Pharmacology

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Chapter 38

Antibiotics Part 1

Community-associated infections

An infection that is acquired by a person who has not been hospitalized or had a medical procedure (such as dialysis, surgery, catheterization) within the past year

Infections: Sites of Origin

Health care–associated infections

Contracted in a hospital or institutional setting

Were not present or incubating in the patient on admission to the facility

More difficult to treat because causative microorganisms are often drug resistant and the most virulent

Occur in 10% of hospitalized patients

MRSA most common

Previously known as nosocomial

Infections: Sites of Origin (cont’d)

Handwashing

Antiseptics

Disinfectants

Health Care–Associated Infections: Prevention

Disinfectant

Kills organisms

Used only on nonliving objects

Antiseptic

Generally only inhibits the growth of microorganisms but does not necessarily kill them

Applied exclusively to living tissue

Health Care–Associated Infections: Prevention (cont’d)

Medications used to treat bacterial infections

Ideally, before beginning antibiotic therapy, the suspected areas of infection should be cultured to identify the causative organism and potential antibiotic susceptibilities

Antibiotics

Empiric therapy: treatment of an infection before specific culture information has been reported or obtained

Definitive therapy: antibiotic therapy tailored to treat organism identified with cultures

Prophylactic therapy: treatment with antibiotics to prevent an infection, as in intraabdominal surgery or after trauma

Antibiotic Therapy

Therapeutic response

Decrease in specific signs and symptoms of infection are noted (fever, elevated WBC, redness, inflammation, drainage, pain)

Subtherapeutic response

Signs and symptoms of infection do not improve

Antibiotic Therapy (cont’d)

Superinfection

Pseudomembranous colitis

Secondary infection

Resistance

Food-drug interactions

Host factors

Allergic reactions

Antibiotic Therapy (cont’d)

Sulfonamides

Penicillins

Cephalosporins

Macrolides

Quinolones

Aminoglycosides

Tetracyclines

Antibiotics: Classes

Interference with cell wall synthesis

Interference with protein synthesis

Interference with DNA replication

Acting as a metabolite to disrupt critical metabolic reactions inside the bacterial cell

Antibiotic Therapy: Mechanism of Action

Bactericidal: kill bacteria

Bacteriostatic: inhibit growth of susceptible bacteria, rather than killing them immediately; will eventually lead to bacterial death

Actions of Antibiotics

One of the first groups of antibiotics

Often combined with another antibiotic

Sulfamethoxazole combined with trimethoprim (a nonsulfonamide antibiotic), known as Bactrim, Septra, or co-trimoxazole and often abbreviated as SMX-TMP, is used commonly in clinical practice

Antibiotics: Sulfonamides

Bacteriostatic action

Prevent synthesis of folic acid required for synthesis of purines and nucleic acid

Do not affect human cells or certain bacteria—they can use preformed folic acid

Only affect organisms that synthesize their own folic acid

Sulfonamides: Mechanism of Action

Effective against both gram-positive and gram-negative bacteria

Treatment of UTIs caused by susceptible strains of:

Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Staphylococcus aureus

Sulfonamides: Indications

Pneumocystis jirovecii pneumonia (PJP)

Co-trimoxazole

Upper respiratory tract infections

Sulfamethoxazole/trimethoprim is commonly used for outpatient Staphylococcus infections, due to the high rate of community-acquired MRSA infections

Sulfonamides: Indications (cont’d)

Body System Adverse Effects

Blood Hemolytic and aplastic anemia, agranulocytosis, thrombocytopenia

Integumentary Photosensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, epidermal necrolysis

Sulfonamides: Adverse Effects

Body System Adverse Effects

GI Nausea, vomiting, diarrhea, pancreatitis

Other Hepatotoxicity, convulsions, crystalluria, toxic nephrosis, headache, peripheral neuritis, urticaria, cough

Sulfonamides: Adverse Effects (cont’d)

Penicillins

Cephalosporins

Carbapenems

Monobactams

Beta-Lactam Antibiotics

Natural penicillins

Penicillinase-resistant penicillins

Aminopenicillins

Extended-spectrum penicillins

Penicillins

Natural penicillins

penicillin G

penicillin V

Penicillinase-resistant drugs

nafcillin

cloxacillin

oxacillin

dicloxacillin

Penicillins (cont’d)

