Nephrol Dial Transplant (1998) 13: 796–798
Nephrology
Dialysis
Transplantation
Teaching Point
(Section Editor: K. Kühn)
Supported by an educational grant from
Subcutaneous nodules and pneumonia in a kidney transplant recipient
Massimo Maccario1, Anna Maria Tortorano2 and Claudio Ponticelli1
1Divisione di Nefrologia e Dialisi, IRCCS, Ospedale Maggiore di Milano, 2Istituto di Igiene e Medicina Preventiva,
Università degli Studi di Milano, IRCCS, Ospedale Maggiore di Milano, Milano, Italy
Key words: kidney transplant; nocardiosis; pneumonia;
subcutaneous
nodules;
trimethoprim–
sulphamethoxazole
Case report
On 22 June 1996 a 51-year-old man received a
cadaveric renal transplant. He had started dialysis
7 years before because of chronic pyelonephritis.
Post-transplant immunosuppressive therapy included
methylprednisolone, cyclosporin A, and azathioprine.
The patient was discharged 18 days after transplantation with plasma creatinine of 2.1 mg/dl. On 9 August,
prophylaxis for Pneumocystis carinii with trimethoprim–sulphamethoxazole ( TMP–SMX ) 80/400 mg
three times a week was started. On 4 September the
patient was admitted to our unit because of fever
(38.5°C ) and extremely severe pain at thighs, at the
right elbow, and at the left clavicle.
Physical examination revealed painful subcutaneous
nodules, with a diameter of approximately 1.5 cm,
located in the right buttock, in the right elbow and in
the left subclavian region. The chest X-ray showed a
nodular infiltrate of the right upper lobe (Figure 1).
Laboratory evaluation revealed a serum creatinine of
1.9 mg/dl and a white blood cell count of 10.8×109/l
with 88% neutrophils. Serology for viral infections was
negative. The cutaneous nodule in the left subclavian
region was immediately removed and sent for analysis.
Extensively branched Gram-positive hyphae, less than
1 mm in diameter, were seen on direct microscopic
examination of the Gram stain of the skin biopsy
smear preparation ( Figure 2). Nocardia infection
was suspected and antimicrobial treatment with
Correspondence and offprint requests to: Massimo Maccario MD,
Divisione di Nefrologia e Dialisi, IRCCS Ospedale Maggiore
Policlinico, Via della Commenda 15, I-20122 Milano, Italy.
TMP–SMX (160/800 mg) every 6 h plus 1 g i.v. ceftriaxone once a day was instituted. In addition, azathioprine was stopped and cyclosporin was reduced from
175 to 100 mg/day, while oral methylprednisolone was
continued unchanged at a dose of 16 mg/day.
A computed tomography (CT ) scan was performed,
which showed a brain abscess with a diameter of
1.5 cm in the left frontal lobe (Figure 3). Several chalky
Nocardia-like colonies grew after 4 days of incubation
at 32°C on 5% sheep blood agar and Sabouraud
dextrose agar without antibiotics inoculated with skin
biopsy specimen. The isolate was identified as Nocardia
farcinica by Dr Patrick Boiron ( Unité de Mycologie,
Institut Pasteur, Paris). The strain was sensitive (disk
diffusion method) to TMP–SMX, ceftriaxone, and
amikacin, and resistant to erythromycin, ampicillin,
cefotaxime, and norfloxacine. Therefore a diagnosis of
nocardiosis of the brain, lung, and skin was made and
the antimicrobial treatment was continued unchanged.
Fig. 1. Chest X-ray revealing a nodular infiltrate of the right upper
lobe.
© 1998 European Renal Association–European Dialysis and Transplant Association
Nocardiosis in a kidney transplant recipient
797
On 14 February 1997 the patient was admitted to
our Unit because plasma creatinine had increased to
2.7 mg/dl. Renal biopsy revealed chronic rejection with
tubular damage. Since the patient was symptomless
and the CT scan showed no more evidence of a cerebral
abscess, TMP–SMX was stopped, while cyclosporin
was increased to 300 mg/day.
At the last check-up, in July 1997, the patient was
doing well, plasma creatinine was 2.6 mg/dl, and there
was no evidence of recurrent Nocardia infection.
Treatment was cyclosporin 300 mg/day, methylprednisolone 8 mg/day, and hypotensive drugs.
Discussion
Fig. 2. Gram staining of skin smear revealing Gram-positive
hyphae (arrows).
Fig. 3. Computed tomography scan revealing a brain abscess in the
left frontal lobe.
After 3 days of antimicrobial therapy fever remitted
and the sites of the subcutaneous nodules diminished
and became less painful. Three weeks after admission
the patient was discharged in good general condition.
