LINCOSAMIDES

Clindamycin

• Better pharmacokinetics
• Less toxicity

Lincomycin

• First derivative developed, now used much less for individual therapy because of toxicity
• Used as feed additive for swine

Structure and Characteristics

Chemistry

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

Lincosamide Structure

Clindamicin: R=CL

Lincomycin: R=OH

Pharmacokinetics

Administration

PO

• HCl & Palmitate salts
  • Food not alter absorption much
  • HCl well absorbed: >90%
  • Palmitate less
• Lincomycin: F = 20 - 30%

Parenteral

• Phosphate salt
  • IM or IV
• Cleocin T Topical

IV Infusion Solution

Physical Incompatibilities of clindamycin

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

Distribution

Broadly distributed

• Adults - 0.66 L/kg
• Children - 0.86 L/kg
• most tissues
• bone
• NOT CNS

Accumulates Some WBCs

• Concentrates
  • PMNs
  • Macrophages
• Explain good activity abscesses?

Elimination

Clindamycin

• Elimination is primarily via BIOTRANSFORMATION in the Liver
• 4% is eliminated 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
• Microflora disruption
• More profound than clindamycin

Adverse Effects

Overview

• AAPC
• NVD
• Cutaneous hypersensitivity
• Rapid IV - cardiac depression
• Post-anesthetic paralysis

Antibiotic-Associated Pseudomembranous Colitis (AAPC)

Cause/RX

• Antibiotic-Associated Pseudomembranous Colitis
• Clostridium difficile overgrowth
• Vancomycin

Occurrence

• 8% of cases
• Usually Days 4 to 9 after starting therapy
• May be 2-6 wks after Rx
• Other antimicrobials also cause. In order of decreasing tendency
  • Lincomycin > Ampicillin > Clindamycin > Cephalosporin

Indications

• Anaerobic infections (empyema, lung abscess, peritonitis, intra-abcominal abscess, pelvic, tubular, ovarian abscess, or endometritis)
• Alternative for G+ cocci -- Staphylococcal infections with methicillin resistant strains
• Streptococcal infections (Pharyngitis, otitis media, cellulitis)
• Pneumococci & Staphylococci
• Not enterococci
• Resistant infections caused by -
  • Anaerobic organisms
  • Staphylococci
• Drug of choice for dogs at risk of cardiac, severe gum disease, prior to prophylactic dental procedures -- give 5 days prior to procedure [AntirobeR]
• VetMed: Used successfully in raptors for abscesses and osteomyelitis. 2-3 months duration with no problems such as diarrheas. Administer to birds by injection into mice before feeding them to the birds. reference: Nicole VanDerHeyden, SVM Class of 1985 regarding experience at Utah Raptor Rehabilitation Center.
• VetMed: Fearful of use in horses (especially lincomycin) because of the risk of 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.

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?