Infection DOI 10.1007/s15010-014-0609-1
CASE REPORT
Disseminated Nocardia paucivorans infection in an immunocompetent host M. Hammoud • C. Kraft • J. Pulst-Korenberg C. Chenoweth • K. S. Gregg
•
Received: 27 February 2014 / Accepted: 28 February 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Nocardia paucivorans is a recently discovered species that has been shown to have a predilection for CNS involvement in cases of disseminated infection. We present a 50-year-old man with one year of weight loss admitted to the hospital with cough and confusion. Imaging revealed pulmonary and iliopsoas masses as well as innumerable ring-enhancing brain lesions. N. paucivorans was eventually identified in a subcarinal lymph node biopsy. The diagnosis was expedited by utilizing 16s rRNA gene sequencing on the biopsy tissue, resulting in species-level identification several weeks prior to culture positivity. He was treated with 12 months of parenteral and oral antibiotics, with resolution of pulmonary and brain lesions on repeat imaging. Keywords Nocardia paucivorans Central nervous system Immunocompetent
Introduction Nocardia paucivorans is an infrequently found species with the potential to cause severe infection in humans. To date, 38 cases have been reported in the literature, both in immunocompromised and immunocompetent individuals. It causes a wide spectrum of illness, ranging from M. Hammoud C. Chenoweth K. S. Gregg (&) Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, 3211 Taubman Center, 1500 E. Medical Center Dr., SPC 5378, Ann Arbor, MI 48109-5378, USA e-mail: [email protected] C. Kraft J. Pulst-Korenberg University of Michigan Medical School, Ann Arbor, MI, USA
cutaneous infection to severe, disseminated disease that often involves the central nervous system (CNS). N. paucivorans is generally susceptible to the common antibiotic therapies used to treat nocardiosis.
Case report A 50-year-old Caucasian man presented to the hospital with several days of severe headache, vomiting and confusion. His family provided additional history of an 80-pound (38 kg) weight loss over one year and oen month of a non-productive cough. The patient lived with his wife and children and worked as a welder. He had no history of immunocompromising disease. He had a 35-year history of cigarette use, occasional marijuana and intranasal cocaine use, and reported prior alcohol abuse from which he had recovered several years earlier. He had no known history of malignancy or immune-compromising conditions. On examination, the patient was cachectic and oriented only to self. He was afebrile, and vital signs were normal. Breath sounds were decreased at the right lung base, and neurologic examination demonstrated photophobia, nuchal rigidity, and slightly diminished right upper extremity strength. Laboratory studies revealed leukocytosis of 15,700 cells/lL and normal liver and kidney function. Brain MRI revealed innumerable cerebral and cerebellar ring-enhancing lesions (Fig. 1), and chest computed tomography (CT) showed a mass encasing the right middle-lobe bronchus with post-obstructive atelectasis and necrotic mediastinal lymph nodes (Fig. 2). Cerebrospinal fluid (CSF) obtained by lumbar puncture identified 48 WBC/lL (2 % neutrophils, 86 % lymphocytes, 12 % histiocytes), 48 RBC/lL, glucose 77 mg/dL and protein 66 mg/dL; CSF bacterial culture and cryptococcal antigen
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Fig. 3 Mediastinal lymph node biopsy. Grocott’s methenamine stain at 1009 magnification showing branching, filamentous organisms consistent with Nocardia species
Fig. 1 T2-weighted brain MRI showing numerous cavitary and noncavitary masses distributed throughout the parenchyma
Fig. 2 Chest CT demonstrates a mass encasing the right middle lobe bronchus with mild post-obstructive atelectasis.
