Nocardiosis: a Review of Clinico- Microbiological Features

Int. J. LifeSc. Bt & Pharm. Res. 2013 Prakriti Vohra et al., 2013

Prakriti Vohra1*, Madhu Sharma1, Aparna Yadav1 and Uma Chaudhary1

*Corresponding Author: Prakriti Vohra,  [email protected]

Nocardiae cause a variety of suppurative infections in humans and animals. The manifestations of nocardiosis can be solely pulmonary, but Nocardia species can also disseminate from a pulmonary or cutaneous focus to virtually any organ. In patients with suspected Nocardial infection and a compatible clinical picture, a definitive diagnosis usually depends on demonstration of the organisms in smears or sections examined microscopically prior to isolation and identification of the causal agent. The greatest clinical experience in the treatment of nocardiosis is with the sulphonamides, and these remain the drugs of choice.

Keywords: Nocardiosis, Clinical manifestations, Laboratory diagnosis, Management

INTRODUCTION 1996; and Saubolle and Sussland, 2003). The disease has universal distribution (Corti and Nocardiosis is an infrequent but severe bacterial Villafañe-Fioti, 2003). Males suffer from infection that commonly presents as a subacute Nocardiosis more frequently than females. Most or chronic, suppurative or less frequently granulo- workers found that males out numbered females matous disease, caused by the soil-inhabiting by a ratio of 3:1 (Curry, 1980). aerobic actinomycetes belonging to the genus Nocardia (Singh et al., 2000). The disease occurs Trevisan named the genus Nocardia for Nocard not only in compromised hosts but may occur in who, in 1889, described an aerobic actinomycete immunologically intact individuals (Malik et al., 1980). from bovine farcy, a lymphatic disease of cattle Nocardiae are saprophytic, making an caused by Nocardia farcinia. Eppinger (1890), important component of the normal soil microflora first described nocardiosis in man in a report of a and are often being associated with water. They pulmonary disease with “pseudotuberculosis” of may also be associated with decomposing plant lungs and pleura, caseous peribronchial lymph material, dust and air. Nocardial infections are not nodes, meningitis and multiple abscesses in the thought to be transmitted from person to person brain. Branched hyphae were present in stained and are not usually acquired nosocomially (Lerner, films of pus. Eppinger erroneuously assigned the

1 Department of Microbiology, Pt. B D Sharma, PGIMS, Rohtak.

This article can be downloaded from http://www.ijlbpr.com/currentissue.php 20 Int. J. LifeSc. Bt & Pharm. Res. 2013 Prakriti Vohra et al., 2013 organism to the genus name Cladothrix and regional nodes and, occasionally, by direct spread Blanchard transferred it to Nocardia in 1895 to contiguous joints and bones. Agricultural work (Emmons Chester et al., 1977). represents an important risk factor, with N. brasiliensis being the most common infecting Nocardia species are ubiquitous soil species (Ambrosioni, 2010). organisms with more than 50 species that have been isolated from clinical infections. The genus Systemic immunosuppression and prior Nocardia is rapidly expanding and at present treatment with corticosteroids are regarded as consists of 22 species. The most frequently important risk factors. Other clinical conditions isolated species belong to the N. asteroides that can also predispose to the development of complex, which is a heterogeneous group that nocardiosis include lymphoma, sarcoidosis, includes N. asteroides sensu strictu, N. farcinica, systemic lupus erythematosus, chronic N. nova and N. abscessus. Other medically granulomatous disease, chronic alcoholism, important species are N. brasiliensis, N. diabetes mellitus, HIV infection, trauma, surgery otitidiscaviarum, N. africana, N. brevicatena and post- transplantation. (Yu and Chua, 2001). complex, N. carnea, N. paucivorans, N. Chronic Granulomatous Disease (CGD) pseudobrasiliensis, N. transvalensis and N. predisposes to infections at an early age with veterana. Identification of clinical isolates beyond Nocardia species. About 1.3% of the reported the genus level is important since Nocardia cases of nocardiosis involve patients with this species differ in the clinical spectrum of the underlying condition. A case has been reported disease they cause and their susceptibility to in which a patient with chronic granulomatous antibiotics. In particular, N. farcinica is much disease had infection due to N. farcinia (Fijen et more resistant than other Nocardia species al.,1998). (Agterof, 2007). A collation of epidemiologic information Nocardia is not part of the normal human flora indicates a minimum of 500-1,000 human cases/ and any isolate must be carefully evaluated. The year in the USA alone, although recent clinical organisms are readily aerosolized with dust, reports from many centres indicate that the especially in dry areas. Consequently, the incidence of infection is rising. This may be due respiratory tract is the main portal of entry, with in part to improvements in diagnosis, and to 50 to 70% of cases presenting with pulmonary improved survival of patients in immuno involvement, most commonly with organisms suppressed state because of more aggressive representing the former N.asteroides complex. therapy of rejection of transplants, and to Bronchiectasis and other structural lung improvements in therapy of other opportunistic abnormalities have been reported as an important infections (leaving the patient vulnerable to the risk factor for respiratory colonization by Nocardia possibility of later infection with Nocardiae). There species. Organisms can also be acquired by seems no geographic predilection, with the direct inoculation, resulting in primary infections exception that mycetomas due to Nocardia of the skin and subcutaneous tissues, often species occur predominantly in tropical areas. In presenting as a localized, nodular process. These Europe and North America, about 85% of the infections can progress via lymphatic spread to infections seen are pulmonary and/ or systemic,

