PJP Slides Final - sites.utexas.edu · ð W } o Ç u Z ] v Z ] } v ~W Z , ] P Z ~ õ ð r í ì ì 9 , ] P Z ~ ó õ r õ ò 9 W µ o u } v Ç & µ v ] } v

1

Pneumocystis jiroveci Pneumonia:

Prophylaxis in Immunocompromised States September 20th, 2019

Arsany Gadallah, PharmD, MBA PGY-1 Pharmacy Corporate Resident

Ascension Seton [email protected]

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Table of Contents Presentation Slides…………………………………………………..…Pages 3 to 10 Appendix A: Abbreviations…………………………………………….......Page 11 Appendix B: Fillatre, et al. Figure………………………………………...Page 12 Appendix C: Schmajuk, et al. Figures………………………………......Page 13

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Learning Objectives

• Describe the epidemiology and pathophysiology of

Pneumocystis jirovecii Pneumonia (PJP) • Review the clinical presentation and prophylaxis for the

disease

• Identify risk factors and susceptible patients for PJP • Explore clinical studies comparing the efficacy and safety

of PJP prophylaxis in HIV-negative and non-chemotherapy patients

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Should Pneumocystis jiroveci Pneumonia (PJP) prophylaxis be initiated?

a) YES

b) NO

5

Patient Case

• GA is a 34 year-old female who presents to the emergency

department with right ear pain/abscess. A moderate amount of fluid was drained surgically and the patient was discharged on ciprofloxacin 500 mg twice daily for 7 days with next-day ENT referral.

• After 3 days, GA starts to experience pain in her jaw (bilateral), right elbow, right neck, hips, knees and 2-3 hours of morning stiffness in left hand. Imaging showed nodules on left ear and nasal septum.

• GA was admitted to the hospital for suspected relapsing polychondritis, for which she was started on methylprednisolone 1 gram IV daily and oral methotrexate 15 mg weekly

3

Pneumocystis (carinii) jiroveci Pneumonia (PJP)

• Carlos Chagas first to discover cystic forms of Pneumocystis in 1909

• In 1910, Antonio Carini found similar cystic forms in the lungs of rats - named Pneumocystis carinii

• In the 1940s, Pneumocystis was linked to pneumonia in premature and malnourished infants

• In 1952, Otto Jirovec identified this organism as the causative agent of interstitial pneumonia in infected infants

• In 1980s, PJP became more prevalent with the widespread of human immunodeficiency virus (HIV)

Tasaka S, Tokuda H. J Infect Chemother. 2012;18(6):793-806.

6

Patient Case Cont’d

• Allergies: morphine, shrimp

• Vital Signs: BP: 99/67 HR: 101 RR: 16

• Ht: 62 in, Wt: 77 kg, eCrCl: 93 ml/min

• PMH: ear trauma secondary to motor vehicle accident, depression, recurrent left ear chondritis

136 95 11 131

4.1 33 0.8

Temp: 99.8

• ESR: 48 mm/h, CRP: 3.11 mg/dL, WBC: 17.3×103/mm3 (20% lymphocyte)

• HIV p24 antigen: negative, HIV-1 & 2 antibodies: negative

• Proteinase 3 (PR3) antibody: positive

• Plan: Cyclophosphamide 852 mg IV monthly, increased methotrexate dose to 25 mg weekly, switched to oral prednisone 60 mg daily

4

Pneumocystis jiroveci Pneumonia:

Prophylaxis in Immunocompromised States

Arsany Gadallah, PharmD, MBA PGY-1 Pharmacy Corporate Resident

Ascension Seton

September 20th, 2019

4

Polymerase Chain Reaction (PCR)

High (94-100%) High (79-96%)

Pulmonary Function Tests

High Low

Diagnosis: Laboratory Indices

Bronchoalveolar Lavage (BAL)

High (>95 %) High (99-100%)

Lactic Dehydrogenase (LDH)

Variable Low

1,3-β-D-glucan blood test (BDG)

High Low

Tasaka S, Tokuda H. J Infect Chemother. 2012;18(6):793-806. Salzer HJF. Respiration. 2018;96(1):52-56. 11

Lung Tissue Biopsy Highest Highest

Diagnostic Index Sensitivity Specificity

Sputum Sample Variable (55-90%) High (99-100%)

Epidemiology

• PJP was the most common opportunistic infection in the years 2008-2010

• CDC reports near 40% of PJP patients are HIV positive and 60% are immunocompromised due to other states

• Mortality rates reported in Non-HIV (nHIV) patients range between 30-50%, compared to 10-12% in HIV patients

• Up to 20% of adults could be carriers at any given point without any symptoms

• Eradication by healthy immune system could take several months

Centers for Disease Control and Prevention. https://www.cdc.gov/fungal/diseases/pneumocystis- pneumonia/index.html#9; Retrieved August 20th, 2019.

