Presentation is made of a 53-year-old woman with pulmonary infection caused by Nocardia asteroides. Tracheal aspirate was obtained and examined microbiologically. Direct smear of the tracheal aspirate stained with Gram stain revealed gram-positive branched filamentous hyphae and numerous leukocytes. Pure culture of colonies of a chalky white appearance grew on the blood agar after prolonged incubation. The Gram stained direct slide prepared from the culture showed gram-positive branching filaments. The microorganism was identified as Nocardia asteroides by standard methods.Prikazana je 53-godišnja bolesnica s plućnom infekcijom uzrokovanom mikroorganizmom Nocardia asteroides. Uzet joj je trahealni aspirat i pretražen je mikrobiološki. U direktnom mikroskopskom preparatu iz aspirata traheje bojenom po Gramu vidljive su gram pozitivne razgranate filamentne hife uz puno leukocita. Na krvnom agaru nakon duže inkubacije porasla je čista kultura kolonija bijelog, kredastog izgleda. Preparat iz kulture bojen po Gramu pokazao je gram pozitivne razgranate filamente. Primjenom standardnih metoda mikroorganizam je identificiran kao Nocardia asteroides

Ines Jajić-Benčić

Ivan Benčić

Petar Gaćina

Vera Katalinić-Janković

English

Jajić-Benčić, Ines

Gaćina, Petar

Katalinić-Janković, Vera

Benčić, Ivan

Repository of the Sestre milosrdnice University Hospital Center

Plućna infekcija izazvana organizmom Nocardia asteroides: prikaz slučaja

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Jajiæ-Benèiæ I. et al. Nocardia asteroides pulmonary infectionActa clin Croat, Vol. 41, No. 3, 2002 259Acta clin Croat 2002; 41:259-262 Case R portNOCARDIA ASTEROIDES PULMONARY INFECTION:A CASE REPORTInes Jajiæ-Benèiæ1, Petar Gaæina2, Vera Kataliniæ-Jankoviæ3 and Ivan Benèiæ41Department of Microbiology, Parasitology and Hospital Infections, 2Department of Hematology, Sestre milosrdnice UniversityHospital, 3Department of Mycobacteriology, Croatian National Institute of Public Health,4University Hospital of Traumatology, Zagreb, CroatiaSUMMARY  Presentation is made of a 53-year-old woman with pulmonary infection caused by Nocardiaasteroides. Tracheal aspirate was obtained and examined microbiologically. Direct smear of the tracheal aspi-rate stained with Gram stain revealed gram-positive branched filamentous hyphae and numerous leuko -cytes. Pure culture of colonies of a chalky white  appearance grew on the blood agar after prolonged incuba-tion. The Gram stained direct slide  prepared from the culture showed gram-positive branching filaments.The microorganism was identified as Nocardia asteroides by standard methods.Key words: Nocardia infections  diagnosis; Pneumonia, bacterial  diagnosis; Pneumonia, bacterial  microbiologyCorrespondence to: Ines Jajiæ-Benèiæ, M.D., M.S., Department of Micro-biology, Parasitology and Hospital Infections, Sestre milosrdnice Univer-sity Hospital, Vinogradska c. 29, HR-10000 Zagreb, CroatiaE-mail: ines.jajic-bencic@zg.hinet.hrReceived April 26, 2002, accepted in revised form June 12, 2002IntroductionPulmonary nocardiosis is a severe infection due to No-cardia spp., microorganisms that may behave as either op-portunistic or primary pathogens. It is a community-ac-quired, late-presenting infection, occurring most frequent-ly in patients who are severely immunocompromised1.Nocardia spp. are ubiquitous, soil-borne, aerobic, veryfine and branching gram-positive and weakly acid-fast fil-amentous actinomycetes with a tendency to fragment intobacillary and coccoid forms2.Care ReportOur patient was a 53-year-old woman, diabetic, with-out other serious illnesses in her case history. Severalmonths before, she had become forgetful and confused.She complained of getting tired easily and having an in-creased need of sleep. She denied headache, nausea, vom-iting, and