Immunosuppressants

Should I treat my patient with community-acquired pneumonia (CAP) with adjunctive corticosteroids?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , Leave a comment

It depends! You should consider ACs in immunocompetent patients with severe bacterial CAP in the absence of concurrent influenza, particularly in patients with a very high inflammatory response (eg, serum C-reactive protein [CRP] >150-200 mg/L). 1-13 In contrast, ACs is NOT recommended for patients with non-severe CAP.

Depending on the study, ACs in severe CAP has been associated with improvement in various patient outcomes, including reduced mortality, need for vasopressor or invasive mechanical ventilation, decrease in ICU stay and decrease in hospital length of stay.1-13 Significantly higher risk of hyperglycemia has been reported in the ACs group without demonstrable increase in the risk of upper GI bleed or hospital-acquired infections.2  

Which definition of severe CAP should we use when considering ACs? Unfortunately, it varies but a commonly cited definition is that proposed by the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA).9  When determining which patients may benefit from ACs, I favor a broader definition of severe CAP through modification of the ATS/IDSA criteria to include several other criteria used in major trials such as the seminal Community-Acquired Pneumonia Evaluation Corticosteroids (CAPE COD) study criteria and the Pneumonia Severity Index. 1-4   According to this “modified ATS/IDSA criteria”, severe CAP is likely in the presence of either one major criterion OR ≥3 minor criteria as detailed below.

Major criteria (1 needed):1. Septic shock with need for vasopressor; 2. Respiratory failure requiring invasive, non-invasive mechanical ventilation or high-flow nasal cannula; OR 3. Pneumonia severity index class IV or V.  Note: high-flow nasal cannula and PSI IV or V have been added to ATS/IDSA criteria

Minor criteria (3 needed):1. Respiratory rate ≥30/min; 2. Pa02/Fi02 ratio ≤250; 3. Multilobar infiltrates; 4. Confusion/disorientation; 5. BUN≥20 mg/dL; 6. Leukopenia (WBC<4,000/uL); 7. Thrombocytopenia (platelet count < 100,000/uL; 8. Hypothermia (core temp <96.8 ⁰ F, 36 ⁰ C); 9. Hypotension requiring aggressive fluid resuscitation.

In addition, a high inflammatory response based on CRP greater than 150-200 mg/L significantly increases the odds of a favorable outcome (eg, reduced mortality) in CAP when ACs is used.2,3,8 In fact, in a meta-analysis involving data-driven analysis of randomized trials, a significant reduction in mortality with ACs was observed only in those with CRP>204 mg/dL (6.1% vs 13%).8  In a subgroup analysis of CAPE COD study, mortality was significantly reduced only in patients with CRP>150 mg/L (risk difference -7.3 %).2  A 2015 study involving only patients with CRP>150 mg/L and meeting ATS/IDSA criteria for severe CAP or PSI class V, treatment failure (composite deterioration/invasive mechanical ventilation and death within 72 h) was significantly lower in the ACs group (13% vs 31%).3   

Collectively, in the absence of any contraindication to corticosteroids or concurrent influenza, the weight of the evidence supports ACs in select patients with severe CAP, particularly when associated with CRP>150 mg/L.  In contrast, for patients with non-severe CAP and presumed lower level of inflammation, the benefit of ACs may not outweigh its risks and is not recommended, unless there are other indications for their use (eg, COPD exacerbation).  For all other patients, including those without severe CAP but with high CRP levels as above or severe CAP with lower CRP levels, ACs should be considered on a case-by-case basis.

When indicated for severe CAP, based on the inclusion criteria used by various clinical trials, ACs should be started as soon as severe CAP is diagnosed, preferably within 24 h.2,13 As for the choice of ACs regimen, no study has proven the superiority of one particular regime vs others.1  The CAPE COD study used IV hydrocortisone 200 mg/day continuous infusion for 4-8 days with taper over total of 8-14 days.2 Some have suggested methylprednisolone 0.5 mg/kg IV q 12 h or “typical doses” of 40-80 mg/day IV methylprednisolone equivalent for 5-7 days.1,3 Yet others have suggested that hydrocortisone 100 mg IV or methylprednisolone 40 mg IV be given in the emergency department as an initial dose when severe CAP is diagnosed. 11 If IV hydrocortisone is selected, a pragmatic approach using 50 mg every 6 hours, similar to that suggested in the management of septic shock by the 2026 Guidelines by the Surviving Sepsis Campaign14 may also be reasonable.

