Article

Disseminated Nocardia farcinica: Literature Review and Fatal Outcome in an Immunocompetent Patient

Department of Pathology, Pritzker School of Medicine, Chicago, Illinois, USA.
Surgical Infections (Impact Factor: 1.45). 05/2012; 13(3):163-70. DOI: 10.1089/sur.2011.012
Source: PubMed

ABSTRACT

Nocardia farcinica is a gram-positive, partially acid-fast, methenamine silver-positive aerobic actinomycete. Nocardia spp. are opportunistic pathogens, and N. farcinica is the least common species of clinical importance.
Review of the recent literature and description of a immunocompetent patient with no known risk factors who contracted fatal N. farcinica sepsis.
Positive pre-mortem and post-mortem cultures from the lung and synovium correlated with acute bronchopneumonia and synovitis at autopsy. Colonies of filamentous bacteria, which were not apparent in conventional hematoxylin and eosin-stained sections, were observed with gram and methenamine silver stains, but acid-fast stains were negative. A literature review revealed that disseminated N. farcinica often is associated with an underlying malignant tumor or autoimmune disease (88% of patients). Chemotherapy or corticosteroid treatments are additional risk factors.
Trimethoprim-sulfamethoxazole typically is the first-line therapy for N. farcinica; treatment with amikacin and imipenem-cilastatin is used less often (7% of patients). Despite aggressive therapy, we observed that the death rate (39%) associated with N. farcinica in recent publications was eight percentage points higher than reported in a review from 2000.

Case Reports
Disseminated Nocardia farcinica: Literature Review
and Fatal Outcome in an Immunocompetent Patient
Jonathan M. Budzik,
1
Mojgan Hosseini,
2
Alexander C. Mackinnon, Jr.,
2,3
and Jerome B. Taxy
2
Abstract
Background: Nocardia farcinica is a gram-positive, partially acid-fast, methenamine silver-positive aerobic acti-
nomycete. Nocardia spp. are opportunistic pathogens, and N. farcinica is the least common species of clinical
importance.
Methods: Review of the recent literature and description of a immunocompetent patient with no known risk
factors who contracted fatal N. farcinica sepsis.
Results: Positive pre-mortem and post-mortem cultures from the lung and synovium correlated with acute
bronchopneumonia and synovitis at autopsy. Colonies of filamentous bacteria, which were not apparent in
conventional hematoxylin and eosin-stained sections, were observed with gram and methenamine silver stains,
but acid-fast stains were negative. A literature review revealed that disseminat ed N. farcinica often is associated
with an underlying malignant tumor or autoimmune disease (88% of patients). Chemotherapy or corticosteroid
treatments are additional risk factors.
Conclusions: Trimethoprim–sulfamethoxazole typically is the first-line therapy for N. farcinica; treatment with
amikacin and imipenem-cilastatin is used less often (7% of patients). Despite aggressive therapy, we observed
that the death rate (39%) associated with N. farcinica in recent publications was eight percentage points higher
than reported in a review from 2000.
N
ocardiosis is a localized or disseminated infection
caused by the soil-dwelling, weakly gram-positive aer-
obic actinomycete Nocardia [1]. The organism, characterized by
filamentous branches measuring less than 1 micron thick, is
not easily observed on conventional hematoxylin and eosin-
stained sections, possibly because of its failure to form the
‘granules characteristic of other actinomycetes. Nocardia is
partially acid-fast by conventional Ziehl–Nielsen staining and
is reactive with Gomori methenamine silver. The typical portal
of entry for Nocardia is the respiratory tract with subsequent
dissemination to distant organs [2]. Nocardia is considered an
opportunistic pathogen [3,4] and is associated with compro-
mised immune function (for example, solid organ or bone
marrow transplant [5], long-term steroid use, connective tissue
disease, or human immunodeficiency virus [HIV] infection),
chronic obstructive pulmonary disease (COPD), alcoholism,
cirrhosis, systemic vasculitis, ulcerative colitis, or renal failure)
[6]. Nocardia asteroides typically is reported as the most fre-
quent cause of nocardiosis in the United States [4–6]. Other
clinically significant species are N. brasiliensis [7], N. farcinica,
N. nova, N. pseudobrasiliens, and N. transvalensis. Nocardia
brasiliensis is commonly associated with primary cutaneous
infection following trauma in immunocompetent patients.
