Interpretive reading analyses the complete resistance profiles of bacteria to multiple antibiotics and infers the resistance mechanisms present; it aids therapeutic choice and enhances surveillance data. We evaluated the Advanced Expert System (AES), which interprets MICs generated by the VITEK 2. Ten European laboratories tested 42 reference strains and 76-106 of their own strains, representing important resistance genotypes. Interpretive reading by the VITEK 2 AES achieved full agreement with genotype data for 88-89% of strains, with the correct mechanism identified as one of two possibilities for a further 5-6%. Mechanisms inferred with 90% agreement with reference data included methicillin resistance in staphylococci, glycopeptide resistance in enterococci, quinolone resistance in staphylococci and Enterobacteriaceae, AAC(6')-APH(2")-mediated aminoglycoside resistance in Gram-positive cocci, erm-mediated macrolide resistance in pneumococci, extended-spectrum beta-lactamases (ESBLs) in Enterobacteriaceae and Pseudomonas aeruginosa, and acquired penicillinases in Enterobacteriaceae. VanA, VanB and VanC phenotypes of enterococci were distinguished reliably, and ESBL production was accurately inferred in AmpC-inducible species as well as Escherichia coli and Klebsiella spp. Mechanisms identified, but only as possibilities among several, included IRT-type beta-lactamases and individual aminoglycoside-modifying enzymes in Enterobacteriaceae. Most disagreements with reference data concerned pneumococci found to have high-level penicillin resistance by the VITEK 2 AES but previously determined, phenotypically, to have intermediate resistance. When ESBL production was inferred in E. coli and klebsiellae, the VITEK 2 AES edited susceptible results for cephalosporins (except cefoxitin) to resistant; when an acquired penicillinase was inferred in Enterobacteriaceae, piperacillin results were edited to resistant; and when staphylococci were found methicillin resistant, resistance was reported for all beta-lactams. Further editing may be desirable (e.g. of cephalosporin results for salmonellas inferred to have ESBLs).

The Oxoid combination disk method for detecting extended-spectrum β-lactamases (ESBLs) depends on comparing the inhibition zones of cefpodoxime (10-μg) and cefpodoxime-plus-clavulanate (10- plus 1-μg) disks. The presence of clavulanate enlarged the zones for all of 180 ESBL-producing klebsiellae by ≥5 mm, whereas zones for cefpodoxime-susceptible isolates and cefpodoxime-resistant isolates with AmpC and K1 β-lactamases were enlarged by ≤1 mm. Good discrimination was achieved with either the NCCLS or the British disk method.

Ertapenem (MK-0826; L-749,345), a new carbapenem with a long serum half-life, was tested, in vitro, against ␤-lactamase-producing bacteria. The new compound had a MIC at which 90% of the isolates were inhibited of 0.06 g/ml for extended-spectrum ␤-lactamase (ESBL)-producing klebsiellas, compared with 0.5 g/ml for imipenem, 16 g/ml for cefepime, and >128 g/ml for ceftazidime and piperacillin-tazobactam. MICs of ertapenem for AmpC-derepressed mutant Enterobacteriaceae were 0.015 to 0.5 g/ml, whereas imipenem MICs were 0.25 to 1 g/ml and those of cefepime were 0.5 to 4 g/ml, and resistance to ceftazidime and piperacillintazobactam was generalized. Despite this good activity, the MICs of ertapenem for ESBL-positive klebsiellas mostly were two-to fourfold above those for ESBL-negative strains, and the MICs for AmpC-hyperproducing Enterobacter cloacae and Citrobacter freundii mutants exceeded those for the corresponding AmpC-basal mutants. These differentials did not increase when the inoculum was raised from 10 4 to 10 6 CFU/spot, contraindicating significant lability. Carbapenemase producers were also tested. The IMP-1 metallo-␤-lactamase conferred substantial ertapenem resistance (MIC, 128 g/ml) in a porin-deficient Klebsiella pneumoniae strain, whereas a MIC of 6 g/ml was recorded for its porin-expressing revertant. SME-1 carbapenemase was associated with an ertapenem MIC of 2 g/ml for Serratia marcescens S6, compared with <0.03 g/ml for Serratia strains lacking this enzyme. In summary, ertapenem had good activity against strains with potent ␤-lactamases, except for those with known carbapenemases.Imipenem and meropenem retain activity against bacteria with extended-spectrum ␤-lactamases (ESBLs) and those that hyperproduce AmpC type ␤-lactamases and against Klebsiella oxytoca strains that hyperproduce the K1 enzyme (16). They also retain activity against strains with many less-frequent cephalosporinases, such as the PER and CTX-M enzymes. This activity gives these carbapenem drugs major advantages over cephalosporins, since potent ␤-lactamases are becoming increasingly prevalent. In recent surveys, ESBLs were found in 23 to 25% of klebsiellas from European intensive care units (2, 19); moreover, Klebsiella strains with multiple ESBLs are increasingly seen (10). AmpC ␤-lactamases are chromosomal and ubiquitous in Enterobacter spp., Citrobacter freundii, Morganella morganii, and Serratia spp., where they give resistance to oxyimino-aminothiazolyl cephalosporins if they are hyperproduced as a consequence of mutation (16); in addition AmpC genes can escape to plasmids, spreading resistance into further species (20). Hyperproduction of the K1 enzyme is seen in an increasing proportion of K. oxytoca isolates in European intensive care units (2, 11).The stability of imipenem and meropenem in the presence of potent ␤-lactamases makes the carbapenems an attractive class for further development (9). Ertapenem (MK-0826, L-749,345) (15) is a new analogue in the class, notable for a long serum half-life (ca. 4 h). We evaluated...

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