 

Bonus Pearls:

  1. Did you know that despite ready availability of antibiotics, mortality from CAP in hospitalized patients remains high with nearly 50,000 people dying each year in the U.S. alone? top-pneumonia-facts.pdf
  2. Did you know that in addition to their immune modulating action, experimental studies have shown that corticosteroids may decrease global bacterial burden in lung tissue and lead to less extensive pneumonia in piglets15 and significant reduction in intracellular bacterial survival in human monocytes?16 Who would have guessed?  

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

References

  1. Chaudhuri D, Nei AM, Rochwerg B, et al. 2024 Focused update: Guidelines on use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia. Crit Care Med 2024;52:e129-33. 2024 Focused Update: Guidelines on Use of… : Critical Care Medicine 
  2. Dequin P.-F, Meziani J.-P, Quenot T, et al. Hydrocortisone in severe community-acquire pneumonia. N Engl J Med 2023; 388: 1931-41. Hydrocortisone in Severe Community-Acquired Pneumonia | New England Journal of Medicine 
  3. Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015;313:677-86 .Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial – PubMed
  4. Metlay JP, Waterer GW. Time to treat severe community-acquired pneumonia with steroids? N Engl J Med 2023; 388:2001-2. Time to Treat Severe Community-Acquired Pneumonia with Steroids? | New England Journal of Medicine
  5. Pitre Ty, Pauley E, Chaudhuri D, et al. Corticosteroids for adult patients hospitalized with non-viral community-acquired pneumonia: a systematic review and meta-analysis. Intensive Care Medicine 2025; 51:917-29. Corticosteroids for adult patients hospitalised with non-viral community-acquired pneumonia: a systematic review and meta-analysis | Intensive Care Medicine | Springer Nature Link
  6. Soumare A, Kapfer T, Botrel T, et al. Systemic corticosteroids, mortality, and infections in pneumonia and acute respiratory distress syndrome. Ann Intern Med 2026; 179L67-80. Systemic Corticosteroids, Mortality, and Infections in Pneumonia and Acute Respiratory Distress Syndrome : A Systematic Review and Meta-analysis – PubMed
  7. Keisham B, Duhan S, Bajaj D, et al. Steroid therapy in community-acquired pneumonia: an updated systematic review and meta-analysis. Heart & Lung 2026;79:102839. Steroid Therapy in Community-Acquired Pneumonia: An Updated Systematic Review and Meta-Analysis – PubMed
  8. Smit JM, Van Der Zee PA, Stoff SCM, et al. Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomized trials. Lancet Resp Med 2025;13:221-33. Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomised trials – The Lancet Respiratory Medicine. 
  9. Jones BE, Ramirez JA, Oren E, et al. Diagnosis and management of community-acquired pneumonia. Am J Resp Crit Care 2026;212:24. Jones BE, Ramirez JA, Oren E, et al. Diagnosis and management of community-acquired pneumonia. Am J Resp Crit Care 2026;212:24. – Search
  10. Reyes LF, Morris AC, Serrano-Mayorga C, et al. Community-acquired pneumonia. Lancet 2025;406:2371-88. Community-acquired pneumonia – The Lancet
  11. Long B, Gottlieb M. 2025 guideline updates for community-acquired pneumonia diagnosis and management. Am J Emerg Med 2026;107:16-20. 2025 guideline updates for community-acquired pneumonia diagnosis and management – EM consulte
  12. Confalonleri M, Urbino R, Potena A, et al. Hydrocortisone infusion for severe community-acquired pneumonia: A preliminary randomized study. Am J Respir Crit Care Med 2005;171:242-8. Hydrocortisone Infusion for Severe Community-acquired Pneumonia | American Journal of Respiratory and Critical Care Medicine | Oxford Academic
  13. Pirracchio R, Venkatesh B, Legrand M. Low-dose corticosteroids for critically ill adults with severe pulmonary infections: A review. JAMA 2024;332:318-328.jama_pirracchio_2024_rv_240011_1721328820.09305 give steroids.pdf
  14. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock 2026. Crit Care Med 2026;54:725-812. Surviving Sepsis Campaign: International… : Critical Care Medicine
  15. Sibila O, Luna CM, Agusti C, et al. Effects of glucocorticoids in ventilated piglets with severe pneumonia. Eur Respir J 2008;32:1037-46. Effects of glucocorticoids in ventilated piglets with severe pneumonia | European Respiratory Society
  16. Meduri GU, Kananagat S, Bronze M, et al. Effects of methylprednisolone on intracellular bacterial growth. Clin Diag Lab Immunol 2001;8:1156-63.Effects of Methylprednisolone on Intracellular Bacterial Growth – PMC

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should I treat my patient with community-acquired pneumonia (CAP) with adjunctive corticosteroids?