were negative. Additional evaluations included human immunodeficiency virus (HIV) test, toxoplasmosis PCR, Mycobacteria tuberculosis interferon gamma release assay and Cytomegalovirus and Epstein-Barr virus serologies, all of which were negative. T cell subsets and quantitative immunoglobulins were normal. He continued to have
123
confusion and was transferred to our institution for further evaluation. Upon arrival, a PET scan showed uptake in the right middle lobe, mediastinal lymph nodes, and the right iliopsoas muscle. Due to the significant number of brain lesions, transesophageal echocardiogram was performed and did not reveal valvular infection. Transbronchial biopsy of a hilar lymph node showed necrotizing granulomatous inflammation; stains and cultures for bacteria, fungi and AFB were negative. Iliopsoas biopsy revealed necrotizing granulomatous inflammation, and few filamentous organisms were seen on Grocott’s methamine silver (GMS) stain, prompting initiation of trimethoprimsulfamethoxazole 5 mg/kg every 8 h and imipenem 1000 mg IV every 8 h for possible nocardiosis. All cultures from the iliopsoas biopsy were negative. Despite aggressive empiric therapy for nocardiosis, the patient had progressive worsening of his mental status. Repeat MRI showed increasing number of cerebral and cerebellar lesions and worsening edema, prompting addition of linezolid to his antibiotic regimen and initiation of corticosteroids with subsequent improvement in his mental status. Video-assisted thorascopic surgery was performed for excision of a subcarinal lymph node to perform additional cultures and exclude malignancy. GMS stain again revealed filamentous bacteria (Fig. 3). Gene sequence analysis utilizing 16s ribosomal RNA and rpoB primer sets on a section of the lymph node biopsy detected Nocardia paucivorans DNA (University of Washington, Seattle). This result was obtained nearly two weeks before branching, gram-positive rods were identified on AFB culture from this biopsy site and four weeks before Nocardia species closely related to Nocardia asteroides complex was identified from this culture. Antibiotic susceptibility testing
Disseminated Nocardia paucivorans infection in an immunocompetent host
of the isolate revealed it to be susceptible to all drugs tested, including imipenem, moxifloxacin, trimethoprimsulfamethoxazole, and linezolid. Treatment continued with trimethoprim-sulfamethoxazole and imipenem for six weeks, with improvement in his neurologic symptoms, after which he was transitioned to trimethoprim-sulfamethoxazole 320/160 mg tablets, two tablets every 8 h, and oral moxifloxacin 400 mg every 24 h. After four months of therapy and improvement of his brain lesions on repeat MRI, he was treated with moxifloxacin alone. He completed nearly 12 months of antibiotic therapy, with resolution of his brain and pulmonary lesions and complete neurologic recovery.
Discussion Nocardia spp. are filamentous, branching, gram-positive rods of the order Actinomycetales. They are ubiquitous in soil, decaying organic matter and water [1]. As such, infection typically occurs through inhalation or direct skin inoculation. Immune-compromising conditions including HIV infection, solid-organ transplantation and hematologic malignancy are risk factors for Nocardia infection, as is receipt of cytotoxic chemotherapy and corticosteroids [2]. However, infections in immunocompetent persons account for 40–50 % of all cases [3]. Pneumonia is the most frequent clinical presentation, but Nocardia infections also frequently cause CNS infection, either as a primary disease or secondary to dissemination from a primary site of infection. In a review of 1,050 cases of Nocardiosis, 39 % presented as pneumonia, 32 % as disseminated infection (C2 sites), and 9 % as isolated CNS infections [4]. In the cases of disseminated infection, 44 % had CNS involvement, highlighting a neurotropism characteristic of Nocardia spp. CNS manifestations of Nocardia infection can include isolated or multifocal brain abscesses and meningitis. In cases of brain abscess, single and multiple abscesses occur in similar frequency [5]. Our patient’s presentation was characteristic of disseminated disease from a primary pulmonary infection, but was particularly striking for the sheer number of brain lesions present at the time of diagnosis. As Nocardia has rarely been shown to be a cause of native valve endocarditis [6], a focus of infection leading to embolic phenomena was of concern, but no endovascular source was identified. Nocardia paucivorans was first discovered in 2000 after isolation from the respiratory secretions of a patient with chronic lung disease and was confirmed to be a distinct species based upon 16s rRNA sequencing and chemotaxonomy [7]. The first two reports of N. paucivorans infection occurred in 2002 [8, 9]. In both of these patients, infection manifested as CNS disease with brain abscesses,
