Clindamycin (Systemic)

• Cleocin
• Cleocin in D5W
• Cleocin Phosphate
• CLIN Single Use

Reversibly binds to 50S ribosomal subunits preventing peptide bond formation thus inhibiting bacterial protein synthesis; bacteriostatic or bactericidal depending on drug concentration, infection site, and organism

Absorption

Oral, hydrochloride: Rapid (90%); clindamycin palmitate must be hydrolyzed in the GI tract before it is active

Distribution

Distributed in body fluids and tissues; no significant levels in CSF, even with inflamed meninges

Metabolism

Biologically inactive clindamycin phosphate (intravenous formulation) is rapidly converted to active clindamycin. Clindamycin is metabolized predominantly by CYP3A4, with minor contribution by CYP3A5, to form clindamycin sulfoxide (major metabolite) and N-desmethylclindamycin (minor metabolite)

Excretion

Urine (~10%) and feces (3.6%) as active drug and metabolites

Time to Peak

Serum: Oral: Within 60 minutes; IM: 1 to 3 hours

Half-Life Elimination

Neonates: Premature: 8.7 hours; Full-term: 3.6 hours; Infants 1 month to 1 year: 3 hours; Children: ~2.5 hours; Adults: 3 hours; Elderly (oral) ~4 hours (range: 3.4 to 5.1 hours)

Protein Binding

94%

Bone and joint infections: Treatment of bone and joint infections, including acute hematogenous osteomyelitis caused by Staphylococcus aureus and as adjunctive therapy in the surgical treatment of chronic bone and joint infections caused by susceptible organisms.

Gynecological infections: Treatment of gynecologic infections, including endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infection caused by susceptible anaerobes.

Intra-abdominal infections: Treatment of intra-abdominal infections, including peritonitis and intra-abdominal abscess caused by susceptible anaerobic organisms.

Lower respiratory tract infections: Treatment of lower respiratory tract infections, including pneumonia, empyema, and lung abscess caused by anaerobes, Streptococcus pneumoniae, other streptococci (except Enterococcus faecalis), and S. aureus.

Septicemia: Treatment of septicemia caused by S. aureus, streptococci (except E. faecalis), and susceptible anaerobes.

Skin and skin structure infections: Treatment of skin and skin structure infections caused by Streptococcus pyogenes, S. aureus, and anaerobes.

Acute bacterial rhinosinusitis

Based on the Infectious Diseases Society of America (IDSA) guidelines for acute bacterial rhinosinusitis (ABRS) in children and adults, clindamycin (in combination with a third-generation cephalosporin) is an effective and recommended therapy for the treatment of ABRS.

Acute otitis media (children)

According to American Academy of Pediatrics (AAP) guidelines on the management of acute otitis media, when an antibiotic is considered necessary, amoxicillin should be prescribed for most children. Oral clindamycin is an alternative option in children with an infection known or presumed to be caused by penicillin-resistant S. pneumoniae. In addition, clindamycin is recommended as an alternative treatment in patients who have failed initial or second courses of antibiotic therapy.

Anthrax

Based on the Centers for Disease Control and Prevention (CDC) expert panel meetings on prevention and treatment of anthrax in adults and recommendations from the American Academy of Pediatrics (AAP) for pediatric anthrax clinical management, clindamycin is an effective and acceptable alternative for postexposure prophylaxis, treatment of cutaneous anthrax, and first-line in combination with other antimicrobials for the treatment of systemic anthrax. Alternative regimens have also been suggested for patients with anthrax, including injectable drug users who develop injectional anthrax [Hicks 2012].

Babesiosis

Based on the Infectious Diseases Society of America (IDSA) guidelines for the clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis, clindamycin (in combination with quinine) is an effective and recommended therapy option for the treatment of babesiosis.

Bacterial vaginosis

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, oral clindamycin is an effective and recommended alternative agent for patients with bacterial vaginosis.

