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The goal of this exercise was to organize external quality assurance (QA) of antibiotic susceptibility testing for laboratories participating in EARSS and to assess the comparability of susceptibility test results across countries, and guidelines. In September 2000, UK NEQAS distributed a set of three Streptococcus pneumoniae strains, two Staphylococcus aureus strains and one Streptococcus haemolyticus strain. Laboratories reported the guideline followed, the interpretation of the susceptibility test result and the MIC, if tested. In this study we considered results 'concordant' if the reported interpretation of the participating laboratory agreed with the designated interpretation of reference laboratories. Overall, 433 (92%) of 471 laboratories from 23 countries reported back. Of the 8685 tests that were assessed, 8322 (96%) were interpreted correctly by the participants. Concordance for detection of penicillin non-susceptibility in the three S. pneumoniae strains was 96%, 90% and 87%, respectively. Laboratories performed extremely well in detecting oxacillin resistance in the homogeneously methicillin-resistant S. aureus (MRSA) strain, but the concordance rate dropped from 100% to 77% in the heterogeneously resistant MRSA strain. Concordance for detection of teicoplanin resistance in the S. haemolyticus strain was 82%. We stratified concordance rates first for country and then for guideline used, but observed only minor differences among countries and guidelines. Quantitative methods yielding an MIC were more concordant than non-MIC methods for penicillin resistance in the S. pneumoniae strains (94% versus 79%). The NCCLS guideline was the most frequently followed, by 61% of laboratories from 19 countries. This exercise shows that, overall, countries participating in EARSS are capable of delivering susceptibility data of good quality. The comparability of susceptibility data for penicillin resistance in S. pneumoniae and for homogeneous methicillin resistance in S. aureus is satisfactory among European countries and across guidelines. However, we emphasize the importance of determining an MIC for suspected penicillin non-susceptible S. pneumoniae and for suspected glycopeptide non-susceptible S. aureus. Laboratories, particularly in some countries, may need to improve their capability to detect oxacillin resistance in heterogeneously resistant MRSA. For continuous external quality assessment we recommend that laboratories participate in national and international schemes with frequent distribution of control strains.

The goal of this exercise was to organize external quality assurance (QA) of antibiotic susceptibility testing for laboratories participating in EARSS and to assess the comparability of susceptibility test results across countries, and guidelines. In September 2000, UK NEQAS distributed a set of three Streptococcus pneumoniae strains, two Staphylococcus aureus strains and one Streptococcus haemolyticus strain. Laboratories reported the guideline followed, the interpretation of the susceptibility test result and the MIC, if tested. In this study we considered results ‘concordant’ if the reported interpretation of the participating laboratory agreed with the designated interpretation of reference laboratories. Overall, 433 (92%) of 471 laboratories from 23 countries reported back. Of the 8685 tests that were assessed, 8322 (96%) were interpreted correctly by the participants. Concordance for detection of penicillin non-susceptibility in the three S. pneumoniae strains was 96%, 90% and 87%, respectively. Laboratories performed extremely well in detecting oxacillin resistance in the homogeneously methicillin-resistant S. aureus (MRSA) strain, but the concordance rate dropped from 100% to 77% in the heterogeneously resistant MRSA strain. Concordance for detection of teicoplanin resistance in the S. haemolyticus strain was 82%. We stratified concordance rates first for country and then for guideline used, but observed only minor differences among countries and guidelines. Quantitative methods yielding an MIC were more concordant than non-MIC methods for penicillin resistance in the S. pneumoniae strains (94% versus 79%). The NCCLS guideline was the most frequently followed, by 61% of laboratories from 19 countries. This exercise shows that, overall, countries participating in EARSS are capable of delivering susceptibility data of good quality. The comparability of susceptibility data for penicillin resistance in S. pneumoniae and for homogeneous methicillin resistance in S. aureus is satisfactory among European countries and across guidelines. However, we emphasize the importance of determining an MIC for suspected penicillin non-susceptible S. pneumoniae and for suspected glycopeptide non-susceptible S. aureus. Laboratories, particularly in some countries, may need to improve their capability to detect oxacillin resistance in heterogeneously resistant MRSA. For continuous external quality assessment we recommend that laboratories participate in national and international schemes with frequent distribution of control strains.