and at least one of the patients was immunocompromised. The largest series of N. paucivorans infection to date describes 33 cases in northeast Australia over a 20-year period [10]. The spectrum of disease in these cases included cutaneous infection, pneumonia, meningitis and endocarditis, and at least eight of the patients were immunocompromised. Dissemination occurred in at least 33 % of cases, with 80 % of disseminated cases having CNS involvement. This finding led the authors to hypothesize that N. paucivorans had a heightened neurotropism that increased the propensity to cause CNS infection. When all published cases of N. paucivorans infection with sufficient reported data to include or exclude CNS disease were evaluated, 11/38 (28.9 %) involved CNS infection, and 11/38 (28.9 %) were disseminated disease. In cases of disseminated infection, CNS involvement occurred in 9 of 11 (81.8 %) [8–10, current report]. In comparison, CNS involvement in the aforementioned report of 1,050 patients occurred in 23.8 % of cases, with 44 % of disseminated cases involving the CNS [4]. Although the number of cases of N. paucivorans infection published to date are insufficient to confirm or refute the hypothesis of a greater neurotropism than other Nocardia species, CNS involvement is frequent in infection by this species. Diagnosis of nocardiosis in our patient was expedited by 16s rRNA sequencing of lymph node tissue. Despite biopsies from three distinct sites, only one sample provided a positive culture and definitive identification of Nocardia spp. from a culturing that occurred more than a month from the date of biopsy. This delay is not unusual for identification of Nocardia spp., as growth in culture may take several weeks, and additional labor-intensive biochemical or chemotaxonomic testing is required to further identify the organism at the complex or species level. Molecular assays such as 16s rRNA gene sequencing are clinically useful in that they allow for more rapid species-level identification. Sequencing of 16s rRNA reliably identifies Nocardia species in culture and differentiates Nocardia spp. from closely related genera such as Rhodococcus and Tsukamurella [11, 12]. In fact, the use of molecular assays to analyze gene sequences has led to the description of more than 80 novel Nocardia species, nearly half of which have been found to cause disease in humans [13]. This technology has also been effectively applied directly to clinical specimens such as biopsy tissue and body fluids, allowing for even more rapid diagnosis [14]. As there are distinct inter-species antibiotic resistance profiles, early identification of Nocardia spp. by 16s rRNA sequencing may allow for more tailored empiric antibiotic therapy while awaiting culture-based susceptibility testing results. N. paucivorans does not typically display resistance to common therapies for nocardiosis, although there is one
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report of tremethaprim/sulfamethoxazole resistance in a patient with pneumonia [15]. Treatment of CNS nocardiosis is largely based upon expert opinion. It is generally accepted to initiate treatment with two or three parenteral antibiotics for 4–6 weeks and until susceptibility results are available. Thereafter, provided there is clinical improvement, maintenance therapy with one or two effective oral antibiotics can be initiated and continued until at least 12 months of therapy [16]. In summary, this case illustrates that N. paucivorans may cause severe, disseminated infection in immunocompetent patients. It remains unclear if this organism has a higher predilection for CNS involvement than other Nocardia species, but CNS involvement is characteristic in disseminated infection based upon previous reports, and we would recommend brain imaging in all cases of disseminated infection. Finally, 16s rRNA gene sequencing is an invaluable tool for expediting the diagnosis of nocardiosis and should be considered for use in cases that do not have a clear diagnosis but in which nocardiosis is in the differential diagnosis. Acknowledgments We would like to thank Maria Pletneva and Stephanie Chen for their assistance in obtaining the photograph of the lymph node biopsy specimen seen in Fig. 3. Conflict of interest The authors have no conflicts of interest to disclose with any of the material presented within the manuscript.
References 1. McNeil MM, Brown JM. The medically important aerobic actinomycetes: epidemiology and microbiology. Clin Microbiol Rev. 1994;7:357–417. 2. Corti ME, Villafane-Fioti MF. Nocardiosis: a review. Int J Infect Dis. 2003;7:243–50. 3. Lederman ER, Crum NF. A case series and focused review of nocardiosis: clinical and microbiologic aspects. Medicine. 2004;83:300–13. 4. Beaman BL, Beaman L. Nocardia species: host-parasite relationships. Clin Microbiol Rev. 1994;7:213–64.
