No abstract

If isolates are speciated and if a sufficient range of antibiotics is tested, underlying resistance mechanisms can often be inferred from the antibiogram data. This allows: (i) anomalous combinations of phenotype and organism to be reconsidered; (ii) prediction of further antibiotics that deserve testing; and (iii) the suppression of susceptibilities that are anomalous in the light of the inferred mechanism. This 'interpretative reading' is widely undertaken in France but is largely precluded in the UK by limited speciation and the testing of narrow ranges of antibiotics. Nevertheless, UK laboratories should be aware of: (i) grossly anomalous combinations of species and phenotype, demanding reference laboratory confirmation; (ii) useful indicator drugs, where resistance implies a mechanism conferring other resistances that may be less obvious in direct tests; and (iii) antibiotics that are prone to select resistant mutants of particular species during therapy. Details of these combinations of organism and resistance are presented. Relationships between antibiogram and mechanism are also presented to allow full interpretative reading for those testing wide panels of drugs versus speciated isolates.

Among Escherichia coli organisms isolated at St. Thomas's Hospital during the years 1990 to 1994, the frequency of resistance to amoxicillin-clavulanic acid (tested by disk diffusion in a ratio of 2:1) remained constant at about 5% of patient isolates (10 to 15% of the 41 to 45% that were amoxicillin resistant). Mechanisms of increased resistance were determined for 72 consecutively collected such amoxicillin-clavulanic acid-resistant isolates. MICs of the combination were 16-8 g/ml for 51 (71%) of these and >32-16 g/ml for the remainder. The predominant mechanism was hyperproduction of enzymes isoelectrically cofocusing with TEM-1 (␤-lactamase activities, >200 nmol of nitrocefin hydrolyzed per min per mg of protein) which was found in 44 isolates (61%); two isolates produced smaller amounts (approximately 150 nmol/min/mg) of such enzymes, and two isolates hyperproduced enzymes cofocusing with TEM-2. Eleven isolates produced enzymes cofocusing with OXA-1 ␤-lactamase, which has previously been associated with resistance to amoxicillinclavulanic acid. Ten isolates produced increased amounts of chromosomal ␤-lactamase, and four of these additionally produced TEM-1 or TEM-2. Three isolates produced inhibitor-resistant TEM-group enzymes. In one of the enzymes (pI, 5.4), the amino acid sequence change was Met-673Val, and thus the enzyme is identical to TEM-34. Another (pI, 5.4) had the substitution Met-673Ile and is identical to IRT-I67, which we propose now be given the designation TEM-40. The third (pI, 5.2) had the substitution Arg-2413Thr; this enzyme has not been reported previously and should be called TEM-41. The rarity and diversity of inhibitor-resistant TEM-group enzymes suggest that they are the result of spontaneous mutations that have not yet spread.