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Fernando Baquero

Publications and source records attributed to Fernando Baquero.

At least 73 records · Page 4Linked to original sources
PubMed2003

Haemophilus influenzae bla(ROB-1) mutations in hypermutagenic deltaampC Escherichia coli conferring resistance to cefotaxime and beta-lactamase inhibitors and increased susceptibility to cefaclor.

The clinical use of cefaclor has been shown to enrich Haemophilus influenzae populations harboring cefaclor-hydrolyzing ROB-1 beta-lactamase. Such a selective process may lead to the increased use of extended-spectrum cephalosporins or beta-lactams plus beta-lactamase inhibitors and, eventually, resistance to these agents, which has not previously been observed in H. influenzae. In order to establish which bla(ROB-1) mutations, if any, could confer resistance to extended-spectrum cephalosporins and/or to beta-lactamase inhibitors, a plasmid harboring bla(ROB-1) was transformed into hypermutagenic strain Escherichia coli GB20 (DeltaampC mutS::Tn10), and this construct was used in place of H. influenzae bla(ROB-1). Strain GB20 with the cloned gene was submitted to serial passages in tubes containing broth with increasing concentrations of selected beta-lactams (cefotaxime or amoxicillin-clavulanate). Different mutations in the bla(ROB-1) gene were obtained during the passages in the presence of the different concentrations of the selective agents. Mutants resistant to extended-spectrum cephalosporins harbored either the Leu169-->Ser169 or the Arg164-->Trp164 substitution or the double amino acid change Arg164-->Trp164 and Ala237-->Thr237. ROB-1 mutants that were resistant to beta-lactams plus beta-lactamase inhibitors and that harbored the Arg244-->Cys244 or the Ser130-->Gly130 replacement were also obtained. The cefaclor-hydrolyzing efficiencies of the ROB-1 variants were strongly decreased in all mutants, suggesting that if bla(ROB-1) mutants were selected by cefaclor, this drug would prevent the further evolution of this beta-lactamase toward molecular forms able to resist extended-spectrum cephalosporins or beta-lactamase inhibitors.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2003

Fluoroquinolone-resistant Streptococcus pneumoniae in Spain: activities of garenoxacin against clinical isolates including strains with altered topoisomerases.

The activity of garenoxacin was assessed against 412 Streptococcus pneumoniae isolates (49.3% from the adult population). Overall penicillin, erythromycin, and ciprofloxacin (MIC, >/=4 micro g/ml) resistance was 51.7, 35.4, and 1.5%, respectively. For all isolates, the garenoxacin MIC was </=1 micro g/ml. Amino acid replacements in GryA (Ser81-->Phe or Tyr), ParC (Ser79-->Phe or Tyr; Asp83-->Gly; Lys137-->Asn), and ParE (Ile460-->Val; Asp435-->Asn), alone or in combination, were ascribed to the reduced garenoxacin susceptibility (MIC range, 0.5 to 1 micro g/ml) found in four isolates. The low impact of these mutations on garenoxacin activity envisages the possible coverage of S. pneumoniae populations resistant to preexisting quinolones.

Anti-Infective Agents↗
PubMed2003

Quality control for beta-lactam susceptibility testing with a well-defined collection of Enterobacteriaceae and Pseudomonas aeruginosa strains in Spain.

Eighteen Enterobacteriaceae and Pseudomonas aeruginosa strains, 16 of them with well-defined beta-lactam resistance mechanisms, were sent to 52 Spanish microbiology laboratories. Interpretative categories for 8 extended-spectrum beta-lactams were collected. Participating laboratories used their own routine susceptibility testing procedures (88% automatic systems, 10% disk diffusion, and 2% agar dilution). Control results were established by two independent reference laboratories by applying the NCCLS microdilution method and interpretative criteria. Interpretative discrepancies were observed in 16% of the results (4.4% for cefepime, 3.0% for aztreonam, 2.8% for piperacillin-tazobactam, 1.7% for cefotaxime [CTX] and ceftazidime, 1.1% for ceftriaxone, 0.9% for meropenem, and 0.3% for imipenem). High consistency with reference values (<5% of major plus very major errors) was observed with (i) American Type Culture Collection quality control strains; (ii) strains with low-efficiency mechanisms inactivating extended-spectrum beta-lactams, such as OXA-1-producing Escherichiacoli or SHV-1-hyperproducing Klebsiella pneumoniae; (iii) strains with highly efficient mechanisms, such as SHV-5 porin-deficient K. pneumoniae, CTX-M-10 in Enterobacter cloacae hyperproducing AmpC, and P. aeruginosa with the MexAB OprM efflux phenotype or hyperproducing AmpC. Low consistency (>30% major plus very major errors) was detected in K1-producing Klebsiella oxytoca, CTX-M-9-producing E. coli, and in OprD(-) P. aeruginosa strains. Extended-spectrum beta-lactamase (ESBL)-producing strains accounted for 86% of very major errors. Recognition of the ESBL phenotype was particularly low in Enterobacter cloacae strains (<35%), due to the lack of NCCLS-specific rules in this genus. A K1-producing K. oxytoca was misidentified by 10% of laboratories as an ESBL producer. The use of well-defined resistant strains is useful for improving proficiency in susceptibility testing in clinical laboratories.

