Clinico-Pathologic ConferencesPulmonary Nocardiosis Review of Cases and an Update
Malini Shariff and Jayanthi Gunasekaran
Department of Microbiology Vallabhbhai Patel Chest Institute University of Delhi Delhi 110007 India
Correspondence should be addressed to Malini Shariff malinishariffgmailcom
Received 22 September 2015 Accepted 9 November 2015
Copyright copy 2016 M Shariff and J Gunasekaran This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited
Nocardia a branching filamentous bacteria is widely distributed in the environment and can cause human infection in immune-compromised hosts Inhalation of Nocardia leads to pulmonary disease Microbiology laboratory processed the clinical samplesfrom patients with respiratory infections Smears were prepared from the samples and were stained and cultured Five cases werepositive for Nocardia They were treated with the trimethoprim-sulfamethoxazole combination The disease was cured in threepatients and two died due to other comorbid conditions leading to complications Nocardiosis is encountered in parts of the worldeven where it is not endemic due to increased world travel So physicians and laboratory staff should be aware of this and try todiagnose it Early detection can lead to the prompt initiation of treatment and reduced mortality in these patients Patients withdisseminated or severe nocardiosis should be treated with combination therapy with two or more active agents
1 Case Presentation
In the present study five cases of pulmonary nocardiosis(PN) four males and one female were encountered amongpatients attendingVallabhbhai Patel Chest Institute a tertiarycare respiratory diseases hospital in Delhi India They wereadmitted with complaints of breathlessness and increasedcough with sputum production from a week to 3-monthduration They all had fever and weight loss All wereimmunocompromised with four of them having the chronicobstructive pulmonary disease (COPD) with tuberculosisand one with COPD and diabetes mellitus Sputum samplesfrom four and bronchial alveolar lavage bronchial aspirateand sputum from one case showed Gram-positive filamen-tous branching rodswith beaded appearance onGramrsquos stain-ing and acid fast branching filamentous rods with beadedappearance on modified Ziehl-Neelsen staining suggestive ofNocardia It was isolated on sheep blood agar from four casesPatients were treated with trimethoprim-sulfamethoxazole(TMP-SMX) along with other antibiotics like amikacin andimipenemmeropenem Three were discharged and advisedto continue TMP-SMX for six months Two of these werefollowed up and were completely free of symptoms andtheir sputum was negative on smear and culture Two of thepatients died Table 1 shows the details of the cases
2 Discussion and Update
21 Introduction Nocardia is widely distributed in dust soilwater and vegetable matter Inhalation of the dust particlesleads to pulmonary involvement commonly caused by Nasteroides complex Direct inoculation of the organism canlead to infections of the skin and subcutaneous tissue Theycan disseminate from pulmonary or cutaneous focus tovirtually any organ
22 Epidemiology and Risk Factors Nocard first describedNocardia in 1888 [1] which was later described by Eppinger(1890) in a man with a pulmonary disease with ldquopseu-dotuberculosisrdquo of lungs and pleura caseous peribronchiallymph nodes meningitis and multiple abscesses in thebrain [2] Nocardia consists of more than 22 species ofwhich N asteroides complex comprising of N asteroidessensu stricto N farcinica N nova and N abscessus is themost common Agricultural occupation is a risk factor forpulmonary nocardiosis Systemic immunosuppression cor-ticosteroid therapy lymphoma sarcoidosis systemic lupuserythematosus chronic alcoholism diabetes mellitus andhuman immunodeficiency virus (HIV) infection are otherpredisposing factors Lately it has been observed that COPDis also a risk factor for Nocardia infection [3]
Hindawi Publishing CorporationCanadian Respiratory JournalVolume 2016 Article ID 7494202 4 pageshttpdxdoiorg10115520167494202
2 Canadian Respiratory Journal
Table1Detailsof
patie
ntsw
ithpu
lmon
aryno
cardiosis
Case1
Case2
Case3
Case4
Case5
Age
7670
5770
42Diagn
osis
COPD
with
pulm
onaryTB
COPD
with
pulm
onaryTB
COPD
with
DM
Treatedpu
lmon
aryTB
Treatedpu
lmon
aryTB
Ho
ATT
Yes
Yes
No
Yes
Yes
HO
DM
No
No
Yes
No
No
HIV
No
No
No
No
No
HO
smok
ing
Yes
Yes
Yes
No
No
COPD
Yes
Yes
Yes
No
No
Chiefcom
plaints
Breathles
snessa
ndincreased
coug
hwith
sputum
for4
-5days
