Johns Hopkins ABX Guide
Clindamycin
INDICATIONS
FDA
- Skin and soft tissue infections caused by streptococci, staphylococci and anaerobes
- Pelvic infections (endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and post-surgical vaginal cuff infections)
- Intra-abdominal infections such as peritonitis and intra-abdominal abscesses caused by anaerobes (note: IDSA guideline no longer recommends clindamycin due to increased B. fragilis resistance rate)
- Streptococcus pneumoniae (empyema, pneumonitis, and lung abscess)
- Septicemia (no longer recommended)
- Acne vulgaris (topical gel)
- Bacterial vaginosis in non-pregnant women and pregnant women during the second and third trimesters (intra-vaginal administration)
NON-FDA APPROVED USES
- Alternative treatment of PCP in combination with primaquine
- Alternative therapy of CNS toxoplasmosis in combination with pyrimethamine and leucovorin
- MRSA skin and soft tissue infections
- Necrotizing fasciitis, including Fournier gangrene, may be considered in combination with other agents to decrease toxin production caused by MRSA, S. pyogenes, C. perfringens
- Oral abscess in patients with PCN allergies
- Acute bacterial sinusitis
- Intrapartum prophylaxis for Group B strep; alternative to beta-lactam only if susceptibility testing is done
- Bacterial vaginosis
- Actinomycosis
- Osteomyelitis
- Acute bacterial sinusitis
- Non-severe malaria as part of the alternative regimen, especially in pregnancy
- Diphtheria
- Alternative therapy for babesiosis in combination with quinine
FORMS
brand name | preparation | manufacturer | route | form | dosage^ | cost* |
Cleocin | Clindamycin | Pfizer and other generic manufacturers | oral | capsule | 75 mg | $0.65 (HCL cost-5.13) |
oral | capsule | 150 mg | $1.19 (HCL cost-10.09) | |||
oral | capsule | 300 mg | $3.71 (HCL cost-20.41) | |||
Cleocin | Clindamycin, Clindamycin phosphate | IV | piggyback in D5W or 0.9% NS | 300 mg 600 mg 900 mg | $8.5-13.07 $12.82-20.93 $15.66-25.57 | |
Cleocin | Clindamycin phosphate | IV | vial (2 ml) vial (4 ml) vial (6 ml) vial (60 ml) | 300 mg 600 mg 900 mg 9 gm | $2.94-4.74 $3.48-5.25 $5.04-6.84 $20.77-27.59 | |
Cleocin | Clindamycin palmitate | oral | solution (100 ml) | 75 mg/5ml | $ 62-149.40 | |
Cleocin T | Clindamycin phosphate external | topical | solution (30 ml) | 1% | $40-88 | |
Cleocin | Clindamycin phosphate | vaginal | ovule suppository | 100 mg | $70 | |
Cleocin | Clindamycin phosphate | vaginal | cream (40 g) | 2% | $108-231 | |
Clindesse | Clindamycin phosphate | vaginal | cream (5 g) | 2% | $139 | |
Evoclin | Clindamycin phosphate external | topical | foam (50 g) | 1% | $347-572 | |
Cleocin T | Clindamycin phosphate external | topical | gel (30 g) | 1% | $86-180 | |
Clindagel | Clindamycin phosphate external | topical | gel (75 ml) | 1% | $2,133 | |
Cleocin T | Clindamycin phosphate external | topical | lotion (60 ml) | 1% | $120-251 |
*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.
USUAL ADULT DOSING
- Systemic dosing: depending on the condition, in combination with other antimicrobials.
- Skin and soft tissue infections (including animal or human bites): 300-450 mg PO q6h-8h or 600 mg IV q8h
- Oral doses > 350 mg are poorly tolerated
- Note: amoxicillin/clavulanate is usually the first line. If severe beta-lactam allergy, suggest using a fluoroquinolone, e.g., moxifloxacin.
