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Citation: Ghosh S, Pal D, Pal S, Roy J and Bhakta A. An Unusual Presentation of Nocardiosis - A Report of Two
Cases. Austin J Trop Med & Hyg. 2015;1(2): 1006.
Austin J Trop Med & Hyg - Volume 1 Issue 2 - 2015
ISSN: 2472-3681 | www.austinpublishinggroup.com
Pal et al. © All rights are reserved
Austin Journal of Tropical Medicine &
Hygiene
Open Access
Abstract
Nocardiosis is an opportunistic infection more common in immune
compromised hosts. Disseminated nocardiosis has a poor outcome. We report
a case of disseminated nocardiosis with nocardaemia (case-1) which is an
extremely rare finding even in immune compromised subjects. In case-2 we
found pulmonary abscess caused by nocardia in a patient of sarcoidosis on
steroids. Vascular thrombosis complicating nocardiosis is not recognized. We
report two cases of nocardiosis with arterial thrombosis.
Keywords: Immunocompromised state; Disseminated nocardiosis;
Cerebral abscess; Pulmonary abscess; Vascular thrombosis
He presented with foot drop in another institution four months
before where he was diagnosed as having mononeuritis multiplex
based on NCV/EMG study showing bilateral peroneal neuropathy.
His connective tissue panel (Anti-nuclear antibody etc.) and vasculitis
screening (ANCA) were all negative at that time. He was started
on oral cyclophosphomide (50 mg/day) and prednisolone (40mg/
day) for mononeuritis multiplex in that institute with significant
improvement of his muscle strength and became ambulatory. He was
also on oral anticoagulant therapy following a massive pulmonary
thromboembolism which he suffered few weeks after starting
immunosuppressive therapy (Figure 1). At the time of admission,
he was receiving prednisolone-40mg/day, cyclophosphomide-50mg/
day, oral anticoagulant and calcium supplement.
Examination of the respiratory system revealed tachypnoea and
coarse crackles in right infrascapular area. Neurological examination
revealed wasting of proximal and distal muscles of both lower limbs
with muscle power of 4/5 in all groups. Deep tendon reflexes were
preserved except left knee jerk. Sensory system, cranial nerves and
cerebellar functions were all normal.
Introduction
Nocardia species are saprophytic aerobic actinomycetes and are
common worldwide in soil causing decay of organic matter. It is an
opportunistic pathogen causing significant morbidity and mortality
in human beings. It predominantly affects lung with pre-existing
structural defects and also with co-existing mycobacterial infection.
Disseminated nocardiosis occurs through haematogenous spread to
distant organs including brain (commonest), bone, soft-tissues and
kidney; whereas peritoneum and heart valves only rarely affected.
Isolating nocardia in blood culture (nocardaemia) is extremely rare
[1]. Endovascular foreign body [2] e.g. prosthetic heart valve is a
unique risk factor for nocardaemia but our patient (case I) did not
posses any such foreign body. Nocardia bacteraemia is also associated
with simultaneous infection with other bacterial pathogens, especially
Gram negative organisms in 30% [2]. First patient had concomitant
Klebsiella infection [Extended-Spectrum Beta-Lactamase (ESBL)
producer] in lung. Surprisingly in both the cases vascular thrombosis
complicated the picture-thrombosis in pulmonary trunk was in case-
1 and lacunar infarcts of brain found in case-2. Nocardiosis and
vascular thrombosis may be causally related.
Case Report
Case I
A 52 yr old gentleman presented to our clinic with fever and
dry cough for 15 days. He also complained of chest tightness and
exertional breathlessness for the same duration. His fever was low
grade, intermittent in nature and subsided only on taking antipyretics.
It was associated with cough without expectoration, hemoptysis or
chest pain.
He had a significant past history. Ten years ago he was treated for
pulmonary tuberculosis.
Case Report
An Unusual Presentation of Nocardiosis - A Report of
Two Cases
Subhasish Ghosh1
, Dipankar Pal2
*, Shekhar Pal3
,
Jayanta Roy4
and Arpita Bhakta5
1
Consultant Pulmonologist, Apollo and AMRI Hospitals,
Kolkata, India
2
RMO cum Clinical Tutor, Dept.of Tropical Medicine,
School of Tropical Medicine, Kolkata, India
3
Assistant Professor, Department of Tropical Medicine,
School of Tropical Medicine, Kolkata, India
4
Consultant Neurologist, Department of Neurology,
Apollo Hospitals, Kolkata, India
5
Head of the Dept.of Microbiology, AMRI Hospitals,
Kolkata, India
*Corresponding author: Dipankar Pal, RMO cum
Clinical Tutor, School of Tropical Medicine, India
Received: December 18, 2014; Accepted: February 17,
2015; Published: February 19, 2015
Figure 1: CT Pulmonary Angiography showing saddle embolus.