andlossof
weightand
lossof
appetite
Breathles
snessa
ndcoug
hwith
sputum
for2
0yearsa
cutely
increasedfortwoweeks
and
feverfor
1week
Breathles
snessa
ndcoug
hwith
sputum
for15days
Breathles
snessa
ndcoug
hwith
sputum
forthree
mon
ths
interm
ittentfever
forthree
mon
thsandlossof
weight
Persistentsym
ptom
soffever
lossof
appetiteand
mucop
urulentspu
tum
fortwo
mon
thsa
fterA
TTcourse
X-ray
Bilateralpneum
onia
Bilateralpneum
onia
mdashRt
lower
zone
opacity
Leftlower
lobe
collapsew
ithconsolidation
Clinicalsamples
Sputum
Sputum
Sputum
Sputum
BALBA
and
sputum
SMEA
RGrams
Gram
positiveb
ranching
filam
entous
rods
with
beads
Gram
positiveb
ranching
filam
entous
rods
with
beads
Gram
positiveb
ranching
filam
entous
rods
with
beads
Gram
positiveb
ranching
filam
entous
rods
with
beads
Gram
positiveb
ranching
filam
entous
rods
with
beads
Mod
ified
acid
fast
staining
Acid
fastbranching
filam
entous
rods
with
beads
Acid
fastbranching
filam
entous
rods
with
beads
Acid
fastbranching
filam
entous
rods
with
beads
Acid
fastbranching
filam
entous
rods
with
beads
Acid
fastbranchingfilam
entous
rods
with
beads
Cultu
reon
sheep
bloo
dagar
Positivea
fter4
8hrsof
incubatio
nPo
sitivea
fter4
8hrsof
incubatio
nCu
lture-negativea
fterseven
days
ofincubatio
nPo
sitivea
fterthree
days
ofincubatio
nPo
sitivea
fter4
8hrsof
incubatio
n
Treatm
ent
TSeptran4days
InjA
mikacin
4days
InjImipenem
4days
TTM
P-SM
X20
days
InjA
mikacin
2wks
InjM
erop
enem
10days
TTM
P-SM
X5days
InjA
mikacin
5days
TVo
ricon
azole5
days
InjA
mikacin
2weeks
TTM
P-SM
X4mon
ths
InjA
mikacin
2weeks
TTM
P-SM
X4mon
ths
Outcome
Patie
ntexpiredaft
ersix
days
ofadmission
Disc
harged
with
advice
tocontinue
TMP-SM
Xforsix
mon
thsa
ndto
comefor
follo
w-up
Patie
ntexpiredaft
ersix
days
ofadmission
Sputum
negativ
eafte
raweek
Disc
harged
with
advice
tocontinue
TMP-SM
Xforsix
mon
thsa
ndto
comefor
follo
w-up
Sputum
was
negativ
eafte
rone
wkof
treatmentDisc
harged
with
advice
tocontinue
TMP-SM
Xforsixmthsa
ndto
comefor
follo
w-up
Follo
w-up
mdashTh
epatient
was
lostto
follo
w-up
mdash
Sputum
samples
takenaton
eandtwomon
thso
ffollow-up
weren
egativeCom
plete
resolutio
nof
thelesionatfour
mon
thso
ftreatmentw
ithTM
P-SM
Xandno
complaints
Smear-negativ
eafterseven
days
andaft
ertwoweeks
follo
w-up
COPD
chron
icob
structiv
epulmon
arydisease
ATT
antitub
erculous
treatment
DMdiabetesm
ellitus
TMP-SM
Xtrim
etho
prim
-sulfametho
xazole
TBtub
erculosis
Canadian Respiratory Journal 3
23 Clinical Presentation Pulmonary nocardiosis can presentas acute subacute or chronic suppurative infection with atendency to remit or exacerbate PN is usually suppurative butgranulomatous or mixed variety may occur Clinical mani-festation includes pneumonia endobronchial inflammatorymasses lung abscess and cavitary disease with contiguousextension leading to effusion and empyema
24 Radiological Findings Irregular nodules reticulonodularor diffuse pneumonic infiltrates and pleural effusions areseen in X-ray The progressive fibrotic disease may developfollowing inadequate therapy and the diagnosis is often dif-ficult It can be fatal in patients with advanced HIV infectionand often presents as alveolar infiltrates rather than cavitarylesion In this situation the X-ray findings are nonspecificand hence should be considered as a differential diagnosisof indolent pulmonary disease along with MycobacteriaActinomyces and Eumycetes (Cryptococcus neoformans andAspergillus species)
25 Laboratory Diagnosis Demonstration of Nocardia inclinical sample clinches the diagnosis Direct demonstrationof Nocardia from sputum bronchoalveolar lavage bronchialaspirate or endotracheal aspirate should be attempted
Gramrsquos stain smear shows Gram-positive beaded fineright-angled branching filaments (lt1 120583m diameter) whichmay fragment to form rods and coccoid forms of varyingsizes Most isolates of Nocardia are acid fast by modifiedKinyoun technique that differentiates it from Actinomyceswhich is not acid fast Silver methenamine stain is equallyuseful and reliable as modified Ziehl-Neelsen staining [4]
Nocardia spp grow on media used for culture of bacte-ria fungi and Mycobacteria Typical colonies appear afterthree to five days Nocardia spp appear as either buff orpigmented waxy cerebriform colonies or have a dry chalky-white appearance with the production of aerial hyphae
Some commercial identification systems like API 20C(Biomerieux) allow for rapid identification of Nocardia sppbut have the limitation of the traditional phenotypic method[5]