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5. Anagnostou T, Arvanitis M, Kourkoumpetis TK, et al. Nocardiosis of the central nervous system: experience from a general hospital and review of 84 cases from the literature. Medicine. 2014;93:19–32. doi:10.1097/MD.0000000000000012 (published online first: Epub date). 6. Watson A, French P, Wilson M. Nocardia asteroides native valve endocarditis. Clin Infect Dis. 2001;32:660–1. doi:10.1086/ 318712 (published online first: Epub date). 7. Yassin AF, Rainey FA, Burghardt J, et al. Nocardia paucivorans sp. nov. Int J Syst Evol Microbiol. 2000;50 Pt 2:803–9. 8. Eisenblatter M, Disko U, Stoltenburg-Didinger G, et al. Isolation of Nocardia paucivorans from the cerebrospinal fluid of a patient with relapse of cerebral nocardiosis. J Clin Microbiol. 2002;40:3532–4. 9. Wellinghausen N, Pietzcker T, Kern WV, et al. Expanded spectrum of Nocardia species causing clinical nocardiosis detected by molecular methods. Int J Med Microbiol. 2002;292:277–82. doi:10.1078/1438-4221-00208 (published online first: Epub date). 10. Gray TJ, Serisier DJ, Gilpin CM, et al. Nocardia paucivorans—a cause of disseminated nocardiosis. J Infect. 2007;54:e95–8. doi:10.1016/j.jinf.2006.05.005 (published online first: Epub date). 11. Laurent FJ, Provost F, Boiron P. Rapid identification of clinically relevant Nocardia species to genus level by 16S rRNA gene PCR. J Clin Microbiol. 1999;37:99–102. 12. Cloud JL, Conville PS, Croft A, et al. Evaluation of partial 16S ribosomal DNA sequencing for identification of nocardia species by using the MicroSeq 500 system with an expanded database. J Clin Microbiol. 2004;42:578–84. 13. Xiao M, Kong F, Sorrell TC, et al. Identification of pathogenic Nocardia species by reverse line blot hybridization targeting the 16S rRNA and 16S-23S rRNA gene spacer regions. J Clin Microbiol. 2010;48:503–11. doi:10.1128/JCM.01761-09 (published online first: Epub date). 14. Couble A, Rodriguez-Nava V, de Montclos MP, et al. Direct detection of Nocardia spp. in clinical samples by a rapid molecular method. J Clin Microbiol. 2005;43:1921–4. doi:10. 1128/JCM.43.4.1921-1924.2005 (published online first: Epub date). 15. Wegerle S, Markus A, Weber N, et al. Pulmonary nocardiosis with trimethoprime/sulphamethoxazole-resistant Nocardia paucivorans in a patient with no signs of immunosuppression. Pneumologie. 2007;61:46–51. doi:10.1055/s-2006-944276 (published online first: Epub date). 16. Lerner PI. Nocardiosis. Clin Infect Dis. 1996;22:891–903 quiz 04-5.
CASE REPORT
Disseminated Nocardia paucivorans infection in an immunocompetent host M. Hammoud • C. Kraft • J. Pulst-Korenberg C. Chenoweth • K. S. Gregg
•
Received: 27 February 2014 / Accepted: 28 February 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Nocardia paucivorans is a recently discovered species that has been shown to have a predilection for CNS involvement in cases of disseminated infection. We present a 50-year-old man with one year of weight loss admitted to the hospital with cough and confusion. Imaging revealed pulmonary and iliopsoas masses as well as innumerable ring-enhancing brain lesions. N. paucivorans was eventually identified in a subcarinal lymph node biopsy. The diagnosis was expedited by utilizing 16s rRNA gene sequencing on the biopsy tissue, resulting in species-level identification several weeks prior to culture positivity. He was treated with 12 months of parenteral and oral antibiotics, with resolution of pulmonary and brain lesions on repeat imaging. Keywords Nocardia paucivorans Central nervous system Immunocompetent
Introduction Nocardia paucivorans is an infrequently found species with the potential to cause severe infection in humans. To date, 38 cases have been reported in the literature, both in immunocompromised and immunocompetent individuals. It causes a wide spectrum of illness, ranging from M. Hammoud C. Chenoweth K. S. Gregg (&) Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, 3211 Taubman Center, 1500 E. Medical Center Dr., SPC 5378, Ann Arbor, MI 48109-5378, USA e-mail: [email protected] C. Kraft J. Pulst-Korenberg University of Michigan Medical School, Ann Arbor, MI, USA
cutaneous infection to severe, disseminated disease that often involves the central nervous system (CNS). N. paucivorans is generally susceptible to the common antibiotic therapies used to treat nocardiosis.
