Infectious Disease Reports 2014; volume 6:5327

A complicated case Introduction Correspondence: Chad J. Cooper, Department of of an immunocompetent Internal Medicine, Texas Tech University Health patient with disseminated Nocardia species are aerobic, gram positive Sciences Center, 4800 Alberta Ave, El Paso, TX nocardiosis filamentous branching bacteria that have the 79905, USA. potential to cause localized or disseminated Tel. +1.915.543.1009. E-mail: [email protected] Chad J. Cooper, Sarmad Said, infection. Nocardia species are ubiquitous in the environment as saprophytic components in Maryna Popp, Haider Alkhateeb, Key words: nocardia, lung abscess, brain abscess, dust, soil, water, decaying vegetation and stag- Carlos Rodriguez, septic emboli. nant matter.1 Nocardiosis mainly affects Mateo Porres Aguilar, Ogechika Alozie immunocompromised patients, although Contributions: the authors contributed equally. Department of Internal Medicine, Texas rarely immunocompetent individuals could Tech University Health Sciences Center, also be affected. The predominant form of Conflict of interests: the authors declare no El Paso, TX, USA nocardiosis is dependent on the species and potential conflict of interests. the geographical location.2 The majority of nocardiosis cases are caused by the N. aster- Received for publication: 28 January 2014. oides complex and N. brasiliensis. In the tropi- Revision received: 17 February 2014. Accepted for publication: 25 February 2014. Abstract cal climate cutaneous and lymphocutaneous infections caused by N. brasiliensis (myce- This work is licensed under a Creative Commons toma) predominate. In the temperate climate Nocardia species are aerobic, gram positive Attribution NonCommercial 3.0 License (CC BY- zone, pulmonary infections with N. asteroides NC 3.0). filamentous branching bacteria that have the complex will be more prevalent.2 The major potential to cause localized or disseminated risk factor for nocardia infection is being ©Copyright C.J. Cooper et al., 2014 infection. Nocardiosis is a rare disease that immunocomprised, specifically those with cell- Licensee PAGEPress, Italy usually affects immunocompromised patients Infectious Disease Reports 2014; 6:5327 mediated immunity defects.3 The main causes and presents as either pulmonary, cutaneous doi:10.4081/idr.2014.5327 of immunocompromise are hematopoietic only or disseminated nocardiosis. Forty-two year- stem cell or solid organ transplantation, HIV old hispanic male presented to our care with infection, chemotherapy, malignancy or gluco- extremity pain for 3 weeks, located at the bilateral lower extremity weakness, frontal corticoid therapy. Risks factors for pulmonary upper thighs with radiation down the legs. He headache, subjective fever, nausea, and vomit- nocardiosis are alcoholism and chronicuse lung also complained of a non-radiating severe, ing. Brain computed tomography (CT) disease. frontal, throbbing headache for one week, revealed multiple hyperdense lesions with Nocardiosis is a rare disease that usually associated with occasional episodes of diplop- vasogenic edema in the frontal, parietal and causes one of three clinical manifestations. ia, without a stiff neck or photophobia. Four left temporal lobes. Chest CT demonstrated Pulmonary nocardiosis is the most common days prior he developed bilateral lower extrem- bilateral cavitary nodules in the lung and right manifestation nocardiosis. Pulmonary infec- ity weakness and could not walk or stand on hilar lymphadenopathy. Brain magnetic reso- tion is acquired through the inhalation of the his own. Other complaints included nausea, nance imaging revealed multiple bilateral organism from dust or soil. Other sites of vomiting and a low-grade fever of 37.7°C. No supratentorial and infratentorial rim enhanc- nocardial dissemination include skin, subcuta- recent travel abroad or sick contacts. He had ing lesions involving the subcortical gray- neous tissues, and the central nervous sys- no medical problems or previous surgical white matter interface with vasogenic edema. tem.4 Disseminated disease is defined by the interventions. He admitted to a 20 pack year Patient was started on empiric therapy for presence of two or more organs infected by history of smoking and chronic alcohol intake unknown infectious etiology with no response. nocardia. Disseminated nocardiosis is charac- of four 8 oz cans of beer every day for the last He eventually expired and autopsy findings terized by hematogenous spread of microbes twenty years. He currently worked as a con- revealed a right hilar lung abscess and multi- into brain, eye, bone, joint, heart, kidney, skin struction worker. All vital signs were stable on ple brain abscesses. Microscopic and culture or other organs and tissues.5 Nocardiosis has admission and within normal range. Physical findings from tissue sample during autopsy the ability to disseminate any organ, most examination demonstrated somnolent but revealed nocardia wallacei speciesNon-commercial with mul- commonly the central