This article can be downloaded from http://www.ijlbpr.com/currentissue.php 21 Int. J. LifeSc. Bt & Pharm. Res. 2013 Prakriti Vohra et al., 2013 with estimates that 75-79% of cases will have granulomatous response with central necrosis some pulmonary involvement and 45% systemic that may mimic tuberculosis or histoplasmosis. dissemination. (Stevens et al.,1983) Progressive fibrosis occurs in inadequately treated patients, with a chronic course similar to CLINICAL MANIFESTATIONS that of tuberculosis (Corti and Villafañe-Fioti, The manifestations of nocardiosis can be solely 2003). pulmonary, but Nocardia species can also Rarely, Nocardia species can invade pre- disseminate from a pulmonary or cutaneous existing lung cavities, producing a ‘fungus ball’ focus to virtually any organ. appearance (Tilak et al., 2008). Nocardiae cause a variety of suppurative The remissions and exacerbations of infections in man and animals. Primary pulmonary pulmonary nocardiosis over periods of several nocardiosis may be subclinical or pneumonic; it weeks are frequent. It mimics pulmonary may be chronic or acute with possible secondary, tuberculosis in both clinical symptoms and often fatal, involvement of other systems. In non- radiological characteristics. The chest radio- tropical countries, most infections are caused by graphic manifestations are pleomorphic and non- Nocardia asteroides, N. farcinia and N. nova, and specific. Consolidations and large irregular relatively few by N.brasiliensis and N. nodules, often cavitary, are most common; otitidiscaviarum. Localized cutaneous and nodules, masses and interstitial patterns also subcutaneous nocardiosis are encountered less occur. Upper lobes are more commonly involved. frequently. Their aetiological agents include N. In countries like India where tuberculosis is very asteroides, N. brasiliensis, N. farcinia, N. otitisdi- common, anti tuberculosis drugs are started on scaviarum and N. transvalensis (Goodfellow, 1996). the basis of radiology and clinical symptoms. A Pulmonary nocardiosis is an acute, subacute classic radiographic picture of tuberculosis that or chronic suppurative infection with a is unresponsive to medication should raise the pronounced tendency for remissions and suspicion of Nocardia infection (Chopra et al., exacerbations. The clinical manifestations are 2001). It is important to consider Nocardiosis in acute or subacute pneumonia with abscess or the differential diagnosis of pulmonary diseases cavity formation. Generally, the initial diagnosis which do not respond to antitubercular treatment is pneumonia, tuberculosis, and carcinoma or and in which the sputum is negative for AFB (Dias lung abscesses of other aetiologies. The most et al., 2009). Although, nocardiosis resembles common symptoms are productive cough, high tuberculosis, the first line anti tubercular drugs fever, chills, sweats and weight loss. 25% of have no role to play in its treatment (Kumar et al., cases present with pleural involvement, including 2011). pleural effusions and empyema. Histopatho- The disease may be erroneously diagnosed logically, pulmonary lesions show tissue necrosis as Wegener’s granulomatosis, if cavitating with polymorphonuclear leukocyte, macrophage pulmonary lesions and vasculitic skin lesions and lymphocyte infiltrates, but usually not the occur concurrently (Gibbs, 1986). hallmark epitheloid cells seen in tuberculosis. Sometimes, tissue sections may reveal a Nocardial lesions in the lungs or elsewhere in