- Necrotizing fasciitis, including gangrene: 600-900 mg IV q8h
- Pelvic inflammatory disease: 900 mg IV q8h (in combination with gentamicin)
- Osteomyelitis: 600-900 mg IV q8h or 300-450 mg PO q6h
- Acute bacterial sinusitis: 300 mg PO q6h
- Actinomycosis: 600 mg IV q 8h x 2-6 weeks, then clindamycin 300 mg PO q6h x 6-12 months
- Malaria:
- PCP: clindamycin 600 mg IV q6h-q8h or 300-450 mg PO q6h-8h in combination with primaquine 15-30 mg (base) PO once daily
- CNS toxoplasmosis: clindamycin 600 mg IV q6h or clindamycin 450 mg-600 mg PO q6h + pyrimethamine 200 mg PO loading dose, then 50-7 5mg PO q24hd + leucovorin 10-20 mg q24h
- Administration instructions: clindamycin capsules should be taken with a full glass of water to avoid esophageal irritation
- Skin and soft tissue infections (including animal or human bites): 300-450 mg PO q6h-8h or 600 mg IV q8h
- Topical applications:
- Bacterial vaginosis
- Vaginal ovules: 1 ovule (100 mg) x 3 days
- Cleocin (vaginal cream): one full applicator (100 mg) inserted intra-vaginally daily for 3-7 days in non-pregnant patients and for fr 7 days in pregnant patients
- Clindesse (vaginal cream): one full applicator inserted intra-vaginally as a single dose at any time during the day in non-pregnant patients
- Alternative dosing: one full applicator (5 g) at bedtime for 7 days
- Acne vulgaris:
- Cleocin T (gel, solution, lotion): apply twice daily to the affected area. More than one pledget can be used.
- Evoclin (foam): apply once daily to the affected area
- Clindagel (gel): apply once daily to the affected area
- Hidradenitis suppurativa: apply twice daily to the affected area
- Bacterial vaginosis
ADULT RENAL DOSING
DOSING IN HEMODIALYSIS
Usual regimen.
DOSING IN PERITONEAL DIALYSIS
Usual regimen.
DOSING IN RENAL REPLACEMENT THERAPY
Usual dose.
Other Adult Renal Dosing
GFR < 10 - 80 ml/min: Usual dose.
PEDIATRIC DOSING
USUAL PEDIATRIC DOSING
- Neonate (Neofax): 5 to 7.5 mg/kg/dose IV or PO
Post-menstrual age (weeks) | Post-natal age (days) | Dosing interval (hours) |
≤ 29 weeks | 0-28 days > 28 days | q12h q8h |
30 to 36 weeks | 0-14 days > 14 days | q12h q8h |
37 to 44 weeks | 0-7 days > 7 days | q12h q8h |
≥ 45 weeks | ALL | q6h |
- Infants/Children/Adolescents:
- General Dosing:
- IV: 20-40 mg/kg/day IV divided q6-8h; max 900 mg/dose given IV
- PO: 20-30 mg/kg/day PO divided q6-8h; max 450 mg/dose given PO
- NOTE: Guidelines for CAP[7], MRSA bone/joint and skin and soft tissue infections[6], and rhinosinusitis[5] state that PO dose can be as high as 40 mg/kg/day; however, most use a max of 30 mg/kg/day PO for tolerability.
- Malaria: see see malaria module for details, usually part of an alternative regimen.
- Uncomplicated (PO therapy): 20 mg/kg/day PO divided q8h plus quinine x 7 days
- Severe (IV therapy): loading dose of 10 mg/kg IV x 1, then 15 mg/kg/day IV divided q8h plus IV quinidine gluconate; switch to PO therapy (clindamycin and quinine) when able for a total treatment duration of 7 days
- Toxoplasmosis[15]:
- Treatment:
- Infants/children: 5 to 7.5 mg/kg/dose IV/PO q6h (max 600 mg/dose IV or PO) with pyrimethamine and leucovorin
- Adolescents: 600 mg IV/PO q6h with pyrimethamine and leucovorin
- Secondary prophylaxis:
- Infants/children: 7 to 10 mg/kg/dose PO q8h with pyrimethamine and leucovorin
- Adolescents: 600 mg PO q8h with pyrimethamine and leucovorin
- Treatment:
- PCP[15]:
- Infants/children: 10 mg/kg/dose IV/PO q6h (max 600 mg IV, max 450 mg PO) with primaquine
- Adolescents: 600 mg IV q6h OR 300 mg PO q6h OR 450 mg PO q8h with primaquine
- General Dosing:
PEDIATRIC RENAL DOSING
- No renal dosage adjustment is necessary.
