Continuing Education Activity

Clindamycin is a medication used for the treatment of numerous infections, including but not limited to septicemia, intra-abdominal infections, lower respiratory infections, gynecological infections, bone and joint infections, and skin and skin structure infections. Clindamycin is also used in the treatment of streptococcal pharyngitis, acne vulgaris, bacterial vaginosis, and severe pelvic inflammatory disease. This activity reviews the indications, action, and contraindications for clindamycin as a valuable agent in managing various infections.

Objectives:

• Identify the indications for clindamycin use.
• Describe the various routes of administration of clindamycin.
• Review the contraindications of clindamycin usage.
• Summarize the importance of antibiotic stewardship and how it affects antimicrobial selection as it pertains to improving care coordination among the interprofessional team when initiating antibiotic therapy with clindamycin.

Indications

Clindamycin is FDA-approved to treat septicemia, intra-abdominal infections, lower respiratory infections, gynecological infections, bone, and joint infections, and skin and skin structure infections. Clindamycin is also used to treat streptococcal pharyngitis, acne vulgaris, bacterial vaginosis, and severe pelvic inflammatory disease. Although not a first-line treatment, The Infectious Diseases Society of America (IDSA) has published guidelines for using intravenous (IV) clindamycin for the inpatient treatment of community-acquired pneumonia and aspiration pneumonia. Dentists will use clindamycin for prophylactic coverage against endocarditis. Anesthesiologists and surgeons will often administer clindamycin per The American Society of Health-System Pharmacists (ASHP) and IDSA guidelines as prophylaxis in the operating room. Gynecologists use clindamycin in combination with gentamycin +/- ampicillin for covering their patients with endometritis. It can also be an alternative to metronidazole for treating Gardnerella vaginosis, which presents with gray, fishy vaginal odor with clue cells on wet prep.[1][2][1]

Additionally, clindamycin can be used to treat babesiosis, anthrax, and malaria. Clindamycin is also commonly used in skin and soft tissue infections that are uncomplicated. Clindamycin is used in soft tissue infections due to its efficacy against MRSA. Clindamycin is also a choice for outpatient treatment because of its cost, availability, and effectiveness against methicillin-resistant Staphylococcus aureus.[3]

Mechanism of Action

Clindamycin prevents peptide bond formation, thereby inhibiting protein synthesis by reversibly binding to 50S ribosomal subunits. Depending on the organism, infection site, and drug concentration, clindamycin may be a bacteriostatic or bactericidal antibiotic. When taken orally, absorption cannot occur until clindamycin palmitate becomes hydrolyzed in the gastrointestinal (GI) tract. It then distributes across the body in tissue and other regions containing blood. Clindamycin cannot efficiently penetrate meninges very well and is therefore not an antibiotic of choice for infections of the cerebrospinal fluid (CSF). As it travels through the bloodstream, clindamycin is primarily bound to protein. Clindamycin is primarily metabolized in the liver by CYP 3A4 (major) and CYP 3A5, which oxidizes the antibiotic into clindamycin sulfoxide (primary metabolite) and N-desmethyl clindamycin, respectively. When administered orally, the antibiotic peaks within 60 minutes. When given intramuscularly (IM), the drug achieves peak concentrations in 1 to 3 hours. The half-life of clindamycin is approximately 3 hours in adults and approximately 2.5 hours in children. At this point, it is excreted in the urine (major) and feces (minor) as active and inactive metabolites.[4][5][6][7]

Administration

Clindamycin can be administered into the body by multiple routes. It is available topically as a foam, gel, lotion, or solution for the treatment of acne vulgaris. A thin film needs to be applied twice a day. For the treatment of bacterial vaginosis, it is available in cream and suppository for intravaginal administration. Systemic infections can be treated orally with a capsule (75 mg, 150 mg, 300 mg) or in solution (75 mg/5 mL). It is also available as an intramuscular injection (9 g/60 mL, 300 mg/2 mL, 600 mg/4 mL, 900 mg/6 mL). Intravenous formulations are available as follows: clindamycin phosphate (300 mg/2 mL, 600 mg/4 mL, 900 mg/6 mL), and clindamycin phosphate in D5W or NaCl (300 mg/50 mL, 600 mg/50 mL, 900 mg/50 mL).

