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Rhodococcus Equi
                     …is it in you?



                  Trey Rumph
             Mercer University
    Internal Medicine Rotation
   PH is a 65 y/o WM admitted 2/5/2010
   CC: N&V for 2 days, cough for weeks and left foot
    pain
   PMH: ESRD, s/p related donor living renal
    transplant, T2DM, HTN, Polycystic Kidney
    disease, hx of Gout, hx of left upper lung pneumonia
   SH: married, lives on farm in South Pittsburg, (-)
    tobacco, (-) EtOH, Owns and manages a demolition
    company, but has been a coal miner for
    approximately 12 years
   Allergies: Demerol and Phenergan




Patient Case
   History of ESRD 2o polycystic kidney disease, s/p living
    related donor renal transplant from his daughter in
    2005 (Baseline Cr ~1.4-1.6).

   Presents to ER with CC of N&V with onset of 2 days ago

   Cough worsened over the last several weeks ever
    since d/c from hospital with left upper lung pneumonia on
    1/15/10

   Left foot pain that has progressively worsened over the last
    several days (Gout)

   BUN/Cr note to be 68/2.1 on presentation and volume




Patient Case (HPI)
Prograf 1mg PO BID    Lasix 40mg BID         Zyloprim 300mg Qdaily
CellCept 1gm PO BID   Verapamil 120mg PO     Starlix 120mg QD
                      BID
Prednisone 5mg PO BID Metoprolol 12.5mg PO   Lantus 20 units QHS
                      BID
                      ASA 81mg BID           Tessalon Perles prn


Immunosuppressants    Heart Medications      Gout
                                             Diabetes




Home Medications
Hospital meds
Cellcept 500mg IV   Morphine 4-8mg     Ambien 5mg QHS
Q12                 Q1/prn
Cytovene 500mg      Lopressor 12.5 BID Mycostatin 5mL
IV BID                                 QID
Solumedrol 10mg     Calan 120mg BID Carafate 1gm Q6
IV Q12
Zithromax 500mg     Bumex 1mg IV        Lantus 30units
QDaily              Q12                 QHS
Vancocin 0.75g IV   Nitrol Ointment 1   NovoLog SSI level
QDaily              inch Q6h            4
Roxicet UDL         Phenergan 6.25-     Procrit 10,000units
Q4/PRN              12.5mg Q6/prn       on MWF @1600
Lortab 7.5mg        Zofran 4mg          Apresoline 10-
Q4/prn              Q4/PRN              20mg Q6

Immunosuppressants Pain Management      Sleep Aid
Antibiotics        Heart Medication     Anti-Fungal
Pain Management    Nausea Medication    Diabetes
Upon Admission
 Admitted via ER with CC of nausea and
  vomiting for 2 days and a cough for
  weeks
 CT scan shows left upper lobe mass of
  6.5cm with lymph node involvement




Patient Case (Hospital Course)
Fig 1: There is an irregular large soft tissue mass in the
left upper lung field which opposes the descending
proximal thoracic aorta measuring some 5.5 x 6.5cm.
Course of Action
 IV Solu-Medrol
 Hold Prograf
    ◦ Use of Rapamune?
 Zosyn 2.25mg Q8- obstructive pneumonia
 Bronchoscopy – left upper lobe mass
Tacrolimus                 Sirolimus

   Post-transplant         Impaired wound
    Diabetes (~20% first     healing
    year)                   ↑K
   At high doses:          ↓ Mg
    ◦ Nephrotoxic           Hyperlipidemia
    ◦ Neurotoxicity
                            Hypertriglyceridemia
   Renal adjustments
                            Leukopenia
   QT prolongation



Prograf vs Rapamune
Results of Bronchoscopy
 Generalized erythema, mucosal bleeding
  with no obstructing mass noted in the left
  upper lobe
   Patient is coughing up blood, productive
    with a green coloration




Patient Case (Hospital Course)
Course of Action
 Add Vancomycin IV 1g Q24o to treatment
  (10.6mg/kg) and Zosyn 2.25mg Q8
 (CrCl ~29.2)

