7.2: Antibiotic, Antiviral/Anti–COVID-19, and Antifungal Drugs
By the end of this section, you should be able to:
- 7.2.1 Identify the characteristics of drugs used to treat infection.
- 7.2.2 Discuss antibiotic drug resistance.
- 7.2.3 Explain the indications, actions, adverse reactions, and interactions of drugs used to treat infection.
- 7.2.4 Describe the nursing implications of drugs used to treat infection.
- 7.2.5 Explain the client education related to drugs used to treat infection.
Antibiotics and Infection
Antibiotics are a group of drugs used specifically to treat infections caused by bacteria, either by directly killing the bacteria ( bactericidal ) or by suppressing their growth and multiplication ( bacteriostatic ). Antibiotics are some of the most commonly prescribed medications in the world; therefore, careful stewardship is necessary to avoid overuse, which can lead to antibiotic resistance.
Antibiotic Drug Resistance
Antibiotic drug resistance is the process by which bacteria become less responsive to antibiotics over time. As bacteria are exposed to antibiotics, evolutionary changes occur, leading to the development of resistant strains that can withstand the antibiotic exposure and continue to thrive. These changes can include modification of antibiotic targets (e.g., bacterial DNA or proteins) or the ability to remove a drug from the bacterial cell more effectively. Some bacteria are even able to share snippets of DNA that code for drug resistance with other bacteria.
Antibiotic resistance is a major public health issue. Having fewer options to treat a client’s infection leads to worsened morbidity and mortality, higher health care costs, and the potential for bacteria to develop against which effective treatment does not exist. Superinfections can occur when the use of broad-spectrum antibiotics kills off normal nonpathogenic bacteria and leaves behind drug-resistant bacteria that can produce a new infection that is more difficult to treat (Figure 7.3). Most antibiotic drug resistance occurs due to antibiotic overuse, both in humans and in agriculture. This is why health care providers should prescribe antibiotics only when there is sufficient probability that the client has a bacterial infection.
Adverse Effects and Contraindications
Most oral antibiotics can cause gastrointestinal discomfort, including nausea, vomiting, and diarrhea. A contraindication to any antibacterial is known hypersensitivity.
Allergic reactions, including anaphylaxis, are possible with penicillins. If a client has a severe allergy to any penicillin, then they should not receive any other drug in the penicillin class because they may experience a cross-sensitivity.
Most cephalosporins, except for ceftriaxone, must be renally dose adjusted to avoid adverse effects in clients with renal insufficiency. For many years there was concern that clients with a penicillin allergy could not receive cephalosporins due to risk for cross-reactivity and anaphylaxis. More recent data have shown that this concern is unfounded and that the largest risk is for clients with true anaphylactic reactions to penicillins receiving a first-generation cephalosporin. Later generations of cephalosporins carry a much lower risk and are safe to administer to clients with a history of penicillin allergy.
Macrolides are known to cause gastrointestinal discomfort because they activate motilin receptors in the intestines, which increases peristalsis, cramping, and diarrhea. Macrolides are also capable of inhibiting potassium efflux out of myocardial cells, leading to prolongation of the heart rate–corrected QT interval (QTc) on an electrocardiogram (ECG/EKG) and increasing the client’s risk for developing torsades de pointes, a potentially fatal ventricular dysrhythmia.
Vancomycin is known to cause a severe flushing reaction when given too quickly intravenously, known as vancomycin flushing syndrome. Vancomycin flushing syndrome can be mistaken for an allergic reaction, but all that is necessary to manage it is to slow the infusion of vancomycin and infuse it over at least 60 minutes. Elevated vancomycin levels are associated with risk for renal injury and hearing damage (ototoxicity). Older adults and those who are critically ill are especially at risk, so close monitoring of renal function and vancomycin blood levels is critical for successful use of the drug.