loss of consciousness. Magnetic resonance im-aging (MRI) of the brain revealed an expansive process inthe frontal region bilaterally. Craniotomy with reductionof a tumor mass was performed. Pathohistologic examina-tion revealed a diffuse, large B-cell non-Hodgkin lympho-ma. Antiedematous therapy with mannitol infusion, dex-amethasone and phenobarbitone was initiated, however,the patients condition deteriorated. She developed fever(38 °C), tachycardia and tachypnea, with the GlasgowComa Scale (GCS) 6. Laboratory tests showed findingsindicating acute infection: leukocytosis 14.5x109/L with87% of neutrophils, erythrocyte sedimentation rate (ESR)105 mm/h, CRP 68.9 mg/L, fibrinogen 7.3 g/L. Transam-inase values were also elevated  (AST 114 U/L and  ALT255 U/L).The following samples for bacteriologic analysis wereobtained: blood, cerebrospinal fluid (CSF), tracheal aspi-rate and urine as well as nasal and pharyngeal swabs. Bloodand CSF cultures remained sterile. A large number ofStreptococcus agalactiae were isolated from the pharyngealswab culture. Staphylococcus aureus was isolated from thenasal swab culture, and Enterococcus sp. from urine culture(>10 E5/ml). Triple antibiotic therapy with amoxicillin +clavulanic acid, gentamicin and metronidazole was applied,but no improvement in the patients condition was not-Jajiæ-Benèiæ I. et al. Nocardia asteroides pulmonary infection260 Acta clin Croat, Vol. 41, No. 3, 2002ed. X-ray of the lungs showed no visible recent foci or in-filtrates. Direct smear of tracheal aspirate was stained withGram stain and examined microscopically. The Gramstained smear showed gram-positive branched filamentoushyphae and numerous leukocytes. Culture of tracheal as-pirate was done and submitted to prolonged incubationbecause of the mentioned findings in the direct microscop-ic preparation. After seven days of incubation, a large num-ber of colonies of a chalky white appearance grew  on bloodagar in pure culture (Fig. 1). The microrganism was re-ferred to the Department of Mycobacteriology, CroatianNational Institute of Public Health, for further identifica-tion and was identified as Nocardia asteroides by using stan-dard methods. The strain was subcultivated in Löwen-stein-Jensen medium and Middlebrook 7H10 agar, and wasobserved to produce branched vegetative hyphae and aerialhyphae, two important criteria for the establishment of anorganism as member of the genus Nocardia. Microscopicexamination of the slide preparation showed gram-positivebranching filaments (Fig. 2), which were partially acid-fastby the modified Kinyoun procedure. Thin-layer chroma-tography showed the isolate to contain mesoisomer of di-amonopimelic acid as well as galactose and arabinose. Thestrain failed to hydrolyze casein, xanthine and tyrosine butdid hydrolyze esculin and urea, and was resistant tolysozyme. No other bacterial pathogens were isolated fromtracheal aspirate. Susceptibility testing of Nocardia aster-oides was performed, and the strain showed sensitivity toamikacin, amoxicillin-clavulonate, ampicillin, cefotaxime,ciprofloxacin, minocycline and sulfonamides.Sulfonamide therapy (sulfamethoxazole + trimetho-prim, dose 15 mg/kg/day) was instituted immediately2,3.Fig. 1. Nocardia asteroides colonies with a chalky white appearance.Fig. 2. Nocardia asteroides branching filaments. A slide preparedfrom a culture (Gram stain).Jajiæ-Benèiæ I. et al. Nocardia asteroides pulmonary infectionActa clin Croat, Vol. 41, No. 3, 2002 261Based on the improved general condition of the patient,it was decided to apply De Angelis chemotherapeutic pro-tocol (intravenous and intrathecal application of methotr-exate)4,5. However, the patients condition deterioratedwith tumor progression and progressive pulmonary insuf-ficiency in the form of adult respiratory distress syndrome.The  