           Vancomycin Dosing and Trough Levels
         Date      Dose      Date      Trough
                                       level
         2/9/10    1g
         2/10/10   1g        2/12/10   17.6
                             2/20/10   30
                             2/21/10   27.6
                             2/24/10   27.3
         2/25/10   0.75g     3/1/10    13.9
         3/9/10    1g        3/9/10    23.6
 Blood in cough resolves, but kidney
  function begins to decline. Patients
  develops a hemothorax.
 Planned Video-Assisted Thoracoscopic
  Surgery (VATS)
    ◦ Retained hemothorax via trapped lung
      procedure
   ID Consulted
    ◦ Differential: CMV or atypical mycobacterium
    ◦ Ordered urine antigens and serology for Q-
      fever
    ◦ d/c Zosyn

Patient Case (Hospital Course)
Atypical Pneumonias
Legionnaires               Q fever                   Psittacosis
disease                    (Coxiella burnetii )      (Chlamydia psittaci )
(Legionella
pneumophila)
• Lung infection           • During birthing the     AKA: Parrot Disease or
(pneumonia)  CAP or       organisms are shed in     Parrot Fever
HAP lasts 2-14 days        high numbers within the   •Found in bird droppings
                           amniotic fluids and the
• Pontiac Fever            placenta and aerolized
symptoms usually last      • Usually inhaled,
for 2 to 5 days and may    extremely virulent
also include fever,        • Resistant to heat,
headaches, and muscle      drying, and many
aches; however, there is   common disinfectants
no pneumonia.
Course of Action
 Lab Evaluation
 ◦   Rare Gram(+) cocci to be identified…
 ◦   ?Malacoplakia or Rhodococcus Equi
 ◦   Vancomycin 1g Qdaily and Ancef 1g Q8o
 ◦   Immunosuppressants started back
      Prednisone 20mg QD
      Cellcept 250mg Q12
      Prograf 1g Daily
   Inflammatory condition that leads to
    formation of papules, plaques and
    ulcerations (usually affecting the genitourinary tract)

   Thought to result from the insufficient
    killing of bacteria by macrophages, that
    accumulate inside depositing iron and
    calcium forming the papules, etc.

   Associated with patients who are
    immunosuppressed


Malakoplakia
Rhodococcus Equi
   Characterized by rod-to-coccus morphologic
    variation during its growth cycle
   Rhodococcus genus due to its ability to form a
    red (salmon-colored) pigment - “red-pigmented
    coccus”
   Primarily causing zoonotic infections in grazing
    animals (ex: horses and foals)
   A soil organism that require simple requirements
    to survive, which seem to be met perfectly by
    herbivore manure and summer temperature in
    temperate climates



Background R. Equi
 R Equi is an obligate aerobic, intracellular,
  nonmotile, non-spore-forming, gram-
  positive coccobacillus
 Commonly transmitted via inhalation on
  farms

                            This latter histologic picture, termed
                            malakoplakia, is extremely rare within
                            the lung and, when present, is highly
                            suggestive of a R. equi infection




Background
   R. Equi is facultative intracellular
    pathogen, surviving inside macrophages
    to cause granulomatous inflammation and
    eventually destruction of macrophage.

   In humans, has only be found in patients
    with compromised immune systems in the
    lungs




Pathogenesis
   #1 Pneumonia (~66%)

   Other possible presentations
    ◦   Penetrating eye wound
    ◦   Inflammatory mass in the pelvis
    ◦   Bloody diarrhea and cachexia
    ◦   Pleural effusion
    ◦   Osteomyelitis
    ◦   Paraspinal abscess
    ◦   Inflammatory pseudotumor




Patient Presentation
   Typical Pathogens for CAP
    ◦ Streptococcus pneumoniae
    ◦ Moraxella catarrhalis
    ◦ Haemophilus influenzae




Primarily CAP Culprits
   Physical Findings
    ◦   Rales heard upon Auscultation over the chest
    ◦   Pleural Effusion
    ◦   Purulent sputum
    ◦   Blood-tinged sputum
    ◦   Signs of consolidation
         Typically seen with Legionella, Q fever, or
          psittacosis




Pneumonia Presentation
Summary of Clinical
Presentation
   Left Upper Lobe Lung Mass – CT directed
    Core Biopsy
    ◦ Malakoplakia of the lung
    ◦ Gram (+) organisms present
    ◦ Cytomegalovirus Inclusions Present               (in adjacent lung
     tissue)


Comment:
  Pulmonary malakoplakia has been described in
  immunocompromised patients, including organ transplant
  patients. The most commonly isolated organism in this
  setting is Rhodococcus equi – initial cultures do show growth
  of a difficult to identify organism; the culture has been referred to
  a reference laboratory for typing.




