Pharm Infectious Diseases

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Questions and Answers

Which of the following bacterial species is NOT a gram-positive cocci?

Staphylococcus aureus

Enterococcus faecalis

Corynebacterium diphtheriae (correct)

Streptococcus pneumoniae

What is the primary advantage of using a narrow-spectrum antibiotic over a broad-spectrum antibiotic in definitive therapy?

Narrow-spectrum antibiotics are less likely to cause allergies.

Narrow-spectrum antibiotics are more effective against a wider range of bacteria.

Narrow-spectrum antibiotics are less prone to be affected by drug resistance.

Narrow-spectrum antibiotics are more likely to target the specific causative organism. (correct)

Why might empiric therapy be beneficial even before culture and sensitivity results are known?

Empiric therapy can reduce the risk of developing antibiotic resistance.

Empiric therapy can provide immediate treatment before the causative organism is identified. (correct)

Empiric therapy can prevent the spread of infection to other individuals.

Empiric therapy can help identify the causative organism more quickly.

Which of the following is NOT a valid reason for using combination therapy in empiric therapy?

Minimizing the risk of drug resistance. (B) Signup and view all the answers

What is the common treatment for Clostridium difficile infection?

Vancomycin (C) Signup and view all the answers

Which of the following is an example of an atypical bacteria?

Mycoplasma (B) Signup and view all the answers

What is the primary purpose of a Gram stain?

To guide the selection of empiric therapy. (D) Signup and view all the answers

A patient presents with a low cardiac output secondary to reduced arterial blood pressure. Which type of shock is most likely responsible for this patient's condition?

Distributive Shock (D) Signup and view all the answers

A patient is experiencing a decline in organ function due to a systemic inflammatory response triggered by a bacterial infection. This situation is best described as:

Sepsis (D) Signup and view all the answers

Which of the following scenarios best exemplifies an obstructive shock mechanism?

A massive pulmonary embolism blocking blood flow to the lungs (D) Signup and view all the answers

A patient with sepsis is exhibiting hypotension despite receiving adequate fluid resuscitation. Which of the following is the most likely explanation for this?

The patient's body is unable to maintain vascular tone due to widespread vasodilation. (C) Signup and view all the answers

In which type of shock does the body's 'container' become too big?

Distributive Shock (D) Signup and view all the answers

A patient presents with oliguria, elevated lactate levels, and a high liver enzyme count. Which of the following is most likely?

The patient is likely experiencing a significant drop in blood pressure and tissue perfusion. (C) Signup and view all the answers

What is the primary goal of fluid resuscitation in the treatment of sepsis?

To reduce the risk of organ failure. (B) Signup and view all the answers

What is the critical threshold for mean arterial pressure (MAP) that defines septic shock?

MAP < 65 mmHg (B) Signup and view all the answers

Which of the following is NOT a core principle of sepsis management?

Immediate surgical intervention for all patients with sepsis. (B) Signup and view all the answers

Which of the following is a FALSE statement regarding the pathophysiology of septic shock?

Septic shock always results in a decrease in cardiac output. (B) Signup and view all the answers

Which of the following fungal infections is commonly seen in immunocompetent individuals?

Histoplasmosis (A) Signup and view all the answers

What is the primary reason why fungal infections are often challenging to treat?

Fungal infections often occur in inaccessible locations. (B) Signup and view all the answers

Why is it important to consider the structure of ergosterol in relation to antifungal drug development?

Ergosterol is the primary component of the fungal cell membrane, making it a critical target for antifungal drug development. (A) Signup and view all the answers

What is the main role of the immune system in antifungal treatment?

The immune system is essential for eradicating the infection after the antifungal drug slows its growth. (A) Signup and view all the answers

Which of the following factors contribute to the difficulty of treating opportunistic fungal infections?

Opportunistic fungal infections frequently occur in immunocompromised individuals, making treatment more challenging. (D) Signup and view all the answers

Which of the following bacterial species is commonly associated with UTIs and is known to be a nitrite producer?

Escherichia coli (A) Signup and view all the answers

Which of the following antibiotic classes is considered bactericidal and typically inhibits cell wall synthesis?

Penicillins (A) Signup and view all the answers

Which of the following antibiotic classes is considered bacteriostatic and is commonly used to treat infections caused by Chlamydia?

Macrolides (D) Signup and view all the answers

Which of the following antibiotics is most likely to be effective against a wide range of bacterial species, including both Gram-positive and Gram-negative bacteria?

Ceftriaxone (D) Signup and view all the answers

Which of the following bacterial species is a non-fermenter and is often associated with hospital-acquired infections, particularly in immunocompromised patients?

Pseudomonas aeruginosa (C) Signup and view all the answers

Which of the following statements accurately describes the concept of drug spectrum of activity?

It describes the range of bacteria a drug is effective against. (C) Signup and view all the answers

Which of the following conditions would likely necessitate the use of a bactericidal antibiotic over a bacteriostatic antibiotic?

A patient with a severe, life-threatening infection. (A) Signup and view all the answers

Which of the following factors is LEAST directly relevant to the effective use of antibiotics?

The patient's nutritional status (B) Signup and view all the answers

Which of the following statements is TRUE regarding the use of bacteriostatic antibiotics?

