The in-vitro activity of colistin sulphomethate sodium was compared with that of other commonly used antimicrobial agents against 377 recent clinical isolates of Gram-negative bacteria (including 94 strains of Pseudomonas aeruginosa from patients with cystic fibrosis) and 16 organisms with defined resistance patterns. Colistin was active against most strains of P. aeruginosa (MIC90 4 mg/L), Shigella spp. (MIC90 0.5 mg/L), Salmonella spp. (MIC90 1 mg/L), Acinetobacter spp. (MIC90 2 mg/L), Citrobacter spp. (MIC90 1 mg/L), Escherichia coli (MIC90 1 mg/L), Klebsiella spp. (MIC90 8 mg/L) and Enterobacter spp. (MIC50 1 mg/L). No useful activity was demonstrated against Providentia spp. or Serratia spp. The results show that colistin remains a useful antimicrobial agent against Gram-negative bacteria, particularly those strains which are resistant to more commonly used antibiotics.

The in vitro activity of L-627, a new parenterally administered carbapenem, was compared with those of imipenem, meropenem, FCE 22101 (a penem), ceftazidime, and ceftriaxone. L-627 was active against members of the family Enterobacteriaceae (MIC for 90%o of strains tested [MIC90] ranging from 0.03 to 4 ,ug/ml). L-627 displayed activity equal to that of meropenem against Pseudomonas aeruginosa (MIC90, 2 ,ug/ml), although, as with other carbapenems, the antipseudomonal activity was reduced against D2-deficient strains. Staphylococci and streptococci were susceptible (MIC90 of 1.0 jiLg/ml for Staphylococcus aureus and 0.015 ,ug/ml for group A streptococci). L-627 also had activity against anaerobic bacteria (MIC90, 2.0 ,ug/ml for Bacteroidesfragilis).Neisseria gonorrhoeae and Neisseria meningitidis were highly susceptible (MIC90, 0.06 ,ug/ml), and against the common respiratory pathogens (Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis), the MIC90s were <2.0 ,ug/ml. The protein binding of L-627 ranged from 13.8 to 22%, depending on the concentration. The presence of human serum had little effect on the MIC or MBC of L-627. These results suggest that L-627 merits further study in the treatment of infections caused by a wide range of pathogens.

The pharmacokinetics of ciprofloxacin following single doses of 400 mg i.v. and 750 mg po were compared in six healthy volunteers. Concentrations of ciprofloxacin were measured in plasma, cantharides induced blister fluid and urine, by microbiological assay and high performance liquid chromatography (HPLC). Mean peak plasma concentration was 6.7 +/- 1.4 mg/L after i.v. and 3.9 +/- 1.7 mg/L after oral administration with mean elimination half-lives of 4.2 and 4.0 h respectively. Mean area under the concentration versus time curve (AUC) was greater following oral administration (19.2 +/- 1.1 mg/L.h versus 14.2 +/- 1.1 mg/L.h). Blister fluid peak concentrations following i.v. and oral administration were 2.6 +/- 1.3 mg/L and 2.28 +/- 1.2 mg/L respectively. The elimination half-life from blister fluid was 4.1 +/- 1.1 h and the AUC 13.8 +/- 1.1 mg/L.h following i.v. administration compared with 4.6 +/- 1.5 h and 20.3 +/- 1.3 mg/L.h for the oral dose. A mean of 50.8% of i.v. administered drug and 39.6% or orally administered drug was excreted in urine in 24 h as measured by HPLC. The corresponding values by microbiological assay were greater, suggesting excretion of active metabolites. Both i.v. and oral doses produced levels in blister fluid concentration above the MICs for most Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae and Neisseria spp. at 12 h post dose. The pharmacokinetic data from inflammatory fluid indicate that ciprofloxacin 400 mg i.v. is more equivalent to 750 mg po than the plasma pharmacokinetic data suggest.

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