Pneumocystis jiroveci pneumonia and HIV/AIDS

General: For years, antibiotics, such as TMP/SMX, dapsone, pentamidine, and atovaquone, were prescribed to cancer patients with weakened immune systems who had Pneumocystic jiroveci pneumonia (also called PCP). It was not until 1985 that a small study proved that the antibiotics could also prevent and treat PCP in AIDS patients. Mortality rates of PCP in AIDS patients have declined by 50% since the antibiotics were introduced.

Because of the severity of the disease, many physicians will treat patients who show symptoms of PCP before a definitive diagnosis is made, if they belong to a high-risk group. Individuals with a CD4 cell (helper T-cells that help fight against disease and infection) lower than 200 cells per microliter of blood have the greatest risk of developing PCP. Once the CD4 cell count falls below 200, the patient's condition has progressed to AIDS. Healthy individuals have a CD4 cell count between 600 and 1,200 per microliter of blood. In addition, people who have CD4 cell counts lower than 300 and have already had another opportunistic infection have an increased risk of developing PCP.

Patients should tell their healthcare providers if they are taking any drugs (prescription or over-the-counter), herbs, or supplements due to possible interactions. Patients should take medications exactly as prescribed by their healthcare providers.

TMP/SMX (Bactrim® or Septra®: TMP/SMX (Bactrim® or Septra®) is a combination of two antibiotics - trimethoprim (TMP) and sulfamethoxazole (SMX). This drug is considered the most effective treatment for PCP. The drug is taken is taken orally. Patients typically take one single- or double-strength tablet daily. The SMX antibiotic is a sulfa drug, which many patients are allergic to. Cutting back from one pill a day to three pills a week reduces the risk of allergy. Allergic reactions to the drug usually cause a skin rash and sometimes a fever. Allergic reactions can be overcome using a desensitization procedure. Patients start with a very small amount of the drug and take increasing amounts until they can tolerate the full dose.

Dapsone: Dapsone is similar to TMP/SMX. Dapsone is almost as effective against PCP and TMP/SMX, and it causes fewer allergic reactions. Dapsone is taken orally. Once a day is the maximum dosage.

Pentamidine (NebuPent®, Pentam®, Pentacarinat®): Pentamidine (NebuPent®, Pentam® or Pentacarinat®) is a drug that is inhaled in an aerosol form to prevent PCP. Pentamidine can also be administered intravenously (IV) to treat active PCP. Patients receiving pentamidine must visit a clinic with a nebulizer once a month to receive treatment. The nebulizer is a machine that produces a very fine mist of the drug. The mist is inhaled directly into the lungs. The procedure takes about 30 to 45 minutes.

Atovaquone (Mepron®): Atovaquone (Mepron®) is a drug used in patients with mild or moderate cases of PCP who cannot take TMP/SMX or pentamidine. Atovaquone is a liquid drug that is taken by mouth. It is typically taken with food, every eight hours for 21 days.

Clindamycin (Cleocin®: Clindamycin has also been used to treat PCP. This drug is taken by mouth for about 21 days.

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Chiropractic: There is not enough reliable scientific evidence to conclude the effects of chiropractic techniques in the management of pneumonia in the elderly.

Use extra caution during cervical adjustments. Use cautiously with acute arthritis, conditions that cause decreased bone mineralization, brittle bone disease, bone softening conditions, bleeding disorders, or migraines. Use cautiously with the risk of tumors or cancers. Avoid with symptoms of vertebrobasilar vascular insufficiency, aneurysms, unstable spondylolisthesis, or arthritis. Avoid with agents that increase the risk of bleeding. Avoid in areas of para-spinal tissue after surgery. Avoid if pregnant or breastfeeding due to a lack of scientific data.

Iodine: Based on one prospective randomized study, regular oropharyngeal application of povidone-iodine may decrease the prevalence of ventilator-associated pneumonia in patients with severe head trauma. Evidence in this area is not conclusive.

Reactions can be severe and deaths have occurred with exposure to iodine. Avoid iodine-based products if allergic or hypersensitive to iodine. Do no use for more than 14 days. Avoid Lugol solution and saturated solution of potassium iodide (SSKI, PIMA) with hyperkalemia (high amounts of potassium in the blood), pulmonary edema (fluid in the lungs), bronchitis, or tuberculosis. Use cautiously when applying to the skin because it may irritate/burn tissues. Use sodium iodide cautiously with kidney failure. Avoid sodium iodide with gastrointestinal obstruction. Iodine is safe in recommended doses for pregnant or breastfeeding women. Avoid povidone-iodine for perianal preparation during delivery or postpartum antisepsis.

Physical therapy: Early evidence suggests that chest physiotherapy techniques, such as postural drainage, external help with breathing, percussion, and vibration, are not better than receiving advice of deep breathing instructions in the treatment of pneumonia. Additional evidence is needed in this area.

Lung hyperinflation is a technique used by physiotherapists to mobilize and remove excess lung secretions, reinflate areas of pulmonary collapse, and improve oxygenation. Studies have compared manual vs. mechanical interventions and found no differences between the two. However, studies are lacking that compare physical therapy to placebo or other interventions. Additional research is needed in this area.

Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with their qualified healthcare providers before beginning any treatments. Based on the available literature, physical therapy appears generally safe when practiced by a qualified physical therapist. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.

Probiotics: Probiotics have been suggested as a possible treatment for pneumonia. Further research is needed before a firm conclusion can be made in this area.

Probiotics are generally considered safe and well tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant.

