Ch24 Drugs Used in Treating Infectious Diseases-1

Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition
Chapter 24
Drugs Used in Treating

Infectious Diseases
Copyright 2016 F.A. Davis Company

Overview
Antimicrobial resistance
Beta-lactams
Penicillins, cephalosporins
Fluoroquinolones
Lincosamides
Macrolides, azalides, ketolides
Oxalodinones
Sulfonamides, trimethoprim, nitrofurantoin

Overview (contd)
Tetracyclines
Vancomycin
Antimycobacterials
Antivirals
Nucleoside analogues
Antivirals for influenza
Systemic azoles and other antifungals
Anthelminthics
Metronidazole and nitazoxanide
Antimicrobial Resistance
Causes of drug resistance
Recent use of antibiotics
Overuse of broad-spectrum antibiotics
Age younger than 2 years or older than 65 years
Daycare center attendance
Exposure to young children
Multiple medical comorbidities
Immunosuppression
Antimicrobial Resistance (contd)

Every antibiotic class has resistance organisms.
Local resistance patterns can be identified by
monitoring the antibiogram of the
local laboratory.
Vaccination with pneumococcal vaccine has
decreased resistance.

Beta-Lactams: Penicillins
Pharmacodynamics
Inhibit the biosynthesis of peptidoglycan bacterial cell wall
Sensitivity
Natural penicillins: Streptococcus, some Enterococcus strains, some non-
penicillinase-producing Staphlococcus
Aminopenicillins greater activity against gram-negative bacteria due to
enhanced ability to penetrate the outer membrane organisms
Used for gram-negative urinary and gastrointestinal (GI) pathogens E. coli,
Proteus mirabilis, Salmonella, some Shigella species, and Enterococcus
faecalis; active against the common gram-negative respiratory pathogens
Moraxella catarrhalis (and Haemophilus influenzae type B)
Combination with beta-lactamase inhibitors to broaden their
spectrum: clavulanate, slbactam, tazobactam

Beta-Lactams: Penicillins (contd)

Pharmacokinetics
Well-absorbed from GI tract, but several are unstable in
acid: dicloxacillin and amoxicillin better absorbed
than ampicillin
Bound to proteins with good distribution to most tissues
Small amount is metabolized, most are excreted as
unchanged drug in the urine.
Probenecid prolongs the half-life and increases risk
for toxicity.

Adverse drug reactions (ADRs)
May cause serious immediate allergic reactions
Reactions occur within 2 to 30 minutes of administration.
Patients may be given desensitization therapy.
Rash: maculopapular rash occurs 9% of time that is not allergic in
origin, appears 7 to 10 days into treatment.
GI: diarrhea, nausea/vomiting (n/v), addition of clavulanate increases
risk of diarrhea
Fungal overgrowth
C. difficile colitis
Most are pregnancy category B.


Clinical use and dosing
Commonly prescribed for infections seen in primary care
Amoxicillin is first-line therapy for acute otitis media
(AOM) and sinusitis.
Penicillin (PCN) is used for streptococcal pharyngitis.
Amoxicillin/clavulanate is first-line therapy for infection
following bites, including human.
Rational drug selection
Defining tests (rapid strep) vs. empiric method
Cost

Monitoring
Return to office for evaluation of symptom relief.
Are symptoms getting better?
Patient education: resistance, ADRs,
completing course

Beta-Lactams: Cephalosporins
Pharmacodynamics: structurally and chemically similar to PCNs
Inhibit mucopeptide synthesis in the bacterial cell wall
Four generations
First generation
Used for skin and soft tissue infections
Primarily active against gram-positive bacteria, S. aureus and S. epidermidis
Second generation
Active against same as first generation, plus Klebsiella, Proteus, E. coli
Third generation
Used for broader indications
More active against gram-negative bacteria
Fourth generation
Resistant to beta-lactamase
Primarily active against gram-positive bacteria
Beta-Lactams: Cephalosporins (contd)

Pharmacokinetics: oral formulations absorbed from
GI tract, widely distributed to most tissues, some
highly bound to proteins, some are metabolized to
less active compounds, most excreted via kidneys, in
various degrees as unchanged drug
ADRs: allergies, skin rashes, arthralgia, coagulation
abnormalities, anemia, neutropenia, leukopenia,
thrombocytosis, fever, seizures, renal/hepatic failure

Beta-Lactams: Cephalosporins (contd)

