Nocardia brasiliensis Pyomyositis in an Immunocompetent Patient Following Gardening Activity

Abstract

Nocardia pyomyositis in immunocompetent patients is a rare occurrence. The diagnosis may be missed or delayed with the risk of progressive infection and suboptimal or inappropriate treatment. We present the case of a 48-year-old immunocompetent firefighter diagnosed with pyomyositis caused by Nocardia brasiliensis acquired by direct skin inoculation from gardening activity. The patient developed a painful swelling on his right forearm that rapidly progressed proximally and deeper into the underlying muscle layer. Ultrasound imaging of his right forearm showed a 7-mm subcutaneous fluid collection with surrounding edema. Microbiologic analysis of the draining pus was confirmed to be N brasiliensis by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry. After incision and drainage deep to the muscle layer to evacuate the abscess and a few ineffective antibiotic options, the patient was treated with intravenous ceftriaxone and oral linezolid for 6 weeks. He was then de-escalated to oral moxifloxacin for an additional 4 months to complete a total antibiotic treatment duration of 6 months. The wound healed satisfactorily and was completely closed by the fourth month of antibiotic therapy. Six months after discontinuation of antibiotics, the patient continued to do well with complete resolution of the infection. In this article, we discussed the risk factors for Nocardia in immunocompetent settings, the occupational risks for Nocardia in our index patient, and the challenges encountered with diagnosis and treatment. Nocardia should be included in the differential diagnosis of cutaneous infections, particularly if there is no improvement of “cellulitis” with traditional antimicrobial regimens and the infection extends into the deeper muscle tissues.

Introduction

Nocardia species, the agent of Nocardiosis, are aerobic, filamentous, Gram-positive, partially acid-fast bacilli that belong to the family of actinomycete.^1,2 Nocardiosis usually affects immunocompromised individuals, but it has also been well-described in immunocompetent individuals who account for approximately 33% of all Nocardiosis. ³ Infections are typically rare with about 500 to 1000 cases diagnosed yearly in the United States. However, the incidence has been on the rise due to the growing population and increasing number of individuals with immunosuppressed states.^1,3 The disseminated form is commonly seen in immunocompromised hosts, with nearly all cases occurring sporadically and typically involving the lungs, central nervous system, and cutaneous tissues.^1,3 Cutaneous manifestations of Nocardia have also been reported in immunocompetent hosts. Still, involvement of the muscle layer is rare with only 2 previously reported cases, one each due to Nocardia brasiliensis and Nocardia farcinicia.^4,5 In this case, we present a 48-year-old immunocompetent male who presents with features of cellulitis in his right forearm with palpable lymph nodes, purulent discharge, and extension into the deeper muscle layers. Intraoperative culture of purulent material returned positive for N brasiliensis. We highlight this case to inform the medical community of the possibility of Nocardia infection extending from the skin and soft tissue into the deeper muscle layer in immunocompetent hosts and the need to facilitate prompt diagnosis and treatment.

Case Presentation

A 48-year-old male firefighter with no known medical history presented to an outside health facility after a painful bite on his right forearm which he attributed to a “brown recluse spider,” although this spider was never seen. The bite occurred while he was gardening in his yard, digging up three stumps and roots. The day after the bite, the area became swollen, painful, and red with a white head which he attempted to pop. Three days later, the area remained painful and indurated and started draining purulent material (Figure 1a). The next day, the swelling extended to his right forearm (Figure 1b) and he developed regional axillary lymph node enlargement. Owing to these symptoms, the patient presented to the emergency room and was started on broad-spectrum antibiotics (intravenous vancomycin and piperacillin-tazobactam). An ultrasound scan of the right forearm revealed a 7-mm subcutaneous fluid collection with surrounding edema. A wound culture of the draining pus sent to the microbiology laboratory isolated scant N brasiliensis, identified by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry. The cellulitis, however continued to spread and there was new concern for tissue necrosis. Antibiotics were then escalated to intravenous meropenem and oral linezolid. The patient showed no significant improvement despite these antibiotics, so meropenem was switched to imipenem and minocycline was added; however, the latter was discontinued the next day due to drug intolerance.

Figure 1.

(a) Swelling, induration, and purulence of the right forearm 3 days after a suspected bite sustained by the patient while working in his yard. (b) Progression of swelling, redness, and induration to the entire right forearm by day 4 following suspected exposure. (c) Deep forearm wound after copious amount of pus was evacuated from the muscle layer on day 8 of hospital admission or day 11 following suspected exposure.

