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The first report of disseminated Nocardia concava infection, in an immunocompromised patient, in South Korea
J Infect Chemother (2012) 18:764–766 DOI 10.1007/s10156-011-0364-5
CASE REPORT
The first report of disseminated Nocardia concava infection, in an immunocompromised patient, in South Korea Seung-Hoon Lee • Heungseop Sung • Sang-Oh Lee • Sang-Ho Choi • Yang-Soo Kim Jun-Hee Woo • Sung-Han Kim
•
Received: 10 August 2011 / Accepted: 22 December 2011 / Published online: 24 April 2012 Ó Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2012
Abstract A new Nocardia species, N. concava, was first reported in Japan in 2005. To date, there have been only 3 case reports of N. concava infection worldwide (2 in Japan and 1 in China), and only 1 of these reports has detailed the clinical characteristics of N. concava, in China. Here we report the first case of disseminated infection caused by N. concava– in a patient with a history of glucocorticoid use–in South Korea. Species identification of N. concava was done with 16S rRNA sequencing and was confirmed by biochemical tests using urea, xanthine, tyrosine, and hypoxanthine decomposition. The patient was successfully treated with trimethoprim–sulfamethoxazole. Keywords Disseminated nocardiosis Korea Nocardia concava
During the past decade, molecular techniques such as polymerase chain reaction (PCR) restriction enzyme assay analysis and 16S rRNA sequencing have enabled the accurate and rapid identification of many Nocardia species [3]. In 2005, Kageyama et al. [4] reported a new Nocardia species, Nocardia concava, which was isolated from the blood of two Japanese patients with cutaneous nocardiosis, in 1991 and 1995, respectively. To our knowledge, there have been only 3 case reports of N. concava infection reported worldwide, the first one in Japan (two cases) [4, 5] and the other in China [4, 5]. We report a case of N. concava infection in a patient who had received longterm corticosteroid therapy who had multiple abscesses in all four extremities and the lung.
Case report Introduction Nocardiosis is an opportunistic infection that occurs mainly in patients with impaired cell-mediated immunity especially associated with lymphoma, transplantation, glucocorticoid therapy, or AIDS [1, 2]. N. asteroids is the most common cause of nocardiosis, and N. brasiliensis, N. otitidiscaviarum, and N. farcinica may also cause human disease [2].
S.-H. Lee S.-O. Lee S.-H. Choi Y.-S. Kim J.-H. Woo S.-H. Kim (&) Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poonganp dong, Songpa-gu, Seoul 138-736, South Korea e-mail: [email protected] H. Sung Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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A 64-year-old man whose medical history included alcoholic liver cirrhosis of Child-Pugh classification B, with membranous glomerulopathy (MGN), was admitted because of fever and chills of 3 weeks’ duration. MGN had been diagnosed from a kidney biopsy when the patient was 58 years old. He had been on corticosteroid therapy for 2 months prior to admission to control the MGN, and was taking 15 mg oral prednisolone every 24 h. He had no cough, sputum, or headache. On examination, there was a tender mass in the right upper arm, and body temperature was 35.8°C. His blood pressure was 69/48 mmHg, pulse rate 85 beats per minute, and respiration rate was 20 per minute. Lung sound was clear with decreased breathing sound in the posterior right lower lung field. A chest X-ray showed haziness in the right lower lobe with a blunted right cardiophrenic angle. Magnetic resonance imaging (MRI) with
J Infect Chemother (2012) 18:764–766
765
Fig. 2 Gram stain (91,000) of the right deltoid muscle abscess showing Gram-positive, crooked, branching, beaded filaments
Fig. 1 T1-weighted magnetic resonance imaging (MRI) with enhancement of the right upper extremity in a patient with membranous glomerulonephropathy and long-term glucocorticoid use. The patient had a deltoid muscle abscess, and the MRI shows a septated cystic lesion of about 4 9 4 9 10 cm in the deltoid muscle with peripheral wall thickening and both cellulitis and fasciitis
enhancement of the right upper extremity was done and there was a septated cystic lesion in the right deltoid muscle with peripheral thickening and septal enhancement (Fig. 1). Aspiration of the right deltoid muscle abscess was performed, followed by incision and a drainage operation. On the 4th hospital day, a Gram stain of the right deltoid muscle abscess showed crooked, branching Gram-positive filaments, and a modified acid-fast bacillus (AFB) stain showed a positive result, suggesting nocardial infection (Fig. 2). The antibiotic agent was changed from cefazolin and ciprofloxacin to intravenous trimethoprim–sulfamethoxazole (TMP–SMX). The patient continued to take oral prednisolone 10 mg every 24 h to control the MGN. On the 5th day, the patient complained of pain and tenderness in both legs and there were 10 9 10 cm movable, fluctuating palpable masses in the right posterior calf and left posterior thigh. Ultrasonography-guided aspiration was done and Gram stain showed crooked, branching, beaded filaments. High-resolution computed tomography (CT), which was carried out to evaluate the focal haziness on the chest radiography, showed multiple irregular consolidations in the right lower lobe (Fig. 3). To identify the dissemination of nocardial infection, brain MRI with enhancement was done, and there was no evidence of nocardiosis involvement in the brain parenchyma or leptomeninges. On the 10th day, cultures from the right
