Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

MACROLIDES AND LINCOSAMIDES
Gram positive
aerobes
Obligate
anaerobes
+ Toxoplasma and Neospora
* Campylobacter are susceptible
Gram negative
aerobes*
Penicillinaseproducing
Staphylococcus
Fig. 8.18 Antibacterial spectrum for clindamycin.
Gram positive
aerobes
Obligate
anaerobes
* Campylobacter are susceptible
Gram negative
aerobes*
Penicillinaseproducing
Staphylococcus
Fig. 8.19 Antibacterial spectrum for erythromycin.
Gram positive
aerobes
Obligate
anaerobes
+ atypical Mycobacteria spp.
* Campylobacter are susceptible
Gram negative
aerobes*
Penicillinaseproducing
Staphylococcus
Fig. 8.20 Antibacterial spectrum for azithromycin.
● Good activity against anaerobic bacteria.
● Virtually all aerobic Gram-negative bacteria are
resistant because of drug impermeability and methylation
of the ribosomal binding site but Campylobacter
jejuni is an exception.
● Erythromycin and lincomycin are more effective
against Staphylococcus than aminopenicillins but
not as effective as antistaphylococcal penicillins,
cephalosporins and amoxicillin-clavulanate.
Pharmacokinetics
Macrolides and lincosamides have high lipid solubility
and wide distribution in the body and across cellular
barriers. They are usually bacteriostatic but erythromycin
can be bactericidal at high concentrations. Because
of their basic nature, ion-trapping occurs in milk and
prostatic fluid where the transcellular pH is lower than
the blood. Ion-trapping also occurs inside cells since
intracellular pH is lower than extracellular fluid pH.
Concentrations in CSF are relatively low (20% of
plasma concentrations) due to extensive plasma protein
binding and relatively rapid elimination. Concentrations
achieved in bone are also relatively low (10–20%
of plasma concentrations) although this can still be
clinically effective.
Lincosamides are well absorbed from the intestine of
nonherbivores. They are eliminated mainly by hepatic
metabolism, although about 20% is eliminated in active
form in the urine.
Adverse effects
The major toxic effect of lincosamides is their ability to
cause serious and fatal diarrhea in humans, horses,
rabbits and other herbivores. The diarrhea is due to
overgrowth of Clostridium difficile because of destruction
of competing anaerobic flora in the colon. However,
lincosamides are relatively nontoxic to dogs and cats.
Erythromycin frequently causes gastrointestinal
upsets in dogs, mainly vomiting. It appears to mimic the
effects of the hormone motilin as well as acting on presynaptic
cholinergic neurones to stimulate gastric,
pyloric and duodenal contractions. Low doses are prokinetic
but higher doses used in antibacterial therapy
stimulate vomiting.
Lincomycin
The combination of lincomycin with spectinomycin
appears to give marginally enhanced activity against
Mycoplasma in vitro and is convenient for treating Mycoplasma
and Chlamydophila infections in catteries.
Lincomycin and clindamycin penetrate well into all
tissues, including bone, and have therefore been popular
for treating osteomyelitis. Concentrations in the extracellular
fluid of bone depend on blood supply. However,
at adequate dose rates most antibacterial drugs attain
therapeutically acceptable concentrations in bone and
synovial fluid, although some achieve higher concentrations
in bone than others. The important features of
treatment of osteomyelitis include the need for high
local concentrations of bactericidal drugs, prolonged
treatment, especially in chronic infections and surgical
removal of necrotic bone. Bacteriostatic agents like lincosamides
are thus not a particularly good choice.
Clindamycin
● Clindamycin is more potent than lincomycin against
all pathogens.
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