Molecular identification of Nocardia is not only quickand accurate but also helps in the recognition of newspecies Various methods like ribotyping polymerase chainreaction restriction fragment length polymorphism analysisand DNA sequencing are available [6]
DNA sequencing is currently the best tool for speciesidentification of Nocardia Sequencing of first 500ndash606 basepairs of the 51015840 end of 16S rRNA gene is the recommendedmethod [6] All these methods have their limitations andshould be used with caution
Currently there are no serological tests available fordiagnosis of active nocardiosis due to the cross-reactivityamong different Nocardia speciesMycobacterium tuberculo-sisMycobacterium leprae and other Actinomycetes [7]
26 Management Trimethoprim-sulfamethoxazole (TMP-SMX) is the mainstay of treatment and has improved theoutcomes In adults with normal renal function and localizeddisease the recommended daily dose of TMP-SMX is 5 to
10mgkgTMPand 25 to 50mgkg SMX in two to four divideddoses depending on the extent of diseaseHigher initial doses(15mgkg TMP and 75mgkg SMX) given intravenously ororally are frequently used in patients with cerebral abscessessevere extensive or disseminated infection or AIDS Sul-fonamides are the treatment of choice for disease due toN brasiliensis However mortality with monotherapy is ashigh as 50 [8] especially in severely ill patients and thosewith cerebral involvement or disseminated nocardiosis andimmune-suppression Empirical combination therapy withamikacin and imipenem (or meropenem) or a three-drugregimen comprising of Sulphonamides amikacin and eitheraCarbapenemor third generationCephalosporin can be usedin such high-risk patients
3 Conclusion
Isolation of nocardiae from sputum or blood occasionallyrepresents colonization transient infection or contami-nation In cases of respiratory tract colonization Gram-stained specimens are usually negative and cultures areonly intermittently positive Until a better tool to determinethe virulence of Nocardia is available the positive cultureoften reflects disease in immune-suppressed patients suchas patients on corticosteroid therapy patients who undergoorgan transplantation patients with chronic lung diseaseand HIV-positive patients Therefore PN must be suspectedin patients with these risk factors and positive imagingfindings Early detection of the organism can lead to theprompt initiation of treatment and reducedmortality in thesepatients Initial combination therapy with two or more activeagents is recommended for patients with disseminated orsevere nocardiosis
Additional Points
Learning Objectives (i) To recognize the importance ofNocardia in causing lung infections (ii) To diagnoseNocardiain the laboratory (iii) To treat infections caused by Nocardia
Pre-Test (1) How to diagnose Pulmonary Nocardiosis (2)How can it be treated effectively
Post-Test
(1) How to Diagnose Pulmonary Nocardiosis Direct demon-stration of Nocardia from clinical samples stained withGramrsquos stain and the modified acid fast stain will help inthe diagnosis of Nocardiosis Nocardia appears as Gram-positive filamentous branching rods with beaded appearanceon Gramrsquos staining and acid fast branching filamentous rodswith beaded appearance on modified Ziehl-Neelsen stainingThe diagnosis can further be confirmed by culturing theorganism in solid media
(2) How Can It Be Treated Effectively Trimethoprim-sulfamethoxazole (TMP-SMX) is the mainstay of treatmentHowever monotherapy may lead to treatment failuresHence empirical combination therapy with amikacin and
4 Canadian Respiratory Journal
imipenem (or meropenem) or a three-drug regimen com-prising Sulphonamides amikacin and either a Carbapenemor third generation Cephalosporin can be used in high-riskpatients
Disclosure
Workwas carried out at Department ofMicrobiology Vallab-hbhai Patel Chest Institute Delhi University Delhi India
Competing Interests
The authors declare that there are no competing interestsassociated with this work
Authorsrsquo Contributions
Jayanthi Gunasekaran processed the samples and compiledthe data Malini Shariff supervised the lab work interpretedthe results reviewed the subject and wrote the paper
Acknowledgments
The study was supported by Vallabhbhai Patel Chest Institutethrough their annual governmental funding
References
[1] M E Nocard ldquoNote sur la maladie des boeufs de la guadeloupeconnue sous le nom de farcinrdquo Annales de lrsquoInstitut Pasteur vol2 pp 293ndash302 1888