Fig. 3 High resolution computed tomography (CT) scan of the patient reported here who had right lower-lobe haziness on chest radiography. The CT scan shows an irregular mass abutting the major fissure and right diaphragmatic pleura and another small nodule in the right lower lobe
deltoid muscle abscess, the right posterior calf abscess, and the left posterior thigh abscess showed Nocardia species. Our Nocardia grew at 37°C but not at 45°C. For species identification, 16S rRNA sequencing with PCR was done. For the identification of this isolate and reference strains of N. concava (IFM 0354) we used two sets of primers covering nucleotides 30–1,370. For sequence comparison, 16S rRNA gene sequences were taken from the GenBank database. The sequence homology of the 16S rRNA gene of our isolate was 100% identical with N. concava IFM 0354T (1,341/1,341), 98.3% identical with N. seriole DSM 44129 (1,322/1,345, gaps 8/1,345), and 98.0% identical with N. seriole ATCC 43993T (1,319/ 1,346, gaps 10/1,346). We were able to identify the genus and species of our Nocardia according to the guidelines for
123
766
DNA sequencing of aerobic actinomycetes, proposed by the Clinical and Laboratory Standards Institute [6]. In addition, we performed biochemical tests. The urea decomposition test result was weakly positive. Xanthine, tyrosine, and hypoxanthine decomposition test results were positive, and the casein decomposition test was negative. With all these results, we were able to discriminate N. concava from N. seriole, which has high similarity of the 16S rRNA sequence to that of N. concava [4]. An antibiotic susceptibility test was done by the broth dilution method, using a Sensititer RGMYCO (Biocentric, Bandol, France) panel. The isolated organism was susceptible to TMP–SMX, amikacin, and linezolid, and showed intermediate resistance to tobramycin, minocycline, ciprofloxacin, and doxycycline; it was resistant to amoxicillin-clavulanic acid, cefepime, clarithromycin, ceftriaxone, and imipenem. The patient was discharged on the 26th hospital day. Oral TMP–SMX was maintained for 6 months after discharge, and the patient has fully recovered from the nocardial infection. On follow up at the outpatient clinic for 1 year, he has had no sequelae related to nocardiosis.
Discussion N. concava is an aerobic Gram-positive, partial acid-alcohol-fast, non-motile actinomycete, and the name refers to its concave colony morphology on agar plates [4]. Until now, only two case reports of N. concava infection have been published worldwide. Interestingly, the previous case reports were from Japan and China, and the present case is from South Korea–all far East Asian countries. Additional isolation and reports of N. concava infection and epidemiologic study may yield further insights on whether this species is mainly distributed in Asian countries. Nocardiosis is characterized by abscess formation with extensive neutrophil infiltration and prominent necrosis [2]. The majority of cases present as pulmonary disease, and in half of the cases of pulmonary nocardiosis, disseminations to other parts of the body are present [2, 7]. Especially, the Nocardia have a predilection for invading the central nervous system, and brain abscesses in nocardial infections result from bacterial dissemination from the lung [8]. In our patient, the chest X-ray showed focal haziness in the right lower lobe, and the chest CT revealed an irregular consolidation, suggestive of organizing pneumonia in the right lower lobe of the lung. We assumed that this was the primary site of the nocardial infection. However, the brain MRI in our patient showed no evidence of dissemination to the brain despite the disseminated multiple muscle abscesses. Sulfa-containing antimicrobials are the drug of choice in nocardiosis, and our patient was treated with the combination of trimethoprim and sulfamethoxazole (TMP–SMX), which is
123
J Infect Chemother (2012) 18:764–766
probably equivalent to a sulfonamide alone [2, 7]. The present report is valuable as it clearly describes the clinical characteristics of N. concava infection, and the patient has completely recovered. In the previously reported Japanese cases, the N. concava was isolated from a 76-year-old female and a 69-year-old male, both with cutaneous nocardiosis [4], but there were no detailed clinical descriptions of the nocardial infections. In the Chinese case, the N. concava isolates were recovered from blood cultures from a 42-year-old man with disseminated nocardiosis, who finally died of multiple organ failure [5]. So, to our best knowledge, this is the first case report that gives a detailed clinical description of disseminated N. concava infection with a successful treatment outcome. Molecular methods such as RNA sequencing based on 16S rRNA are becoming an important tool for the identification of Nocardia species [3, 9], and RNA sequencing based on 16S rRNA is becoming the gold standard for the identification of nocardial isolates [5]. The present case is a good example of confirming newly proposed Nocardia species by a molecular diagnostic method with 16S rRNA sequencing. In conclusion, we report a case of N. concava infection in a patient with multiple abscesses in the extremities and lungs, who was successfully treated with TMP–SMX and abscess drainage.