This article can be downloaded from http://www.ijlbpr.com/currentissue.php 22 Int. J. LifeSc. Bt & Pharm. Res. 2013 Prakriti Vohra et al., 2013 the body frequently erode into blood vessels. Once and there have been few reported cases in the blood borne, organisms can invade other literature ( Li et al., 2008; Chu et al., 2003; Dwyer anatomic locations. This process can also occur et al., 2001; Recule et al., 1994). It appears there following traumatic inoculation from a are no obvious predisposing factors to the contaminated source (e.g., a thorn, wood splinter, development of Nocardia peritonitis. Abscess traumatic accident, bullet wound, insect bite or formation is rare, but once diagnosed, surgical animal bite). Thus, when lesions are found at two treatment and prolonged antimicrobial therapy are or more locations within the body, the infection is indicated. defined as systemic or disseminated nocardiosis. Nocardia synovitis is rare. The majority of the Any anatomic location can be involved, but the previously reported cases have been in most common site that become infected during immunocompromised patients and have been an dissemination include the CNS, cutaneous and expression of disseminated Nocardiosis. subcutaneous tissues, eyes (especially the An unusual presentation of Nocardia asiatica retina), kidneys, joints, bone, and heart. Unlike (N. asiatica) in an Iraqi patient with myasthenia pulmonary infections, disseminated or systemic gravis suffering from a disseminated infection and nocardiosis tend to become relentlessly presenting with an anterior mediastinal cystic progressive, and self-limited or subclinical mass has been described (El-Herte et al., 2012). disease is not recognized frequently. (Beaman A case of disseminated nocardiosis in a and Beaman, 1994). patient without any underlying immuno Cerebral nocardiosis is an uncommon clinical suppression has been reported (Dar et al., 2009). entity, representing only 2% of all cerebral Ocular nocardiosis is an uncommonly reported abscesses. Most common presentation is with clinical entity. Infection may develop after minor evidence of progressively expanding intracerebral trauma to the eye in healthy individuals, following mass lesion which can be multiple or single. ocular surgery such as cataract extraction, or Nocardial brain abscesses are often following hematogenous dissemination in misdiagnosed as malignant brain tumours and a immunocompromised patients. Ocular pathology definitive diagnosis may not be possible without of nocardiosis includes uveitis, exudative detecting bacteria from the lesion. Infection of the choroiditis, retinal abscess, retinal detachment, brain by nocardia is often insidious in onset, keratitis, and iritis. Nocardial endopathalmitis is difficult to diagnose and treat successfully. associated with a high mortality, and survivors Nocardial brain abscesses are frequently solitary have invariably had total blindness in the involved (54%). The mortality rate in patients with multiple eye (Brown-Elliott et al., 2006). abcesses is twice of that among patients with The typical clinical picture in Nocardia keratitis solitary abscesses (66% vs.33 %) (Hymer et al., is a well-defined epithelial defect with scalloped 2011). margins and a white granular appearance. The Peritonitis is a common problem in patients margins of the ulcer have discrete, yellowish- undergoing continuous ambulatory peritoneal white, pinhead-sized infiltrates. The stromal dialysis. Nocardia peritonitis is not symptoma- infiltrate has feathery margins and a wreath tically different from other causes of peritonitis, pattern with satellite lesions (Rao et al., 2000).