Unique adverse effects seen with tetracyclines include photosensitivity, skin discoloration, and risk for skeletal growth stunting and tooth discoloration. These last two effects occur because of the tetracyclines’ ability to bind to calcium in developing bones and teeth. Recommendations to help prevent these effects include avoiding prolonged therapy (more than 21 days) in children who still have their baby teeth and avoiding use in pregnant clients during the second and third trimesters. Oral tetracyclines should not be taken with multivitamins or calcium-containing products. When taken together, tetracyclines will bind to metal ions such as iron and calcium, and the drug will not be absorbed; instead, it will be eliminated in the feces, leading to therapeutic failure.
Fluoroquinolones have a variety of safety issues, making screening for contraindications particularly important. In older adults and in clients with poor kidney function, fluoroquinolones are known to induce neuropsychiatric issues, including hallucinations and psychosis. Fluoroquinolones also increase the risk for tendonitis and tendon rupture. Fluoroquinolones can increase the QTc interval on ECG, which should be monitored for clients taking multiple QTc-prolonging medications and for those with congenital prolonged QTc to reduce risk for torsades de pointes. Fluoroquinolones should not be taken orally with multivitamins or calcium-containing products because this will cause the drug to bind to the metal and not be absorbed.
Table 7.2 is a drug prototype table for antibiotics featuring amoxicillin. It lists drug class, mechanism of action, adult and pediatric dosage , indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Aminopenicillin Mechanism of Action Inhibits bacterial cell wall synthesis, leading to bacterial cell lysis |
Drug Dosage
Adults: 500 mg orally every 12 hours. Children: 80–90 mg/kg/day orally divided every 12 hours. |
|
Indications
Treatment of infections due to susceptible organisms ( only beta-lactamase-negative) Therapeutic Effects Treats infections caused by susceptible organisms |
Drug Interactions
Aminoglycosides Methotrexate Tetracyclines Probenecid Mycophenolate Food Interactions No significant interactions |
|
Adverse Effects
Nausea Vomiting Diarrhea Hypersensitivity Crystalluria Anemia Thrombocytopenia |
Contraindications
Hypersensitivity Caution: Renal impairment |
Nursing Implications
The nurse should do the following for clients who are taking antibiotics:
- Monitor for signs and symptoms of anaphylaxis (e.g., shortness of breath, difficulty breathing, difficulty swallowing).
- Advise the client to take the entire prescribed course of the medication to ensure adequate treatment and to reduce the development of antibiotic drug resistance.
- Instruct the client to maintain adequate hydration; monitor kidney function for renally eliminated medications, such as penicillins, most cephalosporins, vancomycin, aminoglycosides, and particularly fluoroquinolones.
- For clients taking macrolides, always review their medication list for medications metabolized by CYP3A4.
- Monitor for thrombocytopenia, leukopenia, and anemia in clients receiving linezolid. Monitor complete blood count (CBC) periodically. Notify prescriber if blood counts drop.
- If client is taking any medication that can increase serotonin levels (SSRIs, SNRIs, or MAOIs), the nurse should observe for signs of serotonin syndrome, including hyperthermia, headache, confusion, agitation, increased blood pressure, tachycardia, tremor, ataxia, muscle rigidity, and seizures.
- Ensure that any ordered samples for serum levels of agents such as vancomycin and aminoglycosides are obtained at the intended time so that accurate dosage adjustments can be made. Timing may include peak levels drawn after a dose of the antibiotic has been given or trough levels drawn immediately before a dose.
- Monitor for severe or bloody diarrhea and, if ordered, obtain a sample to check for C. difficile .
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking an antibiotic should:
- Alert their health care provider about any signs and symptoms of allergic reactions, including throat swelling, severe itching, rash, or chest tightness.
- Alert their health care provider about any recent antibiotic use prior to starting therapy.
- Alert their health care provider that they are taking antibiotics, including the dose and frequency.
- Take the drug with food if it causes an upset stomach.
- Take the entire course of antibiotics, even if they begin to feel better.
- Take a missed dose as soon as they remember; however, they should not take double doses.
The client taking an antibiotic should not:
- Take multivitamins or calcium-containing products with fluroquinolone or tetracycline drugs.
FDA Black Box Warning
Antibacterials
All antibacterials: Clostridioides difficile –associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile .
