Chronic renal insufficiency complicated by skin infection with Nocardia brasiliensis: A case report

Abstract

BACKGROUND

Nocardiosis is a rare bacterial infection with unclear epidemiology, pathogenesis, and characteristics. Its clinical manifestations are diverse and nonspecific, making diagnosis prone to errors, including misdiagnosis and missed diagnosis. Additionally, this disease is difficult to treat, often requiring months or even years of antibacterial therapy, and can be fatal in patients with underlying conditions.

CASE SUMMARY

A 93-year-old male patient with chronic renal insufficiency sustained a skin injury at the tip of his right thumb. As a result of an initial misdiagnosis and inadequate treatment, the infection progressed, resulting in multiple rashes on his right upper limb. Local incision and drainage of pus, combined with oral antibiotics administered at a different hospital, yielded no significant improvement. Upon hospitalization, the patient’s immune function was assessed, and further local incision and drainage were performed. Cultures of the pus identified Nocardia brasiliensis. Treatment involved intravenous infusion of piperacillin-tazobactam sodium and oral administration of sulfamethoxazole-trimethoprim, leading to the patient’s recovery. After discharge, the patient continued to take sulfamethoxazole tablets for 6 months, with complete healing of the skin lesions and no recurrence.

CONCLUSION

Nocardiosis should be considered in patients with underlying conditions and compromised immunity. Prompt and accurate diagnosis is crucial.

Key Words: Cutaneous nocardiosis; Nocardia brasiliensis; Chronic renal insufficiency; Skin infection; Immunocompromised patients; Case report

Core Tip: This report presents a case of primary cutaneous nocardiosis in a 93-year-old man with chronic renal insufficiency. The patient was hospitalized for immunodeficiency evaluation. After confirming infection with Nocardia brasiliensis, we initiated a low-dose treatment strategy to mitigate potential liver and kidney damage. The dosage was adjusted over time based on blood drug concentration monitoring. The patient experienced no recurrence of the rash.

INTRODUCTION

Nocardia, which is a partially acid-fast, aerobic, gram-positive bacillus belonging to the genus Actinomycetes, is widely distributed in the environment[1]. Its prevention methods are limited[2]. Nocardiosis is a zoonotic infectious disease that is typically subacute or chronic suppurative, although granulomatous cases are occasionally observed. Nocardia is a conditional pathogen that predominantly affects immunocompromised patients[2,3]. The diagnosis of nocardiosis is based on pathogenic culture. The disease is primarily treated with antibacterial drugs[4], often using a combination of two or three agents. Currently, sulfamethoxazole (SMZ) is the first-line treatment, with therapy typically lasting three months or even longer[5]. One study reported a patient with a severe lung infection that had spread to the brain and kidneys via the bloodstream. He was initially treated with high-dose SMZ combined with linezolid and meropenem. After his symptoms improved, he was discharged and continued treatment with linezolid. After 3 months, he was switched to SMZ maintenance therapy for six months, and the condition did not recur after 1 year of follow-up[6]. Another study described a case of lymphocutaneous nocardiosis caused by Nocardia brasiliensis. The patient was treated with SMZ combined with amoxicillin potassium chloroethane for 10 days, then SMZ alone for 20 days, and then debridement and other abscess management. The symptoms subsequently improved[7]. Our report describes a case of cutaneous nocardiosis in an immunocompromised patient with underlying conditions successfully treated with carbapenems combined with SMZ. This case underscores important considerations for the diagnosis and management of this rare infection.

CASE PRESENTATION

Chief complaints

A 93-year-old man was admitted to the hospital with “elevated blood creatinine levels for 5 years and a rash and pain in the right upper limb for 1 week”.

History of present illness

The patient had elevated serum creatinine levels for 5 years, with no significant findings in routine urine tests and no formal diagnosis or treatment. One week prior to admission, the patient sustained trauma to the tip of the right thumb, leading to localized skin damage and pustule formation. After self-performed acupuncture and drainage, swelling and pain developed in the right thumb, which gradually spread to the back of the hand and forearm, accompanied by increased local skin temperature. The patient then went to a community hospital for treatment, where a local incision, drainage, and daily dressing were performed. The specific details of the oral cephalosporin treatment are unknown; however, the patient’s symptoms did not improve. The skin redness, swelling, and pain gradually spread to the entire right upper limb, and some skin redness, swelling, and bulges were accompanied by subcutaneous lumps (Figure 1). Despite a normal body temperature, the patient was admitted on April 10, 2024 for further diagnosis and treatment.

Figure 1  The skin mass turned red, swollen and swelling at first admission.

History of past illness

The medical history included hypertension, gout, chronic obstructive pulmonary disease, and tuberculous pleurisy.

Personal and family history

The patient had no relevant family history.

Physical examination

Multiple rashes were observed on the right upper limb.