Used for therapeutic failure in AOM
First generation: strep pharyngitis, skin infections
Cephalexin, cefpodoxime, cefixime can be prescribed as second-line drugs for
urinary tract infection (UTI).
Ceftriaxone and cefixime used for general condition gonococcus
(GC)/chlamydia
Cefpodoxime, cefuroxime, or parenteral ceftriaxone followed by oral
cefpodoxime are used for community-acquired pneumonia.
Monitoring
For diarrhea (C. difficile)
Renal function, if prolonged therapy
Patient education
Use as prescribed.
Fluoroquinolones
Pharmacodynamics: interfere with bacterial enzymes
required for the synthesis of bacterial DNA
Noted for extensive gram-negative activity
Not recommended for children less than 18 years
of age.
Increasing resistance due to overprescribing
Can no longer be used for gonorrhea
Resistant tuberculosis (TB)

Fluoroquinolones (contd)
Pharmacokinetics
Well-absorbed; take on empty stomach for best absorption.
ADRs
Black Box warning for tendonitis/tendon rupture
Elderly at higher risk
Can have delayed onset, 120 days to months after administration
GI: pseudomembranous colitis
Central nervous system (CNS): sleep disorders, dizziness, acidosis
Renal/hepatic failure
Cardiovascular: angina, atrial flutter
Avoid in pregnancy.
Do not prescribe to children less than 18 years of age.
Complicated UTI, pyelonephritis infections, chronic
bacterial prostatitis
Pneumonia/chronic bronchitis exacerbation
PCN-resistant S. pneumoniae, skin infections, bone/joint
infections, complicated intraabdominal, infectious diarrhea
Monitoring: watch for prolonged use, ECG with at-
risk patients before prescribing moxifloxacin, alcohol
use, monitor for tendonitis/rupture
Patient education
Food delays absorption.
Many drug interactions
Take with full glass of water.
May cause dizziness
If tendon tenderness occurs, stop medication and
notify provider.
Lincosamides: Clindamycin (Cleocin)

Pharmacodynamics: inhibits protein synthesis
No gram-negative activity
Gram-positive activity: corynebacterium acnes, gardnarella
vaginalis, some methicillin-resistant Staphylococcus
aureus (MRSA)
Pharmacokinetics: oral dosing completely absorbed, not
affected by gastric acid
ADRs: boxed warning for severe colitis; dermatological:
rash, burning, itching, erythema; transient eosinophelia,
neutropenia, thrombocytopenia

Lincosamides: Clindamycin
(Cleocin) (contd)
First-line therapy for MRSA in some areas
Infections in PCN-allergic patients
Drug-resistant Streptococcus Pneumoniae infections
Dental infections
Considered second-line therapy, narrow spectrum of
aerobic activity
First-line therapy in special populations (pregnancy
and children)
Lincosamides: Clindamycin
(Cleocin) (contd)
Monitoring
Stop medication if significant diarrhea occurs.
Patient education
Finishing therapy
ADRs: diarrhea

Macrolides, Azalides, Ketolides

Pharmacodynamics: erythromycin
Inhibits ribonucleic acid (RNA)-dependent protein synthesis
Weak bases, activity increases in alkaline media.
Atypical and intracellular organisms commonly resistant to beta-
lactam antibiotics are often susceptible.
Cross-resistance seen to all in class
Pharmacokinetics: well-absorbed from duodenum
Potent inhibitors of CYP 450 3A4
Combination with statins may increase risk for myopathy.
Exhibit enterohepatic recycling, which can lead to buildup in the
system and can cause n/v; tissue levels are higher than serum levels

Macrolides, Azalides, Ketolides (contd)

Precautions and contraindications
Most are safe in pregnancy and children
ADRs
Dose-related GI: n/v, abdominal pain, cramping, diarrhea
Skin: urticaria, bullous eruptions, eczema,
Stevens-Johnson syndrome
Drug interactions
Inhibitors of CYP 3A4


Drug of choice for community-acquired pneumonia (mycoplasma)
Chlamydia
Pertussis
H. Pylori infections (clarithromycin)
Chronic bronchitis
Often as alternatives for PCN allergies
Increasing resistance
Not appropriate for treating AOM or sinusitis


Monitoring
For altered response to concurrent medications
metabolized by CYP 450 3A4 or 2C9
Hepatic/renal impairment
Hearing loss
Patient education
ADRs
Drug interactions
Sulfonamides, Trimethoprim,
Nitrofurantoin
Pharmacodynamics
Sulfonamides block folic acid synthesis, trimethoprim inhibits DNA
synthesis, nitrofurantoin may inhibit acetyl coenzymes.
Inhibit both gram-positive and gram-negative bacteria
E. coli, S. pyogenes, S. pneumoniae, H. influenza, and some protozoa
Resistance an issue
ADRs: GI - anorexia, n/v, diarrhea, stomatitis; rashes,
increased hypersensitivity reactions, photosensitivity;
CNS - headache, dizziness, drug interactions
Avoid in G6PD deficiency.