nervous system (CNS) arousable patient in no acute distress. The tidrug resistance. The cause of death was stat- and has a tendency to relapse or progress complete neurological and lung examination ed as systemic nocadiosis (nocardia pneu- despite being given the appropriate therapy.6 were unremarkable except hypereflexia of the monitis and encephalitis). The presence of We are presenting a case of an immunocom- right brachioradialis and right biceps and a simultaneous lung and brain abscesses is a petent patient with risk factors of chronic alco- decrease of muscle strength of bilateral lower reliable indication of an underlying Nocardia hol abuse and environmental exposure as a extremities. All other body systems of physical infection. An increased awareness of the vari- construction worker that developed dissemi- examination were unremarkable. ous presentations of nocardiosis and a high nated nocardiosis. This case was further com- Initial laboratory work up (Table 1) was index of clinical suspicion can help in a rapid plicated by the inability to obtain a tissue sam- remarkable for mild hyponatremia, mild diagnosis and improve survival in an other- ple to characterize the nocardia species and transaminase elevation and hyperbilirubine- wise fatal disease. This case highlights the give the appropriate therapy. mia. The ammonia level was in the upper nor- importance of obtaining a tissue biopsy for mal range. Urinalysis, urine toxicology screen definitive diagnosis on the initial presentation and alcohol level, hepatitis serology panel and when an infectious process is considered in HIV were negative. Chest x-ray on admission the differential diagnosis and early treatment Case Report was unremarkable. Computer tomography can be initiated. (CT) of the brain (Figure 1A) on admission Forty-two year-old Hispanic male presented revealed multiple intraaxial hyperdense with severe and constant bilateral lower lesions with surrounding vasogenic edema in

[Infectious Disease Reports 2014; 6:5327] [page 9] Case Report the frontal, parietal and left temporal lobes. Table 1. Initial laboratory work up. Hematogenous spread was suggested by the White blood cell count 10.05×103 UL (4.5-11.0×103/UL) presence of several lesions at the gray-white junction. Chest-CT (Figure 1B) on admission Hemoglobin 16.0 g/dL (12.0-15.0 g/dL) demonstrated bilateral cavitary nodules in the Hematocrit 43.4% (36.0-47.0%) lung and right hilar lymphadenopathy. Our dif- Platelet count 233×103/UL (150-450×103/UL) ferential diagnosis included metastatic versus Sodium 130 mmol/L (135-145 mmol/L) infectious etiology. We therefore started the Potassium 4.4 mmol/L (3.5-5.1 mmol/L) patient on empiric antibiotics of vancomycin 1 Serum glucose 137 mg/dL (70-100 mg/dL) gram every 12 hours, ceftriaxone 2 grams every 12 hours, and dexamethasone 6mg IV BUN 15 mg/dL (7-22 mg/dL) every 8 hours for cerebral edema. We then pro- Creatinine 0.8 mg/dL (0.60-1.30 mg/dL) ceeded to obtain a MRI of the brain (Figure 2) AST 66 IU/L (15-37 IU/L) which revealed multiple bilateral supratentori- ALT 66 IU/L (12-78 IU/L) al and infratentorial rim enhancing lesions Alkaline Phosphatase 104 IU/L (50-136 IU/L) involving the subcortical gray-white matter Ammonia 45 umol/L (10-40 umol/L) interface, superficial and deep white matter tracts, brainstem and cerebellum associated with vasogenic edema. These findings were more likely associated with an infectious etiol- ogy causing septic emboli. The initial blood and urine cultures on admission were nega- tive. The pulmonary service was consulted on the second hospital day for bronchoscopy for bron- Table 2. Cerebrospinal fluid studies. only choalveloar lavage (BAL). Bronchoscopy Appearance Clear and colorless revealed normal airway anatomy with diffusely erythematous mucosa and clear secretions. White blood cell count 18/uL BAL was obtained from the left upper lobe and Neutrophils use64% cytology report had no significant findings. Lymphocytes 25% The BAL cultures were negative for fungal, Monocytes 11% bacteria and mycobacteria. AFB stain was per- Red blood cell count 1/uL formed on the BAL and was also negative. The infectious disease service was also consulted Protein 37 mg/dL on the second hospital day and recommended Glucose 55 mg/ dL a PPD, Quaniferon Gold, coccidiodies serology, Corresponding serum glucose 128 mg/ dL aspergillus antigen, toxoplasma IgG antibody, Cerebrospinal fluid serology serum crytococcal antigen and a lumbar punc- Cryptococcal antigen Negative ture for cerebrospinal fluid (CSF) analysis. All Cysticerosis IgG antibody Negative of the stated lab tests were negative. Coccidioides antibody Negative Cerebrospinal fluid analysis (Table 2) was ele- Histoplasma antibody Negative vated WBC count, suggesting an infectious eti- CSF culture Negative

Non-commercial

Figure 1. A) Computed tomography, brain: multiple intraaxial hyperdense lesions with surrounding vasogenic edema. B) Computed tomography, chest: bilateral cavitary nodules in the lung and right hilar lymphadenopathy.