Case report A 50-year-old Caucasian man presented to the hospital with several days of severe headache, vomiting and confusion. His family provided additional history of an 80-pound (38 kg) weight loss over one year and oen month of a non-productive cough. The patient lived with his wife and children and worked as a welder. He had no history of immunocompromising disease. He had a 35-year history of cigarette use, occasional marijuana and intranasal cocaine use, and reported prior alcohol abuse from which he had recovered several years earlier. He had no known history of malignancy or immune-compromising conditions. On examination, the patient was cachectic and oriented only to self. He was afebrile, and vital signs were normal. Breath sounds were decreased at the right lung base, and neurologic examination demonstrated photophobia, nuchal rigidity, and slightly diminished right upper extremity strength. Laboratory studies revealed leukocytosis of 15,700 cells/lL and normal liver and kidney function. Brain MRI revealed innumerable cerebral and cerebellar ring-enhancing lesions (Fig. 1), and chest computed tomography (CT) showed a mass encasing the right middle-lobe bronchus with post-obstructive atelectasis and necrotic mediastinal lymph nodes (Fig. 2). Cerebrospinal fluid (CSF) obtained by lumbar puncture identified 48 WBC/lL (2 % neutrophils, 86 % lymphocytes, 12 % histiocytes), 48 RBC/lL, glucose 77 mg/dL and protein 66 mg/dL; CSF bacterial culture and cryptococcal antigen
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M. Hammoud et al.
Fig. 3 Mediastinal lymph node biopsy. Grocott’s methenamine stain at 1009 magnification showing branching, filamentous organisms consistent with Nocardia species
Fig. 1 T2-weighted brain MRI showing numerous cavitary and noncavitary masses distributed throughout the parenchyma
Fig. 2 Chest CT demonstrates a mass encasing the right middle lobe bronchus with mild post-obstructive atelectasis.
were negative. Additional evaluations included human immunodeficiency virus (HIV) test, toxoplasmosis PCR, Mycobacteria tuberculosis interferon gamma release assay and Cytomegalovirus and Epstein-Barr virus serologies, all of which were negative. T cell subsets and quantitative immunoglobulins were normal. He continued to have
123
confusion and was transferred to our institution for further evaluation. Upon arrival, a PET scan showed uptake in the right middle lobe, mediastinal lymph nodes, and the right iliopsoas muscle. Due to the significant number of brain lesions, transesophageal echocardiogram was performed and did not reveal valvular infection. Transbronchial biopsy of a hilar lymph node showed necrotizing granulomatous inflammation; stains and cultures for bacteria, fungi and AFB were negative. Iliopsoas biopsy revealed necrotizing granulomatous inflammation, and few filamentous organisms were seen on Grocott’s methamine silver (GMS) stain, prompting initiation of trimethoprimsulfamethoxazole 5 mg/kg every 8 h and imipenem 1000 mg IV every 8 h for possible nocardiosis. All cultures from the iliopsoas biopsy were negative. Despite aggressive empiric therapy for nocardiosis, the patient had progressive worsening of his mental status. Repeat MRI showed increasing number of cerebral and cerebellar lesions and worsening edema, prompting addition of linezolid to his antibiotic regimen and initiation of corticosteroids with subsequent improvement in his mental status. Video-assisted thorascopic surgery was performed for excision of a subcarinal lymph node to perform additional cultures and exclude malignancy. GMS stain again revealed filamentous bacteria (Fig. 3). Gene sequence analysis utilizing 16s ribosomal RNA and rpoB primer sets on a section of the lymph node biopsy detected Nocardia paucivorans DNA (University of Washington, Seattle). This result was obtained nearly two weeks before branching, gram-positive rods were identified on AFB culture from this biopsy site and four weeks before Nocardia species closely related to Nocardia asteroides complex was identified from this culture. Antibiotic susceptibility testing
Disseminated Nocardia paucivorans infection in an immunocompetent host
of the isolate revealed it to be susceptible to all drugs tested, including imipenem, moxifloxacin, trimethoprimsulfamethoxazole, and linezolid. Treatment continued with trimethoprim-sulfamethoxazole and imipenem for six weeks, with improvement in his neurologic symptoms, after which he was transitioned to trimethoprim-sulfamethoxazole 320/160 mg tablets, two tablets every 8 h, and oral moxifloxacin 400 mg every 24 h. After four months of therapy and improvement of his brain lesions on repeat MRI, he was treated with moxifloxacin alone. He completed nearly 12 months of antibiotic therapy, with resolution of his brain and pulmonary lesions and complete neurologic recovery.
