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F Baquero

Publications and source records attributed to F Baquero.

At least 73 records · Page 4Linked to original sources

Concentration-dependent selection of small phenotypic differences in TEM beta-lactamase-mediated antibiotic resistance.

In this paper, the first robust experimental evidence of in vitro and in vivo concentration-dependent selection of low-level antibiotic-resistant genetic variants is described. The work is based on the study of an asymmetric competition assay with pairs of isogenic Escherichia coli strains, differing only (apart from a neutral chromosomal marker) in a single amino acid replacement in a plasmid-mediated TEM-1 beta-lactamase enzyme, which results in the new TEM-12 beta-lactamase. The mixture was challenged by different antibiotic concentrations, both in vitro and in the animal model, and the selective process of the variant population was carefully monitored. A mathematical model was constructed to test the hypothesis that measured growth and killing rates of the individual TEM variants at different antibiotic concentrations could be used to predict quantitatively the strength of selection for TEM-12 observed in competition experiments at these different concentrations.

Animals↗

Evaluation of the Wider system, a new computer-assisted image-processing device for bacterial identification and susceptibility testing.

The Wider system is a newly developed computer-assisted image-processing device for both bacterial identification and antimicrobial susceptibility testing. It has been adapted to be able to read and interpret commercial MicroScan panels. Two hundred forty-four fresh consecutive clinical isolates (138 isolates of the family Enterobacteriaceae, 25 nonfermentative gram-negative rods [NFGNRs], and 81 gram-positive cocci) were tested. In addition, 100 enterobacterial strains with known beta-lactam resistance mechanisms (22 strains with chromosomal AmpC beta-lactamase, 8 strains with chromosomal class A beta-lactamase, 21 broad-spectrum and IRT beta-lactamase-producing strains, 41 extended-spectrum beta-lactamase-producing strains, and 8 permeability mutants) were tested. API galleries and National Committee for Clinical Laboratory Standards (NCCLS) microdilution methods were used as reference methods. The Wider system correctly identified 97.5% of the clinical isolates at the species level. Overall essential agreement (+/-1 log(2) dilution for 3,719 organism-antimicrobial drug combinations) was 95.6% (isolates of the family Enterobacteriaceae, 96.6%; NFGNRs, 88.0%; gram-positive cocci, 95.6%). The lowest essential agreement was observed with Enterobacteriaceae versus imipenem (84.0%), NFGNR versus piperacillin (88.0%) and cefepime (88.0%), and gram-positive isolates versus penicillin (80.4%). The category error rate (NCCLS criteria) was 4.2% (2.0% very major errors, 0.6% major errors, and 1. 5% minor errors). Essential agreement and interpretive error rates for eight beta-lactam antibiotics against isolates of the family Enterobacteriaceae with known beta-lactam resistance mechanisms were 94.8 and 5.4%, respectively. Interestingly, the very major error rate was only 0.8%. Minor errors (3.6%) were mainly observed with amoxicillin-clavulanate and cefepime against extended-spectrum beta-lactamase-producing isolates. The Wider system is a new reliable tool which applies the image-processing technology to the reading of commercial trays for both bacterial identification and susceptibility testing.

Anti-Bacterial Agents↗

[National multicenter study of the in vitro activity of moxifloxacin against respiratory tract pathogens. Spanish Study Group on Moxifloxacin].

The activity of moxifloxacin, a novel 8-methoxyquinolone, was evaluated against 1,218 respiratory pathogens isolated in nine Spanish hospitals and was compared with ciprofloxacin, sparfloxacin, amoxicillin, amoxicillin-clavulanic acid, cefuroxime, erythromycin and clarithromycin. Moxifloxacin exhibited an excellent in vitro activity against most tested isolates with MIC90 values of 0.25 mg/l for Streptococcus pneumoniae and viridans group streptococci; 0.12 mg/l for Streptococcus pyogenes; 0.25 mg/l for Streptococcus agalactiae; 0.06 and 4 mg/l for methicillin-susceptible and -resistant Staphylococcus aureus, respectively; 0.06 mg/l for Haemophilus influenzae and 0.12 mg/l for Moraxella catarrhalis. Moxifloxacin susceptibility rates were not affected by penicillin resistance in S. pneumoniae and S. viridans, by the betalactamase production in H. influenzae and M. catarrhalis or by macrolide resistance. Moxifloxacin was twice as active as sparfloxacin and four to sixteen times more active than ciprofloxacin against Gram-positive isolates. Sparfloxacin and ciprofloxacin were slightly more active than moxifloxacin when tested against H. influenzae and M. catarrhalis isolates. The microbiological data obtained confirm that moxifloxacin is a promising antimicrobial agent for treating respiratory tract infections.