[page 10] [Infectious Disease Reports 2014; 6:5327] Case Report ology. No evidence of vegetations was noted on echocardiogram. Due to the unclear etiology of the lung and brain lesions, neurosurgery was consulted for a brain biopsy. The neurosurgeon suggested that brain biopsy would not be pos- sible considering the small size and depth of the lesions. By the tenth hospital day the men- tal status of the patient deteriorated to the point that he was now disoriented to time and place but oriented to person. By the twelfth hospital day the patient developed weakness of the left upper extremity and an unsteady antalgic gait. Then on the next day, he also developed right upper extremity weakness, ptosis and right lower facial weakness. Cardiothoracic surgery was consulted for video-assisted thoracoscopic surgery with biopsy of cavitary lung lesions but the location of the lesion was unsuitable for the surgical access. Eventually, the GCS of the patient decreased to 7, he was bradycardic and had complete right sided paralysis with a positive right side babinski. He was subsequently transferred to the Figure 2. T1 and T2 magnetic resonance imaging, brain: multiple bilateral supratentori- al and infratentorial rim enhancing lesions involving the subcortical gray-white matter medical intensive care unit (MICU) for further interface associated with vasogenic edema. only monitoring and cardiopulmonary support. The repeat head-CT with contrast revealed multiple ring enhancing lesions involving both cere- bral, basal ganglia and brainstem. There was the right hilum abscess showed foci useof necro- empyema or lung abscesses. Our patient in no evidence for acute intracranial hemor- sis with acute inflammation and microabscess particular presented with a major right hilar rhage, herniation, mass effect or midline shift. formation. The macroscopic findings of the lung abscess and several microabscesses. A The infectious disease service decided to start brain revealed multiple bilateral cavities pres- differential diagnosis for a lung abscess should the patient on amphotericin B 450 mg (5 ent in the white matter throughout the entire include aspergillosis, actinomycosis, tubercu- mg/kg) IV every 24 hours and advised us to cerebrum, and also present throughout the losis, bacterial lung abscess and malignancy. continue the same antibiotics and dexametha- basal ganglia, midbrain, substantia nigra and The mortality due to pulmonary nocardiosis is sone. On the nineteenth hospital day the right lobe of the cerebellum. Microscopic about 14-40% which increases significantly patient became tachycardic (HR: 120-130’s) examination findings showed foci of acute when there is dissemination to the central and desaturated to <80%, hence he was intu- inflammation and microabscess formation. nervous system.7 Although 20% of extrapul- bated and placed on mechanical ventilation Grocott methena mine silver (GMS), grain monary Nocardia infections occur in the support. The infectious disease consult service stain and Fite’s stain of the right hilum absence of pulmonary disease, about 50% of all recommended albendazole 15 mg/kg/day abscess and brain abscesses both revealed pulmonary cases disseminate extrapulmonary, through the naso-gastric-tube every 12 hours numerous gram positive branching rods, mor- most commonly the brain.8 for probable neurocysticercosis, and then to phologically consistent with nocardia. Tissue Nocardia appears to have special tropism for initiate toxoplasmosis therapy despite nega- samples from the brain abscess lesions and neural tissue. Nocardia brain abscess are rare tive test result. This therapy included lung cavitary lesions were sent for cultures and and accounts for only 1-2% of all cerebral pyrimethamine 200 mg PO (1 dose)Non-commercial then 75 subsequently grew nocardia species. PCR abscesses.9 The mortality rate is 31% which is mg/day plus sulfadiazine 1.5 g PO every 6 analysis revealed nocardia wallacei species much greater than that of other agents that hours plus leukovorin 20 mg PO every 24 with resistance to ceftriaxone, levofloxacin, can cause cerebral abscesses being less than hours. Despite our best efforts, the patient aminoglycosides (amikacin) and to sulfon- 10%.10 The presence of simultaneous lung and remained tachycardic and begun to spike amides (trimethoprim-sulfamethoxazole – brain abscesses has been documented as a fevers ranging from 38.7°C to 39°C. TMP-SMX). However, this species of nocardia reliable indication of an underlying nocardia Considering the worsening of