N. farcinica is one of the least frequent clinically important
species, with a reported prevalence of 5% in Switzerland and
6.7% in Crete [6, 8] and a modestly increased prevalence in
Turkey [9]. It is found in a 2:1 ratio over other strains of No-
cardia in Germany [10]. A recent report identified N. farcinica
as a nosocomial pathogen that infected three patients in the
same ward over a six-month period [11]. In the United States,
500–1,000 cases of nocardiosis are diagnosed each year [4],
with N. farcinica constituting 19% of isolates [12]. The present
report of fatal systemic nocardiosis concerns N. farcinica in an
immunocompetent patient for whom the portal of entry was
not established definitively. The diagnostic elements of, and
recent literature on, this unusual infection are reviewed.
Case Report
A 78-year old male presented with a one-day history of right
knee pain and swelling. The patient had received a steroid
injection in the same knee one week before admission. Three
1
Department of Pathology, Pritzker School of Medicine, Chicago, Illinois.
2
Department of Pathology, University of Chicago Medical Center, Chicago, Illinois.
3
Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin.
SURGICAL INFECTIONS
Volume 13, Number 3, 2012
ª Mary Ann Liebert, Inc.
DOI: 10.1089/sur.2011.012
163
Page 1
years prior to admission, the patient had an unexplained ill-
ness consisting of one month of fever (100.3F), a 19-pound
weight loss, and an elevated white blood cell count (15,300/
mm
3
). At that time, he also had an infected cyst in the posterior
scalp, which was treated with cephalexin but was not cultured.
The full extent of clinical evaluation at that time is unknown.
On admission, laboratory evaluation revealed hemoglobin
13.4 g/dL, hematocrit 40.1%, white blood cell count 23,300/
mm
3
, and platelets 435,000/mm
3
. Pertinent chemistry find-
ings were blood urea nitrogen 74 mg/dL, creatinine 2.6 mg/
dL, and glucose 151 mg/dL. Cultures from six knee syno-
vial fluid aspirations and peripheral blood grew N. farcinica
susceptible to ciprofloxacin (minimum inhibitory concentra-
tion [MIC] 1 mcg/mL), linezolid (2 mcg/mL), amikacin (2
mcg/mL), and sulfamethoxazole (4 mcg/mL). A computed
tomography (CT) scan revealed numerous subcentimeter
non-calcific pulmonary nodules (Fig. 1). The patient was
treated with intravenous trimethoprim–sulfamethoxazole
(TMP-SMX). The patient’s renal function improved with hy-
dration. Eleven days after admission, the patient developed
tachypnea and respiratory distress acutely and died.
Autopsy findings included bilateral serosanguinous pleural
effusions (200–300 mL) and copious turbid, greenish fluid in
the right knee. Histologically, there was acute suppurative and
chronic synovitis (Fig. 2A). In both lungs, extensive organizing,
nodular, intra-alveolar pneumonia (Fig. 2B, C) with abscesses
and associated miliary granulomas (Fig. 2D) were observed.
Cultures of both lungs and the synovial fluid were positive for
N. farcinica. Gram-positive, methenamine silver-positive, bea-
ded, branching, filamentous bacteria were identified in both
locations. Although acid-fast stains were negative, N. farcinica
was identified by polymerase chain reaction amplification and
sequencing of the bacterial rRNA.
FIG. 1. Chest CT scan demonstrates multiple subcentimeter
nodules in both lungs.