ADVERSE DRUG REACTIONS
COMMON
- Diarrhea (not due to C. difficile): occurs in 10-30%
- GI intolerance: nausea, vomiting and anorexia
OCCASIONAL
- Generalized morbilliform rash
- C. difficile colitis: ~6%
RARE
- Hepatotoxicity
- Stevens-Johnson syndrome
- Allergic-type reactions (including bronchial asthma): patients who have aspirin hypersensitivity (from tartrazine found in the 75 and 150 mg caps)
DRUG INTERACTIONS
- Erythromycin: in vitro antagonism. Clinical significance is unclear. Avoid co-administration.
- Kaolin-pectin: decreases clindamycin absorption.
- Loperamide and diphenoxylate/atropine: may increase the risk of diarrhea and C. difficile-associated colitis. Avoid use with clindamycin.
- Nondepolarizing muscle relaxant (pancuronium, tubocurarine): lincosamides may enhance the action of nondepolarizing muscle relaxants. Use with caution when patients receive such agents.
SPECTRUM
Active against most Gram-positive cocci except Enterococcus. Increasing resistance is seen with B. fragilis.
Pathogen | Line |
Aerobic Gram-positive bacilli | |
Arcanobacterium (haemolyticum | 2nd line |
Bacillus cereus | 2nd line |
Bacillus spp (not anthracis or cereus) | 2nd line |
2nd line | |
2nd line | |
Aerobic Gram-positive cocci | |
Leuconostoc spp | 1st line |
Staphylococcus aureus (methicillin-sensitive) | 2nd line |
2nd line | |
Streptococcus (Group G) | 2nd line |
Streptococcus (Group C) | 2nd line |
Streptococcus agalactiae (Group B) | 2nd line |
Streptococcus iniae | 1st line |
Streptococcus pneumoniae (PCN intermediate sensitive; MIC 0.1-1.0 mcg/ml) | 2nd line |
Streptococcus pneumoniae (PCN sensitive, MIC < 0.1 mcg/ml) | 2nd line |
Streptococcus pyogenes (Group A) | 2nd line |
Streptococcus intermedius group (S. anginosus, S intermedius, S. constellatus) | 2nd line |
Anaerobic Gram-positive bacilli | |
Actinomyces israelii | 2nd line |
Actinomyces naeslundii | 2nd line |
Actinomyces odontolyticus | 2nd line |
Arachniapropionica | 2nd line |
2nd line | |
Lactobacillus spp. | 2nd line |
Anaerobic Gram-positive cocci | |
2nd line | |
Viridans streptococci | 2nd line |
Miscellaneous | |
2nd line | |
Mycoplasma spp | 2nd line |
Spirochete | |
2nd line | |
Spirillum minus | 2nd line |
Aerobic Gram-negative bacilli | |
2nd line | |
Capnocytophaga canimorous(DF-2) | 1st line |
Capnocytophaga ochracea (DF-1) | 1st line |
Chryseobacteriummeningosepticum | 2nd line |
Gardnerella vaginalis | 2nd line |
Anaerobic Gram-negative bacilli | |
Prevotella biviaBacteroides) | 2nd line |
Bacteroides distasonis | 2nd line |
2nd line | |
Bacteroides ovatus | 2nd line |
Bacteroides thetaiotaomicron | 2nd line |
Bacteroides vulgatus | 2nd line |
Leptotrichia buccalis | 2nd line |
Prevotella intermedius | 1st line |
Fusobacterium necrophorum | 1st line |
Prevotella melaninogenicus | 1st line |
RESISTANCE
- The most common resistance mechanisms are target-site modification and efflux pumps (more of them).
- Cross-resistance with macrolides and streptogramins can occur, often referred to as phenotype MLSB.
- The erm gene (ermA or ermC) encodes methylation of the 23S rRNA binding site shared among the three drug classes.
- This resistance may be inducible or constitutive. When inducible, the organism (most commonly S. aureus) will be resistant to macrolides but susceptible to clindamycin in vitro. Treatment with clindamycin can lead to treatment failures. However, this can be avoided by confirming susceptibilities in the laboratory using the "D-zone test."