Surgical Pathology
Hematoxylin-and-Eosin Stain   Calcium Stain
     (Calcospherites)




Pathology
PAS + material               Gram Stain




                 Pathology
Pathology




  CMV inclusion
   From the pathology as well as the culture
    coming back with rare gram (+) cocci
    (Rhodococcus species), Infectious Disease
    concluded the presence of R Equi




Pathology
   Changed Therapy to…
    ◦ ∆ Vancomycin 1 g QDaily and Clindamycin
    ◦ Renal decides to hold Prograf due to declining
      renal function
    ◦ ∆ Clindamycin  Zithromax
    ◦ Added Levaquin for cover for new cultures of
      Klebsiella and Serratia found in the sputum

     Vancocin 1g QDaily/ Levaquin 750mg QDaily/
               Zithromax 250mg QDaily



Patient Case (Hospital Course)
   Must be covered by at least two or more agents

   Combination antibiotics should include one agent with
    intracellular penetration (ex: Erythromycin or
    Rifampin)

   Besides the use of anti-microbial drugs, the approach
    used in treatment of human infection involves
    drainage of the suppurative lesions, surgical resection
    of granulomatous tissue, and control of concurrent
    immunosuppressive drugs or control of underlying
    malignancies.

   Duration of treatment 4-9 weeks

Strategy to treat
R Equi
   Erythromycin
                      Macrolides
   Azithromycin
   Clarithromycin    Lincosamides
   Clindamycin
                      Fluoroquinolones
   Ciprofloxacin
   Aminoglycosides
   Rifampin          Anti-tuberculosis Agent
   Imipenem          Carbapenems
   Meropenem
   Vancomycin
   Linezolid         Oxazolidinones

Antibiotics used to treat
R. Equi
 Patient still in Respiratory failure
 Patient suspected of CMV per Lung biopsy
 Added Cytovene® (Ganciclovir) 200mg
  BID
 Patient was scheduled for Tracheotomy
  Surgery

    Vancocin 1g QDaily/ Levaquin 750mg QDaily/
    Zithromax 250mg QDaily/ Cytovene 200mg BID




Patient Case (Hospital Course)
Patient Case (Hospital Course)
 After 14 days of treatment the Levaquin
  was d/c’d
 Placed DHT bedside via CORTRAK
 Still in Respiratory failure
 Underwent the T-piece Trials on the vent
 Placed catheter




    Vancocin 1g QDaily/ Zithromax 250mg
         QDaily/ Cytovene 200mg BID



Patient Case (Hospital Course)
 Patient feels better
 Case Management refer him to Siskin and
  Kindred  Kindred accepts
 Cytovene d/c, ID was never really clear if
  CMV was a pathogen


    Vancocin 1g Q48h/ Zithromax 250mg
                   QDaily


Patient Case (Hospital Course)
Patient Case (Hospital Course)
    Patient is transferred to Kindred Hospital
     on…
Cellcept 500mg BID    Augmentin 875mg      Zyloprim 300mg
                      Qdaily               Qdaily
Prograf 2mg Qdaily    ASA 325mg Qdaily     Flomax 0.4mg after
                                           supper
Deltasone 5 mg BID    Lopressor 25mg BID   Mag-Ox 400mg BID

Lantus 20 units QHS   Calan SR 240mg       Colace 100mg BID
                      Qdaily
                      Lasix 60mg Qdaily

