Antimicrobial therapy and antiviral Agents

Empiric treatment

Refers to the initiation of medical therapy before a definitive diagnosis is made, based on the most likely cause of a patient's condition

Antimicrobial Terminology

•Bacteriostatic - suppresses organism growth

•Bactericidal - directly destroys organism

•Post antibiotic effect - organisms do not grow for several hours even after discontinuation of medication

•Selective toxicity - ability of medications to affect target organisms only without harming host cells

•Narrow spectrum - active against only a few species of microorganisms

•Broad spectrum - active against a wide variety of microorganisms

•Empiric therapy - therapy started in absence of laboratory data

•Minimum inhibitory concentration - lab measure of lowest drug concentration needed to prevent growth of certain bacteria

•Peak - measurement of highest drug concentrations

•Trough - measurement of lowest drug concentrations

Acyclovir (Zovirax) MOA/Uses

MOA: Inhibits viral replication by suppressing synthesis of viral DNA

Indications

• Topical for HSV1

• PO for HSV2 and VZV

• IV for either in immunocompromised patients

Acyclovir (Zovirax) AE/Nursing considerations

Adverse Effect:

•Can take without regards to meals

•Phlebitis  and inflammation with IV therapy

•Nephrotoxicity (elevated Crt and BUN)

Neurotoxicity (agitation, delirium, tremors)

Nursing consideration:

•Viral resistance to therapy

•Monitor renal function & fluid status

•Monitor neuro status

•Only decreases s/s in genitalis; avoid sexual contact when lesions present and use protection

•Use finger cot/rubber glove with topical

•Valcyclovir represents a more effective way to get acyclovir in the body

Cytomegalovirus (CMV) infection

very common and is transmitted through direct contact with infected bodily fluids, including saliva, urine, blood, tears, breast milk, and semen. Manifestations are usually only seen in immunocompromised patients (e.g. HIV, chemotherapy, immunosuppressive agents).

Ganciclovir (Cytovene) MOA/Uses

MOA:

•Inhibits viral replication by suppressing synthesis of viral DNA and incorporating it into the chain causing chain termination

Indications:

•Prevention & treatment of CMV infection in immunocompromised pts

Ganciclovir (Cytovene) *AE/Nursing considerations

*Adverse Effect:

•Granulocytopenia

•Thrombocytopenia

•Teratogenic

Nursing consideration:

•Monitor complete blood count for changes in WBC and PLT

•Coadministration with G-CSF; administer PO with food

•Education on contraception

Interferon Alfa MOA/Uses

•Conventional therapy SQ/IM 3 times/week

Long acting therapy SQ once/week

MOA:

•Blocks viral entry into cells

•Blocks synthesis of viral messenger RNA and viral proteins

Blocks viral assembly and release

Indications:

•HCV and HBV

*Interferon Alfa AE/Nursing considerations

Adverse Effect:

•Most common are flu-like s/s

•Neuropsychiatric

•Bone marrow suppression with long term

Nursing consideration:

•Acetaminophen PRN for flu-like s/s

•Monitor mental status

•Monitor complete blood count

•Monitor hepatitis s/s and liver enzymes

Simeprevir (Olysio) MOA/Uses

•Not indicated as monotherapy - only used in combination with other agents

•Protease inhibitor class medication

MOA:

•Inhibit viral protease, enzyme needed for HCV replication

Indications:

HCV

Simeprevir (Olysio) AE/Nursing considerations

Adverse Effect:

•Most common are HA, nausea, and fatigue

•Hepatic injury

•Photosensitivity (wear sunscreen)

•Rash

Nursing consideration:

•Monitor hepatitis s/s and liver enzymes

•Caution with sulfa allergies and amiodarone

Daclatasvir (Daklinza) MOA/Uses

•NS5A inhibitor class medication as part of anti-HCV regimens

MOA:

Inhibit NS5A proteins that is necessary for replication and assembly to prevent formation of HCV

Indications:

HCV

*Daclatasvir (Daklinza) AE/Nursing considerations

Adverse Effect:

•Most common are HA and fatigue

•Possible anemia

Nursing consideration:

•Monitor hepatitis s/s and liver enzymes

•*Due to numerous drug interactions, educate patient on not starting new medications without counseling first

Ribavirin (Rebetol) MOA/Uses

•Never used as monotherapy - only effective when combined with interferon alfa

MOA:

•Unclear, but increases patient response to interferon alfa

Indications:

HCV sometimes with HBV as well

Ribavirin (Rebetol) AE/Nursing considerations

Adverse Effect:

•Interferon alfa s/s

•Hemolytic anemia

•Fetal injury

Nursing consideration:

•Monitor mental status

•Monitor complete blood count

•Monitor hepatitis s/s and liver enzymes

Extended use of contraception due to prolonged half-life

Lamivudine (Epivir) MOA/Uses

MOA:

_{suppresses HBV replication by inhibiting viral DNA synthesis}

Indications:

•_{Nucleoside analog used to treat HBV}

Lamivudine (Epivir) AE/Nursing considerations

Adverse Effect:

•_{Lactic acidosis}

•_Pancreatitis

•_Hepatomegaly

Nursing consideration:

•_{Give lowest dose possible to patients who is HIV positive}

•_{Monitor amylase and lipase}

•_{Monitor ABGs}

•_{Educate patient to take medication as prescribed because there is increased relapse after stopping it.}

Oseltamivir (Tamiflu) MOA/Uses

MOA:

inhibits neuraminidase to prevent viral replication and prevents newly formed viral particles from spreading to other cells

Does not keep you from getting the flu, it just decreases the s/s

Indications:

Antiviral for the flu

Oseltamivir (Tamiflu) AE/Nursing considerations

Adverse Effect:

•Generally well-tolerated but better if taken with food

•Most common is N/V

Hypersensitivity (rash) & neuropsychiatric s/s are rare

Nursing consideration:

•Rapid flu testing, possibly before to confirm diagnosis

•Carefully assess for vaccination history and onset of s/s (within 48 hrs)

•Educate patients to monitor allergic reaction s/s, particularly with integumentary system

Baloxavir Marboxil (Xofluza) MOA/Uses

MOA:

Endonuclease inhibitor  that is converted to to baloxavir  which inhibits protein activity for viral gene transcription

Indications:

Antiviral flue A

*Baloxavir Marboxil (Xofluza) AE/Nursing considerations

Adverse Effect:

•Uncommon

•Don’t administer with salts (calcium, iron, magnesium)

Nursing consideration:

•Administration with the LAIV may decrease the effectiveness of the vaccine

•Take within 48 hours of symptom onset

Palivizumab (Synagis) MOA/Uses

MOA:

•antibody binds to surface protein on RSV and prevents replication.

Indications:

•preventing RSV infection

Palivizumab (Synagis) AE/Nursing considerations

Adverse Effect:

•Hypersesnstivity reactions

•Anaphylaxis (rare)

Nursing consideration:

•Use appropriate IM administration techniques

•Use caution with mild hypersensitivity reactions

•Discontinue with severe hypersensitivity reactions

HIV Clinical Progression Phases

Initial phase marked by viral replication and flu-like s/s. Middle phase is typically asymptomatic for ten years as CD4 counts slowly decrease. Late phase (AIDS) characterized by CD4 counts < 200 and onset of opportunistic infections.

Abacavir (Ziagen) MOA/Uses

•PO Nucleoside reverse transcriptase inhibitor (NRTI) class antiviral medication

MOA:

- NRTI that inhibit HIV replication by suppressing synthesis of DNA through acting as substrates for reverse transcriptase

AE/Nursing considerations

*Adverse Effect:

•Lactic acidosis (hyperventilation) & hepatic steatosis r/t mitochondrial toxicity

•Possible evidence for increased risk for MI

Hypersensitivity

Nursing consideration:

•Genetic testing for HLA-B*5701

•Monitor cardiac and LA s/s

•Use of safe practices to prevent transmission

•Other first-line NRTI include lamivudine, tenofovir, & emtricitabine

Efavirenz (Sustiva) MOA/Uses

•PO Non-nucleoside reverse transcriptase inhibitor (NNRTI) class antiviral medication

MOA:

•NNRTI that inhibit HIV replication by suppressing synthesis of DNA through binding to active center of reverse transcriptase enzyme

Indications:

HIV

Efavirenz (Sustiva) AE/Nursing Considerations

Adverse Effect:

•CNS symptoms

are common

•Rash

•Teratogenicity

Nursing consideration:

•Numerous drug interactions, including those for HIV

•Taking med at hs on empty stomach can reduce CNS symptoms

•Educate on CNS symptoms and rash

Darunavir (Prezista) MOA/Uses

•PO Protease inhibitor class antiviral medication

MOA:

dorunavir inhibits protease, an enzyme needed for HIV virion maturation, leaving virus immature and noninfectious; ritonavir helps boost lopinavir’s effects as well as being combined with other medications