They require a functioning immune system to be effective at clearing infection. (A) Signup and view all the answers

Which of the following drugs is NOT classified as a neuraminidase inhibitor?

Baloxavir (B) Signup and view all the answers

What is the most common adverse effect associated with Oseltamivir?

Nausea and vomiting (D) Signup and view all the answers

Which antiviral medication is NOT approved for use in children under 12 years old?

Zanamivir (A) Signup and view all the answers

Which of the following statements regarding influenza vaccination is TRUE?

The effectiveness of the vaccine is dependent upon the match between the circulating strains and the vaccine strains. (C) Signup and view all the answers

What is the main mechanism of action for neuraminidase inhibitors in treating influenza?

Impairing viral replication and spread by inhibiting release of virus from infected cells. (A) Signup and view all the answers

Which of the following is NOT a factor that contributes to the emergence of new influenza viruses?

Vaccination (A) Signup and view all the answers

Which of these is NOT a characteristic of DNA viruses?

They synthesize mRNA from viral RNA. (B) Signup and view all the answers

Which of the following statements about the influenza vaccine is TRUE?

The vaccine is recommended for all individuals aged 6 months and older. (A) Signup and view all the answers

Which of the following statements regarding the use of antiviral medications for influenza is TRUE?

Antivirals may shorten the duration of illness by approximately 1-2 days. (B) Signup and view all the answers

What is the primary reason for the rising resistance of influenza viruses to antiviral medications?

The overuse and misuse of antiviral medications. (A) Signup and view all the answers

What is a common mechanism by which bacteria develop resistance to penicillin?

Production of beta-lactamase enzymes (A) Signup and view all the answers

Which antibiotic class is frequently used in combination therapy to treat infections caused by Pseudomonas aeruginosa, known for its resistance to many antibiotics?

Fluoroquinolones (A) Signup and view all the answers

Which mechanism of antibiotic resistance is particularly common in Gram-negative bacteria like Pseudomonas aeruginosa, often working together with efflux pumps?

Reduced permeability through porin channel mutations (D) Signup and view all the answers

Which of the following antibiotic classes is known to be particularly effective against MRSA (Methicillin-resistant Staphylococcus aureus)?

Vancomycin (B) Signup and view all the answers

What is the primary function of an antibiogram in clinical practice?

To guide the selection of effective antibiotics for a specific bacterial infection (C) Signup and view all the answers

Which of the following best describes the goal of definitive therapy in the context of antimicrobial treatment?

To tailor antibiotic treatment to the specific pathogen identified in culture and sensitivity testing (A) Signup and view all the answers

Which of the following is a primary reason for the increasing prevalence of antibiotic-resistant bacteria?

The overuse and misuse of antibiotics in both human and animal medicine (B) Signup and view all the answers

What is a key difference between empiric therapy and definitive therapy in treating bacterial infections?

Empiric therapy uses broad-spectrum antibiotics initially, while definitive therapy targets the identified pathogen (B) Signup and view all the answers

Which of the following statements regarding the use of Tenofovir is TRUE? (Select all that apply)

Tenofovir also has activity against Hepatitis B, making it particularly valuable for patients co-infected with both viruses. (A), Tenofovir is a nucleoside reverse transcriptase inhibitor that terminates DNA elongation by binding to reverse transcriptase. (B), Tenofovir is effective against both HIV-1 and HIV-2. (C) Signup and view all the answers

Which of the following statements about the administration of ART in HIV-infected patients is TRUE? (Select all that apply)

All patients with HIV, regardless of their CD4 count, should receive ART. (B), Patients with HIV should be on at least 2 antiretroviral agents from at least 2 different pharmacologic classes. (C), ART should be initiated as soon as the diagnosis of HIV is confirmed, to improve patient outcomes and reduce the risk of transmission. (D) Signup and view all the answers

Which of the following antiretroviral medications has been shown to have a potential risk of prolonged QT interval at high doses?

C (D) Signup and view all the answers

Which of the following is NOT a valid reason for using Bactrim as primary prophylaxis for Pneumocystis jirovecii pneumonia in HIV-infected patients?

Bactrim is a highly effective prophylactic agent with minimal risk of adverse effects, even in patients with compromised immune function. (A) Signup and view all the answers

Which of the following bacterial species is a common cause of urinary tract infections (UTIs) and is known for producing nitrite, a metabolic byproduct that can be detected in urine samples?

Proteus (A) Signup and view all the answers

Which of the following antibiotic classes is considered bactericidal and specifically targets the synthesis of bacterial cell walls, disrupting their structural integrity and leading to cell lysis?

Penicillins (C) Signup and view all the answers

Which of the following antibiotic classes is considered bacteriostatic and is often prescribed for infections caused by Chlamydia trachomatis, a common sexually transmitted infection?

Macrolides (B) Signup and view all the answers

Which of the following antibiotics demonstrates broad-spectrum activity, showing effectiveness against a wide range of bacteria, including both Gram-positive and Gram-negative organisms, making it suitable for empiric therapy, particularly in situations where the causative organism is unknown?

