321
Tetracyclines
Oxytetracycline and doxycycline both inhibit bacterial protein
synthesis by binding to the 30S ribosomal subunit and are
therefore bacteriostatic. They have a broad spectrum of
activity including Gram-positive and negative pathogens,
Mycoplasma, Rickettsia, Chlamydiaand Ehrlicia . However,
plasmid mediated resistance, either as a result of decreased
drug uptake into the bacterial cell or increased efflux, is
widespread. Oxytetracycline does not reach therapeutic
concentrations in CSF in healthy patients due to a high degree
of plasma protein binding and moderate lipid solubility (Thea
and Barza 1989). Administration of doxycycline at 10 mg/kg
bwt did not result in measurable concentrations of the drug
within the CSF of healthy horses (Bryant et al.2000).
Aminoglycosides
Aminoglycoside antibiotics also bind to the 30S ribosomal
subunit, interrupting normal bacterial protein synthesis. This
leads to changes in membrane permeability and bacterial cell
lysis. The aminoglycoside antibiotics are bacteriocidal. They
have a wide range of action against Gram-negative
pathogens, most Staphylococcispp. and some Streptococci
spp. However, they are large polar molecules and are highly
ionised at physiological pH. This prevents them from reaching
therapeutic concentrations in the CNS (Dowling 2004). The use of macrolide antibiotics, tetracyclines or
aminoglycoside antimicrobial drugs cannot be recommended
for treatment of bacterial meningitis in horses due to poor
penetration into the CSF. Administration of antimicrobials is a recognised risk factor
in the development of Clostridium difficilediarrhoea in adult
horses (Baverud 2004), and case reports of diarrhoea after
administration of many antimicrobial classes exist in the
equine literature. As with all drug classes, documentation of
patient need (documentation of bacterial infection in the case
of antimicrobials) should be a prerequisite for administration,
weighed against potential adverse effects.
Reported treatment
The mainstay of treatment for bacterial meningitis in human
patients consists of third or fourth generation cephalosporins.
In a 12 year review of 103 cases of human bacterial
meningitis at a large emergency centre, 14% of patients with
bacterial meningitis received a third or fourth generation
cephalosporin alone, 14% received ampicillin alone, 20%
received a third generation cephalosporin plus ampicillin or
penicillin, and the majority (42%) received one or more third
generation cephalosporin, penicillin, ampicillin and/or
chloramphenicol. Ceftriaxone and cefotaxime are commonly
used at twice the standard dose rate to aid CNS penetration
(Nau et al. 1998). Previous case reports in the equine
literature reported the use of streptomycin (Timoney et al.
1983), i.v. or oral TMP/SMZ (Rumbaugh 1977), a combination
of sodium benzyl penicillin and gentamicin (Newton 1988), and chloramphenicol (Mitchell
et al.2006). Three cases of
suspected bacterial meningitis and variable immunodeficiency
were reported to recover after treatment with potassium
penicillin and enrofloxacin, potassium penicillin and rifampin,
and potassium penicillin, rifampin and trimethoprim-
sulphamethoxazole respectively. Two of the cases had
complications related to immunodeficiency after 5 months
and 2 years (Pellegrini-Masini et al.2005). Too few reported
cases exist in the equine literature to make evidence-based
recommendations.
Summary
Reasonable choices of antimicrobial therapy for treatment of
bacterial meningitis in adult horses include ampicillin
and chloramphenicol. Potentiated sulphonamides may be
appropriate depending on the MIC of the organism involved.
Choice of therapeutic agent may initially be based on CSF
cytology and Gram stain, but culture and sensitivity data
should be obtained. Use of enrofloxacin may be appropriate if
antimicrobial isolates show resistance to the aforementioned
drugs, but the possibility of induction of, or worsening of
seizure activity should be considered. Rifampin may be
beneficial when used in combination with other antimicrobial
agents. Use of many of these antimicrobials agents is
extralabel. Use of third and fourth generation cephalosporins
may be appropriate in foals and small ponies or in adult horses
with no financial constraints to treatment.
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EQUINE VETERINARY EDUCATION / AE / July 2007