Immunosuppressants    Antibiotics          Gout
Diabetes              Heart Medications    Prostate Medication
   Munoz P, Palomo J, Guinea J, et al. Relapsing
    Rhodococcus equi infection in a heart transplant
    recipient successfully treated with long-term
    linezolid. Diagn Microbiol Infect
    Dis. Feb 2008;60(2):197-9
   Prescott, John. Rhodococcus Equi: an Animal and
    Human Pathogen. Clinical Microbiology Review.
    Jan 1991; 20-30
   Verville TD, Huycke MM, Greenfield RA, et
    al. Rhodococcus equi infections of humans. 12
    cases and a review of the literature. Medicine
    (Baltimore). May 1994;73(3):119-32



References

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Rhodococcus equi

  • 1. Rhodococcus Equi …is it in you? Trey Rumph Mercer University Internal Medicine Rotation
  • 2. PH is a 65 y/o WM admitted 2/5/2010  CC: N&V for 2 days, cough for weeks and left foot pain  PMH: ESRD, s/p related donor living renal transplant, T2DM, HTN, Polycystic Kidney disease, hx of Gout, hx of left upper lung pneumonia  SH: married, lives on farm in South Pittsburg, (-) tobacco, (-) EtOH, Owns and manages a demolition company, but has been a coal miner for approximately 12 years  Allergies: Demerol and Phenergan Patient Case
  • 3. History of ESRD 2o polycystic kidney disease, s/p living related donor renal transplant from his daughter in 2005 (Baseline Cr ~1.4-1.6).  Presents to ER with CC of N&V with onset of 2 days ago  Cough worsened over the last several weeks ever since d/c from hospital with left upper lung pneumonia on 1/15/10  Left foot pain that has progressively worsened over the last several days (Gout)  BUN/Cr note to be 68/2.1 on presentation and volume Patient Case (HPI)
  • 4. Prograf 1mg PO BID Lasix 40mg BID Zyloprim 300mg Qdaily CellCept 1gm PO BID Verapamil 120mg PO Starlix 120mg QD BID Prednisone 5mg PO BID Metoprolol 12.5mg PO Lantus 20 units QHS BID ASA 81mg BID Tessalon Perles prn Immunosuppressants Heart Medications Gout Diabetes Home Medications
  • 5. Hospital meds Cellcept 500mg IV Morphine 4-8mg Ambien 5mg QHS Q12 Q1/prn Cytovene 500mg Lopressor 12.5 BID Mycostatin 5mL IV BID QID Solumedrol 10mg Calan 120mg BID Carafate 1gm Q6 IV Q12 Zithromax 500mg Bumex 1mg IV Lantus 30units QDaily Q12 QHS Vancocin 0.75g IV Nitrol Ointment 1 NovoLog SSI level QDaily inch Q6h 4 Roxicet UDL Phenergan 6.25- Procrit 10,000units Q4/PRN 12.5mg Q6/prn on MWF @1600 Lortab 7.5mg Zofran 4mg Apresoline 10- Q4/prn Q4/PRN 20mg Q6 Immunosuppressants Pain Management Sleep Aid Antibiotics Heart Medication Anti-Fungal Pain Management Nausea Medication Diabetes
  • 6. Upon Admission  Admitted via ER with CC of nausea and vomiting for 2 days and a cough for weeks  CT scan shows left upper lobe mass of 6.5cm with lymph node involvement Patient Case (Hospital Course)
  • 7. Fig 1: There is an irregular large soft tissue mass in the left upper lung field which opposes the descending proximal thoracic aorta measuring some 5.5 x 6.5cm.
  • 8. Course of Action  IV Solu-Medrol  Hold Prograf ◦ Use of Rapamune?  Zosyn 2.25mg Q8- obstructive pneumonia  Bronchoscopy – left upper lobe mass
  • 9. Tacrolimus Sirolimus  Post-transplant  Impaired wound Diabetes (~20% first healing year)  ↑K  At high doses:  ↓ Mg ◦ Nephrotoxic  Hyperlipidemia ◦ Neurotoxicity  Hypertriglyceridemia  Renal adjustments  Leukopenia  QT prolongation Prograf vs Rapamune
  • 10. Results of Bronchoscopy  Generalized erythema, mucosal bleeding with no obstructing mass noted in the left upper lobe
  • 11. Patient is coughing up blood, productive with a green coloration Patient Case (Hospital Course)