My patient with COPD on prednisone with recurrent pneumonia has a low serum IgG level.  Can corticosteroids lower serum immunoglobulin levels?

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Yes! Both exogenous and endogenous hypercortisolism may be associated with a drop in serum immunoglobulin levels, particularly IgG, which may persist even after discontinuation of steroid treatment.1-4 This means that a low serum IgG level in a patient on corticosteroids should be interpreted with caution and may not necessarily suggest primary antibody deficiency.

Although some early studies did not find a significant impact of corticosteroids on immunoglobulin levels, several subsequent studies found otherwise.  A 1978 study involving atopic asthmatic patients (averaging 16.8 mg prednisone daily) found that mean serum IgG significantly decreased (-22%) with milder drop in IgA levels (-10%) and no drop in serum IgM levels.2 Of interest, IgE level increased significantly initially but later dropped as well. More importantly, mean serum IgG levels remained significantly decreased an average of 22 days after corticosteroids were discontinued.

More recently, in a study involving patients with giant cell arteritis and polymyalgia rheumatica on corticosteroids, 58% developed antibody deficiency with the great majority involving IgG, either alone or along with other immunoglobulins.3 The reduction of IgG persisted even after discontinuation of corticosteroids in nearly 50% of patients, and observed in nearly one-quarter of patients for at least 6 months! Whether low serum immunoglobulins due to corticosteroids alone significantly increase susceptibility to infections is unclear, however.

In our patient with COPD on prednisone, if serum IgG level is found to be low and a primary antibody deficiency is still suspected, a functional assessment of the antibody production after active immunization (eg, polysaccharide pneumococcal vaccine, tetanus toxoid) may be necessary. 1 An adequate antibody response to active immunization makes primary immunodeficiency unlikely. 

 

Bonus Pearl: Did you know that corticosteroid-induced hypogammaglobulinemia may be in part related to reduced IgG production as well as an increase in IgG catabolism?1,4

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

References

  1. Sarcevic J, Cavelti-Weder C, Berger CT, et al. Case report-secondary antibody deficiency due to endogenous hypercortisolism. Frontiers in Immunology 2020;11:1435. https://www.frontiersin.org/articles/10.3389/fimmu.2020.01435/full
  2. Settipane GA, Pudupakkam RK, McGowan JH. Corticosteroid effect on immunoglobulins. J Allergy Clin Immunol 1978;62: 162-6. https://www.jacionline.org/article/0091-6749(78)90101-X/pdf
  3. Wirsum C, Glaser C, Gutenberger S, et al. Secondary antibody deficiency in glucocorticoid therapy clearly differs from primary antibody deficiency. J Clin Immunol 2016;36:406-12. https://link.springer.com/article/10.1007/s10875-016-0264-7
  4. McMillan R, Longmire R, Yelenosky R. The effect of corticosteroids on human IgG synthesis. J Immunol 1976;116:1592-1595. https://www.jimmunol.org/content/116/6/1592

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My patient with COPD on prednisone with recurrent pneumonia has a low serum IgG level.  Can corticosteroids lower serum immunoglobulin levels?

My middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Yes! According to the Centers for Disease Control and Prevention (CDC) of the U.S.,1 persons who are “moderately or severely immunocompromised” and have received 3 doses of an mRNA vaccine (either Pfizer [12+ years old) or Moderna (18+ years old]) should receive a 4th dose (“booster”) at least 3 months after the 3rd dose.  Similarly, those who initially received a J&J vaccine followed by one of the aforementioned mRNA vaccines and are at least 2 months from the 2nd dose should also receive a 3rd dose (booster. 