Tasaka S, Tokuda H. J Infect Chemother. 2012;18(6):793-806. 8

Pathophysiology

• The trophic form of Pneumocystis jiroveci attaches to the alveoli

and replicates freely under immune suppression

• Macrophages are unable to eradicate these organisms without CD4+ cells

• Inflammatory response leads to symptoms of: • Hypoxemia • Respiratory alkalosis • Impaired diffusing capacity • Changes in vital capacity • Respiratory failure


9

Diagnosis: Imaging

• Chest radiography (CXR)

• Diffuse bilateral infiltrates

• Chest high-resolution computed tomography scan (CT)

• Bilateral ground-glass opacities

Tasaka S, Tokuda H. J Infect Chemother. 2012;18(6):793-806. Salzer HJF. Respiration. 2018;96(1):52-56. 12

Clinical Presentation

• PJP in HIV patients presents gradually and progresses to

respiratory failure in 2 weeks - 2 months • Easier to diagnose in HIV patients due to larger fungal load in lungs

• PJP in nHIV* (immunocompromised) patients has an abrupt onset and progresses to respiratory failure in 1 week

• Respiratory insufficiency is more severe in nHIV patients • More severe inflammatory response in nHIV patients (more

bronchoalveolar neutrophils)

• Other symptoms include: • Fever and non-productive cough (HIV = nHIV) • Chest pain (HIV > nHIV) • Weight loss (HIV > nHIV)

*Includes transplant and chemotherapy patients

AIDSinfo Website. h ttps://aidsinfo.nih.gov/guidelines. Retrieved August 26th, 2019.

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Background

• Pneumocystis organisms are fungi that were initially classified as a

protozoa due to different forms • Lack of ergosterol and difficult to be cultured

• Three distinct morphological stages: trophic form (clusters), pre- cystic form (sporozoite) and cyst form (spores)

• Pneumocystis organisms are commonly found in healthy lungs with earliest exposures reported by age 4 years

• Pneumocystis organisms are communicable via airborne transmission

• Pneumonia occurs when both cellular and humoral immunity are defective


7

5

Treatment

• First-line: Trimethoprim-sulfamethoxazole

• Second-line: Atovaquone/Pentamidine/Dapsone

• Salvage: Clindamycin

• Adjunctive: Corticosteroids (for PaO2 <70) • Prednisone/prednisolone

AIDSinfo Website. https://aidsinfo.nih.gov/guidelines. Retrieved August 26th, 2019.

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Populations At Risk Cont’d

• According to the European Conference on Infections in

Leukemia (ECIL):

• Patients receiving glucocorticoid doses greater than 20 mg daily for

at least one month (Expert)

• Bone marrow suppression therapies or antineoplastic therapies (Expert)

• Patients undergoing hematopoietic cell/solid organ transplant (BIII)

Maertens J, et al. J Antimicrob Chemother; 2016;71:2397-2404

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Prophylaxis

• F irst-line: Trimethoprim-sulfamethoxazole (TMP-SMX)

• Double-strength (DS: 160 mg TMP-800 mg SMX) 1 tablet by mouth (PO) daily • Single Strength (SS: 80 mg TMP-400 mg SMX) 1 tablet PO daily

• S econd-line:

• TMP-SMX 1 DS tablet PO three times weekly

• Dapsone 100 mg PO daily or 50 mg PO twice daily

• Dapsone 50 mg PO daily + pyrimethamine 50 mg PO weekly + leucovorin 25 mg PO weekly

• Atovaquone 1500 mg PO daily +/- pyrimethamine 25 mg PO daily with

leucovorin 10 mg PO daily

• Pentamidine 300 mg in 6 mL sterile water nebulized every 4 weeks


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Other Populations?

