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Chapter 39

Antibiotics Part 2

Multidrug resistance

Therapeutic drug monitoring

Minimum inhibitory concentration (MIC)

Time-dependent killing

Concentration-dependent killing

Once-daily dosing vs. multidaily dosing

Peak and trough blood levels

Synergistic effects

Postantibiotic effect (PAE)

Antibiotic Therapy: Concepts

Organisms that are resistant to one or more classes of antimicrobial drugs

Methicillin-resistant Staphylococcus aureus (MRSA)

Vancomycin-resistant Enterococcus (VRE)

Organisms producing extended-spectrum beta-lactamases (ESBLs)

Organisms producing Klebsiella pneumoniae carbapenemase (KPC)

Multidrug-Resistant Organisms

Natural and semisynthetic

Produced from Streptomyces

Poor oral absorption; no PO forms (exception neomycin)

Very potent antibiotics with serious toxicities

Bactericidal; prevent protein synthesis

Kill mostly gram-negative bacteria; some gram-positive

Aminoglycosides

gentamicin

neomycin (Neo-fradin)

tobramycin (TOBI)

amikacin

Aminoglycosides (cont’d)

Used to kill gram-negative bacteria, such as Pseudomonas spp., Escherichia coli, Proteus spp., Klebsiella spp., Serratia spp.

Often used in combination with other antibiotics for synergistic effects

Used for certain gram-positive infections that are resistant to other antibiotics

Aminoglycosides: Indications

Aminoglycosides are poorly absorbed through the GI tract, and given parenterally

Exception: neomycin

Given orally to decontaminate the GI tract before surgical procedures

Also used as an enema for this purpose

Used to treat hepatic encephalopathy

Aminoglycosides: Indications (cont’d)

Cause serious toxicities

Nephrotoxicity (renal damage)

Ototoxicity (auditory impairment and vestibular impairment [eighth cranial nerve])

Must monitor drug levels to prevent toxicities

Minimum inhibitory concentration (MIC)

Aminoglycosides: Adverse Effects

Ototoxicity and nephrotoxicity are the most significant

Headache

Paresthesia

Fever

Superinfections

Vertigo

Skin rash

Dizziness

Aminoglycosides: Adverse Effects (cont’d)

Also called fluoroquinolones

Excellent oral absorption

Absorption reduced by antacids

Effective against gram-negative organisms and some gram-positive organisms

Quinolones

ciprofloxacin (Cipro)

norfloxacin (Noroxin)

levofloxacin (Levaquin)

moxifloxacin (Avelox)

Quinolones (cont’d)

Bactericidal

Alter DNA of bacteria, causing death

Do not affect human DNA

Quinolones: Mechanism of Action

Gram-negative bacteria such as Pseudomonas

Complicated urinary tract, respiratory, bone and joint, GI, skin, and sexually transmitted infections

Anthrax (ciproflaxin)

Quinolones: Indications

Classroom Response Question

During intravenous quinolone therapy in an 88-year-old patient, which potential problem is of most concern when assessing for adverse effects?

Hepatotoxicity

Rhabdomyolysis

Tendon rupture

Nephrotoxicity

Correct answer: C

Rationale: A black box warning is required by the U.S. Food and Drug Administration for all quinolones because of the increased risk of tendonitis and tendon rupture with use of the drugs. This effect is more common in elderly patients, patients with renal failure, and those receiving concurrent glucocorticoid therapy (e.g., prednisone).

Quinolones: Adverse Effects

Body System Adverse Effects

CNS Headache, dizziness, insomnia, depression, restlessness, convulsions

GI Nausea, vomiting, diarrhea, constipation, thrush, increased liver function studies, others

Cardiac Prolonged QT interval

Quinolones: Adverse Effects (cont’d)

Body System Adverse Effects

Integumentary Rash, pruritus, urticaria, flushing

Other Ruptured tendons,* tendonitis,* fever, chills, blurred vision, tinnitus

*Black box warning: Increased risk of tendonitis and tendon rupture

clindamycin (Cleocin)

linezolid (Zyvox)

metronidazole (Flagyl)

nitrofurantoin (Macrodantin)

quinupristin/dalfopristin (Synercid)

daptomycin (Cubicin)

vancomycin (Vancocin)

colistimethate (Coly-Mycin)

telavancin (Vibativ)

Miscellaneous Antibiotics

clindamycin (Cleocin)

Used for chronic bone infections, GU infections, intraabdominal infections, other serious infections

May cause pseudomembranous colitis (also known as antibiotic-associated colitis, Clostridium difficile diarrhea, or C. difficile infection)

Potential interaction with vecuronium

Miscellaneous Antibiotics (cont’d)

linezolid (Zyvox)

New class: oxazolidinones

Used to treat vancomycin-resistant Enterococcus faecium (VREF, VRE), hospital-acquired, and skin structure infections, including those with MRSA

May cause hypotension, serotonin syndrome if taken with SSRIs, and reactions if taken with tyramine-containing foods

Miscellaneous Antibiotics (cont’d)

Classroom Response Question

A patient is prescribed linezolid (Zyvox) to treat hospital-acquired pneumonia. It is most important for the nurse to determine if the patient is also taking which medication?

A diuretic

A selective serotonin reuptake inhibitor

A cardiac glycoside

A thyroid replacement drug

Correct answer: B

Rationale: Linezolid has the potential to strengthen the vasopressor (prohypertensive) effects of various vasopressive drugs such as dopamine by an unclear mechanism. Also, there have been postmarketing case reports of this drug causing serotonin syndrome when used concurrently with serotonergic drugs such as the selective serotonin reuptake inhibitor (SSRI) antidepressants. It is recommended that the SSRI be stopped while the patient is receiving linezolid therapy if possible.

metronidazole (Flagyl)

Used for anaerobic organisms

Intraabdominal and gynecologic infections

Protozoal infections

Several drug interactions

Miscellaneous Antibiotics (cont’d)

nitrofurantoin (Macrodantin)

Primarily used for urinary tract infections (UTIs) (E. coli, Staphylococcus aureus, Klebsiella spp., Enterobacter spp.)

Use carefully if renal function is impaired

Drug concentrates in the urine

May cause fatal hepatotoxicity

Miscellaneous Antibiotics (cont’d)

quinupristin/dalfopristin (Synercid)

30:70 combination, work synergistically

Used for bacteremia and infections caused by vancomycin-resistant Enterococcus (VRE) and for treatment of complicated skin and skin structure infections caused by S. pyogenes and S. aureus, including MRSA

May cause arthralgias, myalgias

Miscellaneous Antibiotics (cont’d)

vancomycin (Vancocin)

Treatment of choice for MRSA and other gram-positive infections

Oral vancomycin is indicated for the treatment of antibiotic-induced colitis (C. difficile) and for the treatment of staphylococcal enterocolitis

Must monitor blood levels to ensure therapeutic levels and prevent toxicity

May cause ototoxicity and nephrotoxicity

Miscellaneous Antibiotics (cont’d)

Classroom Response Question

A 58-year-old man is receiving vancomycin as part of the treatment for a severe bone infection. After the infusion, he begins to experience some itching and flushing of the neck, face, and upper body. He reports no chills or difficulty breathing. The nurse should suspect:

an allergic reaction has occurred.

an anaphylactic reaction is about to occur.

the medication will not be effective for the bone infection.

the IV dose may have infused too quickly.

Correct answer: D

Rationale: These symptoms are know as red man syndrome and may occur during or after an infusion of vancomycin. This syndrome is characterized by flushing and/or itching of the head, face, neck, and upper trunk area. Symptoms can usually be alleviated by slowing the rate of infusion to at least 1 hour. Red man syndrome is bothersome but usually not harmful. Rapid infusions may also cause hypotension.

vancomycin (Vancocin) (cont’d)

Red man syndrome may occur

Flushing/itching of head, neck, face, upper trunk

Antihistamine may be ordered to reduce these effects

Additive neuromuscular blocking effects in patients receiving neuromuscular blockers

Should be infused over 60 minutes

Rapid infusions may cause hypotension

Miscellaneous Antibiotics (cont’d)

daptomycin (Cubicin)

Only drug of the new class known as lipopeptides

Mechanism of action is not completely known

Binds to gram-positive cells in a calcium-dependent process and disrupts the cell membrane potential

Used to treat complicated skin and soft-tissue infections caused by susceptible gram-positive bacteria, including MRSA and VRE

Miscellaneous Antibiotics (cont’d)

colistimethate (Coly-Mycin)

Polypeptide antibiotic that penetrates and disrupts the bacterial membrane of susceptible strains of gram-negative bacterial

Commonly referred to as colistin

Serious adverse effects

Can cause acute respiratory failure when administered by inhalation

Miscellaneous Antibiotics (cont’d)

telavancin (Vibativ)

Lipoglycopeptide

Indicated for the treatment of skin and skin structure infections caused by susceptible gram-positive organisms

Effective against MRSA and VRE

Most common adverse effects include renal toxicity, infusion-related reactions, and QT prolongation

Miscellaneous Antibiotics (cont’d)

Before beginning therapy, assess drug allergies; hepatic, renal, 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

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

Nursing Implications (cont’d)

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

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)

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

Nursing Implications (cont’d)

Classroom Response Question

A group of office workers is concerned because a package was opened that contained a white powder substance. There is a concern that the white powder is anthrax. Which drug does the nurse anticipate being prescribed for the office workers?

daptomycin (Cubicin)

colistimethate (Coly-Mycin)

ciprofloxacin (Cipro)

quinupristin/dalfopristin (Synercid)

Correct answer: C

Rationale: Ciprofloxacin (Cipro) is the drug of choice for the treatment of anthrax (infection with Bacillus anthracis).

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)