- Resistance rates to S. aureus are variable, and higher rates were reported in MRSA (26.8%) than in MSSA (5.2%) in a recent US surveillance report.
- Increasing resistance to group B Streptococcus has been reported in recent years: 33-38% in patients undergoing prenatal screening.
- In a recent evaluation of outcomes for all beta-hemolytic Streptococcus, resistance was documented to exceed 30%. New evaluations are underway to assess the use of linezolid as adjunctive therapy for streptococcal necrotizing soft tissue infections.
- Bacteroides fragilis: increasing resistance seen in up to 40% of isolates in the U.S.
- P. acnes, Prevotella, Porphyromonas, Peptostreptococcus, Fusobacterium: variable resistance, may be as high as 10%.
PHARMACOLOGY
MECHANISM
Inhibits protein synthesis by binding to 50S ribosomal subunits, interfering with transpeptidation and early chain termination.
PHARMACOKINETIC PARAMETERS
Absorption
90% absorbed.
Metabolism and Excretion
Metabolized to sulfoxide and N-dimethyl metabolites. Only 10% is excreted in urine within 24 hours. The majority is excreted as an inactive metabolite in feces and bile.
Protein Binding
85-94%
Cmax, Cmin, and AUC
Cmax 10 mcg/ml after 600 mg IV and 2.5 mcg/ml after 150 mg IV and po dose administration, respectively.
T1/2
2.4 hrs
Distribution
Distributed to many body tissues and fluids, including ascites fluid, pleural fluid, synovial fluid, bone, bile and saliva. Poor CNS penetration.
DOSING FOR DECREASED HEPATIC FUNCTION
Dose reduction is recommended for severe hepatic failure.
PREGNANCY RISK
Category B-In a surveillance study of Michigan Medicaid recipients, 647 exposures to clindamycin during the first trimester resulted in 4.8% birth defects. These data do not support an association between clindamycin and congenital effects.
BREASTFEEDING COMPATIBILITY
Excreted into breast milk. The American Academy of Pediatrics considers clindamycin to be compatible with breastfeeding.
COMMENTS
- Clindamycin is one of the most common antimicrobials that cause C. difficile colitis, but many more patients get diarrhea (antibiotic-related) without C. difficile colitis.
- Prescribe with caution in individuals with a history of C. difficile colitis.
- Clindamycin is frequently added to beta-lactam antibiotics for severe infections caused by MRSA, S. pyogenes, and C. perfringens to suppress toxin production. Better outcomes were observed in retrospective case series when clindamycin was combined with beta-lactam than beta-lactam alone[9]. Furthermore, experimental data suggest increased clearance when a combination is used[8].
- Clindamycin-primaquine is an excellent second-line regimen for PCP in patients who can not tolerate TMP/SMX.
- It is inferior to pyrimethamine/sulfadiazine for treating CNS toxoplasmosis, but clindamycin/pyrimethamine can be considered an alternative treatment regimen in sulfa-allergic patients.
- Clindamycin is often an oral treatment option for MRSA soft tissue infection.
- Four-times-a-day dosing may limit patient adherence to the oral regimen.
- Osteomyelitis: In adult patients, it is often used as a step-down oral therapy but rarely as IV therapy.
- Note: resistance rates described in dermatological literature for C. acnes are far higher than those described in isolates from sterile sites.
References
- Cortés-Penfield N, Ryder JH. Should Linezolid Replace Clindamycin as the Adjunctive Antimicrobial of Choice in Group A Streptococcal Necrotizing Soft Tissue Infection and Toxic Shock Syndrome? A Focused Debate. Clin Infect Dis. 2023;76(2):346-350. [PMID:36056891]
Comment: Data reviewed assessing the use of clindamycin versus linezolid for necrotizing streptococcal infections.
- Horn DL, Roberts EA, Shen J, et al. Outcomes of β-Hemolytic Streptococcal Necrotizing Skin and Soft-tissue Infections and the Impact of Clindamycin Resistance. Clin Infect Dis. 2021;73(11):e4592-e4598. [PMID:33151283]
Comment: In 445 necrotizing soft tissue infections, 31% were caused by beta-hemolytic strep species, and 31% were resistant to clindamycin. More significant limb loss was seen in those with beta strep recovered in culture, particularly those resistant to clindamycin.