• Connective Tissue Disorders

• Granulomatosis with polyangiitis (GPA) • Reported risk between 0.89% to 6%

• Dermatomyositis/polymyositis (PM/DM) • Reported increasing risk

• Disorders requiring immunosuppressive/corticosteroid therapy • Reported increasing risk due to emergence of biologics

• Rheumatoid arthritis (RA) • Reported low risk (0.02%)

• Inflammatory Bowl Diseases (IBD) • Few reports/low rates due to younger patients


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Populations At Risk • According to the National Institutes of Health (NIH), Centers for

Disease Control and Prevention (CDC), and the HIV Medicine Association of the Infectious Diseases Society of America (IDSA):

• HIV-infected patients with:

• CD4+ count below 200 cells/microL (AI) • Oral thrush (AII) • CD4+ less than 14% of total lymphocyte count (BII) • CD4+ of 200-250 cells/microL when antiretroviral treatment

(ART) cannot be started (BII) • Inability to monitor CD4+ count every 3 months (BII)


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Risk Factors

Immunocompromised

HIV nHIV

Colonization Cancer Solid organ transplant Hematopoietic stem cell

transplant


13

6

The Risks

Wolfe RM, Peacock Jr. JE. Curr Rheumatol Rep. 2017;19(6):35.

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Notable Side Effects/Cautions Est. Cost-per-month

Trimethoprim- sulfamethoxazole (oral)

GI discomfort, hypersensitivity reactions, elevated creatinine, hyperkalemia, Stevens-Johnson

Syndrome (SJS)

$13 - $19

Dapsone (oral)

G6PD testing, Anemia, hemolysis, methemoglobinemia

$80-$90

Atovaquone (oral) Nausea, diarrhea, rash, hepatitis $1,061

Pentamidine (aerosolized)

Cough, bronchospasm, wheezing, pneumothorax, fever, pancreatitis

$201

Fillatre et al.

Fillatre P, et al. Am J Med. 2014;127(12):1242.e11-7.

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Potential Benefit Groups

• A retrospective analysis by Fillatre et al. estimates incidence rates

within each disease state documented at their institution

• Study population • 293 cases of PJP documented from 1990 to 2010

• Positive bronchoalveolar lavage + PCR • Excluded HIV-positive patients


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Fillatre et al.

Authors’ Interpretation • Prophylaxis should be given in high-risk disease states

• Granulomatosis with polyangiitis (GPA) • Polymyositis (PM), dermatomyositis (DM), Polyarteritis nodosa (PAN)

• Prophylaxis should not be given in low-risk disease states • Inflammatory diseases

• Observed a 15.2% discontinuation rate due to TMP-SMX intolerance with a 3.1% rate of severe adverse events

• TMP-SMX prophylaxis should be started when PJP risk is above 3.5%

• Limitations • Single center study • Missing data for some risk populations • Findings based on incidence rates only


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Fillatre et al.

Incidence rate

Vasculitis

• Polyarteritis nodosa (1.9%) • Granulomatosis with Polyangiitis (1.5%) • Giant cell arteritis (0.2%)

% of total PJP cases (nHIV)

Vasculitis 9%

Inflammatory Diseases

• Polymyositis/dermatomyositis (1.1%) • Rheumatoid Arthritis (0.5%) • Polymyalgia rheumatica (0.2%)

Inflammatory Diseases

14%

Hematological Malignancies

30%

Others 11%

Others

• Glomerulonephritis* • Interstitial Lung Disease* • Cirrhosis*

Solid Organ Transplant

11% Solid Tumors

25%

*total number of patients not provided Fillatre P, et al. Am J Med. 2014;127(12):1242.e11-7.

22 19

Risk-Benefit Analysis

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Schmajuk et al.

• Primary Endpoint • Prescription for PJP prophylaxis after initiating immunosuppression

• Results • Out of the 316 patients, 124 (39%) of patients received qualifying

prophylactic antibiotics • TMP-SMX (73%), dapsone (16%), atovaquone (10%), pentamidine (1%)

Schmajuk G, et al. Semin Arthritis Rheum. 2019;48(6):1087-1092.

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Immunosuppressant % of Patients Receiving PJP Prophylaxis

Cyclophosphamide 77%

Rituximab 68%

Glucocorticoid 39%

Azathioprine 33%

Methotrexate 21%

Schmajuk et al.

• Authors’ interpretation:

• Incidence rate of PJP in the non-prophylaxis group was 3.7/375 patient-years (1% per year)

• Findings show efficacy of selective use of PJP prophylaxis in high-risk diagnoses and immunosuppressants

• Due to significant rate of adverse events (2.2% per year), PJP prophylaxis should be personalized

• Limitations: • Excluding antibiotic prescription ordered for less than 30 days (29

patients) • Single center without a standard diagnostic process


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Schmajuk et al.