Aminopenicillins

amoxicillin (Amoxil), ampicillin (generic only)

Extended-spectrum drugs

carbenicillin

piperacillin

ticarcillin

Penicillins (cont’d)

Penicillins enter the bacteria via the cell wall

Inside the cell they bind to penicillin-binding protein

Once bound, normal cell wall synthesis is disrupted

Result: bacteria cells die from cell lysis

Penicillins do not kill other cells in the body

Penicillins: Mechanism of Action

Prevention and treatment of infections caused by susceptible bacteria, such as:

Gram-positive bacteria, including Streptococcus spp., Enterococcus spp., Staphylococcus spp.

Penicillins: Indications

Allergic reactions to the penicillins occur in 0.7% to 4% of treatment courses

Urticaria, pruritus, angioedema

Those allergic to penicillins have an increased risk of allergy to other beta-lactam antibiotics

Only those patients with a history of throat swelling or hives from penicillin should not receive cephalosporins

Penicillins: Adverse Effects

Common adverse effects

Nausea, vomiting, diarrhea, abdominal pain

Other adverse effects are less common

Penicillins: Adverse Effects (cont’d)

MANY interactions!

NSAIDs

Oral contraceptives

Warfarin

Others

Penicillins: Interactions

Classroom Response Question

A patient is receiving Augmentin (amoxicillin and clavulanic acid) liquid solution through a PEG tube. What is the purpose of the clavulanic acid?

It works synergistically with the antibiotic to improve potency.

It inhibits the action of the enzymes produced by beta-lactamase–producing bacteria.

It protects the antibiotic from the harmful gastric acid secretions in the stomach.

It enhances the absorption of the antibiotic in the small intestine.

Correct answer: B

Rationale: The clavulanic acid works to inhibit the action of the enzymes produced by the bacteria, which would normally inactivate the antibiotic.

First generation

Second generation

Third generation

Fourth generation

Fifth generation

Cephalosporins

Semisynthetic antibiotics

Structurally and pharmacologically related to penicillins

Bactericidal action

Broad spectrum

Divided into groups according to their antimicrobial activity

Cephalosporins (cont’d)

Good gram-positive coverage

Poor gram-negative coverage

Parenteral and PO forms

Examples

cefadroxil (Duricef, Ultracef)

cephradine (Velosef)

cefazolin (Ancef)

cephalexin (Keflex)

Cephalosporins: First Generation

Used for surgical prophylaxis, and for susceptible staphylococcal infections

cefazolin (Ancef and Kefzol): IV or IM

cephalexin (Keflex): PO

Cephalosporins: First Generation (cont’d)

Good gram-positive coverage

Better gram-negative coverage than first generation

Examples:

cefaclor (Ceclor)

cefprozil (Cefzil)

cefoxitin (Mefoxin)

cefuroxime (Zinacef)

cefotetan (Cefotan)

Cephalosporins: Second Generation

cefoxitin (Mefoxin): IV and IM

Used prophylactically for abdominal or colorectal surgeries

Also kills anaerobes

cefuroxime

Zinacef is parenteral form; Ceftin is PO

Surgical prophylaxis

Does not kill anaerobes

Cephalosporins: Second Generation (cont’d)

Most potent group against gram-negative bacteria

Less active against gram-positive bacteria

Examples

cefotaxime (Claforan)

ceftazidime (Fortaz)

cefdinir (Omnicef)

ceftizoxime (Cefizox)

ceftriaxone (Rocephin)

Cephalosporins: Third Generation

ceftriaxone (Rocephin)

IV and IM, long half-life, once-a-day dosing

Elimination is primarily hepatic

Easily passes meninges and diffused into CSF to treat CNS infections

Cephalosporins: Third Generation (cont’d)

ceftazidime (Ceptaz, Fortaz, Tazidime)

IV and IM forms

Excellent gram-negative coverage

Used for difficult-to-treat organisms such as Pseudomonas spp.

