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Florentina 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
 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
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
 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
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
http://galleryhip.com/cutaneous-nocardiosis.html
http://dermchallenge.blogspot.com/2012/08/sporotrichoid-spread-of-nocardia.html
 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
 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
 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
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
 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
• 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
Mootsikapun P, Intarapoka B, Liawnoraset W. Int J Infect Dis.
2005 May;9(3):154-8
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.
16
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.
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.
 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
Florentina Eller, PharmD Candidate
11/24/2014

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Florentina Eller Patient Case Cutaneous Nocardia

  • 1. Florentina Eller, PharmD Candidate 11/24/2014
  • 2.  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
  • 3.  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
  • 4. 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
  • 5.
  • 6.  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
  • 7. 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
  • 9.  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
  • 10.  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
  • 11.  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
  • 12. 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
  • 13.  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 • 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
  • 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
  • 15. Mootsikapun 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. 16
  • 17. 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.
  • 18. 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.
  • 19.  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
  • 20. Florentina Eller, PharmD Candidate 11/24/2014

Editor's Notes

  1. She first noticed a small painful nodular eruption that drained pustular debris when pressed. After starting bactrim, original lesion started to dry Her PCP swab the first nodule and send her to VUMC for IV abx ( employee of vandi- cytophatologist) While here the cultures came back positive for Nocardia Denies any inciting injuries, recent outdoors activities, gardening, and has 2 cats but denies any scratches- the cats’ claws are capped Ros otherwise negative No recent fever, chills, n/v, no chest pain, no SOB, no abdominal pain or recent diarrhea Proctocolitis is an inflammation involving the rectum and colon and is associated with a number of root causes. Some patients develop this condition as a result of sexually transmitted infections, while others may experience it in conjunction with inflammatory bowel disease, ulcerative colitis, and related conditions. Management of proctocolitis can include medications to kill infectious organisms along with drugs to reduce inflammation. In severe chronic forms, surgery sometimes needs to be explored as a treatment option.
  2. Disseminated: eyes, skin, kidneys, joints, bone, heart
  3. .
  4. Fluoroquinolones often have demonstrable in vitro activity against Nocardia species but have failed therapeutically
  5. Nocardia (off-label use): Oral, IV: Cutaneous infections: 5-10 mg TMP/kg/day in 2-4 divided doses Severe infections (pulmonary/cerebral): 15 mg TMP/kg/day in 2-4 divided doses for 3-4 weeks, then 10 mg TMP/kg/day in 2-4 divided doses. Treatment duration is controversial; an average of 7 months has been reported.
  6. Nocardia (off-label use): Oral, IV: Cutaneous infections: 5-10 mg TMP/kg/day in 2-4 divided doses Severe infections (pulmonary/cerebral): 15 mg TMP/kg/day in 2-4 divided doses for 3-4 weeks, then 10 mg TMP/kg/day in 2-4 divided doses. Treatment duration is controversial; an average of 7 months has been reported.