Anti-Infective Agents↗

[National Multicenter study of the in vitro activity of moxifloxacin against respiratory tract pathogens]

The activity of moxifloxacin, a novel 8-methoxyquinolone, was evaluated against 1,218 respiratory pathogens isolated in nine Spanish hospitals and was compared with ciprofloxacin, sparfloxacin, amoxicillin, amoxicillin-clavulanic acid, cefuroxime, erythromycin and clarithromycin. Moxifloxacin exhibited an excellent in vitro activity against most tested isolates with MIC90 values of 0.25 mg/l for Streptococcus pneumoniae and viridans group streptococci; 0.12 mg/l for Streptococcus pyogenes; 0.25 mg/l for Streptococcus agalactiae; 0.06 and 4 mg/l for methicillin-susceptible and -resistant Staphylococcus aureus, respectively; 0.06 mg/l for Haemophilus influenzae and 0.12 mg/l for Moraxella catarrhalis. Moxifloxacin susceptibility rates were not affected by penicillin resistance in S. pneumoniae and S. viridans, by the betalactamase production in H. influenzae and M. catarrhalis or by macrolide resistance. Moxifloxacin was twice as active as sparfloxacin and four to sixteen times more active than ciprofloxacin against Gram-positive isolates. Sparfloxacin and ciprofloxacin were slightly more active than moxifloxacin when tested against H. influenzae and M. catarrhalis isolates. The microbiological data obtained confirm that moxifloxacin is a promising antimicrobial agent for treating respiratory tract infections.

Journal Article↗

Comparative in vitro activity of quinolones against Stenotrophomonas maltophilia.

The susceptibility of 109 Stenotrophomonas maltophilia isolates, all characterized by pulsed-field gel electrophoresis, to nine quinolones was studied. Grepafloxacin, trovafloxacin, and moxifloxacin displayed similar intrinsic activities (MIC90, 0.5 microg/ml), which were lower than those of ofloxacin and ciprofloxacin (MIC90, 4 microg/ml), norfloxacin (MIC90, 64 microg/ml), and nalidixic acid (MIC90, 32 microg/ml). Nalidixic acid was generally one- to twofold dilutions more active than norfloxacin. According to the criteria of the National Committee for Clinical Laboratory Standards (NCCLS), the percentage of isolates susceptible to ciprofloxacin (breakpoint < or = 1 microg/ml) was 76.1%. Using the NCCLS breakpoint for comparative purposes, the percentage of isolates susceptible to grepafloxacin, moxifloxacin, and trovafloxacin was 95.4, 96.4, and 96.4%, respectively. These results indicate that new quinolones may potentially be used for the management of Stenotrophomonas maltophilia infections.

4-Quinolones↗

Antimicrobial susceptibility of 1,422 Haemophilus influenzae isolates from respiratory tract infections in Spain. Results of a 1-year (1996-97) multicenter surveillance study. Spanish Surveillance Group for Respiratory Pathogens.

A Haemophilus influenzae multicenter antimicrobial susceptibility surveillance was carried out. An overall beta-lactamase production rate of 25.7% was found, with significant differences between hospitals ranging between 7.9 and 47.9%. Presumable intrinsic resistance was found in 4.6% of strains. No differences in susceptibility were observed between beta-lactamase positive and beta-lactamase negative strains for all antibiotics, except for penicillin, amoxicillin and cefaclor. A higher prevalence of resistance was found for clarithromycin vs azithromycin (22.6 vs 0.7%). Differences in all these factors make surveillance essential as a guideline for empiric treatment in community-acquired respiratory tract infections.

Drug Resistance, Microbial↗

Mycobacterium tuberculosis subsp. caprae subsp. nov.: a taxonomic study of a new member of the Mycobacterium tuberculosis complex isolated from goats in Spain.