Discussion Nocardia spp. are filamentous, branching, gram-positive rods of the order Actinomycetales. They are ubiquitous in soil, decaying organic matter and water [1]. As such, infection typically occurs through inhalation or direct skin inoculation. Immune-compromising conditions including HIV infection, solid-organ transplantation and hematologic malignancy are risk factors for Nocardia infection, as is receipt of cytotoxic chemotherapy and corticosteroids [2]. However, infections in immunocompetent persons account for 40–50 % of all cases [3]. Pneumonia is the most frequent clinical presentation, but Nocardia infections also frequently cause CNS infection, either as a primary disease or secondary to dissemination from a primary site of infection. In a review of 1,050 cases of Nocardiosis, 39 % presented as pneumonia, 32 % as disseminated infection (C2 sites), and 9 % as isolated CNS infections [4]. In the cases of disseminated infection, 44 % had CNS involvement, highlighting a neurotropism characteristic of Nocardia spp. CNS manifestations of Nocardia infection can include isolated or multifocal brain abscesses and meningitis. In cases of brain abscess, single and multiple abscesses occur in similar frequency [5]. Our patient’s presentation was characteristic of disseminated disease from a primary pulmonary infection, but was particularly striking for the sheer number of brain lesions present at the time of diagnosis. As Nocardia has rarely been shown to be a cause of native valve endocarditis [6], a focus of infection leading to embolic phenomena was of concern, but no endovascular source was identified. Nocardia paucivorans was first discovered in 2000 after isolation from the respiratory secretions of a patient with chronic lung disease and was confirmed to be a distinct species based upon 16s rRNA sequencing and chemotaxonomy [7]. The first two reports of N. paucivorans infection occurred in 2002 [8, 9]. In both of these patients, infection manifested as CNS disease with brain abscesses,
and at least one of the patients was immunocompromised. The largest series of N. paucivorans infection to date describes 33 cases in northeast Australia over a 20-year period [10]. The spectrum of disease in these cases included cutaneous infection, pneumonia, meningitis and endocarditis, and at least eight of the patients were immunocompromised. Dissemination occurred in at least 33 % of cases, with 80 % of disseminated cases having CNS involvement. This finding led the authors to hypothesize that N. paucivorans had a heightened neurotropism that increased the propensity to cause CNS infection. When all published cases of N. paucivorans infection with sufficient reported data to include or exclude CNS disease were evaluated, 11/38 (28.9 %) involved CNS infection, and 11/38 (28.9 %) were disseminated disease. In cases of disseminated infection, CNS involvement occurred in 9 of 11 (81.8 %) [8–10, current report]. In comparison, CNS involvement in the aforementioned report of 1,050 patients occurred in 23.8 % of cases, with 44 % of disseminated cases involving the CNS [4]. Although the number of cases of N. paucivorans infection published to date are insufficient to confirm or refute the hypothesis of a greater neurotropism than other Nocardia species, CNS involvement is frequent in infection by this species. Diagnosis of nocardiosis in our patient was expedited by 16s rRNA sequencing of lymph node tissue. Despite biopsies from three distinct sites, only one sample provided a positive culture and definitive identification of Nocardia spp. from a culturing that occurred more than a month from the date of biopsy. This delay is not unusual for identification of Nocardia spp., as growth in culture may take several weeks, and additional labor-intensive biochemical or chemotaxonomic testing is required to further identify the organism at the complex or species level. Molecular assays such as 16s rRNA gene sequencing are clinically useful in that they allow for more rapid species-level identification. Sequencing of 16s rRNA reliably identifies Nocardia species in culture and differentiates Nocardia spp. from closely related genera such as Rhodococcus and Tsukamurella [11, 12]. In fact, the use of molecular assays to analyze gene sequences has led to the description of more than 80 novel Nocardia species, nearly half of which have been found to cause disease in humans [13]. This technology has also been effectively applied directly to clinical specimens such as biopsy tissue and body fluids, allowing for even more rapid diagnosis [14]. As there are distinct inter-species antibiotic resistance profiles, early identification of Nocardia spp. by 16s rRNA sequencing may allow for more tailored empiric antibiotic therapy while awaiting culture-based susceptibility testing results. N. paucivorans does not typically display resistance to common therapies for nocardiosis, although there is one
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M. Hammoud et al.