Austin J Trop Med & Hyg 1(2): id1006 (2015) - Page - 02
Dipankar Pal Austin Publishing Group
Submit your Manuscript | www.austinpublishinggroup.com
Total leucocyte count was 15,500/cu mm with neutrophilia,
procalcitonin-0.14 (normal < 0.05), INR-5.27. Platelet count-3.80lac/
cu mm. Blood culture was sent. Chest x-ray showed nodular opacity
in right lower lobe with pleural reaction (Figure 2). CT thorax
with CT pulmonary angiography revealed nodular consolidation
involving anterior and lateral segment of right lower lobe with area
of necrosis abutting pleura with adjoining pleural reaction. No
pulmonary thrombosis or embolism was evident (Figure 3) this time
Fibre Optic Bronchoscopy (FOB) and Bronchoalveolar Lavage (BAL)
with washing from right basal and apical segment of right lower lobe
was done and sent for Gram stain , AFB stain, culture, fungal stain
and modified AFB and silver stain.
Gram positive branching, fine, delicate, filamentous organisms
positive on modified AFB stain (using 1% sulphuric acid as
decolourising agent) (Figure 4) [3] was detected on BAL along
with growth of Klebsiella aerogenes [ESBL producer] and Nocardia
asteroides on culture. Blood culture also grew Nocardia asteroides
(growth time 59 hrs) [1]. The colonies of Nocardia grown from
both BAL and blood were adherent, dry, wrinkled, chalky white
on sheep blood agar .The isolate was identified as Nocardia
asteroides by Vitek 2 Compact system (Biomerieux).Isolate was
sensitive to ceftriaxone, amikacin, imipenem, co-amoxiclav and
trimethoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole
[TMP 640 mg/day in divided doses] and imipenem [4] were started,
cyclophosphamide was stopped after discussion with neurologist.
A tapering regimen of steroid was initiated. He started to show
positive response to above treatment of pulmonary nocardiosis [5]
with subsidence of fever. However, on the third day of treatment
he complained of giddiness and soon had a brief generalized tonic
clonic seizure. CT brain showed a right temporal hypodensity. MRI
revealed multiple cerebral abscesses with ring enhancement and
Figure 2: CXR showed nodular opacity in right lower lobe with pleural
reaction.
Figure 3: CT Scan thorax showing nodular consolidation involving right lower
lobe.
Figure 4: Modified AFB stain showing branched filamentaous organisms.
Figure 5: CT Brain showing right temporal hypodense lesion. (B) MRI picture
of cerebral abscess.
Figure 6: Chest X-ray post discharge showing significant resolusion.
ANTIBIOTICS I ANTIBIOTICS I
Penicillin G Combinations
Amoxycillin S Amoxy-clav S
Pipericillintazobactum S
Vanconnycin S Aminoglycosides
Clindamycin S Gentamycin S
Tobramycin S
Fluroquinolones Netilmycn S
Noriloxacin Amikacin S
Ciprofloxacin S
Ofloxacin S Others
Levofloxacin S Cotrimoxazole S
Gatifloxacin S
Carbapenems
Imipenem S
Table 1: Antibiogram of (Case 1).
S: Sensitive, R: Resistant, I: Intermediate
Austin J Trop Med & Hyg 1(2): id1006 (2015) - Page - 03
Dipankar Pal Austin Publishing Group
Submit your Manuscript | www.austinpublishinggroup.com
perilesional edema (Figure 5) [6]. We started meropenem in place of
imipenem and phenytoin was added to control seizure. He remained
stable on this combination. We discharged him after a week on
above medications and readmitted 2 weeks later for craniotomy and
drainage of cerebral abscess. The cerebral abscess material also grew
Nocardia asteroides on culture Co-trimoxazole and meropenem were
continued for 4 weeks in view of disseminated disease and he was
discharged home on oral co-trimoxazole, co-amoxiclav, prednisolone
- 5mg daily and oral anti-coagulant with monthly follow-up advice
(Table 1). He remained a febrile without neurological sequel, with
chest x-ray showing excellent resolution (Figure 6).
Case II
A 53 yr old lady was admitted in our institution with a febrile
illness for 2 weeks associated with right sided pleuritic chest pain and
easy fatiguability . Ten months ago she first presented to a local doctor
with persistent cough. A CT thorax at that time showed nodular
opacities with some of the nodules along the bronchovascular bundles
and consolidation of apical segment of left lower lobe with ground
glass opacity. There was widespread mediastinal lymphadenopathy
involving right paratracheal, pretracheal, precarinal, AP window and
subcarinal stations (Figures 7 & 8). As she refused bronchoscopy,
prednisolone (60mg/d) [7]was started with a provisional diagnosis of
sarcoidosis. Her cough got better and chest x-ray (Figure 9) showed
significant resolution, especially of left lung opacities. There was
no history suggestive of pulmonary tuberculosis/connective tissue
disease/ischaemic heart disease or asthma. She was a nonsmoker and
non-alcoholic but she became diabetic, likely steroid induced.
On clinical examination, she had cushingoid facies with oral
thrush, was febrile and appeared toxic. There was no palpable
peripheral lympadenopathy, engorged jugular veins, pedal edema.