References 1. Ambrosioni J, Lew D, Garbino J. Nocardiosis: updated clinical review and experience at a tertiary center. Infection. 2010;38: 89–97. 2. Filice GA. Norcardiosis. In: Longo DL, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J, editors. Harrison’s principles of internal medicine. 18th ed. New York: McGraw-Hill Professional; 2011. p. 1322–6. 3. Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ Jr. Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev. 2006;19:259–82. 4. Kageyama A, Yazawa K, Taniguchi H, Chibana H, Nishimura K, Kroppenstedt RM, et al. Nocardia concava sp. nov., isolated from Japanese patients. Int J Syst Evol Microbiol. 2005;55:2081–3. 5. Hu Y, Zheng D, Takizawa K, Mikami Y, Dai L, Yazawa K, et al. Systemic nocardiosis caused by Nocardia concava in China. Med Mycol. 2011;49:662–6. 6. CLSI. Interpretative criteria for identification of bacteria and fungi by DNA target sequencing; approved guideline. CLSI document MM18-A. Wayne: Clinical and Laboratory Standards Institute; 2008. p. 1–71. 7. Saubolle MA, Sussland D. Nocardiosis: review of clinical and laboratory experience. J Clin Microbiol. 2003;41:4497–501. 8. Frederick SS. Nocardiosis. In: Goldman L, Schafer AI, editors. Goldman’s Cecil medicine. 24th ed. Philadelphia: Elsevier Saunders; 2011. p. 1970. 9. Conville PS, Witebsky FG. Multiple copies of the 16S rRNA gene in Nocardia nova isolates and implications for sequence-based identification procedures. J Clin Microbiol. 2005;43:2881–5.
CASE REPORT
The first report of disseminated Nocardia concava infection, in an immunocompromised patient, in South Korea Seung-Hoon Lee • Heungseop Sung • Sang-Oh Lee • Sang-Ho Choi • Yang-Soo Kim Jun-Hee Woo • Sung-Han Kim
•
Received: 10 August 2011 / Accepted: 22 December 2011 / Published online: 24 April 2012 Ó Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2012
Abstract A new Nocardia species, N. concava, was first reported in Japan in 2005. To date, there have been only 3 case reports of N. concava infection worldwide (2 in Japan and 1 in China), and only 1 of these reports has detailed the clinical characteristics of N. concava, in China. Here we report the first case of disseminated infection caused by N. concava– in a patient with a history of glucocorticoid use–in South Korea. Species identification of N. concava was done with 16S rRNA sequencing and was confirmed by biochemical tests using urea, xanthine, tyrosine, and hypoxanthine decomposition. The patient was successfully treated with trimethoprim–sulfamethoxazole. Keywords Disseminated nocardiosis Korea Nocardia concava
During the past decade, molecular techniques such as polymerase chain reaction (PCR) restriction enzyme assay analysis and 16S rRNA sequencing have enabled the accurate and rapid identification of many Nocardia species [3]. In 2005, Kageyama et al. [4] reported a new Nocardia species, Nocardia concava, which was isolated from the blood of two Japanese patients with cutaneous nocardiosis, in 1991 and 1995, respectively. To our knowledge, there have been only 3 case reports of N. concava infection reported worldwide, the first one in Japan (two cases) [4, 5] and the other in China [4, 5]. We report a case of N. concava infection in a patient who had received longterm corticosteroid therapy who had multiple abscesses in all four extremities and the lung.
Case report Introduction Nocardiosis is an opportunistic infection that occurs mainly in patients with impaired cell-mediated immunity especially associated with lymphoma, transplantation, glucocorticoid therapy, or AIDS [1, 2]. N. asteroids is the most common cause of nocardiosis, and N. brasiliensis, N. otitidiscaviarum, and N. farcinica may also cause human disease [2].