[2] H Eppinger ldquoUeber eine neue pathogenic Cladothrix und einedurch sie hervorgerufene PseudotuberculosisrdquoWiener KlinischeWochenschrift vol 3 article 321 1890
[3] C W Emmons C H Binford J P Utz and K J Kwon-ChungMedical Mycology Lea amp Febiger Philadelphia Pa USA 3rdedition 1977
[4] L Garcia-Bellmunt O Sibila I Solanes F Sanchez-Reus andV Plaza ldquoPulmonary nocardiosis in patients with COPDcharacteristics and Prognostic Factorsrdquo Archivos de Bronconeu-mologia vol 48 no 8 pp 280ndash285 2012
[5] S Mathur R Sood M Aron V K Iyer and K Verma ldquoCyto-logic diagnosis of pulmonary nocardiosis a report of 3 casesrdquoActa Cytologica vol 49 no 5 pp 567ndash570 2005
[6] B A Brown-Elliott J M Brown P S Conville and R JWallaceJr ldquoClinical and laboratory features of the Nocardia spp basedon currentmolecular taxonomyrdquoClinicalMicrobiology Reviewsvol 19 no 2 pp 259ndash282 2006
[7] M M Mcneil and J M Brown ldquoThe medically important aer-obic actinomycetes epidemiology and microbiologyrdquo ClinicalMicrobiology Reviews vol 7 no 3 pp 357ndash417 1994
[8] R J Wallace Jr E J Septimus T W Williams Jr et al ldquoUse oftrimethoprim-sulfamethoxazole for treatment of infections duetoNocardiardquoReviews of InfectiousDiseases vol 4 no 2 pp 315ndash325 1982
Submit your manuscripts athttpwwwhindawicom
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Behavioural Neurology
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OncologyJournal of
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Research and TreatmentAIDS
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Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
2 Canadian Respiratory Journal
Table1Detailsof
patie
ntsw
ithpu
lmon
aryno
cardiosis
Case1
Case2
Case3
Case4
Case5
Age
7670
5770
42Diagn
osis
COPD
with
pulm
onaryTB
COPD
with
pulm
onaryTB
COPD
with
DM
Treatedpu
lmon
aryTB
Treatedpu
lmon
aryTB
Ho
ATT
Yes
Yes
No
Yes
Yes
HO
DM
No
No
Yes
No
No
HIV
No
No
No
No
No
HO
smok
ing
Yes
Yes
Yes
No
No
COPD
Yes
Yes
Yes
No
No
Chiefcom
plaints
Breathles
snessa
ndincreased
coug
hwith
sputum
for4
-5days
andlossof
weightand
lossof
appetite
Breathles
snessa
ndcoug
hwith
sputum
for2
0yearsa
cutely
increasedfortwoweeks
and
feverfor
1week
Breathles
snessa
ndcoug
hwith
sputum
for15days
Breathles
snessa
ndcoug
hwith
sputum
forthree
mon
ths
interm
ittentfever
forthree
mon
thsandlossof
weight
Persistentsym
ptom
soffever
lossof
appetiteand
mucop
urulentspu
tum
fortwo
mon
thsa
fterA
TTcourse
X-ray
Bilateralpneum
onia
Bilateralpneum
onia
mdashRt
lower
zone
opacity
Leftlower
lobe
collapsew
ithconsolidation
Clinicalsamples
Sputum
Sputum
Sputum
Sputum
BALBA
and
sputum
SMEA
RGrams
Gram
positiveb
ranching
filam
entous
rods
with
beads
Gram
positiveb
ranching
filam
entous
rods
with
beads
Gram
positiveb
ranching
filam
entous
rods
with
beads
Gram
positiveb
ranching
filam
entous
rods
with
beads
Gram
positiveb
ranching
filam
entous
rods
with
beads
Mod
ified
acid
fast
staining
Acid
fastbranching
filam
entous
rods
with
beads
Acid
fastbranching
filam
entous
rods
with
beads
Acid
fastbranching
filam
entous
rods
with
beads
Acid
fastbranching
filam
entous
rods
with
beads
Acid
fastbranchingfilam
entous
rods
with
beads
Cultu
reon
sheep
bloo
dagar
Positivea
fter4
8hrsof
incubatio
nPo
sitivea
fter4
8hrsof
incubatio
nCu
lture-negativea
fterseven
days
ofincubatio
nPo
sitivea
fterthree
days
ofincubatio
nPo
sitivea
fter4
8hrsof
incubatio
n
Treatm
ent
TSeptran4days
InjA
mikacin
4days
InjImipenem
4days
TTM
P-SM
X20
days
InjA
mikacin
2wks
InjM
erop
enem
10days
TTM
P-SM
X5days
InjA
mikacin
5days
TVo
ricon
azole5
days
InjA
mikacin
2weeks
TTM
P-SM
X4mon
ths
InjA
mikacin
2weeks
TTM
P-SM
X4mon
ths
Outcome
Patie
ntexpiredaft
ersix
days
ofadmission
Disc
harged
with
advice
tocontinue
TMP-SM
Xforsix
mon
thsa
ndto
comefor
follo
w-up
Patie
ntexpiredaft
ersix
days
ofadmission
Sputum
negativ
eafte
raweek
Disc
harged
with
advice
tocontinue
TMP-SM
Xforsix
mon
thsa
ndto
comefor
follo
w-up
Sputum
was
negativ
eafte
rone
wkof
treatmentDisc
harged
with
advice
tocontinue
TMP-SM
Xforsixmthsa
ndto
comefor
follo
w-up
Follo
w-up
mdashTh
epatient
was
lostto
follo
w-up
mdash
Sputum
samples
takenaton
eandtwomon
thso
ffollow-up
weren
egativeCom
plete
resolutio
nof
thelesionatfour
mon
thso
ftreatmentw
ithTM
P-SM
Xandno
complaints
Smear-negativ
eafterseven
days
andaft
ertwoweeks
follo
w-up
COPD
chron
icob
structiv
epulmon
arydisease
ATT
antitub
erculous
treatment
DMdiabetesm
ellitus
TMP-SM
Xtrim
etho
prim
-sulfametho
xazole
TBtub
erculosis
Canadian Respiratory Journal 3