Laboratory examinations

The laboratory test results obtained on April 10, 2024 are shown in Table 1. In addition to those results, the blood tuberculosis T-SPOT test was positive, and tests for human immunodeficiency virus, syphilis, 1,3-β-D-glucan test, galactomannan test, and blood culture were all negative. Some laboratory results are as follows: Procalcitonin 0.075 ng/mL; immunoglobulin + complement immunoglobulin G 7.98 g/L, immunoglobulin A 0.71 g/L, complement 3 0.98 g/L, complement 4 0.17 g/L; lymphocyte subset CD4⁺ cells 21.8%, and B cells (CD19⁺) 4.1%.

Table 1 Relevant laboratory indicators during treatment.

Parameter	April 10, 2024 (admission)	April 24, 2024 (discharged)
White blood cell count (× 109/L)	9.6	4.6
Neutrophils (%)	75.6	59.2
Hypersensitive C-reactive protein (mg/L)	64.2	2.3
Biochemical albumin (g/L)	38.7	35.3
Alanine aminotransferase (U/L)	21	18
Aspartate aminotransferase (U/L)	26	24
Serum creatinine (μmol/L)	133	129
Estimated glomerular filtration rate (mL/minute/1.73 m2)	39	41

Imaging examinations

Type B ultrasound examination on April 11, 2024 showed changes in subcutaneous tissue echo (inflammatory changes) in the red and swollen right forearm. Vascular ultrasound prompts: There are no obvious abnormalities in the axillary, brachial, ulnar, and radial artery vein of the upper limbs on both sides. Pointed plaques in bilateral lower limb arteries.

FINAL DIAGNOSIS

Disseminated skin infection caused by Nocardia brasiliensis.

TREATMENT

After admission, the patient was administered 4.5 g of piperacillin-tazobactam sodium (2.25 g/plug) via micro-pump injection every 8 hours for anti-infective treatment (April 10 to 18, 2024). Additionally, symptomatic treatment with Shuxuning injection (Shenwei, 5 mL/plus) was administered as a 20 mL intravenous drip once daily to improve microcirculation (April 10 to 24, 2024). On the third day of admission, pustule formation was observed in the red, swollen, and indurated areas of the patient’s right forearm skin (Figure 2). Local incision and drainage were performed, and the pus was sent for a smear examination for acid-fast bacilli and other bacteria. The smear examination for fungi was negative, while bacterial and fungal cultures of the pus revealed Nocardia brasiliensis 2 (+).

Figure 2  On the third day after admission, obvious pustules were seen on the patient’s right forearm redness, swelling and clumps, swelling and clumps are visible pustules.

A consultation was requested from the Department of Infection. Given that the first-line treatment for Nocardia is SMZ-trimethoprim (TMP), it was recommended that SMZ-TMP and carbapenems be administered first. Considering that the patient was old and had chronic kidney disease, we also consulted a pharmacist. Due to the prolonged treatment course and the risk of recurrence, as well as the potential for liver and kidney damage, it was recommended to administer SMZ-TMP (SMZ:TMP 0.4 g: 0.08 g) at a dose of 2.5-5 mg/kg (calculated based on TMP) orally, twice daily. Since the patient’s weight was 57 kg, SMZ-TMP was administered orally three times daily, one tablet each time, starting on April 17, 2024. After 2 days, the blood SMZ concentration was measured at 54 μg/mL, which was suboptimal. The dose was adjusted to 2 SMZ tablets twice daily. The blood concentration was retested, and a concentration of 95 μg/mL was achieved 2 days later. A comparison of relevant laboratory data before and after treatment and the blood SMZ concentration during treatment are shown in Tables 1 and 2, respectively.

Table 2 Blood concentration of sulfamethoxazoleduring treatment.

Date	April 19, 2024 (2 days after initiating SMZ)	April 21, 2024 (2 days after increasing the SMZ dose)
Blood SMZ concentration (μg/mL)	54	95

SMZ: Sulfamethoxazole.

OUTCOME AND FOLLOW-UP

The patient’s redness and swelling subsided, and the subcutaneous nodules shrank and softened (Figure 3). He was discharged with instructions to continue oral SMZ for 6 months.

Figure 3  After treatment, the redness and swelling of the skin disappear, and the subcutaneous nodules shrink and become soft.

DISCUSSION

The taxonomy of Nocardia has historically been contradictory and confusing[8]. According to the current classification, there are 119 validly named Nocardia species, 54 of which are associated with human infections[8-11]. Molecular methods, particularly gene sequencing, are the most accurate for differentiating Nocardia species. The species distributions and sensitivity spectra of Nocardia isolates show geographical variations over time, requiring continuous monitoring.