Bite wounds (animal)

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), clindamycin, in combination with a second- or third-generation cephalosporin, levofloxacin, or sulfamethoxazole and trimethoprim, is an effective and recommended alternative for treatment of animal bite wounds.

Community-acquired pneumonia (children)

Following clinical guideline recommendations on the management of CAP reduces the incidence of morbidity and mortality related to pneumonia. Clindamycin is the preferred oral option for treatment of CAP caused by MRSA and should be added to empiric beta-lactam therapy when S. aureus is suspected. It can be used for pathogen-directed therapy aimed at penicillin-resistant S. pneumoniae, GAS, or MSSA in children older than 3 months of age. Clindamycin has been associated with severe, fatal colitis.

Diabetic foot infections

Based on the IDSA guidelines for the diagnosis and treatment of diabetic foot infections, clindamycin is an effective and recommended treatment option for mild diabetic foot infection due to Staphylococcus aureus or Streptococcus spp and, in combination with ciprofloxacin or levofloxacin, for moderate diabetic foot infection

Group A streptococcal pharyngitis (adults)

Group A streptococcus is the most common bacterial cause of acute pharyngitis. When treating beta-lactam–allergic patients, clindamycin is a suitable alternative. Guideline dosage regimens are for 3-times-daily administration rather than the Food and Drug Administration (FDA)–approved 4-times-daily administration.

Group B Streptococcus (GBS) infection (maternal use for neonatal prophylaxis in penicillin-allergic women)

Based on the Centers for Disease Control and Prevention (CDC) guidelines for the prevention of perinatal group B streptococcal disease, the use of clindamycin is effective and recommended if the GBS isolate is sensitive to clindamycin and erythromycin or if testing for inducible clindamycin resistance is negative when the isolate is resistant to erythromycin in patients at high risk for anaphylaxis due to penicillin allergy.

Infective endocarditis (prophylaxis)

Based on the American Heart Association (AHA) guidelines for the prevention of infective endocarditis, in patients with certain cardiac conditions who are allergic to penicillins or ampicillin the use of clindamycin is effective and recommended as an alternative antibiotic for the prevention of infective endocarditis associated with dental or respiratory tract procedures.

Malaria

Based on the Centers for Disease Control and Prevention (CDC) guidelines for the treatment of malaria, the use of clindamycin, in combination with quinidine or quinine, is effective and recommended for the treatment of this condition.

Methicillin-resistant Staphylococcus aureus (MRSA) infection

Based on the Infectious Diseases Society of America (IDSA) guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children, clindamycin is effective and recommended in the treatment of community-acquired MRSA infection including cellulitis, skin and soft tissue infections, osteomyelitis, pneumonia, and septic arthritis.

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), clindamycin is an effective and recommended treatment option for skin and soft tissue infections caused by MRSA.

Pneumocystis pneumonia (PCP) in HIV-infected patients (adolescents and adults)

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, clindamycin (with primaquine) is an effective and recommended alternative regimen for the treatment of Pneumocystis pneumonia (PCP) in adolescent and adult HIV-infected patients.

Prophylaxis in patients with prosthetic joint implants undergoing dental procedures which produce bacteremia

Although currently not recommended for routine use prior to dental procedures in patients with prosthetic joint implants to prevent prosthetic joint infection as stated within the American Academy of Orthopaedic Surgeons/American Dental Association Prevention of Orthopaedic Implant Infection in Patients Undergoing Dental Procedures guidelines and a subsequent report of the American Dental Association Council on Scientific Affairs, if deemed to be necessary for select patients at risk for prosthetic joint infection (eg, history of complications associated with joint replacement surgery), antibiotic prophylaxis may be considered. Dentists planning invasive oral procedures should therefore consult with the patient's orthopedic surgeon to determine the risk associated with infection and the need for antibiotics. Based on a retired advisory statement from the American Dental Association and American Academy of Orthopaedic Surgeons, the use of clindamycin was suggested for patients allergic to penicillin [ADA/AAOS 2003].

