A case of High Dose

Steroids and

Pulmonary Nodules Adrian Tramontana

Western Health

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45 year old immunocompromised man admitted with “septic pulmonary

emboli” in March 2014

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Background History

FSGS, Interstitial nephritis, ATN

Dx on biopsy Dec 2013

Nephrotic range proteinuria

moderate chronic renal parenchymal injury

Rx – Prednisolone 25 mg tds – steroid induced diabetes

DVT/ PE Feb 2014

Factor V Leiden

6/2/14 - R leg DVT – Started Warfarin

12/2 - R basal subsegmental PE on V/Q – IVC filter isnerted

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Background History

Hypertension

Dyslipidaemia

Gout

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History

Presented 7/3/14

General malaise and fatigue for 3 weeks

lump in Right axilla – 1 week

Pimple that grew into an painful and tender lump

left sided pleuritic chest pain with dyspnoea – 1 dy

Feeling hot and cold

Polyuria and polydipsia

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Examination

P-75, 125/85, R – 16, sats 97% on 3L O2, afebrile

3cm tender erythematous abscess R upper arm

Chest – scattered crackles throughout

Bilateral oedema to knees

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Investigations

FBE 16.6/ 16.5/ 125 neut 14.4

UEC – Cr 157, eGFR 45

LFTs – bili 8, ALP 215, GGT 177, ALT 55, Alb 16

INR 1.7

Ck 67

Protein electrophoresis – Inflammatory response with low IgG 1.5 g/L

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Initial Management

Initial Antibiotics in Emergency

Ceftriaxone and Azithromycin

Vancomycin

I + D abscess on right arm

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Microbiology Results

7/3/14

Blood cultures – negative

8/3/14

Axillary Swab – Large polymorphs,

Large numbers of GPC,

Large numbers of GPB resembling diptheroids

Growth – mixed skin flora

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Microbiology Results

BC from 8/3/15

After 3 days incubation

Footer Text 13 Photo Courtesy Jenny Wong Dorevitch Pathology

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Blood Culture Isolate

Nocardia farcinica

Cotrimoxazole – S Imipenem - I

Linezolid – S Amikacin - S

Augmentin – S Ciprofloxacin - R

Ceftriaxone – R Clarithromycin - R

Minocycline – I

Tobramycin - R

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Treatment

Bactrim DS

Imipenem – 500mg q8hrly

CT brain – no abscess

Weaning of prednisolone –

17/3 37.5mg

2/4 10mg daily

19/6/ Ceased

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Complications

Psoas haematoma – Requiring embolisation

Seizure – no CNS involvement on CT brain

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Progress

4 April Responding to Treatment

Sensitivities – Preliminary sensitivities

Imipenem dose increased to 1g q8hrly – 4 weeks total Rx

Bactrim rash – 13/5/14

Augmentin started 15/5/14

Rash in June with lip swelling and blistering on hands

June 30 – Rpt CT chest – resolution of nodules

14 weeks Rx completed

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Progress

? Rash due to scabies as wife also had rash

14/7/15

Rx scabies with invermectin and permethrine

Minocycline 100mg bd

Rx until 24/11/14

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Nocardia

Ubiquitous environmental bacteria

Found in

Soil,

Decomposing Vegetation,

other Organic Matter,

Fresh and Salt Water.