Excellent spectrum of coverage

Resistance is limiting usefulness

Cephalosporins: Third Generation (cont’d)

Broader spectrum of antibacterial activity than third generation, especially against gram-positive bacteria

Uncomplicated and complicated UTI

cefepime (Maxipime)

Cephalosporins: Fourth Generation

ceftaroline (Teflaro)

Broader spectrum of antibacterial activity

Effective against a wide variety of organisms

MRSA

Cephalosporins: Fifth Generation

Similar to penicillins

Mild diarrhea, abdominal cramps, rash, pruritus, redness, edema

Potential cross-sensitivity with penicillins if allergies exist

Cephalosporins: Adverse Effects

Broadest antibacterial action of any antibiotics to date

Reserved for complicated body cavity and connective tissue infections in acutely ill hospitalized patients

May cause drug-induced seizure activity

This risk can be reduced with proper dosage

Carbapenems

imipenem/cilastatin (Primaxin)

Used for treatment of bone, joint, skin, and soft-tissue infections; many other uses

Cilastatin inhibits an enzyme that breaks down imipenem

meropenem (Merrem)

ertapenem (Invanz)

doripenem (Doribax)

Carbapenems

aztreonam (Azactam)

Synthetic beta-lactam antibiotic

Primarily active against aerobic gram-negative bacteria (E. coli, Klebsiella spp., Pseudomonas spp.)

Bactericidal

Parenteral use only

Used for moderately severe systemic infections and UTIs

Monobactams

erythromycin (E-mycin, E.E.S, others)

azithromycin (Zithromax)

clarithromycin (Biaxin)

Macrolides

Prevent protein synthesis within bacterial cells

Considered bacteriostatic

Bacteria will eventually die

In high enough concentrations, may also be bactericidal

Macrolides: Mechanism of Action

Strep infections

Streptococcus pyogenes (group A beta-hemolytic streptococci)

Mild to moderate URI and LRI

Haemophilus influenzae

Spirochetal infections

Syphilis and Lyme disease

Gonorrhea, Chlamydia, Mycoplasma

Macrolides: Indications

azithromycin and clarithromycin

Approved for Mycobacterium avium-intracellulare complex infection (opportunistic infection associated with HIV/AIDS)

clarithromycin

Recently approved for use in combination with omeprazole for treatment of active ulcer disease associated with Helicobacter pylori infection

Macrolides: Indications (cont’d)

GI effects, primarily with erythromycin

Nausea, vomiting, diarrhea, hepatotoxicity, flatulence, jaundice, anorexia

Azithromycin and clarithromycin: fewer GI adverse effects, longer duration of action, better efficacy, better tissue penetration

Macrolides: Adverse Effects

telithromycin (Ketek)

Only drug in this class

Better antibacterial coverage than macrolides

Associated with severe liver disease

Use is limited

Ketolide

demeclocycline (Declomycin)

oxytetracycline (Terramycin)

tetracycline

doxycycline (Doryx, Vibramycin)

minocycline (Minocin)

tigecycline (Tygacil)

Tetracyclines

Natural and semisynthetic

Obtained from cultures of Streptomyces

Bacteriostatic—inhibit bacterial growth

Inhibit protein synthesis

Stop many essential functions of the bacteria

Tetracyclines (cont’d)

Bind (chelate) to Ca+++ and Mg++ and Al+++ ions to form insoluble complexes

Dairy products, antacids, and iron salts reduce oral absorption of tetracyclines

Should not be used in children under age 8 or in pregnant/lactating women because tooth discoloration will occur if the drug binds to the calcium in the teeth

Tetracyclines (cont’d)

Wide spectrum

Gram-negative and gram-positive organisms, protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis, Lyme disease, acne, others

Demeclocycline is also used to treat SIADH by inhibiting the action of ADH

Tetracyclines: Indications

Strong affinity for calcium

Discoloration of permanent teeth and tooth enamel in fetuses and children, or nursing infants if taken by the mother

May retard fetal skeletal development if taken during pregnancy

Tetracyclines: Adverse Effects

Alteration in intestinal flora may result in:

