Prophylaxis for Pneumocystis jiroveci pneumonia: is it a necessity in pulmonary patients on high-dose, chronic corticosteroid therapy without AIDS?

Abstract

The benefit of prophylaxis for Pneumocystis jirovecii pneumonia (PJP) is well documented in immunocompromised patients, particularly those with HIV and/or AIDS; therefore, guidelines dictate this as standard of care. However, there is a paucity of literature regarding those without HIV and/or AIDS who are potentially predisposed to PJP, including patients with sarcoidosis, cryptogenic organizing pneumonia, interstitial lung disease, asthma and chronic obstructive pulmonary disease, who may require high dose of prolonged corticosteroids for disease maintenance or to prevent relapses. In this review, the authors examine the available literature regarding prophylaxis in these groups, elaborate on the pathogenesis of PJP, when to suspect PJP in these patients, as well as explore current recommendations that guide clinical practice regarding implementation of PJP prophylaxis, namely with trimethoprim/sulfamethoxazole being the preferred agent. In summary, the role of PJP prophylaxis in non-HIV patients on chronic steroids remains controversial. The authors present a review of the literature to provide better guidance to the clinician regarding the need to initiate PJP prophylaxis in this patient population.

Keywords:

• asthma
• chronic obstructive pulmonary disease
• corticosteroids
• cryptogenic organizing pneumonia
• immunosuppression
• interstitial lung disease
• Pneumocystis jirovecii pneumonia
• prophylaxis
• sarcoidosis
• trimethoprim/sulfamethoxazole

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Prophylaxis has had a major impact in reducing the incidence of Pneumocystis jirovecii pneumonia (PJP) in patients with HIV and/or AIDS, but such practice is not routine in patients without these disorders who may have a compromised immune state, as there are no published guidelines regarding the need for PJP prophylaxis (i.e., trimethoprim/sulfamethoxazole as the agent of choice) in HIV-negative patients.

• When considering immunosuppression, there appears to be a possible pathophysiologic association between P. jirovecii and the use of exogenous corticosteroids, especially at a median daily dose of 30 mg Prednisone or the equivalent for 12 weeks according to the literature; nonetheless, there remains a poor understanding of what is the minimum dose and duration of corticosteroids that may constitute a significant risk of a patient acquiring PJP.

• Various disorders have been cited as having a higher predisposition at these relatively low corticosteroid doses; however, studies have not sufficiently investigated the role of routine prophylaxis in many respiratory disorders that may often require similar high-dose, prolonged corticosteroid therapy, such as sarcoidosis, cryptogenic organizing pneumonia, interstitial lung disease, asthma and chronic obstructive pulmonary disease (COPD).

• The benefit of PJP prophylaxis poses a clinical challenge in the setting of a scarcity of data in that the use of trimethoprim/sulfamethoxazole (the preferred agent) carries a risk for significant side effects including skin rashes (with the most severe Stevens–Johnson syndrome being rarely reported), fever, hepatitis, renal failure, hyperkalemia and myelosuppression.

• The clinical manifestations of PJP in HIV and/or AIDS-infected individuals may differ considerably when compared to those patients without HIV and/or AIDS, and it has been recognized that patients without HIV/AIDS and PJP may have a ‘paradoxical’ increase in morbidity and mortality due to their enhanced inflammatory response as a result of their relatively more intact immune system as opposed to the more subtle, smoldering disease presentation seen in patients with HIV/AIDS. Also, delayed diagnosis and treatment may play an integral role in increased mortality due to PJP in HIV-negative patients.

• Data have been emerging in regards to the role of PJP in Stage IV COPD, being not only an acute infectious pathogen but also a colonizer, which may make it difficult to discern if PJP is the cause of worsening COPD or if worsening COPD is a predisposing factor leading to the colonization; thus, this may further confound indications for PJP routine prophylaxis in these patients.

• In patients with HIV and/or AIDS, PJP prophylaxis is indicated when CD4⁺ counts become less than 250 cells/μl; however, the utility in measuring CD4⁺ counts in HIV-negative patients to stratify their risk to develop either asymptomatic or active P. jirovecii infection has not been clearly defined or definitively supported.

• It is imperative that more studies be performed to obtain a better understanding as to why certain HIV-negative populations are at higher risk for PJP, in order to identify those patients who need prophylaxis, hopefully leading to the establishment of clinical guidelines as the standard of care.