Ceftriaxone (A) Signup and view all the answers

Which of the following bacterial species is a non-fermenter, often associated with hospital-acquired infections, especially in immunocompromised patients? It is known for its remarkable resistance to a wide variety of antibiotics, making it a challenging pathogen to treat.

Pseudomonas (C) Signup and view all the answers

Which of the following statements accurately describes the concept of a drug's spectrum of activity in the context of antibiotic therapy?

Spectrum of activity refers to the range of bacterial species that the antibiotic can effectively treat. (B) Signup and view all the answers

Which of the following conditions or situations would likely necessitate the use of a bactericidal antibiotic over a bacteriostatic antibiotic, emphasizing the importance of eradicating the bacterial infection?

A case of pneumonia in a patient with a compromised immune system. (D) Signup and view all the answers

A patient presents with a history of recurring HSV outbreaks. The patient reports having had 10 or more episodes in the past year. Which of the following antiviral medications is most appropriate for daily suppressive therapy in this case?

Valacyclovir - 1000mg once a day (C) Signup and view all the answers

Which of the following is the most likely reason for the CDC's recommendation against using adamantanes for the treatment of influenza?

Adamantanes are ineffective against the predominant H1N1 variant circulating currently. (A) Signup and view all the answers

A patient presents with a severe case of HSV encephalitis. Which of the following antiviral agents would be the most appropriate choice for intravenous therapy in this case?

Acyclovir (A) Signup and view all the answers

A patient with a history of frequent herpes outbreaks is concerned about the potential for drug resistance. Which of the following actions would be LEAST likely to reduce the risk of drug resistance?

Using a single antiviral agent for prolonged periods. (A) Signup and view all the answers

A patient with a compromised immune system is receiving a bone marrow transplant and is at high risk for CMV infection. Which of the following agents would be most effective in preventing CMV reactivation in this patient?

Valganciclovir (B) Signup and view all the answers

A patient with a recent diagnosis of HSV infection is prescribed Acyclovir. The patient is also taking Probenecid for gout. What potential drug interaction should be considered in this case?

Probenecid may decrease the renal clearance of Acyclovir, leading to potential accumulation and increased risk of adverse effects. (A) Signup and view all the answers

A patient is hospitalized with severe COVID-19 and requires mechanical ventilation. Which of the following medications is MOST likely to be used in this patient's treatment?

Remdesivir (A) Signup and view all the answers

A patient with mild to moderate COVID-19, who is considered high risk for progression to severe disease, is seeking treatment. Which of the following medications would be the MOST appropriate option for this patient?

Paxlovid (D) Signup and view all the answers

A patient is diagnosed with HIV and is initiating antiretroviral therapy (ART). What is the primary goal of this therapy?

To reduce the viral load and prevent depletion of CD4 cells. (C) Signup and view all the answers

A patient is being treated with Ganciclovir for CMV retinitis. Which of the following adverse effects should be carefully monitored during therapy?

Myelosuppression (B) Signup and view all the answers

A patient presents with a respiratory illness exhibiting symptoms like fever, sore throat, cough, and rhinitis. The patient reports receiving the influenza vaccine last season but has not received the current season's vaccine. Which of the following statements best explains this situation?

The patient may have contracted a different influenza strain for which their previous vaccination did not confer immunity. (D) Signup and view all the answers

A healthcare provider is treating a patient with a suspected influenza infection. When should they begin administering antiviral medications for the most effective outcome?

Within 48 hours of symptom onset, as early treatment significantly improves outcomes. (C) Signup and view all the answers

A patient with a history of asthma and chronic obstructive pulmonary disease (COPD) is diagnosed with influenza. Which antiviral medication would be most appropriate for this patient, considering their respiratory condition?

Peramivir (Rapivab), as it is administered intravenously, bypassing the respiratory tract and minimizing potential complications. (C) Signup and view all the answers

An elderly patient with a history of heart disease and diabetes is diagnosed with influenza. Which of the following antiviral medications would be most appropriate, considering their high risk for complications?

Baloxavir (Xofluza), as it has a single-dose regimen and is especially effective in high-risk patients for developing complications. (C) Signup and view all the answers

A young patient presents with influenza symptoms accompanied by significant neurological changes, including confusion, delirium, and hallucinations. Which antiviral medication is the most likely culprit for these adverse effects?

Oseltamivir (Tamiflu), as it has been associated with neuropsychiatric effects, particularly in children and adolescents. (A) Signup and view all the answers

Which of these is the most concerning complication that can be linked to both the inactivated influenza vaccine (IIV) and the live attenuated influenza vaccine (LAIV)?

Guillain-Barre Syndrome, with a possible link to both vaccine formulations. (D) Signup and view all the answers

A healthcare provider is treating a patient with a suspected influenza infection. The patient has received their influenza vaccine this season and had a runny nose, sore throat, and congestion for the past few days. Which of the following factors is most likely contributing to the patient's symptoms?

The patient is experiencing an unrelated viral or bacterial infection, coinciding with the influenza season. (D) Signup and view all the answers

Which of these options is CORRECT regarding the treatment of influenza?
(Select all that apply)

Symptoms can be managed with over-the-counter remedies, such as acetaminophen and antihistamines, in conjunction with antiviral therapy. (A), Antiviral medications are most effective when started within 48 hours of symptom onset. (C) Signup and view all the answers

A patient tests positive for influenza A and asks about the influenza vaccine. Which option BEST explains why the patient is still sick despite vaccination?