Superinfection (overgrowth of nonsusceptible organisms such as Candida)

Diarrhea

Pseudomembranous colitis

Tetracyclines: Adverse Effects (cont’d)

May also cause:

Vaginal candidiasis

Gastric upset

Enterocolitis

Maculopapular rash

Other effects

Tetracyclines: Adverse Effects (cont’d)

Before beginning therapy, assess drug allergies; renal, liver, and cardiac function; and other lab studies

Be sure to obtain thorough patient health history, including immune status

Assess for conditions that may be contraindications to antibiotic use or that may indicate cautious use

Assess for potential drug interactions

Nursing Implications

It is ESSENTIAL to obtain cultures from appropriate sites BEFORE beginning antibiotic therapy

Nursing Implications (cont’d)

Instruct patients to take antibiotics exactly as prescribed and for the length of time prescribed; they should not stop taking the medication early when they feel better

Assess for signs and symptoms of superinfection: fever, perineal itching, cough, lethargy, or any unusual discharge

Nursing Implications (cont’d)

For safety reasons, check the name of the medication carefully because there are many drugs that sound alike or have similar spellings

Nursing Implications (cont’d)

Classroom Response Question

When completing an admission assessment, the patient states that she is allergic to sulfa drugs. What will the nurse do next?

Mark the allergy on her medical record.

Place an “allergy” armband on the patient.

Ask the patient for more information about the allergic reaction she had.

Notify the physician about the patient’s allergy.

Correct answer: C

Rationale: Some patients will say they are “allergic” to drugs when in fact what they experienced was a common and mild adverse effect. The nurse should clarify the patient’s statements with open-ended questions.

Each class of antibiotics has specific adverse effects and drug interactions that must be carefully assessed and monitored

The most common adverse effects of antibiotics are nausea, vomiting, and diarrhea

All oral antibiotics are absorbed better if taken with at least 6 to 8 ounces of water

Nursing Implications (cont’d)

Classroom Response Question

A patient has a prescription for a sulfa drug as treatment for a urinary tract infection. She is also taking an oral contraceptive, an oral sulfonylurea antidiabetic drug, and phenytoin for a history of seizures. Which drug may pose a potential serious interaction with the sulfa drug?

The oral contraceptive

The oral antidiabetic drug

The phenytoin

All of these

Correct answer: D

Rationale: The combination of the sulfa drug with the oral contraceptive may reduce the effectiveness of the contraceptive. The combination with the oral antidiabetic drug may potentiate the hypoglycemic effect of the sulfonylurea drug, while the combination with the phenytoin may potentiate the toxic effects of the phenytoin.

Sulfonamides

Take with 2000 to 3000 mL of fluid/24 hr

Assess RBCs prior to beginning therapy

Take oral doses with food

Nursing Implications (cont’d)

Penicillins

Take oral doses with water (not juices) as acidic fluids may nullify drug’s antibacterial action

Monitor patients taking penicillin for an allergic reaction for at least 30 minutes after administration

Nursing Implications (cont’d)

Cephalosporins

Assess for penicillin allergy; may have cross allergy

Give orally administered forms with food to decrease GI upset, even though this will delay absorption

Some of these drugs may cause a disulfiram (Antabuse)-like reaction when taken with alcohol

Nursing Implications (cont’d)

Macrolides

These drugs are highly protein-bound and will cause severe interactions with other protein-bound drugs

The absorption of oral erythromycin is enhanced when taken on an empty stomach, but because of the high incidence of GI upset, many drugs are taken after a meal or snack

Nursing Implications (cont’d)

Tetracyclines

Avoid milk products, iron preparations, antacids, and other dairy products because of the chelation and drug-binding that occurs

Take all medications with 6 to 8 ounces of fluid, preferably water

Because of photosensitivity, avoid sunlight and tanning beds

Nursing Implications (cont’d)

Monitor for therapeutic effects

Improvement of signs and symptoms of infection

Return to normal vital signs

Negative culture and sensitivity tests

Disappearance of fever, lethargy, drainage, and redness

Monitor for adverse reactions

Nursing Implications (cont’d)