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1.  Antimicrobial resistance in community and nosocomial Escherichia coli urinary tract isolates, London 2005 – 2006 
Escherichia coli is the commonest cause of community and nosocomial urinary tract infection (UTI). Antibiotic treatment is usually empirical relying on susceptibility data from local surveillance studies. We therefore set out to determine levels of resistance to 8 commonly used antimicrobial agents amongst all urinary isolates obtained over a 12 month period.
Antimicrobial susceptibility to ampicillin, amoxicillin/clavulanate, cefalexin, ciprofloxacin, gentamicin, nitrofurantoin, trimethoprim and cefpodoxime was determined for 11,865 E. coli urinary isolates obtained from community and hospitalised patients in East London.
Nitrofurantoin was the most active agent (94% susceptible), followed by gentamicin and cefpodoxime. High rates of resistance to ampicillin (55%) and trimethoprim (40%), often in combination were observed in both sets of isolates. Although isolates exhibiting resistance to multiple drug classes were rare, resistance to cefpodoxime, indicative of Extended spectrum β-lactamase production, was observed in 5.7% of community and 21.6% of nosocomial isolates.
With the exception of nitrofurantoin, resistance to agents commonly used as empirical oral treatments for UTI was extremely high. Levels of resistance to trimethoprim and ampicillin render them unsuitable for empirical use. Continued surveillance and investigation of other oral agents for treatment of UTI in the community is required.
PMCID: PMC2440378  PMID: 18564430
2.  In-vitro activity of polymyxin B in combination with imipenem, rifampicin and azithromycin versus multidrug resistant strains of Acinetobacter baumannii producing OXA-23 carbapenemases 
Acinetobacter baumannii has emerged as a major nosocomial pathogen worldwide. Many of the circulating strains exhibit multi-drug resistance remaining consistently susceptible only to polymyxins. In-vitro studies have reported that polymyxins combined with carbapenems, rifampicin or azithromycin are synergistic against these strains despite in-vitro resistance to these agents alone. The use of antimicrobial combinations have therefore been advocated for the treatment of severe A. baumannii infection in man. In order to determine whether such combinations are synergistic against the prevalent clones of multi-drug resistant A. baumannii causing infection in the UK, we performed synergy testing against representative isolates using two rapid Etest methods.
The activity of polymyxin in combination with imipenem, azithromycin or rifampicin was assessed against five strains of multi-drug resistant A. baumannii encoding OXA-23 carbapenemases. Synergy studies were performed by Etest-agar dilution and a combined Etest strip method. Synergy was defined as a FICI of ≤ 0.5.
All strains were resistant to β-lactams, carbapenems, quinolones and aminoglycosides but susceptible to polymyxins. Marked synergy was not seen with polymyxin in combination with imipenem, rifampicin or azithromycin against any of the strains. Borderline synergy (FICI = 0.5) was seen against one strain belonging to OXA-23 clonal group 2, using the Etest-agar dilution method only.
In-vitro synergy with polymxyin in combination with imipenem, rifampicin or azithromycin is highly strain and method dependent. As reliable synergy could not be demonstrated against the prevalent UK multi-drug resistant strains, use of such combinations should not be used for empirical treatment of these infections in the UK. The optimal treatment for serious multi-drug A. baumannii infection and the role of combination therapy should be addressed in a prospective clinical trial.
PMCID: PMC1484489  PMID: 16630352

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