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Isolated Nocardia scleritis is rare and usually Culture occurs as an extension of corneal infection Several general purpose media can be used to involving the limbus. The common predisposing isolate Nocardiae from clinical material. They factors are surgery and injury. A number of cases include brain-heart infusion, sabouraud dextrose of scleritis due to Nocardia spp. have been and yeast extract- malt extract agars. reported (De Croos et al., 2011; Jain et al., 2009; Nevertheless, selective media are needed to Das et al., 2007; Maruo et al., 2011; Sahu et al., isolate Nocardiae from clinical specimens that 2012). harbour large number of contaminating bacteria. Several media have been recommended for the LABORATORY DIAGNOSIS selective isolation of Nocardiae, notably In patients with suspected Nocardial infection and chemically defined formulations supplemented a compatible clinical picture, a definitive diagnosis with paraffin, Czapek’s agar amended with yeast usually depends on demonstration of the extract, Diagnostic sensitivity Test agar organisms in smears or sections examined supplemented with tetracyclines, Nocardia microscopically prior to isolation and identification selective agar, buffered charcoal yeast extract of the causal agent. Clinical materials, such as agar supplemented with anisomycin, polymyxin bronchial washings, sinus discharge and biopsy and vancomycin and Sabouraud dextrose agar and autopsy specimens, need to be examined supplemented with chloramphenicol. Nocardiae as soon as possible to prevent overgrowth by usually form well sized colonies on most contaminants. Fluid material can be examined in standard laboratory media, including modified wet mounts under the microscope without Bennett’s, brain-heart infusion, Sabouraud staining (Goodfellow, 1996). dextrose, modified Sauton’s, Yeast extract- Microscopy glucose and yeast extract-malt extract agars, Nocardia species have a Gram positive mycelium within 14 days at 37 °C (Goodfellow M., 1996). with branched hyphae which rarely exceed one Other media which may be useful include- micron in width. The partially acid fastness of the Modified Thayer Martin’s medium (Murray et al., organism is a characteristic feature (Randhawa 1988), Paraffin agar, Gelatin agar (Shawar et al., et al., 1977). Acid-fastness, which is usually more 1990). pronounced in clinical than cultured material, is Nocardia species can be recovered on best seen using the modified Kinyoun acid-fast isolation media for bacteria, fungi or procedure. Even with this technique, Nocardiae mycobacteria, but growth is slow and incubation may be only partially acid-fast; that is, they show should be continued for at least two weeks. They both acid-fast and non-acid-fast bacilli and can grow at high temperatures (37 to 45 °C) and filaments (Goodfellow, 1996). growth is accelerated by CO2. Premature Silver methamine stain has been found to be discontinuation of culture will decrease the equally effective and reliable as modified Ziehl- sensitivity of recovery and may contribute to Nelson staining technique in demonstrating these underestimation of the true incidence of bacteria in these samples (Mathur et al., 2005). nocardiosis. Typically, colonies are chalky white,

This article can be downloaded from http://www.ijlbpr.com/currentissue.php 24 Int. J. LifeSc. Bt & Pharm. Res. 2013 Prakriti Vohra et al., 2013 but they can also be yellow, pink or orange. A to evolve and be refined for the aerobic characteristic smell is produced, vividly described actinomycetes (Forbes Betty et al., 2007). as a musty basement odour or earthy smell Wellinghausen et al. reported three new (Agterof et al., 2007). species of Nocardia (i.e., N. paucivorans, N. Recognition of the Nocardiae can be optimized abscessus and N. veterana) while investigating by seeing the filamentous, white to yellow to seven patients of nocardiosis with clinical infection orange colonies with aerial mycelia and delicate, by conventional biochemical methods and 16S dichotomously branched substrate mycelia with rRNA sequencing. (Wellinghausen et al., 2002) a dissecting microscope (Saubolle and Sussland, Serology 2003). Currently, no serologic test is available for rapid Identification diagnosis of active nocardiosis. Attempts to Accurate identification of Nocardia to the species develop serologic tests such as hemagglutination, level is important, in that differences among immunodiffusion for precipitins and complement species have emerged in terms of virulence, fixation met with only partial success because of antibiotic susceptibility, and epidemiology. cross- reactivity among heterogeneous Nocardia However, identification of the pathogenic Nocardia species, Mycobacterium tuberculosis, Mycobac- to the species level can be problematic because terium leprae and other actinomycetes (Mc Neil no single method can identify all Nocardia isolates and Brown et al., 1994). and because the methods employed are time However, a 55/54 kD culture filtrate antigen has consuming, often requiring 2 weeks. Useful also been under investigation as a strong phenotypic tests include the use of casein, candidate for a specific antibody marker of active xanthine, and tyrosine hydrolysis; growth at nocardiosis (Kjelstrom and Beaman et al., 1993). 45 °C; acid production from rhamnose; gelatin hydrolysis; opacification of Middlebrook agar and Management antimicrobial susceptibility patterns (Forbes Betty The greatest clinical experience in the treatment et al., 2007). of nocardiosis is with the sulphonamides, and Molecular Diagnosis these remain the drugs of choice. Trimethoprim- sulphamethoxazole is the most commonly A number of molecular approaches such as available sulfa-containing drug, and although Polymerase Chain Reaction (PCR)-restriction there is some uncertainty regarding the proportion fragment length polymorphism analysis and PCR of the two components of the drug with optimal of a sequence of 16S rRNA gene with subsequent synergy against the organism. Trimethoprim- sequencing have been used to rapidly and Sulphamethoxazole is found to be effective in the accurately identify these organisms. Of note, using the MicroSeq system for identification, treatment of the majority of isolates of all Nocardia almost 15% of isolates were identified as species. The excellent oral bioavailability of the Nocardia but no definitive species was given. drug and its good tissue and cerebrospinal fluid Therefore, identification approaches employing penetration are advantages. Dosages used with phenotypic and molecular methods will continue success vary from 25 to 75 mg/kg d of SMX. If