The following are considered moderately or severely immunocompromised conditions by CDC: 

  • Active cancer treatment for tumors or cancers of the blood
  • Organ transplant with immunosuppressants on board
  • Stem cell transplant within the last 2 years or taking immunosuppressants
  • Moderate or severe primary immunodeficiency (eg, DiGeorge or Wiskott-Aldrich syndromes)
  • Advanced or untreated HIV infection
  • Active treatment with high-dose corticosteroids or other immunosuppressants

A published study2 of Covid-19-associated emergency department (ED) and urgent care (UC) encounters and hospitalization among adults during a period including Omicron variant predominance in 10 states found vaccine effectiveness for ED/UC visits dropping to 66% and for hospitalization to 78% by the 4th month after a 3rd dose (vs 87% and 91%, respectively during the 2 months after a 3rd dose).  This study did not distinguish immunocompromised from non-immunocompromised persons, however.  More data on the vaccine effectiveness in non-immunocompromised persons at high risk of Covid-19 related complications would be welcome.

Bonus Pearl: Did you know that of American adults who are fully vaccinated against Covid-19, only about 30% have received an additional Covid vaccine dose beyond the primary series ? 3 

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Covid-19 vaccines for moderately or severely immunocompromised people (Updated Feb 17, 2022). Accessed Feb 21, 2022.  https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html?s_cid=10483:immunocompromised%20and%20covid%20vaccine:sem.ga:p:RG:GM:gen:PTN:FY21
  2. Waning 2-doe and 3-dose effectiveness of mRNA vaccines against Covid-10-associated emergency department and urgent care encounters and hospitalizations among adults during periods of delta and omicron variant predominance—Vision Network, 10 states, August 2021-January 2022. MMWR 2022; 71:255-63. https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm?s_cid=mm7107e2_w
  3. Hubler S, Harman A. As Cov id surges, experts say U.S. booster effort is falling behind. NY Times, December 18, 2021. https://www.nytimes.com/2021/12/18/us/omicron-booster-shots-americans.html

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?

My patient with rheumatoid arthritis might have been exposed to tuberculosis. Does immunosuppressive therapy affect the results of interferon gamma release assay (IGRA) testing for latent tuberculosis?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , Leave a comment

The weight of the evidence to date suggests that immunosuppressive therapy, including steroids, other oral immunosuppressants and anti-tumor-necrosis factor (TNF) agents, may negatively impact IGRA results.1

In some ways the finding of false-negative IGRA in the setting of immunosuppression is intuitive since many immunosuppressive agents are potent inhibitors of T cells and interferon-gamma response. 1,2 Despite this, the initial reports have been somewhat conflicting which makes a 2016 meta-analysis of the effect of immunosuppressive therapy on IGRA results in patient with autoimmune diseases (eg, rheumatoid arthritis, lupus, inflammatory bowel disease) particularly timely. 1

This meta-analysis found a significantly lower positive IGRA results among patients on immunosuppressive therapy ( O.R. 0.66, 95% C.I. 0.53-0.83). Breakdown by IGRA test showed a significant association between QuantiFERON-TB Gold In-Tube and lower positive results and a trend toward the same with T-SPOT though the latter did not reach statistical significance with fewer evaluable studies (O.R. 0.81, 95% C.I 0.6-1.1).   Breakdown by type of immunosuppressant showed significantly negative impact of corticossteroids, other oral immunosuppressants, and anti-TNF agents for all. Some studies have reported daily steroid doses as low as 7.5 mg-10 mg may adversely impact T-cell responsiveness in IGRA. 3,4

So, whenever possible, testing for latent TB should be performed before immunosuppressants are initiated.

Bonus Pearl: Did you know that an estimated one-third of the world’s population may have latent TB?