FIG. 2. Histologic views. (A) Acute fibrinous and chronic synovitis. No organisms are visible by hematoxylin and eosin
stain. Insets show fibrinous exudates. Lower right: Gram stain demonstrating gram-positive thin, branching, filamentous
forms. Lower left: Gomori methenamine silver (GMS) stain, similarly demonstrating organism morphology. (B) Lung
nodule. Low-magnification view of lung with centrally necrotic nodule of organizing pneumonia, lower left. (C) Higher-
magnification view of the nodule showing central necrotic focus and peripheral lymphoid infiltrate. Lower right: Gram stain
of center of nodule demonstrating numerous gram-positive thin, branching, filamentous organisms. Lower left: GMS stain
showing similar organisms. (D) Microscopic, non-necrotic granulomas were associated with nodular abscess.
164 BUDZIK ET AL.
Page 2
Table 1. Clinical Characteristics of 67 Patients with Nocardia farcinica
Infections since Last Review by Torres et al. [13]
Age/sex Underlying condition
Systemic
steroids?
Prophylaxis
with TMP-SMX Disease Therapy Outcome Ref.
78/M None No No Lung, joint, blood TMP-SMX (11 days) Death This study
85/M NHL, DM, chronic bronchitis Yes
a
No Lung, blood IV CTX (1 g qid) + IND
(20 days)
Death 14
67/M Liver transplant Yes Yes Lung TMP-SMX (12 mos) Survived 48
28/M Sarcoidosis Yes No CNS TMP-SMX + MER (15 days);
TMP-SMX (6 mos)
Survived 48
81/M COPD Yes No Lung
b
AMK + AMX/CLAV (12 days) Death: Related 48
65/F CLL, hemolytic anemia No Yes Disseminated TMP-SMX + MER (1.5 mos);
TMP-SMX + AMK (4 mos);
TMP-SMX + AMX/CLAV
(6 mos)
Survived 48
38/F Transplantation of intestine
(Gardner’s syndrome)
Yes No Lung, liver
c
TMP-SMX (800 mg/160 mg
qd); CPX (200 mg q
12 h) + AMX/CLAV (2.2g q
8h)+ CFZ + IMI
Death: Related 8
77/M COPD, invasive Aspergillus No No Lung TMP-SMX (3 mos) Survived 48
29/M HIV No No Cerebral Surgery Died 49
30/F HIV, MAC No No Cerebral, pulmonary TMP-SMX; MIN (6 weeks) Died 49
34/F SLE, drug abuse Yes No Brain abscess,
subcutaneous leg
abscess
Died 50
70/M COPD, pneumoconiosis Yes No Lung TMP-SMX (10 mg/kg/d;
7 mos)
Death: Related 51
62/M Kidney transplant NR NR Soft tissue/blood TMP-SMX + CPX Survived 38
60/F Kidney transplant NR NR Soft tissue/blood TMP-SMX Survived 38
51/M Kidney transplant NR NR Soft tissue/lung/brain TMP-SMX + CTR Survived 38
50/F Lymphoma NR NR Blood IMI Survived 38
58/F COPD NR NR Lung TMP-SMX + IMI + AMK Survived 38
74/F Glioma Yes No Lung MER (7 days); TMP-SMX
(3 mos)
Survived 48
47/F Lung transplant Yes
d
No Lung TMP-SMX + CTR + IMI Death 20
46/M Lung transplant Yes
e
Yes Lung TMP-SMX + CTR Death 20
54/M Alcoholism No No Spine, CNS, psoas Surgery, DXN + GEN Survived 52
2 mo/M None No No Disseminated lymphatic
abscesses
CTX + CXN + MET; AMK
(3 weeks); TMP-SMX
(3 mos)
Survived 24
37/M HIV No No Lung TMP-SMX (7 mos) Survived 48
Leg fracture/trauma No No Brain abscesses VAN + GEN + CTZ;
TEI + CTZ, TMP-SMX;
VAN + AMK; LIN + MIN
Survived 53
62/M Evans syndrome Yes No CNS TMP-SMX + IMI (90 days) Death: Not related 48
68/M COPD, DM2 Yes No Septic arthritis of knee
f
TMP-SMX (6 mos) Survived 54
(continued)
165
Page 3
Table 1. (Continued)
Age/sex Underlying condition
Systemic
steroids?
Prophylaxis
with TMP-SMX Disease Therapy Outcome Ref.