On hospital day 8, the patient underwent incision and drainage deep into the muscle layer (Figure 1c). Bacterial cultures again grew N brasiliensis (MALDI-TOF). At this time, the susceptibility of the Nocardia isolate from the pus culture became available. The isolate by broth dilution was susceptible to moxifloxacin, linezolid, ceftriaxone, amikacin, and amoxicillin-clavulanate; intermediate to minocycline and doxycycline but resistant to imipenem, ciprofloxacin, and clarithromycin. The isolate was also susceptible to trimethoprim/sulfamethoxazole (TMP/SMX) and tobramycin; although the referring hospital did not have this information, we were able to obtain it directly from the microbiology reference laboratory where the susceptibility studies were done. At this point in the patient’s care, he was transitioned to our institution’s outpatient clinic. After reviewing the available information and based on the susceptibility results, imipenem was switched to intravenous ceftriaxone and oral linezolid was continued for an additional 6 weeks. Afterward, antibiotics were de-escalated to oral moxifloxacin for an additional 4 months to complete a total antibiotic treatment duration of approximately 6 months. The wound healed satisfactorily and was completely closed by the fourth month after the initial “insect bite.” Six months after discontinuation of antibiotics, the patient continued to do well with complete resolution of the infection.

Discussion

This immunocompetent patient was ultimately diagnosed with N brasiliensis pyomyositis through culture of the abscess fluid. The persistent, worsening symptoms could be explained by the fact that he received several antibiotics which were later discovered to be non-susceptible. After transitioning to a dual antibiotic regimen of ceftriaxone and linezolid in which both agents were susceptible, the patient improved.

Nocardia is typically found in the environment, especially in the soil, decaying plants, and standing water. Our patient was likely exposed to a high burden of bacteria while gardening with direct inoculation being the source of entry rather than from inhalation. The short time interval between exposure and symptom development in our patient is not unusual, as Nocardia spp. has been known to grow within 48 hours of incubation. ⁶ Furthermore, N brasiliensis has been shown to be more prevalent in regions with tropical and subtropical climates. A study by Gupta et al examined invasive Nocardia infections across distinct geographic regions and found that 17.3% of Nocardia infections in Florida, USA were due to N brasiliensis. ⁷

Our patient was deemed immunocompetent after a workup including HIV screening as well as testing for CD4, immunoglobulins, and complement resulted as normal. Although Nocardia infections more commonly affect immunocompromised patients, the literature has shown upward of 30% of cases from otherwise healthy and immunocompetent hosts, especially for cutaneous infections and by extension those with muscle involvement.^2,3,8 Immunocompromised patients are much more likely to experience lung cavitation, dissemination, bloodstream infection, hospitalization, and ultimately death. Although Nocardia typically affects males more than females, an even gender distribution of Nocardiosis has also been reported in both groups. ⁹

Although any pathogenic Nocardia species can cause cutaneous nocardiosis, it is most commonly caused by N brasiliensis. The most obvious risk factors are those associated with immunosuppression, such as malignancy and steroid use. However, other risk factors include environmental factors (hot/arid areas of Africa, Latin America, Asia, and tropical/subtropical climates), male gender, recent surgical procedures, soil exposure, and non-penetrating trauma. In addition, a notable risk includes traumatic inoculation through insect bites, animal scratches, puncture wounds, or gardening—which is typified by our patient.^1,3,4,8-10 Our patient was a male firefighter. Although several health risks including heart disease, cancer, sleep problems, and post-traumatic stress disorder have been associated with firefighters to a higher degree than the general population, it is unclear if there is an increased susceptibility to impaired immune function that could be a predisposition for Nocardiosis. In addition, firefighters often encounter different risk situations in the environment that may include skin trauma and contact with soil, decaying organic matter, and standing water which all together may increase their risk of Nocardiosis.

Once N. brasiliensis was detected, our patient was treated with intravenous meropenem and oral linezolid. We believe the decision to start this regimen, which predated our involvement, was based on the 2019 Nocardia guidelines. Linezolid is a promising option and meropenem has better activity against N. brasiliensis than other species. ¹¹ Trimethoprim/sulfamethoxazole, amikacin, amoxicillin/clavulanate, linezolid, and tigecycline have been reported to have the highest susceptibility rates for N. brasiliensis, and for our isolate, all these drugs were susceptible with the exception of tigecycline which was never tested. For drugs known to have variable activity, moxifloxacin and ceftriaxone were susceptible, and minocycline was intermediate. Imipenem, ciprofloxacin, and macrolides have high resistance rates, and this was in accordance with our results. As such, our isolate displayed a typical susceptibility pattern for N. brasiliensis.

Our report has limitations. It is unclear why TMP/SMX was not considered as empiric therapy and if including TMP/SMX as a treatment option could have made any difference in minimizing the extent of infection or treatment response. The switch from meropenem to imipenem empirically is also a poor choice, especially given the fact that most N. brasiliensis isolates have been reported to be resistant to Imipenem. ¹² Notably, our patient was employed as a firefighter. Firefighters are known to have a small to moderate increase in cancer risk as compared to the general population. ¹³ Given the Nocardia infection and occupational risk, perhaps our patient should have undergone a malignancy workup (which was later recommended after his recovery) and also, perhaps investigated for underlying primary immunodeficiency or inborn immunity errors. ¹⁰

In conclusion, Nocardia should be included in the differential diagnosis list of cutaneous infections, particularly if there is no improvement with traditional antimicrobial regimens and the infection is spreading and extending into the deeper muscle tissues. Both immunocompromised and immunocompetent patients are at risk. Future research on the frequency and characteristics of Nocardia infections in immunocompetent patients would allow for a greater understanding of any unique risk factors and clinical presentations.