The influenza vaccine only protects against specific influenza strains, and the patient’s infection may be with a different strain not covered in the vaccine. (A) Signup and view all the answers

A patient with a severe egg allergy is seeking the influenza vaccine. Which type of influenza vaccine is MOST suitable for this patient?

Inactivated Influenza Vaccine (IIV) can be administered to patients with severe egg allergies without an increased risk of allergic reaction. (D) Signup and view all the answers

Study Notes

Antimicrobial Therapy

Antibiotics are life-saving drugs
Antibiotics only treat bacterial infections
Most sore throats do not require an antibiotic
Some ear infections do not require an antibiotic
Green colored mucus is not a sign that an antibiotic is needed
Risks can include allergies, diarrhea, and rashes
Consult a clinician on appropriate antibiotic use

Some Semantics

Antibiotics inhibit or kill pathogens; inhibit the growth, or kill a pathogen
Antibacterial drugs target bacteria
Antifungal drugs target fungi
Antiviral drugs target viruses

Empiric Therapy

Infection is present but the causative agent is not known
Therapy is started before culture and sensitivity results
Antibiotic selection is based on typical pathogens associated with a particular infection
Empiric therapy is the most common use of antibiotics
Definitive pathogen identification takes up to 48 hours
Delay can be detrimental to the patient
Combination therapy may be common
Broad-spectrum antibiotics are often used
Treating most common pathogens

Definitive Therapy

Therapy is tailored to culture and sensitivity results
The clinician knows which antibiotics work for the infection
Adjustment to empiric therapy may be necessary
Monotherapy is preferred
Narrow-spectrum antibiotics help minimize resistance

Gram Stain vs. Bacterial Culture

Gram stain indicates a possible bacterial cause, differentiating bacteria based on cell wall characteristics.
Quicker results (than bacterial culture)
Does not definitively identify an organism
Helps guide empiric therapy
Bacterial culture takes 24-48 hours
Organism-specific criteria allow for definitive diagnosis, targeting therapy against the specific organism

Bacteria Review

Gram-positive bacteria
Gram-negative bacteria
Atypical bacteria
Spirochetes
Rickettsia
Mycobacteria
Mycoplasma
Legionella

Gram-Positive Cocci

Staphylococcus (S. aureus, S. epidermidis)
Streptococcus (S. pneumonia, S. pyogenes, S. agalactiae)
Enterococci (E. faecalis)

Gram-Positive Rods

Clostridia (C. tetani, C. botulinum, C. difficile)
Corynebacterium (C. diphtheria)
Listeria (L. monocytogenes)

Gram-Negative Bacteria

Enterobacteriaceae (E. coli, Proteus, Klebsiella, Shigella, Salmonella, Yersinia, Citrobacter)
Non-fermenters (Moraxella, Pseudomonas)
Neisseria
Chlamydia
Haemophilus
H. pylori

Bactericidal vs. Bacteriostatic

Bactericidal drugs kill bacteria
Bacteriostatic drugs inhibit bacterial growth
Bactericidals are better for immunocompromised patients, and can eradicate bacteria even if the immune system is ineffective
PCNs and cephalosporins are very cidal for microbes, aminoglycosides, vancomycin, fluoroquinolones, and metronidazole, are examples
Bacteriostatics are designed to give the immune system an upper hand, requiring a competent immune system
Tetracyclines, macrolides, Bactrim, linezolid, and chloramphenicol are examples

Mnemonic

A way to remember which drugs fall under bacteriostatic or bactericidal
ECSTaTiC for bacteriostatic drugs
Very ProFicient At Complete Cell Murder for bactericidal drugs

Spectrum of Activity

Broad spectrum covers many types of bacteria (gram +, gram -, often atypicals)
Good for empiric therapy, but increased risk of adverse effects, superinfections and resistance
Examples include fluoroquinolones, carbapenems, some penicillins (augmentin, piperacillin-tazobactam, ampicillin-sulbactam), some cephalosporins (ceftriaxone, cefepime), tetracyclines, and Bactrim
Narrow spectrum is targeted therapy for a specific organism; lower risk of superinfections and resistance.
Examples include penicillins (PCN V, PCN G, nafcillin), cephalosporins (cefazolin), vancomycin, clindamycin, and metronidazole

Keys to Effective Antibiotic Use

Identify the causative organism; confirm the drug is effective against the specific organism
Consider potential harm to the patient
Ensure drug reaches the site of infection
Confirm adequate duration for the drug to work effectively

Antibiotic Targets

Cell wall synthesis
Nucleic acid synthesis
Protein synthesis
Cell membrane

Different Classes of Antibiotics

B-lactams, aminoglycosides, glycopeptides, ansamycins, quinolones, streptogramins, lipopeptides, sulfonamides, chloramphenicol, tetracyclines, macrolides, oxazolidinones, and others

Mechanisms of Antibiotic Resistance

Enzymatic or metabolic inactivation
Alteration of target sites
Efflux pumps
Reduced permeability

How Antibiotic Resistance Happens

Lots of germs exist, but a number is resistant
Antibiotics kill "good" bacteria in addition to harmful bacteria
Resistant bacteria flourish.
Resistance is passed on, potentially through horizontal gene transfer

Viral Illnesses

A general topic, covering various viral infections

What is a Virus?