Isolates from the Mycobacterium tuberculosis complex cultured from caprine pathological tissue samples were biochemically and genetically characterized. The isolates were negative for nitrate reduction and niacin accumulation, they weakly hydrolysed Tween 80, were sensitive to pyrazinamide (50 micrograms ml-1) and were resistant to 1 and 2 micrograms tiophene-2-carboxylic acid hydrazide ml-1 but not to 5 or 10 micrograms tiophene-2-carboxylic acid hydrazide ml-1. Sequencing of the pncA gene revealed a polymorphism characteristic of M. tuberculosis, whereas oxyR, katG and gyrA sequences were characteristic of Mycobacterium bovis. The fingerprinting patterns obtained with IS6110, direct repeats and polymorphic G+C-rich sequence-associated RFLP and direct variable repeat-spacer oligonucelotide typing (spoligotyping) segregated these isolates from the other members of the complex. The results of this testing, together with the repeated association of this micro-organism with goats, suggest that a new member of this taxonomic complex not matching any of the classical species had been identified. This unusual mycobacterium may play a role in the epidemiology of animal and human tuberculosis in Spain. The name Mycobacterium tuberculosis subsp. caprae subsp. nov. is proposed for these isolates. The type strain of Mycobacterium tuberculosis subsp. caprae subsp. nov. is gM-1T (= CIP 105776T).

Amidohydrolases↗

The complexed structure and antimicrobial activity of a non-beta-lactam inhibitor of AmpC beta-lactamase.

Beta-lactamases are the major resistance mechanism to beta-lactam antibiotics and pose a growing threat to public health. Recently, bacteria have become resistant to beta-lactamase inhibitors, making this problem pressing. In an effort to overcome this resistance, non-beta-lactam inhibitors of beta-lactamases were investigated for complementarity to the structure of AmpC beta-lactamase from Escherichia coli. This led to the discovery of an inhibitor, benzo(b)thiophene-2-boronic acid (BZBTH2B), which inhibited AmpC with a Ki of 27 nM. This inhibitor is chemically dissimilar to beta-lactams, raising the question of what specific interactions are responsible for its activity. To answer this question, the X-ray crystallographic structure of BZBTH2B in complex with AmpC was determined to 2.25 A resolution. The structure reveals several unexpected interactions. The inhibitor appears to complement the conserved, R1-amide binding region of AmpC, despite lacking an amide group. Interactions between one of the boronic acid oxygen atoms, Tyr150, and an ordered water molecule suggest a mechanism for acid/base catalysis and a direction for hydrolytic attack in the enzyme catalyzed reaction. To investigate how a non-beta-lactam inhibitor would perform against resistant bacteria, BZBTH2B was tested in antimicrobial assays. BZBTH2B significantly potentiated the activity of a third-generation cephalosporin against AmpC-producing resistant bacteria. This inhibitor was unaffected by two common resistance mechanisms that often arise against beta-lactams in conjunction with beta-lactamases. Porin channel mutations did not decrease the efficacy of BZBTH2B against cells expressing AmpC. Also, this inhibitor did not induce expression of AmpC, a problem with many beta-lactams. The structure of the BZBTH2B/AmpC complex provides a starting point for the structure-based elaboration of this class of non-beta-lactam inhibitors.

Anti-Bacterial Agents↗

Antimicrobial resistance of 914 beta-hemolytic streptococci isolated from pharyngeal swabs in Spain: results of a 1-year (1996-1997) multicenter surveillance study. The Spanish Surveillance Group for Respiratory Pathogens.

A nationwide susceptibility surveillance study of beta-hemolytic streptococcal isolates from pharyngeal swabs obtained in 11 Spanish hospitals between May 1996 and April 1997 against 12 antibiotics was carried out. Of the isolates 86% (786 of 914 isolates) were group A and 8.4% (77 of 914 isolates) were group C. No resistance was found to beta-lactam antibiotics, but significant differences (P < 0.001) with respect to lack of susceptibility to macrolides were found between groups (27% for group A and 12% for group C) and between seasons (13.2% in summer and 31.7% in winter). Most of these isolates displayed the M phenotype (low-level resistance to erythromycin and susceptibility to clindamycin).

Drug Resistance, Microbial↗

In vitro activities of ketolide HMR3647, macrolides, and other antibiotics against Lactobacillus, Leuconostoc, and Pediococcus isolates.

Testing of susceptibility to 13 antibiotics was performed with 90 isolates of Lactobacillus, Leuconostoc, and Pediococcus. MICs at which 90% of the isolates tested were inhibited by HMR3647, erythromycin, and ciprofloxacin were 0.015, 0.125 and 32 microg/ml, respectively. The penicillin MIC was > or = 16 microg/ml against 26.2% of the studied Lactobacillus sp. isolates and 50% of Lactobacillus plantarum. HMR3647 showed excellent activity against these genera.