Examination of the respiratory system revealed diminished vesicular
breath sound with coarse crepitations at places of right infrascapular
and infraaxillary area with an evanescent rub. Examination of all
other systems was normal. She was on 30 mg/day of prednisolone
[7] and chest x-ray revealed dense nodular shadows in right lower
zone (Figure 10) [6,9] during admission. Hemoglobin-12.1gm%,total
leucocyte count-8100(Neutrophil-87%), platelets-6.87lac/ul, ESR-
103, CRP> 250, Procalcitonin-0.29 (normal<0.05), SGOT/SGPT-
normal, GGT-319, Alkaline-phosphatase-222, urea, creatinine,
electrolytes–normal. Blood culture was sent, Sputum was sent for
gram stain, AFB stain and culture.
Management was focused in the line of pneumonia in an
immune compromised host (steroid induced). A tapering regime
of prednisolone was initiated. Broad spectrum antibiotic cover was
commenced with ertapenem, linezolid and moxifloxacin. CT scan
thorax showed right middle and lower lobe necrotizing pneumonia
with right sided multi loculated pleural effusion (Figure 11) [6,9]. The
opacity at apical segment of left lower lobe had regressed considerably
with sparse nodules. Blood culture was unyielding. Sputum
examination however revealed plenty of gram positive, beaded,
branched filamentous organisms suggestive of nocardia species which
was also positive on modified acid fast stain. Ertapenem was changed
to meropenem [4], linezolid was continued and co-trimoxazole was
started (TMP 15mg/kg/day) in place of moxifloxacin.
After being put on this regimen she became a febrile in 48 hours
and continued to show good clinical response. CT scan brain did not
show any abscess. MRI brain however showed tiny foci of lacunar
Figure 7: CT Thorax showing (A)nodular lesions in peri lymphatic distribution
with ground glass opacity. (B) Mediastinal lymphadinopathy.
Figure 8: Chest X-ray showing nodular opacities.
Figure 9: Chest X-ray showing improvement following steroids.
Figure 10: Chest X-ray showing dence nodular opacities involving right lower
lobe.
Figure 11: CT Scan showing (A)Right middle lobe consolidation with air
bronchogram. (B) showing right sided multiloculated pleural effusion.
Austin J Trop Med & Hyg 1(2): id1006 (2015) - Page - 04
Dipankar Pal Austin Publishing Group
Submit your Manuscript | www.austinpublishinggroup.com
infarcts in temoro-parietal (bilateral) and left occipital regions. She
remained a febrile with the above regime. In the meantime, sputum
culture yielded Nocardia asteroides. Meropenem was stopped after 14
days and co-amoxiclav was added based on the sensitivity pattern of
the organism in sputum culture. Linezolid was also stopped as there
was no evidence of disseminated disease.
Patient was discharged after 2 weeks on oral cotrimoxazole and
coamoxiclav (Table 2). CRP was 35 on discharge. She was also on
maintenance dose of steroid (5 mg in morning and 2.5 mg in evening)
and clopidogrel. She continued to do well without drug related
adverse events noted so far. Chest X-ray one month post-discharge
showed significant improvement (Figure 12).
Discussion
Nocardiosis remains an elusive diagnosis despite its discovery
by Edmond Nocard in 1888. There are more than 50 species of
nocardia with at least 30 species recognized as pathogenic to human.
Fragmented bacterial mycelia enter lungs via aerosol route. Although
pulmonary nocardiosis is a common presentation [2/3rds of cases]
[5], human to human transmission is not documented. It is a disease
unique to immunosuppressed individuals. But 30% of infections
ANTIBIOTICS I II ANTIBIOTICS I II
Penicillins     Combinations    
Amoxycillin S   Amoxy-clav S  
Piperacillin     Ampicillin-sulbactam    
Ticarcillin     Piperacillin-tazobacta m    
      Ticarcillin-clavulunic acid    
Cephalosporins     Cefoperazone-sulbactam    
Cefuroxime          
Cefdinir     Aminoglycosides    
Cefixime     Gentamycin    
Ceftriaxone S   Tobramycin    
Cefotaxime     Netilmycn    
Ceftazidime     Amikacin S  
Cefepime          
      Fluroquinolones    
Cefamycin     Norfioxacin    
Cefoxitin     Ciprofloxacin S  
      Ofloxacin    
Monobactam     Levofloxacin    
Aztreonam     Gatifloxacin  
 
Carbapenems Others
Imipenem S Nitrofurantoin
Meropenem Chloramphenicol
Ertapenem Cotrimoxazole S
Erythromycin S
Linezolid
S
Tetracycline
Polymyxin B
Table 2: Antibiogram of (Case 2).
SPECIMEN: SPUTUM			
METHOD: Aerobic bacterial culture	
REPORT : Culture shows growth of Nocardia asteroides
Colony count :104
cfu/m1			
ANTIBIOGRAM (Disc Diffusion method)
S: Sensitive, R: Resistant, I: Intermediate
are also seen in immune competent hosts [6], Chronic Obstructive
Pulmonary Disease (COPD) is a risk factor among such groups [7].
Glucocorticoidtherapyandmalignancyanditstreatmentarecommon
risk factors [7]. Pulmonary nocardiosis presents as necrotizing
pneumonia with or without cavitation. They may also present as
a slowly enlarging pulmonary nodule with or without empyema,
Figure 12: Chest X-ray showing significant improvement with treatment.