Prosthetic joint infection

Based on the IDSA guidelines for the diagnosis and treatment of diabetic foot infections, clindamycin is an effective and recommended treatment option for mild diabetic foot infection due to Staphylococcus aureus or Streptococcus spp and, in combination with ciprofloxacin or levofloxacin, for moderate diabetic foot infection

Skin and soft tissue necrotizing infections

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), clindamycin is an effective and recommended treatment option for necrotizing infections of the skin, fascia, and muscle. It should be used in combination with cefotaxime or ceftriaxone for empiric treatment of mixed (polymicrobial) infections; in combination with penicillin IV for infections due to group A streptococci or Clostridium species; or may be used as monotherapy for necrotizing infections due to methicillin-sensitive Staphylococcus aureus (MSSA).

Surgical (perioperative) prophylaxis (injection)

Clinical guidelines recommend use of clindamycin as alternative therapy for surgical prophylaxis in patients with a beta-lactam allergy, and if risk of infection from gram-negative bacteria is present, in combination with an aminoglycoside, aztreonam, or a fluoroquinolone.

Toxoplasma gondii encephalitis (treatment/chronic maintenance) in HIV-infected patients (adolescents and adults)

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, clindamycin (with pyrimethamine and leucovorin) is an effective and recommended alternative regimen in the treatment and chronic maintenance therapy of Toxoplasma gondii encephalitis in adolescent and adult HIV-infected patients.

Usual dose:

Neonates: IM, IV: Manufacturer’s labeling: 15 to 20 mg/kg/day divided every 6 to 8 hours.

Infants, Children, and Adolescents:

Oral: 8 to 40 mg/kg/day in 3 to 4 divided doses; Manufacturer’s labeling: 8 to 20 mg/kg/day (as hydrochloride) or 8 to 25 mg/kg/day (as palmitate) in 3 to 4 divided doses; minimum dose of palmitate: 37.5 mg 3 times daily

IM, IV: Manufacturer’s labeling: 20 to 40 mg/kg/day or 350 to 450 mg/m2/day in 3 to 4 divided doses

Acute bacterial rhinosinusitis (off-label use): Oral: 30 to 40 mg/kg/day divided every 8 hours with concomitant cefixime or cefpodoxime for 10 to 14 days. Note: Recommended in patients with non-type I penicillin allergy, after failure of initial therapy or in patients at risk for antibiotic resistance (eg, daycare attendance, age <2 years, recent hospitalization, antibiotic use within the past month) (Chow 2012).

Acute otitis media (off-label use): Oral: 30 to 40 mg/kg/day in 3 divided doses for 5 to 10 days. Use with or without concomitant third-generation cephalosporin for failure of initial antibiotic therapy; use with a third-generation cephalosporin is recommended for failure of a second course of antibiotics. Duration depends upon illness severity and patient age: Severe illness or <2 years: 10 days; 2 to 5 years: 7 days; children ≥6 years: 5 to 7 days (Lieberthal 2013).

Anthrax (off-label use) (Bradley 2014):

Postexposure prophylaxis: Oral: 30 mg/kg/day divided every 8 hours for 60 days after exposure (maximum: 900 mg/dose)

Cutaneous, treatment: Oral: 30 mg/kg/day divided every 8 hours for 7 to 10 days after naturally acquired infection; up to 60 days following biological weapon related event (maximum: 900 mg/dose)

Systemic, treatment: IV: 40 mg/kg/day divided every 8 hours for ≥14 days (maximum: 900 mg/dose); use in combination with a bactericidal antimicrobial (eg, fluoroquinolone, penicillin G); if meningitis is suspected or cannot be ruled out, use in combination with 2 bactericidal antimicrobials (eg, fluoroquinolone and beta-lactam or glycopeptide). Continue with prophylaxis therapy for up to 60 days from onset of illness.

