Pneumonia Pneumocystis jiroveci

TABLE 52-7. Prophylactic Options for Pneumocystis jiroveci Pneumonia and CMV50 51... 

This patient has the subjective symptoms of weight loss, decreased appetite, shortness of breath, and cough. Abnormal laboratory values include elevated temperature, decreased hemoglobin and hematocrit, and decreased CD4 count. Chest x-ray shows diffuse interstitial infiltrates bilaterally. Physical exam reveals thrush. The assessment is possible AIDS with CD4 count of 150 cells/mm3, thrush, a respiratory illness (possibly Pneumocystis jiroveci pneumonia), and anemia of chronic disease. He also has a history of hepatitis B, hypertension, and GERD (on famotidine), poor adherence to his anti hypertensive medications, and likely has an irregular daily regimen due to his occupation as a truck driver. 

Briel M, Bucher HC, Boscacci R, Furrer H. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HlV-infection. Cochrane Database Syst Rev 2006. 

Clindamycin is indicated for the treatment of skin and soft-tissue infections caused by streptococci and staphylococci. It is often active against community-acquired strains of methicillin-resistant S aureus, an increasingly common cause of skin and soft tissue infections. Clindamycin is also indicated for treatment of anaerobic infection caused by bacteroides and other anaerobes that often participate in mixed infections. Clindamycin, sometimes in combination with an aminoglycoside or cephalosporin, is used to treat penetrating wounds of the abdomen and the gut infections originating in the female genital tract, eg, septic abortion and pelvic abscesses and aspiration pneumonia. Clindamycin is now recommended rather than erythromycin for prophylaxis of endocarditis in patients with valvular heart disease who are undergoing certain dental procedures. Clindamycin plus primaquine is an effective alternative to trimethoprim-sulfamethoxazole for moderate to moderately severe Pneumocystis jiroveci pneumonia in AIDS patients. It is also used in combination with pyrimethamine for AIDS-related toxoplasmosis of the brain. 

Trimethoprim- sulfamethoxazole Synergistic combination of folate antagonists blocks purine production and nucleic acid synthesis Bactericidal activity against susceptible bacteria Urinary tract infections Pneumocystis jiroveci pneumonia toxoplasmosis nocardiosis Oral, IV renal clearance (half-life 8 h) dosed every 8-12 h t formulated in a 5 1 ratio of sulfamethoxazole to trimethoprim Toxicity Rash, fever, bone marrow suppression, hyperkalemia... 

Several drugs closely related to the sulfonamides have been used effectively in the long-term treatment of leprosy. The most widely used is dapsone (diaminodiphenylsulfone). Like the sulfonamides, it inhibits folate synthesis. Resistance can emerge in large populations of M leprae, eg, in lepromatous leprosy, if very low doses are given. Therefore, the combination of dapsone, rifampin, and clofazimine is recommended for initial therapy. Dapsone may also be used to prevent and treat Pneumocystis jiroveci pneumonia in AIDS patients. 

Pneumocystis jiroveci pneumonia (PCP) High-risk patients (eg, AIDS, leukemia, transplant) Trimethoprim-sulfamethoxazole, dapsone, or atovaquone Excellent... 

In a retrospective study, the use of glucocorticoids during Pneumocystis jiroveci pneumonia (mean total dose methylprednisolone 420 mg, mean treatment duration 12 days) did not increase the risk of development or relapse of tuberculosis or other AIDS-related diseases (SEDA-20, 377 322). The study included 129 patients (72 who took glucocorticoids and 57 who did not) who were... 

Pneumocystis jiroveci pneumonia has been precipitated or aggravated by glucocorticoids (SEDA-20, 377 SEDA-22, 450 272,350,351). There is some concern about the use of glucocorticoids as adjunctive therapy in patients with AIDS who develop Pneumocystis jiroveci pneumonia. The immunosuppressant properties of glucocorticoids have been reported to enhance the risk of tuberculosis and other AIDS-related diseases (for example Kaposi s sarcoma or cytomegalovirus infection). 

Pneumocystis jiroveci Pneumonia Trimethoprim-sulfamethoxazole, pentamidine, or atovaquone... 

AZATHIOPRINE LEFLUNOMIDE T risk of serious infections (sepsis) and of opportunistic infections (Pneumocystis jiroveci pneumonia, tuberculosis, aspergillosis) Additive immunosuppression Monitor platelets, white bloods cell, haemoglobin and haematocrit at baseline and regularly - weekly, during concomitant therapy. With evidence of bone marrow suppression, discontinue leflunomide and administer colestyramine or charcoal to T elimination of leflunomide - For signs and symptoms of immunosuppression, see Qinical Features of Some Adverse Drug Interactions, Immunosuppression and blood dyscrasias... 

PENTAMIDINE ISETIONATE NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS t adverse effects with didanosine, tenofbvir and zidovudine Additive toxicity Monitor FBC and renal function closely. Consider stopping didanosine while pentamidine is required for Pneumocystis jiroveci pneumonia... 