60/M Insulin-dependent DM2,
systemic vasculitis with
ESRD
Yes No Brain abscess MER (2 g/d) + AMP (2 g/d)
(7 days)
Death 55
52/M Non-small-cell lung cancer,
radiation, chemotherapy
No No Bacteremia IV CFZ 1 g tid; AMK 500 mg
bid; MET (600 mg tid) (24 h)
Death 56
58/M Immunosuppression Yes No Brain abscesses CFZ + MER; LIN + MER Survived 57
75/M Immunosuppression Yes No Thyroid, psoas, spine,
basal ganglia, lungs
TMP-SMX (320/1600 mg q 6
h; 2 days)
Death: Related 34
NR Renal transplant, DM Yes No Lung CTR + AMK; IMI; TMP-SMX
(6 mos)
Survived 11
NR Bullous pemphigoid, DM Yes No Pulmonary and cerebral CTR + AMK; IMI; TMP-SMX,
surgery (37 days)
Death 11
NR None No No Brain abscess CTR + AMK; MER; TMP-SMX,
surgery (6 mos)
Survived 11
NR None No No Brain abscess CTR + AMK; TMP-SMX,
surgery
(6 mos)
Survived 11
NR None No No Brain abscess CTR + AMK; MER; TMP-SMX,
surgery (6 mos)
Survived 11
75/M Interstitial pneumonia Yes No Lung CFP; TMP-SMX (12 mos) Survived 7
28/M Ulcerative colitis Yes No Subcutaneous abscess in
left popliteal space
Surgery, TMP-SMX Survived 7
72/F BOOP, cirrhosis Yes No Lung IMI + ITC; TMP-SMX Death 7
68/M ITP Yes No Lung, brain abscesses,
blood
AMP/SULB (1.5 g/day; TMP-
SMX (160 mg/800 mg/day)
Survived 58
12/M Renal transplant Yes Yes Brain abscesses TEI + CTR; LIN 600 mg bid,
MER (20 days); AMX/
CLAV (PO)
Survived 22
91/M IPF Yes
g
No Lung IV TMP-SMX Death 41
76/F COPD, vasculitis Yes
a
Yes Lung LVX + CTX; MER Survived 41
49/M Renal transplant, alcoholism Yes No Lung, brain IMI (1 g tid) + TMP-SMX
(320 mg/1600 mg qid);
MOX
Survived 44
42/M DM, alcoholism No No Brain abscess CTR + MET + TMP-SMX Survived 36
26/F SLE Yes
a
No Subretinal abscess, lung
abscess
Vitreous tap with injection of
AMK; BAL; TMP-SMX IV
(80 mg/400 mg/q 6 h); CPX
PO
(1 g qd)
Survived 42
57/M None No No Brain abscess Surgery, TMP-SMX + IMI;
MOX + IMI; MOX (1 yr)
Survived 59
62/F SLE, COPD, DM Yes NR Lung Unknown Death 60
35/M HIV, COPD No NR Lung, disseminated SUF Death 60
(continued)
166
Page 4
Table 1. (Continued)
Age/sex Underlying condition
Systemic
steroids?
Prophylaxis
with TMP-SMX Disease Therapy Outcome Ref.