- Boyanova L, Kolarov R, Mitov I. Recent evolution of antibiotic resistance in the anaerobes as compared to previous decades. Anaerobe. 2015;31:4-10. [PMID:24875330]
Comment: Though not commonly tested in many laboratories, increasing resistance to many agents is seen in anaerobes, especially B. fragilis. Resistance to clindamycin has generally increased over the years.
- Brook I, Wexler HM, Goldstein EJ. Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev. 2013;26(3):526-46. [PMID:23824372]
Comment: Vagaries and nuances of anaerobic testing, along with resistance mechanisms, are well-discussed in this review.
- Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54(8):e72-e112. [PMID:22438350]
Comment: IDSA guideline recommendations for the use of clindamycin for the treatment of rhinosinusitis.
- Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18-55. [PMID:21208910]
Comment: IDSA guideline recommendations for the use of clindamycin in the treatment of MRSA infections. Archived, with an update in progress.
Rating: Important - Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-76. [PMID:21880587]
Comment: IDSA/PIDS dosing recommendations for clindamycin for treating CAP in children.
- Coyle EA, Cha R, Rybak MJ. Influences of linezolid, penicillin, and clindamycin, alone and in combination, on streptococcal pyrogenic exotoxin a release. Antimicrob Agents Chemother. 2003;47(5):1752-5. [PMID:12709354]
Comment: Experimental study looking at linezolid, penicillin and clindamycin alone or in combination with respect to toxin suppression produced by Group A strep. Linezolid and clindamycin, combined with penicillin, increased toxin clearance.
- Zimbelman J, Palmer A, Todd J. Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection. Pediatr Infect Dis J. 1999;18(12):1096-100. [PMID:10608632]
Comment: Retrospective case series of pediatric patients with S. pyogenes infection. Patients with deep infection were more likely to have a favorable outcome if initial treatment included clindamycin compared to beta-lactam alone (83% vs. 14%, p = 0.006), with a similar trend in those with superficial disease (83% vs. 48%, p = 0.07).
Rating: Important - Safrin S, Finkelstein DM, Feinberg J, et al. Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group. Ann Intern Med. 1996;124(9):792-802. [PMID:8610948]
Comment: Clindamycin-primaquine is an acceptable alternative to TMP-SMX or dapsone-trimethoprim in managing mild or moderately severe PCP.
- Katlama C, De Wit S, O'Doherty E, et al. Pyrimethamine-clindamycin vs. pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS. Clin Infect Dis. 1996;22(2):268-75. [PMID:8838183]
Comment: Pyrimethamine-clindamycin is less effective than sulfadiazine-pyrimethamine but can be used as an alternative treatment regimen in sulfa allergic pts.
- Stevens DL, Gibbons AE, Bergstrom R, et al. The Eagle effect revisited: efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis. J Infect Dis. 1988;158(1):23-8. [PMID:3292661]
Comment: PCN works by inhibiting bacterial replication, but clindamycin shuts down the production of toxins, and its activity is independent of inoculum size. Clindamycin or clindamycin + PNC are advocated for devastating streptococcal soft tissue infections, including necrotizing fasciitis, myositis and TSS (NEJM 334: 240, 1996).
- Gall SA, Kohan AP, Ayers OM, et al. Intravenous metronidazole or clindamycin with tobramycin for therapy of pelvic infections. Obstet Gynecol. 1981;57(1):51-8. [PMID:7005778]
Comment: Clindamycin is equivalent to metronidazole in the treatment of pelvic infection.
- Clindamycin. In: Neofax(R). Truven Health Analytics, Inc. Greenwood Village, CO. http://neofax.micromedexsolutions.com/ . Accessed 12/2/24.
Comment: Neofax dosing recommendations for clindamycin based on post-menstrual and post-natal age.
- Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV.
Comment: DHHS guideline recommendations for the use of clindamycin in the management of PCP and Toxoplasmosis in adults. The website also has info for children HIV-infected. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-a... (last updated 12/10/2024).
- CDC. Clinical Guidance: Malaria Diagnosis & Treatment in the U.S. https://www.cdc.gov/malaria/hcp/clinical-guidance/index.html (accessed 12/10/2024)
Comment: CDC guideline recommendations for the use of clindamycin in the treatment of malaria.