Anti-Bacterial Agents↗
PubMed2002

[Antibiotic resistance in blood isolates of Staphylococcus aureus in 31 Spanish hospitals participating in the European Antimicrobial Resistance Surveillance System (2000)].

BACKGROUND: In 1998, the European Union funded the European Antimicrobial Resistance Surveillance System. We present here Staphylococcus aureus data in 2000 in Spain. MATERIAL AND METHOD: 31 hospitals were involved, covering almost 25% Spanish total population. All nosocomial blood isolates of S. aureus were included. Each laboratory carried out microbiological studies with its own usual methods. Quality control was carried out by UK National External Quality (NEQAS). A questionnaire including hospital, patient and specimen data was filled out for each isolate. Results were registered in a single database and analyzed and validated with Whonet. 5 software. RESULTS: Invasive S. aureus was isolated in 903 patients. Overall incidence was 1.45/1000 admitted patients. Resistance was 28.1% (95% CI, 25.2-31.1) to oxacillin (O), 26.6% to ciprofloxacin (C), 23.8% to erythromycin (E) and 16.6% to gentamicin (G). Multiresistance was noticed in 80% oxacillin-resistant strains. More frequent multiresistance profiles were OECG (11.3% of all isolates) and OEC (6.3%). Oxacillin resistance was higher in ICU units (44.5%) than in other medical departments (27.4%) (p < 0.001). Hospitals with 500 beds or more showed 36.4% prevalence of O resistance, while in hospitals having less than 500 beds it was 18.8% (p < 0.001). A decreased susceptibility to vancomycin was not detected. CONCLUSIONS: In Spain, invasive S. aureus shows a high prevalence of resistance to oxacillin, ciprofloxacin, erythromycin and gentamicin. Most oxacillin-resistant strains were resistant to three or more antibiotics. Nearly 50% oxacillin-resistant isolates were susceptible to gentamicin. Oxacillin resistance and resistance to multiple antibiotics was more frequent in ICU units and in hospitals with 500 beds or more.

Adolescent↗
PubMed2002

Allodemics.

Explore the source record for details and available documents.

Bacteria↗
PubMed2002

The mismatch repair system (mutS, mutL and uvrD genes) in Pseudomonas aeruginosa: molecular characterization of naturally occurring mutants.

We have recently described the presence of a high proportion of Pseudomonas aeruginosa isolates (20%) with an increased mutation frequency (mutators) in the lungs of cystic fibrosis (CF) patients. In four out of 11 independent P. aeruginosa strains, the high mutation frequency was found to be complemented with the wild-type mutS gene from P. aeruginosa PAO1. Here, we report the cloning and sequencing of two additional P. aeruginosa mismatch repair genes and the characterization, by complementation of deficient strains, of these two putative P. aeruginosa mismatch repair genes (mutL and uvrD). We also describe the alterations in the mutS, mutL and uvrD genes responsible for the mutator phenotype of hypermutable P. aeruginosa strains isolated from CF patients. Seven out of the 11 mutator strains were found to be defective in the MMR system (four mutS, two mutL and one uvrD). In four cases (three mutS and one mutL), the genes contained frameshift mutations. The fourth mutS strain showed a 3.3 kb insertion after the 10th nucleotide of the mutS gene, and a 54 nucleotide deletion between two eight nucleotide direct repeats. This deletion, involving domain II of MutS, was found to be the main one responsible for mutS inactivation. The second mutL strain presented a K310M mutation, equivalent to K307 in Escherichia coli MutL, a residue known to be essential for its ATPase activity. Finally, the uvrD strain had three amino acid substitutions within the conserved ATP binding site of the deduced UvrD polypeptide, showing defective mismatch repair activity. Interestingly, cells carrying this mutant allele exhibited a fully active UvrABC-mediated excision repair. The results shown here indicate that the putative P. aeruginosa mutS, mutL and uvrD genes are mutator genes and that their alteration results in a mutator phenotype.