Obligatory intracellular microorganism
Dependent on host cell mechanisms for reproduction; has a basic structure including DNA or RNA, protein coat (capsid), and envelope (derived from host cell membrane)
Replicates through a cycle of attachment, penetration, uncoating, synthesis, assembly, and release.

DNA Viruses

Examples include smallpox, herpesviruses, adenoviruses, hepatitis B virus, and HPV.
DNA is transcribed to mRNA, which is then translated into viral proteins; new viruses assemble in the cytoplasm before release.

RNA Viruses

Examples include rubella, influenza, hepatitis A and C, coronavirus, Zika, and retroviruses.
Retroviruses have a different replication cycle; RNA is converted to DNA before mRNA production of viral proteins and new viruses.
Viruses are packaged and released into the extracellular environment.

Influenza

RNA virus, enveloped, subdivided by hemagglutinin and neuraminidase antigens
Causes upper respiratory and GI symptoms like fever, sore throat, headache, cough, rhinitis, nausea, and vomiting
Vaccine is the primary prevention, antiviral therapy is limited, but resistance is increasing

No Lasting Immunity to Influenza

Immunity to one subtype does not confer immunity to other types
Antigenic drift (small changes) leads to seasonal epidemics and the need for annual vaccination
Antigenic shift (large changes) leads to new influenza viruses and potential pandemics.

Vaccination

Recommended for all persons 6 months and older; patients 6 months to <2 years should only receive the inactivated influenza vaccine (IIV)
Vaccine works best with seasonal viruses that are well-matched; two types: inactivated (IIV) and live attenuated (LAIV)
Best given in October/November.
Not recommended for patients with severe egg allergies; IIV4 HD recommended for patients 65 and older.

Antiviral Treatment of Influenza

Early identification is key for effective treatment.
Antiviral drugs are most effective if started within 48 hours of symptom onset; shorten symptom duration.
Other medications like acetaminophen and antihistamines can help with symptoms.

Neuraminidase Inhibitors

Impair viral replication and spread by inhibiting release of virus from infected cells.
Drugs include oseltamivir (Tamiflu), zanamivir (Relenza), and peramivir (Rapivab)
Treatment should be administered within 48 hours of symptom onset; reduce illness duration by 1-2 days and the risk of complications/hospitalizations by ~50%

Oseltamivir

Approved for use in patients 14 days and older; administered orally for 5 days.
Preferred antiviral drug in pregnancy (most common side effects are nausea and vomiting, neuropsych effects, and hepatotoxicity)
Can be used prophylactically
Important to check for drug interactions and resistance issues for certain strains.

Zanamivir and Peramivir

Zanmivir administered via inhalation; poor oral bioavailability; consider the patient's ability to use the device.
Not recommended for patients with asthma or COPD
Approved for patients 7 years and older, or 2 years for peramivir (administered intravenously).
Single dose peramivir, and 5 day dosing in zanamivir.

Cap-Dependent Endonuclease Inhibitor

Blocks viral replication by interfering with viral RNA transcription; Baloxavir (Xofluza)
Approved for those 12 years and older, especially high-risk patients (with asthma, diabetes, heart disease, etc.).
Best when started within 48 hours of symptom onset
Decreases duration of illness in patients with influenza by 2.5 days
Not recommended in pregnancy or breastfeeding, avoid use with certain substances.
Adverse side effects include nausea, diarrhea, and elevated liver enzymes

Adamantanes

Inhibit uncoating and replication; amantadine and rimantadine
Only effective against certain strains of influenza A, not recommended currently due to high resistance issues.

Herpes Viruses

Common pathogenic herpesviruses include HSV-1, HSV-2, varicella zoster, cytomegalovirus, and epstein-barr virus.
Viruses cause mucocutaneous and CNS diseases (e.g., chicken pox)

Pharmacotherapy of HSV Infections

Suppresses viral replication, but does not cure
Virus remains latent; oral therapy is the most common
IV therapy available; topical forms available, but less effective
Daily suppressive therapy may be used in patients with frequent outbreaks.

Acyclovir

Prodrug that inhibits viral DNA synthesis, targeting viral DNA polymerase for HSV infections.
Effective against HSV-1, HSV-2—less effective against Varicella Zoster, EBV, and CMV.
Poor oral bioavailability - needs more frequent dosing
Widely distributed in the body (including CNS)—treats infections in many body areas
Resistance can occur

Acyclovir Adverse Effects

Generally well-tolerated; common side effects include nausea, diarrhea, rash, and headache.
Considered safe for use during pregnancy, although rare, more serious side effects are possible (especially with IV dosing).
Nephrotoxicity usually resolves with cessation and fluid administration.
CNS symptoms like confusion and hallucinations are possible.
Drug-drug interactions can increase risk of nephrotoxicity.