To minimize esophageal ulceration, administer orally with a full glass of water. The absorption of clindamycin flavored granules is not adversely affected by co-administration with food. When administered intramuscularly, the sites must require rotation with no dose exceeding 600 mg in a single injection. Clindamycin is administered by intravenous (IV) intermittent infusion over at least 10 to 60 minutes at a maximum rate of 30 mg/minutes. The final concentration of the IV solution should not exceed 18 mg/mL. Pediatric dosing for neonates is 15 to 20 mg/kg per day, given IM/IV divided over 6 to 8 hours. Infants, children, and adolescents are treated with 8 to 40 mg/kg per day orally divided over 3 to 4 doses. For IM/IV administration, 20 to 40 mg/kg per day can be given over 3 to 4 doses.[8]

Adverse Effects

The adverse effects of clindamycin vary based on how its mode of administration. The most common side effects experienced with topical use include pruritis, xeroderma, erythema, burning, exfoliation, or oily skin. The most common side effects of intravaginal administration are vaginal candidiasis, pruritis, vulvovaginal disease, and vulvovaginitis. The primary adverse effects of clindamycin with systemic administration are pseudomembranous colitis, nausea, vomiting, and diarrhea, resulting from clindamycin destroying much of the GI tract’s healthy flora. Clostridium difficile is allowed to overgrow in this environment. Toxins A and B, which are produced by C. difficile, cause Clostridium difficile-associated diarrhea (CDAD). If suspected, a stool antigen test should is in order. Severe cases that result from hypertoxic-producing strains occur in an increase in morbidity and mortality, which may require colectomy for definitive treatment. Other adverse effects include thrombophlebitis or metallic taste with IV administration, azotemia, agranulocytosis, anaphylactic shock, abscess formation, induration, or irritation at the site of IM injection.[9][10][11][12]

Contraindications

Clindamycin is contraindicated in patients with a history of pseudomembranous colitis or ulcerative colitis. Care is also necessary for antibiotic use as bacterial and fungal superinfections may occur. It is also contraindicated in patients with hypersensitivity to clindamycin, lincomycin, or any of their components. Special care must also be taken in patients with atopic dermatitis as colonization is more prevalent in this patient population. The pathogenicity of skin infections is higher in this population; this is important for future infections as antibiotic resistance is a problematic complication.[13]

Monitoring

Monitor for changes in bowel frequency, colitis, and resolution of symptoms.[13] Monitor liver function tests periodically in patients with severe liver disease. In prolonged therapy, monitor complete blood cell count (CBC), liver, and renal function. It is vital to manage fluid and electrolyte replacement in this patient population adequately.

Toxicity

The most common adverse effects that occur with clindamycin toxicity are GI or allergic. There is no antidote for clindamycin toxicity, and the adverse effects will resolve with dose adjustment or discontinuation of the antibiotic. The treatment is supportive. The recommendation is to measure serum electrolytes in patients with vomiting and/or diarrhea. Vital signs need to be monitored along with CBC with differential, platelets, LFTs, and renal function in symptomatic patients. It is also essential to get an ECG and maintain continuous cardiac monitoring as cardiac arrhythmias, although rare, may occur. Evaluation for C. difficile toxin will be needed when colitis is suspected.

It is important to look out for severe allergic reactions like DRESS or Steven-Johnson syndrome. In these situations, immediate discontinuation of the antibiotic is imperative, along with supportive management that includes: IV fluids, oxygen therapy, diphenhydramine, and corticosteroids. In cases of severe hypotension, it may be necessary to administer fluid boluses and start vasopressors. Airway management is likely not needed, but severe anaphylactic reactions will require airway management with endotracheal intubation. Rarely clindamycin toxicity will lead to cardiac arrhythmias and cardiac arrest, in which case advanced cardiovascular life support will be required.[14]

Enhancing Healthcare Team Outcomes

Clindamycin is a widely prescribed drug by many healthcare professionals, including the nurse practitioner, primary care provider, internist, infectious disease consultant, and emergency department physician. All healthcare workers who prescribe this agent should monitor the patient for changes in bowel frequency, colitis, and resolution of symptoms. Clindamycin is well known to cause Clostridium colitis, which extends hospital stays and increases healthcare costs. If diarrhea develops, it is essential to manage fluid and electrolyte replacement in this patient population adequately. Healthcare workers should limit the duration of clindamycin therapy and abstain from the empirical prescribing of this agent.

Management of clindamycin therapy will benefit from the efforts of an interprofessional healthcare team that includes the prescribing/order clinician (including mid-level practitioners), nursing staff, and pharmacists, all coordinating activity and engaging in open communication about the case and monitoring of the drug to optimize patient outcomes. [Level 5]