Adenosine Triphosphatases↗
PubMed2002

Fitness of in vitro selected Pseudomonas aeruginosa nalB and nfxB multidrug resistant mutants.

Overproduction of multidrug resistance (MDR) efflux pumps is involved in the resistance to a wide range of compounds in bacteria. These determinants extrude antibiotics, but also bacterial metabolites like quorum-sensing signals. Non-regulated extrusion of bacterial metabolites might produce a metabolic burden, so that MDR-overproducing mutants could have a reduced fitness when compared with their parental strains. To test such a possibility, we have compared the behaviour of two MDR Pseudomonas aeruginosa in vitro selected mutants (nalB and nfxB) with their isogenic parental strain with respect to some properties with potential relevance for the survival in the environment and the virulence of this bacterial species. Overproduction of the MDR determinants MexABOprM (nalB mutant) and MexCDOprJ (nfxB mutant) decreased the survival in water, the production of phenazines and proteases, and the virulence (using a Caenorhabditis elegans model system) of the P. aeruginosa mutants. In contrast, the capability of forming biofilms was not impaired. The simple models tested in the present work can enable the analysis of the fitness of large numbers of antibiotic-resistant bacteria by using more realistic approaches than the in vitro competition assays currently used.

Drug Resistance, Multiple, Bacterial↗
PubMed2002

Risk factors associated with ampicillin resistance in patients with bacteraemia caused by Enterococcus faecium.

Epidemiological characteristics of ampicillin-resistant, vancomycin-susceptible Enterococcus faecium are not well known. Recently, these strains have been proposed as the substratum for the later appearance of vancomycin-resistant E. faecium. To analyse this problem, the medical charts of patients with bacteraemia caused by E. faecium diagnosed in our institution during a 6 year period (1994-1999) were reviewed. Demographic data, clinical characteristics, antibiotic exposure and outcome were compared among patients with ampicillin-resistant (MIC > 16 mg/L, NCCLS criteria) and ampicillin-susceptible strains. Clonality between different strains was analysed by pulsed-field gel electrophoresis (PFGE). We evaluated 49 cases of E. faecium bacteraemia; 29 patients with ampicillin-resistant strains and 20 patients with -susceptible strains were identified. By logistic regression analysis, only previous administration of beta-lactams (OR: 6.3; 95% CI: 1.12-20.0) and urinary catheterization (OR:4.2; 95% CI: 1.3-30.0) were identified as predictors of ampicillin resistance in enterococcal bacteraemic patients. An elevated APACHE II score was the only independent factor associated with mortality in enterococcal bacteraemia (OR:13.5; 95% CI: 1.04-175.4). PFGE analysis revealed a strong association between specific ampicillin-resistant clones and the location of patients during hospitalization, suggesting nosocomial transmission. Bacteraemia caused by ampicillin-resistant enterococci was not associated with increased mortality when compared with bacteraemias caused by ampicillin-susceptible strains.

Ampicillin Resistance↗
PubMed2002

High occurrence of esp among ampicillin-resistant and vancomycin-susceptible Enterococcus faecium clones from hospitalized patients.

The ability to colonize patients successfully may be essential for the emergence and spread of resistant nosocomial strains. We determined the presence of Esp, a surface protein involved in colonization ability in Enterococcus faecalis, in 96 Enterococcus faecium isolates from hospitalized patients (77 PFGE clones), 33 faecal isolates from healthy volunteers (32 clones) and 20 environmental isolates (20 clones). Esp was found significantly more often in E. faecium isolated from hospitalized patients than in isolates from the community setting (26% versus 6%, P < 0.01) and was significantly more common among ampicillin-resistant than among ampicillin-susceptible strains (37% versus 4%, P < 0.001), regardless of the isolation site. The frequency of the esp gene in the hospital clearly correlates with antibiotic-resistant E. faecium clones. This observation indicates that antibiotic-resistant variants may frequently arise under antibiotic selective pressure among esp-positive clones reaching ecological abundance in the nosocomial habitat.