Valacyclovir

Prodrug of acyclovir
Improved oral bioavailability; less frequent dosing
Rapidly converted to acyclovir in the body.
Similar adverse effects as acyclovir

Clinical Uses

Genital HSV infections, herpetic gingivostomatitis, recurrent herpes cold sores, topical acyclovir/hydrocortisone combinations, herpetic keratoconjunctivitis/herpes ophthalmicus, herpes zoster (shingles), suppressive therapy, bell's palsy.
Intravenous (IV) therapy may be necessary in certain clinical contexts.

Chronic Suppressive Therapy

For patients with 6 or more HSV outbreaks yearly.
Regimens include acyclovir (400mg BID), famciclovir (250mg BID), or valacyclovir (500mg once daily or 1000mg once daily for patients with >10 outbreaks).
Often considered safe for up to 10 years of treatment.

Ganciclovir and Valganciclovir

Same mechanism of action as acyclovir
Effective against all herpes viruses, especially CMV.
Poor oral bioavailability for ganciclovir; typically given intravenously (IV).
Valganciclovir is the prodrug of ganciclovir with superior oral bioavailability.
Major clinical use is for treatment and prevention of CMV infections, particularly retinits.

Adverse Effects

Black box warnings: myelosuppression (neutropenia), pancytopenia (rare).
G-CSF may be required, potential infertility in both sexes.
Teratogenic risk—avoid during pregnancy.
Potentially carcinogenic. Valganciclovir preferable for pregnancy

COVID-19

SARS-CoV-2; Older adults or with comorbidities at risk.
Remdesivir, Nirmatrelvir/Ritonavir (Paxlovid) target the virus; potentially dangerous if not followed correctly.
Other treatment options include: glucocorticoids (dexamethasone), various immune modulators, anticoagulants, nebulized respiratory drugs, monoclonal antibodies, and convalescent plasma.

Remdesivir

Developed to treat RNA viruses (ebola, MERS, SARS); FDA granted emergency use in 2020.
Inhibits RNA synthesis by binding to RNA polymerase.
Indicated for patients 12 years and older with severe COVID-19 requiring hospitalization.
Initial loading dose followed by maintenance doses; marginal clinical benefit in clinical trials.

Paxlovid

Combination of nirmatrelvir and ritonavir (protease inhibitors).
Indicated for mild to moderate COVID-19.
Approved for patients 12 and older; given within 5 days of symptom onset
Half-dose if moderate kidney dysfunction and not recommended for severe kidney dysfunction.
Multiple drug interactions.

HIV and AIDS

Three main routes of infection: sexual, parenteral, and perinatal
Infects immune cells (T-helper lymphocytes, monocytes, macrophages, and dendritic cells) expressing the CD4 receptor
Untreated HIV infection leads to severe depletion of CD4 T cells, and increased incidence of infections caused by nonpathogenic normally organisms
The mainstay of treatment is ART, the goal is suppression of viral load, thus preventing further depletion of CD4 cells.

Facts About HIV

HIV is an enveloped, single-stranded RNA retrovirus
Two types: HIV-1 and HIV-2.
Viral load suppression is important for survival and preventing transmission; patients with early or late HIV are more likely to transmit the disease.
Only ~13% of those living with HIV in the US are aware of their status.

What is a Retrovirus?

Retroviruses have a unique replication cycle.
DNA is converted to an RNA strand (transcription) and RNA functions as a blueprint for creating an end product, usually a protein (translation).
Retroviruses use RNA as a template to create DNA, which is then transcribed into mRNA and translated into viral proteins.
This creates the new virus, and is critically relevant to antiretroviral treatment.

Pharmacological Implications of a Retrovirus

An enzyme unique to retroviruses is required to make DNA from RNA (reverse transcriptase); Major target of ART.
Mistakes are frequently made during transcription → rapid mutation of HIV.
Enables the HIV virus to evade immune responses.
Makes vaccine development challenging & HIV develops resistance to treatments.
Integrase—another enzyme unique to HIV, integrates HIV viral DNA into the host cell's chromosome (established persistent infection), is another crucial reason for continual ART and why patients must adhere.

Antiretroviral Therapy

Goals: restoring and preserving immune function, preventing transmission.
HIV infection is always harmful; increased viral replication → increased CD4 cell destruction.
Suppressing HIV replication (maximal suppression) → decreases potential for resistant HIV variants.
All patients with HIV should receive ART regardless of CD4 count.

Principles of Antiretroviral Therapy

Patients with HIV should be on 2-3 antiretroviral agents from at least 2 different pharmacologic classes; treatment should be initiated as soon as the diagnosis of HIV is made.
ART medications are the only FDA-approved treatment for HIV.
Many drug-to-drug interactions exist with ART drugs.

