monotherapy was deemed appropriate based on the isolate's susceptibility; the absence of deep tissue or systemic dissemination; and the patient's immunocompetent status. Concurrently, early and aggressive local debridement and drainage played a vital adjunctive role in management. The patient's rapid and marked clinical response validates the effectiveness of this regimen. The total planned treatment duration was 3 months (including 2 months of outpatient oral therapy), consistent with literature recommendations for immunocompetent hosts with localized cutaneous infection (3–6 months) [9], [25], [28], [29]. More extensive disease, immunocompromised hosts, or central nervous system involvement necessitate longer courses (6–12 months) and potentially more intensive regimens (e.g., combination therapy with agents like imipenem ± amikacin) [7], [9], [14], [15], [29], [30], [31], [32], [33]. The favorable outcome in this case (symptom resolution, lymphadenitis regression) corroborates the literature: localized cutaneous nocardiosis carries an excellent prognosis when managed with early diagnosis, thorough debridement, and appropriate antibiotic therapy [25], [34].

Limitations

Several limitations of this case report should be acknowledged. First, molecular confirmation of the Nocardia brasiliensis isolate by 16S rRNA gene sequencing was not performed due to the unavailability of this technique at our center; species identification relied on MALDI-TOF MS and phenotypic characteristics. Second, comprehensive immune profiling beyond lymphocyte subset analysis (e.g., specific anti-Nocardia antibody responses, cytokine profiling, or genetic testing for primary immunodeficiencies) was not conducted, and therefore an occult immune abnormality cannot be definitively excluded. Third, follow-up was limited to 2 months post-discharge; the planned 3-month treatment course had not been completed at the time of reporting, and long-term outcomes including potential relapse remain to be assessed. Fourth, this is a single case, and the generalizability of the diagnostic and therapeutic observations requires validation in larger case series. Despite these limitations, this case provides clinically relevant insights into the recognition, diagnosis, and management of periorbital cutaneous nocardiosis in immunocompetent hosts.

Summary

This report details a rare case of Nocardia brasiliensis causing a periorbital skin abscess with lymphadenitis in an immunocompetent host lacking identifiable predisposing factors. The rapidly progressive course underscores the pathogen's inherent invasiveness and the unique risks associated with periorbital location (dissemination to orbit/central nervous system). Clinicians should maintain a high index of suspicion for cutaneous nocardiosis (particularly Nocardia brasiliensis) in patients presenting with progressive periorbital/facial abscesses accompanied by lymphadenitis, even in the absence of classic risk factors. Diagnostic vigilance, especially in cases refractory to initial empirical antibacterial therapy, and timely pursuit of microbiological diagnostics (culture, modified acid-fast stain) are key. NGS may accelerate diagnosis in complex or urgent scenarios where available. Treatment must be guided by susceptibility testing. TMP-SMX represents an effective monotherapy choice for uncomplicated or localized infections, supplemented by adequate surgical debridement and drainage. For infections involving critical sites like the periorbital region or associated with lymphadenitis, comprehensive imaging is recommended to exclude deep extension, informing individualized management decisions regarding antimicrobial selection (mono- vs. combination therapy) and duration. The successful management of this case highlights the importance of integrated clinical assessment, precise etiological diagnosis, and targeted antimicrobial therapy.

Ethical approval and Consent

This retrospective case report was conducted in accordance with the Declaration of Helsinki. The medical records and biological specimens used in this study were obtained during routine clinical diagnosis and treatment. None of the patients/participants had previously explicitly refused the use of their medical records or specimens for research purposes. Patient privacy and personal identifiable information have been strictly protected throughout the study. According to the regulations of the Institutional Review Board of Mianyang Central Hospital, formal ethical approval is waived for retrospective case reports involving a single patient. The study was registered and approved by the Clinical Research Management Committee of Mianyang Central Hospital (Registration No. 2025KY-LW044, approved on June 30, 2025).Due to the retrospective nature of this report and the patient having been discharged and lost to follow-up, written informed consent could not be obtained. However, the patient provided verbal informed consent during hospitalization for the use of clinical data and images for academic publication. This verbal consent was documented in the patient's medical record. The patient was informed that all data would be anonymized to protect privacy.

Authors’ contribution

PY and QY conceived and designed the study, analyzed the data, and wrote the draft of the manuscript. PY and QY collected clinical data and reviewed and edited the manuscript. XM contributed to discussion and reviewed and edited the manuscript.

CRediT authorship contribution statement

Yiyun Pu: Writing – original draft. Xue Ma: Writing – review & editing, Conceptualization. Qing Yang: Writing – original draft.

Declaration of Competing Interest

The authors declare no conflict of interest.