Aminoglycosides can cause neurotoxicity, manifested by ototoxicity, both vestibular and auditory. This can occur in clients treated with gentamicin, primarily in those with preexisting renal damage and in clients with healthy renal function treated with higher doses and/or for longer periods than recommended. Aminoglycoside-induced ototoxicity is usually irreversible. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. Monitor serum concentrations of aminoglycosides when feasible to ensure adequate levels and to avoid potentially toxic levels.
Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including tendinopathy and tendon rupture, peripheral neuropathy, and central nervous system effects. Discontinue ciprofloxacin immediately and avoid the use of fluoroquinolones in clients who experience any of these serious adverse reactions. Because fluoroquinolones have been associated with serious adverse reactions, ciprofloxacin is reserved for use in clients who have no alternative treatment options for the following indications: acute exacerbation of chronic bronchitis, acute sinusitis, and acute uncomplicated cystitis.
Fluoroquinolones also may exacerbate muscle weakness in clients with myasthenia gravis. Avoid ciprofloxacin in clients with known history of myasthenia gravis.
Vancomycin: A formulation of this injection contains the excipients polyethylene glycol (PEG 400) and N-acetyl D-alanine (NADA), which resulted in fetal malformations in animal reproduction studies at dose exposures approximately 8 and 32 times, respectively, higher than the exposures at the human equivalent dose. If use of vancomycin is needed during the first or second trimester of pregnancy, use other available formulations of vancomycin.
Viruses and Antiviral Drugs
Compared to bacteria, viruses are simple microorganisms made up of single or double strands of DNA or RNA inside a cellular coating known as a capsid. Viruses are unique in that they are unable to replicate on their own. Instead, a virus will harness the host’s cellular mechanisms to make new copies of itself to then infect other cells. Most viral infections (e.g., adenoviruses, rhinoviruses) are minor and self-limited, meaning they rarely require drug therapy. More serious viral infections, including those caused by the hepatitis viruses, pose much more significant risks to clients and require specific antiviral therapy. Clients at risk for more serious viral infections include individuals at the extremes of age (i.e., the very young and the very old) and those who are immunocompromised.
The following section covers the common antiviral drugs used to treat a variety of viral infections, including those caused by hepatitis, herpes, and influenza viruses. The mechanisms of action, drug interactions, adverse effects, and indications are discussed, including special considerations for use.
Hepatitis Antivirals
Hepatitis viruses are clinically important because they can cause inflammation and damage to the liver. The three main types are hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). HAV infection is usually self-limited, with many individuals being able to rid themselves of it without any intervention. HBV and HCV infections are of more clinical concern because without intervention, many clients will develop chronic infection, which can lead to cirrhosis, liver failure, and risk for liver cancer. HAV is spread via the fecal–oral route, and HBV and HCV are usually spread through parenteral transmission (such as by sharing contaminated needles) and during sexual intercourse. Vaccines can prevent HAV and HBV infections.
Medications to treat chronic HBV infection are not always curative and are used with the goal of preventing complications such as cirrhosis and liver cancer. HBV infection is typically managed with nucleoside/nucleotide antivirals, which include entecavir, tenofovir, lamivudine, adefovir, and telbivudine. These drugs work against viral DNA polymerase, an enzyme critical for DNA production and viral replication. They are incorporated into the viral DNA and function as “chain terminators,” meaning that no other nucleotides may be added onto them in the chain of DNA, and DNA production is thereby halted. Another treatment option is interferon (interferon alfa); however, due to toxicity, this medication is considered a last resort when all else fails.
HCV infection previously was a chronic disease with no definitive cure and consisted of treatment with parenteral medications with poor tolerability (e.g., interferons). This condition has radically changed, and now many clients with HCV can achieve virologic cure (no presence of the virus in the body) with 12–24 weeks of oral drug therapy using a direct-acting antiviral (DAA) agent such as sofosbuvir. The DAAs can work on a variety of steps in the HCV life cycle to prevent replication or transmission of active virus. Nurses should stress to clients that they must take the entire course of their DAA regimen because resistance can develop if the virus is not completely suppressed. More resistant cases may require treatment with the injectable drug ribavirin, the action of which is not currently understood.