Austin J Trop Med & Hyg 1(2): id1006 (2015) - Page - 05
Dipankar Pal Austin Publishing Group
Submit your Manuscript | www.austinpublishinggroup.com
confusing with malignancy [6,9]. Subacute onset of fever, cough and
constitutional symptoms makes pulmonary tuberculosis a common
misdiagnosis [10]. The median time to diagnosis is therefore long
(42days to 12 months). Its special staining characteristics [modified
Kinyuon procedure] and fastidious nature of growth adds to this
problem [7]. Extra-pulmonary nocardiosis occurs in half of all cases
of pulmonary disease. Because of the long median time to diagnosis
and its neurotropism Central Nervous System (CNS) nocardiosis is
a common phenomenon [3,6]. CNS nocardiosis usually present as
single or multiple abscesses [6]. Dissemination to the brain heralds a
poor prognosis with mortality in some studies reported close to 100%
[7]. TMP-SMX (TMP15mg/kg) is the first line of treatment because
of its excellent penetration and wide susceptibility. Combination
treatment should be prescribed in disseminated disease and in
immune compromised hosts [10]. Severe disease is to be treated
with parenteral therapy with at least two drugs initially (induction
phase).Amikacin, imipenem and 2nd
/3rd
generation cephalosporins,
co-amoxiclav are suitable candidates [4].
The duration of the induction therapy is six weeks which is
followed by oral combination of two drugs for total period of twelve
months [10]. TMP-SMX (TMP 10mg/kg) and co-amoxiclav are good
choices here [8]. Some recommend parenteral therapy all through
for CNS infection. Prolonged treatment with combination drugs are
advised because the two characteristics of nocardia infection are a)
wide dissemination and b)tendency to relapse inspite of appropriate
treatment.
Although our selection of antibiotics was purely empiric initially,
we saw significant clinical response prompting us to continue with
this regime. However routine susceptibility tests were available
soon (Tables 1 & 2) and we switched to a targeted regime. Drug
susceptibility test is strongly recommended in all cases because of
prolonged treatment and variable susceptibility among different
species.
Conclusion
We describe two cases of severe nocardiosis presenting as
necrotizing pneumonia with pleural reaction in patients on
immunosuppressive drugs. Our first case is disseminated nocardiosis
with positive blood culture (nocardaemia), an extremely rare finding.
The finding of pulmonary nocardiosis in an immune compromised
individual should prompt us to get brain imaging studies done before
commencing an effective anti-nocardial agent like imipenem which
has otherwise excellent activity against nocardia. Brain imaging
detected multiple right temporal abscesses in our first case. In the
second one, we did not find any abscess in brain but there were
lacunar infarct.
Literature does not provide information on whether nocardiosis
predisposes individuals to vascular thrombosis. An incidental
finding in both of our cases was vascular thrombosis (pulmonary
thromboembolism in Case I and lacunar infarcts brain in Case II)
which can be explained by heightened platelet aggregation probably
secondary to thrombocytosis.
Three unique features drew our attention: a) occurrence
of nocardaemia without endovascular prosthesis, b) vascular
thrombosis complicating nocardiosis, c) learning the lesson that
all cases of pulmonary nocardiosis should be evaluated thoroughly
with brain imaging to exclude central nervous system involvement as
disseminated nocardiosis can be a silent killer.
References
1.	 Ming-Huang Tuo, Ying-Huang Tsai, Hsiang-Kuang Tseng, Wei-sheng wang.
Clinical experiences of pulmonary and bloodstream nocardiosis in two tertiary
care hospitals in northern Taiwan. 2000-2004.
2.	 Nocardia bacteremia: report of 4 cases & review of literature. Medicine
(Bultimore). 1998; 77: 255-267.
3.	 McNeil MM, Brown JM. The medically important aerobic Actinomycetes:
Epidemiology and microbiology. Clin Microbiol Rev. 1994; 7: 357-417.
4.	 Lo W, Rolston KV. Use of Imipenem in treatment of Pulmonary nocardiosis.
Chest. 1993: 103; 951-952.
5.	 Lederman ER, Crum NF. A case series and focused review of nocardiosis:
clinical and microbiologic aspects. Medicine (Baltimore). 2004; 83: 300-313.
6.	 Beaman BL, Beaman L. Nocardia species: Host-parasite relationships. Clin
Microbiol Rev. 1994; 7: 213-264.
7.	 Martinez Tomas R, Menendez Villanueva R, Reyes Calzada S, Santos
Durantez M, Vallés Tarazona JM, Modesto Alapont M, et al. Pulmonary
nocardiosis: risk factors and outcomes. Respirology. 2007; 12: 394-400.
8.	 Sorrell TC, Mitchell DH, Iredell JR. Nocardia species. Mandell GL, Bennett
JE, Dolin R, editors. 6th
edn. In: Principles and Practice of Infectious Diseases.
Elsevier, Philadelphia. 2005; 916.
9.	 Hwang JH, Koh WJ, Suh GY, Chung MP, Kim H, Kwon OJ, et al.
Pulmonary nocardiosis with multiple cavitary nodules in a HIV-negative
immunocompromised patient. Intern Med. 2004; 43: 852-854.