78/M COPD Yes NR Lung SUF Survived 60
73/F Hodgkin’s disease No NR Disseminated TMP-SMX Death 60
46/M HIV No NR Lung, disseminated TMP-SMX Death 60
65/F COPD No NR Lung TMP-SMX Death 60
79/M Rheumatoid arthritis Yes NR Lung, disseminated IMI; AMK Death 60
85/M Lymphoma, COPD Yes NR Lung, disseminated CTR Death 60
68/M Renal transplant, HCV Yes NR Lung SUF Survived 60
NR NHL No
h
No Lung, gluteal region,
iliac fossa, kidney,
cerebrum
TMP-SMX + IMI; AMK + TMP-
SMX; TMP-SMX (630 days)
Survived 33
NR Multiple myeloma No
h
No Lung TMP-SMX 2 · 1920 mg IV (60
days)
Survived 33
NR Polymyalgia rheumatica Yes No Upper leg abscess TMP-SMX 2 · 1920 mg IV (90
days)
Survived 33
49/M ITP Yes No Lung TMP-SMX (3 mos) Death 61
8/M CF, ABPA Yes No Lung TMP-SMX 80/400 mg (62
days)
Survived 23
73/M Multiple myeloma Yes No Disseminated
subcutaneous
nodules
TMP-SMX 800 mg (6 mos) Survived 37
65/F HIV, COPD, vasculitis Yes No Lungs IV TMP-SMX + IMI (5 days) Death 62
43/M None No No Brain abscess CTR; TMP-SMX + MOX Survived 63
64/M Lung transplant No
i
Yes Lung IMI + AMK; TMP-SMX IV Survived 25
NR Lung transplant Yes
d,g
Yes Lung TMP-SMX 160/800 mg PO
bid)
Survived 31
53/M None No No Brain abscess, lung TMP-SMX (7 days); IMI; LIN;
TMP-SMX
(1 yr)
Survived 19
71/M Bladder cancer Yes No Lung IMI + AMK Survived 10
a
Plus cyclophosphamide.
b
Co-infection with cytomegalovirus and Pneumocystis jirovecii.
c
Co-infection with Pseudomonas aeruginosa.
d
Plus tacrolimus.
e
Plus cyclosporine.
f
Co-infection of lungs with P. aeruginosa, and Escherichia coli.
g
Plus azathioprine.
h
Patients were treated with chemotherapy and immunotherapy for cancer.
i
Microphenolate + tacrolimus immunosuppression.
ABPA = allergic bronchopulmonary aspergillosis; AMK = amikacin; AMP/SULB = ampicillin/sulbactam; AMX/CLAV = amoxicillin/clavulanic acid; BAL = bronchoalveolar lavage; BOOP = bronch-
iolitis obliterans organizing pneumonia; CF = cystic fibrosis; CFP = cefozopran; CFZ = ceftazidime; CLL = chronic lymphocytic leukemia; CPX = ciprofloxacin; COPD = chronic obstructive pulmonary
disease; CTR = ceftriaxone; CTX = cefotaxime; CTZ = ceftazidine; CXN = cloxacillin; DXN = dicloxacillin; DM = diabetes mellitus; ESRD = end-stage renal disease; GEN = gentamicin; HCV = hepatitis C
virus; HIV = human immunodeficiency virus; IMI = imipenem-cilastatin; IND = indomethacin; IPF = idiopathic pulmonary fibrosis; ITC = itraconazole; ITP = idiopathic thrombocytopenic purpura;
IV = intravenous; LIN = linezolid; LVX = levofloxacin; MAC = Mycobacterium avium complex; MER = meropenem; MET = metronidazole; MIN = minocycline; MOX = moxifloxacin; NHL = non-Hodgkin
lymphoma; NR = not reported; PO = orally; SLE = systemic lupus erythematosus; SUF = sulfadiazine; TEI = teicoplanin; TMP-SMX = trimethoprim–sulfamethoxazone; VAN = vancomycin.
167
Page 5
Discussion
A relatively infrequent cause of nocardiosis, N. farcinica is a
clinically aggressive infection, particularly in immunocom-
promised patients. For unknown reasons, small numbers of
immunocompetent patients also are affected. In the last re-
view of N. farcinica sepsis by Torres et al. in 2000, a retro-
spective analysis of 53 patients identified eight cases (15%) in
which no predisposing factors for infection were discernible
[13]. Of the eight patients, one presented with a brain abscess
[14] and two had lung or kidney involvement or both [15,16].
Similarly, Beaman et al. reported that 15% of patients infected
with Nocardia had no identifiable underlying condition [4]. In
most cases, the pathogenesis of Nocardia infection is presumed
to be via an airborne route from soil inhabited by latent forms.
Following colonization of the respiratory tract, T lymphocyte-
mediated cellular immunity is activated after phagocytosis of
the organism [15,16]. The infection may remain localized or
disseminate promptly. If the infection is localized, latency and
subsequent reactivation may occur, resembling the patho-
genesis of tuberculosis.