Sulfonamides, Trimethoprim,
Nitrofurantoin (contd)
Most commonly used with UTI infections
MRSA is susceptible in some areas
Low-cost alternative in children less than 2 months and PCN allergies
Monitoring
Control and status if treating UTI
Long-term use check CBC
Chest x-ray for patients that develop a cough when on
nitrofurantoin
Patient education: finish course, ADRs, resistance,
Oxalodinones: Linezolid
Pharmacodynamics
Inhibitors of bacterial ribosomal protein synthesis
Most effective against aerobic gram-positive bacteria
Resistance emerging
Pharmacokinetics
Well-absorbed orally
Does not use CYP 450 enzymes
ADRs
Diarrhea, headache, nausea
Myelosuppression has been reported, resolves with discontinuation
of drug.

Oxalodinones: Linezolid (contd)

Pneumonia
Complicated skin infections
Use less expensive drugs first
Expensive ($1,152 for 20)
Patient education
Administration
ADRs
Tetracyclines
Pharmacodynamics
Tetracycline and doxycycline
Bind reversibly to the 30S subunit of the bacterial ribosome
Pharmacokinetics
Food decreases absorption.
Milk and calcium decrease absorption.
Precautions and contraindications
Do not prescribe to pregnant women, lactating women, or children
less than age 8 years.
Drug interactions: many

Tetracyclines (contd)
Doxycycline is considered first-line therapy for
C. trachomatis and Ureaplasma urealyticum.
Tetracycline and minocycline are used to treat P. acnes.
Some H. pylori regimens include tetracycline.
Doxycycline and minocycline can be taken with food.
Patient education
Administration, ADRs, avoid pregnancy

Lipoglycopeptides: Vancomycin
Pharmacodynamics
Vancomycin, telavancin (Vibativ), dalbavancin (Zeven)
Used for severe gram-positive infections, such as MRSA-resistant to
first-line antibiotics
Inhibits cell wall synthesis
Pharmacokinetics
Poor oral absorption, given IV
ADRs
Ototoxicity (transient or permanent)
Nephrotocity
Red Man syndrome if infused too fast

Lipoglycopeptides: Vancomycin (contd)

Serious gram-positive infections resistant to
other medications
Monitoring
Hearing and renal function
Patient education
Administration
ADRs

Mycobacteria
Grow slowly and are relatively resistant to drugs that are
largely dependent on how rapidly cells are dividing
Have a lipid-rich cell wall relatively impermeable to
many drugs
Are usually intracellular and inaccessible to drugs that do not
have good intracellular penetration
Have the ability to go into a dormant state
Easily develop resistance to any single drug
Antimycobacterials
Pharmacodynamics
Isoniazid (INH) and ethambutol inhibit synthesis of mycolic acids.
Rifampin binds to the beta subunit of mycobacteria DNA-dependent
RNA polymerase and inhibits RNA synthesis.
Ethambutol inhibits synthesis of arabinogalactan, an essential
component of mycobacteria cell walls.
Resistance develops rapidly to monotherapy.
Cross-resistance with INH and ethionamide
Pharmacokinetics
Well-absorbed orally
Metabolism of isoniazid is highly variable and dependent on
acetylator status.
Antimycobacterials (contd)
ADRs
INH: peripheral neuropathy
INH, rifampin, and pyrazinamide: hepatotoxicity
Ethambutol: optic neuritis
Streptomycin and capreomycin: ototoxic
Rifabutin: neutropenia and thrombocytopenia
Drug interactions
Many drug interactions
Rifampin is an inducer of CYP 450 enzyme.

