Treatment of nocardiosis
- Denis Spelman, MBBS, FRACP, FRCPA, MPH
Denis Spelman, MBBS, FRACP, FRCPA, MPH
- Adjunct Professor, Monash University
- Alfred Hospital, Victoria, Australia
Nocardiosis is an uncommon gram-positive bacterial infection caused by aerobic actinomycetes in the genus Nocardia. Nocardia spp have the ability to cause localized or systemic suppurative disease in humans and animals [1-5]. Nocardiosis is typically regarded as an opportunistic infection, but approximately one-third of infected patients are immunocompetent .
Two characteristics of nocardiosis are its ability to disseminate to virtually any organ, particularly the central nervous system, and its tendency to relapse or progress despite appropriate therapy.
The treatment of nocardiosis will be reviewed here. The microbiology, epidemiology, pathogenesis, clinical manifestations, and diagnosis of nocardiosis are discussed separately. (See "Microbiology, epidemiology, and pathogenesis of nocardiosis" and "Clinical manifestations and diagnosis of nocardiosis".)
Reported antimicrobial susceptibility patterns have varied among different studies, countries, and Nocardia species (table 1). In a retrospective review of 765 isolates submitted voluntarily to the United States Centers for Disease Control and Prevention (CDC) between 1995 and 2004, 42 percent were resistant to trimethoprim-sulfamethoxazole (TMP-SMX) and 61 percent were resistant to sulfamethoxazole . This incidence of resistance is significantly higher than in other reports. There are limitations to this study, with the authors concluding that the presented data are probably not representative of all United States cases. As an example, patients who were not responding to treatment due to resistance may have been more likely to have had their isolates sent to the CDC than patients with susceptible isolates who were responding to treatment.
In contrast, in a study of 552 clinical isolates collected from six major medical referral centers in the United States between 2005 and 2011, which was prompted by the unexpected results of the CDC study, only 2 percent of isolates were resistant to TMP-SMX and/or sulfamethoxazole . Possible reasons for the discrepancy between these results and the results of the CDC study are that there might have been differences in the preparation of samples and/or the interpretation of results of in vitro susceptibility testing .
- 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.
- Lerner PI. Nocardiosis. Clin Infect Dis 1996; 22:891.
- Lederman ER, Crum NF. A case series and focused review of nocardiosis: clinical and microbiologic aspects. Medicine (Baltimore) 2004; 83:300.
- Beaman BL, Burnside J, Edwards B, Causey W. Nocardial infections in the United States, 1972-1974. J Infect Dis 1976; 134:286.
- Beaman BL, Beaman L. Nocardia species: host-parasite relationships. Clin Microbiol Rev 1994; 7:213.
- Uhde KB, Pathak S, McCullum I Jr, et al. Antimicrobial-resistant nocardia isolates, United States, 1995-2004. Clin Infect Dis 2010; 51:1445.
- Brown-Elliott BA, Biehle J, Conville PS, et al. Sulfonamide resistance in isolates of Nocardia spp. from a US multicenter survey. J Clin Microbiol 2012; 50:670.
- Conville PS, Brown-Elliott BA, Wallace RJ Jr, et al. Multisite reproducibility of the broth microdilution method for susceptibility testing of Nocardia species. J Clin Microbiol 2012; 50:1270.
- Lai CC, Liu WL, Ko WC, et al. Antimicrobial-resistant nocardia isolates, Taiwan, 1998-2009. Clin Infect Dis 2011; 52:833.
- Ambrosioni J, Lew D, Garbino J. Nocardiosis: updated clinical review and experience at a tertiary center. Infection 2010; 38:89.
- Coussement J, Lebeaux D, van Delden C, et al. Nocardia Infection in Solid Organ Transplant Recipients: A Multicenter European Case-control Study. Clin Infect Dis 2016; 63:338.
- Valdezate S, Garrido N, Carrasco G, et al. Epidemiology and susceptibility to antimicrobial agents of the main Nocardia species in Spain. J Antimicrob Chemother 2017; 72:754.
- McTaggart LR, Doucet J, Witkowska M, Richardson SE. Antimicrobial susceptibility among clinical Nocardia species identified by multilocus sequence analysis. Antimicrob Agents Chemother 2015; 59:269.
- Wallace RJ Jr, Tsukamura M, Brown BA, et al. Cefotaxime-resistant Nocardia asteroides strains are isolates of the controversial species Nocardia farcinica. J Clin Microbiol 1990; 28:2726.