5 Classes of Antiretrovirals

Entry inhibitors
Nucleoside reverse transcriptase inhibitors (NRTIs)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Integrase strand transfer inhibitors (InSTIs)
HIV protease inhibitors.
Newer versions of each drug often offer better efficacy, fewer side effects, and improved tolerance.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Important viral enzyme = reverse transcriptase, which allows HIV to create DNA from RNA.
NRTIs terminate DNA elongation by binding to reverse transcriptase; effective against HIV-1 and HIV-2.
Tenofovir has activity against HBV—should be used in co-infected patients.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Cause a change in shape to reverse transcriptase
Not effective against HIV-2
These drugs often end in -vir, generally newer.
Development of resistance is fairly common.
Should be combined with other ART drugs to prevent resistance

HIV Protease Inhibitors

Inhibit the protein involved in viral maturation (production of immature, non-infectious viruses.)
Active against HIV-1 and HIV-2; often used in combination with CYP3A inhibitors (often ritonavir or cobicistat) to increase drug concentrations.
Adverse side effects can include GI distress, increased lipids, insulin insensitivity

HIV Entry Inhibitors

Block the entry of HIV into cells
Drugs include enfuvirtide, maraviroc, ibalizumab, and fostemsavir (Temsavir)
Usually used in patients who have been on other ART for a while, or who have a multi-drug resistant infection

Integrase Inhibitors (InSTIs)

Inhibits HIV DNA from being added to the patient's DNA
Active against both HIV-1 and HIV-2; produces more rapid decline in HIV viral RNA than other ART.
Drugs include bictegravir, cabotegravir, dolutegravir, and raltegravir
Generally better tolerated than other ART options, low resistance.
Adverse effects can include nausea, rash, headache, psychiatric effects (insomnia, depression), and weight gain.

Recommended Regimen

1 INSTI (e.g., bictegravir) + 2 NRTIs (e.g., tenofovir/emtricitabine) commonly recommended for patients.

Management of Opportunistic Infections

Opportunistic infections arise due to the compromised immune system of HIV patients.
The probability of an opportunistic infection developing is closely tied to CD4 counts
It is best to prevent them by maintaining effective viral load suppression and proper preventative care, vaccination, or prophylactic therapies.
Initiation of prophylactic medications at specific CD4 count thresholds.

Management Principles

Prevent exposure to opportunistic pathogens (vaccination for example)
Utilize primary chemoprophylaxis at appropriate CD4 thresholds. Prophylactic medications are initiated at diagnosis or at the appropriate time.
Treat any opportunistic infection that arises.
Use secondary prophylaxis to prevent repeat infections
Discontinue prophylactic medications when the patient has maintained a sustained ART response and the immune system has recovered.

Management of Pneumocystis Jirovecii

PCP pneumonia is a life-threatening opportunistic infection, a fungus that has protozoan characteristics and most common among AIDS patients
Occurs with a CD4 count below 200
Treatment of choice is Trimethoprim-sulfamethoxazole (Bactrim) IV therapy; usually lasts 21 days, and may require repeated/additional courses.
Corticosteroids should be administered within 72 hours of initiating Bactrim
ART should be started concurrently within 2 weeks of PCP treatment

Trimethoprim-Sulfamethoxazole (Bactrim)

Both drugs inhibit folate synthesis.
Have wide range of clinical uses: GI, respiratory, UTIs, and PCP infections
Bacterial resistance can impact effectiveness, and sensitivity testing is recommended
Effective against MRSA; not effective against Pseudomonas.

Antifungals

Diverse class, treating various kinds of fungal infections; many are for topical use, but some can be administered systemically.

Fungi - Key Facts

Eukaryotic, more complex than bacteria.
May be unicellular or multicellular; lack chlorophyll, obtaining nutrients from the environment.
Cell walls composed of chitin, having ergosterol-containing cytoplasmic membranes.

Fungal Disease in Humans

Pathogenic fungi (e.g., Histoplasma, Coccidioides, Cryptococcus) can cause diseases in immunocompetent AND immunocompromised hosts in some circumstances.
Opportunistic fungi (e.g., Aspergillus) are causative factors in infections in immunocompromised hosts; most often caused by Candida or Aspergillus infections.
Common commensal fungi = Candida

Types of Antifungal Drugs

Topical (most dermatology care) and/or systemic agents.
Classified by mechanism of action; examples - azoles, polyenes, echinocandins, and miscellaneous.

Amphotericin B

Broadest-spectrum antifungal drug.
Commonly used to treat serious fungal infections in immunocompromised patients.
Active against pathogenic and opportunistic fungi; not active against bacteria
Fungicidal—removes ergosterol from fungal cell membrane—leading to fungal cell death.
Administered intravenously (IV), not absorbed from GI tract; available in conventional and lipid formulations
Resistance is rare

Amphotericin B Adverse Effects

Infusion reactions (anaphylaxis possible), fever/chills.
Nephrotoxicity is a significant concern, especially with conventional amphotericin B (C-AMB); cumulative doses exceeding 3 to 5 grams may lead to permanent renal damage.
May require potassium supplementation—premature neonates tolerate C-AMB better than older children or adults
Avoid use with other nephrotoxic agents (e.g., aminoglycosides). Administering one liter of saline on the day of an administration can decrease the risk of nephrotoxicity.

Nystatin

Topically used antifungal.
Extremely toxic for systemic use (not absorbed GI tract)
Used for treating candidiasis (oral and vaginal), but not as effective for fungal nail infections or moist lesions (e.g., diaper rash)
Available as a topical powder or oral suspension.