Antimycobacterials (contd)
Follow Centers for Disease Control (CDC) guidelines.
Active TB requires four-drug therapy.
Preventive therapy with INH
Follow CDC guidelines.
Monitoring
Directly observed therapy
Patient education
Importance of taking medication daily
Reporting of ADRs
Antivirals: Nucleoside Analogues

Pharmacodynamics
Antiviral drugs must either block entry into the cells or be
active inside host cells to be effective.
Acyclovir: active against herpes simplex viruses 1 and 2
(HSV-1 and HSV-2); varicella-zoster virus (VZV); Epstein-Barr
virus (EBV), cytomegalovirus (CMV), and herpes virus 6
Valacyclovir is converted to acyclovir after oral
administration and is active against the same viruses.
Famciclovir: active against HSV-1 and HSV-2, VZV, EBV, and
hepatitis B virus
Ganciclovir is active against CMV.
Antivirals: Nucleoside Analogues

ADRs
Acyclovir/valacyclovir: few ADRs when given orally
Valacyclovir may cause thrombocytopenia purpura,
hemolytic uremic syndrome in
immunocompromised patients.
Famciclovir: headache
Ganciclovir: granulocytopenia, anemia and
thrombocytopenia; may be carcinogenic
Drug interactions
Few
Antivirals: Nucleoside
Analogues (contd)
Herpes simplex virus: genital herpes, both initial outbreak
and suppression therapy
Herpes zoster (shingles): Start therapy within 3 days
of outbreak.
Varicella (chickenpox): Start within 24 hours of outbreak.
Gingivostomatitis in children
Bells palsy
Choice based on cost and convenience
Antivirals: Nucleoside
Analogues (contd)
Monitoring
Rash for resolution
Temperature
Blood urea nitrogen and creatinine high-risk patients
Patient education
Drug started at earliest sign of infection
Good hydration
Educate regarding symptoms of renal failure,
encephalopathic changes, blood dyscrasias
Antivirals for Influenza

Pharmacodynamics
Oseltamivir (Tamiflu), peramivir (Rapivab), zanamivir
(Relenza) are used to treat influenza A and B.
Sensitivity varies by year.
Resistance to amantadine and rimantadine is common, no
longer recommended for influenza.
Pharmacokinetics
Oseltamivir is well-absorbed after oral administration.
Zanamivir is inhaled, 4% to 17% absorbed.
Peramivir is administered IV.
Antivirals for Influenza (contd)

ADRs
Zanamivir: bronchitis and shortness of breath
Oseltamivir, zanamivir are approved for the prophylaxis
and treatment of influenza type A and B.
Peramivir is approved for acute influenza in those 18 years
and older.
CDC updates prescribing recommendations annually.
See: www.cdc.gov/flu

Antivirals for Influenza (contd)

Monitoring
Renal function in elderly and debilitated patients
Older patients: evaluate for confusion, hallucinations, and
cognitive impairment
Patient education
Take full course of therapy.
ADRs
Advise annual influenza vaccination

Systemic Azoles and Other Antifungals

Pharmacodynamics
Polyene macrolides: amphotericin B and nystatin
Azoles have broad spectrum activity: butoconazole,
clotrimazole, ketoconazole, minonazole, terconazole,
tioconazole, fluconazole, itraconazole
Allylamines active against yeast and dermatophytes:
naftifine, terbinafine
Nuclear acid synthesis inhibitors: flucytosine
Griseofulvin

Systemic Azoles and Other

Antifungals (contd)
Pharmacokinetics
Absorption of itraconazole is enhanced by food.
Absorption of griseofulvin is enhanced by fat.
Fluconazole is an inhibitor of CYP 450 3A4 and 2C9.
Itraconazole is an inhibitor of CYP 450 3A4.
Ketoconazole is an inhibitor of CYP 450 3A4.
ADRs
All of the azoles and terbinafine have been associated
with hepatotoxicity.
Drug interactions
Multiple due to CYP 450 3A4 inhibition


Antifungals (contd)
Oral antifungals used to treat superficial infections by
yeasts (Candida, pityriasis versicolor) and dermatophytes
(tinea infections) and invasive systemic mycoses
Fluconazole requires loading dose.
Fluconazole has the fewest drug interactions.


Antifungals (contd)
Monitoring
Ketoconazole: aspartate amino transferase, alanine
aminotransferase, alkaline phosphatase, and bilirubin
before and every 3 to 4 months
Patient education
Instruct to take with food.
Discourage alcohol use.
Educate regarding signs of liver toxicity.
Anthelminthics
Pharmacodynamics
Intestinal nematodes are treated with mebendazole, pyrantel,
and thiabendazole.
Tissue nematodes are treated with mebendazole, thiabendazole,
albendazole, or ivermectin.
In the United States pinworms are common: 50 million cases per year
ADRs
Nausea, vomiting, diarrhea, transient abdominal pain
Mebendazole may cause transient neutropenia.
Ivermectin may cause Mazzotti reaction.