his clinical sta- was sensitive to imipenem. The final autopsy infection.11 Central nervous system (CNS) tus we continued to advocate the attempt for a diagnosis revealed nocardia pneumonitis and involvement with disseminated nocardiosis tissue biopsy in order to help us guide in the encephalitis. The cause of death was stated as results in up to a 55% mortality rate in diagnosis and treatment but to no avail. The systemic nocadiosis (nocardia pneumonitis immunocompromised patients.12 If left patient continued to deteriorate, did not and encephalitis). untreated, disseminated nocardiosis has a respond and subsequently expired on the mortality rate of greater than 85%.13 twentieth hospital day after the family with- The main challenge with nocardiosis is the drew care. ability to arrive at a definitive diagnosis. Even Autopsy was subsequently performed two Discussion though it has been reported in the medical liter- days later. Macroscopic findings of respiratory ature, the relative rarity of this infection can system included bilateral serosanguineous The primary clinical presentation of nocar- lead to it being overlooked and misdiagnosed as pleural effusions and a lung abscess at the diosis is pulmonary involvement. Reported other pathologies.14 The nonspecific presenta- right hilum. The microscopic examination of cases have been associated with pneumonia, tion and imaging findings of the disease war-

[Infectious Disease Reports 2014; 6:5327] [page 11] Case Report rant culture and tissue diagnosis. Diagnosis of but can be very challenging. However, if a tis- infection caused by Nocardia wallacei: a case nocardia can only be confirmed by microbiolog- sue biopsy can be obtained then nocardia can report. J Med Case Rep 2013;7:103. ical techniques for which adequate material be quickly diagnosed by examination of patho- 11. Sirisena1 D, Swedan LA, Jayne D, must be obtained.15 Gram staining is the most logical material with gram stain or a modified Chakravarty K. A case of systemic nocardio- sensitive method for visualizing and recogniz- acid fast. This case highlights the importance sis in systemic vasculitis and a review of the ing nocardia. Nocardia is partially acid-fast by of obtaining a tissue biopsy for microbiological literature. Singapore Med J 2013;54:e127-30. conventional Ziehl-Nielsen staining and is reac- and culture identification for organisms such 12. Montoya JP, Carpenter JL, Holmes GP, et al. tive with Gomori methenamine silver.16 It is as nocardia on the initial presentation when Disseminated nocardia transvalensis important to obtain cultures from tissue biop- an infectious process is considered in the dif- Infection with osteomyelitis and multiple sies when disseminated infection is considered ferential diagnosis and early treatment can be brain abscesses. Scand J Infect Dis to allow for prompt organism identification and initiated. Another important point that this 2003;35:189-212. perhaps better patient care.17 Biochemical tests case presents is the existence of a less com- 13. Paramythiotou E, Papadomichelakis E, may be used for identification of a subset of mon nocardia species with multidrug resist- Vrioni G, et al. A life-threatening case of dis- nocardia species. It is important to distinguish ance especially to aminoglycosides and sulfon- seminated nocardiosis due to Nocardia nocardia species because of the resistance to amides. We stress the importance of determin- brasiliensis. Indian J Crit Care Med certain antimicrobial agents and a higher risk ing the species of nocardia and antibiotic sus- 2012;16:234-7. of dissemination.18 This is important for epi- ceptibility to help guide the management of 14. Menkü A, Kurtsoy A, Tucer B, et al. Nocardia demiological reasons due to the rising resist- this devastating infectious disease. brain abscess mimicking brain tumour in ance of nocardia spp. to TMP-SMX. immunocompetent patients: report of two Initial treatment for presumed nocardiosis cases and review of the literature. Acta must be empiric, due to the fact that it could Neurochir 2004;146:411-4. take up to 3 weeks to speciate and determine References 15. Höpler W, Laferl H, Szell M, et al. Blood cul- sensitivities to nocardia.19 In general, the anti- ture positive Nocardia asteroides infection: bacterial agents most active against N. aster- 1. Brown-Elliott BA, Brown JM, Conville PS, a case report. Wien Med Wochenschr oides are the sulfonamides, amikacin, minocy- Wallace RJ Jr. Clinical and laboratory fea- 2013;163:37-9. cline and imipenem.20 Sulfonamides