nocardia & actinomycosis nattaya mangkalapiwat 28 april 2008 infect topic
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Nocardia &Actinomycosis
Nattaya Mangkalapiwat28 April 2008
Infect topicInfect topic
Nocardia :History Edmond Nocard,
1888 Aerobic actinomycete
from cattle with bovine farcy
NocardiaNocardia
GenusGenus : aerobic actinomycetes G+ branching filamentous bacteria SubgroupSubgroup: aerobic nocardiform actinomycetes -Mycobacterium -Corynebacterium -Nocardia -Rhodococcus -Gordona -Tsukamurella
NocardiaNocardiaAt least 13 species : cause human infection 7most important 11. . Nocardia asteroidesNocardia asteroides complex complex :80% of noncutaneous dz. :most systemic & CNS nocardiosis *** 2. Nocardia farcinicaNocardia farcinica :less common,more virulent :more antibiotic-resistant member
3.Nocardia nova 4.Nocardia brasiliensis: skin,cutaneous,lymphocutaneous 5.Nocardia pseudobrasiliensis:systemic infections, CNS 6.Nocardia otitidiscaviarum 7.Nocardia transvalensis .
NocardiaNocardia :ECOLOGY& EPIDEMIOLOGY
Ubiquitous environmental saphrophyte Soil, organic matter,water Tropical and subtropical regions
:Mexico, Central and South America,Africa and India
NocardiaNocardia :ECOLOGY& EPIDEMIOLOGY
Nearly all cases :sporadic Human-to-human Animal-to-human not documented OutbreaksOutbreaks : Contamination of the
hospital environment, solutions,drug injection equipment.
NocardiaNocardia :ECOLOGY& EPIDEMIOLOGY
The risk of pulmonary or The risk of pulmonary or disseminated diseasedisseminated disease
*deficient celldeficient cell--mediatedmediated * -Alcoholism
-Diabetes -Lymphoma
-Transplantation -Glucocorticoid therapy -AIDS CD4+ < 250
TransmissionTransmission
Inhalation Skin
NocardiaNocardia : PATHOLOGY Acute pyogenic inflammatory reaction.
Branching, beaded, filamentous bacteria
G/S from a nocardial lung abscess G/S from nocardial pneumonia
NocardiaNocardia :PATHOGENESIS
Neutralization of oxidants Prevention of phagosome-lysosome fusion Prevention of phagosome acidification.
Mycolic acid polymers:ass.with virulence
CLINICAL MANIFESTATIONS: 4 main form4 main form
Lymphocutaneous syndrome Pulmonary :Pneumonia CNS : Brain abscess Disseminated disease CNS Eyes (particularly the retinaKeratitis), Skin& subcutaneous Kidneys, Joints, bone Heart
Lymphocutaneous syndromeLymphocutaneous syndrome
Ubiquitous in soil inoculation injuries, Insect and animal bites contaminated abrasions N. brasiliensis : most common N. asteroides : self-limited Because initial response Rx as staphylococcus
underdiagnosedunderdiagnosed Mycetoma Mycetoma Days to months ,typical:distal limb
-Cellulitis-Lymphocutaneous syndrome -Actinomycetoma
Nocardial actinomycetoma swelling, multiple sinus tracts,
Pulmonary diseasePulmonary disease Pneumonia
Subacute(more acute in immunosuppressed) Cough**
Small amounts of thick, purulent sputum Fever, anorexia, weight loss, malaise
Endobronchial inflammatory mass Lung abscess Cavitary disease Inadequate therapy Progressive fibrotic diseaseฆ
Cerebral imaging,should be performed in all Cerebral imaging,should be performed in all cases of pulmonary and disseminated cases of pulmonary and disseminated
nocardiosisnocardiosis
Nocardial pneumonia. Discrete nodular in midlung on both sides
CT scan (A),CXR (B) from : multiple abscesses : Nocardia farcinica
CNS : Brain abscessCNS : Brain abscess
Insidious presentations : mistaken for neoplasiamistaken for neoplasia !!! Granulomatous , abscesses Cerebral cortex, basal ganglia and midbrainCerebral cortex, basal ganglia and midbrain****** Less commonly: spinal cord or meninges. Brain tissue diagnosis in pulmonary nocardiosis : not necessary However, cerebral biopsy:considered early in immunocompromised
brain abscess ; Nocardia farcinica Nocardial abscess :rt. occipital lobe
LABORATORY DIAGNOSISLABORATORY DIAGNOSIS Gram-positive, beaded, branching filaments usually weak acid fast+ve . Standard blood cultureStandard blood culture :48 hrs to several wks, but typical = 3 to 5 days Colonization of sputumColonization of sputum :underlying pulmonary dz + not receiving steroid therapy no specific therapy Susceptibility testing
-Deep-seated /disseminated dz. fail initial therapy -Relapse after therapy-Alternatives to sulfonamides are being considered
MANAGEMENTMANAGEMENT:Medication:Medication
Sulfonamides : the mainstay of therapy treatment of choice :N. brasiliensis
N. asteroides complex N. transvalensis. severely ill patients, CNS /disseminated/
immunosuppressed patients =/> 2 drugs Amikacin and Carbapenem or 3rd generation cephalosporin.