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

References

  1. Wong SH, Gao Q, Tsoi KKF, et al. Effect of immunosuppressive therapy on interferon gamma release assay for latent tuberculosis screening in patients with autoimmune diseases: a systematic review and meta-analysis. Thorax 2016;71:64-72. https://thorax.bmj.com/content/thoraxjnl/71/1/64.full.pdf
  2. Sester U, Wilkens H, van Bentum K, et al. Impaired detection of Mycobacterium tuberculosis immunity in patents using high levels of immunosuppressive drugs. Eur Respir J 2009;34:702-10. https://erj.ersjournals.com/content/34/3/702
  3. Kleinert S, Kurzai O, Elias J, et al. Comparison of two interferon-gamma release assays and tuberculin skin test for detecting latent tuberculosis in patients with immune-mediated inflammatory diseases. Ann Rheum Dis 2010;69:782-4. https://ard.bmj.com/content/69/4/782
  4. Ponce de Leon D, Acevedo-Vasquez E, Alvizuri S, et al. Comparison of an interferon-gamma assay with tuberculin skin testing for detection of tuberculosis (TB) infection in patients with rheumatoid arthritis in a TB-endemic population. J Rheumatol 2008;35:776-81. https://www.ncbi.nlm.nih.gov/pubmed/18398944
My patient with rheumatoid arthritis might have been exposed to tuberculosis. Does immunosuppressive therapy affect the results of interferon gamma release assay (IGRA) testing for latent tuberculosis?

When should I suspect invasive pulmonary aspergillosis in my patient with COPD exacerbation?

FA Manian MD, MPH, , , , , Leave a comment

Think of invasive pulmonary aspergillosis (IPA) in your patient when she or he has a COPD exacerbation that appears refractory to broad-spectrum antibiotics and high doses of steroids. Heighten your suspicion even more in patients with severe-steroid dependent COPD, presence of a new pulmonary infiltrate or isolation of Aspergillus spp from respiratory cultures. 1

It’s worth remembering that although dyspnea and bronchospasm are found in most COPD patients with IPA, in contrast to haematological patients, fever, chest pain and hemoptysis are usually absent in this patient population.1

Diagnosis of IPA in this patient population is challenging for several reasons including: 1. A definitive or “proven” diagnosis requires histopathologic evidence of Aspergillus invasion of lung tissue which is not possible without subjecting an already fragile patient to invasive procedures (eg, lung aspiration or biopsy); 2. In contrast to IPA in highly susceptible immunocompromised patients with cancer and recipients of hematopoietic stem cell transplants, standardized definition of IPA in patients with COPD is lacking; 1,3 and 3. Frequent colonization of the respiratory tract of COPD patients with Aspergillus spp (16.3 per 1000 COPD admission in 1 study) 4,5, makes it difficult to diagnose IPA based on cultures alone.

Aside from respiratory cultures, another non-invasive test, serum galactomannan (GM, a polysaccharide antigen that exists primarily in the cell walls of Aspergillus spp and released into the blood during its growth phase 6) may have some utility in suggesting IPA in COPD patients, albeit with a mediocre sensitivity (~30-60%) but respectable specificity (>80 %). In contrast, bronchoalveolar lavage fluid GM may have better sensitivity  (~75%-90%) with similar specificity as that of serum GM in the diagnosis of IPA in these patients 7-8

Bonus pearl: Did you know that the incidence of IPA appears to be increasing in COPD patients requiring ICU admission, with reported mortality rates of 67% to 100%? 7

If you liked this post, download P4P app and sign up under MENU to catch future pearls right into your inbox, all for free!

 

References

  1. Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Res J 2007;30:782-800. https://www.ncbi.nlm.nih.gov/pubmed/17906086
  2. Bulpa P, Bihin B, Dimopoulos G, et al. Which algorithm diagnoses invasive pulmonary aspergillosis best in ICU patietns with COPD? Eur Resir J 2017;50:1700532 https://www.ncbi.nlm.nih.gov/pubmed/28954783
  3. Barberan J, Garcia-Perez FJ, Villena V, et al. Development of aspergillosis in a cohort of non-neutropenic, non-transplant patients colonized by Aspergillus spp. BMC Infect Dis 2017;17:34. https://link.springer.com/article/10.1186/s12879-016-2143-5
  4. Guinea J, Torres-Narbona M, Gijon P, et al. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect 2010; 16:870-77. https://www.sciencedirect.com/science/article/pii/S1198743X14617432
  5. Blot Stijn I, Taccone FS, Van den Abeele A-M, et al. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med 202;186:56-64. https://www.atsjournals.org/doi/full/10.1164/rccm.201111-1978OC
  6. Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006;42:1417-27. https://academic.oup.com/cid/article/42/10/1417/278148
  7. He H, Ding L, Sun B, et al. Role of galactomannan determinations in bronchoalveolar lavage fluid samples from critically ill patients with chronic obstructive pulmonary disease for the diagnosis of invasive pulmonary aspergillosis: a prospective study. Critical Care 2012;16:R138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066034/
  8. Zhou W, Li H, Zhang Y, et al. Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid samples from patients with nonneutropenic invasive pulmonary aspergillosis. J Clin Microbiol 2017;55:2153-61. https://www.ncbi.nlm.nih.gov/pubmed/28446576
When should I suspect invasive pulmonary aspergillosis in my patient with COPD exacerbation?

