Bacteremia due to Rhodococcus equi: a case report and review of the literature

Bacteremia due to Rhodococcus equi : a case report and review of the literature 1 first-author 1 corresp ‡Corresponding Author ‡Corresponding Author †E-mail:xufeng99@yahoo.com †E-mail:xufeng99@yahoo.com xufeng99@yahoo.com 2 1 1 Department of Respiratory Medicine, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China Department of Respiratory Medicine, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China Department of Radiotherapy, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China Department of Radiotherapy, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China Rhodococcus equi , previously known as Corynebacterium equi , is one of the most important causes of zoonotic infections in grazing animals. Increased cases of human infection with R . equi have been reported, especially in immunocompromised patients, within recent years. We present a case of R . equi bacteremia in a 51-year-old man with diabetes and liver cirrhosis, on long-term corticosteroid therapy after skin-grafting surgery. The patient recovered soon after he was treated with vancomycin. This review focuses on the microbiological characteristics of this organism, and the diagnosis and treatment of this infection. Rhodococcus equi Bacteremia Opportunistic pathogen INTRODUCTION 1 Since the advent of the acquired immunodeficiency syndrome (AIDS) epidemic, Rhodococcus equi has been emerging as an opportunistic pathogen, especially in immunocompromised patients (Puthucheary et al., 2006 2006 ). Most patients infected with R . equi present with a pulmonary syndrome. Other infections include gastrointestinal infections, pericarditis, meningitis, mastoiditis, and abscesses in the liver, kidney, psoas muscles, and cutaneous wounds (Weinstock and Brown, 2002 2002 ; Roda et al., 2009 2009 ). Only a few cases of isolated bacteremia have been reported. Here we present a case of R . equi bacteremia in a 51 year-old man. The patient was treated with vancomycin and recovered quickly. The diagnosis of R . equi is often difficult due to microbiological and clinical similarities with other pathogens such as diphtheroids, mycobacterium species, or Nocardia , although it is easily cultured from sputum or blood. The aim of this report is to increase physician awareness about R . equi infection in immunocompromised patients. CASE REPORT 1 A 51-year-old man was admitted to our hospital with fever, dizziness, nausea, vomiting, and diarrhea. Eighteen days before admission, he had a fever followed by dizziness. He went to a local hospital where antibiotics (specific type unknown) were prescribed, and his dizziness was eased, while the temperature remained around 38.5 °C. Three days before admission, he developed nausea, vomiting, and diarrhea. He denied headache, seizure, cough, chest, or abdominal pain. The patient could not recall any contact with animals recently. His past medical history included diabetes and cirrhosis secondary to chronic viral hepatitis B. He had a history of a skin-grafting surgery on his left leg one year prior and received prolonged treatment with antibiotics and systemic glucocorticoids. He did not travel recently and had no known illness contacts. On admission, physical examination was only remarkable for fever of 38.9 °C. The results of laboratory examinations were as follows: White blood cell (WBC) count was 11 100 cells/μl with 87% neutrophils, C reactive protein (CRP) level was 185.2 mg/L, and erythrocyte sedimentation rate (ESR) level was 91 mm/h. The results of both tuberculin skin testing with purified protein derivative (PPD) and PPD antibodies were negative. Anti-nuclear antibody (ANA), anti-ds-DNA antibody, extractable nuclear antigen (ENA), and serum tumor markers were also negative. Human immunodeficiency virus (HIV) serology was negative. Urine and stool examination revealed no abnormal findings. Liver and renal function tests and a chest X-ray were normal. An ultrasonic cardiography revealed mild pericardial effusion and an electrocardiogram showed low voltages. After empiric antibiotic treatment with levofloxacin for 4 d, the patient’s condition showed no improvement with persistent fever as high as 39 °C, and new symptoms of cough and white sputum appeared. One week after his