Indications:

HIV

Darunavir (Prezista) AE/Nursing Considerations

Adverse Effect:

• •Most common is N/D/HA

• •Rash due to sulfa drugs

• •Hyperglycemia occurs much less compared to other PIs

• •Lipodystrophy and hyperlipidemia

• •Can increase serum levels of other antiretrovirals (abacavir)\

• •Drug interactions with HCV medications and antidysrhythmic

Nursing consideration:

• •Virus less resistant to drug combination

• •Stable at room temperature for short-term; put in refrigerator for long-term

• •Educate patients on lipid control and low cholesterol diet

Raltegravir (Isentress) MOA/Uses

•PO Integrase strand transfer inhibitor (INSTI) class antiviral medication

MOA:

•inhibit integrase, an enzyme needed for HIV replication, by preventing insertion into host DNA

Indications:

HIV (first choice drug)*

Raltegravir (Isentress) AE/Nursing Considerations

Adverse Effect:

•Generally well tolerated

•Elevated liver enzymes *

•Skin hypersensitivity reactions rare

Viral medication resistance more common

Nursing consideration:

•Assess for hepatic injury and trend LFT *

•Instruct patients to report skin manifestations and stop med immediately

•Other first-line INSTI is dolutegravir

Enfuvirtide (Fuzeon) MOA/Uses

•SQ fusion inhibitor class antiviral medication indicated for infections resistant to other initial treatments

MOA:

Blocks HIV entry into CD4 T cells by preventing fusion of the HIV lipid bilayer with the CD4 T cell’s lipid bilayer through binding of medication to glycoprotein in HIV envelope

Indications:

HIV

Enfuvirtide (Fuzeon) AE/Nursing Considerations

Adverse Effect:

•SQ injection site reactions

•Pneumonia s/s

Hypersensitivity reactions

Nursing consideration:

•Medication administration technique

•Monitor respiratory and integumentary systems

Maraviroc (Selzentry) MOA/Uses

•PO CCR5 antagonist class antiviral medication indicated for infections resistant to other initial treatments

MOA: •CCR5 antagonist that blocks HIV entry into CD4 T cells by binding with CCR5, a co-receptor needed for entry

Indications:

HIV

Maraviroc (Selzentry) AE/Nursing Considerations

Adverse Effect:

•Hepatic injury

•Possible increased risk for CV events, including MI

Nursing consideration:

•Educate and assess for liver injury

•Assess CV status

•CCR5 tropism assay is performed first to determine if use is appropriate

Cabotegravir/Rilpilvirine (Cabenuva) MOA/Uses

•Single dose gluteal IM injection given once monthly every month or every 2 months.

INSTI and NNRTI

MOA:

inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration that is essential for the HIV replication cycle

Indications:

HIV-1 infection in adults and adolescents 12 years of age and older

Cabotegravir/Rilpilvirine (Cabenuva) AE/Nursing Considerations

Adverse Effect:

•Hypersensitivity reactions

•Post injection reactions

•Hepatotoxicity

Depressive disorders

Nursing consideration:

•Administer each injection at separate gluteal injection sites

•A complete dose requires 2 injections

•Allow 15 minutes for the medicine to become room temperature.

•May remain in a syringe for 2 hours.

•Patient education on adverse reactions and signs and symptoms

Emtricitabine and Tenofovir Alafenamide (Descovy) MOA/Uses

PO combination NRTI and NNRTI

MOA:

•same as NRTI and NNRTI

Indications:

prevention and  treatment of HIV 1

Emtricitabine and Tenofovir Alafenamide (Descovy) AE/Nursing Considerations

Adverse Effect:

•Nausea

•Diarrhea

Nursing consideration:

•Educate patients report AE to provider

•Educate patient on adherence

•Can not use alone for a patient with a positive status.