Azole Antifungals

MOA = inhibits ergosterol biosynthesis, fungistatic
Triazoles are less toxic than imidazoles—more commonly used systemically.
Clinically relevant uses include treating fungal skin and nail infections, many types of Candida, and sometimes Histoplasmosis/Blastomycosis.
Aspergillus is less susceptible.
Drug interactions with azole antifungals are common—avoid use with other drugs

Itraconazole

Triazole antifungal; effective for fungal skin, nail, and mild/moderate infections, including Aspergillus and Histoplasmosis.
Can cause or worsen heart failure, QT prolongation; hepatotoxicity is a concern.
Cautious use in patients with liver dysfunction and should not be administered concurrently with other hepatoxic drugs, or other medications that affect liver enzymes. Drug-drug interactions are common to itraconazole.

Fluconazole

Extremely versatile azole antifungal.
Excellent bioavailability and good distribution.
Often used to manage candidiasis (oral and vaginal), in patients with AIDS or cryptococcosis, and as first-line therapy for coccidioidal meningitis.
Not effective against Histoplasmosis, Sporotrichosis, or aspergillosis.

Fluconazole Adverse Effects

Hepatotoxicity (range from mild to hepatic failure), alopecia (prolonged, high-dose therapy); rare but potential side effects include SJS/TEN; and QT prolongation.

Voriconazole

Triazole antifungals, IV or oral forms.
Extended spectrum of activity compared to fluconazole, better absorption potential, but with a tighter Therapeutic Window.
Typically given 1 hour before or after meals.
Primary clinical use - invasive Aspergillosis, and esophageal candidiasis.
Hepatotoxicity, QT prolongation, and renal toxicity are concerns associated with its use

Ketoconazole

Imidazole antifungal; activity similar to that of itraconazole (however, it lacks activity against Aspergillus.)
Primarily used topically; use as an oral antifungal has been mostly replaced by itraconazole except in circumstances of a lower cost option

Echinocandins

Inhibit 1,3-beta-D-glucan synthesis, an essential fungal cell wall component.
Active against candidiasis (fungicidal) and aspergillosis (fungistatic)
Available as Caspofungin, Anidulafungin, and Micafungin.
Primarily delivered intravenously (IV); not used orally.
Often well-tolerated, but has some adverse effects (redness/inflammation at infusion site).
Contraindicated for use during pregnancy

Other Systemic Antifungal Agents

Flucytosine—an antifungal related to fluorouracil; penetrates various body parts, including CSF and aqueous humor
Used in combo therapy with Amp B to treat severe cryptococcal infections in the nervous system.
Resistance can limit use as a single agent; the drug can be metabolized to 5-Fluorouracil, and human bodies do not have the corresponding enzymes; Dosage must be adjusted for renal function.

Antimalarials

A general topic; treatment of disease causes by plasmodium infections (parasites)

Artemisinins

Fast-acting antimalarials, derived from sweet wormwood (Artemisia annua)
Effective against multidrug-resistant strains of malaria parasites.
Often administered in combination, but parental artesunate was approved as a component of a first-line therapy for severe P. falciparum cases in 2020.

Quinine and Quinolines (Chloroquine and Hydroxychloroquine)

Long-standing antimalarial drugs, with chloroquine being used alone or in combination therapy.
Widespread resistance to chloroquine among P. falciparum, which makes alternative treatments to treat more effectively more critical.
Agent of choice for P. ovale and P. malariae
Narrow therapeutic index; high doses can be fatal.
Common adverse effects – headache, visual disturbances, urticaria (hives); May cause hemolysis (breaking down of red blood cells) in those with G6PD deficiency. Avoid in pregnancy or breastfeeding

Primaquine

Effective against the liver stage of certain malaria parasites (P. vivax and P. ovale)
Used to prevent relapse; must rule out G6PD deficiency before use.
Contraindicated during pregnancy.

Second-Line Drugs

Aminoglycosides such as streptomycin, amikacin, capreomycin, and rarely utilized due to side effects (hearing loss.)
Clofazamine is a treatment for multidrug-resistant tuberculosis.
Cycloserine has neuropsychiatric effects (seizures, psychoses, suicidal ideations)
Fluoroquinolones such as moxifloxacin.

Helminth Infections

Caused by infections by roundworms, tapeworms, and flatworms.
Benzimidazoles (albendazole, mebendazole), ivermectin, and praziquantel are frequently used treatments.

Benzimidazoles (treatment)

Albendazole and mebendazole. Considered safe in short courses.
Potential for GI upset (abdominal pain, distention, diarrhea) can occur in some patients.
Generally not recommended during pregnancy.
Limited data in children under 2 years.

Praziquantel

Drug of choice for schistosomiasis
May cause drowsiness; should not drive or operate machinery or perform other tasks requiring high levels mental alertness
Dose reduction in hepatic impairment.
WHO recommends use during any trimester of pregnancy.

Ivermectin

Derived from Streptomyces avermitilis
Broad activity against many types of helminths; some activity against ectoparasites like scabies and head lice.
Potential adverse effects: Dizziness, nausea, fatigue, pruritis; Mazzotti reaction
Caution in pregnancy, breastfeeding, meningitis.

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