The in-vitro activity of MEN 10700, a novel penem, was compared with that of imipenem, ritipenem, ampicillin/sulbactam, cefotaxime, ciprofloxacin and amikacin against 1088 strains taken from 21 genera, including Gram negative, Gram-positive and anaerobic bacteria. MIC data showed that MEN 10700 was very active against staphylococci and streptococci (MIC90≤0.5 mg/L) and against most members of the Enterobacteriaceae (MIC90≤2 mg/L), with reduced activity only against Providencia stuartii (MIC90=8 mg/L). MEN 10700 was also active against anaerobic species such as Clostridium perfringens and Bacteroides fragilis as well as Moraxella catarrhalis. It was moderately active against Enterococcus faecalis and inactive against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Aeromonas spp. and Acinetobacter spp. Its antibacterial spectrum was thus slightly narrower than that of imipenem, but compared favourably with those of a third-generation cephalosporin and ritipenem. MEN 10700 was highly stable to a number of β-lactamases and was a poor inducer of class I enzymes. It bound penicillin-binding protein 2 with the highest affinity and easily permeated the outer membrane of Escherichia coli.

The binding of ceftriaxone, a cephalosporin that exhibits high serum protein binding and prolonged serum half-life, to penicillin-binding proteins (PBPs) of Escherichia coli K12 in the presence of human serum albumin was compared with plasma concentrations of cefotaxime, a cephalosporin with low serum protein binding and a short serum half-life. Ceftriaxone concentrations equivalent to those maintained in plasma for 8 h after an intravenous infusion of 1 g saturated PBPs 2 and 3. Cefotaxime saturated both PBPs at concentrations equivalent to those maintained for 2 h, and PBP 3 only at concentrations maintained for 2-8 h. These results indicate that high serum protein binding does not impair the ability of ceftriaxone to inhibit essential PBPs, and explain the high in-vivo efficacy of the drug.

The in-vitro activity of MEN 10700, a novel penem, was compared with that of imipenem, ritipenem, ampicillin/sulbactam, cefotaxime, ciprofloxacin and amikacin against 1088 strains taken from 21 genera, including Gram-negative, Gram-positive and anaerobic bacteria. MIC data showed that MEN 10700 was very active against staphylococci and streptococci (MIC90 < or = 0.5 mg/L) and against most members of the Enterobacteriaceae (MIC90 < or = 2 mg/L), with reduced activity only against Providencia stuartii (MIC90 = 8 mg/L). MEN 10700 was also active against anaerobic species such as Clostridium perfringens and Bacteroides fragilis as well as Moraxella catarrhalis. It was moderately active against Enterococcus faecalis and inactive against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Aeromonas spp. and Acinetobacter spp. Its antibacterial spectrum was thus slightly narrower than that of imipenem, but compared favourably with those of a third-generation cephalosporin and ritipenem. MEN 10700 was highly stable to a number of beta-lactamases and was a poor inducer of class I enzymes. It bound penicillin-binding protein 2 with the highest affinity and easily permeated the outer membrane of Escherichia coli.

&lt;it>Objectives&lt;/it>: To investigate whether telithromycin is a substrate for efflux pumps in &lt;it>Streptococcus pyogenes&lt;/it>. &lt;it>Methods&lt;/it>: The distribution of telithromycin MICs was analysed for two distinct collections of Italian (&lt;it>n&lt;/it>=486) and Spanish (&lt;it>n&lt;/it>=210) &lt;it>S. pyogenes&lt;/it> strains. The effect of an efflux mechanism was investigated using [3H]telithromycin. &lt;it>Results&lt;/it>: Telithromycin MIC ranges were ≤ 0.004–0.06 mg/L (MIC&lt;inf>50&lt;/inf> and MIC&lt;inf>90&lt;/inf>, 0.01 mg/L) in erythromycin-susceptible strains (lacking both &lt;it>mef&lt;/it> and &lt;it>erm&lt;/it> genes) and 0.01–1 mg/L (MIC&lt;inf>50&lt;/inf> and MIC&lt;inf>90&lt;/inf>, 0.5 mg/L) in strains endowed with the M phenotype and expressing the &lt;it>mef&lt;/it>(A) gene. A distinct telithromycin efflux was detected in the strains expressing the &lt;it>mef&lt;/it>(A) gene, but not in those expressing the &lt;it>erm&lt;/it>(B) gene, nor in the susceptible strains lacking &lt;it>mef&lt;/it>(A) or &lt;it>erm&lt;/it> genes. Efflux reversibility by addition of an inhibiting compound (sodium arsenate) was demonstrated. An &lt;it>msr&lt;/it>-like sequence was also found in all strains effluxing telithromycin, but not in the others. &lt;it>Conclusions&lt;/it>: This study shows that telithromycin can be removed from &lt;it>S. pyogenes&lt;/it> by efflux. That the efflux is related to the presence of the &lt;it>mef&lt;/it>(A) gene is demonstrated, but—owing to the increasingly evident complexity of &lt;it>S. pyogenes&lt;/it> efflux systems—the possibility that other genes may contribute to the efflux cannot be excluded.