Infectious Disease Compendium

Pneumocystis jirovecii

Microbiology

A fungus, when last I checked. (not P. carinii as of 2002)

Epidemiologic Risks

AIDS and hematologic malignancies have been the classic risk, there has been increasing cases in rheumatologic and other patients and may be causing more disease than suspected (PubMed).

Part of normal flora of human upper airway. There has been an outbreak with probable human to human transmission in kidney transplant patients who were not on prophylaxis (PubMed). The data does suggest that it is spread by air and nosocomial spread amongst the immunoincompetent.

Patients on temozolomide is an oral alkylating agent for glioblastoma multiforme and refractory anaplastic astrocytoma can get PJP and Cytomegalovirus infections.

Biologics increase the risk for PJP, but for Listeria, Salmonella, and Legionella and it has been suggested that all patients on biologics be on TMP/Sulfa to prevent all of the above (PubMed).

Steroids as a risk? Probably. But how much and how long? 50 mg prednisone not 10 mg (PubMed)?

Endogenous steroids? Yep. Cushings is a risk and should get prophylaxis.

Syndromes

Pneumonia, usually bilateral and diffuse, and often indolent, in AIDS with CD4 < 200, any lymphocytic malignancy (Hodgkin's especially on steroids (the 'P' in CHOP)), transplant patients (especially on steroids). Rare cases of disseminated disease in end stage HIV.

Can also occur in any patients on steroids with or without methotrexate (like patients with collagen vascular diseases (PubMed)) and patients on infliximab (PubMed).

What are the risks?

"Estimated incidence rates could be ranked in three categories:

i) high risk (incidence rates > 45 cases per 100,000 patient­year): polyarteritis nodosa, granulomatosis with polyangiitis, polymyositis/dermatopolymyositis, acute leukemia, chronic lymphocytic leukemia, and non­Hodgkin lymphoma;

ii) intermediate risk (25­-45 cases per 100,000 patient­year): Waldenström macroglobulinemia, multiple myeloma, and central nervous system cancer; and

iii) low risk (< 25 cases per 100,000 patient­year): other solid tumors, inflammatory diseases, and Hodgkin lymphoma (PubMed)."

Although it is popular in my institution to give prophylaxis to almost anyone (like COPD) on steroids, as of 2014 the data isn't there and tmp/sulfa is not benign.  Not that anyone pays attention to me.

The serum (1-3)-beta-D-glucan is probably the best non-invasive way to make the diagnosis (induced sputum looks great in the literature, stink in real life, and who really wants a bronch?), although remember many yeasts and molds make (1-3)-beta-D-glucan. Using a cutoff of 80 pg/will have a sensitivity of 92%, not bad.

Serum LDH level tends to roughly correlate with severity of disease, as does the serum (1-3)-beta-D-glucan level (PubMed).

"The most promising cutoff levels for diagnosis of PcP were determined to be 400 pg/ml of BG and 350 U/l of LDH, which combined with clinical data presented 92.8 % sensitivity, 83.9 % specificity, 92.8 % PPV, 83.9 % NPV (PubMed)."

Treatment

TMP/Sulfa 4-5 mg/kg q 6 h is best (15 to 20 mg/kg/day (TMP) or 75 to 100 mg/kg/day (SMX) in 3 or 4 divided doses), then, in no particular order, pentamidine OR clindamycin (600-900 mg q 8) AND primaquine OR trimetrexate OR dapsone AND trimethoprim OR atovaquone. Adding (not substituting) caspofungin may help a failing TMP/Sulfa therapy (PubMed), although the clinical data is variable (PubMed).

Duration of treatment is at least 21 d.

There is resistance that is mediated by alterations in the dihydropteroate synthase and dihydrofolate reductase.; however it may need to be combined with genotype 7 to result in failure (CDC).

In AIDS if pO2 < 60, prednisone will prevent progression: 40 bid x 7 d, 40 q d x 7 d then 20 q d x 7 d. How about non AIDS PJP? The data suggests that steroids do little (PubMed), regardless of recent steroid use.

Primary and secondary prophylaxis is the same list above; TMP/Sulfa should be 1 ds po qd and is preferred; in HIV can stop if CD4 > 200 for 3 months (primary prophylaxis) or 6 months (secondary prophylaxis) on HAART and the viral load remains undetectable.

Inhaled pentamidine (300 q 3-4 weeks) can lead to upper lobe cavitary PJP and is the prophylaxis associated with disseminated disease.

Besides HIV with CD4 < 200, do not forget prophylaxis in lymphoma patients on steroids, transplant patients, and some patients on collagen vascular disease, although the data outside of HIV and transplant is problematic (PubMed).

Notes

If the serum LDH is normal the patient almost certainly does not have PJP, in most patients the LDH level roughly follows the severity of disease.

The second P in PJP is pneumonia. So please, lets not say 'PJP pneumonia.' OK? Like PIN number. Moronic.

The use of TMP/Sulfa prophylaxis has increased point mutations in the binding site of TMP; how important this resistance is remains uncertain but can be as high as 70% in some series. They is as of yet no way to test for this clinically, but to be considered a reason for breakthrough of PJP while on TMP/Sulfa. These resistant strains can be spread from person to person (PubMed).

As best as can be determined, the use of TMP/Sulfa does not increase resistance to other classes of antibiotics and may be protective, but I am skeptical (PubMed).