Vitamin A (retinol): One study found no effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal weight children under five years of age. However, a beneficial effect was seen in children with high basal serum retinol concentrations. Further research is needed before a firm conclusion can be made.

Yerba santa: There is extensive clinical history of the use of Eriodictyon extracts in pulmonary conditions such as influenza, bacterial pneumonia, asthma, bronchitis, and tuberculosis. This includes traditional use by Chumash and other California Indians, and subsequent formalized use in the United States and Britain from the late 1800s until the 1960s. However, there are no available human trials in this area. Therefore, there is insufficient scientific evidence to determine efficacy.

Avoid if allergic or hypersensitive to the Eriodictyon species. Use cautiously in children. Avoid if pregnant or breastfeeding.

General: Preventative antibiotics should be administered as a preventative treatment for Pneumocystic jiroveci pneumonia (also called PCP) in HIV patients who have CD4 cell counts lower than 200 cells per microliter of blood or with a history of Pneumocystis jiroveci pneumonia or oral thrush (fungal infection in the mouth). It may also be considered in patients who have a CD4 cell counter higher than 200 if their CD4 cell percentage is below 14%, they have other opportunistic infections, or they have a fever above 100 degrees Fahrenheit that has lasted for longer than two weeks. Preventative treatment can be discontinued if the patient's CD4 cell count increases above 200 cells per microliter of blood for at least three months, in response to antiretroviral therapy.

Since PCP occurs in individuals with a weakened immune system, HIV/AIDS patients should receive highly active antiretroviral therapy (HAART) to suppress the virus and restore the body's immune system.

TMP-SMX (Bactrim® or Septra®): Trimethoprim-sulfamethoxazole (Bactrim® or Septra®), also called TMP-SMX, is a combination of two antibiotics - trimethoprim and sulfamethoxazole. TMP-SMX is the standard preventative treatment for Pneumocystis jiroveci pneumonia. Patients typically take one single- or double-strength tablet daily. Allergic reactions to the drug usually cause a skin rash and sometimes a fever. Allergic reactions can be overcome using a desensitization procedure. Patients start with a very small amount of the drug and take increasing amounts until they can tolerate the full dose.

Dapsone: Patients who have a history of drug-induced allergic reactions may take dapsone instead. Dapsone is similar to TMP/SMX. Dapsone is almost as effective against PCP and causes fewer allergic reactions than TMP/SMX. 100 milligrams of Dapsone may be taken orally daily, or 50 milligrams may be taken orally twice a day.

Alternatively, 50 milligrams of dapsone may be taken orally once a day with 50 milligrams of oral pyrimethamine once per week and 25 milligrams of oral leucovorin once per week.

A third treatment option is 200 milligrams of dapsone with 75 milligrams of pyrimethamine and 25 milligrams of leucovorin once per week.

Atovaquone (Mepron®): Atovaquone (Mepron®) is a drug used in people with mild or moderate cases of PCP who cannot take TMP/SMX or pentamidine.

Highly active antiretroviral therapy (HAART): Currently there is no cure for HIV/AIDS, but highly active antiretroviral therapy (HAART) has proven to effectively suppress the virus, which subsequently restores the body's immune system. HAART usually combines drugs from at least two different classes of antiretroviral drugs, and it has been shown to suppress the virus.

Currently, the U.S. Food and Drug Administration (FDA) has approved 28 antiretroviral drugs to treat HIV infected individuals. These drugs fall into four major classes: reverse transcriptase (RT) inhibitors, fusion inhibitors, and protease inhibitors. In July 2006, the FDA approved a multi-class combination called Atripla®.

Reverse transcriptase (RT) inhibitors disrupt the reverse transcription stage in the HIV lifecycle. During this stage, an HIV enzyme, known as reverse transcriptase, converts HIV RNA to HIV DNA. There are two main types of RT inhibitors - non-nucleoside RT inhibitors and nucleoside/nucleotide RT inhibitors.

Non-nucleosideRT inhibitors bind to reverse transcriptase, preventing HIV from converting the HIV RNA into HIV DNA. Approved non-nucleoside RT inhibitors include Rescriptor®, Sustiva® and Viramune®.

Nucleoside/nucleotide RT inhibitors serve as faulty DNA building blocks. Once they are incorporated into the HIV DNA, the DNA chain cannot be completed. Therefore, the drugs prevent HIV from replicating inside a cell. Approved drugs include Combivir®, Emtriva®, Epivir®, Epzicom®, Hivid®, Retrovir®, Trizivir®, Truvada®, Videx EC®, Videx®, Viread®, Zerit®, and Ziagen®.

Fusion inhibitors prevent the virus from fusing with the cellular membrane, thus blocking entry into the cell. Only one fusion inhibitor, Fuzeon®, is FDA-approved.

Protease inhibitors (PIs) interfere with the protease enzyme that HIV uses to produce infectious viral particles. PIs prevent viral replication by inhibiting the activity of protease, an enzyme used by the virus to cleave nascent proteins for final assembly of new virons. FDA-approved protease inhibitors include Agenerase®, Aptivus®, Crixivan®, Invirase®, Kaletra®, Lexiva®, Norvir®, Prezista®, Reyataz®, and Viracept®.

HAART can make the patient's CD4 cell count go up. If it goes over 200 and stays there for three months, it may be safe to stop taking PCP prophylactic antibiotics. However, because PCP medications are inexpensive and have mild side effects, some researchers think they should be continued until the CD4 cell count reaches 300.