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Comparative in vitro activity of sulfametrole/trimethoprim and sulfamethoxazole/trimethoprim and other agents against multiresistant Gram-negative bacteria. 2014

David M Livermore, and Shazad Mushtaq, and Marina Warner, and Neil Woodford
Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, London NW9 5EQ, UK.

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.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D006090 Gram-Negative Bacteria Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. Gram Negative Bacteria
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D013420 Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p208) Sulfamethylisoxazole,Gantanol,Sulfisomezole,Sulphamethoxazole
D013424 Sulfanilamides Compounds based on 4-aminobenzenesulfonamide. The '-anil-' part of the name refers to aniline. Sulphanilamides
D014295 Trimethoprim A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to PYRIMETHAMINE. It is potentiated by SULFONAMIDES and the TRIMETHOPRIM, SULFAMETHOXAZOLE DRUG COMBINATION is the form most often used. It is sometimes used alone as an antimalarial. TRIMETHOPRIM RESISTANCE has been reported. Proloprim,Trimpex
D016905 Gram-Negative Bacterial Infections Infections caused by bacteria that show up as pink (negative) when treated by the gram-staining method. Bacterial Infections, Gram-Negative,Infections, Gram-Negative Bacterial,Bacterial Infection, Gram-Negative,Gram Negative Bacterial Infections,Gram-Negative Bacterial Infection,Infection, Gram-Negative Bacterial
D024901 Drug Resistance, Multiple, Bacterial The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Drug Resistance, Extensive, Bacterial,Drug Resistance, Extensively, Bacterial,Extensive Antibacterial Drug Resistance,Extensively Antibacterial Drug Resistance,Multidrug Resistance, Bacterial,Multiple Antibacterial Drug Resistance,Bacterial Multidrug Resistance,Bacterial Multidrug Resistances,Resistance, Bacterial Multidrug

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