When should I consider prophylaxis for Pneumocystis pneumonia (PCP) in my patient on prednisone?

FA Manian MD, MPH, , , , , Leave a comment

It is generally recommended that patients on ≥20 mg of daily prednisone (or its equivalent) for ≥1 month be considered for PCP prophylaxis. 1

Couple of studies in 1990s helped define the dose and duration of corticosteroids (CS) that should prompt PCP prophylaxis. A Mayo Clinic study of patients without AIDS found that a median daily CS dose of 30 mg of prednisone or equivalent—with 25% of patients receiving as little as 16 mg of prednisone daily— was associated with PCP.2  The median duration of CS therapy before PCP was 12 weeks. A similar study found a mean CS dose of 33 mg of prednisone or equivalent with mean duration of 7 months (range 1-154 months) among patients with PCP without AIDS. 3

A 2018 retrospective study4  of patients with rheumatic diseases receiving prolonged high-dose CS therapy (≥30 mg prednisone for ≥4 weeks) found that PCP prophylaxis with trimethoprim/sulfamethoxazole (TMP/STX) resulted in 93% reduction in the incidence of PCP with an overall number needed to treat (NNT) of 52. It was suggested that PCP prophylaxis could be discontinued in patients receiving < 15 mg of prednisone daily.

Bonus Pearl: Did you know that TMP/STX may be given either as double-strength 3x/week or single-strength daily? 5,6

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

1. Limper AH, Knox KS, Sarosi SA, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med 2011;183:96-128. https://www.ncbi.nlm.nih.gov/pubmed/21193785

2. Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc 1996;71:5-13. https://www.sciencedirect.com/science/article/abs/pii/S0025619611649148

3. Arend SM, Kroon FP, van’t Wout JW. Pneumocystis carinii pneumonia in patients without AIDS, 1980 through 1993: An analysis of 78 cases. Arch Intern Med 1995;155:2436-2441. https://www.ncbi.nlm.nih.gov/pubmed/7503602

4. Park JW, Curtis JR, Moon J, et al. Prophylactic effect of trimethoprim-sulfamethoxazole for Pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoieds. Ann Rheum Dis 2018;77:664-9. https://www.ncbi.nlm.nih.gov/pubmed/29092853

5. Anevlavis S, Kaltsas K, Bouros D. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV infected patients. PNEUMON 2012;25, October-December.http://www.pneumon.org/assets/files/789/file483_273.pdf

6. Stern A, Green H, Paul M, Leibovici L. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients (Review). Cochrane data of Systematic Reviews 2014, issue 10. DOI: 10.1002/14651858.CD005590.pub3. https://www.ncbi.nlm.nih.gov/pubmed/25269391

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

When should I consider prophylaxis for Pneumocystis pneumonia (PCP) in my patient on prednisone?

Should my hospitalized patient with ulcerative colitis flare-up receive pneumococcal vaccination?

FA Manian MD, MPH, , , , , , Leave a comment

There are at least 2 reasons for considering pneumococcal vaccination in hospitalized patients with ulcerative colitis flare.

First, these patients are often on immunosuppressants (eg, glucocorticoids) or biological agents (eg, infliximab) that qualifies them for both 13-valent conjugate (PCV13) and 23-valent polysaccharide (PPSV23) pneumococcal vaccines under the Advisory Committee on Immunization Practices (ACIP) Guidelines’ “Immunocompromised persons” risk group.1-4

Another reason is the possibility of  UC patients having coexisting hyposplenism, a major risk factor for pneumococcal disease. Although this association has been described several times in the literature since 1970s, it is relatively less well known.  In a study of patients with UC, hyposplenism (either by the presence of Howell-Jolly bodies in the peripheral blood smear or prolongation of clearance from blood of injected radioactively labelled heat-damaged red blood cells) was found in over one-third with some developing life-threatening septicemia in the early postcolectomy period.5

Another study found the majority of patients with UC having slow clearance of heat damaged RBCs despite absence of Howell-Jolly bodies in the peripheral smear.6 Fulminant and fatal pneumococcal sepsis has also been reported in patients with UC.7