Our search of the literature for cases of N. farcinica published
since the last review [14] demonstrates the continued rare oc-
currence of N. farcinica infection in immunocompetent patients
[17]. Of the 67 cases reported since 2000, 59 (88%) patients
suffered from a predisposing illness or had risk factors asso-
ciated with diminished immunocompetence (Table 1). Of the
eight immunocompetent patients in this cohort, six presented
with brain abscesses and two with disseminated disease.
Previous reports indicate that Nocardia spp. were responsible
for 2%–20% of cerebral abscesses in immunocompromised
patients [18,19], with a mortality rate of 30%–80% [14,20].
In agreement with previously published reports [13], the
ratio of male:female infection was 3:1. Although typically re-
sponsible for infections in adults, N. farcinica also infected a
12-year-old adolescent following renal transplant [21], an
8-year-old boy with cystic fibrosis [22], and an otherwise-
healthy 2-month-old boy [23]. Our review of the literature
demonstrated that 10.4% of patients receiving TMP-SMX
prophylaxis became infected. Nocardia infection also is re-
ported in 60% of lung transplant recipients [19,24]. Further-
more, most of the patients (61.2%) infected with N. farcinica
were receiving systemic steroids or chemotherapy. Corticos-
teroid treatment inhibits the cytokine response and phago-
cytic killing of microbes by macrophages [25].
Table 2 summarizes the co-morbid ity factors most com-
monly associated with infection for the cases in Table 1. Hui
et al. [26] reported that 63% of pulmonary nocardiosis pa-
tients had underlying respira tory disorders. In particular,
COPD was identified as a risk factor in 23% of patients with
pulmonary nocardiosis [27]. Nocard ia infection is reported
in as many as 3% of transplant recipients [7] with an asso-
ciated mortality rate ranging from 0% to 75% in lung trans-
plant recipients [19,28]. Alcoholism (3.0%), hematologic
malignancy (4.5%), HIV infection (7.5%), idiopathic thrombo-
cytopenic purpura (ITP) (3.0%), systemic lupus erythematosus
(SLE)(4.5%), neoplastic disease (7.5%), diabetes mellitus (9.0%),
and vasculitis (4.5%) were co-morbid conditions identified in
at least two patients.
Disseminated nocardiosis is associated with a mortality
rate ranging from 7% to 85% in immunocompromised hosts
[29]. Disseminated disease and bacteremia occurred in 37% of
the cases reported since 2000 (Table 3). Assuming that patients
with central nervous system lesions also had a lung infection
that was unrecognized [13], 39 patients (58%) had dissemi-
nated disease. Soft tissue infection involving muscles or con-
nective tissue, including subcutaneous abscesses, was present
in 17.9% of the cases. Torres et al. [13] reported a mortality rate
of 31% in cases diagnosed before 2000; the mortality rate in the
cases reported since then was 39%.
The diagnosis rests on the demonstration of organisms in
tissue, cultures, or both. Histologically, organisms are difficult
to recognize by hematoxylin and eosin stains. Also, as dem-
onstrated here, acid-fast staining is variable and unreliable [1,
13]. Gram and methenamine silver (GMS) stains usually are
positive, although gram staining may be weak. Cultures of
Nocardia can take more than five days to grow [30]. Bio-
chemical tests may be used for identification of a subset of
Nocardia spp., but 16S rRNA gene sequencing or restriction
analysis of amplified DNA (16S rRNA or hsp65 genes) allows
rapid identification [31, 32]. This is significant, as it is im-
portant to distinguish N. farcinica from N. asteroides—the
former is more resistant to antimicrobial agents and has a
Table 2. Co-Morbid Conditions in 67 Cases
of Nocardia farcinica Infection
a
Predisposing factor
No. (%)
of patients
Solid organ transplant recipient 12 (17.9)
Chronic obstructive pulmonary
disease
9 (13.4)
Hematologic neoplasm 3 ( 4.5)
Human immunodeficiency virus
infection
5 ( 7.5)
Idiopathic thrombocytopenic
purpura
2 ( 3.0)
Systemic lupus erythematosus 3 ( 4.5)
Solid neoplasm 5 ( 7.5)
Alcoholism 2 ( 3.0)
Diabetes mellitus 6 ( 9.0)
Vasculitis 3 ( 4.5)
Immunosuppression (steroids
or chemotherapy)
41 (61.2)
Miscellaneous
b
17 (25.4)
a
Some patients presented with more than one factor.