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The Benefits: Rheumatoid Arthritis (RA)

• A retrospective cohort study conducted by Yukawa et al. shows

increasing incidence of PJP in rheumatoid arthritis patients based on certain risks

• 2,640 RA patients from 2010 to 2014, 19 patients developed PJP

• Diagnosis was based on respiratory samples (microscopic examination) OR positive PCR + positive 1,3-β-D-glucan (BDG)

• PJP patients were hospitalized over an average period of 5 days

• TMP/SMX was changed to pentamidine in 3 patients due to adverse events

• Thrombocytopenia, skin eruptions, hyponatremia, vomiting

• 15 patients tolerated treatment, 4 patients died due to pulmonary failure secondary to bacterial/viral infections

Yukawa K, et al. J Clin Rheum. 2018;24(7):355-360.

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Schmajuk et al.


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The Benefits: Rheumatic Diseases

• A retrospective study by Schmajuk et al. explored practice patterns of PJP

prophylaxis in rheumatic diseases at the University of California – San Francisco

• Study population composed of 316 patients followed for an average of 23.1 months:

• A diagnosis of granulomatosis with polyangiitis (GPA), Microscopic Polyagiitis (MPA), dermatomyositis (DM), polymositis (PM), or Systemic Lupus Erythematosus (SLE)

• At least 1 of the following immunosuppressants: azathioprine,

cyclophosphamide, methotrexate, mycophenolate mofetil, rituximab, and prednisone 20 mg daily or equivalent

• Excluded: age below 18 years, any diagnosis of HIV/AIDS, pregnancy, active

malignancy, and solid organ transplant.


25

8

Yukawa et al.

• Conclusion:

• Authors’ Interpretation: • PCP prophylaxis may not be necessary in RA patients unless risk score is at least

5 points

• Limitations • Single center study • Using odds ratios may not depict true severity of risk factors • Diagnosis was not standardized


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Metraiah et al.

• Authors’ Interpretation

• PJP could occur after the induction phase in AAV, especially during escalation of immunosuppressants

• Extended PJP prophylaxis might be valuable when augmented immunosuppression is given, especially in patients with lymphopenia (potential risk factor)

• Limitations • Single center study • 2 PJP patients missing information • Different immunosuppression regimen during maintenance

Metraiah EH, et al. Clin Rheumatol. 2018;37(7):1991-1996.

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The Benefits: Vasculitis

• A retrospective cohort by Metraiah et al. analyzes all institutional PJP

positive cases with anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (AAV) to determine onset of PJP infection

• Study population • 142 patients with positive PJP PCR from April of 2006 to July of 2016 • 16 PJP+ and AAV+ patients were identified and studied retrospectively • Immunosuppressants used with steroid therapy during induction and

maintenance phases: • Cyclophosphamide (first-line for induction), rituximab, mycophenolate

mofetil, azathioprine (first-line for maintenance), methotrexate


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The Benefits: Inflammatory Bowel Disease (IBD) • A retrospective cohort study by Long et al. compares in the incidence of PJP

in IBD patients compared to non-IBD patients. • S tudy population

• IBD patients of 64 years of age and younger • 50,932 patients with Crohn’s Disease (CD); 56,403 with Ulcerative Colitis

(UC); 1,269 with unspecified IBD; compared to 434,416 with non-IBD

• All patients were required to have at least 12 months of continuous health plan and pharmacy coverage (to capture medication history)

• At least 1 pharmacy claim for:

• Mesalamine, olsalazine, balsalazide, sulfasalazine, 6-mercaptopurine, azathiopurine, methotrexate, infliximab, adalimumab, certolizumab pegol, natalizumab, and enteral budesonide

• All individuals with any ICD-9 code for HIV were excluded

Long MD, et al. Inflamm Bowel Dis. 2013;19(5):1-13.

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Metraiah et al.

• Primary outcome

• Onset of PJP from the time of diagnosis of AAV in patients

• Results • Majority (75%) of AAV patients were positive for GPA • 14 out of the 16 PJP+ patients had received co-trimoxazole prophylaxis

during induction phase (first 3-6 months) – not reintroduced during escalation of immunosuppression

• 2 patients were intolerant to treatment and proceeded with clindamycin + primaquine combination

• 2 patients died accounting for mortality rate of 12.5% in PJP+ group • The median time from AAV diagnosis to PJP was 8 months • Lymphopenia was present in all AAV cases


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Yukawa et al.