Although the immunological response to pneumococcal vaccination may be lower among immunosuppressed patients in general, including those with UC, it should still be administered to this population given its potential benefit in reducing the risk of serious pneumococcal disease. 2,3  

References

  1. CDC. Intervals between PCV13 and PSV23 vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2015;64:944-47. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6434a4.htm
  2. Carrera E, Manzano r, Garrido. Efficacy of the vaccination in inflammatory bowel disease. World J Gastroenterol 2013;19:1349-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602493/
  3. Reich J, Wasan S, Farraye FA. Vaccinating patients with inflammatory bowel disease. Gastroenterol Hepatol 2016;12:540-46. http://www.gastroenterologyandhepatology.net/archives/september-2016/vaccinating-patients-with-inflammatory-bowel-disease/
  4. Chaudrey K, Salvaggio M, Ahmed A, et al. Updates in vaccination: recommendations for adult inflammatory bowel disease patients. World J Gastroenterol 2015;21:3184-96. https://www.ncbi.nlm.nih.gov/pubmed/25805924
  5. Ryan FP, Smart RC, Holdworth CD, et al. Hyposplenism in inflammatory bowel disease. Gut 1978;19:50-55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1411782/
  6. Jewell DP, Berney JJ, Pettit JE. Splenic phagocytic function in patients with inflammatory bowel disease. Pathology 1981;13:717-23. https://www.ncbi.nlm.nih.gov/pubmed/7335378
  7. Van der Hoeven JG, de Koning J, Masclee AM et al. Fatal pneumococcal septic shock in a patient with ulcerative colitis. Clin Infec Dis 1996;22:860-1. https://www.ncbi.nlm.nih.gov/pubmed/8722951

If you liked his post, sign up with your email under menu and receive future pearls straight into your mailbox! Thank you!

Should my hospitalized patient with ulcerative colitis flare-up receive pneumococcal vaccination?

My hospitalized patient has developed acute nausea, vomiting, and diarrhea. Is there an association between proton pump inhibitors and acute gastroenteritis?

FA Manian MD, MPH, , , , , , , , , Leave a comment

 

Proton pump inhibitors (PPIs) have been associated with increased risk of Clostridium difficile infection, as well as acute gastroenteritis (AG) caused by Salmonella, Campylobacter, and most recently, norovirus. 1,2

A recent prospective study1 of over 38,000 patients (mean age ~ 70 y) found a significant association between PPI use and AG leading to hospitalization with a dose-response relationship.  PPI use increased the risk of Salmonella, Campylobacter, and C. difficile infections.  Of note, H2 receptor antagonists were not associated with AG-related hospitalization in this study.

A 2017 retrospective case-control study also showed an association between PPI use and norovirus infection in hospitalized patients (mean age ~80 y in both groups). Most cases occurred during epidemic years with a median hospital stay of 5 days before onset of symptoms. Given the usually short incubation period of norovirus AG (typically 12-48 h), many of these cases likely acquired the infection during their hospital stay.

Besides reducing the acidity of gastric juice, PPIs may increase the risk of AG by causing an overgrowth of bacteria in the GI tract, reduce its motility and adversely affect the immune response, including neutrophil chemotaxis. 3

Does your patient really need a PPI?

 

References

  1. Chen Y, Liu B, Glass K, et al. Use of proton pump inhibitor and the risk of hospitalization for infectious gastroenteritis. PLoS One 2016;11:e0168618. Doi:10.1371/journal.pone. 0168618.   http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168618    
  2. Prag C, Prag M, Fredlund H. Proton pump inhibitors as a risk factor for norovirus infection. Epidemiol Infect 2017;145:1617-23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426289/pdf/S0950268817000528a.pdf
  3. Wandall JH. Effects of omeprazole on neutrophil chemotaxis, super oxide production, degranulation, and translocation of cytochrome b-245. Gut 1992;33:617-21. https://www.ncbi.nlm.nih.gov/pubmed/1319381
My hospitalized patient has developed acute nausea, vomiting, and diarrhea. Is there an association between proton pump inhibitors and acute gastroenteritis?

My patient with spontaneous bacterial peritonitis (SBP) is requiring IV albumin. Does IV albumin do anything other than expand the plasma volume?