Ampicillin Resistance↗
PubMed2002

Antimicrobial resistance amongst isolates of Streptococcus pyogenes and Staphylococcus aureus in the PROTEKT antimicrobial surveillance programme during 1999-2000.

The pattern of susceptibility to a range of antimicrobials was tested for 1485 isolates of Streptococcus pyogenes and 1547 isolates of Staphylococcus aureus included in the international PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance study (1999-2000). Overall, almost 10% of S. pyogenes isolates were erythromycin A resistant. There was a wide heterogeneity of resistance, with high levels of macrolide resistance in Poland (42%), Hong Kong (28%), Italy (25%), Portugal (24%) and Spain (21%), and no macrolide resistance in Indonesia, Austria, Belgium, the Netherlands or the UK. Using NCCLS tentative breakpoints, 97.6% of isolates were susceptible to telithromycin, with MIC(90) < or = 0.015 mg/L in most regions. Resistance among S. pyogenes to the beta-lactams (MIC(90) < or = 0.12 mg/L for all except cefaclor) and fluoroquinolones was not detected. Macrolide resistance was present among the S. aureus isolates, and as with S. pyogenes, there was a wide heterogeneity of resistance, with lower rates in Australia, Indonesia, Hungary, Austria, Germany, the Netherlands, Portugal, Sweden and Switzerland. Methicillin-resistant isolates were resistant to the beta-lactams and the macrolides. Resistance to telithromycin was detected in methicillin-resistant isolates in Latin and North America, Asia and Europe. Telithromycin resistance was non-existent or low (MIC(90 )range 0.06-0.25 mg/L) in Australia, Indonesia, Hungary, Austria, Germany, the Netherlands, Portugal, Sweden and Switzerland. Regardless of methicillin susceptibility, resistance to linezolid, teicoplanin or vancomycin was not apparent globally.

Anti-Bacterial Agents↗
PubMed2002

Genes encoding TEM-4, SHV-2, and CTX-M-10 extended-spectrum beta-lactamases are carried by multiple Klebsiella pneumoniae clones in a single hospital (Madrid, 1989 to 2000).

Over a 12-year period (1989 to 2000), 159 Klebsiella pneumoniae isolates harboring extended-spectrum beta-lactamases (ESBLs) (4.8% of the total number of K. pneumoniae isolates obtained) were recovered from 58 patients, who were mainly hospitalized in intensive care and surgery units. For 62 representative isolates from 58 patients, 31 clonal types harboring TEM-4 (n = 5), SHV-2 (n = 7), SHV2a (n = 4), SHV-5 (n = 1), CTX-M-10 (n = 13), or CTX-M-9 (n = 1) beta-lactamases were identified by pulsed-field gel electrophoresis. This is the first report to document the presence of the CTX-M-10 or the CTX-M-9 beta-lactamase in K. pneumoniae. These beta-lactamases were previously identified in Escherichia coli isolates from Spain. Only two of five K. pneumoniae TEM-4 clones caused more than a single case of infection, with one of them spreading for 9 months. A single plasmid was detected among these TEM-4 clones. Only two of seven K. pneumoniae clones containing SHV-2 and three of four strains harboring SHV-2a were detected in more than one case of infection. Plasmids encoding SHV-2 or SHV-2a were unrelated. Four of 13 K. pneumoniae CTX-M-10 clones were found in more than one patient, with two of them recovered 2 and 5 years apart. As in the case of the SHV-2 isolates, we were unable to document a common transmissible genetic element that could explain the polyclonal structure of our isolates. Nevertheless, the spread of a single gene may be suggested by the presence of a conserved set of noncoding polymorphisms in the sequences. Most ESBL-producing K. pneumoniae clones were ephemeral, being poorly selected and maintained in the hospital setting, but the genes encoding ESBL persisted successfully over the years that the strains were recovered, probably as a minority gene population in the hospital metagenome.

DNA, Bacterial↗
PubMed2002

Very low cefotaxime concentrations select for hypermutable Streptococcus pneumoniae populations.

A mixed culture of an hypermutable hexA Streptococcus pneumoniae mutant strain and its hexA(+) isogenic ancestor was challenged with low cefotaxime concentrations. Despite identical original cefotaxime MICs, the hexA mutant population was significantly selected at very low concentrations, and all of the tested selected variants harbored the Thr550-->Ala mutation in pbp2x. Since cefotaxime selects hypermutators, the risk of secondary acquisition of antibiotic resistance is increased; as expected, the cefotaxime-resistant mutants had a mutation frequency 10 times higher in response to to ciprofloxacin. The present study presents a model (not necessarily reflecting the clinical setting) illustrating the risk of selection of mutators in the evolution of multiple resistance.