• Primary outcome:

• Incidence rate of PJP in rheumatoid arthritis based on risk factors present

• Results: • Scoring system based on odds ratios (OR)

• Methotrexate ≥ 6 mg/wk, OR = 4.5 (1 point) • Age ≥ 65 years, OR = 3.7 (1 point) • ≥ 2 immunosuppressants, OR = 3.7 (1 point)

• Methotrexate, azathioprine, leflunomide, cyclosporine, tacrolimus

• Infliximab, etanercept, golimumab, certolizumab, tocilizumab, abatacept

• Prednisolone ≥ 5 mg/day, OR = 12.4 (3 points)


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9

Summary of Literature

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Study Risk Population (nHIV) PJP Prophylaxis Recommended?

Fillatre et al. Inflammatory diseases, vasculitis

Only in vasculitis (GPA,PAN) & PM/DM

Schmajuk et al.

GPA, PM, DM, SLE

No

Yukawa et al.

RA Only for scores 5 and

above

Metraiah et al.

AAV Yes (induction and maintenance)

Long et al.

IBD

Depends on other factors

Long et al.

• Authors’ Interpretation

• IBD increases risk of developing PJP • Despite increased relative risk of PJP in IBD, the absolute risk remains low

• NNT estimated to be between 2070 to 2952 for immunosuppressant use alone

• Other risk factors must be considered before initiating prophylaxis

• Limitations • Patients older than 65 and uninsured patients were not represented in this

study

• Study does not take into account the number of immunosuppressants


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Conclusion

• Immunosuppression is key in developing PJP

• Initiating PJP prophylaxis should be based on all risk factors present in the patient

• More studies are needed to evaluate the severity of each risk factor

• In some disease states, such as rheumatoid arthritis and systemic lupus erythematosus, risks may outweigh the benefit of PJP prevention

• In high-risk disease states, such as vasculitis, prophylaxis may be necessary

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Future Direction

• Lack of randomized controlled trials is impeding implementation

of new recommendations into practice guidelines

• Comparing safety and efficacy of different prophylaxis regimens in the nHIV population

• PJP risk does not take into account other important factors, such as patient-level differences in drug metabolism

• Pharmacy involvement to help individualize PJP prophylaxis based on patient-specific attributes

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• GA is a 34 year-old female admitted for relapsing polychondritis with lymphocytopenia

• GA has a complex

autoimmune disorder (PR3+)

• GA is on cyclophosphamide,

prednisone and methotrexate

• Multiple readmissions for

abscess and ear pain

40

Back to GA

• Do you recommend starting PJP prophylaxis?

• YES • NO

Long et al.

• Primary outcome

• Incidence of PJP in IBD patients without HIV

• Results • Annual incidence of PJP of 10.6/100,000 patient years in IBD compared to

3.0/100,000 patient years in non-IBD (IRR = 3.48, 95% CI 2.10-5.81)

• In IBD cohort, annual incidence of PJP was higher in patients taking immunosuppressants than in those who were not (32/100,000 vs. 5.5/100,000 patient years)

• Risk for CD compared to non-IBD (IRR = 4.49, 95% CI 2.14-9.75) was greater

than risk for UC compared to non-IBD (IRR = 2.40, 95% CI 1.11-5.10)

• Incidence of PJP increased with age, with highest at 60+ years (32.8/100,000 patient years)


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10

Questions?

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References 1. Tasaka S, Tokuda H. Pneumocystis jirovecii pneumonia in non-HIV-infected patients in the era of novel

immunosuppressive therapies. J Infect Chemother. 2012 Dec;18(6):793-806. doi:10.1007/s10156-012-0453-0.

2. Centers for Disease Control and Prevention Website. h ttps://www.cdc.gov/fungal/diseases/pneumocystis- p neumonia/index.html#9; Retrieved August 20th, 2019.

3. AIDSinfo Website. h ttps://aidsinfo.nih.gov/guidelines. Retrieved August 26th, 2019.

4. Salzer HJF, Schäfer G, Hoenigl M, et al. Clinical, diagnostic, and treatment disparities between HIV-Infected and Non-HIV-Infected immunocompromised patients with Pneumocystis jirovecii pneumonia. Respiration. 2018;96(1):52-65. doi: 10.1159/000487713.