  • 12. Course of Action  Add Vancomycin IV 1g Q24o to treatment (10.6mg/kg) and Zosyn 2.25mg Q8 (CrCl ~29.2) Vancomycin Dosing and Trough Levels Date Dose Date Trough level 2/9/10 1g 2/10/10 1g 2/12/10 17.6 2/20/10 30 2/21/10 27.6 2/24/10 27.3 2/25/10 0.75g 3/1/10 13.9 3/9/10 1g 3/9/10 23.6
  • 13.  Blood in cough resolves, but kidney function begins to decline. Patients develops a hemothorax.  Planned Video-Assisted Thoracoscopic Surgery (VATS) ◦ Retained hemothorax via trapped lung procedure  ID Consulted ◦ Differential: CMV or atypical mycobacterium ◦ Ordered urine antigens and serology for Q- fever ◦ d/c Zosyn Patient Case (Hospital Course)
  • 14. Atypical Pneumonias Legionnaires Q fever Psittacosis disease (Coxiella burnetii ) (Chlamydia psittaci ) (Legionella pneumophila) • Lung infection • During birthing the AKA: Parrot Disease or (pneumonia)  CAP or organisms are shed in Parrot Fever HAP lasts 2-14 days high numbers within the •Found in bird droppings amniotic fluids and the • Pontiac Fever placenta and aerolized symptoms usually last • Usually inhaled, for 2 to 5 days and may extremely virulent also include fever, • Resistant to heat, headaches, and muscle drying, and many aches; however, there is common disinfectants no pneumonia.
  • 15. Course of Action  Lab Evaluation ◦ Rare Gram(+) cocci to be identified… ◦ ?Malacoplakia or Rhodococcus Equi ◦ Vancomycin 1g Qdaily and Ancef 1g Q8o ◦ Immunosuppressants started back  Prednisone 20mg QD  Cellcept 250mg Q12  Prograf 1g Daily
  • 16. Inflammatory condition that leads to formation of papules, plaques and ulcerations (usually affecting the genitourinary tract)  Thought to result from the insufficient killing of bacteria by macrophages, that accumulate inside depositing iron and calcium forming the papules, etc.  Associated with patients who are immunosuppressed Malakoplakia
  • 18. Characterized by rod-to-coccus morphologic variation during its growth cycle  Rhodococcus genus due to its ability to form a red (salmon-colored) pigment - “red-pigmented coccus”  Primarily causing zoonotic infections in grazing animals (ex: horses and foals)  A soil organism that require simple requirements to survive, which seem to be met perfectly by herbivore manure and summer temperature in temperate climates Background R. Equi
  • 19.  R Equi is an obligate aerobic, intracellular, nonmotile, non-spore-forming, gram- positive coccobacillus  Commonly transmitted via inhalation on farms This latter histologic picture, termed malakoplakia, is extremely rare within the lung and, when present, is highly suggestive of a R. equi infection Background
  • 20. R. Equi is facultative intracellular pathogen, surviving inside macrophages to cause granulomatous inflammation and eventually destruction of macrophage.  In humans, has only be found in patients with compromised immune systems in the lungs Pathogenesis
  • 21. #1 Pneumonia (~66%)  Other possible presentations ◦ Penetrating eye wound ◦ Inflammatory mass in the pelvis ◦ Bloody diarrhea and cachexia ◦ Pleural effusion ◦ Osteomyelitis ◦ Paraspinal abscess ◦ Inflammatory pseudotumor Patient Presentation
  • 22. Typical Pathogens for CAP ◦ Streptococcus pneumoniae ◦ Moraxella catarrhalis ◦ Haemophilus influenzae Primarily CAP Culprits
  • 23. Physical Findings ◦ Rales heard upon Auscultation over the chest ◦ Pleural Effusion ◦ Purulent sputum ◦ Blood-tinged sputum ◦ Signs of consolidation  Typically seen with Legionella, Q fever, or psittacosis Pneumonia Presentation
