Macrolides

Macrolides are antibiotics with a macrocyclic lactone structure that has one or more deoxy sugars attached. They include the following drugs;

• Azithromycin
• Clarithromycin
• Erythromycin
• Roxithromycin
• Fidaxomicin
• Telithromycin

Erythromycin was the first to be used as a drug of first choice and as an alternative to patients allergic to penicillins.

Pregnancy Category: B or C

They may be acceptable but can be used if benefits outweigh the risks.

Mechanism of Action

They are bacteriostatic or bactericidal at higher doses in susceptible bacteria. They bind irreversibly to the 50S subunit of the bacterial ribosome, thus interfering with the translocation and sometimes transpeptidation steps of protein synthesis.

Pharmacokinetics

• Administration: All macrolides are adequately absorbed upon oral administration. Erythromycin and azithromycin are available IV. Erythromycin base is easily destroyed by gastric acid and therefore only enteric-coated tablets or its esterified forms are administered. Clarithromycin, azithromycin, and telithromycinare stable in gastric acid. Food increases the absorption of clarithromycin but can inhibit the absorption of erythromycin and azithromycin.
• Distribution: Clarithromycin, azithromycin, and telithromycin distribute widely in the tissues. Erythromycin distributes well to all body fluids including prostate fluid and macrophages only that it does not go into the CSF. These drugs concentrate in the liver. Azithromycin concentrates in neutrophils, macrophages, and fibroblasts, but its serum levels are low. It also has the longest half-life and the largest distribution volume of the macrolides.
• Elimination: Erythromycin and telithromycin are metabolized extensively in the liver. Erythromycin and azithromycin are concentrated and excreted in the bile as active drugs and are partially reabsorbed through the enterohepatic circulation.
  In contrast, clarithromycin and its metabolites are eliminated by the kidney as well as the liver.

Indications

• Treatment of acute infections caused by sensitive strains of Streptococcus pneumoniae, Mycoplasma pneumoniae, Listeria monocytogenes, Legionella pneumophila
• Treatment of URIs, lower respiratory tract infections, skin and soft-tissue infections caused by group A beta-hemolytic streptococci when oral treatment is preferred to injectable benzathine penicillin
• Treatment of PID caused by Neisseria gonorrhoeae in patients allergic to penicillin
• Treatment of intestinal amebiasis caused by Entamoeba histolytica
• Treatment of infections in the newborn and in pregnancy that are caused by Chlamydia trachomatis and in adult chlamydial infections when tetracycline cannot be used
• Treatment of primary syphilis (Treponema pallidum) in penicillin-allergic patients
• Used in eliminating Bordetella pertussis organisms from the nasopharynx of infected individuals and as prophylaxis in exposed and susceptible individuals
• Treatment of superficial ocular infections caused by susceptible strains of microorganisms
• Used in the prophylaxis of ophthalmia neonatorum caused by N. gonorrhoeae or C. trachomatis
• Used in conjunction with sulfonamides to treat URIs caused by Haemophilus influenzae
  Adjunct to antitoxin in infections caused by Corynebacterium diphtheriae and Corynebacterium minutissimum
• Used as prophylaxis against alpha-hemolytic streptococcal endocarditis before dental or other procedures in patients allergic to penicillin who have valvular heart disease and against infection in minor skin abrasions
• Unlabeled uses: Treatment of severe diarrhea associated with Campylobacter enteritis or enterocolitis; treatment of genital, inguinal, or anorectal lymphogranuloma venereum infection; treatment of Haemophilus ducreyi (chancroid); treatment of acne vulgaris and skin infections caused by sensitive microorganisms
  
  

Cautions and Contraindications

• Use cautiously with hepatic impairment or lactation (secreted and may be concentrated in breast milk; may modify bowel flora of breast-fed infant and interfere with fever workups). Clarithromycin dosage should be adjusted in patients with renal impairment since it is metabolized in the kidney.
• Contraindicated in patients allergic to any macrolide antibiotic.

Adverse Effects

• CNS: Reversible hearing loss, confusion, uncontrollable emotions, abnormal thinking, headache
• Dermatologic: Edema, urticaria, dermatitis, angioneurotic edema
• GI: Abdominal cramping, anorexia, diarrhea, vomiting,pseudomembranous colitis, hepatotoxicity
• Hypersensitivity: Allergic reactions ranging from rash to anaphylaxis
• Local: Irritation, burning, itchingat site of application
• Other: Superinfections

Interactions

• Increased serum levels of digoxin
• Increased effects of oral anticoagulants, theophylline, carbamazepine
• Increased therapeutic and toxic effects of corticosteroids
• Increased levels of cyclosporine and risk of renal toxicity
• Increased irritant effects with peeling, desquamating, or abrasive agents used with dermatologic preparations
• Risk of prolonged QT interval if combined with other drugs that prolong QT interval
• Interferes with fluorometric determination of urinary catecholamines  
• Decreased urinary estriol levels caused by inhibition of hydrolysis of steroids in the gut

Nursing Considerations

Assessment

• Assess for allergy to macrolides,
• Assess for renal and hepatic impairment,
• Assess for lactation,
• Assess for viral, fungal, mycobacterial infections of the eye
• Site of infection, skin color, lesions;
• Assess orientation, affect, hearing tests;
• Assess respiratory adventitious sounds;
• Assess GI output, bowel sounds, liver evaluation;
• Assess for culture and sensitivity tests of infection,
• Assess urinalysis, LFTs

Interventions

• Culture site of infection before therapy.
• Administer oral erythromycin base or stearate on an empty stomach, 1 hour before or 2–3 hours after meals, with a full glass of water.
• Administer drug around the clock to maximize therapeutic effect; scheduling may have to be adjusted to minimize sleep disruption.
• Monitor liver function in patients on prolonged therapy; serious toxicity can occur.
• Institute hygiene measures and treatment if superinfections occur.
• If GI upset occurs with oral therapy, some preparations (see previous) may be given
  with meals, or it may be possible to substitute one of these preparations.
• Provide frequent small meals if GI problems occur.
• Establish safety measures (accompany patient, side rails) if CNS changes occur.
• Give patient support and encouragement to continue with therapy.
• Wash affected area, rinse well, and dry before topical application.

Patient/Family Teaching

• Take oral drugs on an empty stomach, 1 hour before or 2–3 hours after meals, with a full glass of water, or, as appropriate, drug may be taken without regard to meals. These drugs should be taken around the clock;
  schedule to minimize sleep disruption. It is important that you finish the full course of the drug therapy
• Wash and rinse area and pat it dry before applying topical solutions; use fingertips or an applicator; wash hands thoroughly after application.
• You may experience these side effects: Stomach cramping, discomfort (taking the drug with meals, if appropriate, may alleviate this problem); uncontrollable emotions, crying, laughing, abnormal thinking (will end when the drug is stopped).
• Report severe or watery diarrhea, severe nausea or vomiting, dark urine, yellowing of the skin or eyes, loss of hearing, skin rash or itching.

References

• Karch M. (2014). Lippincott’s Nursing Drug Guide.Wolter’s Kluwer/Lippincott Williams and Wilkins. New York, USA.
• Vallerand A., Sanoski C., Deglin J. (2015). Davis’s Drug Guide for Nurses (14^th Ed). F.A Davis Company. Philadelphia, Pennsylvania, USA.
• Whalen K., Finkel R., Panavelil T. (2015). Lippincott Illustrated Reviews Pharmacology (6^th Ed). Wolter’s Kluwer. USA.