Herpes Antivirals
Two main types of herpes viruses are responsible for causing clinically significant disease. Herpes simplex virus (HSV)-1 is usually responsible for causing lesions (e.g., cold sores) on the mouth, face, and skin. HSV-2 is usually responsible for infections in the genitals and rectum. No curative therapy for HSV-1 or HSV-2 currently exists, but medication is useful to reduce the duration and severity of symptoms a client experiences and to help prevent spread of the virus to other individuals. Agents used to treat herpes viruses include acyclovir and its oral prodrug, valacyclovir, as well as famciclovir. Ganciclovir, valganciclovir, and cidofovir also have activity against herpes viruses, but due to multiple adverse effects, they are reserved for cases of resistance to the first-line agents. These agents work by inhibiting the formation of new viral DNA by acting as chain terminators.
Clients with herpes virus infections may take these medications either when symptoms occur (episodic therapy) or every day for chronic suppression. Chronic suppression is linked to lower incidence of transmission of the virus to uninfected individuals and is useful for clients who have multiple outbreaks each year. Clients using the episodic method must be instructed to begin taking their therapy within 24 hours of symptom onset for the medication to be effective. They should also be informed that viral shedding can occur even without an active lesion, which may increase transmission risk.
Influenza Antivirals
Influenza refers to a diverse set of viruses known to cause upper respiratory tract illnesses, most commonly in the winter months. Annual vaccination will not prevent all infections but may help reduce the symptoms that individuals experience, and it is critical for protecting people most at risk for complications, such as older adults and immunocompromised individuals. However, vaccines are able to protect against only four strains each year with the current quadrivalent vaccines, which protect against two strains of influenza A and two of influenza B. This means that many people still go on to develop influenza infections that require treatment with medications.
The primary class of drugs used to treat influenza infection includes the neuraminidase inhibitors oseltamivir, zanamivir, and peramivir. Neuraminidase inhibitors work by inhibiting the enzyme neuraminidase, which is used to cleave mature copies of the virus from an infected cell to allow it to go infect other cells. Inhibiting this enzyme prohibits the virus from infecting host cells. If the client has had flulike symptoms for more than 48 hours, neuraminidase inhibitors should not be used due to lack of efficacy.
Oseltamivir is considered the first-line option for treatment of influenza and is given orally over 5 days. Zanamivir is an inhaled neuraminidase inhibitor that can be used as an alternative to oral oseltamivir. Peramivir is the only intravenous neuraminidase inhibitor and should be reserved for clients who cannot take oral or inhaled medications.
Table 7.3 lists common antivirals and typical routes and dosing for adult and pediatric clients .
| Drug | Routes and Dosage Ranges |
|---|---|
|
Acyclovir
( Zovirax ) |
Herpes simplex virus, mucocutaneous infection:
Adults: Oral: 400 mg 3 times daily for 7–10 days. IV: 10 mg/kg/dose every 8 hours for 7 days. Children: Oral: 40–80 mg/kg/day divided into 3–4 doses per day for 7–10 days; maximum dose: 1200 mg/day. IV: 5 mg/kg/dose every 8 hours for 7 days. |
|
Oseltamivir
( Tamiflu ) |
Influenza: 75 mg orally twice daily for 5 days. |
|
Sofosbuvir
( Sovaldi ) |
Chronic hepatitis C virus infection: 400 mg orally once daily for 16 weeks. |
|
Tenofovir
( Viread ) |
Hepatitis B virus infection: 300 mg orally once daily for 28 days. |
Adverse Effects and Contraindications
Antiviral agents are known to cause gastrointestinal discomfort, including nausea, vomiting, and diarrhea. A contraindication to any antiviral drug is known hypersensitivity.
The nucleoside/nucleotide analogs used to treat HBV infection are considered safer than interferon products, but individual agents may be linked to serious complications such as entecavir-induced lactic acidosis and adefovir-induced nephrotoxicity.
Side effects of herpes antivirals are mild but can include blood cell production suppression, malaise, and risk for renal injury.
