LINCOSAMIDES
Outline

Notice

• "**" Not in version put in library

Members

• Clindamycin [Antirobe^R]
  • Better pharmacokinetics
  • Less toxicity
• Lincomycin [Lincocin^R]
  • First derivative developed,
  • Now -- primarily herd Rx
  • e.g., Used as feed additive for swine

Structure and Characteristics

Lincosamide Structure

• Clindamicin: R=CL
• Lincomycin: R=OH

Chemistry

• water soluble
• ethanol soluble
• Acid stable
• Weakly basic

Physical Incompatibilities of clindamycin

• ampicillin
• phenytoin
• barbiturates
• aminophylline
• calcium gluconate
• magnesium sulfate

Pharmacokinetics

Administration

• Topical
• Cleocin T Top.ical
• PO
• Clindamycin -- HCl & Palmitate salts
• Food not alter absorption much
• HCl well absorbed: >90%
• Palmitate less
• Lincomycin: F = 20 - 30%
• Parenteral
• Phosphate salt
• IM or IV

Distribution

• Broadly distributed
• Human adults - 0.66 L/kg
• Children - 0.86 L/kg
• most tissues
• bone
• NOT CNS
• Accumulates Some WBCs
• PMNs
• Macrophages
• Explain good activity abscesses?

Elimination

• Clindamycin
  • Primarily hepatic BIOTRANSFORMATION
  • 4% in BILE as active compound. (Contrast to lincomycin!)
  • Elim bile more than 5 days after stop therapy
  • GI flora altered longer than 2 weeks
  • Urine 10% unchanged
• Lincomycin
• 40% eliminated in liver - BILE as ACTIVE
• Remember! F =20-40%!
• Remember! Spectrum of activity
• Microflora disruption

Adverse Effects
(Both drugs)

Overview

• Relatively nontoxic - dogs, cats **
• Highly toxic to rabbits, guinea pigs, hamsters**
• AAPC
• Nausea , Vomiting, Diarrhea
• Cutaneous hypersensitivity
• Rapid IV - cardiac depression
• Post-anesthetic paralysis

Antibiotic-Associated Pseudomembranous Colitis (AAPC)

• Primarily lincomycin!
• Clostridium difficile overgrowth
• Vancomycin -- Rx of choice
• 8% of cases -- humans
• Usually Days 4 to 9 after starting therapy
• May be 2-6 wks after Rx
• Other antimicrobials also cause. In order of decreasing tendency
• Think! Access & spectrum
• Lincomycin
• Ampicillin
• Clindamycin
• Cephalosporins
• Horses **
  • Parenteral or PO
  • hemorrhagic colitis & ciarrhaea
  • May be fatal
• Cattle **
  • 7.5 ppm lincomycin in feed caused
    inappetance,
    diarrhea,
    ketosis,
    decreased milk production
• Rabbits**
  • also Cl. spiroforme
  • 8 ppm lincomycin in feed
    • severe & fatal typhlitis

Indications
(Both drugs)

• Anaerobic infections
  (empyema, lung abscess, peritonitis, intra-abcominal abscess, pelvic, tubular, ovarian abscess, or endometritis)
• Alternative for G+ cocci
  • Methicillin resistant staph
  • Streptococcal infections (Pharyngitis, otitis media, cellulitis)
  • Not enterococci
• Vet Med
  • Dogs -- prophylactic dental procedures if high risk give 5 days prior to procedure
  • Raptors for abscesses and osteomyelitis (VanderHeyden)
  • Horses -- caution! -- especially lincomycin -- risk severe colitis

References

• Simon, et al., '85; Simon, C., Ww. Stille, P.J. Wilkinson, Antibiotic Therapy in Clinical Practice Shattauer Verlag, Stuttgart, New York, 1985.
• USPDI
• Bowersock, T., personal communication, 1995.
• Vanderheyden -- Nicole VanDerHeyden, SVM Class of 1985 regarding experience at Utah Raptor Rehabilitation Center. Used 2-3 months duration with no problems such as diarrheas. Administer to birds by injection into mice before feeding them to the birds.
  (NOTE: Note clear from context whether this was lincomycin or clindamycin

Study Questions

1. What is the antibacterial spectrum of the lincosamides? Note that in addition to other organisms, these drugs are active against anaerobic bacteria, e.g., Bacteroides spp. This is expeicaly important for Bacteroides fragilis which tends to be resistant to penicillins.
2. Note the high incidence of diarrhea under some circumstances with the lincosamides (lincomycin, esp), particularly in humans and horses. What is the usual cause of this diarrhea when it is severe and ulcerative? Why is lincomycin much worse than clindamycin in inhibiting the normal intestinal flora?
3. What antibiotic is specifically recommended for treating the Clostridium difficile infections mentioned in the previous question?