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Taxonomy

Sub-order – aerobic Actinomycetes

Includes – Mycobacterium, Corynebacterium,

Gordona, Tsukamurella

Family – Nocardiaceae

Includes – Nocardia and Rhodococcus

Nocardia asteroides

later named Nocardia asteroids complex

now multiple species

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Microbiology

Aerobic gram positive bacteria

Filamentous bacteria

hyhaelike branching on direct microscopy

Varying degress of Acid Fastness

Depending on mycolic acid composition in the cell wall

Modified Kinyoun stain

1% sulphuric acid as decolorizer instead of HCl acid in ZN

Beaded Acid fast bacilli compared to Mycobacteria

Resemble Actinomyces on gram stain – Actinomyces NOT acid fast

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Risk factors for infection

• Corticosteroids

• Cell Mediated Immune Deficits

Solid organ transplant 0.6% to 3%

• Anti – TNFα therapy

• Chronic Lung Disease particularly with steroid use

• 1/3 not immunocompromised

eg. Traumatic cutaneous inoculation

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Clinical Presentation

Wide spectrum

Acute presentations

fever

leukocytosis – 54%

Chronic presentation

Symptoms of organ involvement – Not always present

Pulmonary

Pleural involvement with chest pain frequent

Cutaneous abscess useful clue

Can resemble – lung Ca, fungal and mycobacterial infections

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Sites of Diseases

Pulmonary – via inhalation

Contiguous spread – pleura, pericardium, mediastinum, vena cava

Can resemble actinomyces

Haematogenous spread – CNS 20-50%

Extra-pulmonary

Abscess formation chronic granulomatous inflammation

Primary cutaneous nocardiosis – direct implantation from soil

Resembling Staph and Strep abscesses – although more indolent

Localised Cellulitis

Sporotichoid like Nodules

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Discrete Pulmonary Nodules – 62%

May also be spiculated

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Cavitation of Pulmonary Nodules – 40%

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Consolidation – 54%

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Lung Cancer like presentation

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Pleural effusion/ Empyema – 40%

Aspirates often yield straw coloured fluid.

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Inhalation versus Haematogenous

Inoculation

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Inhalation versus Haematogenous

Inoculation

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Brain Abscess – Single or multiple

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Wide spectrum of sites of Dissemination

Co-Infections

Sputum Culture

H influenzae

A fumigatus x 3

Nocardia cyriacigeorgica x2

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Co-Infections

Concomitant bacteraemia – up to 63% in pulmonary infections

Gram negative – P. aeruginosa, others

Gram Positive – S. aureus

Candida

Other co-infections

Fungal – Aspergillus, Histoplasma

CMV

TB – 21% of pulmonary infections in one study from Taiwan

Non-Tuberculous Mycobacteria

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Differential Diagnosis versus Co-

infections

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Nocardia bacteraemia

64% have pulmonary nocardiosis

28% concurrent cutaneous nocardiosis

19% CNS disease

Can be radiologically occult – post mortem finding in 1 case report

Cases related to infected intravascular devices

CVC and AVR

Mortality – better for subacute presentations (>4 weeks of symptoms)

Blood Culture isolates – may be contaminant (particularly in newborns)

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Nocardia Species

Likely Geographic variation

Pulmonary and Disseminated Disease

N. asteroides – Pulmonary and CNS

N. farcinica – Pulmonary and blood

N. nova – Peleg study of Tx patients on bactrim prophylaxis

Isolated Cutaneous Disease

N. Basiliensis

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Antimicrobial Susceptibility pattern

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Treatment

Agents Used

Bactrim 10mg/kg

higher dose often used in CNS and disseminated disease

Minocycline

Imipenem/ Meropenem

Ceftriaxone

Linezolid

Amikacin

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Mouse model of Bactericidal Effect

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Treatment

No RCT

evidence from case series

no regimen demonstrated to be clinically superior

Combination therapy

Not superior to monotherapy in case series

Provides increased coverage whilst awaiting sensitivities

Bactrim + imipenem - widely used for CNS/ disseminated

Imipenem + amikacin

Linezolid + meropenem

Bactrim + ceftriaxone

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Treatment

Time to improvement

usually 7-10 days

Duration of Antibiotic therapy

Skin – 1-3 months unless mycetoma

Pulmonary

4-6 weeks intravenous

6 months total

Disseminated, CNS and ongoing immunosuppression

12 months +

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Treatment

Additional management

Source control

Drainage of abscesses

Removal of infected prosthesis –eg CVC, AVR

Reduce immunosuppression

Effect of Reducing Immunosuppression

Patient Initially refused treatment

Anti-TNFα ceased 2 months and methotrexate 1 week before presentation

Prednisolone 5mg

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Summary

Risk factors for Nocardia

High dose steroid and impaired cell mediated immunity

Clinical features to suspect Nocardia

pulmonary infection + skin abscesses

Imaging features

Nodules +/- cavitation,

Consolidation +/- Cavitation

Pleural effusions/ empyema

Co-infections common

Treatment poorly defined