Zanamivir is given via inhalation and should not be used in clients with a history of asthma or chronic obstructive pulmonary disease due to risk for bronchospasm (tightening of the airways).
Table 7.4 is a drug prototype table for antivirals featuring acyclovir. It lists drug class, mechanism of action, adult and pediatric dosage , indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Antiviral agent Mechanism of Action Inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA |
Drug Dosage
Herpes simplex virus, mucocutaneous infection: Adults: Oral: 400 mg 3 times daily for 7–10 days. IV: 10 mg/kg/dose every 8 hours for 7 days. Children: Oral: 40–80 mg/kg/day divided into 3–4 doses per day for 7–10 days; maximum dose: 1200 mg/day. IV: 5 mg/kg/dose every 8 hours for 7 days. |
|
Indications
Treatment of infections due to susceptible viruses (e.g., herpes simplex virus, cytomegalovirus) Therapeutic Effects Treats viral infections caused by susceptible organisms |
Drug Interactions
Clozapine Theophylline Tizanidine Zidovudine Food Interactions No significant interactions |
|
Adverse Effects
Nausea Vomiting Diarrhea Hypersensitivity Crystalluria Malaise Increased serum creatinine/acute kidney injury |
Contraindications
Hypersensitivity Caution: Intravenous injection extravasation Renal impairment |
Nursing Implications
The nurse should do the following for clients who are taking antivirals:
- Monitor for signs and symptoms of anaphylaxis (e.g., shortness of breath, difficulty breathing, difficulty swallowing).
- Advise the client to take the entire prescribed course of the medication to ensure adequate treatment and to reduce the development of drug resistance.
- Instruct the client to maintain adequate hydration; monitor kidney function for renally eliminated antivirals such as acyclovir and valacyclovir.
- Monitor the client’s complete blood count to check for bone marrow suppression.
- Monitor for mental status changes in clients receiving intravenous antivirals who have poor renal function.
- For clients using antiviral medication episodically, teach them to begin taking it as soon as possible after symptom onset.
- Use appropriate personal protective equipment (e.g., mask and gloves) when clients are diagnosed with influenza to prevent infection spread.
- Check a pregnancy test in clients capable of pregnancy prior to initiating antiviral therapy.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking an antiviral should:
- Alert their health care provider about any signs of allergic reactions, including throat swelling, severe itching, rash, or chest tightness.
- Alert their health care provider about any recent antiviral use prior to starting therapy.
- Alert their health care provider that they are taking these medications, including the dose and frequency.
- Take the drug with food if it causes an upset stomach.
- Take a missed dose as soon as they remember; however, they should not take double doses.
- For episodic use, begin taking the antiviral as soon as possible (within 24 hours of symptom onset) to reduce symptom duration.
- Stay well hydrated while using these medications to avoid kidney issues.
FDA Black Box Warning
Antivirals
Ganciclovir: Granulocytopenia, anemia, thrombocytopenia, and pancytopenia have been reported with ganciclovir.
Ganciclovir: Based on animal data and limited human data, ganciclovir may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females, may cause birth defects in humans, and has the potential to cause cancer in humans.
Cidofovir: Renal impairment is the major toxicity of cidofovir. Cases of acute renal failure resulting in dialysis and/or contributing to death have occurred with as few as one or two doses of cidofovir. Cidofovir is contraindicated in clients who are receiving other nephrotoxic agents.
Sofosbuvir: HBV reactivation has been reported in HCV/HBV coinfected clients who were treated with HCV antivirals but were not receiving HBV antiviral therapy.
Tenofovir: Acute exacerbations of HBV have been reported in clients who have discontinued HBV antiviral therapy.
COVID-19 and Anti–COVID-19 Drugs
In 2020, the coronavirus disease 2019 ( COVID-19 ) caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a global pandemic that resulted in millions of deaths (World Health Organization, n.d.). Given the severity of illness and the propensity of the virus to kill individuals with poor immune systems and multiple comorbidities, there was a rush to develop both vaccines against the virus and medications to treat individuals with COVID-19 infections.