5. Maertens J, Cesaro S, Maschmeyer G,et al. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother. 2016;71(9):2397-2404. doi:10.1093/jac/dkw157.

6. Fillatre P, Decaux O, Jouneau S, et al. Incidence of Pneumocystis jiroveci pneumonia among groups at risk in HIV- negative patients. Am J Med. 2014;127(12):1242.e11-7. doi:10.1016/j.amjmed.2014.07.010.

7. Wolfe RM, Peacock JE Jr. Pneumocystis pneumonia and the rheumatologist: which patients are at risk and how can PCP be prevented? Curr Rheumatol Rep. 2017;19(6):35. doi:10.1007/s11926-017-0664-6.

8. Schmajuk G, Jafri K, Evans M, et al. Pneumocystis jirovecii pneumonia (PJP) prophylaxis patterns among patients with rheumatic diseases receiving high-risk immunosuppressant drugs. Semin Arthritis Rheum. 2019;48(6):1087- 1092. doi:10.1016/j.semarthrit.2018.10.018.

9. Yukawa K, Nagamoto Y, Watanabe H, et al. Risk factors for Pneumocystis jirovecii pneumonia in patients with rheumatoid arthritis and a prophylactic indication of trimethoprim/sulfamethoxazole. J Clin Rheumatol. 2018;24(7):355-360. doi:10.1097/RHU.0000000000000731

10. Metraiah EH, Olisaka N, Philipos M, et al. Late-onset Pneumocystis jirovecii pneumonia (PJP) in patients with ANCA-associated vasculitis. J Clin Rheumatol. 2018;37(7):1991-1996. doi:10.1007/s10067-018-4155-6

11. Long MD, Farraye FA, Okafor PN, Martin C, Sandler RS, Kappelman MD. Increased risk of Pneumocystis jiroveci pneumonia among patients with inflammatory bowel disease. Inflamm Bowel Dis. 2013;19(5):1018-24. doi:10.1097/MIB.0b013e3182802a9b.

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Acknowledgements Emily Ong, PharmD, BCACP Joyce Mateo, PharmD Patrick J. Davis, PhD Dusten T. Rose, PharmD, BCIDP, AAHIVP

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Appendix A Abbreviations AAV- Anti-neutrophil cytoplasmic

antibody Associated Vasculitis ART- Antiretroviral Treatment BAL- Bronchoalveolar Lavage BDG- 1,3-β-D-Glucan blood test BP- Blood Pressure CD- Crohn’s Disease CDC- Centers for Disease Control

and Prevention CI- Confidence Interval CRP- C-reactive Protein CT- Computed Tomography CXR- Chest X-ray DM- Dermatomyositis DS- Double Strength eCrCl- Estimated Creatinine

Clearance ENT- Ears, Nose, and Throat ESR- Erythrocyte Sedimentation Rate G6PD- Glucose-6-Phosphate

Dehydrogenase GPA- Granulomatosis with

Polyangiitis HIV- Human Immunodeficiency Virus HR- Heart Rate Ht- Height IBD- Inflammatory Bowl Diseases ICD- International Classification of

Diseases IRR- Incidence Rate Ratio IV- Intravenous LDH- Lactic Dehydrogenase nHIV- Non- HIV population

NNT- Number Needed to Treat PAN- Polyarteritis Nodosa PCR- Polymerase Chain Reaction PJP- Pneumocystis jiroveci

Pneumonia PM- Polymyositis PMH- Past Medical History PO- Oral PR3- Proteinase RA- Rheumatoid Arthritis RR- Respiratory Rate SLE- Systemic Lupus Erythematosus SS- Single Strength TMP-SMX- Trimethoprim-

sulfamethoxazole UC- Ulcerative Colitis WBC- White Blood Cell Wt- Weight

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Appendix B

Figure 1. Fillatre et al.: Incidence of PJP across study disease states

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Appendix C

Figure 2. Schmajuk et al.: Rate of patients receiving PJP prophylaxis in each disease state

Figure 3. Schmajuk et al.: Rate of adverse events associated with PJP Prophylaxis

Documents

PJP Slides Final - sites.utexas.edu · ð W } o Ç u Z ] v Z ] } v ~W Z , ] P Z ~ õ ð r í ì ì 9 , ] P Z ~ ó õ r õ ò 9 W µ o u } v Ç & µ v ] } v