23 Clinical Presentation Pulmonary nocardiosis can presentas acute subacute or chronic suppurative infection with atendency to remit or exacerbate PN is usually suppurative butgranulomatous or mixed variety may occur Clinical mani-festation includes pneumonia endobronchial inflammatorymasses lung abscess and cavitary disease with contiguousextension leading to effusion and empyema
24 Radiological Findings Irregular nodules reticulonodularor diffuse pneumonic infiltrates and pleural effusions areseen in X-ray The progressive fibrotic disease may developfollowing inadequate therapy and the diagnosis is often dif-ficult It can be fatal in patients with advanced HIV infectionand often presents as alveolar infiltrates rather than cavitarylesion In this situation the X-ray findings are nonspecificand hence should be considered as a differential diagnosisof indolent pulmonary disease along with MycobacteriaActinomyces and Eumycetes (Cryptococcus neoformans andAspergillus species)
25 Laboratory Diagnosis Demonstration of Nocardia inclinical sample clinches the diagnosis Direct demonstrationof Nocardia from sputum bronchoalveolar lavage bronchialaspirate or endotracheal aspirate should be attempted
Gramrsquos stain smear shows Gram-positive beaded fineright-angled branching filaments (lt1 120583m diameter) whichmay fragment to form rods and coccoid forms of varyingsizes Most isolates of Nocardia are acid fast by modifiedKinyoun technique that differentiates it from Actinomyceswhich is not acid fast Silver methenamine stain is equallyuseful and reliable as modified Ziehl-Neelsen staining [4]
Nocardia spp grow on media used for culture of bacte-ria fungi and Mycobacteria Typical colonies appear afterthree to five days Nocardia spp appear as either buff orpigmented waxy cerebriform colonies or have a dry chalky-white appearance with the production of aerial hyphae
Some commercial identification systems like API 20C(Biomerieux) allow for rapid identification of Nocardia sppbut have the limitation of the traditional phenotypic method[5]
Molecular identification of Nocardia is not only quickand accurate but also helps in the recognition of newspecies Various methods like ribotyping polymerase chainreaction restriction fragment length polymorphism analysisand DNA sequencing are available [6]
DNA sequencing is currently the best tool for speciesidentification of Nocardia Sequencing of first 500ndash606 basepairs of the 51015840 end of 16S rRNA gene is the recommendedmethod [6] All these methods have their limitations andshould be used with caution
Currently there are no serological tests available fordiagnosis of active nocardiosis due to the cross-reactivityamong different Nocardia speciesMycobacterium tuberculo-sisMycobacterium leprae and other Actinomycetes [7]
26 Management Trimethoprim-sulfamethoxazole (TMP-SMX) is the mainstay of treatment and has improved theoutcomes In adults with normal renal function and localizeddisease the recommended daily dose of TMP-SMX is 5 to
10mgkgTMPand 25 to 50mgkg SMX in two to four divideddoses depending on the extent of diseaseHigher initial doses(15mgkg TMP and 75mgkg SMX) given intravenously ororally are frequently used in patients with cerebral abscessessevere extensive or disseminated infection or AIDS Sul-fonamides are the treatment of choice for disease due toN brasiliensis However mortality with monotherapy is ashigh as 50 [8] especially in severely ill patients and thosewith cerebral involvement or disseminated nocardiosis andimmune-suppression Empirical combination therapy withamikacin and imipenem (or meropenem) or a three-drugregimen comprising of Sulphonamides amikacin and eitheraCarbapenemor third generationCephalosporin can be usedin such high-risk patients
3 Conclusion
Isolation of nocardiae from sputum or blood occasionallyrepresents colonization transient infection or contami-nation In cases of respiratory tract colonization Gram-stained specimens are usually negative and cultures areonly intermittently positive Until a better tool to determinethe virulence of Nocardia is available the positive cultureoften reflects disease in immune-suppressed patients suchas patients on corticosteroid therapy patients who undergoorgan transplantation patients with chronic lung diseaseand HIV-positive patients Therefore PN must be suspectedin patients with these risk factors and positive imagingfindings Early detection of the organism can lead to theprompt initiation of treatment and reducedmortality in thesepatients Initial combination therapy with two or more activeagents is recommended for patients with disseminated orsevere nocardiosis