Anti-Bacterial Agents↗

Antimicrobial resistance of 1,113 Streptococcus pneumoniae isolates from patients with respiratory tract infections in Spain: results of a 1-year (1996-1997) multicenter surveillance study. The Spanish Surveillance Group for Respiratory Pathogens.

A nationwide susceptibility surveillance of 1,113 Streptococcus pneumoniae isolates was carried out and found the following percentages of resistance: cefuroxime, 46%; penicillin, 37%; macrolides, 33%; aminopenicillins, 24%; cefotaxime, 13%; and ceftriaxone, 8%. A significant (P < 0.05) seasonality pattern for beta-lactam antibiotics was observed. Resistance to macrolides was higher (P < 0.05) in middle-ear samples. Higher percentages of resistance to cefuroxime and macrolides were observed among penicillin-intermediate and -resistant strains, whereas high frequencies of resistance to aminopenicillins and expanded-spectrum cephalosporins were observed only among penicillin-resistant strains.

Cefuroxime↗

Mutations in 23S rRNA in Helicobacter pylori conferring resistance to erythromycin do not always confer resistance to clarithromycin.

Mutations conferring resistance to erythromycin or clarithromycin in Helicobacter pylori were studied. Mutation A2142G was consistently associated with clarithromycin MIC of > 256 micrograms/ml, whereas mutants carrying A2143G had MICs ranging from < or = 0.016 to > 256 micrograms/ml, suggesting that additional factors account for the observed multiple levels of resistance to clarithromycin.

Anti-Bacterial Agents↗

Efficacy of ampicillin plus ceftriaxone in treatment of experimental endocarditis due to Enterococcus faecalis strains highly resistant to aminoglycosides.

The purpose of this work was to evaluate the in vitro possibilities of ampicillin-ceftriaxone combinations for 10 Enterococcus faecalis strains with high-level resistance to aminoglycosides (HLRAg) and to assess the efficacy of ampicillin plus ceftriaxone, both administered with humanlike pharmacokinetics, for the treatment of experimental endocarditis due to HLRAg E. faecalis. A reduction of 1 to 4 dilutions in MICs of ampicillin was obtained when ampicillin was combined with a fixed subinhibitory ceftriaxone concentration of 4 micrograms/ml. This potentiating effect was also observed by the double disk method with all 10 strains. Time-kill studies performed with 1 and 2 micrograms of ampicillin alone per ml or in combination with 5, 10, 20, 40, and 60 micrograms of ceftriaxone per ml showed a > or = 2 log10 reduction in CFU per milliliter with respect to ampicillin alone and to the initial inoculum for all 10 E. faecalis strains studied. This effect was obtained for seven strains with the combination of 2 micrograms of ampicillin per ml plus 10 micrograms of ceftriaxone per ml and for six strains with 5 micrograms of ceftriaxone per ml. Animals with catheter-induced endocarditis were infected intravenously with 10(8) CFU of E. faecalis V48 or 10(5) CFU of E. faecalis V45 and were treated for 3 days with humanlike pharmacokinetics of 2 g of ampicillin every 4 h, alone or combined with 2 g of ceftriaxone every 12 h. The levels in serum and the pharmacokinetic parameters of the humanlike pharmacokinetics of ampicillin or ceftriaxone in rabbits were similar to those found in humans treated with 2 g of ampicillin or ceftriaxone intravenously. Results of the therapy for experimental endocarditis caused by E. faecalis V48 or V45 showed that the residual bacterial titers in aortic valve vegetations were significantly lower in the animals treated with the combinations of ampicillin plus ceftriaxone than in those treated with ampicillin alone (P < 0.001). The combination of ampicillin and ceftriaxone showed in vitro and in vivo synergism against HLRAg E. faecalis.

Algorithms↗

Ampicillin-sulbactam and amoxicillin-clavulanate susceptibility testing of Escherichia coli isolates with different beta-lactam resistance phenotypes.

