Eflornithine for the Treatment of Pneumocystis carinii Pneumonia in Patients with the Acquired Immunodeficiency Syndrome: A Preliminary Review

Abstract

Pneumocystis carinii pneumonia (PCP) is the most common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). Eflornithine is an antiprotozoal agent active against P. carinii. It acts by inhibiting ornithine decarboxylase, an enzyme that is essential for cellular function. The drug is initially administered intravenously, followed by oral therapy. Eflornithine has been used on a compassionate basis in AIDS patients with PCP who were intolerant of or unresponsive to traditional agents. Overall, the response rate has been about 35%; however, conclusions are difficult to make since patients had different stages of disease and received treatment for varying periods of time. Side effects include depression of bone marrow function, diarrhea, hearing loss, seizures, alterations in liver function tests, and rash. While the need for safer and more efficacious antipneumocystis drugs grows, widespread use of seemingly promising agents should be based on well-conducted clinical trials.

Polyamine Transport as a Target for Treatment ofPneumocystisPneumonia

“…DFMO has also been shown to inhibit the growth of P. carinii in short-term cultures at a concentration of 1 mM (11) and used to treat PCP in humans with various success rates (33 to 57%) (14,32,36,38,39). This partial success suggests that antipolyamine therapy can be effective against PCP, but inhibiting polyamine synthesis alone may not be sufficient.…”

“…However, TMP-SMZ may cause adverse effects, such as fever and rash (37), and TMP-SMZ-resistant Pneumocystis strains have emerged (28), probably due to point mutations at codon 55 or 57 of the DHPS gene of Pneumocystis jirovecii (18,41). Clindamycin-primaquine, atovaquone, and pentamidine are alternative therapies for PCP; however, they are also associated with the issues of side effects.Another potential target for treatment of PCP is polyamine synthesis (8,9,14,32,36,39). Polyamines are essential organic compounds for cell growth (20,26).…”

“…Another potential target for treatment of PCP is polyamine synthesis (8,9,14,32,36,39). Polyamines are essential organic compounds for cell growth (20,26).…”

“…It also has activity against Plasmodium falciparum (30), Giardia lamblia (13), Eimeria tenella (16), and Trichomonas vaginalis (47). DFMO has also been used to treat PCP in humans, with success rates ranging from 33 to 57% (14,32,36,38,39). This partial success suggests that targeting polyamine synthesis alone is not sufficient for treatment of PCP.…”

Therapeutic progress IV: Treatment and prophylaxis of Pneumocystis carinii infection

“…Eflomithine (a-difluoromethylomithine, DFMO) inhibits polyamine synthesis and has been shown to be effective against PCP in an animal model (31), although in clinical trials only 3 5 4 8 % have responded (63,64). In a comparative study with co-trimoxazole, eflomithine was less effective, with a primary treatment failure of 49% compared with 21% on co-trimoxazole (65).…”