Patient Case: Cutaneous NocardiosisFlorentina Eller, PharmD Candidate

11/24/2014

KT is a 33yo F who presents with 2.5 weeks of erythematous nodular eruption over the right forearm not improving on outpatient antibiotics.◦ Treated with 500 mg Keflex PO BID x3 days◦ Went back to PCP after appearance of 2 new nodules◦ Bactrim DS 1 PO BID replaced Keflex

PMH: Ulcerative proctocolitis, scalp psoriasis SH: no tobocco, EtOH, drugs, no recent travels, not sexually active FH: mother with HLD, OA, aunt with arthritis, dad with alchoholic liver

disease

Patient Case

Home Medications:◦ Olux-E ( clobetasol) 0.05% topical foam, 1QD prn◦ Vitamin C 1 tab PO QD◦ Mesalamine (Apriso) ER 0.375 g tabs 4 tabs QD

Micro (11/13) ◦ Gram Stain (abscess) : GPR probable Nocardia spp

Virology ( 11/19): HIV Ag/Ab 1 & 2 non-reactive

Chest XR ( 11/19): slightly abnormal ◦ Granulomatous calcification in the right lung

Old granulomatous disease◦ Otherwise normal chest

Patient Case

BMP CBC VS

Na 137 WBC 8.6 T 37C

K 4.3 Hgb 12.3 P 93

Cl 105 Hct 31.1 Resp 18

CO2 21 Plt 177 BP 109/60

BUN 16

SCr 0.79

eGFR > 60

AN-GAP 11

Labs on Admission

Nocardiosis

Aerobic, branching, beaded, gram-positive rods, acid fast positive Genus: Actinomycetes, Subgroup: Corynebacterium Found worldwide in soil and water

30 known species can cause human infections:◦ Pulmonary disease only (39%) ◦ Disseminated disease (32%)

N.asteroides and N. farcinica◦ CNS only (9%)◦ Cutaneous nocardiosis ( ~8 % of cases)

N. brasiliensis

• Brooks GF, Carroll KC, Butel JS, et al. Chapter 12. Aerobic Non–Spore-Forming Gram-Positive Bacilli: Corynebacterium, Listeria, Erysipelothrix, Actinomycetes, and Related Pathogens. In: Jawetz, Melnick, & Adelberg's Medical Microbiology, 26e. New York, NY: McGraw-Hill; 2013. http://accesspharmacy.mhmedical.com. Accessed November 23, 2014.

• Spelman D, Sexton D, Thorner A. Clinical manifestations and diagnosis of nocardiosis. UpToDate. Last Updated Apr 24, 2014. www.uptodate.com. Accessed 11/21/14

Nocardia spp.

Cutaneous Nocardiosis: Caused by direct inoculation of organism into skin

◦ Gardening, animal scratch or insect bites◦ Trauma, surgery, vascular catheter, professional exposure

Presentation:◦ Nodules, cellulitis, ulcerations, subcutaneous abscess◦ Lymphocutaneous manifestation ( “sporotrichoid nocardiosis”)

Nocardia is not transmitted from person to person

• Greenfield RA, Stuart BM. Nocardiosis. Updated Sep 25, 2014. Medscape http://emedicine.medscape.com/article/224123-overview. Accessed 11/23/14

• Spelman D, Sexton D, Thorner A. Clinical manifestations and diagnosis of nocardiosis. UpToDate. Last Updated Apr 24, 2014. www.uptodate.com. Accessed 11/21/14

Pathophysiology

http://galleryhip.com/cutaneous-nocardiosis.htmlhttp://dermchallenge.blogspot.com/2012/08/sporotrichoid-spread-of-nocardia.html

Cutaneous and Lymphocutaneous Nocardiosis

500-1000 cases per year in US Cure rates with appropriate therapy:

◦ ~ 100% in SSTI◦ 90% pleuropulmonary infections ◦ 63% disseminated nocardiosis ◦ 50% brain abscesses

Gender◦ More common in males than in females, with a male-to-female ratio of 3:1

Age◦ All ages are susceptible to nocardiosis◦ The mean age at diagnosis is in the fourth decade of life

Greenfield RA, Stuart BM. Nocardiosis. Updated Sep 25, 2014. Medscape http://emedicine.medscape.com/article/224123-overview. Accessed 11/23/14

Epidemiology

Immunocompromised patients ◦ 60% of cases are associated with preexisting immune dysfunction◦ Chronic pulmonary disorders◦ HIV/AIDS◦ Malignancy◦ Ulcerative colitis◦ Organ transplantation◦ Corticosteroid use◦ Diabetes◦ Alcoholism

Brooks GF, Carroll KC, Butel JS, et al. Chapter 12. Aerobic Non–Spore-Forming Gram-Positive Bacilli: Corynebacterium, Listeria, Erysipelothrix, Actinomycetes, and Related Pathogens. In: Jawetz, Melnick, & Adelberg's Medical Microbiology,

26e. New York, NY: McGraw-Hill; 2013. http://accesspharmacy.mhmedical.com. Accessed November 23, 2014

Risk Factors for Pulmonary and Disseminated Nocardiosis

Gram stain and Acid Fast staining :◦ Respiratory secretions◦ Abscesses aspirates ◦ Cultures takes 5-21 days to grow◦ AF positive: presumptive diagnosis

Kinyoun procedure most reliable

Antibiotics susceptibility and PCR for Nocardia speciation◦ Bactrim resistance◦ Resistance patterns varies by species◦ 16S rRNA-based assay is sensitive and specific