10.	Lerner PI. Nocardiosis. Clin Infect Dis. 1996; 22: 891-903.
Citation: Ghosh S, Pal D, Pal S, Roy J and Bhakta A. An Unusual Presentation of Nocardiosis - A Report of Two
Cases. Austin J Trop Med & Hyg. 2015;1(2): 1006.
Austin J Trop Med & Hyg - Volume 1 Issue 2 - 2015
ISSN: 2472-3681 | www.austinpublishinggroup.com
Pal et al. © All rights are reserved

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Austin Journal of Tropical Medicine & Hygiene

  • 1. Citation: Ghosh S, Pal D, Pal S, Roy J and Bhakta A. An Unusual Presentation of Nocardiosis - A Report of Two Cases. Austin J Trop Med & Hyg. 2015;1(2): 1006. Austin J Trop Med & Hyg - Volume 1 Issue 2 - 2015 ISSN: 2472-3681 | www.austinpublishinggroup.com Pal et al. © All rights are reserved Austin Journal of Tropical Medicine & Hygiene Open Access Abstract Nocardiosis is an opportunistic infection more common in immune compromised hosts. Disseminated nocardiosis has a poor outcome. We report a case of disseminated nocardiosis with nocardaemia (case-1) which is an extremely rare finding even in immune compromised subjects. In case-2 we found pulmonary abscess caused by nocardia in a patient of sarcoidosis on steroids. Vascular thrombosis complicating nocardiosis is not recognized. We report two cases of nocardiosis with arterial thrombosis. Keywords: Immunocompromised state; Disseminated nocardiosis; Cerebral abscess; Pulmonary abscess; Vascular thrombosis He presented with foot drop in another institution four months before where he was diagnosed as having mononeuritis multiplex based on NCV/EMG study showing bilateral peroneal neuropathy. His connective tissue panel (Anti-nuclear antibody etc.) and vasculitis screening (ANCA) were all negative at that time. He was started on oral cyclophosphomide (50 mg/day) and prednisolone (40mg/ day) for mononeuritis multiplex in that institute with significant improvement of his muscle strength and became ambulatory. He was also on oral anticoagulant therapy following a massive pulmonary thromboembolism which he suffered few weeks after starting immunosuppressive therapy (Figure 1). At the time of admission, he was receiving prednisolone-40mg/day, cyclophosphomide-50mg/ day, oral anticoagulant and calcium supplement. Examination of the respiratory system revealed tachypnoea and coarse crackles in right infrascapular area. Neurological examination revealed wasting of proximal and distal muscles of both lower limbs with muscle power of 4/5 in all groups. Deep tendon reflexes were preserved except left knee jerk. Sensory system, cranial nerves and cerebellar functions were all normal. Introduction Nocardia species are saprophytic aerobic actinomycetes and are common worldwide in soil causing decay of organic matter. It is an opportunistic pathogen causing significant morbidity and mortality in human beings. It predominantly affects lung with pre-existing structural defects and also with co-existing mycobacterial infection. Disseminated nocardiosis occurs through haematogenous spread to distant organs including brain (commonest), bone, soft-tissues and kidney; whereas peritoneum and heart valves only rarely affected. Isolating nocardia in blood culture (nocardaemia) is extremely rare [1]. Endovascular foreign body [2] e.g. prosthetic heart valve is a unique risk factor for nocardaemia but our patient (case I) did not posses any such foreign body. Nocardia bacteraemia is also associated with simultaneous infection with other bacterial pathogens, especially Gram negative organisms in 30% [2]. First patient had concomitant Klebsiella infection [Extended-Spectrum Beta-Lactamase (ESBL) producer] in lung. Surprisingly in both the cases vascular thrombosis complicated the picture-thrombosis in pulmonary trunk was in case- 1 and lacunar infarcts of brain found in case-2. Nocardiosis and vascular thrombosis may be causally related. Case Report Case I A 52 yr old gentleman presented to our clinic with fever and dry cough for 15 days. He also complained of chest tightness and exertional breathlessness for the same duration. His fever was low grade, intermittent in nature and subsided only on taking antipyretics. It was associated with cough without expectoration, hemoptysis or chest pain. He had a significant past history. Ten years ago he was treated for pulmonary tuberculosis. Case Report An Unusual Presentation of Nocardiosis - A Report of Two Cases Subhasish Ghosh1 , Dipankar Pal2 *, Shekhar Pal3 , Jayanta Roy4 and Arpita Bhakta5 1 Consultant Pulmonologist, Apollo and AMRI Hospitals, Kolkata, India 2 RMO cum Clinical Tutor, Dept.of Tropical Medicine, School of Tropical Medicine, Kolkata, India 3 Assistant Professor, Department of Tropical Medicine, School of Tropical Medicine, Kolkata, India 4 Consultant Neurologist, Department of Neurology, Apollo Hospitals, Kolkata, India 5 Head of the Dept.of Microbiology, AMRI Hospitals, Kolkata, India *Corresponding author: Dipankar Pal, RMO cum Clinical Tutor, School of Tropical Medicine, India Received: December 18, 2014; Accepted: February 17, 2015; Published: February 19, 2015 Figure 1: CT Pulmonary Angiography showing saddle embolus.