admission, blood cultures showed large Gram-positive coccobacillus with the microbiologic characteristics shown in Table 1 1 , and this organism was finally identified as R . equi . After aggressive treatment with vancomycin for 4 d, the temperature of the patient started to return to normal. The patient finally recovered with a combination of vancomycin and sulbactam/cefoperazone administered for another 5 d. He was discharged on oral rifampin after the two negative blood cultures. Test Result  Catalase +  Urease +  CAMP +  Oxidase −  Carbohydrate fermentation −  Mannitol −  Gelatin hydrolysis −  Indole −  Nitrate reduction −  Citric acid − REVIEW OF THE LITERATURE 1 Rhodococcus equi , previously known as Corynebacterium equi , is a Gram-positive pleomorphic coccobacillus. The natural habitat of R . equi is soil contaminated with animal manure. It primarily causes zoonotic infections that affect grazing animals, mainly horses and foals. Since the first case of human infection of R . equi reported in 1967 (Golub et al., 1967 1967 ), only 12 additional cases were reported by Lipsky et al.( 1982 1982 ). However, with the AIDS epidemic, this number has greatly increased. Since then, hundreds of cases of human infection with R . equi have been reported (Weinstock and Brown, 2002 2002 ). Contact with animals or animal-contaminated soil is thought to initiate infection, but a specific exposure is recalled in less than 50% of cases. The route of infection from animals to humans remains unclear. However, transmission via respiratory secretions was postulated in some case reports (Cronin et al., 2008 2008 ). R . equi mainly affects immunocompromised patients, especially those with HIV infection. Cases have also been reported after solid organ transplantation, hematopoietic stem cell transplantation, splenectomy, corticosteroid use, and in patients with end stage liver disease (Roda et al., 2009 2009 ; Tse et al., 2008 2008 ; Kedlaya et al., 2001 2001 ). Infection in immunocompetent patients is thus extremely rare. The mortality rate among immunocompetent patients is approximately 11%, compared with rates of 50%~55% among HIV-infected patients and 20%~25% among non-HIV-infected immunocompromised patients (Alonso et al., 2001 2001 ). Our patient had a history of diabetes and liver cirrhosis, and also received long-term corticosteroid therapy after skin-grafting surgery. Most patients initially have a pulmonary syndrome, with findings including infiltrates, empyema, and cavitary lesions (Marchiori et al., 2006 2006 ). It has been concluded that the most common finding in patients with AIDS and pulmonary infection due to R . equi was consolidated with cavitation (Kamboj et al., 2005 2005 ). Less frequent manifestations include gastrointestinal infections, pericarditis, meningitis, mastoiditis, and abscesses in the liver, kidney, psoas muscles, and contaminated cutaneous wounds. The disease is commonly chronic and recurrent. Relapse may follow a course of brief antimicrobial therapy, but can also occur during treatment. Malakoplakia is an uncommon inflammatory disorder associated with immunosuppression. In a rare report, R . equi was even isolated from malakoplakia lesions (Wagner et al., 2007 2007 ). R . equi is an intracellular pathogen that can survive inside macrophages. The typical histologic pattern shows a predominance of macrophages having granular cytoplasm that is filled with periodic acid-Schiff (PAS)-positive coccobacilli. Blood and sputum cultures offer the best yield for the diagnosis of this infection. The bacterium grows optimally at 30 °C on solid ordinary non-selective media and forms large, irregular, mucoid colonies that turn to a salmon-pink color within 48 h (Cronin et al., 2008 2008 ). It is a facultative, encapsulated, nonmotile, non-spore forming, Gram-positive coccobacillus, which is partially acid-fast staining and bears a similarity to diphtheroids. R . equi can be differentiated from other pathogenic corynebacteria by its mycolic acid staining content and lack of ability to ferment carbohydrates or liquefy gelatin (Perez et al., 2002 2002 ). A particular characteristic of this organism is that it causes synergistic hemolytic reaction with sphingomyelinase-producing bacteria such as Staphylococcus aureus and Listeria ivanovii , based on Christie Atkins