This section focuses on drug therapy for clients with an existing COVID-19 infection. It is important to note that treatment for COVID-19 is still an evolving topic and more research is still being conducted, so health care professionals should always consult the Centers for Disease Control and Prevention (CDC) COVID-19 website for up-to-date guidance.
Note that COVID-19 can present as asymptomatic or with potentially life-threatening symptoms. The variation can be due to issues such as vaccination status, medical comorbidities, immune system status, and age. These factors should always be considered when deciding whether COVID-19 drug therapy is needed. Clients without risk factors for progression to severe disease and those who are asymptomatic can be managed with supportive care and without drug treatment.
Nirmatrelvir
Nirmatrelvir is an oral antiviral medication that works by inhibiting the protease enzyme that is necessary to develop mature proteins. Because these proteins are prevented from being made, new mature virus copies cannot be made. Nirmatrelvir is combined with ritonavir, which is used as a strong CYP3A4 inhibitor to boost levels of nirmatrelvir and reduce dosing frequency. Because ritonavir is combined with nirmatrelvir, the nurse must review a client’s medication profile to avoid any significant CYP3A4 interactions. Nirmatrelvir should be taken as soon as possible once symptoms occur because it loses efficacy and is not recommended after 5 days of symptom onset.
Remdesivir
Remdesivir works by inhibiting viral RNA polymerase, causing inhibition of viral protein synthesis and reproduction. Remdesivir is an intravenous product, so it is usually reserved for hospitalized clients or those who cannot receive nirmatrelvir within 7 days of symptom onset.
Molnupiravir
Molnupiravir is an oral product that works by being incorporated into the SARS-CoV-2 RNA; it then induces errors that lead to inhibited viral reproduction. There are some questions about the efficacy of molnupiravir in the treatment of COVID-19, so it is recommended as an alternative if clients cannot receive nirmatrelvir due to drug interactions or impaired renal function. Initiation of molnupiravir should occur within 5 days of symptom onset.
Table 7.5 lists anti–COVID-19 drugs and typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
|
Molnupiravir
( Lagevrio ) |
800 mg orally every 12 hours for 5 days. |
|
Nirmatrelvir/ritonavir
( Paxlovid ) |
300 mg nirmatrelvir plus 100 mg ritonavir orally twice daily for 5 days. |
|
Remdesivir
( Veklury ) |
200 mg IV once on day 1, then 100 mg IV once daily for 4 days. |
Adverse Effects and Contraindications
Anti–COVID-19 drugs are known to cause gastrointestinal discomfort, including nausea, vomiting, and diarrhea. A contraindication to any antiviral drug is known hypersensitivity.
Nirmatrelvir is well tolerated, with diarrhea and dysgeusia (impaired sense of taste) being the most frequently reported adverse effects. Adverse effects seen with the use of remdesivir include elevated serum glucose levels and reduced kidney function. Remdesivir should be administered only when emergency airway tools (e.g., laryngoscope) are available in case of a severe allergic reaction.
Table 7.6 is a drug prototype table for anti–COVID-19 drugs featuring nirmatrelvir/ritonavir. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Antiviral agent Mechanism of Action Inhibits the SARS-CoV-2 main protease, which inhibits viral replication |
Drug Dosage
300 mg nirmatrelvir plus 100 mg ritonavir orally twice daily for 5 days. |
|
Indications
COVID-19 infection Therapeutic Effects Treats infections caused by the SARS-CoV-2 virus |
Drug Interactions
CYP3A4 substrates Alprazolam Buprenorphine Cabotegravir Food Interactions No significant interactions |
|
Adverse Effects
Diarrhea Dysgeusia Bradycardia Pruritus |
Contraindications
Hypersensitivity Caution: Liver impairment |
Nursing Implications
The nurse should do the following for clients who are taking anti–COVID-19 drugs:
- Monitor for signs and symptoms of anaphylaxis (e.g., shortness of breath, difficulty breathing, difficulty swallowing).
- Advise the client to take the entire prescribed course of the medication to ensure adequate treatment and to reduce the development of drug resistance.
- Monitor clients taking remdesivir for elevated serum glucose levels and renal function abnormalities.
