Aerosolized Pentamidine for Pneumocystis Pneumonia

• Aerosolized antiinfective agents are used to treat respiratory infections.

Clinical Indications for Pentamidine

• Aerosolized pentamidine is indicated for the prevention of Pneumocystis pneumonia (PCP) in HIV-infected patients.
• It is used in patients with a history of one or more episodes of PCP or with a peripheral CD4+ (T4 helper cell) lymphocyte count of 200/mm³ or less.
• Local targeted lung delivery is a rationale for aerosol administration.
• Aerosolized administration results in fewer or less severe side effects compared to systemic administration.
• Pneumocystis is also known as Pneumocystis jiroveci.

Dosage of Pentamidine

• The dosage for pentamidine is 300 mg, given by inhalation once every 4 weeks.
• The treating physician can alter the dosage.
• Pentamidine is administered as a dry powder.
• It comes in 300 mg/vial.
• It should be reconstituted with 6 mL of sterile water.
• Mixing with saline can cause precipitation.

Administration of Pentamidine

• Pentamidine should be administered using a Respirgard II nebulizer.
• The nebulizer should be powered by a flow rate of 5–7 L/min from a 50-psi gas source.
• Escaped particles may be filtered to limit exposure of healthcare workers.
• The nebulizer performance characterized by mass median diameter (MMD) of 1–2 μm.

Side Effects of Pentamidine

• Common side effects include cough and bronchial irritation (36% of patients in one study).
• Other side effects include shortness of breath, bad taste, bronchospasm, wheezing, spontaneous pneumothoraces, conjunctivitis, rash, neutropenia, pancreatitis, renal insufficiency, dysglycemia, digital necrosis in both feet, and appearance of extrapulmonary P. jiroveci infection.

Environmental Contamination of Pentamidine

• There is a risk of environmental contamination by nebulized pentamidine.
• This includes exposure to the drug itself from the exhaust aerosol, and a risk of infection with tuberculosis.
• Pentamidine is not known to be teratogenic or mutagenic.
• It has minimal carcinogenic potential.

Clinical Indications for Ribavirin

• Aerosolized ribavirin is indicated for the treatment of hospitalized infants with severe lower respiratory tract infection caused by respiratory syncytial virus (RSV).
• Ribavirin is classified as an antiviral drug and it is virostatic, not virucidal.
• It is active against RSV, influenza viruses, and herpes simplex virus.
• Ribavirin is a nucleoside analog, resembling guanosine and inosine.
• It inhibits both DNA and RNA (retrovirus) viruses.

Nature of Viral Infection

• The process of viral infection involves adsorption to the cell, penetration of the cell, uncoating itself, recoding cell DNA, assembling itself, and shedding from the cell.
• Viruses are obligate intracellular parasites.
• Diagnosis of viral infections is usually based on clinical signs.
• This requires isolating the virus or demonstrating antibody titer increase.

Dosage of Ribavirin

• Ribavirin solution concentration is 20-mg/mL.
• The Small Particle Aerosol Generator (SPAG-2) is used for administration.
• The recommended treatment is 12 to 18 hours per day.
• Treatments last for a minimum of 3 days and not more than 7 days.
• Ribavirin is supplied as 6 g of powder in 100-mL vial.
• The concentration is 6 g/300 mL.

Side Effects of Ribavirin

• Pulmonary side effects: Deterioration of pulmonary function and worsening of asthma or chronic obstructive disease; pneumothorax, apnea, and bacterial pneumonia.
• Cardiovascular side effects: Cardiovascular instability, including hypotension, cardiac arrest, and digitalis toxicity.
• Hematological effects: Effects on blood cells have been reported with oral or parenteral administration but not with aerosol use.
• Reticulocytosis (excess of young erythrocytes in circulation) has been reported with aerosol use.
• Dermatological/topical: Rash, eyelid erythema, and conjunctivitis.

Environmental Contamination: Ribavirin

• There is potential for mutagenic and carcinogenic effects with aerosolized ribavirin.
• The effect on fertility is uncertain, since it has caused testicular lesions in rats.
• Effect on pregnancy is of particular concern, due to teratogenic or embryocidal effects in animal species.

