eMedicine Specialties > Pulmonology > Infectious Lung Diseases

Pneumonia, Viral: Treatment & Medication

Author: Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St. Boniface General Hospital
Contributor Information and Disclosures

Updated: Apr 28, 2009

Treatment

Medical Care

Table 2. Treatment and Prevention of Common Causes of Viral Pneumonia*

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^* All viral pneumonia patients must receive supportive care with oxygen, rest, antipyretics, analgesics, nutrition, and close observation.

• Influenza
  • Antiviral therapy is available for treatment of influenza virus infection. The treatment of uncomplicated influenza is supportive in nature, consisting of rest and administration of antipyretics and analgesics. Table 3. Characteristics of Anti-Influenza Drugs

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    Table

    	Amantadine (Symmetrel)	Rimantadine (Flumadine)	Zanamivir (Relenza)	Oseltamivir (Tamiflu)
    Mechanism of action	M2 ion channel blockade inhibits HA* cleavage Þ block RNA encoding, which reduces early viral replication.		Viral NA† inhibition prevents sialic acid cleavage from HA Þ virus gets trapped inside cells, and epithelial spread is blocked.
    Spectrum	Influenza A only	Influenza A only	Influenza A and B	Influenza A and B
    Oral bioavailability	Good	Good	Poor	Good
    Protein binding, %	67	40	None	Minimal
    Half-life, h	12-18	24-36	2.5-5	1-3
    Excretion	Renal (not removed by hemodialysis)		Renal and gastrointestinal	Renal
    Drug interaction	Synergistic CNS toxicity with antihistamines, anticholinergics, CNS stimulants	ßPlasma level: ASA§, acetaminophen	None	None
    Renal clearance	TMP-SMZ¶, triamterene, hydrochlorothiazide, quinine sulfate, quinidine	Cimetidine	None	None

    	Amantadine (Symmetrel)	Rimantadine (Flumadine)	Zanamivir (Relenza)	Oseltamivir (Tamiflu)
    Mechanism of action	M2 ion channel blockade inhibits HA* cleavage Þ block RNA encoding, which reduces early viral replication.		Viral NA† inhibition prevents sialic acid cleavage from HA Þ virus gets trapped inside cells, and epithelial spread is blocked.
    Spectrum	Influenza A only	Influenza A only	Influenza A and B	Influenza A and B
    Oral bioavailability	Good	Good	Poor	Good
    Protein binding, %	67	40	None	Minimal
    Half-life, h	12-18	24-36	2.5-5	1-3
    Excretion	Renal (not removed by hemodialysis)		Renal and gastrointestinal	Renal
    Drug interaction	Synergistic CNS toxicity with antihistamines, anticholinergics, CNS stimulants	ßPlasma level: ASA§, acetaminophen	None	None
    Renal clearance	TMP-SMZ¶, triamterene, hydrochlorothiazide, quinine sulfate, quinidine	Cimetidine	None	None