- Monitor clients receiving nirmatrelvir/ritonavir for hepatic dysfunction.
- Advise the client to begin taking medications as soon as possible after symptom onset to ensure efficacy.
- Review the client’s medication list prior to initiating ritonavir to evaluate for CYP3A4 interactions.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking an anti–COVID-19 drug should:
- Alert their health care provider about any signs of allergic reactions, including throat swelling, severe itching, rash, or chest tightness.
- Alert their health care provider that they are taking these medications, including the dose and frequency.
- Take the drug with food if it causes an upset stomach.
- Take a missed dose as soon as they remember; however, they should not take double doses.
Fungi and Antifungal Drugs
Fungi make up a diverse group of microorganisms that includes yeasts, molds, and mushrooms. Some of the key differences between human and fungal cell structures are that fungi introduce sterols into the cell membrane, and they have a cell wall that includes products such as chitin and glucans. These differences form the basis for drug therapy designed to eliminate fungi. Fungal infections can vary in presentation from less severe infections of the scalp, skin, or nails, which may require topical antifungal therapy, to severe systemic fungal infections that may be life-threatening. The latter are primarily found in immunocompromised clients and require aggressive systemic therapy to avoid serious morbidity and mortality.
This section will cover commonly used antifungal drugs , including their mechanisms of action, adverse effects, indications, and contraindications. Given the wide variety of fungi that can cause disease (e.g., Aspergillus , Candida , Blastomyces ), positive identification is ideal to ensure that the appropriate drug is selected. Unfortunately, fungal cultures can take weeks for identification. In severely ill clients, broad-spectrum antifungals are used until culture results are available.
Polyenes
Polyene antifungal drugs include amphotericin B and nystatin. These are broad-spectrum antifungals that bind to ergosterol in the fungal cell membrane, leading to membrane breakdown and fungal cell death. Amphotericin B is used intravenously to treat severe systemic fungal infections. Nystatin is used orally for infections such as oropharyngeal candidiasis (thrush). Nystatin is not absorbed systemically when taken orally or topically; therefore, it is ineffective for systemic infections.
Azoles
The azole antifungals include two broad classes: imidazoles and triazoles. Examples of imidazoles include clotrimazole, miconazole, and ketoconazole. Examples of triazoles include fluconazole, voriconazole, and posaconazole. These drugs work by inhibiting the enzyme 14-alpha-sterol demethylase. This enzyme is necessary for the fungal cell to produce ergosterol, which is then transferred to the cell membrane. Inhibition of this enzyme leads to arrest of fungal cell growth.
Antimetabolites
Flucytosine is the only antifungal antimetabolite. It works by being converted to 5-fluorouracil (5-FU) in the fungal cell; 5-FU inhibits the enzyme thymidylate synthase as well as DNA, RNA, and protein production in fungal cells, leading to arrested growth.
Echinocandins
The echinocandins include the drugs caspofungin, anidulafungin, and micafungin. These work by inhibiting the enzyme 1,3-beta-glucan synthase, which is responsible for providing structural integrity to the fungal cell wall. Inhibiting this enzyme decreases glucan synthesis and disrupts the cell wall, leading to fungal cell death.
Table 7.7 lists antifungal drugs and typical routes and dosing for adult and pediatric clients .
| Drug | Routes and Dosage Ranges |
|---|---|
|
Amphotericin B
(Fungizone) |
Progessive, potentially life-threatening fungal infections:
Adults: 0.25–0.3 mg/kg IV daily over 2–6 hours. Total daily dose of 1.5 mg/kg should not be exceeded. |
|
Anidulafungin
( Eraxis ) |
Candida:
Adults: 200 mg IV on day 1, then 100 mg IV once daily. Children: 3 mg/kg (not to exceed 200 mg) on day 1, followed by a once daily IV maintenance dose of 1.5 mg/kg (not to exceed 100 mg) thereafter for 14 days. Esophageal candidiasis: Adults: 100 mg IV loading dose on day 1, followed by a 50 mg IV once daily maintenance dose for 14 days. |
|
Fluconazole
( Diflucan ) |
Oropharyngeal or esophageal candidiasis:
Adults: 200 mg orally on the first day, followed by 100 mg orally once daily for 2 weeks to prevent relapse. |
|
Flucytosine
( Ancoban ) |
Symptomatic cystitis:
Adults: 50–150 mg/kg/day administered in divided doses at 6-hour intervals for 10 days. |
|
Nystatin
( Nystat ) |
Oropharyngeal candidiasis:
Adults and children: Swish and swallow 400,000–600,000 units 4 times daily for 7–14 days. Continue for 48 hours after symptoms resolve and a negative culture is obtained. Infants: 200,000 units 4 times daily using a dropper. |
Adverse Effects and Contraindications
Antifungals are known to cause gastrointestinal discomfort, including nausea, vomiting, and diarrhea. A contraindication to any antifungal drug is known hypersensitivity.
