Fiona J. Boswell

In this study the in vitro activities and pharmacodynamic properties of moxifloxacin, levofloxacin, gatifloxacin and gemifloxacin were compared on recently isolated respiratory pathogens and strains of Streptococcus pneumoniae with known mechanisms of fluoroquinolone resistance. In addition, the resistance selection frequencies of moxifloxacin and levofloxacin on three recently isolated respiratory pathogens and four strains of S. pneumoniae with known mechanisms of fluoroquinolone resistance were investigated. The four fluoroquinolones had similar activities against both Moraxella catarrhalis (MIC₉₀s 0.015–0.06 mg/L) and Haemophilus influenzae (MIC₉₀s 0.008–0.03 mg/L). More marked differences in activity were noted with S. pneumoniae, with MIC₉₀s of 0.25, 1, 0.5 and 0.03 mg/L for moxifloxacin, levofloxacin, gatifloxacin and gemifloxacin, respectively. With the S. pneumoniae strains, the four fluoroquinolones exhibited similar concentration-dependent time–kill kinetics. The resistance selection frequencies of levofloxacin were higher than those of moxifloxacin at concentrations equivalent to those at the end of the dosing interval. Therefore moxifloxacin may have less of an impact on the development of resistance than levofloxacin.

The influence of protein binding upon different aspects of the in vitro activity of faropenem on recently isolated Staphylococcus aureus and respiratory pathogens was determined. The protein binding of faropenem was investigated in inactivated human serum and albumin by ultrafiltration. The effect of the presence of inactivated human serum and albumin on the in vitro activity of faropenem and amoxicillin was established and the influence of protein binding on the pharmacodynamic properties of faropenem and amoxicillin was compared. The protein binding of faropenem was 96% and 95% in pooled inactivated human serum and 99% and 98% in 45 mg/L human albumin, at 8 and 25 mg/L, respectively. The presence of inactivated human serum (20% and 70%) increased the mean faropenem MICs by two dilution steps and albumin increased the mean faropenem MICs by three dilution steps. The mean amoxicillin MICs were less affected than faropenem by the presence of either inactivated human serum or albumin. Faropenem and amoxicillin exhibited similar time-dependent kinetics. Faropenem was bacteriostatic on Moraxella catarrhalis, Haemophilus influenzae and group A streptococci, and bactericidal for Streptococcus pneumoniae (after 4 h with concentrations equivalent to 5 × and 10 × MIC) in Iso-Sensitest broth. In 70% inactivated human serum faropenem was slowly bactericidal against M. catarrhalis, H. influenzae (one strain) and S. pneumoniae (one strain) but not group A streptococci and the other S. pneumoniae strain. A significant inoculum effect was observed with all strains except S. pneumoniae. Both faropenem and amoxicillin appeared more active in 70% inactivated human serum than in Iso-Sensitest broth.

Anaerobes are often involved in human pathology, including oral infections. The therapy of anaerobic infection requires certain antibiotics such as: metronidazole, tetracycline or amoxicillin. But the incidence of resistant strains among anaerobes is continuously increasing and it is necessary to find some new agents effective against these bacteria. The aim of our study was to establish the bactericidal activity of two new quinolones against 14 strains of gram-negative anaerobic bacilli. The MIC of tested strains was first detected and then time-kill kinetics was determined by using Miles and Misra methodology. Ciprofloxacin was used as standard-quinolone. The results show that trovafloxacin and moxifloxacin have good activity against anaerobes, better than that of ciprofloxacin. Bactericidal curves suggest a rapid action of moxifloxacin (within the first 4 hours), but a prolonged cidal activity for trovafloxacin (24 hours). For both agents, the antimicrobial effect is concentration-dependent. As previous studies suggest, the new quinolones have good activity against both aerobic and anaerobic bacteria so they are useful in the treatment of mixed infections (common feature of anaerobic infections).

