title: Comparative in vitro activity of sulfametrole/trimethoprim and sulfamethoxazole/trimethoprim and other agents against multiresistant Gram-negative bacteria.
abstract: OBJECTIVE
  Sulfamethoxazole/trimethoprim is standard therapy for infections caused by opportunist non-fermenters except Pseudomonas aeruginosa and Acinetobacter. Sulfametrol(e)/trimethoprim is an alternative to sulfamethoxazole/trimethoprim available in some EU countries, with possible pharmacological advantages. We compared their activities against (i) non-fermenters, (ii) multiresistant Enterobacteriaceae and (iii) reference strains with sul1 and sul2.
  
  
  METHODS
  Test isolates were recent submissions to the reference laboratory, or were Escherichia coli previously shown to have sul1 or sul2. Identification was by MALDI-ToF, by 16S rRNA gene sequencing or with API20NE strips. MICs were determined by CLSI agar dilution. The Stenotrophomonas maltophilia and Burkholderia series were enhanced by inclusion of 25% sulfamethoxazole/trimethoprim-resistant isolates; other series were not enhanced.
  
  
  RESULTS
  MICs of sulfametrole/trimethoprim for non-fermenters tracked those of sulfamethoxazole/trimethoprim, being equal in 97/170 cases, 2-fold higher in 57/170 cases and 2-fold lower in 12/170 cases. Despite supplementing the Burkholderia and S. maltophilia collections with sulfamethoxazole/trimethoprim-resistant organisms, the antifolate combinations retained better activity against these and other non-fermenters than did piperacillin/tazobactam, moxifloxacin, ticarcillin/clavulanate, tigecycline, cefotaxime or imipenem. By contrast, few (5%-20%) of the extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacteriaceae were susceptible to the sulphonamides or their trimethoprim combinations, probably reflecting widespread co-carriage of sul1 and sul2, which both conferred resistance.
  
  
  CONCLUSIONS
  Antifolate combinations remain the most active antimicrobials against less common non-fermenters, importantly including S. maltophilia and Burkholderia spp., but resistance is prevalent among ESBL- and carbapenemase-producing Enterobacteriaceae. Sulfametrole/trimethoprim had similar activity to sulfamethoxazole/trimethoprim against non-fermenters.
authors.affiliation: Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, London NW9 5EQ, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Livermore
authors.forename: Shazad
authors.initials: S
authors.lastname: Mushtaq
authors.forename: Marina
authors.initials: M
authors.lastname: Warner
authors.forename: Neil
authors.initials: N
authors.lastname: Woodford
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D013420:Sulfamethoxazole / Q000494:pharmacology*; D013424:Sulfanilamides / Q000494:pharmacology*; D014295:Trimethoprim / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D013424:Sulfanilamides; D014295:Trimethoprim; C012047:sulfametrole; D013420:Sulfamethoxazole
keywords: Stenotrophomonas maltophilia; cystic fibrosis; non-fermenters