At chest X-ray, the pulmonary lesion had disappeared,
and the subcutaneous nodules were not palpable.
However, in the CT scan the cerebral abscess persisted
unchanged. The patient continued treatment with
TMP–SMX (320 mg/1600 mg) every 12 h plus 1 g i.m.
ceftriaxone every 12 h; cyclosporin was increased to
150 mg/day, and methylprednisolone was continued
according to our protocol.
Nocardiosis is caused by a Gram-positive soilinhabiting aerobic actinomycetes. Nocardia asteroides
accounts for 90% of the cases of nocardiosis [1]. In a
recent taxonomic revision two new species, N. farcinica
and N. nova, were separated from N. asteroides.
N. farcinica is characterized by a high degree of resistance to various antibiotics [2,3].
Usually nocardiosis is acquired by inhalation of
airborne spores, which may also be followed by
haematogenous dissemination of the micro-organism.
Percutaneous inoculation is also possible, but it is rare.
Nocardiosis occurs more frequently in immunocompromised or immunosuppressed hosts. Pneumonia is
very frequent. Almost 90% of patients with nocardiosis
have pulmonary involvement. Symptoms are not distinctive and may mimic other bacterial or viral bronchitis or pneumonia. The diagnosis is also difficult
because the radiological manifestations are pleomorphic
and may include alveolar or interstitial infiltrates, single
or multiple nodules with or without cavitation and, less
frequently, subpleural plaques and pleural effusion. The
skin and the brain are the most frequent non-pulmonary
sites involved in disseminated nocardiosis accounting
for 20 and 17% of patients respectively. The cutaneous
involvement, resulting from haematogenous spread, is
characterized by nodules (which are the most typical
lesion) or by abscesses or cellulitis. In disseminated
disease, involvement of the central nervous system may
occur. Brain lesions may be multiple, but a large single
abscess may result by extension or coalescence. Cerebral
involvement is often asymptomatic. Therefore, a CT
investigation of the brain is mandatory. The infection
may also involve other organs such as the kidney, liver,
spleen, pancreas, and bone.
Renal transplant patients are predisposed to the
development of nocardial infections, this organism being
responsible for 4% of the infections following transplantation [4]. The disease affects males more frequently
than females (ratio 2–351). The risk factors include age
(<10 or >40 years), multiple early rejection episodes
(2 or more in the first 2 months), high-dose prednisone,
and the development of neutropenia [5–7].
Nocardiosis is a life-threatening infection in renal
transplant patients and a rapid diagnosis and a prompt
institution of specific therapy can substantially reduce
798
the fatality rate. The coexistence of pneumonia, fever,
and subcutaneous nodules during the first posttransplant period can be indicative of nocardiosis or
aspergillosis. The laboratory microscopic examination
of the biopsied skin nodules may allow prompt and
appropriate antimicrobial treatment. The presence of
long, branching Gram-positive filaments, less than
1 mm in diameter, are indicative of Nocardia, while
filaments with diameter more than 2.5–4.5 mm are
indicative of fungal organism such as Aspergillus. The
use of culture media without added antibiotics and the
prolonged incubation period allow the growth of
Nocardia isolates from the biological samples and the
identification of the correct antimicrobial therapy.
TMP–SMX is now regarded as the therapy of choice
for nocardiosis. In patients with kidney transplant the
use of a sulpha-containing regimen (sulpha alone or
as TMP–SMX ) achieved a 82% survival rate compared
to 36% of those treated with drugs not containing
sulpha-agents [4]. Imipenem, ceftriaxone, cefotaxime,
meropenem, amikacin, minocycline, ampicillin, and
amoxycillin–clavulanic acid have been shown to be
efficacious alone or in combination with TMP–SMX,
provided that the micro-organism is in vitro sensitive
[8–13]. Although the duration of treatment of nocardiosis is not well defined, a prolonged therapy for up
to 1 year is recommended to prevent relapses [14].
Some authors even suggest that in immunosuppressed
patients antibiotic treatment should be given for life
[4,15,16 ]. Cerebral abscesses, if not responsive to antimicrobial therapy, should be surgically removed
[17,18]. The fatality rate of nocardiosis in transplanted
patients depends on the extent and involvement of the
infection. Prognosis is excellent in patients with isolated
skin involvement, while the mortality rate is about
25% in patients with disseminated disease and increases
to 42% when cerebral nervous system is involved [4].
Clearly the earlier the diagnosis and treatment the
better the prognosis.
Teaching point
Suspect nocardiosis in a kidney transplant patient who
presents with pneumonia and painful subcutaneous
nodules.
M. Maccario et al.
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