b
One case each of invasive aspergillosis, Mycobacterium avium
complex, drug abuse, pneumoconiosis, Evans syndrome, bullous
pemphigoid, interstitial pneumonia, ulcerative colitis, bronchiolitis
obliterans organizing pneumonia, idiopathic pulmonary fibrosis,
polymyalgia rheumatica, cystic fibrosis, allergic bronchopulmonary
aspergillosis, cirrhosis, sarcoidosis, trauma, and chronic bronchitis.
Table 3. Organ Involvement in 67 Patients
with Nocardia farcinica Infection
Organ or site No. (%) of patients
Lung 40 (59.7)
Brain 22 (32.8)
Soft tissue 12 (17.9)
Spine 2 ( 3.0)
Kidneys 1 ( 1.5)
Lymphatics 1 ( 1.5)
Disseminated
a
25 (37.3)
a
‘ ‘Disseminated’ ’ includes bacteremia or more than one organ involved.
168 BUDZIK ET AL.
Page 6
higher risk of dissemination [33]. The treatment for N. farcinica
is complicated by its resistance to most b-lactam anti-
microbials, tobramycin, and tetracyclines [12, 34]. The treat-
ment of choice is TMP-SMX [35]. However, side effects such as
skin reactions may necessitate alternative therapy [6,24,36]. In
addition, as many as 50% of isolates demonstrate TMP-SMX
resistance, emphasizing the need for antibiotic susceptibility
testing of clinical isolates [13,37,38].
N. farcinica is susceptible to TMP-SMX, minocycline, linezolid,
moxifloxacin, and amikacin and demonstrates variable suscep-
tible to imipenem-cilastatin and ciprofloxacin [20, 39-43]. It is
recommended that immunocompetent patients be treated for at
least six months [44]. If the central nervous system is involved, 12
months of therapy is recommended [44]. Therapy for N. farcinica
has become more aggressive, with increasing administration of
multiple antimicrobials. In this review, 74.6% of patients (n = 50)
received TMP-SMX as part of their treatment. Carbapenems
(n = 25; 37.3%), amikacin (n = 16; 23.9%), and ceftriaxone (n = 12;
17.9%) also were used commonly (see Table 1). A previous
review found TMP-SMX was administered in 54% of patients
infected with N. farcinica, whereas amikacin with imipenem-
cilastatin and amoxicillin/clavulanic acid were used in only 7%
[13]. Nevertheless, the death rate was 31% with TMP-SMX and
38.8% with carbapenems and amikacin [13].
The patient described here was unusual in that he was
immunocompetent. Although the primary origin of his in-
fection is not documented, it is tempting to speculate that the
prior febrile episode and infected cyst of three years earlier
was his initial encounter with the organism. Subsequent re-
activation with dissemination may have been prompted by
unknown factors and perhaps facilitated by the local steroid
injection. The distribution of his infection was pulmonary and
musculoskeletal (limited to the right knee) with no radiologic
or post-mortem evidence of central nervous system involve-
ment. Despite therapy, the patient died from Nocardia sepsis,
attesting to the virulence N. farcinica.
Acknowledgments
JMB is a trainee of the National Institutes of Health Medical
Scientist Training Program (Grant GM07281) at the University
of Chicago.
Author Disclosure Statement
No conflicting financial interests exist.
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Address correspondence to:
Dr. Alexander C. Mackinnon, Jr.