Munch-Petersen (CAMP) test (Puthucheary et al., 2006 2006 ). Characteristics used in routine clinical microbiology laboratories to identify R . equi are catalase (+), oxidase (−), carbohydrate fermentation (−), alcohol fermentation (−), gelatin hydrolysis (−), indole (−), urease (+), hippurate hydrolysis (−), esculin hydrolysis (−), nitrate reduction (+), equi factors (+), lipase (+), and phosphatase (+) (Prescott, 1991 1991 ). R . equi may be misidentified as diphtheroids, Mycobacterium species, or Nocardia . The isolation of difficult-to-identify, Gram-positive rods from the patients with decreased cell-mediated immunity should raise the possibility of R . equi . Additionally, R . equi -specific polymerase chain reaction (PCR), which is based on the amplification of a fragment of the choE gene, can be a useful confirmatory test in human infection (Ladrón et al., 2003 2003 ). The organism has generally shown in vitro susceptibility to erythromycin, rifampin, vancomycin, fluoroquinolones, aminoglycosides, and imipenem/cilastatin, and resistance to penicillins, although this can vary in specific geographic areas or from previous antibiotic therapy (Torres-Tortosa et al., 2003 2003 ). This organism can inhibit macrophage phagosome-lysosome fusion and survives intracellularly. Although there is no consensus on the optimal duration and regimen of antibiotic treatment, combination antimicrobial therapy using bactericidal and intracellularly active agents should be considered (Torres-Tortosa et al., 2003 2003 ). A carbapenem and a glycopeptide, such as meropenem and vancomycin, are good choices (Tse et al., 2008 2008 ). The use of combination therapy may decrease the risk of developing resistance during therapy, which has been described with penicillin and other beta-lactam antibiotics. The combination of macrolides and rifampin can also be considered (Prescott, 1991 1991 ). After initial improvement, the patient can be treated with an oral regimen that could include combinations of quinolones, tetracycline, macrolides, and rifampin. The optimal duration of treatment is unknown. Based on similar experiences with difficult-to-treat organisms like Mycobacterium tuberculosis , and on the fact that distant relapses of Rhodococcus infection are common, prolonged therapy is recommended (e.g., 9 months) (Kedlaya et al., 2001 2001 ). Torres-Tortosa et al.( 2003 2003 ) reported that highly active antiretroviral therapy can improve prognosis of patients with HIV infected by R . equi . In conclusion, R . equi mainly affects immunocompromised patients, especially those with HIV infection. The isolation of Gram-positive rods from immunosuppressed patients should raise the possibility of R . equi and ongoing communication with the microbiology laboratory can help identify this difficult-to-treat organism. References P Alonso , KT Tashima , IJ Goldstein . Disseminated Rhodococcus equi infection . Clin Infect Dis , 2001 . 32 ( 6 ): 970 - 971 . DOI: 10.1086/319367 http://doi.org/10.1086/319367 . Disseminated Rhodococcus equi infection SM Cronin , MH Abidi , CJ Shearer , PH Chandrasekar , RB Ibrahim . Rhodococcus equi lung infection in an allogeneic hematopoietic stem cell transplant recipient . Transpl Infect Dis , 2008 . 10 ( 1 ): 48 - 51 . 17714438 DOI: 10.1111/j.1399-3062.2007.00274.x http://doi.org/10.1111/j.1399-3062.2007.00274.x . Rhodococcus equi lung infection in an allogeneic hematopoietic stem cell transplant recipient B Golub , G Falk , WW Spink . Lung abscess due to Corynebacterium equi . Report of first human infection . Ann Intern Med , 1967 . 66 ( 6 ): 1174 - 1177 . 6067513 . Lung abscess due to Corynebacterium equi. Report of first human infection M Kamboj , A Kalra , V Kak . Rhodococcus equi brain abscess in a patient without HIV . J Clin Pathol , 2005 . 58 ( 4 ): 423 - 425 . 15790711 DOI: 10.1136/jcp.2004.019471 http://doi.org/10.1136/jcp.2004.019471 . Rhodococcus equi brain abscess in a patient without HIV I Kedlaya , MB Ing , SS Wong . Rhodococcus equi infections in immunocompetent hosts: case report and review . Clin Infect Dis , 2001 . 32 ( 3 ): 39 - 46 . DOI: 10.1086/318520 http://doi.org/10.1086/318520 . Rhodococcus equi infections in immunocompetent hosts: case report and review N Ladrón , M Fernández , J Aguero , BG Zörn , JA Vázquez-Boland , J Navas . Rapid identification of Rhodococcus equi by a PCR assay targeting the choE gene . J Clin Microbiol , 2003 . 