Babesiosis (off-label use): Oral: 20 to 40 mg/kg/day divided every 8 hours for 7 to 10 days plus quinine (Red Book [AAP 2015])

Impetigo: Oral: 20 mg/kg/day divided every 8 hours for 7 days, depending on response (IDSA [Stevens 2014])

Malaria, severe (off-label use): IV: Load: 10 mg/kg followed by 15 mg/kg/day divided every 8 hours plus IV quinidine gluconate; switch to oral therapy (clindamycin plus quinine) when able for total clindamycin treatment duration of 7 days (Note: Quinine duration is region specific, consult CDC for current recommendations) (CDC 2013)

Malaria, uncomplicated treatment (off-label use): Oral: 20 mg/kg/day divided every 8 hours for 7 days plus quinine (CDC 2013)

Osteomyelitis due to MRSA (off-label use): IV, Oral: 10 to 13 mg/kg/dose every 6 to 8 hours for a minimum of 4 to 6 weeks (maximum: 40 mg/kg/day) (IDSA [Liu 2011])

Pharyngitis, group A streptococci (IDSA recommendations): Oral:

Acute treatment in penicillin-allergic patients: 21 mg/kg/day divided every 8 hours (maximum: 300 mg per dose) for 10 days (IDSA [Shulman 2012])

Chronic carrier treatment: 20 to 30 mg/kg/day divided every 8 hours (maximum: 300 mg per dose) for 10 days (IDSA [Shulman 2012])

Pneumocystis pneumonia (PCP) in HIV-infected patients (alternative to preferred therapy) (off-label use): Adolescents: Refer to adult dosing.

Pneumonia:

Community-acquired pneumonia (CAP) (IDSA/PIDS [Bradley 2011]): Infants >3 months and Children: Note: In children ≥5 years, a macrolide antibiotic should be added if atypical pneumonia cannot be ruled out.

Group A Streptococcus:

Moderate to severe infection (alternative to ampicillin/penicillin): IV: 40 mg/kg/day divided every 6 to 8 hours

Mild infection, step-down therapy (alternative to amoxicillin/penicillin): Oral: 40 mg/kg/day divided every 8 hours

Presumed bacterial (in addition to recommended antibiotic therapy), S. pneumoniae moderate to severe (MICs to penicillin ≤2.0 mcg/mL) (alternative to ampicillin/penicillin): IV: 40 mg/kg/day divided every 6 to 8 hours

S. pneumoniae:

Moderate to severe infection (MICs to penicillin ≥4.0 mcg/mL) (alternative to ceftriaxone): IV: 40 mg/kg/day divided every 6 to 8 hours

Mild infection, step-down therapy (MICs to penicillin ≥4.0 mcg/mL) (alternative to levofloxacin or linezolid): Oral: 30 to 40 mg/kg/day divided every 8 hours

S. aureus (methicillin-susceptible):

Moderate to severe infection (alternative to cefazolin or oxacillin): IV: 40 mg/kg/day divided every 6 to 8 hours

Mild infection, step-down therapy (alternative to cephalexin): Oral: 30 to 40 mg/kg/day divided every 6 to 8 hours

S. aureus (methicillin-resistant/clindamycin-susceptible):

Moderate to severe infection (preferred): IV: 40 mg/kg/day divided every 6 to 8 hours; recommended duration: 7 to 21 days (IDSA [Liu 2011])

Mild infection, step-down therapy (preferred): Oral: 30 to 40 mg/kg/day divided every 6 to 8 hours; recommended duration: 7 to 21 days (IDSA [Liu 2011])

Health care-associated pneumonia (HAP) (methicillin-resistant/clindamycin-susceptible): Children: Oral, IV: 30 to 40 mg/kg/day divided every 6 to 8 hours for 7 to 21 days (IDSA [Liu 2011])

Prophylaxis against infective endocarditis (off-label use):

Oral: 20 mg/kg 30 to 60 minutes before procedure (Wilson 2007)

IM, IV: 20 mg/kg 30 to 60 minutes before procedure. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications (Wilson 2007).

Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.