This article can be downloaded from http://www.ijlbpr.com/currentissue.php 25 Int. J. LifeSc. Bt & Pharm. Res. 2013 Prakriti Vohra et al., 2013 there is prompt clinical response, the dose may were trimethoprim-sulfamethoxazole resistant be lowered after the first 6-8 weeks of therapy. At (Larruskain, 2011). times, a sulfa drug cannot be used because of allergy, intolerance or toxicity. Non sulfa drugs CONCLUSION found most often to be effective in vivo for N. Infections caused by Nocardia species are asteroides are amikacin (7.5 mg/kg q12 h), infrequent but challenging to the clinicians. minocycline (200 mg bid.), imipenem-cilastatin Alertness to the possibility of nocardiosis can (500mg q6h), ceftriaxone (1-2 mg q12h) and expedite the diagnostic work-up, especially in cefotaxime (2g q8h). General recommendations patients with predisposing factors. are for a treatment duration of 3 months for the immunocompetent host with isolated cutaneous REFERENCES or pulmonary disease, 6 months for the 1. Agterof M J, Bruggen T, Tersmette M, Borg immunocompromised host with cutaneous or E J, Bosch J M M and Biesma D H (2007), pulmonary disease, 6 months for immuno- “Nocardiosis: A Case Series and a Mini competent host with central nervous system or Review of Clinical and Microbiological disseminated disease, and 12 months for the Features”, Journal of Medicin., Vol. 65, pp. immunocompromised host with central nervous 199-202. system or disseminated disease. Possibility of 2. Ambrosioni J, Lew D and Garbino J (2010), relapse may be lower and survival may be “Nocardiosis: Updated Clinical Review and improved when treatment is given for longer than Experience at a Tertiary Center”, J. Infection., 6 months (Burgert, 1999). Vol. 38. pp. 89-97. Linezolid can be effective alternative to 3. Beaman B L and Beaman L (1994), trimethoprim/sulfamethoxazole for the treatment of nocardiosis. Unfortunately, the high cost and “Nocardia Species: Host-Parasite Relation- potentially long term serious toxicities of linezolid ships”, Clin. Microbiol. Rev., Vol. 7, pp. 213- appear to limit its use and relegate it to salvage 264. therapy alone or in combination with other 4. Brown-Elliott B A, Brown J M, Conville P S antimicrobials (Jodlowski, 2007). and Wallace R J (2006), “Clinical and In a recent study, the antimicrobial suscep- Laboratory Features of the Nocardia spp., tibilities of 186 clinical isolates of Nocardia spp. Based on Current Molecular Taxonomy”, isolated was determined in Gipuzkoa, northern Clin. Microbiol. Rev., Vol. 19, pp. 259-282. Spain, between 1998 and 2009. Most isolates 5. Burgert S J (1999), “Nocardiosis: A Clinical were recovered from respiratory samples, Review”, J. Infectious Diseases in Clinical Nocardia nova, N. farcinica, N. cyriacigeorgica, Practice, Vol. 8, pp. 27-32. N. abscessus, and N. carnea being the species most frequently isolated. Linezolid and amikacin 6. Chopra V, Ahir G C, Gian C and Jain P K were the only two antimicrobials to which all (2001), “Pulmonary Nocardiosis Mimicking isolates were susceptible. The majority of N. Pulmonary Tuberculosis”, Indian Journal of flavorosea, N. carnea, and N. farcinica isolates Tuberculosis, Vol. 48, pp. 211-213.

