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