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Postgrad Med JT 1996; 72: 680- 693 (© The Fellowship of Postgraduate Medicine, 1996

Short reports Postgrad Med J: first published as 10.1136/pgmj.72.853.680 on 1 November 1996. Downloaded from Mixed pulmonary with Nocardia, Candida, methicillin-resistant Staphylococcus aureus, and group D Streptococcus species

Joseph Vassallo, Alfred Caruana Galizia, Paul Cuschieri

Summary to vancomycin, and ampicillin was A 67-year-old man on prednisolone and cultured. The latter organism is increasingly azathioprine for ulcerative colitis, being identified as a pathogen in immunocom- developed severe pneumonia due to promised patients. Candida albicans and No- Nocardia otitidis caviarum, methicillin- cardia species were also cultured. The latter resistant Staphylococcus aureus, a group was later identified as Nocardia otitidis caviar- D Streptococcus and Candida albicans. um. The patient responded well to aggressive Subsequently the patient was started on antimicrobial therapy. additional parenteral vancomycin and fusidic acid and his condition improved markedly as Keywords: pneumonia, Nocardia otitidis caviarum, assessed by repeated clinical and radiological Staphylococcus aureus, Streptococcus, Candida albicans examinations and laboratory investigation. The latter included regular Gram staining and culturing of the sputum. The Nocardia organ- A 67-year-old man with a long-standing history isms were detectable in the sputum on direct of ulcerative colitis, on azathioprine and high Gram stains for up to 10 days after starting dose prednisolone, was admitted with a one- effective therapy. Vancomycin was stopped week history of fever and productive cough. after eight days oftherapy. Fluconazole, fusidic His general practitioner had previously given acid, imipenem and intravenous co-trimoxa- him a course of oral cefuroxime axetil, 250 mg zole were given for 14 days, while the latter bid, with no effect. preparation was changed to oral form and On admission he had clinical and radiologi- continued for a further eight weeks at a dose of cal features of left lower lobe pneumonia. His 960 mg bid. The patient has remained asymp- initial white cell count was 10.1 x 109 cells/l. tomatic since then. He was started on intravenous ceftazidime, 2 g

8 hourly, and , 80 mg 8 hourly, Discussion http://pmj.bmj.com/ without any response and his clinical and radiological condition continued to deterio- To our knowledge this is the first reported case rate. A direct Gram stain, a Ziehl -Neelsen of multiple pulmonary infection of such and a modified Ziehl -Neelsen stain, per- magnitude involving Nocardia otitidis caviarunm, formed on freshly expectorated sputum, and having a favourable outcome. We believe yielded packed fields of Gram-positive cocci, that all the organisms cultured, played a and and weakly acid- role. The presence of large num- numerous yeasts hyphae, pathogenic on September 25, 2021 by guest. Protected copyright. fast, Gram-positive, branching filaments. A bers offungal hyphae support a pathogenic role presumptive diagnosis of a mixed infection for Candida, while the presence of large due to Nocardia, Candida and Staphylococcus numbers of MRSA and group D Streptococcus and/or Streptococcus was made and the anti- similarly supports a pathogenic role for these microbial therapy was changed to intravenous organisms. The clinical condition ofthe patient imipenem 500 mg 6 hourly, co-trimoxazole, indicated aggressive antimicrobial therapy 120 mg/kg daily in four divided doses, and against all these organisms. We believe that fluconazole, 50 mg bid. The azathioprine was this contributed to the rapid improvement in discontinued and the dose of prednisolone was the patient's condition, as did the early gradually tapered down. His condition im- discontinuation of azathioprine. proved but sputum culture yielded a methicil- Nocardia species are a group of aerobic lin-resistant Staphylococcus aureus (MRSA) Gram-positive branching, filamentous organ- St Lukes Hospital, which was resistant to cloxacillin, gentamicin, isms which cause an acute or chronic, often Malta are J Vassallo , co-trimoxazole, ciprofloxacin disseminated disease. They important AC Galizia and imipenem, but sensitive to vancomycin, members of the soil microflora worldwide. P Cuschieri fusidic acid, and netilmicin. The Nocardia can infect any individual but is much sputum specimens were all cultured without more common in patients with impaired Correspondence to Dr J were at immunity (box 1). It is not a rare condition, Vassallo, Department of significant delays and rapidly digested Geriatrics, Burton House, room temperature with N-acetyl cysteine, to a though it is not given prominent attention in Withington Hospital, Nell final dilution of 1 in 200 before culture, the medical literature. It can be easily missed if Lane, Manchester M20, UK effectively diluting out commensals. the index of suspicion is low as it can resemble Accepted 12 January 1996 A group D Streptococcus which was sensitive more common diseases, such as tumours and Mixed pulmonary infection 681