    ^* HA - Hemagglutinin
    ^† NA - Neuraminidase
    ^§ ASA - Acetylsalicylic acid
    ^¶ TMP-SMZ - Trimethoprim and sulfamethoxazole
  • Amantadine hydrochloride and rimantadine hydrochloride are approved for the prevention and treatment of Influenza A virus infection; they are not active against Influenza B virus infection.
    • Both drugs are absorbed well orally, block the viral M2 protein ion channel, and inhibit the uncoating of the virus. Rimantadine is a synthetic analog of amantadine and has comparable therapeutic efficacy. Treatment with amantadine or rimantadine, given within 48 hours of the onset of symptoms, decreases the duration of fever and other symptoms by approximately 1 day in adults with uncomplicated disease. Their efficacy in patients with influenza viral pneumonia or severe influenza is unknown, but most clinicians are comfortable trying these agents in that setting.
    • Treatment with these compounds has been associated with emergence of viral resistance; the clinical significance of this is not known. Amantadine and rimantadine were not recommended by the CDC for the 2005-2006 influenza season because of resistance. Laboratory testing by CDC on the predominant strain of influenza (H3N2) currently circulating in the United States showed that it was resistant to these drugs.
  • Oseltamivir and zanamivir block the neuraminidase surface protein on both influenza A and influenza B viruses.^{17,18,19,20,21,22}
  • These drugs trap the virus inside the infected respiratory epithelial cells and prevent spread to other cells. They are active against both influenza A and influenza B viruses. These newer drugs have a different safety profile and lower potential for inducing resistance, but they are much more expensive. The results of zanamivir studies have confirmed its efficacy only if therapy is started within 24-48 hours of symptom onset in febrile patients. Most studies have reported a similar window of opportunity for oseltamivir. Like the older agents, they reduce the course of influenza by approximately 1 day. Their role in influenza pneumonia is unclear, but most clinicians would use some influenza therapy in all patients with life-threatening influenza.
  • Oseltamivir (Tamiflu) resistance has emerged in the United States during the 2008-2009 influenza season. The US Centers for Disease Control and Prevention (CDC) has issued revised interim recommendations for antiviral treatment and prophylaxis of influenza. Preliminary data from a limited number of states indicate a high prevalence of influenza A (H1N1) virus strains resistant to oseltamivir (Tamiflu). Because of this, zanamivir (Relenza) is recommended as the initial choice for antiviral prophylaxis or treatment when influenza A infection or exposure is suspected.²³ A second-line alternative is a combination of oseltamivir plus rimantadine rather than oseltamivir alone. Local influenza surveillance data and laboratory testing can assist the physician regarding antiviral agent choice.
  • Influenza A viruses, including 2 subtypes (H1N1) and (H3N2), and influenza B viruses currently circulate worldwide, but the prevalence of each can vary among communities and within a single community over the course of an influenza season. In the United States, 4 prescription antiviral medications (oseltamivir, zanamivir, amantadine, rimantadine) are approved for treatment and chemoprophylaxis of influenza. Since January 2006, the neuraminidase inhibitors (oseltamivir, zanamivir) have been the only recommended influenza antiviral drugs because of widespread resistance to the adamantanes (amantadine, rimantadine) among influenza A (H3N2) virus strains. The neuraminidase inhibitors have activity against influenza A and B viruses, while the adamantanes have activity against only influenza A viruses.
  • In 2007-2008, a significant increase in the prevalence of oseltamivir resistance was reported among influenza A (H1N1) viruses worldwide. During the 2007-2008 influenza season, 10.9% of H1N1 viruses tested in the United States were resistant to oseltamivir. Complete recommendations are available in a CDC Health Advisory.
  • Whether the newer agents are superior to amantidine/rimantidine is not clear for Influenza A virus infection, but they are effective for Influenza B virus infection while the older agents are not.
• Respiratory syncytial virus
  • As with influenza, treatment of uncomplicated RSV infection is supportive in nature.
  • Ribavirin, a nucleoside analog of guanosine, is the only effective antiviral agent currently available for the treatment of RSV pneumonia.²⁴ Ribavirin acts by interfering with viral transcription; this drug is delivered as a small-particle aerosol. Conflicting data exist regarding the efficacy of ribavirin therapy in RSV pneumonia. Recent studies have not demonstrated a beneficial effect of this drug. Current recommendations are that ribavirin therapy should be considered only for severe illness.
• Parainfluenza virus: Treatment is supportive in nature. Ribavirin has been used (without good evidence) to treat lower respiratory tract infections.
• Herpes simplex virus
  • Acyclovir inhibits viral DNA synthesis by competitively binding to viral DNA polymerase. Intravenous acyclovir (250 mg/m² q8h) currently is the treatment of choice for HSV pneumonia.
  • Because a significant proportion of patients may have concomitant bacterial pneumonia, empirical broad-spectrum antibiotic therapy that includes an antistaphylococcal drug should be instituted in patients with progressive HSV pneumonia who are unresponsive to antiviral therapy.
• Varicella-zoster virus pneumonia²⁵
  • Treatment of varicella pneumonia includes respiratory isolation until skin lesions heal, supportive care, administration of antiviral agents, and active and passive immunization.
  • For treatment of documented varicella pneumonia in patients who are immunocompromised, acyclovir (10 mg/kg IV q8h) has been shown to be effective.
• Measles pneumonia
  • Treatment of measles pneumonia generally is supportive in nature.
  • Children infected with HIV and adults who are immunosuppressed with measles pneumonia have been treated successfully with intravenous and aerosolized ribavirin, similar to the therapy for severe infections with RSV.²⁶
• Adenovirus
  • Treatment of adenovirus pneumonia primarily is supportive care.
  • Ribavirin has in vitro activity against adenoviruses and has been used in severe adenovirus pneumonia in adults. However, the efficacy has not been evaluated in controlled clinical trials.
• Cytomegalovirus
  • CMV infection and pneumonia are self-limited conditions in hosts who are immunocompetent. Treatment of CMV infection in patients who are immunocompromised has focused on prevention, acute therapy, and passive immunization.
  • The recommended treatment for acute CMV pneumonia is ganciclovir (2.5 mg/kg IV q8h for 20 d, followed by 2 wk of PO therapy at 5 mg/kg 3-5 times/wk for 20 doses). Ganciclovir prevents viral DNA replication by inhibiting the enzyme DNA polymerase.
  • High-dose intravenous immunoglobulin has been used successfully in conjunction with ganciclovir for the treatment of CMV pneumonia. Combination therapy is based on the premise that lung injury is not due solely to direct damage by the virus but is a result of the effects of a virally induced immunological reaction.
  • Foscarnet sodium, an inhibitor of viral DNA polymerase and reverse transcriptase, is an alternative drug for use in cases of ganciclovir-resistant CMV infection. Resistance to the drug frequently is encountered in patients infected with HIV who receive long-term suppressive ganciclovir therapy.
  • Cidofovir represents a third option, but few data exist regarding its use in CMV pneumonia.
• Epstein-Barr virus: No specific treatment is available for EBV infections.
• Hantavirus
  • Patients with Hantavirus pulmonary syndrome may have secondary infections from gram-positive or gram-negative organisms. Therefore, the recommendation is that these patients receive broad-spectrum antibiotic therapy.
  • The treatment of Hantavirus infection primarily is supportive in nature, aiming to correct hypoxemia, lactic acidosis, and hypotension.
  • Mechanical ventilation and optimal fluid management guided by hemodynamic monitoring are recommended.
  • Intravenous ribavirin has been used, but its efficacy has not been clearly demonstrated.
• Because most adult pneumonias are bacterial rather than viral, covering for bacterial pneumonia while awaiting a final etiologic diagnosis always is prudent.

