Journal of Antimicrobial Chemotherapy, Vol 42, 171-178, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
RM Richards, VE Hamilton and MR Thomas
The effect of triple therapy with ciprofloxacin, trimethoprim and either
sulphadiazine or sulphamethoxazole on the MICs and development of
resistance of three strains of Pseudomonas aeruginosa, two strains of
Staphylococcus aureus and one of Burkholderia cepacia was compared with
that of single or dual therapy with these agents using an agar dilution
method. Ciprofloxacin MICs were 0.2-0.8 mg/L for the P. aeruginosa and S.
aureus strains. For trimethoprim the MIC ranges were 64-128 and 0.25-1 mg/L
for P. aeruginosa and S. aureus, respectively. For the sulphonamides the
ranges were 64-2500 and 20-39 mg/L for P. aeruginosa and S. aureus,
respectively. All combinations of agents were effective at lower
concentrations than the single agents. The combination of ciprofloxacin,
sulphonamide and trimethoprim showed enhanced activity against all test
organisms. The highest ciprofloxacin concentration was one-tenth of the
normally attainable serum concentration of 2.5 mg/L. Thus peak plasma
concentrations of > or =8 x MIC for ciprofloxacin against P. aeruginosa
and S. aureus are theoretically achievable in the presence of clinically
acceptable concentrations of trimethoprim and a sulphonamide, making the
development of resistance less likely. The development of resistance, as
shown by the proportional increase in MICs, was repressed by the triple
regimen as compared with the development of resistance to agents used
singly or in pairs. Killing curve determinations also demonstrated the
advantage of the triple-agent therapy against all organisms tested: the
combination of ciprofloxacin 0.5 mg/L, trimethoprim 1 mg/L and
sulphadiazine 20 mg/L had an initial bactericidal effect against log- phase
inocula of 10(6) cfu/mL of two clinical strains of P. aeruginosa and one
clinical strain of S. aureus. The pseudomonas strains were reduced by 2-4
log cycles. Both recovered over 24 h but did not exceed the initial
inoculum. The S. aureus was reduced to 10(2) cfu/mL in 4 h and did not
recover over 24 h. A repeat dose of the triple therapy against the more
resistant of the P. aeruginosa strains after 12 h also had a bactericidal
effect. These data suggest the possibility of an effective exclusively oral
therapy for the treatment of lung infections in cystic fibrosis patients.
ORIGINAL ARTICLES
In-vitro investigation of the antibacterial activity of agents which may be used for the oral treatment of lung infections in CF patients
School of Pharmacy, The Robert Gordon University, Schoolhill, Aberdeen, UK. r.richards@rgu.ac.uk
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