When atovaquone was compared with intravenous pentamidine in the treatment of mild and moderate Pneumocystis jiroveci pneumonia in an open trial, the success rates were similar. However, withdrawal of the original treatment was much more frequent with pentamidine (36%) than atovaquone (4%) (4). However, the authors conclusion that the two approaches have a similar success rate has been challenged, and their series was small (5,6). Treatment-limited adverse effects occurred in only 7% of patients given atovaquone, compared with 41 % given pentamidine. They included cases of rash and an increase in creatinine concentrations atovaquone (unlike pentamidine) produced no vomiting, nausea, hypotension, leukopenia, acute renal insufficiency, or electrocardiographic abnormalities, but it did cause one case of dementia (4). 

In a multicenter, double-blind, randomized trial in 87 patients, clindamycin + primaquine was compared with co-trimoxazole as therapy for AIDS-related Pneumocystis jiroveci pneumonia efficacy was similar. In patients with a Pa02 under 70 mmHg, clindamycin + primaquine was associated with fewer adverse events and less glucocorticoid use, but more rashes (2). 

In patients with definite or probable methotrexate-induced lung injury, the predominant clinical features include shortness of breath, cough, and fever (13). Pathological examination usually shows an interstitial inflammatory cell infiltrate (sometimes granulomatous or with alveolar damage), and variable degrees of interstitial fibrosis. Unfortunately, confirmatory evidence is sometimes hard to obtain, particularly in patients with rheumatoid arthritis in whom rheumatoid interstitial lung disease can also occur. Infectious pneumonias, particularly viral or Pneumocystis jiroveci pneumonia, which resemble methotrexate pneumonitis and can occur as a result of immunosuppression, should also be carefully excluded. 

An accumulating series of case reports has focused on the possible more frequent occurrence of opportunistic infections despite normal leukocyte counts in patients treated for rheumatoid arthritis or, less often, psoriasis (97,100,101). Various bacterial, fungal, and viral opportunistic infections have been described, with Pneumocystis jiroveci pneumonia as the most frequently reported (SEDA-21, 389) (SEDA-22, 417). Although the most severe, sometimes fatal, infectious diseases were usually observed in patients also taking glucocorticoids (SEDA-22, 417) (102,103), severe infections can also occur in occasional patients not taking concomitant glucocorticoids (SEDA-21, 389) (101,104-107). 

Pentamidine, an aromatic diamine, has been known since the late 1930s as a treatment for trypanosomiasis and some forms of leishmaniasis. In recent times it has been extensively used in the treatment of Pneumocystis jiroveci pneumonia. Its mechanism of action is probably related to inhibition of dihydrofolate reductase and inhibition of oxidative phosphorylation and nucleic acid synthesis, as well as an effect on aerobic glycolysis. 

Intravenous pentamidine caused megaloblastic anemia in a 38-year-old woman with Pneumocystis jiroveci pneumonia (9). 

When the pyrimethamine + dapsone combination was used in the prophylaxis of Pneumocystis jiroveci pneumonia in 173 patients with AIDS, there was anemia in about 20, and in all 117 cases for which data were available, serum haptoglobin concentrations had fallen (SEDA-18, 287). 

There have been no reports on the risk of Pneumocystis jiroveci pneumonia in patients taking rifampicin plus co-trimoxazole prophylaxis. Until such time as more data are available, it is prudent to use double-strength co-trimoxazole tablets twice daily for prophylaxis of toxoplasmosis and P. jiroveci pneumonia in patients taking concomitant rifampicin. 

A 42-year-old HIV-positive man with a prior history of Pneumocystis jiroveci pneumonia who had been treated with zidovudine and dideoxycytidine started to take saquinavir 600 mg tds. His CD4 cell count rose from 28 X 10 /1 to 101 X 10 /1 and zidovudine and dideoxycytidine were replaced by stavudine and lamivudine, because of mild peripheral neuropathy. Saquinavir was continued unchanged. A few months later he developed left-sided loin pain and hematuria and a left renal calculus was seen on ultrasound. A month later the same signs and symptoms recurred and a few weeks later he passed a small black stone in the urine. Ultrasonic lithotripsy was performed, with a good result. Saquinavir was discontinued, after which he had no further renal problems. 

New folate antagonists have been identified that are better substrates for the reduced folate carrier and appear to have significant advantages in clinical chemotherapy (see pemetrexed below). In efforts to bypass the obligatory membrane transport system and to facilitate penetration of the blood—brain barrier, lipid-soluble folate antagonists also have been synthesized. Trime-trexate (NEVTREXIN) has modest antitumor activity, primarily in combination with leucovorin rescue. However, it is beneficial in the treatment Pneumocystis jiroveci pneumonia, where leucovorin provides differential rescue of the host but not the parasite. 

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