Bacterial Proteins↗
PubMed2002

Topoisomerase II and IV quinolone resistance-determining regions in Stenotrophomonas maltophilia clinical isolates with different levels of quinolone susceptibility.

The quinolone resistance-determining regions (QRDRs) of topoisomerase II and IV genes from Stenotrophomonas maltophilia ATCC 13637 were sequenced and compared with the corresponding regions of 32 unrelated S. maltophilia clinical strains for which ciprofloxacin MICs ranged from 0.1 to 64 microg/ml. GyrA (Leu-55 to Gln-155, Escherichia coli numbering), GyrB (Met-391 to Phe-513), ParC (Ile-34 to Arg-124), and ParE (Leu-396 to Leu-567) fragments from strain ATCC 13637 showed high degrees of identity to the corresponding regions from the phytopathogen Xylella fastidiosa, with the degrees of identity ranging from 85.0 to 93.5%. Lower degrees of identity to the corresponding regions from Pseudomonas aeruginosa (70.9 to 88.6%) and E. coli (73.0 to 88.6%) were observed. Amino acid changes were present in GyrA fragments from 9 of the 32 strains at positions 70, 85, 90, 103, 112, 113, 119, and 124; but there was no consistent relation to higher ciprofloxacin MICs. The absence of changes at positions 83 and 87, commonly involved in quinolone resistance in gram-negative bacteria, was unexpected. The GyrB sequences were identical in all strains, and only one strain (ciprofloxacin MIC, 16 microg/ml) showed a ParC amino acid change (Ser-80-->Arg). In contrast, a high frequency (16 of 32 strains) of amino acid replacements was present in ParE. The frequencies of alterations at positions 437, 465, 477, and 485 were higher (P < 0.05) in strains from cystic fibrosis patients, but these changes were not linked with high ciprofloxacin MICs. An efflux phenotype, screened by the detection of decreases of at least twofold doubling dilutions of the ciprofloxacin MIC in the presence of carbonyl cyanide m-chlorophenylhydrazone (0.5 microg/ml) or reserpine (10 microg/ml), was suspected in seven strains. These results suggest that topoisomerases II and IV may not be the primary targets involved in quinolone resistance in S. maltophilia.

4-Quinolones↗
PubMed2002

Interactions among strategies associated with bacterial infection: pathogenicity, epidemicity, and antibiotic resistance.

Infections have been the major cause of disease throughout the history of human populations. With the introduction of antibiotics, it was thought that this problem should disappear. However, bacteria have been able to evolve to become antibiotic resistant. Nowadays, a proficient pathogen must be virulent, epidemic, and resistant to antibiotics. Analysis of the interplay among these features of bacterial populations is needed to predict the future of infectious diseases. In this regard, we have reviewed the genetic linkage of antibiotic resistance and bacterial virulence in the same genetic determinants as well as the cross talk between antibiotic resistance and virulence regulatory circuits with the aim of understanding the effect of acquisition of resistance on bacterial virulence. We also discuss the possibility that antibiotic resistance and bacterial virulence might prevail as linked phenotypes in the future. The novel situation brought about by the worldwide use of antibiotics is undoubtedly changing bacterial populations. These changes might alter the properties of not only bacterial pathogens, but also the normal host microbiota. The evolutionary consequences of the release of antibiotics into the environment are largely unknown, but most probably restoration of the microbiota from the preantibiotic era is beyond our current abilities.

Animals↗
PubMed2002

Importance of local variations in antibiotic consumption and geographical differences of erythromycin and penicillin resistance in Streptococcus pneumoniae.

