Clindamycin

Edina Avdic, Pharm.D., Paul A. Pham, Pharm.D.
Pediatric Dosing Author: Alice Jenh Hsu, PharmD, BCPS, AQ-ID

INDICATIONS

FDA

NON-FDA APPROVED USES

  • Alternative treatment of PCP in combination with primaquine
  • Alternative treatment 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 alternative regimen, especially in pregnancy
  • Diphtheria
  • Alternative therapy for bebesiosis 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:
    • Skin and soft tissue infections (including animal or human bites): 300-450 mg PO q6h-8h or 600 mg IV q8h
    • 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
  • 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

PEDIATRIC DOSING

USUAL PEDIATRIC DOSING

  • Neonate (Neofax): 5 to 7.5 mg/kg/dose IV or PO
Clindamycin Dosing Interval Chart

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[4], MRSA bone/joint and skin and soft tissue infections[5], and rhinosinusitis[3] 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 malaria module for details, usually part of 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 total treatment duration of 7 days
    • Toxoplasmosis[14]:
      • 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
    • PCP[14]:
      • 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

PEDIATRIC RENAL DOSING

  • No renal dosage adjustment necessary.

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose.

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Usual dose.

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

Usual dose.

DOSING IN HEMODIALYSIS

Usual regimen.

DOSING IN PERITONEAL DIALYSIS

Usual regimen.

DOSING IN HEMOFILTRATION

Usual dose.

ADVERSE DRUG REACTIONS

COMMON

  • Diarrhea (not due to C. difficile): occurs in 10-30%
  • GI intolerance: nausea, vomiting and anorexia

OCCASIONAL

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 unclear. Avoid co-administration.
  • Kaolin-pectin: decreases clindamycin absorption.
  • Loperamide and diphenoxylate/atropine: may increase risk of diarrhea and C. difficile-associated colitis. Avoid use with clindamycin.
  • Nondepolarizing muscle relaxant (pancuronium, tubocurarine): lincosamides may enhances the action of nondepolarizing muscle relaxants. Use with caution in pts receiving such agents.

SPECTRUM

Active against most Gram-positive cocci except Enterococcus. Active against most community-acquired MRSA, although resistance is increasing (if CA-MRSA is resistant to erythromycin, D-test should performed to confirm clindamycin sensitivity). Increasing resistance seen with B. fragilis.

Spectrum of Activity

Pathogen

Line

Aerobic gram-positive bacilli

Arcanobacterium (haemolyticum

2nd line

Bacillus cereus

2nd line

Bacillus spp (not anthracis or cereus)

2nd line

Propionibacterium acnes

2nd line

Corynebacterium diphtheriae

2nd line

Aerobic gram-positive cocci

Leuconostoc spp

1st line

Staphylococcus aureus (methicillin-sensitive)

2nd line

Streptobacillus moniliformis

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

Clostridium species

2nd line

Lactobacillus spp.

2nd line

Anaerobic gram-positive cocci

Peptostreptococcus spp

2nd line

Viridans streptococci

2nd line

Miscellaneous

Chlamydia trachomatis

2nd line

Mycoplasma spp

2nd line

Spirochete

Leptospira interrogans

2nd line

Spirillum minus

2nd line

Aerobic gram-negative bacilli

Campylobacter jejuni

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 bivia(Bacteroides)

2nd line

Bacteroides distasonis

2nd line

Bacteroides fragilis

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

  • Most common mechanisms of resistance: target site modification, efflux pumps (msrA).
  • Cross-resistance with macrolides and streptogramins can occur which is often referred to as phenotype MLSB. The erm gene (ermA or ermC) encodes methylation of the 23S rRNA binding site that is shared among the 3 drug classes. This resistance maybe inducible or constituitive. When is inducible, organism (most commonly S. aureus) is going to 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 "D-zone test"[6].
  • Resistance rates to S. aureus are variable, higher rates were reported in MRSA (26.8%) compared to 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.
  • Bacteroides fragilis: increasing resistance seen, up to 40% of isolates in 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 24hrs. Majority excreted as 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 recommended for severe hepatic failure.

PREGNANCY RISK

Category B-In a surveillance study of Michigan Medicaid recipients, 647 exposures to clindamycin during the 1st trimester resulted in 4.8% birth defects. These data do not support an association between clindamycin and congenital effects.

BREAST FEEDING COMPATIBILITY

Excreted into breast milk. The American Academy of Pediatrics considers clindamycin to be compatible with breast feeding.