This article can be downloaded from http://www.ijlbpr.com/currentissue.php 26 Int. J. LifeSc. Bt & Pharm. Res. 2013 Prakriti Vohra et al., 2013

7. Chu K H, Fung K S, Tsang W K, Chan H W 15. El-Herte R I, Kanj S S, Araj G F, Chami H and Tong K L (2003), “Nocardia peritonitis: and Gharzuddine W (2012), “First Report Satisfactory Response to Intraperitoneal of Nocardia asiatica Presenting as an Trimethoprim-Sulfamethoxazole”, Perit. Anterior Mediastinal Mass in a Patient with Dial. Int., Vol. 23, pp. 197-198. Myasthenia Gravis: A Case Report and 8. Corti M E and Villafañe-Fioti M F (2003), Review of the Literature”, Case Reports in ”Nocardiosis: A Review”, International J. Infectious Diseases, Vol. 2012, pp. 325-767. Infectious Disease, Vol. 7, pp. 243-250. 16. Emmons Chester W, Binford Chapman H, 9. Curry W A (1980), “Human Nocardiosis: A Utz John P and Kwon-Chung K J (1977), Clinical Review with Selected Case Ed. Medical Mycology, 3rd Edition, Lea & Reports”, Arch. Intern. Med., Vol. 140, pp. Febiger Publisher, pp. 103-116. 818-826. 17. Fijen C A P, Schrama J, Kuijper E J, Boiron 10. Dar I H, Dar S H and Samia R (2009), P, Gerritsen W and Speelman P (1998), “Disseminated Nocardiosis: A Case Report “Infection Due to Nocardia farcinica in a with Review of the Literature”, J. Turk. Acad. Woman with Chronic Granulomatous Dermatol., Vol. 3, pp. 93402c. Available at Disease”, CID, Vol. 26, pp. 222-224. http://www.jtad.org/2009/4/jtad93402c.pdf 18. Forbes Betty A., Sahm Daniel F. and 11. Das S, Saunders M, Cheng A C and Whiting Weissfeld Alice S., Ed. Bailey & Scott’s M (2007), “Nodular Nonnecrotising Anterior Diagnostic Microbiology,12th Edn, Mosby Scleritis due to Nocardia Nova Infection”, publisher: 311-322 (2007) Eye, Vol. 21, pp. 276-278. 19. Gibb W and Williams A (1986), “Nocardiosis 12. DeCroos F C, Garg P, Reddy A K, Sharma mimicking Wegener’s granulomatosis”, A, Krishnaiah S, Mungale M and Mruthyunjaya Scand. J. Infect. Dis., Vol. 18, pp. 593-595. P (2011), “Hyderabad Endoph-thalmitis Research Group Optimizing Diagnosis and 20. Goodfellow M (1996) in Collee J G, Marmion Management of Nocardia keratitis, Scleritis, B P, Fraser A G and Simmons A (Eds.), and Endophthalmitis: 11-year Microbial and Mackie & McCartney, Practical Medical Clinical Overview”, Ophthalmology, Vol. 118, Microbiology, Churchill Livingstone, pp. 343- pp. 1193-1200. 359, New York. 13. Dias M, Antony B and Pinto H (2009), 21. Jain V, Garg P and Sharma S (2009), “Spectrum of nocardiosis: A Report of Three “Microbial scleritis—experience from a Cases”, J. Clin. & Diag. Research, Vol. 3, developing country”, Eye, Vol. 23, pp. 255- pp. 1682-1684. 261. 14. Dwyer K M, Daffy J R and Murphy B F (2001), “Nocardia peritonitis and abdominal 22. Jodlowski T Z, Melnychuk I and Conry J Abscess Complicating Continuous Ambula- (2007), “Linezolid for the treatment of tory Peritoneal Dialysis”, Nephrology, Vol. Nocardia spp. Infection”, Ann. Pharmacother, 6, pp. 263-265. Vol. 41, pp. 1694-1699.

This article can be downloaded from http://www.ijlbpr.com/currentissue.php 27 Int. J. LifeSc. Bt & Pharm. Res. 2013 Prakriti Vohra et al., 2013