  • 2. Austin J Trop Med & Hyg 1(2): id1006 (2015) - Page - 02 Dipankar Pal Austin Publishing Group Submit your Manuscript | www.austinpublishinggroup.com Total leucocyte count was 15,500/cu mm with neutrophilia, procalcitonin-0.14 (normal < 0.05), INR-5.27. Platelet count-3.80lac/ cu mm. Blood culture was sent. Chest x-ray showed nodular opacity in right lower lobe with pleural reaction (Figure 2). CT thorax with CT pulmonary angiography revealed nodular consolidation involving anterior and lateral segment of right lower lobe with area of necrosis abutting pleura with adjoining pleural reaction. No pulmonary thrombosis or embolism was evident (Figure 3) this time Fibre Optic Bronchoscopy (FOB) and Bronchoalveolar Lavage (BAL) with washing from right basal and apical segment of right lower lobe was done and sent for Gram stain , AFB stain, culture, fungal stain and modified AFB and silver stain. Gram positive branching, fine, delicate, filamentous organisms positive on modified AFB stain (using 1% sulphuric acid as decolourising agent) (Figure 4) [3] was detected on BAL along with growth of Klebsiella aerogenes [ESBL producer] and Nocardia asteroides on culture. Blood culture also grew Nocardia asteroides (growth time 59 hrs) [1]. The colonies of Nocardia grown from both BAL and blood were adherent, dry, wrinkled, chalky white on sheep blood agar .The isolate was identified as Nocardia asteroides by Vitek 2 Compact system (Biomerieux).Isolate was sensitive to ceftriaxone, amikacin, imipenem, co-amoxiclav and trimethoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole [TMP 640 mg/day in divided doses] and imipenem [4] were started, cyclophosphamide was stopped after discussion with neurologist. A tapering regimen of steroid was initiated. He started to show positive response to above treatment of pulmonary nocardiosis [5] with subsidence of fever. However, on the third day of treatment he complained of giddiness and soon had a brief generalized tonic clonic seizure. CT brain showed a right temporal hypodensity. MRI revealed multiple cerebral abscesses with ring enhancement and Figure 2: CXR showed nodular opacity in right lower lobe with pleural reaction. Figure 3: CT Scan thorax showing nodular consolidation involving right lower lobe. Figure 4: Modified AFB stain showing branched filamentaous organisms. Figure 5: CT Brain showing right temporal hypodense lesion. (B) MRI picture of cerebral abscess. Figure 6: Chest X-ray post discharge showing significant resolusion. ANTIBIOTICS I ANTIBIOTICS I Penicillin G Combinations Amoxycillin S Amoxy-clav S Pipericillintazobactum S Vanconnycin S Aminoglycosides Clindamycin S Gentamycin S Tobramycin S Fluroquinolones Netilmycn S Noriloxacin Amikacin S Ciprofloxacin S Ofloxacin S Others Levofloxacin S Cotrimoxazole S Gatifloxacin S Carbapenems Imipenem S Table 1: Antibiogram of (Case 1). S: Sensitive, R: Resistant, I: Intermediate
  • 3. Austin J Trop Med & Hyg 1(2): id1006 (2015) - Page - 03 Dipankar Pal Austin Publishing Group Submit your Manuscript | www.austinpublishinggroup.com perilesional edema (Figure 5) [6]. We started meropenem in place of imipenem and phenytoin was added to control seizure. He remained stable on this combination. We discharged him after a week on above medications and readmitted 2 weeks later for craniotomy and drainage of cerebral abscess. The cerebral abscess material also grew Nocardia asteroides on culture Co-trimoxazole and meropenem were continued for 4 weeks in view of disseminated disease and he was discharged home on oral co-trimoxazole, co-amoxiclav, prednisolone - 5mg daily and oral anti-coagulant with monthly follow-up advice (Table 1). He remained a febrile without neurological sequel, with chest x-ray showing excellent resolution (Figure 6). Case II A 53 yr old lady was admitted in our institution with a febrile illness for 2 weeks associated with right sided pleuritic chest pain and easy fatiguability . Ten months ago she first presented to a local doctor with persistent cough. A CT thorax at that time showed nodular opacities with some of the nodules along the bronchovascular bundles and consolidation of apical segment of left lower lobe with ground glass opacity. There was widespread mediastinal lymphadenopathy involving right paratracheal, pretracheal, precarinal, AP window and subcarinal stations (Figures 7 & 8). As she refused bronchoscopy, prednisolone (60mg/d) [7]was started with a provisional diagnosis of sarcoidosis. Her cough got better and chest x-ray (Figure 9) showed significant resolution, especially of left lung opacities. There was no history suggestive of pulmonary tuberculosis/connective tissue disease/ischaemic heart disease or asthma. She was a nonsmoker and non-alcoholic but she became diabetic, likely steroid induced. On clinical examination, she had cushingoid facies with oral thrush, was febrile and appeared toxic. There was no palpable peripheral lympadenopathy, engorged jugular veins, pedal edema. Examination