41 ( 7 ): 3241 - 3245 . 12843070 DOI: 10.1128/JCM.41.7.3241-3245.2003 http://doi.org/10.1128/JCM.41.7.3241-3245.2003 . Rapid identification of Rhodococcus equi by a PCR assay targeting the choE gene BA Lipsky , AC Goldberger , LS Tompkins , JJ Plorde . Infections caused by nondiphtheria corynebacteria . Rev Infect Dis , 1982 . 4 ( 6 ): 1220 - 1235 . 6760340 . Infections caused by nondiphtheria corynebacteria E Marchiori , RG de Mendonça , D Capone , EM de Cerqueira , AS Souza Júnior , G Zanetti , D Escuissato , E Gasparetto . Rhodococcus equi infection in acquired immunodeficiency syndrome. Computed tomography aspects . J Bras Pneumol , 2006 . 32 ( 5 ): 405 - 409 . 17268743 DOI: 10.1590/S1806-37132006000500006 http://doi.org/10.1590/S1806-37132006000500006 . Rhodococcus equi infection in acquired immunodeficiency syndrome. Computed tomography aspects MG Perez , T Vassilev , SA Kemmerly . Rhodococcus equi infection in transplant recipients: a case of mistaken identity and review of the literature . Transpl Infect Dis , 2002 . 4 ( 1 ): 52 - 56 . 12123427 DOI: 10.1034/j.1399-3062.2002.01001.x http://doi.org/10.1034/j.1399-3062.2002.01001.x . Rhodococcus equi infection in transplant recipients: a case of mistaken identity and review of the literature JF Prescott . Rhodococcus equi : an animal and human pathogen . Clin Microbiol Rev , 1991 . 4 ( 1 ): 20 - 34 . 2004346 . Rhodococcus equi: an animal and human pathogen SD Puthucheary , V Sangkar , A Hafeez , R Karunakaran , NS Raja , HH Hassan . Rhodococcus equi —an emerging human pathogen in immunocompromized hosts: a report of four cases from Malaysia . Southeast Asian J Trop Med Public Health , 2006 . 37 ( 1 ): 157 - 161 . 16771229 . Rhodococcus equi—an emerging human pathogen in immunocompromized hosts: a report of four cases from Malaysia RH Roda , M Young , J Timpone , J Rosen . Rhodococcus equi pulmonary-central nervous system syndrome: brain abscess in a patient on high-dose steroids-a case report and review of the literature . Diagn Microbiol Infect Dis , 2009 . 63 ( 1 ): 96 - 99 . 19073303 DOI: 10.1016/j.diagmicrobio.2008.08.024 http://doi.org/10.1016/j.diagmicrobio.2008.08.024 . Rhodococcus equi pulmonary-central nervous system syndrome: brain abscess in a patient on high-dose steroids-a case report and review of the literature M Torres-Tortosa , J Arrizabalaga , JL Villanueva , J Gálvez , M Leyes , ME Valencia , J Flores , JM Peña , E Pérez-Cecilia , C Quereda . Prognosis and clinical evaluation of infection caused by Rhodococcus equi in HIV-infected patients. A multicenter study of 67 cases . Chest , 2003 . 123 ( 6 ): 1970 - 1976 . 12796176 DOI: 10.1378/chest.123.6.1970 http://doi.org/10.1378/chest.123.6.1970 . Prognosis and clinical evaluation of infection caused by Rhodococcus equi in HIV-infected patients. A multicenter study of 67 cases KC Tse , SC Tang , TM Chan , KN Lan . Rhodococcus lung abscess complicating kidney transplantation: successful management by combination antibiotic therapy . Transpl Infect Dis , 2008 . 10 ( 1 ): 44 - 47 . 17428277 DOI: 10.1111/j.1399-3062.2007.00231.x http://doi.org/10.1111/j.1399-3062.2007.00231.x . Rhodococcus lung abscess complicating kidney transplantation: successful management by combination antibiotic therapy D Wagner , J Joseph , J Huang , H Xu . Malakoplakia of the prostate on needle core biopsy: a case report and review of the literature . Int J Surg Pathol , 2007 . 15 ( 1 ): 86 - 89 . 17172507 DOI: 10.1177/1066896906295892 http://doi.org/10.1177/1066896906295892 . Malakoplakia of the prostate on needle core biopsy: a case report and review of the literature DM Weinstock , AE Brown . Rhodococcus equi : an emerging pathogen . Clin Infect Dis , 2002 . 34 ( 10 ): 1379 - 1385 . 11981734 DOI: 10.1086/340259 http://doi.org/10.1086/340259 . Rhodococcus equi: an emerging pathogen 10.1631/jzus.B0920214 Project supported by the National Natural Science Foundation of China (No. 30871130) and the Youth Talent Special Fund of the Health Bureau of Zhejiang Province, China (No. 2008QN016) 2009-07-21 2009-11-16 2009-10-22 2022-01-05 Copyright © 2009, Journal of Zhejiang University Science 2009 Journal of Zhejiang University-SCIENCE B (Biomedicine and Biotechnology) 12 10