Pneumonia pentamidine

The answer is d. (Hardman, p 989.) Both trimethoprim-sulfamethoxazole and pentamidine are effective in pneumonia caused by E carinii. This protozoal disease usually occurs in immunodeficient patients, such as those with AIDS. Nifurtimox is effective in trypanosomiasis and metronidazole in amebiasis and leishmaniasis, as well as in anaerobic bacterial infections. Penicillins are not considered drugs of choice for this particular disease state. 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Pentamidine is active against Pneumocystis carinii, trypanosomes, and leishmaniasis unresponsive to pentavalent antimonials. It is an alternative agent for the treatment of P. carinii pneumonia. Although it is more toxic than trimethoprim-sulfamethoxazole, it has been widely used in patients with acquired immunodeficiency syndrome (AIDS), in whom P. carinii infection is common. 

The combination of clindamycin and primaquine is an alternative regimen in the treatment of pneumocystosis, particularly mild to moderate disease. This regimen offers improved tolerance compared with high-dose trimethoprim-sulfamethoxazole or pentamidine, although its efficacy against severe pneumocystis pneumonia is not well studied. 

This route presents not only a quick, efficient way to deliver drugs into the bloodstream but a vulnerable route for poisoning. In early 1989 the FDA gave "Treatment IND" status to an aerosol form of pentamidine for the prevention and treatment of Pneumocystis carnii pneumonia which is the most common life-threatening infection seen in AIDS patients. 

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

Clinical Use. Atovaquone (Mepron) is used primarily to treat the protozoon that causes toxoplasmosis and the fungus that causes pneumocystis pneumonia in immunocompromised patients.6 This drug is not typically the primary treatment for pneumocystis, but is often reserved for patients who cannot tolerate more traditional treatments using sulfamethoxazole and trimethoprim (see Chapter 34) or pentamidine (see later). Atovaquone can also be used to prevent and treat resistant cases of malaria, and the antimalarial effects of this drug seem especially useful when combined with proguanil.48... 

Adverse Effects. The primary adverse effect of systemic pentamidine administration is renal toxicity. Renal function may be markedly impaired in some patients, but kidney function usually returns to normal when the drug is withdrawn. Other adverse effects include hypotension, hypoglycemia, gastrointestinal distress, blood dyscrasias (leukopenia, thrombocytopenia), and local pain and tenderness at the site of injection. Adverse effects are reduced substantially when the drug is given by inhalation, and this method of administration is desirable when pentamidine is used to prevent pneumocystis pneumonia in patients with human immunodeficiency virus (HIV) disease. 

There are many commercially available nebulizers with differing mass output rates and aerosol size distributions which will be a function of operating conditions, such as compressed air flow rate. As described above, for maximum efficacy, the drug-loaded droplets need to be less than 5 pm. In the treatment or prophylaxis of P.carinii pneumonia with nebulized pentamidine where the target is the alveolar space it is preferable to use nebulizers capable of generating droplets of less than 2 pm. 

A series of 2,7- and 3,6-bis-cationic carbazoles, for example, 49, shows activity against a rat model of Pneumocystis carinii pneumonia (PCP), and some are more potent and less toxic than the standard anti-PCP drug pentamidine <1997EJM781>. While no quantitative correlation was seen between anti-PCP activity, topoisomerase inhibition, and DNA binding, a minimal level of DNA binding was found to be necessary for antimicrobial activity. 

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... 

Pneumocystosis, caused by Pneumoq/stis carinii (now classified as a fungus), is an important cause of potentially fatal pneumonia in the immimo-suppressed. It is treated with co-trimoxazole in high dose (120 mg/kg daily in 2-4 divided doses for 14 days by mouth or i.v. infusion). Intolerant or resistant cases may benefit from pentamidine or, if mild to moderate, from atovaquone, or trimetrexate (given with calcium folinate). Co-trimoxazole by mouth or intermittent inhaled pentamidine are used for prophylaxis in patients with AIDS. 

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). 