Nocardiosis: predisposing factors Nocardiosis: chest X-ray findings Postgrad Med J: first published as 10.1136/pgmj.72.853.680 on 1 November 1996. Downloaded from * cytotoxic chemotherapy * solitary pulmonary mass * immunosuppressants including corticosteroids * pulmonary infiltrates * post-splenectomy * pleural thickening * haematological malignancies * chest wall involvement * AIDS * diabetes * alcoholism Box 2 * underlying lung disease, eg, , bronchiectasis In vitro they show susceptibility to several including sulphonamides, co-tri- Box 1 moxazole, imipenem, , , fusidic acid, ceftriaxone, cefotaxime, and co- amoxyclav.4 Resistance is, however, common, other granulomatous diseases.' Most cases especially with Nfarcinica. begin as pulmonary infection and disseminate The standard therapy for nocardiosis is co- haematogenously, with abscess formation in trimoxazole; the combination of amikacin and the brain, kidneys, bones, etc. Infection may imipenem is usually reserved for resistant strains also start as skin or subcutaneous abscess. or for patients allergic to sulpha drugs. Minocy- Several species have been documented to be cline and co-amoxyclav are alternative medica- pathogenic in man. These are N asteroides, N tions.5 It is usually recommended that treatment brasiliensis, N farcinica, N otitidis caviarum, N be continued for three to six months in mild nova and N transvalensis.' The diagnosis is and for six to 12 months in severe made by culture of the organism. However, as infections, because of the risk of relapse. this can take weeks, therapy should be started Patients who are on steroids or other immuno- on microscopic morphology. A chest X-ray is suppressants should have the dose ofthe steroid useful in narrowing the differential diagnosis tapered and the immunosuppressant drug but is nonspecific (box 2).' should be stopped if possible. In this case 10 Sputum examination is diagnostic in only a weeks oftreatment proved adequate. This could third of cases, and although oropharyngeal possibly be due to the intensive initial therapy; colonisation can occur, isolation of Nocardia imipenem, co-trimoxazole and fusidic acid all from the sputum of an immunocompromised show activity against Nocardia. Further investi- host should be regarded as pathogenic. It is gations to study the of short-course imperative that in immunocompromised pa- therapy is warranted. This would improve tients with lung infiltrates of uncertain causa- patient compliance and reduce . tion, bronchoscopy should be performed in with BAL or even open lung conjunction We would like to thank Mr MD Yates, Principal biopsy to get a diagnosis. The organism can Microbiologist at the Public Health Laboratory of also sometimes be isolated from blood cul- Dulwich Hospital, London, for his help in identifying tures. our Nocardia isolate. http://pmj.bmj.com/

1 Curry WA. Human nocardiosis - a clinical review with 5 Thomas CF Jr, Jones TK, Edson RS. A 74-year-old woman selected case reports. Arch Intern Med 1980; 140: 818-26. with dyspnoea, fever, and cough. Mayo Clin Proc 1995; 70: 2 Beaman BL, Beaman L. Nocardia species: host-parasite 397-400. relationships. Clin Microbiol Rev 1994; 7: 213- 64. 3 Feigin DS. Nocardiosis of the lung: chest radiographic findings in 21 cases. Radiology 1986; 159: 9-14. 4 Gutmann L, Goldstein FW, Kitzis MD, Hautefort B, Darmon C, Acar JF. Susceptibility of Nocardia asteroides to 46 antibiotics, including 22 /3-lactams. Antimicrob Agents on September 25, 2021 by guest. Protected copyright. Chemother 1983; 23: 248-51.