Consultations

Patients suspected of having viral pneumonia may benefit from consultation with pulmonary and infectious diseases specialists.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Antiviral agents

Acute lower respiratory tract infection from viral etiologies can be treated with antiviral agents. Amantadine, rimantadine, zanamivir, oseltamivir, ribavirin, acyclovir, ganciclovir, and foscarnet are used. The influenza drugs may be used as either prophylactic or therapeutic agents. Hyperimmune globulin is used primarily for passive immunization in some viral illnesses.

Amantadine (Symmetrel)

Prevents penetration of virus into host by inhibiting uncoating of influenza A. Was not recommended by the CDC for the 2005-2006 influenza season because of resistance. Laboratory testing by CDC on the predominant strain of influenza (H3N2) showed that it is resistant.

Rimantadine (Flumadine)

Inhibits viral replication of Influenza A virus H1N1, H2N2, and H3N2. Prevents penetration of the virus into the host by inhibiting uncoating of influenza A. Was not recommended by the CDC for the 2005-2006 influenza season because of resistance. Laboratory testing by CDC on the predominant strain of influenza (H3N2) showed that it is resistant.

Zanamivir (Relenza)

Inhibitor of neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, release of viruses from infected cells and viral spread are decreased. Effective against both influenza A and B.
To be inhaled through Diskhaler oral inhalation device. Circular foil discs containing 5-mg blisters of drug are inserted into supplied inhalation device.

Oseltamivir (Tamiflu)

Inhibits neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys an infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, decreases release of viruses from infected cells and thus viral spread. Effective for treatment of influenza A or B infection. Start within 40 h of symptom onset.
Oseltamivir (Tamiflu) resistance has emerged in the United States during the 2008-2009 influenza season. The US Centers for Disease Control and Prevention (CDC) has issued revised interim recommendations for antiviral treatment and prophylaxis of influenza. Preliminary data from a limited number of states indicate a high prevalence of influenza A (H1N1) virus strains resistant to oseltamivir (Tamiflu). Because of this, zanamivir (Relenza) is recommended as the initial choice for antiviral prophylaxis or treatment when influenza A infection or exposure is suspected. A second-line alternative is a combination of oseltamivir plus rimantadine rather than oseltamivir alone. Local influenza surveillance data and laboratory testing can assist the physician regarding antiviral agent choice.

Ribavirin (Virazole)

Inhibits viral replication by inhibiting DNA and RNA synthesis. In vitro antiviral against RSV, parainfluenza, Hanta virus, measles, and many others.

Palivizumab (Synagis)

Humanized monoclonal antibody directed against the F (fusion) protein of RSV. Given monthly through the RSV season, it has been demonstrated to decrease the chances of RSV hospitalization in premature babies who are at increased risk for severe RSV-related illness.

Acyclovir (Zovirax)

Inhibits activity of both HSV-1 and HSV-2. Has affinity for viral thymidine kinase and, once phosphorylated, causes DNA chain termination when acted on by DNA polymerase. Patients experience less pain and faster resolution of HSV or VZV lesions when used within 24-48 h of rash onset. Early initiation of therapy is imperative.

Ganciclovir (Cytovene, Vitrasert)

Synthetic guanine derivative active against CMV, HSV, HHV-6, and HHV-8. An acyclic nucleoside analog of 2'-deoxyguanosine that inhibits replication of herpesviruses both in vitro and in vivo. Levels of ganciclovir-triphosphate are as much as 100-fold greater in CMV-infected cells than in uninfected cells, possibly due to preferential phosphorylation of ganciclovir in virus-infected cells. An oral prodrug, valganciclovir, is now available.

Foscarnet (Foscavir)

Organic analog of inorganic pyrophosphate that inhibits replication of known herpesviruses, including CMV, HSV-1, and HSV-2. Inhibits viral replication at pyrophosphate-binding site on virus-specific DNA polymerases. Poor clinical response or persistent viral excretion during therapy may be due to viral resistance. Patients who can tolerate foscarnet well may benefit from initiation of maintenance treatment at 120 mg/kg/d early in treatment. Individualize dosing based on renal function status.

Immune globulin IV (Gamimune, Gammagard, Sandoglobulin, Gammar-P)

Neutralizes circulating myelin antibodies through antiidiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T cells and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).

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