MANAGEMENTMANAGEMENT:Medication:Medication TMP-SMXTMP-SMX :currently preferred :drugs in serum:CSF = 1:20
:high MICs good therapeutic responses -General:5-10 mg/kgTMP & 25-50 mg/kgSMX divide2- 4times -Cerebral abscesses,severe,disseminated,AIDS :15 mg/kg TMP and 75 mg/kg SMX) -Cutaneous infection: 5 mg/kg/day (TMP) + DB
Hypersensitivity reactions :DesensitizationHypersensitivity reactions :Desensitization
MANAGEMENTMANAGEMENTMedication:alternative therapeutic drugsMedication:alternative therapeutic drugs Failed sulfonamide Rx: N. otitidiscaviarum Intolerant : hypersensitivity,GI toxicity, myelotoxicity) Parenteral : Imipenem & amikacin
: Meropenem : 3rd-gen cephalosporins Ceftriaxone,
cefotaxime
Oral:Amoxicillin clavulanate :Minocycline(100–200 mg twice daily) :Linezolid :new oxazolidinone ;effective orally
(bioavailability~100%), good CSF penetration
MANAGEMENTSurgical drainage: depend on sitedepend on site Extraneural aspirate,drainage, excision Brain abscessesBrain abscesses
1) Accessible and relatively large AND
2.1) Lesions progress within 2 wks or
2.2) No reduction in abscess size within a month.
Duration of Therapy
HIV-negative immunosuppressed
:12 mo or longer if there are intercurrent increases in immunosuppression
AIDS
: at least 12 mo. +
low-dose maintenance
(long life)
Clinical improvement: most 7 -10 days Parenteral 3 to 6 wks oral regimen Primary cutaneous infection :1-3 mo.Nonimmunosuppressed
-Pulmonary /systemic nocardiosis: at least 6 mo -CNS involvement : for 12 months
Immunocompromised
Outcome of therapyOutcome of therapy
Cure ratesCure rates -skin or soft tissue : almost 100% -pleuropulmonary disease : 90% -disseminated infection : 63% -brain abscess : 50%
Mortality Mortality -brain abscesses :31%
-multiple abscesses :41% -immunocompromised patients :55%
Actinomycosis
Genus : Actinomyces
Slowly progressive infection Colonize : mouth, colon, vagina Infection : mucosal disruption In vivo : Grains / Sulfur granules The most misdiagnosed disease
3 clinical presentations3 clinical presentations 1.chronicity, progress across tissue boundaries,
masslike 2. develop sinus tract, resolve and recur
3. refractory/relapsing after a short course therapy
Etiologic AgentsEtiologic Agents
A. israelii*** A. naeslundii/viscosus A. odontolyticus A. viscosus A. meyeri A. gerencseriae
pelvic disease ass. IUCDs & “lumpy jaw”IUCDs & “lumpy jaw” 16S rRNA gene sequencing led to identification of an
ever-expanding list of Actinomyces spp
Concomitant bacteriaConcomitant bacteria
Staphylococcus / Streptococcus Enterobacteriaceae Actinobacillus comitans Eikenella corrodens HACEK Fusobacterium Bacteroides Capnocytophaga (Dog bite)
EpidemiologyEpidemiology Members of oral, GI, and genital floraoral, GI, and genital flora Never been cultured from nature No document of person-to-person transmissionNo document of person-to-person transmission The peak incidence : mid-decades Male > Female (poorer dental hygiene & oral trauma )
Pathogenesis & PathologyPathogenesis & Pathology Disruption of the mucosal barrier. Spreads : slow progressive manner, ignoring tissue planes.
Hallmark : chronic, indolent phase (single /multiple indurations) Wooden – fibrotic wall As mature lesion : soft , fluctuant and suppurates centrally. The fibrous walls :wooden absence of suppuration: neoplasm??? Sinus tracts : spontaneously close and re-form skin adjacent organs(bone)
Pathology :Central necrosis consisting of neutrophils + sulfur granulesPathology :Central necrosis consisting of neutrophils + sulfur granules.