- Torres OH, Domingo P, Pericas R, et al. Infection caused by Nocardia farcinica: case report and review. Eur J Clin Microbiol Infect Dis 2000; 19:205.
- Wallace RJ Jr, Brown BA, Tsukamura M, et al. Clinical and laboratory features of Nocardia nova. J Clin Microbiol 1991; 29:2407.
- Khardori N, Shawar R, Gupta R, et al. In vitro antimicrobial susceptibilities of Nocardia species. Antimicrob Agents Chemother 1993; 37:882.
- Sorrell TC, Mitchell DH, Iredell JR. Nocardia species. In: Principles and Practice of Infectious Diseases, 6th ed, Mandell GL, Bennett JE, Dolin R (Eds), Elsevier, Philadelphia 2005. p.2916.
- McNeil MM, Brown JM, Georghiou PR, et al. Infections due to Nocardia transvalensis: clinical spectrum and antimicrobial therapy. Clin Infect Dis 1992; 15:453.
- Wallace RJ Jr, Steele LC, Sumter G, Smith JM. Antimicrobial susceptibility patterns of Nocardia asteroides. Antimicrob Agents Chemother 1988; 32:1776.
- Wilson RW, Steingrube VA, Brown BA, et al. Recognition of a Nocardia transvalensis complex by resistance to aminoglycosides, including amikacin, and PCR-restriction fragment length polymorphism analysis. J Clin Microbiol 1997; 35:2235.
- Cercenado E, Marín M, Sánchez-Martínez M, et al. In vitro activities of tigecycline and eight other antimicrobials against different Nocardia species identified by molecular methods. Antimicrob Agents Chemother 2007; 51:1102.
- Brown-Elliott BA, Ward SC, Crist CJ, et al. In vitro activities of linezolid against multiple Nocardia species. Antimicrob Agents Chemother 2001; 45:1295.
- Larruskain J, Idigoras P, Marimón JM, Pérez-Trallero E. Susceptibility of 186 Nocardia sp. isolates to 20 antimicrobial agents. Antimicrob Agents Chemother 2011; 55:2995.
- Al Akhrass F, Hachem R, Mohamed JA, et al. Central venous catheter-associated Nocardia bacteremia in cancer patients. Emerg Infect Dis 2011; 17:1651.
- 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 (Baltimore) 2014; 93:19.
- Wilson JP, Turner HR, Kirchner KA, Chapman SW. Nocardial infections in renal transplant recipients. Medicine (Baltimore) 1989; 68:38.
- Peleg AY, Husain S, Qureshi ZA, et al. Risk factors, clinical characteristics, and outcome of Nocardia infection in organ transplant recipients: a matched case-control study. Clin Infect Dis 2007; 44:1307.
- Smego RA Jr, Moeller MB, Gallis HA. Trimethoprim-sulfamethoxazole therapy for Nocardia infections. Arch Intern Med 1983; 143:711.
- Beaumont RJ. Trimethoprim as a possible therapy for nocardiosis and melioidosis. Med J Aust 1970; 2:1123.
- Wallace RJ Jr, Septimus EJ, Williams TW Jr, et al. Use of trimethoprim-sulfamethoxazole for treatment of infections due to Nocardia. Rev Infect Dis 1982; 4:315.
- Smith PW, Steinkraus GE, Henricks BW, Madson EC. CNS nocardiosis: response to sulfamethoxazole-trimethoprim. Arch Neurol 1980; 37:729.
- Threlkeld SC, Hooper DC. Update on management of patients with Nocardia infection. Curr Clin Top Infect Dis 1997; 17:1.
- McNeil MM, Brown JM, Hutwagner LC, Schiff TA . Evaluation of therapy for Nocardia asteroides complex infections. Infect Dis Clin Prac 1995; 4:287.
- Vera-Cabrera L, Gonzalez E, Choi SH, Welsh O. In vitro activities of new antimicrobials against Nocardia brasiliensis. Antimicrob Agents Chemother 2004; 48:602.
- Beaman BL, Boiron P, Beaman L, et al. Nocardia and nocardiosis. J Med Vet Mycol 1992; 30 Suppl 1:317.
- Fihman V, Berçot B, Mateo J, et al. First successful treatment of Nocardia farcinica brain abscess with moxifloxacin. J Infect 2006; 52:e99.