Amphotericin B is very toxic and can cause flulike symptoms during infusion, hypotension, renal toxicity, and electrolyte disturbances. To reduce these adverse effects, several formulations have been developed that incorporate the drug into a lipid membrane. This significantly increases medication costs but is much better in reducing client harm.
Safety Alert
Oral/Intravenous Azole Antifungals
Some oral and intravenously administered azole antifungals are strong inhibitors of CYP3A4, which can affect many medications. Affected medications will have higher levels in the body and increase the risk for drug toxicity. The health care provider should screen a client’s medication profile for interactions before initiating therapy with an oral or intravenous azole antifungal.
Table 7.8 is a drug prototype table for antifungal drugs featuring fluconazole. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
|
Drug Class
Azole antifungal Mechanism of Action Inhibits fungal cytochrome P450 activity, decreasing ergosterol synthesis and inhibiting cell membrane formation |
Drug Dosage
Oropharyngeal or esophageal candidiasis: Adults: 200 mg orally on the first day, followed by 100 mg orally once daily for 2 weeks to prevent relapse. |
|
Indications
Treatment of fungal infections caused by susceptible fungi Therapeutic Effects Treats fungal infections caused by susceptible organisms |
Drug Interactions
CYP3A4 substrates Amiodarone Carvedilol Diazepam Food Interactions No significant interactions |
|
Adverse Effects
Headache Skin rash Abdominal pain Diarrhea Dizziness QT interval prolongation |
Contraindications
Hypersensitivity Pregnancy Coadministration with QT interval–prolonging drugs Caution: Central nervous system impairment Renal impairment |
Nursing Implications
The nurse should do the following for clients who are taking antifungal drugs:
- Monitor for signs and symptoms of anaphylaxis (e.g., shortness of breath, difficulty breathing, difficulty swallowing).
- Advise the client to take the entire prescribed course of the drug to ensure adequate treatment and to reduce the development of drug resistance.
- Instruct the client to maintain adequate hydration; monitor kidney function with renally eliminated medications.
- Ensure that blood samples for any drug levels ordered are obtained at the intended time in order to allow accurate assessments regarding dosage adjustments.
- Monitor the ECG for prolongation of the QTc interval when clients are taking systemically acting agents.
- Monitor liver function tests to assess for liver injury.
- Check a client’s medication list prior to administering a systemic azole antifungal because oral and intravenous azole antifungals inhibit CYP3A4 and can cause many drug interactions.
- Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.
Client Teaching Guidelines
The client taking an antifungal should:
- Alert their health care provider about any signs of allergic reactions, including throat swelling, severe itching, rash, or chest tightness.
- Alert their health care provider about any recent antifungal medication use prior to starting therapy.
- Alert their health care provider that they are taking these medications, including the dose and frequency.
- Take the drug with food if it causes an upset stomach.
- Take a missed dose as soon as they remember; however, they should not take double doses.
- Alert their health care provider about starting any new medications that may interact with their antifungal therapy.
FDA Black Box Warning
Amphotericin B
Amphotericin B should be used primarily for treatment of clients with progressive and potentially life-threatening fungal infections; it should not be used to treat noninvasive forms of fungal disease such as oral thrush, vaginal candidiasis, and esophageal candidiasis in clients with normal neutrophil counts.