Nocardial infections are broadly classified as lung, central nervous system, skin, or disseminated nocardiosis, with no body part being immune to infection[2]. The sites and routes of infection vary among Nocardia species. For instance, Nocardia abscesses, Nocardia dermatophytes, and Nocardia gelsekirchen are primarily associated with lung and disseminated infections[12], whereas Nocardia brasiliensis is more commonly associated with skin infections[13]. Cutaneous nocardiosis can be classified as primary or secondary. Primary cutaneous Nocardia infections are further divided into three types: Superficial skin infections, cutaneous lymphangiogenic infections, and Nocardia mycetoma. The clinical manifestations of primary cutaneous nocardiosis lack specificity and are relatively rare, leading to frequent misdiagnosis as infections caused by the Sporothrix complex, nontuberculous mycobacteria, Streptococcus, and Staphylococcus aureus[14], making clinical diagnosis particularly challenging.

Nocardia is a conditional pathogen, with approximately 60% of infections occurring in immunocompromised individuals[15,16]. Diseases affecting cell-mediated immunity significantly increase the risk of nocardiosis[17]. The human immune response to Nocardia begins with innate immunity, where monocytic granulocytes and neutrophils phagocytose most Nocardia, limiting their growth[18,19]. Adequate T lymphocyte activation is essential for bacterial lysis and clearance[2], which helps prevent pulmonary or systemic Nocardia infections. Given the ubiquity of Nocardia in soil, effective prevention strategies are limited[20]. Existing literature is limited in its ability to accurately estimate the incidence of nocardiosis and provide a general description of high-risk populations and risk factors. The incidence rates of nocardiosis and antibiotic resistance are constantly evolving[21,22]. Early clinical suspicion, diagnosis, and antimicrobial susceptibility testing in immunocompromised patients are essential to prevent adverse outcomes[23]. The assessment of CD4⁺ cell counts assists in comprehending the pathogenesis of nocardiosis without complications. Few studies have examined the association between idiopathic CD4⁺ lymphocytopenia and nocardiosis; however, a low absolute lymphocyte count may indicate more obvious immune dysfunction, making it a valuable indicator for assessing disease severity[24]. After admission, the patient’s immune status was assessed; the patient exhibited low blood albumin, low immunoglobulins, and a CD4⁺ T-cell count of approximately 336, indicating that he was immunocompromised and, therefore, was at increased risk of infection with opportunistic pathogens.

Treatment strategies for nocardiosis involve a combination of local and pharmacological approaches. Local treatments include lesion resection, abscess incision, and drainage. Drug treatment primarily involves antibiotics. Sulfa drugs are recommended for treating Nocardia infections, for instance, SMZ-TMP, which is usually the drug of first choice[25] because it is effective against most pathogenic Nocardia species. Other drugs, such as amikacin, ceftriaxone, and imidazole, are also utilized, particularly in combination therapies, to address increasing resistance to sulfa drugs[26,27]. According to the literature, patients with localized infections with normal immune function should be treated for 3 months; if immunosuppression is present, 6 months of treatment is recommended. Our patient was initially treated with piperacillin and tazobactam sodium injections for anti-infective treatment during hospitalization, and a local incision was made to drain the pus. The patient’s symptoms improved slightly. Nocardia brasiliensis infection was eventually confirmed. As the patient was 93 years old and had chronic renal insufficiency, he was considered at risk of drug-induced liver and kidney injury. Therefore, low-dose treatment was initiated, and the dose was adjusted in time based on the blood drug concentration. The literature suggests that the effective blood concentration for Nocardia skin infection is 75-100 μg/mL. A smaller dose is utilized to achieve an effective blood concentration, which reduces the incidence of adverse reactions caused by the drug. At present, the patient’s treatment period has reached 6 months, the skin lesions have completely healed, and kidney-related indicators are stable during regular reviews. The patient continues to receive regular follow-up care.

The clinical manifestations of nocardiosis are diverse and similar to those of other skin infections. This variability makes diagnosis challenging, resulting in delays in diagnosis and treatment[28]. If nocardiosis had been considered earlier in this case, timely prevention and treatment could have been achieved. In this study, we successfully attained effective therapeutic concentrations using an adjusted low-dose SMZ-TMP while minimizing adverse drug reactions in the elderly patient with compromised immune function. We believe that our findings contribute to the understanding of Nocardia brasiliensis infection, emphasizing the importance of personalized treatment, immune status assessment, and the role of CD4⁺ T cell counts. However, this study has some limitations. The criteria for determining which patients require immune status evaluation and the best methods for assessing specific immune function still need further systematic research and improvement.

CONCLUSION

Nocardiosis is a rare but serious condition, often presenting in immunocompromised patients. Its nonspecific clinical manifestations complicate early diagnosis. Evaluating the immune status of suspected patients is critical. High vigilance is required for patients with underlying conditions or compromised immunity, with prompt microbial testing recommended for suspected cases. Antibiotic selection should be recommended based on drug susceptibility results, and treatment should adhere to principles of standardization, adequate dosage, and sufficient duration. Clinical treatment must also comprehensively consider the infection site, immune status, drug metabolism, efficacy kinetics, and potential adverse reactions. Adopting a comprehensive and tailored approach to treatment can significantly improve patient outcomes.