•HIV tests every 6 months

Management of HIV Infection

●Initial phase needs 3-4 medications due to high viral load

●Middle phase treatment is when resistance can develop, but continued treatment helps to decrease viral load, boost immune system, and delay AIDS onset

●Late phase may use medications from other classes, including PI, NNRTI, & HIV fusion inhibitors

CD4 count, HIV viral load, & resistance testing help track patient’s response to therapy. HLA-B*5701 and tropism assist in choosing specific medications

Nirmatrelvir & ritonavir (Paxlovid)

MOA:

●Nirmatrelvir acts as a protease inhibitor, with ritonavir increasing nirmatrelvir’s plasma concentrations via metabolism inhibition

Indications:

●Oral therapy indicated for symptomatic, nonsevere COVID-19 infection with risk factors for the development of severe COVID-19 infection

Nirmatrelvir & ritonavir (Paxlovid) AE/Nursing Considerations

Adverse Effect:

○Hypertension

○Diarrhea, impaired or altered sense of taste

○Myalgia

Rebound COVID-19 infection

Nursing consideration:

○Patient education on medication regimen (twice daily x 5 days) and adherence

○Numerous drug interactions; thoroughly assess medication usage during the patient interview

○Risk of HIV resistance if a patient has an uncontrolled or undiagnosed infection

Molnupiravir (Lageviro) MOA/Uses

MOA:

●Oral therapy indicated for symptomatic, nonsevere COVID-19 infection with risk factors for development of severe COVID-19 infection

Indications:

Once metabolized and phosphorylated, it is incorporated into viral RNA polymerase resulting in viral genome errors and replication inhibition

Molnupiravir (Lageviro) AE/Nursing Considerations

Adverse Effect:

○Erythema, rash, urticaria

○Hypersensitivity, including anaphylaxis, angioedema

Nursing consideration:

○Alternative outpatient option for those who cannot take Paxlovid

○Patient education on medication regimen (twice daily x 5 days) and adherence

○Not commercially available; current use is under EUA from AmerisourceBergen

○Capsules can be administered with or without food; do not crush, open, or break

Remdesevir (Veklury) MOA/Uses

●IV SARS-CoV-2 nucleotide analog RNA polymerase inhibitor class medication

MOA:

- inhibits RNA polymerase, which is necessary for viral replication, by acting as an ATP analog which results results in delayed chain termination during replication

Indications:

●Indicated for COVID-19 infection requiring hospitalization & supplemental oxygen in adults and pediatric patients aged 12 or older and weighing at least 40 kg

Remdesevir (Veklury) AE/Nursing Considerations

Adverse Effect:

●Potentially severe bradycardia

○Elevated ALT and AST levels

○Hypersensitivity reactions resulting in anaphylaxis, angioedema, rash, etc.

○Prolonged prothrombin time

Nursing consideration:

○Monitor CMP and RUQ s/s

○Although unlikely, monitor renal function for impairment for duration of therapy

○Discontinue infusion and provide appropriate interventions if hypersensitivity reactions occur

*BNT162b2 (Pfizer-BioNTech COVID-19 Vaccine) MOA/Uses

MOA:

After delivery of lipid nanoparticle, RNA is translated to express full-length spike protein to elicit a systemic immune response to produce immunity

Indications:*

●Two-dose IM mRNA vaccine for prevention of symptomatic COVID-19 at or after day 7 following the second dose (95% efficacy)

*BNT162b2 (Pfizer-BioNTech COVID-19 Vaccine) AE/Nursing Considerations

Adverse Effect:

○Injection site soreness

○Fever, chills, fatigue, headache, & lymphadenopathy within 24-48 hours

○Anaphylaxis, very rarely; milder allergic reactions

Nursing consideration:

○Patient education, including duration of protection and time between doses (21 days)

○Careful preparation to maximize doses per vial and appropriate amount of diluent (1.8 mL of NS; 0.3 mL administered per dose)

○Once reconstituted, must be used within 6 hours

○Intramuscular injection soreness can be treated with OTC analgesics

○Monitor patients for 15 minutes post-administration

*mRNA-1273 (Moderna COVID-19 Vaccine) MOA/Uses

MOA:

●After delivery of lipid nanoparticle, RNA is translated to express full-length spike protein to elicit a systemic immune response to produce immunity

Indications:

●Two-dose IM mRNA vaccine for prevention of symptomatic COVID-19 at or after day 7 following the second dose (94.1% efficacy)

*mRNA-1273 (Moderna COVID-19 Vaccine) AE/Nursing Considerations

Adverse Effect:

○Injection site soreness

○Fever, chills, fatigue, headache, myalgia, arthralgia

○Anaphylaxis, very rarely; milder allergic reactions also reported

Nursing consideration:

○Patient education, including duration of protection and time between doses (28 days)

○Careful preparation to maximize doses per vial

○Once vial is punctured, must be used within 6 hours

○Intramuscular injection soreness can be treated with OTC analgesics

○Monitor patients for 15 minutes post-administration