23. Kjelstrom J A and Beaman B L (1993), Medically Important Aerobic Actinomycetes: ”Development of serologic panel for the Epidemiology and Microbiology”, J. Clinical recognition of Nocardial infections in a microbiology reviews, Vol. 7, pp. 357-417. murine model”, Diagn. Microbiol. Infect Dis., 32. Murray Patrick R, Heeren Roberta L and Vol. 16, pp. 291-301. Niles Ann C (1988), “Modified Thayer Martin 24. Kumar A, Mehta A, Kavathia G, Madan M Medium for recovery of Nocardia species (2011), “Pulmonary and Extrapulmonary from contaminated specimens”, J. of Clin. Tuberculosis along with Pulmonary Micro., Vol. 26, pp. 1219-1220 Nocardiosis In a patient with human Immunodeficiency Virus Infection: A case 33. Rao S K, Madhavan H N, Sitalakshmi G, report”, Journal of Clinical and Diagnostic Padmanabhan P (2000), “Nocardia asteroides Research, Vol. 5, pp. 109-111. Keratitis: report of seven patients and literature review”, Indian journal of 25. Larruskain J., Idigoras P., Marimo´n J M, ophthalmology, Vol. 48, pp. 217-221. Pe´rez-Trallero E (2011),”Susceptibility of 186 Nocardia sp. Isolates to 20 Antimicrobial 34. Recule C, Milongo R, Boiron P, Croize J Agents”, Antimicrobial Agents And Chemo- (1994), “Nocardia peritonitis complicating therapys, Vol. 55, pp. 2995-2998. CAPD”, Perit. Dial. Int., Vol. 14, pp. 297–298. 26. Lerner P I (1996), “Nocardiosis”, J.Clin. 35. Sahu S K, Sharma S and Das S (2012), Infectious diseases, Vol. 22, pp. 891-905. ”Nocardia scleritis—clinical presentation 27. Li S Y, Yu K W, Yang W C, Chen T W, Lin C and management: A report of three cases C (2008), “Nocardia peritonitis: A Case and review of literature”, J. Ophthal. Report and Literature Review”, Perit. Dial. Inflamm. Infect., Vol. 2, pp. 7-11. Int., Vol. 28, pp. 544-547. 36. Saubolle M A and Sussland D (2003), 28. Malik A K, Sabharwal U and Chugh T D ”Nocardiosis: Review of Clinical and (1980), “Pulmonary Nocardiosis”, Indian J. Laboratory Experience”, J. Clin.Microbiol., pathol. Microbiol., Vol. 23, pp. 209-211. Vol. 41, pp. 4497-4501. 29. Maruo H, Shiraishi A, Hara Y, Maruo Y, Ohashi 37. Shawar Ribhi M, Moore David G and Y (2011), “Necrotizing nocardial scleritis Larocco Mark T (1990), “Cultivation of successfully treated with surgical Nocardia species on chemically defined debridement and topical polyvinyl alcohol media for selective recovery of isolates from iodine and antibiotics”, J. Ocul. Pharmacol. clinical specimens”, Journal of Clinical Ther., Vol. 27, pp. 415-418. microbiology, Vol. 28, pp. 508-512.

30. Mathur S, Sood R, Aron M, Iyer V K, Verma 38. Singh M, Sandhu R S, Randhawa H S and K (2005), ”Cytologic Diagnosis of Pulmonary Kallan B M (2000), “Prevalence of pulmonary Nocardiosis. A report of three cases”, Acta. nocardiosis in a tuberculosis hospital in Cytol., Vol. 49, pp. 567-570. Amritsar, Punjab”, Indian J. Chest Ds. Allied 31. Mc Neil M M and Brown M J (1994), “The Sci., Vol. 42, pp. 325-339.

This article can be downloaded from http://www.ijlbpr.com/currentissue.php 28 Int. J. LifeSc. Bt & Pharm. Res. 2013 Prakriti Vohra et al., 2013

39. Stevens D A (1983), “Clinical and clinical Literature Review”, AJNS, Vol. 30, available laboratory aspects of Nocardial infection”, at: www.ajol.info/index.php/ajns/article/ J. Hyg. Camb., Vol. 91, pp. 377-384. viewFile/77334/67782. 40. Tilak R, Agarwal D, Lahiri T K and Tilak V 42. Wellinghausen N, Pietzckar T, Kern W V, (2008), “Pulmonary nocardiosis presenting Essig A and Marre R (2002), “Expanded as fungal ball-a rare entity: A case report”, spectrum of Nocardia species causing J. Infect. Developing Countries, Vol. 2, pp. clinical nocardiosis detected by molecular 143-145. methods”, International Journal of Medical 41. W El Hymer, Mohamed L, Mohamed S, Microbiology, Vol. 292, pp. 277-282. Khalid A, Houssine G and Idmoussa A (2011), 43. Yu C T and Chua J A (2001), “Nocardiosis”, “Nocardia Brain Abscess – Case Report and PJMID, Vol. 30, pp. 56-61.

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