COMMENTS

  • Clindamycin is one of the most common antimicrobials to cause C. difficile colitis, but many more patients get diarrhea (antibiotic-related) without C. difficile colitis.
    • Prescribe with caution in individuals with history of C. difficile colitis.
  • Clindamycin is frequently added to beta-lactam antibiotics for severe infections caused by MRSA, S. pyogenes, C. perfringens to suppresses toxin production. Better outcomes were observed in retrospective case series when clindamycin was used in combination with beta-lactams than beta-lactam alone[8]. Furthermore, experimental data suggest increases clearance when combination is used[7].
  • Clindamycin-primaquine is a good second-line regimen for PCP in patients who can not tolerate TMP/SMX.
  • It is inferior to pyrimethamine/sulfadiazine for treatment to CNS toxoplasmosis but clindamycin/pyrimethamine can be considered as an alternative treatment regimen in sulfa allergic patients.
  • Clindamycin is often used as an oral treatment option for CA-MRSA soft tissue infection.
  • Four times a day dosing may limit patient adherence with oral regimen.
  • Osteomyelitis: In adult patients, it is often used as step-down oral therapy, but rarely used as IV therapy.
  • Note: resistance rates described in dermatological literature for P. acnes are far higher than that described in isolates from sterile sites.

References

  1. Boyanova L, Kolarov R, Mitov I: Recent evolution of antibiotic resistance in the anaerobes as compared to previous decades. Anaerobe May 26  [PMID:24875330]

    Comment: Though not commonly tested in many laboratories, increasing resistance to many agents seen in anaerobes, especially B. fragilis. Resistance to clindamycin has generally increased over the years.

  2. Brook I, Wexler HM, Goldstein EJ: Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev 26:526, 2013  [PMID:23824372]

    Comment: Vagaries and nuances of anaerobic testing are well-discussed in this review, along with resistance mechanisms.

  3. Chow AW et al: IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis 54:e72, 2012  [PMID:22438350]

    Comment: IDSA guideline recommendations for the use of clindamycin for the treatment of rhinosinusitis.

  4. Bradley JS 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 53:e25, 2011  [PMID:21880587]

    Comment: IDSA/PIDS dosing recommendations for clindamycin for the treatment of CAP in children.

  5. Liu C 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 52:e18, 2011  [PMID:21208910]

    Comment: IDSA guideline recommendations for the use of clindamycin in the treatment of MRSA infections.

  6. Lewis JS, Jorgensen JH: Inducible clindamycin resistance in Staphylococci: should clinicians and microbiologists be concerned? Clin Infect Dis 40:280, 2005  [PMID:15655748]
  7. 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 47:1752, 2003  [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, alone or in combination with penicillin, increased toxin clearance.

  8. 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 18:1096, 1999  [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

  9. Safrin S 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 124:792, 1996  [PMID:8610948]

    Comment: Clindamycin-primaquine is an acceptable alternative to TMP-SMX , or dapsone-trimethoprim in the management of mild or moderately severe PCP.

  10. Katlama C et al: Pyrimethamine-clindamycin vs. pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS. Clin Infect Dis 22:268, 1996  [PMID:8838183]

    Comment: Pyrimethamine-clindamycin is less effective than sulfadiazine-pyrimethamine but can be used as an alternative treatment regimen in sulfa allergic pts.

  11. Stevens DL et al: The Eagle effect revisited: efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis. J Infect Dis 158:23, 1988  [PMID:3292661]

    Comment: PCN works by inhibiting bacterial replication, but clindamycin shuts down 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).

  12. Gall SA et al: Intravenous metronidazole or clindamycin with tobramycin for therapy of pelvic infections. Obstet Gynecol 57:51, 1981  [PMID:7005778]

    Comment: Clindamycin is equivalent to metronidazole in the treatment of pelvic infection.

  13. CDC guidelines for the treatment of malaria in the United States. Centers for Disease Control and Prevention. Available at: https://www.cdc.gov… Accessed 7/9/18.

    Comment: CDC guideline recommendations for the use of clindamycin in the treatment of malaria.

  14. Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children.Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Department of Health and Human Services. Available at https://aidsinfo.nih.gov…. Section accessed 7/9/18.

    Comment: DHHS guideline recommendations for the use of clindamycin in the management of PCP and Toxoplasmosis in HIV infected children.

  15. Clindamycin. In: Neofax(R). Truven Health Analytics, Inc. Greenwood Village, CO. http://neofax.micromedexsolutions.com/ . Accessed June 1, 2018.

    Comment: Neofax dosing recommendations for clindamycin based on post-menstrual and post-natal age.

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Last updated: July 9, 2018

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TY - ELEC T1 - Clindamycin ID - 540131 A1 - Avdic,Edina,Pharm.D. AU - Pham,Paul,Pharm.D. Y1 - 2018/07/09/ PB - Johns Hopkins ABX Guide UR - https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540131/all/Clindamycin ER -