- Moylett EH, Pacheco SE, Brown-Elliott BA, et al. Clinical experience with linezolid for the treatment of nocardia infection. Clin Infect Dis 2003; 36:313.
- Naik S, Mateo-Bibeau R, Shinnar M, et al. Successful treatment of Nocardia nova bacteremia and multilobar pneumonia with clarithromycin in a heart transplant patient. Transplant Proc 2007; 39:1720.
- Nizam I, Kohan L, Kerr D. Nocardia nova septic arthritis following total knee replacement: a case report. J Orthop Surg (Hong Kong) 2007; 15:390.
- Attassi K, Hershberger E, Alam R, Zervos MJ. Thrombocytopenia associated with linezolid therapy. Clin Infect Dis 2002; 34:695.
- Bishop E, Melvani S, Howden BP, et al. Good clinical outcomes but high rates of adverse reactions during linezolid therapy for serious infections: a proposed protocol for monitoring therapy in complex patients. Antimicrob Agents Chemother 2006; 50:1599.
- Arenas R, Ameen M. Giant grains of nocardia actinomycetoma. Lancet Infect Dis 2010; 10:66.
- Ameen M, Arenas R, Vásquez del Mercado E, et al. Efficacy of imipenem therapy for Nocardia actinomycetomas refractory to sulfonamides. J Am Acad Dermatol 2010; 62:239.
- Clark NM, Reid GE, AST Infectious Diseases Community of Practice. Nocardia infections in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:83.
- Uttamchandani RB, Daikos GL, Reyes RR, et al. Nocardiosis in 30 patients with advanced human immunodeficiency virus infection: clinical features and outcome. Clin Infect Dis 1994; 18:348.
- Lebeaux D, Freund R, van Delden C, et al. Outcome and Treatment of Nocardiosis After Solid Organ Transplantation: New Insights From a European Study. Clin Infect Dis 2017; 64:1396.
- Geiseler PJ, Andersen BR. Results of therapy in systemic nocardiosis. Am J Med Sci 1979; 278:188.
- Hardak E, Yigla M, Berger G, et al. Clinical spectrum and outcome of Nocardia infection: experience of 15-year period from a single tertiary medical center. Am J Med Sci 2012; 343:286.
- Mamelak AN, Obana WG, Flaherty JF, Rosenblum ML. Nocardial brain abscess: treatment strategies and factors influencing outcome. Neurosurgery 1994; 35:622.
- Lee GY, Daniel RT, Brophy BP, Reilly PL. Surgical treatment of nocardial brain abscesses. Neurosurgery 2002; 51:668.
- Poland GA, Jorgensen CR, Sarosi GA. Nocardia asteroides pericarditis: report of a case and review of the literature. Mayo Clin Proc 1990; 65:819.
- Leang B, Lynen L, Lim K, et al. Disseminated nocardiosis presenting with cardiac tamponade in an HIV patient. Int J STD AIDS 2004; 15:839.
- Wallis RS, Broder MS, Wong JY, et al. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 2004; 38:1261.
- Simpson GL, Stinson EB, Egger MJ, Remington JS. Nocardial infections in the immunocompromised host: A detailed study in a defined population. Rev Infect Dis 1981; 3:492.
- King CT, Chapman SW, Butkus DE. Recurrent nocardiosis in a renal transplant recipient. South Med J 1993; 86:225.
- van Burik JA, Hackman RC, Nadeem SQ, et al. Nocardiosis after bone marrow transplantation: a retrospective study. Clin Infect Dis 1997; 24:1154.
- Chouciño C, Goodman SA, Greer JP, et al. Nocardial infections in bone marrow transplant recipients. Clin Infect Dis 1996; 23:1012.
- Walensky, RP, Moore, RD. A case series of 59 patients with nocardiosis. Infect Dis Clin Pract 2001; 10:249.
- ANTIBIOTIC SUSCEPTIBILITY
- Approach to antimicrobial therapy
- - Trimethoprim-sulfamethoxazole
- - Other agents
- Cutaneous infection
- - Isolated cutaneous infection
- - Mycetoma
- - Duration of treatment
- Mild to moderate pulmonary disease
- Severe infection
- - Initial intravenous therapy
- - Switch to oral therapy
- - Sulfonamide resistance or allergy
- - Duration of treatment
- - Outcomes
- - Monitoring
- Treatment failures
- Patients on immunosuppressive therapy
- Secondary prophylaxis
- SUMMARY AND RECOMMENDATIONS