Actinomycosis
G/S :Variable cellular morphology, ranging from diphtheroidal to coccoid filaments มั�กพบ sulfur granule จากการย้�อมั gram ได้� และย้�อมัไมั�ติ�ด้ ย้�อมัไมั�ติ�ด้ mAFBmAFB
Actinomycosis
G/S :sulfur granuleSulfur granules
Risk FactorsRisk Factors
Foreign bodies : IUCDs Abnormal host defense : HIV Post transplantation Radio-Chemotherapy Ulcerative mucosal infection: HSV/CMV
Clinical ManifestationsClinical Manifestations
Oral-Cervicofacial Disease Thoracic Disease Abdominal Disease Pelvic Disease Central Nervous System Disease Musculoskeletal & Soft tissue infection Disseminated Disease
Oral-Cervicofacial DiseaseOral-Cervicofacial Disease
Most frequently site Soft tissue swelling / mass/ abscess : mistaken
for a neoplasm Most common site : Angle of jaws Dx: mass lesion/relapsing infection in head &neckhead &neck Complication :-Otitis, sinusitis, and canaliculitis
:-extend to cranium,c- spine, thorax
Most common site : Angle of jaws
Thoracic DiseaseThoracic Disease
Chest pain, fever, and weight loss ***. Cavitary disease / hilar adenopathy >50% pleural thickening / effusion / empyema pulmonary nodules or endobronchial lesions :
Rare CT scan:central low attenuation + ringlike rim enh
ancement ComplicationComplication: - Mediastinal infection*** : uncommon, usually from thoracic extension - Breast disease - Primary Endocarditis
B and C: Chest x-ray + CTscan :pulmonary infiltrate, pleural effusion,
pleural and chest wall extension (arrow).
A:Chest wall
mass
D:Purulent pleural fluid (aspiration)
Abdominal Disease(1)Abdominal Disease(1) Usually pass from inciting event
Appendicitis Diverticulitis PUD Foreign bodies Bowel surgery ascension from IUCD-associated pelvic disease
Abscess, mass, mixed lesion : mistaken—tumor??? CT: heterogeneous enhance+ thick adjacent bowel. Sinus tracts abd. wall / perianal/ between bowel (Mimic inflammatory bowel disease) Clue : Recurrent dz /wound or fistula : fails to heal Imaging and percutaneous techniques :Therapeutic diagnosis
A.CTscan:multiple hepatic abscesses and small splenic lesion extend out side liver. Inset: Gram's stain of abscess
B.Subsequent formation of a sinus tract.
Abdominal Disease(2)Abdominal Disease(2)
KUB Disease All levels: can be infected
- pyelonephritis
- renal and perinephric abscess Bladder involvement:usually due to pelvic disease urine : stains and cultures
Pelvic DiseasePelvic Disease
Risk:IUD in place >1yr-months after removed S&S: Typically indolent fever, wt loss, abd pain, abnormal vaginal bleeding or discharge Endometritis masses/tuboovarian abscess delayed Rxfrozen pelvisfrozen pelvis
Removed as early as possible :but not removal not removal of the IUCD unless a suitable contraceptiveof the IUCD unless a suitable contraceptive
An IUCD encased by endometrial fibrosis (solid arrowhead) paraendometrial fibrosis (open arrow)
CNS DiseaseCNS Disease Rare Single/multiple abscess** Irregular nodular Rim-
enhancing thick wall Meningitis / Epidural /
Subdural space infection Cavernous sinus syndrome
MS & Soft tissueMS & Soft tissue Associated trauma:Fx Adjacent soft tissue Bone Periostitis / Osteomyelitis/ Cutaneous sinus tracts** .
Disseminated Disease Disseminated Disease :Lung* / Liver* :multiple nodules ~ CA metas but, indolent
MS & Soft tissue: MS & Soft tissue: Cutaneous sinus tracts
DiagnosisDiagnosis
Avoid unnecessary surgery Aspirations & Biopsy Material for C/S + microscopic identification Sulfur granulesSulfur granules : In vivo matrix of bacterial + CaPO4 + host debris Grossly identified from sinus tract DDx : Mycetoma / Botryomycosis
C/S isolated in 5-7 d but 2-4 wk. if previous ATB 16S rRNA gene amplification and sequencing : not routinely used
Can cure with medical Rx alone even in extensive dzCan cure with medical Rx alone even in extensive dz
Medical ManagementMedical Management High doses and prolonged period 1. serious infections and bulky disease Intravenous PGS 18-24 mU /day : 2-6 wk.
then Oral Penicillin / Amoxycillin : 6-12 mo. 2.Less extensive disease, e.g. oral-cervicofacial : cured with shorter course.
Combined medical-surgical therapyCombined medical-surgical therapy initial attempt cure with medical Rx alone, CT and MRI : monitor Critical organs : Reproductive /CNS e.g. epidural space Fails suitable medical therapy
TreatmentTreatment
Thank you foryour attention
ReferenceReference-Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases,6TH Edition-Harrison's PRINCIPLES OF INTERNAL MEDICINE,17th Edition-CLINICAL MICROBIOLOGY REVIEWS, Apr. 2006, p. 259–282
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