Septic arthritis due to MRSA (off-label use): IV, Oral: 10 to 13 mg/kg/dose every 6 to 8 hours for minimum of 3 to 4 weeks (maximum: 40 mg/kg/day) (IDSA [Liu 2011])

Skin and soft tissue infections due to MSSA:

Oral: 25 to 30 mg/kg/day divided every 8 hours for 7 to 14 days (IDSA [Stevens 2014])

IV: 25 to 40 mg/kg/day divided every 8 hours for 7 to 14 days (IDSA [Stevens 2014])

Skin and soft tissue infections due to MRSA (off-label use):

Oral: 30 to 40 mg/kg/day divided every 8 hours for 7 to 14 days (IDSA [Stevens 2014])

IV: 25 to 40 mg/kg/day divided every 8 hours for 7 to 14 days (IDSA [Stevens 2014])

Complicated infections: Oral, IV: 10 to 13 mg/kg/dose every 6 to 8 hours for 7 to 14 days (maximum: 40 mg/kg/day) (IDSA [Liu 2011])

Cellulitis: Oral: 10 to 13 mg/kg/dose every 6 to 8 hours for 5 to 10 days (maximum: 40 mg/kg/day) (IDSA [Liu 2011])

Skin and soft tissue necrotizing infections (off-label use): IV: 10 to 13 mg/kg/dose every 8 hours, in combination with cefotaxime for empiric therapy of polymicrobial infections or in combination with penicillin IV for the treatment of group A streptococcal or Clostridium species necrotizing infections. May give as monotherapy for MSSA. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (IDSA [Stevens 2014])

Streptococcal skin infections: IV: 10 to 13 mg/kg/dose every 8 hours (IDSA [Stevens 2014])

Surgical (perioperative) prophylaxis (off-label use): IV: 10 mg/kg within 60 minutes prior to surgical incision. Doses may be repeated in 6 hours if procedure is lengthy (maximum single dose: 900 mg) (Bratzler 2013).

Toxoplasma gondii encephalitis in HIV-exposed/-positive patients (off-label use):

Children:

Treatment: IV, Oral: 5 to 7.5 mg/kg/dose (maximum dose: 600 mg) every 6 hours (plus pyrimethamine and leucovorin) (HHS [pediatric] 2016).

Secondary prevention: Oral: 7 to 10 mg/kg/dose (maximum dose: 600 mg) every 8 hours (plus pyrimethamine and leucovorin) (HHS [pediatric] 2016).

Adolescents: Refer to adult dosing.

Never administer undiluted as bolus. For IV infusion, dilute vials with 50 to 100 mL of compatible diluent (eg, D5W, NS); concentration of clindamycin for IV infusion should not exceed 18 mg/mL.

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Clindamycin (Systemic). Refer to the specific clindamycin (systemic) - rifampin drug interaction monograph for information concerning that combination. Exceptions: RifAMPin. Monitor therapy

Erythromycin (Systemic): Lincosamide Antibiotics may diminish the therapeutic effect of Erythromycin (Systemic). Avoid combination

Kaolin: May decrease the absorption of Lincosamide Antibiotics. Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Mecamylamine: Lincosamide Antibiotics may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

Neuromuscular-Blocking Agents: Lincosamide Antibiotics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Clindamycin crosses the placenta and can be detected in the cord blood and fetal tissue (Philipson 1973; Weinstein 1976). Clindamycin injection contains benzyl alcohol which may also cross the placenta. Clindamycin pharmacokinetics are not affected by pregnancy (Philipson 1976; Weinstein 1976). Clindamycin is recommended for use in pregnant women for the prophylaxis of group B streptococcal disease in newborns (alternative therapy) (ACOG 485, 2011); prophylaxis and treatment of Toxoplasma gondii encephalitis (alternative therapy), or Pneumocystis pneumonia (PCP) (alternative therapy) (HHS [OI adult 2015]); bacterial vaginosis (CDC [Workowski 2015]); anthrax (Meaney-Delman 2014); or malaria (CDC 2013). Clindamycin is also one of the antibiotics recommended for prophylactic use prior to cesarean delivery and may be used in certain situations prior to vaginal delivery in women at high risk for endocarditis (ACOG 120, 2011).