such as tures of the Nocardia spp. based on current 16. Budzikonly JM, Hosseini M, Mackinnon AC Jr., trimethoprim-sulfamethoxazole are the treat- molecular taxonomy. Clin Microbiol Rev Taxy JB. Disseminated nocardia farcinica: ment of choice for N. asteroides, with the best 2006;19:259-82. literature review and fatal outcome in an alternative being minocycline. The most effec- 2. Smeets LC, van Agtmael MA, van der Vorm immunocompetent patient. Surg Infect tive intravenous regimen for N. asteroides is ER. Successful treatment of a disseminateduse 2012;13:163-70. the combination of amikacin plus imipenem.21 Nocardia brasiliensis infection. Eur J Clin 17. Dodiuk-Gad R1, Cohen E, Ziv M, Goldstein In patients with a sulfa allergy or disseminated Microbiol Infect Dis 2005;24:350-1. LH, et al. Cutaneous nocardiosis: report of nocardiosis a combination of amikacin and 3. Benes J, Viechova J, Picha D, et al. two cases and review of the literature. Int J ceftriaxone should be used.22 It is recommend- Disseminated Nocardia asteroides infection Dermatol 2010:49:1380-5. ed that immunocompetent patients be treated in an immunocompetent woman following 18. Brown-Elliott BA, Biehle J, Conville PS, et al. for at least six months. Treatment for dissemi- an arm injury. Infection 2003;31: 112-4. Sulfonamide resistance in isolates of nated nocardia will depend upon the presence 4. Ramamoorthi K, Pruthvil BC, Rao NR. Nocardia spp. from a US multicenter survey. or absence of CNS involvement and/or multiple Pulmonary nocardiosis due to Nocardia oti- J Clin Microbiol 2012;50:670-2. organ involvement.23 Treatment for 12 months tidiscaviarum in an immunocompetent host- 19. Mosel D, Harris L, Fisher E, et al. is recommended if the central nervous system a rare case report. Asian Pac J Trop Med Disseminated Nocardia infection presenting is involved. No randomized trials have been 2011;4;14-6. as hemorrhagic pustules and ecthyma in a performed to determine the most effective 5. Cattaneo C, Antoniazzi F, Caira M, et al. woman with systemic lupus erythematosus antibiotic regimen for nocardiosis. However, Nocardia spp infections among hematologi- and antiphospholipid antibody syndrome. J TMP-SMX is considered the mainstay of thera- cal patients: results of a retrospective multi- Derm Case Rep 2013;7:52-5. py since most studies have shown a favorable center study. Int J Infect Dis 2013; 17:e610-4. 20. Uhde KB, Pathak S, McCullum I Jr, et al. suspectibility to this antibiotic.24 6. Beaman BL, Beaman L. Nocardia species: Antimicrobial-resistant nocardia isolates, Non-commercialhost-parasite relationships. Clin Microbiol United States, 1995-2004. Clin Infect Dis Rev 1994;7:213-64. 2010;51:1445-8. 7. Chow E, Moore T, Deville J, Nielsen K. 21. Wakamatsu K, Nagata N, Kumazoe H, et al. Conclusions Nocardia asteroides brain abscesses and Nocardia transvalensis pulmonary infection meningitis in an immunocompromized 10- in an immunocompetent patient with radi- Nocardiosis is often misdiagnosed because year-old child. Scand J Infect Dis 2005; ographic findings consistent with nontuber- of its rarity and nonspecific clinical picture. It 37:511-3. culous mycobacterial infections. J Infect is important to emphasize that an increased 8. Devi P, Malhotra S, Chadha A. Nocardia Chemother 2011;17:716-9. awareness of the various presentations of brasiliensis primary pulmonary nocardiosis 22. Sethi PK, Khandewal D, Sethi NK, et al. nocardiosis in combination with a high index with subcutaneous involvement in an Neuroimage: disseminated nocardiosis. Clin of clinical suspicion can precipitate a rapid immunocompetent patient. Indian J Med Neurol Neurosurg 2008;100:97-100. diagnosis and improve survival in an other- Microbiol 2011;29:68-70. 23. Arora G, Friedman M, MacDermott RP. wise fatal disease. Nocardia should be includ- 9. Al Tawfiqa JA, Maymanb T, Memishc ZA. Disseminated nocardia nova infection. ed in the differential diagnosis when evaluat- Nocardia abscessus brain abscess in an South Med J 2010;103:1269-71. ing any patient with risk factors for immuno- immunocompetent host. J Infect Publ Health 24. Rosman Y, Grossman E, Keller N, et al. suppression and a possible opportunistic 2013;6:158-61. Nocardiosis: a 15-year experience in a terti- infection. Obtaining an accurate diagnosis and 10. Cassir N, Million M, Noudel R, et al. ary medical center in Israel. Eur J Intern the initiation of early treatment are essential Sulfonamide resistance in a disseminated Med 2013;24:552-7.

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