Additional Points
Learning Objectives (i) To recognize the importance ofNocardia in causing lung infections (ii) To diagnoseNocardiain the laboratory (iii) To treat infections caused by Nocardia
Pre-Test (1) How to diagnose Pulmonary Nocardiosis (2)How can it be treated effectively
Post-Test
(1) How to Diagnose Pulmonary Nocardiosis Direct demon-stration of Nocardia from clinical samples stained withGramrsquos stain and the modified acid fast stain will help inthe diagnosis of Nocardiosis Nocardia appears as Gram-positive filamentous branching rods with beaded appearanceon Gramrsquos staining and acid fast branching filamentous rodswith beaded appearance on modified Ziehl-Neelsen stainingThe diagnosis can further be confirmed by culturing theorganism in solid media
(2) How Can It Be Treated Effectively Trimethoprim-sulfamethoxazole (TMP-SMX) is the mainstay of treatmentHowever monotherapy may lead to treatment failuresHence empirical combination therapy with amikacin and
4 Canadian Respiratory Journal
imipenem (or meropenem) or a three-drug regimen com-prising Sulphonamides amikacin and either a Carbapenemor third generation Cephalosporin can be used in high-riskpatients
Disclosure
Workwas carried out at Department ofMicrobiology Vallab-hbhai Patel Chest Institute Delhi University Delhi India
Competing Interests
The authors declare that there are no competing interestsassociated with this work
Authorsrsquo Contributions
Jayanthi Gunasekaran processed the samples and compiledthe data Malini Shariff supervised the lab work interpretedthe results reviewed the subject and wrote the paper
Acknowledgments
The study was supported by Vallabhbhai Patel Chest Institutethrough their annual governmental funding
References
[1] M E Nocard ldquoNote sur la maladie des boeufs de la guadeloupeconnue sous le nom de farcinrdquo Annales de lrsquoInstitut Pasteur vol2 pp 293ndash302 1888
[2] H Eppinger ldquoUeber eine neue pathogenic Cladothrix und einedurch sie hervorgerufene PseudotuberculosisrdquoWiener KlinischeWochenschrift vol 3 article 321 1890
[3] C W Emmons C H Binford J P Utz and K J Kwon-ChungMedical Mycology Lea amp Febiger Philadelphia Pa USA 3rdedition 1977
[4] L Garcia-Bellmunt O Sibila I Solanes F Sanchez-Reus andV Plaza ldquoPulmonary nocardiosis in patients with COPDcharacteristics and Prognostic Factorsrdquo Archivos de Bronconeu-mologia vol 48 no 8 pp 280ndash285 2012
[5] S Mathur R Sood M Aron V K Iyer and K Verma ldquoCyto-logic diagnosis of pulmonary nocardiosis a report of 3 casesrdquoActa Cytologica vol 49 no 5 pp 567ndash570 2005
[6] B A Brown-Elliott J M Brown P S Conville and R JWallaceJr ldquoClinical and laboratory features of the Nocardia spp basedon currentmolecular taxonomyrdquoClinicalMicrobiology Reviewsvol 19 no 2 pp 259ndash282 2006
[7] M M Mcneil and J M Brown ldquoThe medically important aer-obic actinomycetes epidemiology and microbiologyrdquo ClinicalMicrobiology Reviews vol 7 no 3 pp 357ndash417 1994
[8] R J Wallace Jr E J Septimus T W Williams Jr et al ldquoUse oftrimethoprim-sulfamethoxazole for treatment of infections duetoNocardiardquoReviews of InfectiousDiseases vol 4 no 2 pp 315ndash325 1982
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Canadian Respiratory Journal 3
23 Clinical Presentation Pulmonary nocardiosis can presentas acute subacute or chronic suppurative infection with atendency to remit or exacerbate PN is usually suppurative butgranulomatous or mixed variety may occur Clinical mani-festation includes pneumonia endobronchial inflammatorymasses lung abscess and cavitary disease with contiguousextension leading to effusion and empyema
24 Radiological Findings Irregular nodules reticulonodularor diffuse pneumonic infiltrates and pleural effusions areseen in X-ray The progressive fibrotic disease may developfollowing inadequate therapy and the diagnosis is often dif-ficult It can be fatal in patients with advanced HIV infectionand often presents as alveolar infiltrates rather than cavitarylesion In this situation the X-ray findings are nonspecificand hence should be considered as a differential diagnosisof indolent pulmonary disease along with MycobacteriaActinomyces and Eumycetes (Cryptococcus neoformans andAspergillus species)
25 Laboratory Diagnosis Demonstration of Nocardia inclinical sample clinches the diagnosis Direct demonstrationof Nocardia from sputum bronchoalveolar lavage bronchialaspirate or endotracheal aspirate should be attempted