FA Manian MD, MPH, , , , Leave a comment

Yes! Besides expanding the circulatory plasma volume by raising the oncotic pressure, albumin appears to have a vasoconstricting effects by binding to endotoxins, nitric oxide (NO), bilirubin and fatty acids1,2.

Splanchnic vasodilatation, a feature of decompensated cirrhosis (eg ascites, bleeding varices, hepatorenal syndrome, and hepatic encephalopathy), is accentuated by superimposed infections through cytokine-mediated release of endothelial vasodilators3.  By binding to potential vasodilators such as bile acids, endotoxins and NO, albumin may also help restore endothelial function and act as a vasoconstrictor.  

In a cool study involving patients with SBP randomized to either albumin or hydroxyethyl starch (HS, a synthetic volume expander), the albumin (not HS) group had a significant increase in mean arterial pressure, right atrial pressure, pulmonary artery pressure,  systolic volume, left ventricular stroke work, and systemic vascular resistance3.

Albumin may also have an immune-modulating activity in patients with cirrhosis or acute liver decompensation by binding to prostaglandin E-2 (PGE-2), generated as a result of inflammatory reaction in the liver and bacterial translocation4.  PGE-2 is a suppressor of macrophage cytokine secretion and bacterial killing.  By binding to PGE-2, albumin can reverse this immunosuppression by reducing the availability of serum PGE-2.

References

  1. Baraldi O, Valenini C, Donati G, et al. Hepatorenal syndrome: update on diagnosis and treatment 2015;4:511-20. https://www.ncbi.nlm.nih.gov/pubmed/26558188
  2. Angeli P, Volpin R, Piovan D, et al. Acute effects of the oral administration of midodrine, an α-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites. Hepatology 1998;28:937-43. https://www.ncbi.nlm.nih.gov/pubmed/9755229
  3. Fernandez J, Monteagudo J, Bargallo X, et al. A randomized unblended pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis. Hepatology 2005;42:627-634. https://www.ncbi.nlm.nih.gov/pubmed/16108036
  4. Gleeson, MW, Dickson RC. Albumin gains immune boosting credibility. Clin Transl 2015;6:e86;doi:10.1038/ctg.2015.11. http://www.nature.com/ctg/journal/v6/n4/full/ctg201511a.html
My patient with spontaneous bacterial peritonitis (SBP) is requiring IV albumin. Does IV albumin do anything other than expand the plasma volume?

When should I consider Pneumocystis jirovecii pneumonia (PCP) prophylaxis in my non-HIV patient?

FA Manian MD, MPH, , , , Leave a comment

The most significant risk factor for PCP prophylaxis is defect in cell-mediated immunity including high-dose glucocorticoid (HDGC, ≥20 mg of prednisone daily) treatment1.  A systematic review concluded that at a PCP rate of 6.2% in control groups, PCP prophylaxis with trimethoprim/sulfamethoxazole (TMP/STX) is highly effective (85% risk reduction) in non-HIV patients with acute leukemia or solid organ/autologous bone marrow  transplantation (number needed to treat 19)2.

Other Indications for PCP prophylaxis include1:

  1. HDGC treatment for ≥1month plus another cause of immunocompromise.
  2. Combination of immunosuppressive drugs, such as tumor-necrosing factor- α inhibitors plus HDGC or other immunosuppression.
  3. Polymyositis/dermatomyositis with interstitial pulmonary fibrosis on glucocorticoids.
  4. Certain primary immunodeficiencies (eg idiopathic CD4-lymphopenia, hyper-IgM syndrome).
  5. Granulomatosis with polyangiitis (Wegener’s) on methotrexate and HDGC
  6. Rheumatologic diseases on HDGC and a second immunosuppressive drug
  7. T-cell depleting agents (eg, fludarabine)
  8. Severe malnutrition

TMP/STX may be given either as double-strength 3x/week or single-strength daily1,2.

 

References

  1. Anevlavis S, Kaltsas K, Bouros D. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV infected patients. PNEUMON 2012;25, October-December.
  2. Stern A, Green H, Paul M, Leibovici L. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients (Review). Cochrane data of Systematic Reviews 2014, issue 10. DOI: 10.1002/14651858.CD005590.pub3. 
When should I consider Pneumocystis jirovecii pneumonia (PCP) prophylaxis in my non-HIV patient?