Department of Pathology
Medical College of Wisconsin
Room 1176 FMLH West
Milwaukee, WI 53226
E-mail: amackinnon@mcw.edu
170 BUDZIK ET AL.
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  • Source
    • "As intrinsic infection, N. farcinica caused community-acquired pneumonia associated with influenza A virus infection this time. Nocardia infections are rare but potentially fatal, typically more problematic in patients with cell-mediated immunosuppressive conditions [21], but occasionally inimmunocompetent patients as well [22]. N. farcinica is a ubiquitous, Gram-positive actinomycete saprophyte that lives in soil, organic matter and water. "
    [Show abstract] [Hide abstract] ABSTRACT: Nocardia spp. has not been reported previously as a cause of post-influenza pneumonia. Here we present a first case of post-influenza bacterial pneumonia due to Nocardia farcinica. Initial reason for hospitalization of the 90 year old female patient was a pneumonia with the symptoms of fever and productive cough. A rapid test for influenza antigen was positive for influenza A virus. Treatment with Zanamivir and piperacillin was initiated. However, after 1 week of treatment, the infiltration shadows on chest X-ray had worsened. Because the expectorated sputum collected on admission for culture was found to be positive for Nocardia spp., piperacillin was replaced with trimethoprim/sulfamethoxazole, and a chest X-ray showed some improvement. Although pulmonary nocardiosis with co-infection with influenza A is extremely rare, clinicians should be alert to the possibility.
    Full-text · Article · May 2014 · Journal of Infection and Chemotherapy
  • Source
    • "Gram staining is the most sensitive method for visualizing and recognizing nocardia. Nocardia is partially acid-fast by conventional Ziehl-Nielsen staining and is reactive with Gomori methenamine silver.16 It is important to obtain cultures from tissue biopsies when disseminated infection is considered to allow for prompt organism identification and perhaps better patient care.17 "
    [Show abstract] [Hide abstract] ABSTRACT: Nocardia species are aerobic, gram positive filamentous branching bacteria that have the potential to cause localized or disseminated infection. Nocardiosis is a rare disease that usually affects immunocompromised patients and presents as either pulmonary, cutaneous or disseminated nocardiosis. Forty-two year-old hispanic male presented to our care with bilateral lower extremity weakness, frontal headache, subjective fever, nausea, and vomiting. Brain computed tomography (CT) revealed multiple hyperdense lesions with vasogenic edema in the frontal, parietal and left temporal lobes. Chest CT demonstrated bilateral cavitary nodules in the lung and right hilar lymphadenopathy. Brain magnetic resonance imaging revealed multiple bilateral supratentorial and infratentorial rim enhancing lesions involving the subcortical gray-white matter interface with vasogenic edema. Patient was started on empiric therapy for unknown infectious etiology with no response. He eventually expired and autopsy findings revealed a right hilar lung abscess and multiple brain abscesses. Microscopic and culture findings from tissue sample during autopsy revealed nocardia wallacei species with multidrug resistance. The cause of death was stated as systemic nocadiosis (nocardia pneumonitis and encephalitis). The presence of simultaneous lung and brain abscesses is a reliable indication of an underlying Nocardia infection. An increased awareness of the various presentations of nocardiosis and a high index of clinical suspicion can help in a rapid diagnosis and improve survival in an otherwise fatal disease. This case highlights the importance of obtaining a tissue biopsy for definitive diagnosis on the initial presentation when an infectious process is considered in the differential diagnosis and early treatment can be initiated.
    Full-text · Article · Feb 2014 · Infectious disease reports
  • [Show abstract] [Hide abstract] ABSTRACT: : Anti-tumor necrosis factor (anti-TNF) therapy is beneficial in the management of many chronic immune-mediated inflammatory diseases. However, its use is associated with increased risk of bacterial, fungal and viral infections. We present a case of cutaneous nocardiosis that occurred in a 61-year-old man, whose Crohn's disease was treated for nearly 1.5 years with infliximab. Prompt therapy with trimethoprim-sulfamethoxazole led to complete resolution. Only few cases of nocardiosis complicating anti-TNF therapy are reported in the literature. We present the case report and summary of the available literature with updates on the management and the treatment of the disease.
    No preview · Article · Mar 2013 · The American Journal of the Medical Sciences
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