Sir, BMS-284756 is a novel des-fluoro(6) quinolone, without the C-6 position fluorine characteristic of the existing fluoroquinolones. BMS-284756 has a broad spectrum of in vitro activity against both Gram-positive and Gram-negative bacteria. 1 Resistance to fluoroquinolones in Streptococcus pneumoniae may be due to a number of stepwise mutations in the quinolone-resistance determining regions of the subunits of DNA gyrase and topoisomerase IV. 2,3 Low-level fluoroquinolone resistance also occurs in S. pneumoniae due to the increased expression of the multidrug efflux pumps. 4 In this communication we compare the in vitro activity of BMS-284756 (Bristol-Myers Squibb, New York, NY, USA), norfloxacin (Merck, Sharpe & Dohme Ltd, Hoddesdon, UK) with and without reserpine, an efflux pump inhibitor (10 mg/L) (Sigma-Aldrich Co. Ltd, Poole, UK), 4 sparfloxacin (Aventis Pharma, Cedex, France), moxifloxacin and ciprofloxacin (Bayer AG, Wuppertal, Germany) against 53 clinical strains of S. pneumoniae

In this study the Oxoid Aura image antibiotic sensitivity test system, used as a stand-alone device, was compared with manual zone measurement and use of a template, for the determination of sensitivities. An overall correlation coefficient of 0.99 was observed for zone diameters measured using the Aura image system and zones measured manually, when the differences between zones were within 3 mm; 5.4% of zones showed a difference in zone diameter between manual and automated measurement of >3 mm. The results obtained using the template method for interpretation were less reliable than zone measurement, with cefuroxime and ampicillin tested against Enterobacteriaceae and Acinetobacter spp. When linked to a laboratory patient database, the bar code and disc identification facilities avoided errors that were associated with manual data entry.

J Antimicrob Chemother 2000; 45: 259–261

The time-kill kinetics and post-antibiotic effect (PAE) of moxifloxacin were studied for strains of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Staphylococcus aureus and Escherichia coli. Moxifloxacin had a bactericidal effect against all strains tested, with the least rapid bactericidal effect being against S. pyogenes and the most rapid effect against S. aureus and E. coli. The PAE of moxifloxacin was similar to that of other fluoroquinolones and increased with increasing concentration. No association was found between the bactericidal effect of moxifloxacin and the duration of PAE. Gram-positive and gram-negative organisms were also exposed to concentrations of moxifloxacin, sparfloxacin and amoxycillin that simulated the drug concentrations obtained in human serum after standard oral dosing schedules. Simulation of moxifloxacin concentrations in human serum reduced viable counts more effectively and more rapidly than shown in time-kill experiments; in contrast, sparfloxacin and amoxycillin were less effective than when constant concentrations of these antibacterials were used.

The in-vitro activity of HMR 3647, a novel ketolide, was investigated in comparison with those of erythromycin A, roxithromycin, clarithromycin (14-membered ring macrolides), amoxycillin-clavulanate and ciprofloxacin against 719 recent clinical Gram-positive, Gram-negative and anaerobic isolates and type cultures. HMR 3647 generally demonstrated greater activity than the other compounds with MIC90s of < or =0.5 mg/L, except for Staphylococcus epidermidis (MIC90 > 128 mg/L), Haemophilus influenzae (MIC90 = 2 mg/L), Enterococcus faecalis (MIC90 = 2 mg/L), Enterococcus faecium (MIC90 = 1 mg/L) and the anaerobes, Bacteroides fragilis (MIC90 = 2 mg/L) and Clostridium difficile (MIC90 = 1 mg/L). In general, an increase in the size of the inoculum from 10(4) to 10(6) cfu on selected strains had little effect on the MICs of HMR 3647. Additionally, the in-vitro activity of HMR 3647 was not affected by the presence of either 20 or 70% (v/v) human serum. The antichlamydial activity of HMR 3647 was generally greater than that of commonly used antichlamydial antimicrobials.

The in-vitro activity of linezolid, a novel oxazolidinone, was investigated in comparison with those of amoxycillin, cefuroxime, quinupristin/dalfopristin, trovafloxacin and vancomycin against 420 recent Gram-positive and anaerobic clinical isolates. Linezolid was equally active (MIC90 1 mg/L) against methicillin-susceptible and -resistant Staphylococcus aureus. It demonstrated uniform activity against streptococci and enterococci and no cross-resistance with other agents. The time-kill kinetic data demonstrated that the in-vitro activity of linezolid was predominantly bacteriostatic; slow bactericidal activity was only observed at the higher concentration with streptococci. An increase in inoculum from 10(4) to 10(6) cfu on selected strains had little effect on the MICs (MIC90 within one dilution step) of linezolid and an increase in inoculum from 10(5) to 10(7) cfu/mL had no notable effect on the in-vitro bactericidal activity. A tentative linezolid breakpoint of 2 mg/L was chosen after analysis of distribution of susceptibilities.