of the respiratory system revealed diminished vesicular breath sound with coarse crepitations at places of right infrascapular and infraaxillary area with an evanescent rub. Examination of all other systems was normal. She was on 30 mg/day of prednisolone [7] and chest x-ray revealed dense nodular shadows in right lower zone (Figure 10) [6,9] during admission. Hemoglobin-12.1gm%,total leucocyte count-8100(Neutrophil-87%), platelets-6.87lac/ul, ESR- 103, CRP> 250, Procalcitonin-0.29 (normal<0.05), SGOT/SGPT- normal, GGT-319, Alkaline-phosphatase-222, urea, creatinine, electrolytes–normal. Blood culture was sent, Sputum was sent for gram stain, AFB stain and culture. Management was focused in the line of pneumonia in an immune compromised host (steroid induced). A tapering regime of prednisolone was initiated. Broad spectrum antibiotic cover was commenced with ertapenem, linezolid and moxifloxacin. CT scan thorax showed right middle and lower lobe necrotizing pneumonia with right sided multi loculated pleural effusion (Figure 11) [6,9]. The opacity at apical segment of left lower lobe had regressed considerably with sparse nodules. Blood culture was unyielding. Sputum examination however revealed plenty of gram positive, beaded, branched filamentous organisms suggestive of nocardia species which was also positive on modified acid fast stain. Ertapenem was changed to meropenem [4], linezolid was continued and co-trimoxazole was started (TMP 15mg/kg/day) in place of moxifloxacin. After being put on this regimen she became a febrile in 48 hours and continued to show good clinical response. CT scan brain did not show any abscess. MRI brain however showed tiny foci of lacunar Figure 7: CT Thorax showing (A)nodular lesions in peri lymphatic distribution with ground glass opacity. (B) Mediastinal lymphadinopathy. Figure 8: Chest X-ray showing nodular opacities. Figure 9: Chest X-ray showing improvement following steroids. Figure 10: Chest X-ray showing dence nodular opacities involving right lower lobe. Figure 11: CT Scan showing (A)Right middle lobe consolidation with air bronchogram. (B) showing right sided multiloculated pleural effusion.
  • 4. Austin J Trop Med & Hyg 1(2): id1006 (2015) - Page - 04 Dipankar Pal Austin Publishing Group Submit your Manuscript | www.austinpublishinggroup.com infarcts in temoro-parietal (bilateral) and left occipital regions. She remained a febrile with the above regime. In the meantime, sputum culture yielded Nocardia asteroides. Meropenem was stopped after 14 days and co-amoxiclav was added based on the sensitivity pattern of the organism in sputum culture. Linezolid was also stopped as there was no evidence of disseminated disease. Patient was discharged after 2 weeks on oral cotrimoxazole and coamoxiclav (Table 2). CRP was 35 on discharge. She was also on maintenance dose of steroid (5 mg in morning and 2.5 mg in evening) and clopidogrel. She continued to do well without drug related adverse events noted so far. Chest X-ray one month post-discharge showed significant improvement (Figure 12). Discussion Nocardiosis remains an elusive diagnosis despite its discovery by Edmond Nocard in 1888. There are more than 50 species of nocardia with at least 30 species recognized as pathogenic to human. Fragmented bacterial mycelia enter lungs via aerosol route. Although pulmonary nocardiosis is a common presentation [2/3rds of cases] [5], human to human transmission is not documented. It is a disease unique to immunosuppressed individuals. But 30% of infections ANTIBIOTICS I II ANTIBIOTICS I II Penicillins     Combinations     Amoxycillin S   Amoxy-clav S   Piperacillin     Ampicillin-sulbactam     Ticarcillin     Piperacillin-tazobacta m           Ticarcillin-clavulunic acid     Cephalosporins     Cefoperazone-sulbactam     Cefuroxime           Cefdinir     Aminoglycosides     Cefixime     Gentamycin     Ceftriaxone S   Tobramycin     Cefotaxime     Netilmycn     Ceftazidime     Amikacin S   Cefepime                 Fluroquinolones     Cefamycin     Norfioxacin     Cefoxitin     Ciprofloxacin S         Ofloxacin     Monobactam     Levofloxacin     Aztreonam     Gatifloxacin     Carbapenems Others Imipenem S Nitrofurantoin Meropenem Chloramphenicol Ertapenem Cotrimoxazole S Erythromycin S Linezolid S Tetracycline Polymyxin B Table 2: Antibiogram of (Case 2). SPECIMEN: SPUTUM METHOD: Aerobic bacterial culture REPORT : Culture shows growth of Nocardia asteroides Colony count :104 cfu/m1 ANTIBIOGRAM (Disc Diffusion method) S: Sensitive, R: Resistant, I: Intermediate are also seen in immune competent hosts [6], Chronic Obstructive Pulmonary Disease (COPD) is a risk factor among such groups [7]. Glucocorticoidtherapyandmalignancyanditstreatmentarecommon risk factors [7]. Pulmonary nocardiosis presents as necrotizing pneumonia with or without cavitation. They may also present as a slowly enlarging pulmonary nodule with or without empyema, Figure 12: Chest X-ray showing significant improvement with treatment.