report of tremethaprim/sulfamethoxazole resistance in a patient with pneumonia [15]. Treatment of CNS nocardiosis is largely based upon expert opinion. It is generally accepted to initiate treatment with two or three parenteral antibiotics for 4–6 weeks and until susceptibility results are available. Thereafter, provided there is clinical improvement, maintenance therapy with one or two effective oral antibiotics can be initiated and continued until at least 12 months of therapy [16]. In summary, this case illustrates that N. paucivorans may cause severe, disseminated infection in immunocompetent patients. It remains unclear if this organism has a higher predilection for CNS involvement than other Nocardia species, but CNS involvement is characteristic in disseminated infection based upon previous reports, and we would recommend brain imaging in all cases of disseminated infection. Finally, 16s rRNA gene sequencing is an invaluable tool for expediting the diagnosis of nocardiosis and should be considered for use in cases that do not have a clear diagnosis but in which nocardiosis is in the differential diagnosis. Acknowledgments We would like to thank Maria Pletneva and Stephanie Chen for their assistance in obtaining the photograph of the lymph node biopsy specimen seen in Fig. 3. Conflict of interest The authors have no conflicts of interest to disclose with any of the material presented within the manuscript.
References 1. McNeil MM, Brown JM. The medically important aerobic actinomycetes: epidemiology and microbiology. Clin Microbiol Rev. 1994;7:357–417. 2. Corti ME, Villafane-Fioti MF. Nocardiosis: a review. Int J Infect Dis. 2003;7:243–50. 3. Lederman ER, Crum NF. A case series and focused review of nocardiosis: clinical and microbiologic aspects. Medicine. 2004;83:300–13. 4. Beaman BL, Beaman L. Nocardia species: host-parasite relationships. Clin Microbiol Rev. 1994;7:213–64.
123
5. Anagnostou T, Arvanitis M, Kourkoumpetis TK, et al. Nocardiosis of the central nervous system: experience from a general hospital and review of 84 cases from the literature. Medicine. 2014;93:19–32. doi:10.1097/MD.0000000000000012 (published online first: Epub date). 6. Watson A, French P, Wilson M. Nocardia asteroides native valve endocarditis. Clin Infect Dis. 2001;32:660–1. doi:10.1086/ 318712 (published online first: Epub date). 7. Yassin AF, Rainey FA, Burghardt J, et al. Nocardia paucivorans sp. nov. Int J Syst Evol Microbiol. 2000;50 Pt 2:803–9. 8. Eisenblatter M, Disko U, Stoltenburg-Didinger G, et al. Isolation of Nocardia paucivorans from the cerebrospinal fluid of a patient with relapse of cerebral nocardiosis. J Clin Microbiol. 2002;40:3532–4. 9. Wellinghausen N, Pietzcker T, Kern WV, et al. Expanded spectrum of Nocardia species causing clinical nocardiosis detected by molecular methods. Int J Med Microbiol. 2002;292:277–82. doi:10.1078/1438-4221-00208 (published online first: Epub date). 10. Gray TJ, Serisier DJ, Gilpin CM, et al. Nocardia paucivorans—a cause of disseminated nocardiosis. J Infect. 2007;54:e95–8. doi:10.1016/j.jinf.2006.05.005 (published online first: Epub date). 11. Laurent FJ, Provost F, Boiron P. Rapid identification of clinically relevant Nocardia species to genus level by 16S rRNA gene PCR. J Clin Microbiol. 1999;37:99–102. 12. Cloud JL, Conville PS, Croft A, et al. Evaluation of partial 16S ribosomal DNA sequencing for identification of nocardia species by using the MicroSeq 500 system with an expanded database. J Clin Microbiol. 2004;42:578–84. 13. Xiao M, Kong F, Sorrell TC, et al. Identification of pathogenic Nocardia species by reverse line blot hybridization targeting the 16S rRNA and 16S-23S rRNA gene spacer regions. J Clin Microbiol. 2010;48:503–11. doi:10.1128/JCM.01761-09 (published online first: Epub date). 14. Couble A, Rodriguez-Nava V, de Montclos MP, et al. Direct detection of Nocardia spp. in clinical samples by a rapid molecular method. J Clin Microbiol. 2005;43:1921–4. doi:10. 1128/JCM.43.4.1921-1924.2005 (published online first: Epub date). 15. Wegerle S, Markus A, Weber N, et al. Pulmonary nocardiosis with trimethoprime/sulphamethoxazole-resistant Nocardia paucivorans in a patient with no signs of immunosuppression. Pneumologie. 2007;61:46–51. doi:10.1055/s-2006-944276 (published online first: Epub date). 16. Lerner PI. Nocardiosis. Clin Infect Dis. 1996;22:891–903 quiz 04-5.