RSV Infection—Other Agents: Palivizumab

• Palivizumab (Synagis) is indicated for the prevention of a serious lower respiratory tract disease caused by RSV in children and infants at high risk.
• The safety and efficacy of Palivizumab has been established for infants with BPD, premature infants (<35 weeks), and children with congenital heart disease.
• The dosage is 15 mg/kg, given IM monthly in RSV season.
• Palivizumab's Mechanism of action is via Monoclonal antibodies.
• It provides neutralizing and fusion-inhibiting activity; prevents viral replication.

Clinical Indications for Tobramycin

• Aerosolized tobramycin is indicated for the management of chronic Pseudomonas aeruginosa infection in cystic fibrosis (CF).
• Clinical use of inhaled tobramycin includes Pulmonary infections (CF)
• Aerosolized tobramycin helps treat or prevent early colonization with P. aeruginosa.
• Also, to maintain present lung function or reduce the rate of deterioration.

Aerosolized Tobramycin

• Dosage and administration is 300 mg BID
• Tobramycin should be used for 28 days consecutively/following 28 days off
• 300 mg in 5-mL ampule, administered with PARI LC Plus
• Mechanism of action: Binds irreversibly to 30S subunit of bacterial ribosomes
• Blocks protein synthesis in bacteria and causes cellular death, bactericidal

General Considerations: Tobramycin

• General considerations in aerosolizing antibiotics
• May affect nebulizer performance
• Environmental contamination
• Incompatibility with other drugs

Clinical Indications for Aztreonam

• Aztreonam is indicated to improve symptoms in CF patients with P. aeruginosa infection
• Clinical use: pulmonary infections (CF)
• Improves pulmonary symptoms in CF patients colonized with P. aeruginosa
• Not indicated for patients <7 years old
• Studies have only been done in patients having an FEV1 about 25% or below 75% of predicted

Aerosolized Aztreonam

• Dosage and administration
• Must be reconstituted
• 2-mL single use glass vials contain 75 mg of lyophilized aztreonam; must be mixed with the provided 1 mL of sterile diluent (0.17% sodium chloride)
• Comes in a 28-day kit
• Delivered by itself using Altera Nebulizer System

Clinical Indications for Zanamivir

• Inhaled zanamivir is indicated for influenza in adults and children 5 years and over who have been symptomatic for no more than 2 days
• Off-labeled use for treatment and prophylaxis of H1N1 influenza A (swine flu)
• Dosage and administration
• DPI (Diskhaler)
• 5 mg/blister
• Adults and children 5 years and older
• Two inhalations (two blisters, for a total of 10 mg) taken twice a day, approximately 12 hours apart, for 5 days

Inhaled Zanamivir (Cont.)

• Adverse effects
• Bronchospasm and deterioration of lung function in patients with underlying asthma or COPD
• Undertreatment of bacterial infection
• Allergic reactions
• Other adverse effects
  • Gastrointestinal
  • Respiratory
  • Dizziness/headache

Inhaled Zanamivir

• Clinical efficacy and safety
  • Treatment with 10 mg of zanamivir twice daily resulted in approximately 1 day less to the median time to improvement in symptoms compared with placebo
  • Treatment with zanamivir 30 hours or less after the onset of symptoms resulted in 3 days or less to the median time to alleviation of symptoms
  • Not generally recommended for patients with underlying airway disease
  • Not approved for prophylaxis

Respiratory Care Assessment: Before Treatment

• Assess the patient for the presence of a disease in which use of the agent is indicated
  • Pentamidine: risk of PCP
  • Ribavirin: presence of severe RSV infection
  • Tobramycin: chronic P. aeruginosa infection in CF patient
  • Aztreonam: chronic P. aeruginosa infection in CF patient
  • Zanamivir: acute influenza infection within two days of onset
• Assess equipment
• Initial patient assessment

General Contraindications

• Pentamidine: Bronchospasm and cough
• Ribavirin: Pregnant caregiver should avoid exposure
• Tobramycin: Drug resistance
• Aztreonam: Drug resistance
• Zanamivir: Caution in patients with preexisting airway disease