Resistance to ceftriaxone and cefotaxime in non-typhoidal Salmonella enterica in England and Wales, 1998-99

Sir, Antibiotics are not usually recommended for the treatment of uncomplicated salmonellosis. However, therapy is essential in extra-intestinal infections and ciprofloxacin is the drug of choice. With the increase in isolates with decreased susceptibility to this antimicrobial agent,1 treatment has been jeopardized2 and third-generation cephalosporins such as ceftriaxone and cefotaxime may provide an alternative therapy. Following reports of the emergence of resistance to extended-spectrum cephalosporins in isolates of non-typhoidal Salmonella enterica from several countries,3,4 concern has been expressed that the efficacy of these antimicrobials may no longer be universal. To assess the occurrence of resistance to third-generation cephalosporins, we have screened 41906 non-typhoidal salmonellae isolated from humans in England and Wales in the 2 year period 1998–99, for resistance to ceftriaxone and cefotaxime. Strains were tested for resistance to ceftriaxone and cefotaxime at 1 mg/L5 using an agar dilution breakpoint method in Isosensitest agar. Isolates showing resistance to these antimicrobials were also tested for resistance to (mg/L): ampicillin (8), chloramphenicol (8), gentamicin (4), kanamycin (16), streptomycin (16), sulphonamides (64), tetracyclines (8), trimethoprim (2), furazolidone (8), ciprofloxacin (0.125 and 1.0) and amikacin (4).6 For those isolates showing resistance to ceftriaxone and cefotaxime at 1 mg/L, the full MICs were determined by agar dilution.6 The full MIC of ciprofloxacin was also determined by doubling dilution and Etest for isolates showing resistance to this antimicrobial agent at 0.125 mg/L. In 1998, seven (0.03%) of 23728 salmonellas were resistant to ceftriaxone and cefotaxime, and in 1999, 14 (0.08%) of 18178 isolates were resistant (Table). The MICs ranged from 16 to 512 mg/L for ceftriaxone and from 8 to 256 mg/L for cefotaxime. Strains resistant to ceftriaxone and cefotaxime were also resistant to ampicillin and, with one exception, were also resistant to at least one additional antimicrobial agent. Nineteen of the ceftriaxone/cefotaxime-resistant isolates were multiresistant (resistant to at least three additional antimicrobial agents), with 11 being resistant to ciprofloxacin at 0.5 mg/L and two at 16 mg/L. Resistance to ceftriaxone and cefotaxime was identified in 10 serotypes but was most common in Salmonella typhimurium (12 isolates), followed by Salmonella senftenberg (three isolates) and Salmonella virchow (two isolates). Sixteen (76%) of the 21 ceftriaxone/cefotaxime-resistant isolates were from patients who had recently travelled abroad, with the most common area visited being Pakistan (eight patients). Other countries visited included India (three patients), Iraq (one), Guatemala (one) and Albania (one); the destinations of two patients with a history of recent travel was not recorded (Table). These results demonstrate that resistance to third-generation cephalosporins remains uncommon in non-typhoidal salmonellae from humans in England and Wales, with <0.1% of isolates being resistant at 1 mg/L. However, resistance is beginning to emerge. Travel to developing countries is a particularly important factor, with 76% of patients with strains resistant to ceftriaxone and cefotaxime giving a history of recent foreign travel. It is also concerning that 62% of ceftriaxone/cefotaxime-resistant isolates were also resistant to ciprofloxacin at 0.25 mg/L, as treatment failures at this level have been described.2 We suggest, therefore, that should antimicrobial therapy be indicated for travellers with a history of recent return from developing countries, physicians should be aware of the possibility of treatment failures and in such cases full MICs to third-generation cephalosporins and to ciprofloxacin should be determined. Table. Characteristics of 21 non-typhoidal salmonella strains with resistance to ceftriaxone and cefotaxime Table. Characteristics of 21 non-typhoidal salmonella strains with resistance to ceftriaxone and cefotaxime