  • 5. Austin J Trop Med & Hyg 1(2): id1006 (2015) - Page - 05 Dipankar Pal Austin Publishing Group Submit your Manuscript | www.austinpublishinggroup.com confusing with malignancy [6,9]. Subacute onset of fever, cough and constitutional symptoms makes pulmonary tuberculosis a common misdiagnosis [10]. The median time to diagnosis is therefore long (42days to 12 months). Its special staining characteristics [modified Kinyuon procedure] and fastidious nature of growth adds to this problem [7]. Extra-pulmonary nocardiosis occurs in half of all cases of pulmonary disease. Because of the long median time to diagnosis and its neurotropism Central Nervous System (CNS) nocardiosis is a common phenomenon [3,6]. CNS nocardiosis usually present as single or multiple abscesses [6]. Dissemination to the brain heralds a poor prognosis with mortality in some studies reported close to 100% [7]. TMP-SMX (TMP15mg/kg) is the first line of treatment because of its excellent penetration and wide susceptibility. Combination treatment should be prescribed in disseminated disease and in immune compromised hosts [10]. Severe disease is to be treated with parenteral therapy with at least two drugs initially (induction phase).Amikacin, imipenem and 2nd /3rd generation cephalosporins, co-amoxiclav are suitable candidates [4]. The duration of the induction therapy is six weeks which is followed by oral combination of two drugs for total period of twelve months [10]. TMP-SMX (TMP 10mg/kg) and co-amoxiclav are good choices here [8]. Some recommend parenteral therapy all through for CNS infection. Prolonged treatment with combination drugs are advised because the two characteristics of nocardia infection are a) wide dissemination and b)tendency to relapse inspite of appropriate treatment. Although our selection of antibiotics was purely empiric initially, we saw significant clinical response prompting us to continue with this regime. However routine susceptibility tests were available soon (Tables 1 & 2) and we switched to a targeted regime. Drug susceptibility test is strongly recommended in all cases because of prolonged treatment and variable susceptibility among different species. Conclusion We describe two cases of severe nocardiosis presenting as necrotizing pneumonia with pleural reaction in patients on immunosuppressive drugs. Our first case is disseminated nocardiosis with positive blood culture (nocardaemia), an extremely rare finding. The finding of pulmonary nocardiosis in an immune compromised individual should prompt us to get brain imaging studies done before commencing an effective anti-nocardial agent like imipenem which has otherwise excellent activity against nocardia. Brain imaging detected multiple right temporal abscesses in our first case. In the second one, we did not find any abscess in brain but there were lacunar infarct. Literature does not provide information on whether nocardiosis predisposes individuals to vascular thrombosis. An incidental finding in both of our cases was vascular thrombosis (pulmonary thromboembolism in Case I and lacunar infarcts brain in Case II) which can be explained by heightened platelet aggregation probably secondary to thrombocytosis. Three unique features drew our attention: a) occurrence of nocardaemia without endovascular prosthesis, b) vascular thrombosis complicating nocardiosis, c) learning the lesson that all cases of pulmonary nocardiosis should be evaluated thoroughly with brain imaging to exclude central nervous system involvement as disseminated nocardiosis can be a silent killer. References 1. Ming-Huang Tuo, Ying-Huang Tsai, Hsiang-Kuang Tseng, Wei-sheng wang. Clinical experiences of pulmonary and bloodstream nocardiosis in two tertiary care hospitals in northern Taiwan. 2000-2004. 2. Nocardia bacteremia: report of 4 cases & review of literature. Medicine (Bultimore). 1998; 77: 255-267. 3. McNeil MM, Brown JM. The medically important aerobic Actinomycetes: Epidemiology and microbiology. Clin Microbiol Rev. 1994; 7: 357-417. 4. Lo W, Rolston KV. Use of Imipenem in treatment of Pulmonary nocardiosis. Chest. 1993: 103; 951-952. 5. Lederman ER, Crum NF. A case series and focused review of nocardiosis: clinical and microbiologic aspects. Medicine (Baltimore). 2004; 83: 300-313. 6. Beaman BL, Beaman L. Nocardia species: Host-parasite relationships. Clin Microbiol Rev. 1994; 7: 213-264. 7. Martinez Tomas R, Menendez Villanueva R, Reyes Calzada S, Santos Durantez M, VallĂ©s Tarazona JM, Modesto Alapont M, et al. Pulmonary nocardiosis: risk factors and outcomes. Respirology. 2007; 12: 394-400. 8. Sorrell TC, Mitchell DH, Iredell JR. Nocardia species. Mandell GL, Bennett JE, Dolin R, editors. 6th edn. In: Principles and Practice of Infectious Diseases. Elsevier, Philadelphia. 2005; 916. 9. Hwang JH, Koh WJ, Suh GY, Chung MP, Kim H, Kwon OJ, et al. Pulmonary nocardiosis with multiple cavitary nodules in a HIV-negative immunocompromised patient. Intern Med. 2004; 43: 852-854. 10. Lerner PI. Nocardiosis. Clin Infect Dis. 1996; 22: 891-903. Citation: Ghosh S, Pal D, Pal S, Roy J and Bhakta A. An Unusual Presentation of Nocardiosis - A Report of Two Cases. Austin J Trop Med & Hyg. 2015;1(2): 1006. Austin J Trop Med & Hyg - Volume 1 Issue 2 - 2015 ISSN: 2472-3681 | www.austinpublishinggroup.com Pal et al. © All rights are reserved