Anthelminthics (contd)
Pinworms: single dose of mebendazole, pyrantel pamoate,
or albendazole
Whipworms: pyrantel pamoate, albendazole, mebendazole
Roundworms: mebendazole
Hookworms: pyrantel pamoate, albendazole, mebendazole
Threadworm: ivermectin or thiabendazole
Scabies: off-label ivermectin in immunocompromised patients
Use CDC recommendations.

Anthelminthics (contd)
Monitoring
Assess for the eradication of the helminth.
Roundworms, hookworms, ascariasis, trichuriasis, and whipworms;
stool samples are obtained before and 1 to 3 weeks after treatment
for proof of cure
Patient education
Albendazole and mebendazole are given with a high-fat meal.
Ivermectin is taken on an empty stomach.
Albendazole should not be taken if pregnant and back-up
contraception should be used for 1 month after taking.

Metronidazole and Nitazoxanide

Pharmacodynamics
Metronidazole treats both parasitical and
bacterial infections.
Active against Trichomonas vaginalis, Entamoeba histolytica,
H. pylori, Clostridium, C. difficile
Nitazoxanide is used to treat Giardia lamblia and
Cryptosporidium.
Tinidazole is active against amebiasis, giardiasis,
and trichomoniasis.
Pharmacokinetics
Metronidazole is well-absorbed when taken orally.
Metronidazole and
Nitazoxanide (contd)
ADRs
Mitronidazole: anorexia, nausea, abdominal pain, dizziness, headache,
metallic taste
Metronidazole and tinidazole are used against the protozoal infections
T. vaginalis, G. lamblia, and E. histolytica.
Metronidazole is used for anaerobic bacterial infections, bacterial
vaginosis, and is one of the drugs in H. pylori treatment.
Metronidazole is on $4 retail lists.
Avoid metronidazole in first trimester of pregnancy.

Metronidazole and
Nitazoxanide (contd)
Monitoring
Resolution of symptoms
Signs of leukopenia
Patient education
Administration
Metallic taste with metronidazole
Avoid alcohol if taking metronidazole or tinidazole due to
disulfiram-like reaction.
Concurrent treatment of partner if sexually transmitted
infection

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Pharmacotherapeutics for Advanced Nurse Practitioner Prescribers, 4th Edition

Drugs Used in Treating

Copyright 2016 F.A. Davis Company

Copyright 2016 F.A. Davis Company

Antimicrobial Resistance (contd)

Copyright 2016 F.A. Davis Company

Copyright 2016 F.A. Davis Company

Beta-Lactams: Penicillins (contd)

Beta-Lactams: Penicillins (contd)

Copyright 2016 F.A. Davis Company

Beta-Lactams: Penicillins (contd)

Beta-Lactams: Penicillins (contd)

Copyright 2016 F.A. Davis Company

Beta-Lactams: Cephalosporins (contd)

Copyright 2016 F.A. Davis Company

Beta-Lactams: Cephalosporins (contd)

Copyright 2016 F.A. Davis Company

Lincosamides: Clindamycin (Cleocin)

Copyright 2016 F.A. Davis Company

Copyright 2016 F.A. Davis Company

Macrolides, Azalides, Ketolides

Copyright 2016 F.A. Davis Company

Macrolides, Azalides, Ketolides (contd)

Copyright 2016 F.A. Davis Company

Macrolides, Azalides, Ketolides (contd)

Copyright 2016 F.A. Davis Company

Macrolides, Azalides, Ketolides (contd)

Copyright 2016 F.A. Davis Company

Copyright 2016 F.A. Davis Company

Oxalodinones: Linezolid (contd)

Copyright 2016 F.A. Davis Company

Copyright 2016 F.A. Davis Company

Copyright 2016 F.A. Davis Company

Lipoglycopeptides: Vancomycin (contd)

Copyright 2016 F.A. Davis Company

Copyright 2016 F.A. Davis Company

Antivirals: Nucleoside Analogues

Antivirals: Nucleoside Analogues

Antivirals for Influenza

Antivirals for Influenza (contd)

Copyright 2016 F.A. Davis Company

Antivirals for Influenza (contd)

Copyright 2016 F.A. Davis Company

Systemic Azoles and Other Antifungals

Copyright 2016 F.A. Davis Company

Systemic Azoles and Other

Copyright 2016 F.A. Davis Company

Systemic Azoles and Other

Copyright 2016 F.A. Davis Company

Systemic Azoles and Other

Copyright 2016 F.A. Davis Company

Copyright 2016 F.A. Davis Company

Copyright 2016 F.A. Davis Company

Metronidazole and Nitazoxanide

Copyright 2016 F.A. Davis Company

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