S.-H. Lee S.-O. Lee S.-H. Choi Y.-S. Kim J.-H. Woo S.-H. Kim (&) Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poonganp dong, Songpa-gu, Seoul 138-736, South Korea e-mail: [email protected] H. Sung Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
123
A 64-year-old man whose medical history included alcoholic liver cirrhosis of Child-Pugh classification B, with membranous glomerulopathy (MGN), was admitted because of fever and chills of 3 weeks’ duration. MGN had been diagnosed from a kidney biopsy when the patient was 58 years old. He had been on corticosteroid therapy for 2 months prior to admission to control the MGN, and was taking 15 mg oral prednisolone every 24 h. He had no cough, sputum, or headache. On examination, there was a tender mass in the right upper arm, and body temperature was 35.8°C. His blood pressure was 69/48 mmHg, pulse rate 85 beats per minute, and respiration rate was 20 per minute. Lung sound was clear with decreased breathing sound in the posterior right lower lung field. A chest X-ray showed haziness in the right lower lobe with a blunted right cardiophrenic angle. Magnetic resonance imaging (MRI) with
J Infect Chemother (2012) 18:764–766
765
Fig. 2 Gram stain (91,000) of the right deltoid muscle abscess showing Gram-positive, crooked, branching, beaded filaments
Fig. 1 T1-weighted magnetic resonance imaging (MRI) with enhancement of the right upper extremity in a patient with membranous glomerulonephropathy and long-term glucocorticoid use. The patient had a deltoid muscle abscess, and the MRI shows a septated cystic lesion of about 4 9 4 9 10 cm in the deltoid muscle with peripheral wall thickening and both cellulitis and fasciitis
enhancement of the right upper extremity was done and there was a septated cystic lesion in the right deltoid muscle with peripheral thickening and septal enhancement (Fig. 1). Aspiration of the right deltoid muscle abscess was performed, followed by incision and a drainage operation. On the 4th hospital day, a Gram stain of the right deltoid muscle abscess showed crooked, branching Gram-positive filaments, and a modified acid-fast bacillus (AFB) stain showed a positive result, suggesting nocardial infection (Fig. 2). The antibiotic agent was changed from cefazolin and ciprofloxacin to intravenous trimethoprim–sulfamethoxazole (TMP–SMX). The patient continued to take oral prednisolone 10 mg every 24 h to control the MGN. On the 5th day, the patient complained of pain and tenderness in both legs and there were 10 9 10 cm movable, fluctuating palpable masses in the right posterior calf and left posterior thigh. Ultrasonography-guided aspiration was done and Gram stain showed crooked, branching, beaded filaments. High-resolution computed tomography (CT), which was carried out to evaluate the focal haziness on the chest radiography, showed multiple irregular consolidations in the right lower lobe (Fig. 3). To identify the dissemination of nocardial infection, brain MRI with enhancement was done, and there was no evidence of nocardiosis involvement in the brain parenchyma or leptomeninges. On the 10th day, cultures from the right
Fig. 3 High resolution computed tomography (CT) scan of the patient reported here who had right lower-lobe haziness on chest radiography. The CT scan shows an irregular mass abutting the major fissure and right diaphragmatic pleura and another small nodule in the right lower lobe
deltoid muscle abscess, the right posterior calf abscess, and the left posterior thigh abscess showed Nocardia species. Our Nocardia grew at 37°C but not at 45°C. For species identification, 16S rRNA sequencing with PCR was done. For the identification of this isolate and reference strains of N. concava (IFM 0354) we used two sets of primers covering nucleotides 30–1,370. For sequence comparison, 16S rRNA gene sequences were taken from the GenBank database. The sequence homology of the 16S rRNA gene of our isolate was 100% identical with N. concava IFM 0354T (1,341/1,341), 98.3% identical with N. seriole DSM 44129 (1,322/1,345, gaps 8/1,345), and 98.0% identical with N. seriole ATCC 43993T (1,319/ 1,346, gaps 10/1,346). We were able to identify the genus and species of our Nocardia according to the guidelines for
123
766
DNA sequencing of aerobic actinomycetes, proposed by the Clinical and Laboratory Standards Institute [6]. In addition, we performed biochemical tests. The urea decomposition test result was weakly positive. Xanthine, tyrosine, and hypoxanthine decomposition test results were positive, and the casein decomposition test was negative. With all these results, we were able to discriminate N. concava from N. seriole, which has high similarity of the 16S rRNA sequence to that of N. concava [4]. An antibiotic susceptibility test was done by the broth dilution method, using a Sensititer RGMYCO (Biocentric, Bandol, France) panel. The isolated organism was susceptible to TMP–SMX, amikacin, and linezolid, and showed intermediate resistance to tobramycin, minocycline, ciprofloxacin, and doxycycline; it was resistant to amoxicillin-clavulanic acid, cefepime, clarithromycin, ceftriaxone, and imipenem. The patient was discharged on the 26th hospital day. Oral TMP–SMX was maintained for 6 months after discharge, and the patient has fully recovered from the nocardial infection. On follow up at the outpatient clinic for 1 year, he has had no sequelae related to nocardiosis.