patient died three weeks after the initiation of anti-Nocardia therapy. Autopsy was not performed because thefamily refused it.DiscussionSince Nocardia sp. are ubiquitous microorganisms, theisolation of this microorganism from sputum culture of animmunocompetent host may not always indicate invasiveinfection but may instead reflect respiratory colonization6.Respiratory tract colonization with Nocardia sp. has beennoted to occur in patients with underlying pulmonary dis-orders (chronic obstructive pulmonary disease, asthma,bronchiectasis). The development of clinical disease oc-curs, and the most common clinical presentations causedby Nocardia sp. are invasive pulmonary infection and dis-seminated infection1,6. The development of clinical  dis-ease occurs in patients with impared local pulmonary de-fense, chronic obstructive pulmonary disease, asthma,bronchiectasis, and alveolar proteinosis. Patients with sys-temic immunosuppression are also predisposed to thedevelopment of invasive pulmonary nocardiosis. Treat-ment with corticosteroids, cytotoxic agents appear to bean important risk factor for the development of this infec-tion. Invasive pulmonary nocardiosis has been reported tooccur in renal and cardiac patients, transplant recipients,and patients with malignant neoplasms, lymphoma, sarcoi-dosis, collagen vascular diseases (especially systemic lupuserythematosus), dysgammaglobulinemia, chronic granulo-matous disease, chronic alcoholism, diabetes mellitus, trau-ma or surgery, and human immunodeficiency virus infec-tion. Thus, Nocardia sp. are uncommon pathogens in hu-mans, involving mainly immunosuppressed or debilitatedpatients1,7-11.Our patient had several risk factors for the develop-ment of Nocardia infection. She was diabetic, was treatedwith corticosteroids, and had a malignant disease, lympho-ma. During the past decade, there has been a marked in-crease in the number of severely immunocompromisedpatients. Many of them are extremely susceptible to thedevelopment of nocardiosis. Since the number  of severe-ly immunocompromised patients shows no tendency todiminish, Nocardia sp. infection will likely continue toemerge as an important opportunistic disease6.Nocardiae are difficult to recognize and identify in adiagnostic laboratory because they are slowly growing mi-croorganisms that require a prolonged period of incubation.Their relatively slow growth results in the cultures beingdiscarded before the nocardiae can be visualized. Thus,isolation of Nocardia asteroides in a clinical microbiology lab-oratory is a kind of success and quality of the diagnosticprocedure. Therefore, all microbiologic laboratories shouldconsider the introduction of a prolonged incubation timefollowing findings of gram-positive branched filamentoushyphae in direct microscopic smear in view of the possi-ble isolation of Nocardia  sp.The pathologic feature of pulmonary nocardiosis isusually a suppurative response, however, a granulomatousresponse or a mixture of these resulting in radiographicpresentations that are pleomorphic and not specific mayoccur. The manifestation within the lungs may vary froma mild, diffuse infiltration to a lobar or multilobar consol-idation. There may be solitary masses, reticulonodularinfiltrates, large irregular nodules, interstitial infiltrates,and pleural effusions. The lesions produced in the lungsmay be necrotizing abscesses. Granulomas may occur11-13.There are no specific clinical signs diagnostic of pul-monary nocardiosis, whereas clinical presentation of thedisease may run the full spectrum of either acute or chronicpulmonary infection. There may be pneumonia, abscessformation, or granulomatous response similar to tubercu-losis6. An accurate diagnosis can be reached by isolation ofthe organism in pure culture from the affected area6.In our case, the