A geographical analysis of how commonly prescribed oral antibiotics are quantitatively and qualitatively responsible for the different local rates of erythromycin and penicillin resistance in Streptococcus pneumoniae in Spain is presented. From 1998 to 1999 a multicenter surveillance study yielded 1,684 consecutive S. pneumoniae isolates from community-acquired respiratory infections. Data on antibiotic sales in the retail market for the same period were gathered, and the corresponding defined doses per 1,000 inhabitants per day were calculated. Macrolides and beta-lactams were considered separately. Macrolides were subdivided into thrice-, twice-, and once-a-day macrolides, and beta-lactams were split into aminopenicillins and cephalosporins. Univariate Spearman nonparametric coefficients (R) were calculated, and variables proving to be significantly associated (P < 0.1) were entered into several multiple lineal regression models. Ample variation in both resistance rates and antibiotic consumption was seen. Multivariate analyses showed that integrated consumption of both macrolides and beta-lactams accounted well for erythromycin (R(2) = 0.722; P = 0.002) and penicillin (R(2) = 0.706; P = 0.002) resistance. Macrolides were more important drivers for local differences in both erythromycin and penicillin resistance than beta-lactams were. Consumption of once-a-day macrolides was key for local erythromycin resistance variations. Cephalosporins were slightly more important penicillin resistance drivers than aminopenicillins were.

Anti-Bacterial Agents↗
PubMed2002

Epidemiology of extended-spectrum beta-lactamase-producing Enterobacter isolates in a Spanish hospital during a 12-year period.

Fifteen Enterobacter clinical isolates (11 Enterobacter cloacae isolates, 3 Enterobacter aerogenes isolates, and 1 Enterobacter gergoviae isolate), representing 0.4% of all Enterobacter isolates recovered in our hospital from 1989 to 2000, were suspected of harboring an extended-spectrum beta-lactamase (ESBL). These isolates were recovered from 14 different patients. ESBLs were transferred by conjugation into an Escherichia coli recipient strain. Pulsed-field gel electrophoresis (PFGE) revealed a single clone of E. aerogenes and six different clones of E. cloacae. Four of these E. cloacae clonal types were represented by only one isolate each, but the other two were represented by three and four isolates, respectively. Isoelectric focusing, susceptibility phenotyping, PCR analysis, and sequencing demonstrated the presence of three different ESBLs. The most frequent was the recently characterized CTX-M-10 ESBL, which was found in the E. gergoviae isolate and in all but one of the E. cloacae isolates. The remaining E. cloacae isolate harbored a TEM-27 ESBL, and the three E. aerogenes isolates harbored a TEM-24 ESBL. PFGE revealed that our E. aerogenes strain was indistinguishable from the French TEM-24-producing E. aerogenes endemic clone. Although a low prevalence of ESBL-producing Enterobacter isolates was found in our institution over a 12-year period, a diversity of nonepidemic E. cloacae clones was detected, as was the persistence of the CTX-M-10 beta-lactamase. The presence of the TEM-24-producing E. aerogenes French clone in our institution also demonstrates the intercountry dissemination of ESBL-producing isolates.

Bacterial Proteins↗
PubMed1999

MIC distribution and inoculum effect of LY333328: a study of vancomycin-susceptible and VanA-type and VanC-type enterococci obtained from intensive care unit patient surveillance cultures.

OBJECTIVE: To determine the in vitro activity and inoculum effect of LY333328, a semisynthetic glycopeptide, against vancomycin-susceptible and vancomycin-resistant enterococcal isolates. METHODS: One hundred and seventy-six enterococcal isolates (117 vancomycin-susceptible, 29 VanA-type and 30 VanC-type isolates) obtained from surveillance cultures of 139 intensive care unit patients were studied by the standard agar dilution method. Vancomycin resistance determinants were characterized by PCR. RESULTS: The activity of LY333328 was comparable (MIC range, 0.1-2 mg/L) to those of vancomycin (0.1-4 mg/L) and teicoplanin (0.06-1 mg/L) for vancomycin-susceptible isolates. LY333328 was more active (0.1-8 mg/L) than vancomycin (256 to >1024 mg/L) and teicoplanin (32-512 mg/L) against VanA-type isolates, and similar (0.2-1 mg/L) to teicoplanin (0.1-0.5 mg/L) against VanC-type isolates. The MIC distribution of LY333328 displayed a narrower range than that of vancomycin, with no clear distinction between susceptible and resistant populations. The increment in the inoculum size, from 104 to 106 CFU/spot, of susceptible isolates increased the MIC values of LY333328, vancomycin and teicoplanin by factors of 11.4, 1.6 and 3.8, respectively. The corresponding factors for LY333328 for VanA-type and VanC-type isolates were 3.5 and 6.4, respectively. CONCLUSIONS: LY333328 displays an excellent in vitro activity against vancomycin-susceptible and -resistant enterococci. Nevertheless, the inoculum size used in susceptibility tests should be carefully controlled.

Journal Article↗