Gramrsquos stain smear shows Gram-positive beaded fineright-angled branching filaments (lt1 120583m diameter) whichmay fragment to form rods and coccoid forms of varyingsizes Most isolates of Nocardia are acid fast by modifiedKinyoun technique that differentiates it from Actinomyceswhich is not acid fast Silver methenamine stain is equallyuseful and reliable as modified Ziehl-Neelsen staining [4]
Nocardia spp grow on media used for culture of bacte-ria fungi and Mycobacteria Typical colonies appear afterthree to five days Nocardia spp appear as either buff orpigmented waxy cerebriform colonies or have a dry chalky-white appearance with the production of aerial hyphae
Some commercial identification systems like API 20C(Biomerieux) allow for rapid identification of Nocardia sppbut have the limitation of the traditional phenotypic method[5]
Molecular identification of Nocardia is not only quickand accurate but also helps in the recognition of newspecies Various methods like ribotyping polymerase chainreaction restriction fragment length polymorphism analysisand DNA sequencing are available [6]
DNA sequencing is currently the best tool for speciesidentification of Nocardia Sequencing of first 500ndash606 basepairs of the 51015840 end of 16S rRNA gene is the recommendedmethod [6] All these methods have their limitations andshould be used with caution
Currently there are no serological tests available fordiagnosis of active nocardiosis due to the cross-reactivityamong different Nocardia speciesMycobacterium tuberculo-sisMycobacterium leprae and other Actinomycetes [7]
26 Management Trimethoprim-sulfamethoxazole (TMP-SMX) is the mainstay of treatment and has improved theoutcomes In adults with normal renal function and localizeddisease the recommended daily dose of TMP-SMX is 5 to
10mgkgTMPand 25 to 50mgkg SMX in two to four divideddoses depending on the extent of diseaseHigher initial doses(15mgkg TMP and 75mgkg SMX) given intravenously ororally are frequently used in patients with cerebral abscessessevere extensive or disseminated infection or AIDS Sul-fonamides are the treatment of choice for disease due toN brasiliensis However mortality with monotherapy is ashigh as 50 [8] especially in severely ill patients and thosewith cerebral involvement or disseminated nocardiosis andimmune-suppression Empirical combination therapy withamikacin and imipenem (or meropenem) or a three-drugregimen comprising of Sulphonamides amikacin and eitheraCarbapenemor third generationCephalosporin can be usedin such high-risk patients
3 Conclusion
Isolation of nocardiae from sputum or blood occasionallyrepresents colonization transient infection or contami-nation In cases of respiratory tract colonization Gram-stained specimens are usually negative and cultures areonly intermittently positive Until a better tool to determinethe virulence of Nocardia is available the positive cultureoften reflects disease in immune-suppressed patients suchas patients on corticosteroid therapy patients who undergoorgan transplantation patients with chronic lung diseaseand HIV-positive patients Therefore PN must be suspectedin patients with these risk factors and positive imagingfindings Early detection of the organism can lead to theprompt initiation of treatment and reducedmortality in thesepatients Initial combination therapy with two or more activeagents is recommended for patients with disseminated orsevere nocardiosis
Additional Points
Learning Objectives (i) To recognize the importance ofNocardia in causing lung infections (ii) To diagnoseNocardiain the laboratory (iii) To treat infections caused by Nocardia
Pre-Test (1) How to diagnose Pulmonary Nocardiosis (2)How can it be treated effectively
Post-Test
(1) How to Diagnose Pulmonary Nocardiosis Direct demon-stration of Nocardia from clinical samples stained withGramrsquos stain and the modified acid fast stain will help inthe diagnosis of Nocardiosis Nocardia appears as Gram-positive filamentous branching rods with beaded appearanceon Gramrsquos staining and acid fast branching filamentous rodswith beaded appearance on modified Ziehl-Neelsen stainingThe diagnosis can further be confirmed by culturing theorganism in solid media
(2) How Can It Be Treated Effectively Trimethoprim-sulfamethoxazole (TMP-SMX) is the mainstay of treatmentHowever monotherapy may lead to treatment failuresHence empirical combination therapy with amikacin and