Nocardia asteroides related pulmonaryinfection was not confirmed by x-rays. However, our as-sumption that this microorganism had caused respiratoryinfection was supported by the following: 1) laboratoryfindings indicating the presence of acute infection afteradministration of corticosteroids; 2) isolation and identi-fication of Nocardia asteroides in pure culture associated witha large number of leukocytes in direct microscopic slidepreparation from tracheal aspirate; and 3) improved gen-eral condition of the patient after the introduction of sul-fonamides.In conclusion, clinicians should maintain a high degreeof suspicion for this pathogen in severely immunocompro-mised patients, because Nocardia is far from rare in thegroup of immunocompromised patients. Close collabora-tion between clinicians and medical microbiologists is re-quired for early diagnosis and therapy.Jajiæ-Benèiæ I. et al. Nocardia asteroides pulmonary infection262 Acta clin Croat, Vol. 41, No. 3, 2002AcknowledgmentWe thank Mr. Tomislav Beus for his valuable assistancein taking photographs.References1. McNEIL MM, BROWN JM. The medically important aerobic Ac-tinomycetes: epidemiology and microbiology. Clin Microbiol Rev1994;7:357-417.2. BROWN JM, McNEIL MM, DESMOND EP. Nocardia, Rhodococ-cus, Gordona, Actiomadura, Streptomyces, and other Actinomycetes ofmedical importance. In: MURRAY PR, BARON EJ, PFALLER MA,TENOVER FC, YOLKEN RH, eds.  Manual  of clinical microbiol-ogy. 7th Ed. Washington, DC: American Society for Microbiology,1999:370-92.3. SCHOLAR EM, PRATT WB. Antimicrobial drugs. 2nd Ed. OxfordUniversity Press, 2000:215.4. DeANGELIS LM, JAHALOM J, THALER HT, et al. Combinedmodality therapy for primary CNS lymphoma. J Clin Oncol1992;10:635-43.5. LUTZ JM, COLEMAN MP. Trends in primary cerebral lymphoma.Br J Cancer 1994;70:716-8.6. BEAMAN BL, BEAMAN L. Nocardia species: host  parasite rela-tionships. Clin Microbiol Rev 1994;7:213-64.7. PATEL R, PAYA CV. Infections in solid-organ transplant recipients.Clin Microbiol Rev 1997;10:86-124.8. KOUPPARI G, ZAPHIROPOULOU A, SKANDAMI V, et al. Dis-seminated Nocardia asteroides complex infection in an immunocom-promised child. Clin Microbiol Infect 2000;6:287-8.9. ZWERSKI A, WITEBSKY FG, CONCILLE PS, et al. Fatal Nocar-dia pulmonary infection in a child with acquired immunodeficien-cy syndrome and lymphoid interstitial pneumonitis. Pediatr InfectDis J 1997;16:1088-9.10. MENENDEZ R, CORDERO PJ, SANTOS M, et al. Pulmonaryinfection with Nocardia species: a report of 10 cases and review. EurRespir J 1997;10:1542-6.11. FARINA C, BOIRON P, GOGLIO A, et al. Human nocardiosis innorthern Italy from 1982 to 1992. Scand J Infect Dis 1995;27:23-7.12. FEIN A, GROSSMAN R, OST D, FARBER B, CASSIERE H. Di-agnosis and management of pneumonia and other respiratory infec-tions. First Edition. Professional Communications, 1999:181-207.13. KUZMAN I. Pneumonije. Zagreb: Medicinska naklada, 1999:377-82.SaetakPLUÆNA INFEKCIJA IZAZVANA ORGANIZMOM NOCARDIA ASTEROIDES: PRIKAZ SLUÈAJAI. Jajiæ-Benèiæ, P. Gaæina, V. Kataliniæ-Jankoviæ i I. BenèiæPrikazana je 53-godinja bolesnica s pluænom infekcijom uzrokovanom mikroorganizmom Nocardia asteroides. Uzet joj jetrahealni aspirat i pretraen je mikrobioloki. U direktnom mikroskopskom preparatu iz aspirata traheje bojenom po Gramu vidljivesu gram pozitivne razgranate filamentne hife uz puno leukocita. Na krvnom agaru nakon due inkubacije porasla je èista kulturakolonija bijelog, kredastog izgleda. Preparat iz kulture bojen po Gramu pokazao je gram pozitivne razgranate filamente. Primjenomstandardnih metoda mikroorganizam je identificiran kao Nocardia asteroides.Kljuène rijeèi: Nocardia infekcije  dijagnostika; Pneumonija, bakterijska  dijagnostika; Pneumonija, bakterijska  mikrobiologija

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