Dohn MN, Weinberg WG, Torres RA, Follansbee SE, Caldwell PT, Scott JD, Gathe JC Jr, Haghighat DP, Sampson JH, Spotkov J, Deresinski SC, Meyer RD, Lancaster DJ. Oral atovaquone compared with intravenous pentamidine for Pneumocystis carinii pneumonia in patients with AIDS. Atovaquone Study Group. Ann Intern Med 1994 121(3) 174-80. 

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. 

Acute eosinophilic pneumonia after one dose of inhaled pentamidine of 300 mg has been reported the reaction subsided within 2 weeks but recurred on rechallenge (SEDA-18, 292). 

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

Cheung TW, Matta R, Neibart E, Hammer G, Chusid E, Sacks HS, Szabo S, Rose D. Intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus. Clin Infect Dis 1993 16(l) 22-5. 

Wharton JM, Coleman DUWofsyCB, Luce JM, Blumenfeld W, Hadley WK,etal.Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective randomized trial. Annals of internal medicine. 1986 Jul 105(1 ) 37-44. 

Western KA, Perera DR, Schultz MG. Pentamidine Isethlonate In the treatment of Pneumocystis carinll pneumonia. Annals of Internal medicine. 1970 Nov 73(5) 695-702. 

Hughes WT, Feldman S, Chaudhary SC, OssI MJ, Cox E, Sanyal SK. Comparison of pentamidine Isethlonate and trimethoprim-sulfamethoxazole In the treatment of Pneumocystis carinll pneumonia.The Journal of pediatrics. 1978 Eeb 92(2) 285-91. 

Pearson RD, Hewlett EL. Pentamidine for the treatment of Pneumocystis carinll pneumonia and other protozoal diseases. Annals of internal medicine. 1985 Nov 103(5) 782-6. 

Haley. Pentamidine in Pneumocystis carinll pneumonia. Microlink Update. 1987 3 1-4. 

O Brien JG, Dong BJ, Coleman RL,Gee L, Balano KB. A 5-year retrospective review of adverse drug reactions and their risk factors in human immunodeficiency virus-infected patients who were receiving intravenous pentamidine therapy for Pneumocystis carinll pneumonia. Clin Infect Dis. 1997 May 24(5) 854-9. 

Lid man C, Bronner U, Gustafsson LL, Rombo L. Plasma pentamidine concentrations vary between individuals with Pneumocystis carinii pneumonia and the drug is actively secreted bythe kidney. The Journal of antimicrobial chemotherapy. 1994 Apr 33(4) 803-10. 

Waskin El, Stehr-GreenJK, ElelmickCG,SattlerER. Risk factors for hypoglycemia associated with pentamidine therapy for Pneumocystis pneumonia. Jama. 1988Jul 15 260(3) 345-7. 

Sensakovic JW, Suarez M, Perez G, Johnson ES, Smith LG. Pentamidine treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Association with acute renal failure and myoglobinuria. Archives of internal medicine. 

Golden JA, Chernoff D, Hollander H, Feigal D, Conte JE. Prevention of Pneumocystis carinii pneumonia by inhaled pentamidine. 

Jensen BN, Nielsen TL, Lerche B, Jensen TH, Backer V,Mathiesen L, et al. Prevention of Pneumocystis carinii pneumonia relapse by aerosolised pentamidine, 60 mg biweekly, using an Acorn System 22 nebuliser. Scandinavian journal of infectious diseases. 1990 22(5) 533-6. 

Link H, Vohringer HF, Wingen F, Bragas B, Schwardt A, EhningerG. Pentamidine aerosol for prophylaxis of Pneumocystis carinii pneumonia after BMT. Bone marrow transplantation. 1993 May 11 (5) 403-6. 

Saukkonen K, Garland R, Koziel H. Aerosolized pentamidine as alternative primary prophylaxis against Pneumocystis carinii pneumonia in adult hepatic and renal transplant recipients. Chest. 1996 May 109(5) 1250-5. 

Balslev U, Berild D, Nielsen TL. Cardiac arrest during treatment of Pneumocystis carinii pneumonia with intravenous pentamidine isethionate. Scandinavian journal of infectious diseases. 1992 24(1) 111-2. 

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