Blood cultures when pulmonary or disseminated nocardiosis is suspected

Brain imaging in all immunocompromised patients• Spelman D, Sexton D, Thorner A. Clinical manifestations and diagnosis of nocardiosis. UpToDate. Last

Updated Apr 24, 2014. www.uptodate.com. Accessed 11/21/14 • Greenfield RA, Stuart BM. Nocardiosis. Updated Sep 25, 2014. Medscape

http://emedicine.medscape.com/article/224123-overview. Accessed 11/23/14

Diagnosis

Sulfonamides ◦ TMP/SMX

DOC At the outset, 10–20 mg /Kg of TMP

50–100 mg/Kg of SMX kg QD BID Later, can decrease to 5 mg/kg and 25 mg/kg, respectively

◦ Sulfonamide allergies: Desensitization usually allows continuation of therapy Imipenem plus amikacin in real sulfonamide allergies

• Filice G.A. Chapter 162. Nocardiosis. In: Longo DL, Fauci AS, Kasper DL, et al. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012. http://accesspharmacy.mhmedical.com. Accessed November 23, 2014.

• Greenfield RA, Stuart BM. Nocardiosis. Updated Sep 25, 2014. Medscape http://emedicine.medscape.com/article/224123-overview. Accessed 11/23/14

Treatment

Alternative parenteral therapies:◦ Carbapenems (imipenem or meropenem)◦ Third-generation cephalosporins (cefotaxime or ceftriaxone) ◦ Amikacin, alone or in combination◦ Linezolid or Tigecycline

Alternative oral therapies Minocycline and amoxicillin/clavulanate, in addition to linezolid Used initially in mild-to-moderately severe disease or after an induction course

of parenteral therapy

Treatment

• Filice G.A. Chapter 162. Nocardiosis. In: Longo DL, Fauci AS, Kasper DL, et al. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012. http://accesspharmacy.mhmedical.com. Accessed November 23, 2014.

• Greenfield RA, Stuart BM. Nocardiosis. Updated Sep 25, 2014. Medscape http://emedicine.medscape.com/article/224123-overview. Accessed 11/23/14

Prolonged to minimize risk of disease relapse Immunocompetent patients with non-CNS nocardiosis

◦ 6-12 months Immunosuppressed patients and those with CNS disease

◦ 12 months

Monitoring: Baseline culture and sensitivity testing CBC, serum K+, SCr, BUN Pregnancy category D Use with caution in patients with G6PD deficiency; hemolysis may occur (dose-

related) Follow-up radiographic studies

• Filice G.A. Chapter 162. Nocardiosis. In: Longo DL, Fauci AS, Kasper DL, et al. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012. http://accesspharmacy.mhmedical.com. Accessed November 23, 2014.

• Greenfield RA, Stuart BM. Nocardiosis. Updated Sep 25, 2014. Medscape http://emedicine.medscape.com/article/224123-overview. Accessed 11/23/14

Treatment Duration

Nocardiosis in Srinagarind Hospital, Thailand: review of 70

cases from 1996-2001Mootsikapun P, Intarapoka B, Liawnoraset W. Int J Infect

Dis. 2005 May;9(3):154-8

16

Methods: Retrospective study, from 1996-2001 Medical records of 70 patients with nocardiosis were

reviewed

Objectives: Characterize the clinical manifestation, underlying

diseases, radiologic findings, antimicrobial susceptibility and treatment of Nocardia infection.

Mootsikapun P, Intarapoka B, Liawnoraset W. Nocardiosis in Srinagarind Hospital, Thailand: review of 70 cases from 1996-2001. Int J Infect Dis. 2005 May;9(3):154-8. Review.

Int J Infect Dis. 2005 May;9(3):154-8

Results: 80% of cases were male

◦ Mean age was 39.7+/-14.9 years 80 % of patients had underlying diseases

• HIV infection was the most common (34.3%)

Most common symptoms:◦ Fever (69%)◦ Cough (60%)◦ Cutaneous abscess (23%)

The most common clinical disease:• Pleuropulmonary infection (44.3%)• Skin and soft tissue infection (22.8%)• Multiorgan dissemination (11.4% )

Chest X-rays were abnormal in 46 cases (65.7%) 70% had positive cultures for Nocardia spp.

Int J Infect Dis. 2005 May;9(3):154-8

Results (Cont.):

95% of patients received TMP-SMX ◦ 15 mg/Kg/day TMP

TMP-SMX resistance rate was high (57.9%)

Susceptibilities of Nocardia isolates:◦ 42% were susceptible to TMP-SMX

5 cases did not respond to TMP-SMX and died◦ 98% susceptible to imipenem◦ 95% amoxicillin/clavulanate

In-hospital mortality was 20%◦ Dissemination, brain abscesses or infection with TMP-SMX-resistant strains

Long-term prognosis was good, with a treatment success rate of 93.75%Mootsikapun P, Intarapoka B, Liawnoraset W. Nocardiosis in Srinagarind Hospital, Thailand: review of 70 cases from 1996-2001. Int J Infect Dis. 2005 May;9(3):154-8. Review.

Int J Infect Dis. 2005 May;9(3):154-8

Preliminary Gram Stain from wound: GPR probable Nocardia spp.◦ Final cultures takes 5-21 days for growth

AF was not performed HIV was ruled out Granulomatous calcification in the right lung

◦ Old granulomatous disease

Bactrim 2 DS PO BID was started 640 mg TMP ( ~10mg/kg)

KT discharged next day with 3-6 months therapy Follow up in 2 weeks, when final gram stain cultures available

KT: clinical course

Patient Case: Cutaneous NocardiosisFlorentina Eller, PharmD Candidate

11/24/2014