Discussion N. concava is an aerobic Gram-positive, partial acid-alcohol-fast, non-motile actinomycete, and the name refers to its concave colony morphology on agar plates [4]. Until now, only two case reports of N. concava infection have been published worldwide. Interestingly, the previous case reports were from Japan and China, and the present case is from South Korea–all far East Asian countries. Additional isolation and reports of N. concava infection and epidemiologic study may yield further insights on whether this species is mainly distributed in Asian countries. Nocardiosis is characterized by abscess formation with extensive neutrophil infiltration and prominent necrosis [2]. The majority of cases present as pulmonary disease, and in half of the cases of pulmonary nocardiosis, disseminations to other parts of the body are present [2, 7]. Especially, the Nocardia have a predilection for invading the central nervous system, and brain abscesses in nocardial infections result from bacterial dissemination from the lung [8]. In our patient, the chest X-ray showed focal haziness in the right lower lobe, and the chest CT revealed an irregular consolidation, suggestive of organizing pneumonia in the right lower lobe of the lung. We assumed that this was the primary site of the nocardial infection. However, the brain MRI in our patient showed no evidence of dissemination to the brain despite the disseminated multiple muscle abscesses. Sulfa-containing antimicrobials are the drug of choice in nocardiosis, and our patient was treated with the combination of trimethoprim and sulfamethoxazole (TMP–SMX), which is
123
J Infect Chemother (2012) 18:764–766
probably equivalent to a sulfonamide alone [2, 7]. The present report is valuable as it clearly describes the clinical characteristics of N. concava infection, and the patient has completely recovered. In the previously reported Japanese cases, the N. concava was isolated from a 76-year-old female and a 69-year-old male, both with cutaneous nocardiosis [4], but there were no detailed clinical descriptions of the nocardial infections. In the Chinese case, the N. concava isolates were recovered from blood cultures from a 42-year-old man with disseminated nocardiosis, who finally died of multiple organ failure [5]. So, to our best knowledge, this is the first case report that gives a detailed clinical description of disseminated N. concava infection with a successful treatment outcome. Molecular methods such as RNA sequencing based on 16S rRNA are becoming an important tool for the identification of Nocardia species [3, 9], and RNA sequencing based on 16S rRNA is becoming the gold standard for the identification of nocardial isolates [5]. The present case is a good example of confirming newly proposed Nocardia species by a molecular diagnostic method with 16S rRNA sequencing. In conclusion, we report a case of N. concava infection in a patient with multiple abscesses in the extremities and lungs, who was successfully treated with TMP–SMX and abscess drainage.
References 1. Ambrosioni J, Lew D, Garbino J. Nocardiosis: updated clinical review and experience at a tertiary center. Infection. 2010;38: 89–97. 2. Filice GA. Norcardiosis. In: Longo DL, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J, editors. Harrison’s principles of internal medicine. 18th ed. New York: McGraw-Hill Professional; 2011. p. 1322–6. 3. Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ Jr. Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev. 2006;19:259–82. 4. Kageyama A, Yazawa K, Taniguchi H, Chibana H, Nishimura K, Kroppenstedt RM, et al. Nocardia concava sp. nov., isolated from Japanese patients. Int J Syst Evol Microbiol. 2005;55:2081–3. 5. Hu Y, Zheng D, Takizawa K, Mikami Y, Dai L, Yazawa K, et al. Systemic nocardiosis caused by Nocardia concava in China. Med Mycol. 2011;49:662–6. 6. CLSI. Interpretative criteria for identification of bacteria and fungi by DNA target sequencing; approved guideline. CLSI document MM18-A. Wayne: Clinical and Laboratory Standards Institute; 2008. p. 1–71. 7. Saubolle MA, Sussland D. Nocardiosis: review of clinical and laboratory experience. J Clin Microbiol. 2003;41:4497–501. 8. Frederick SS. Nocardiosis. In: Goldman L, Schafer AI, editors. Goldman’s Cecil medicine. 24th ed. Philadelphia: Elsevier Saunders; 2011. p. 1970. 9. Conville PS, Witebsky FG. Multiple copies of the 16S rRNA gene in Nocardia nova isolates and implications for sequence-based identification procedures. J Clin Microbiol. 2005;43:2881–5.