Comparative study of the in vitro activity of a new fluoroquinolone, ABT-492.

OBJECTIVES: The in vitro activity of a new fluoroquinolone, ABT-492, was determined. METHODS: MICs were compared with those of two beta-lactams, telithromycin, ciprofloxacin and four later generation fluoroquinolones. The effects of human serum and of inoculum concentration were also investigated. RESULTS: MIC data indicate that ABT-492 has potent activity against Gram-positive organisms with enhanced anti-staphylococcal activity compared with earlier fluoroquinolones, in addition to activity against beta-haemolytic streptococci, pneumococci including penicillin- and fluoroquinolone-resistant strains and vancomycin-susceptible and -resistant Enterococcus faecalis but not Enterococcus faecium. ABT-492 was the most active agent tested against Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, fluoroquinolone-susceptible Neisseria gonorrhoeae and anaerobes. Good activity was observed for ABT-492 amongst the Enterobacteriaceae and anaerobes tested, but ciprofloxacin showed superior activity for species of Proteus, Morganella and Providencia, as well as for Pseudomonas spp. In common with the other fluoroquinolones tested, organisms with reduced susceptibility to ciprofloxacin had raised MIC(90)s to ABT-492. The one isolate of H. influenzae tested with reduced fluoroquinolone susceptibility had an ABT-492 MIC close to that of the population lacking a mechanism of quinolone resistance. ABT-492 was more active than ciprofloxacin against Chlamydia spp. An inoculum effect was observed with a number of isolates of Staphylococcus aureus, Streptococcus pneumoniae, E. faecium, Klebsiella spp. and Escherichia coli, in addition to moderately raised MICs in the presence of 70% serum protein. The clinical significance of these findings is yet to be determined. CONCLUSIONS: ABT-492 is a new fluoroquinolone with excellent activity against both Gram-positive and Gram-negative organisms, with many potential clinical uses.

Emergence of a fluoroquinolone-resistant strain of Streptococcus pneumoniae in England.

OBJECTIVE: To determine the epidemiological relationship between pneumococci of serotype 9V, with reduced susceptibility to ciprofloxacin, penicillin and erythromycin, referred to the Reference Laboratory during 1997-2001. METHODS: Isolates were characterized by multilocus sequence typing (MLST), PFGE, and sequencing of parC and gyrA. Relevant clinical data were sought. RESULTS: Forty-eight isolates were received from nine laboratories in England, but 35 (73%) were from one laboratory in Birmingham, and were mostly from elderly patients receiving ofloxacin or ciprofloxacin for respiratory infections. There were two quinolone resistance phenotypes, with ciprofloxacin, moxifloxacin and gemifloxacin MICs of 8-32, 0.5-1 and 0.125-0.25 mg/L, and 64-256, 4-16 and 1-4 mg/L, respectively. Each of three isolates from the former group had mutations in parC, whereas each of nine isolates from the more resistant group had mutations in both parC and gyrA. Several also had increased quinolone efflux. Typing of 27 quinolone-resistant isolates showed that eight were indistinguishable from the epidemic Spain9V-3 (ST156) clone, while the remainder belonged to a novel but related type (ST609), that differed from Spain9V-3 at 2/7 alleles (2 bp changes in aroE and 1 bp change in gdh). Both MLST types were represented among isolates with high- and low-level quinolone resistance. Three of five serotype 9V isolates from Birmingham, with reduced susceptibility to penicillin and erythromycin, and ciprofloxacin MICs of 1-2 mg/L, belonged to MLST type ST609, while another was indistinguishable from the Spain9V-3 clone. Review of records of 32 patients from Birmingham indicated that some isolates were nosocomial, whereas others were acquired in the community. CONCLUSIONS: In the late 1990s, a quinolone-resistant strain, clonally related to Spain9V-3, emerged in England, principally in Birmingham.

Critical care unit outbreak of Serratia liquefaciens from contaminated pressure monitoring equipment.

Between October and December 1999, Serratia liquefaciens was isolated from 11 patients in an adult critical care unit. One patient was infected on two separate occasions. In total, there were 10 positive blood cultures and five positive intravascular catheter tips. Eight cases were clinically infected, three were possibly infected and one was not. All patients with clinical isolates received appropriate empirical antibiotic treatment and responded well. Environmental investigation revealed S. liquefaciens in syringes and connector tubing used to calibrate the intravascular line pressure monitoring equipment of eight patients. Three of these patients also had clinical isolates of S. liquefaciens. Analysis by pulsed-field gel electrophoresis found clinical and environmental isolates to be of the same strain. The most likely mode of transmission was a non-sterile sphygmomanometer tip used daily for calibration. Inadequate microbiological sampling methods may have limited detection of S. liquefaciens. Several other examples of poor infection control techniques were identified during the outbreak, notably lapses in hand hygiene during intravascular pressure monitoring. It was also observed that unlabelled multidose heparin and insulin vials were shared between patients and personal hand creams were used by staff. However, these were not directly implicated in the outbreak. The outbreak ended when poor infection control practices were corrected. Calibration syringes and connector tubing were discarded after a single use. The sphygmomanometer was replaced by a pneumatic pressure transducer tester with connector tube and the frequency of calibration reduced to a single test following line insertion only. The non-disposable tube was disinfected with alcohol wipes between patients.