4 Canadian Respiratory Journal
imipenem (or meropenem) or a three-drug regimen com-prising Sulphonamides amikacin and either a Carbapenemor third generation Cephalosporin can be used in high-riskpatients
Disclosure
Workwas carried out at Department ofMicrobiology Vallab-hbhai Patel Chest Institute Delhi University Delhi India
Competing Interests
The authors declare that there are no competing interestsassociated with this work
Authorsrsquo Contributions
Jayanthi Gunasekaran processed the samples and compiledthe data Malini Shariff supervised the lab work interpretedthe results reviewed the subject and wrote the paper
Acknowledgments
The study was supported by Vallabhbhai Patel Chest Institutethrough their annual governmental funding
References
[1] M E Nocard ldquoNote sur la maladie des boeufs de la guadeloupeconnue sous le nom de farcinrdquo Annales de lrsquoInstitut Pasteur vol2 pp 293ndash302 1888
[2] H Eppinger ldquoUeber eine neue pathogenic Cladothrix und einedurch sie hervorgerufene PseudotuberculosisrdquoWiener KlinischeWochenschrift vol 3 article 321 1890
[3] C W Emmons C H Binford J P Utz and K J Kwon-ChungMedical Mycology Lea amp Febiger Philadelphia Pa USA 3rdedition 1977
[4] L Garcia-Bellmunt O Sibila I Solanes F Sanchez-Reus andV Plaza ldquoPulmonary nocardiosis in patients with COPDcharacteristics and Prognostic Factorsrdquo Archivos de Bronconeu-mologia vol 48 no 8 pp 280ndash285 2012
[5] S Mathur R Sood M Aron V K Iyer and K Verma ldquoCyto-logic diagnosis of pulmonary nocardiosis a report of 3 casesrdquoActa Cytologica vol 49 no 5 pp 567ndash570 2005
[6] B A Brown-Elliott J M Brown P S Conville and R JWallaceJr ldquoClinical and laboratory features of the Nocardia spp basedon currentmolecular taxonomyrdquoClinicalMicrobiology Reviewsvol 19 no 2 pp 259ndash282 2006
[7] M M Mcneil and J M Brown ldquoThe medically important aer-obic actinomycetes epidemiology and microbiologyrdquo ClinicalMicrobiology Reviews vol 7 no 3 pp 357ndash417 1994
[8] R J Wallace Jr E J Septimus T W Williams Jr et al ldquoUse oftrimethoprim-sulfamethoxazole for treatment of infections duetoNocardiardquoReviews of InfectiousDiseases vol 4 no 2 pp 315ndash325 1982
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
4 Canadian Respiratory Journal
imipenem (or meropenem) or a three-drug regimen com-prising Sulphonamides amikacin and either a Carbapenemor third generation Cephalosporin can be used in high-riskpatients
Disclosure
Workwas carried out at Department ofMicrobiology Vallab-hbhai Patel Chest Institute Delhi University Delhi India
Competing Interests
The authors declare that there are no competing interestsassociated with this work
Authorsrsquo Contributions
Jayanthi Gunasekaran processed the samples and compiledthe data Malini Shariff supervised the lab work interpretedthe results reviewed the subject and wrote the paper
Acknowledgments
The study was supported by Vallabhbhai Patel Chest Institutethrough their annual governmental funding
References
[1] M E Nocard ldquoNote sur la maladie des boeufs de la guadeloupeconnue sous le nom de farcinrdquo Annales de lrsquoInstitut Pasteur vol2 pp 293ndash302 1888
[2] H Eppinger ldquoUeber eine neue pathogenic Cladothrix und einedurch sie hervorgerufene PseudotuberculosisrdquoWiener KlinischeWochenschrift vol 3 article 321 1890
[3] C W Emmons C H Binford J P Utz and K J Kwon-ChungMedical Mycology Lea amp Febiger Philadelphia Pa USA 3rdedition 1977
[4] L Garcia-Bellmunt O Sibila I Solanes F Sanchez-Reus andV Plaza ldquoPulmonary nocardiosis in patients with COPDcharacteristics and Prognostic Factorsrdquo Archivos de Bronconeu-mologia vol 48 no 8 pp 280ndash285 2012
[5] S Mathur R Sood M Aron V K Iyer and K Verma ldquoCyto-logic diagnosis of pulmonary nocardiosis a report of 3 casesrdquoActa Cytologica vol 49 no 5 pp 567ndash570 2005
[6] B A Brown-Elliott J M Brown P S Conville and R JWallaceJr ldquoClinical and laboratory features of the Nocardia spp basedon currentmolecular taxonomyrdquoClinicalMicrobiology Reviewsvol 19 no 2 pp 259ndash282 2006
[7] M M Mcneil and J M Brown ldquoThe medically important aer-obic actinomycetes epidemiology and microbiologyrdquo ClinicalMicrobiology Reviews vol 7 no 3 pp 357ndash417 1994
[8] R J Wallace Jr E J Septimus T W Williams Jr et al ldquoUse oftrimethoprim-sulfamethoxazole for treatment of infections duetoNocardiardquoReviews of InfectiousDiseases vol 4 no 2 pp 315ndash325 1982
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom