CHAPTER 39 Antibiotics Part 2

Antibiotic Therapy: Concepts Multidrug resistance Therapeutic drug monitoring Minimum inhibitory concentration (MIC) Time-dependent killing Concentration-dependent killing Once-daily dosing vs. multi-daily dosing Peak and trough blood levels Synergistic effects Post-antibiotic effect (PAE)

Antibiotic Therapy: Toxicities Ototoxicity Temporary or permanent hearing loss, balance problems Nephrotoxicity Varying degrees of reduced renal function Rising serum creatinine may indicate reduced creatinine clearance Monitor trough levels every 5 to 7 days while on therapy or as ordered Monitor serum creatinine levels at least every 3 days as an index of renal function

Aminoglycosides gentamicin (Garamycin) neomycin (Neo-fradin) tobramycin (Nebcin) amikacin (Amikin) kanamycin streptomycin

Aminoglycosides (cont’d) Natural and semisynthetic Produced from Streptomyces Poor oral absorption; no PO forms Very potent antibiotics with serious toxicities Bactericidal; prevent protein synthesis Kill mostly gram-negative bacteria; some gram-positive also

Aminoglycosides: Indications Used to kill gram-negative bacteria such as Pseudomonas spp., E. 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 (cont’d) 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

Aminoglycosides: Adverse Effects Cause serious toxicities Nephrotoxicity (renal damage) Ototoxicity (auditory impairment and vestibular impairment [eighth cranial nerve]) Must monitor drug levels to prevent toxicities

Aminoglycosides: Adverse Effects (cont’d) Ototoxicity and nephrotoxicity are the most significant Headache Paresthesia Fever Superinfections Vertigo Skin rash Dizziness

Quinolones ciprofloxacin (Cipro) norfloxacin (Noroxin) levofloxacin (Levaquin) moxifloxacin (Avelox)

Quinolones (cont’d) Also called “fluoroquinolones” Excellent oral absorption Absorption reduced by antacids Effective against gram-negative organisms and some gram-positive organisms

Quinolones: Mechanism of Action Bactericidal Alter DNA of bacteria, causing death Do not affect human DNA

Quinolones: Indications Gram-negative bacteria such as pseudomonas Respiratory infections Bone and joint infections GI infections Skin infections Sexually transmitted diseases Anthrax

Fluoroquinolones: Adverse Effects Body System Adverse Effects CNS Headache, dizziness, fatigue, depression, restlessness, insomnia GI Nausea, vomiting, diarrhea, constipation, thrush, increased liver function studies, others Cardiac Prolonged QT interval

Fluoroquinolones: Adverse Effects (cont’d) Body System Adverse Effects Integumentary Rash, pruritus, urticaria, flushing, photosensitivity (with lomefloxacin) Other Fever, chills, blurred vision, tinnitus Black box warning: increased risk of tendonitis and tendon rupture

Other Antibiotics clindamycin (Cleocin) linezolid (Zyvox) metronidazole (Flagyl) nitrofurantoin (Macrodantin) quinupristin and Dalfopristin (Synercid) daptomycin (Cubicin) vancomycin (Vancocin) colistimethate (Coly-mycin)

Other Antibiotics (cont’d) clindamycin (Cleocin) Used for chronic bone infections, GU infections, intraabdominal infections, other serious infections May cause pseudomembranous colitis

Other Antibiotics (cont’d) linezolid (Zyvox) New class: oxazolidinones Used to treat vancomycin-resistant Enterococcus faecium (VREF, VRE), hospital-acquired skin 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

Other Antibiotics (cont’d) metronidazole (Flagyl) Used for anaerobic organisms Intraabdominal and gynecologic infections Protozoal infections Several drug interactions

Other Antibiotics (cont’d) nitrofurantoin (Macrodantin) Primarily used for UTIs (E. coli, S. aureus, Klebsiella spp., Enterobacter spp.) Use carefully if renal function is impaired Drug concentrates in the urine May cause fatal hepatotoxicity Usually well-tolerated if patient is kept well-hydrated

Other Antibiotics (cont’d) quinupristin and dalfopristin (Synercid) 30:70 combination, work synergistically Used for bacteremia and infections caused by vancomycin-resistant Enterococcus (VRE) and other complicated skin infections May cause arthralgias, myalgias

Other Antibiotics (cont’d) daptomycin (Cubicin) New class: lipopeptide Used to treat complicated skin and soft-tissue infections

Other Antibiotics (cont’d) vancomycin (Vancocin) Natural, bactericidal antibiotic Destroys cell wall Treatment of choice for MRSA and other gram-positive infections Must monitor blood levels to ensure therapeutic levels and prevent toxicity May cause ototoxicity and nephrotoxicity Should be infused over 60 minutes Rapid infusions may cause hypotension

Other Antibiotics (cont’d) vancomycin (Vancocin) (cont’d) Monitor IV site closely Red man syndrome may occur Flushing/itching of head, neck, face, upper trunk Antihistamine may be ordered to reduce these effects Ensure adequate hydration (2 L fluids/24 hr) if not contraindicated to prevent nephrotoxicity Monitor trough levels carefully

Nursing Implications 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 (cont’d) 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 when 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) Aminoglycosides Monitor peak and trough blood levels of these drugs to prevent nephrotoxicity and ototoxicity Symptoms of ototoxicity include dizziness, tinnitus, and hearing loss Symptoms of nephrotoxicity include urinary casts, proteinuria, and increased BUN and serum creatinine levels

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