  • 25. Left Upper Lobe Lung Mass – CT directed Core Biopsy ◦ Malakoplakia of the lung ◦ Gram (+) organisms present ◦ Cytomegalovirus Inclusions Present (in adjacent lung tissue) Comment: Pulmonary malakoplakia has been described in immunocompromised patients, including organ transplant patients. The most commonly isolated organism in this setting is Rhodococcus equi – initial cultures do show growth of a difficult to identify organism; the culture has been referred to a reference laboratory for typing. Surgical Pathology
  • 26. Hematoxylin-and-Eosin Stain Calcium Stain (Calcospherites) Pathology
  • 27. PAS + material Gram Stain Pathology
  • 28. Pathology CMV inclusion
  • 29. From the pathology as well as the culture coming back with rare gram (+) cocci (Rhodococcus species), Infectious Disease concluded the presence of R Equi Pathology
  • 30. Changed Therapy to… ◦ ∆ Vancomycin 1 g QDaily and Clindamycin ◦ Renal decides to hold Prograf due to declining renal function ◦ ∆ Clindamycin  Zithromax ◦ Added Levaquin for cover for new cultures of Klebsiella and Serratia found in the sputum Vancocin 1g QDaily/ Levaquin 750mg QDaily/ Zithromax 250mg QDaily Patient Case (Hospital Course)
  • 31. Must be covered by at least two or more agents  Combination antibiotics should include one agent with intracellular penetration (ex: Erythromycin or Rifampin)  Besides the use of anti-microbial drugs, the approach used in treatment of human infection involves drainage of the suppurative lesions, surgical resection of granulomatous tissue, and control of concurrent immunosuppressive drugs or control of underlying malignancies.  Duration of treatment 4-9 weeks Strategy to treat R Equi
  • 32. Erythromycin Macrolides  Azithromycin  Clarithromycin Lincosamides  Clindamycin Fluoroquinolones  Ciprofloxacin  Aminoglycosides  Rifampin Anti-tuberculosis Agent  Imipenem Carbapenems  Meropenem  Vancomycin  Linezolid Oxazolidinones Antibiotics used to treat R. Equi
  • 33.  Patient still in Respiratory failure  Patient suspected of CMV per Lung biopsy  Added Cytovene® (Ganciclovir) 200mg BID  Patient was scheduled for Tracheotomy Surgery Vancocin 1g QDaily/ Levaquin 750mg QDaily/ Zithromax 250mg QDaily/ Cytovene 200mg BID Patient Case (Hospital Course)
  • 34. Patient Case (Hospital Course)  After 14 days of treatment the Levaquin was d/c’d  Placed DHT bedside via CORTRAK
  • 35.  Still in Respiratory failure  Underwent the T-piece Trials on the vent  Placed catheter Vancocin 1g QDaily/ Zithromax 250mg QDaily/ Cytovene 200mg BID Patient Case (Hospital Course)
  • 36.  Patient feels better  Case Management refer him to Siskin and Kindred  Kindred accepts  Cytovene d/c, ID was never really clear if CMV was a pathogen Vancocin 1g Q48h/ Zithromax 250mg QDaily Patient Case (Hospital Course)
  • 37. Patient Case (Hospital Course)  Patient is transferred to Kindred Hospital on… Cellcept 500mg BID Augmentin 875mg Zyloprim 300mg Qdaily Qdaily Prograf 2mg Qdaily ASA 325mg Qdaily Flomax 0.4mg after supper Deltasone 5 mg BID Lopressor 25mg BID Mag-Ox 400mg BID Lantus 20 units QHS Calan SR 240mg Colace 100mg BID Qdaily Lasix 60mg Qdaily Immunosuppressants Antibiotics Gout Diabetes Heart Medications Prostate Medication
  • 38. Munoz P, Palomo J, Guinea J, et al. Relapsing Rhodococcus equi infection in a heart transplant recipient successfully treated with long-term linezolid. Diagn Microbiol Infect Dis. Feb 2008;60(2):197-9  Prescott, John. Rhodococcus Equi: an Animal and Human Pathogen. Clinical Microbiology Review. Jan 1991; 20-30  Verville TD, Huycke MM, Greenfield RA, et al. Rhodococcus equi infections of humans. 12 cases and a review of the literature. Medicine (Baltimore). May 1994;73(3):119-32 References