The activities of ampicillin-sulbactam and amoxicillin-clavulanate were studied with 100 selected clinical Escherichia coli isolates with different beta-lactam susceptibility phenotypes by standard agar dilution and disk diffusion techniques and with a commercial microdilution system (PASCO). A fixed ratio (2:1) and a fixed concentration (clavulanate, 2 and 4 micrograms/ml; sulbactam, 8 micrograms/ml) were used in the agar dilution technique. The resistance frequencies for amoxicillin-clavulanate with different techniques were as follows: fixed ratio agar dilution, 12%; fixed concentration 4-micrograms/ml agar dilution, 17%; fixed ratio microdilution, 9%; and disk diffusion, 9%. Marked discrepancies were found when these results were compared with those obtained with ampicillin-sulbactam (26 to 52% resistance), showing that susceptibility to amoxicillin-clavulanic acid cannot be predicted by testing the isolate against ampicillin-sulbactam. Interestingly, the discrimination between susceptible and intermediate isolates was better achieved with 4 micrograms of clavulanate per ml than with the fixed ratio. In contrast, amoxicillin susceptibility was not sufficiently restored when 2 micrograms of clavulanate per ml was used, particularly in moderate (mean beta-lactamase activity, 50.8 mU/mg of protein) and high-level (215 mU/mg) TEM-1 beta-lactamase producer isolates. Four micrograms of clavulanate per milliliter could be a reasonable alternative to the 2:1 fixed ratio, because most high-level beta-lactamase-hyperproducing isolates would be categorized as nonsusceptible, and low- and moderate-level beta-lactamase-producing isolates would be categorized as nonresistant. This approach cannot be applied to sulbactam, either with the fixed 2:1 ratio or with the 8-micrograms/ml fixed concentration, because many low-level beta-lactamase-producing isolates would be classified in the resistant category. These findings call for a review of breakpoints for beta-lactam-beta-lactamase inhibitors combinations.

Amoxicillin↗

From vanA Enterococcus hirae to vanA Enterococcus faecium: a study of feed supplementation with avoparcin and tylosin in young chickens.

Fifteen newborn chickens were isolated in separate cages after 1 month of living together, divided into three groups, and challenged for 5 weeks with seed food which either was supplemented with avoparcin (10 mg/kg of animal food) or tylosin (40 mg/kg) or was nonsupplemented. At 9 weeks of age and after the 5-week challenge, all chickens received nonsupplemented feed for 4 additional weeks. At 4, 9, and 13 weeks of life, feces were collected and inoculated on M-Enterococcus agar plates with and without vancomycin (4 micrograms/ml). vanA-containing Enterococcus hirae was isolated from 11 of 15 chickens before antibiotic challenge, without detection of vancomycin-resistant Enterococcus faecium. At 9 weeks of age and after the 5-week avoparcin challenge, vanA E. hirae strains were no longer detected, but five of five chickens now had vanA E. faecium. At a lower frequency, vanA E. faecium had also displaced vanA E. hirae in both the tylosin group (one of four chickens) and the control group (two of five chickens). One month after avoparcin discontinuation, the number of chickens colonized with vanA E. faecium decreased from five to one. All vanA-containing E. hirae strains detected in the first month of life and most of the vanA-containing E. faecium strains detected in the second month of life showed identical ApaI and SmaI restriction patterns, respectively, when analyzed by pulsed-field gel electrophoresis. All vanA E. hirae isolates transferred glycopeptide and macrolide resistance to Enterococcus faecalis JH2-2 in vitro; the level of glycopeptide resistance was higher in the transconjugants than in the donor E. hirae strains. These data suggest that E. hirae may be a significant source of vanA determinants with the potential of transfer to other enterococcal species from humans or animals.

Animals↗

Hepatitis E virus: relevance in blood donors and risk groups.

BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) infection usually causes acute self-limited disease. HEV is associated with faecal-contaminated drinking water, but other vectors, such as blood, are possible. The aim of this study was to investigate the prevalence of HEV in blood donors and in two groups at high risk for parenteral infections, namely, haemodialysis patients, and children infected with HCV via blood transfusion. MATERIALS AND METHODS: We investigated the prevalence of anti-HEV in 863 blood donors, 63 haemodialysis patients, and 42 children infected post transfusion with HCV. RESULTS: The prevalence rates were 2.8, 6.3%, and zero, respectively. CONCLUSIONS: (1) The incidence of HEV in Spain is similar to that in other Western European countries, and (2) HEV is probably not transmitted parenterally to children.

Adolescent↗

Evolving resistance patterns of Streptococcus pneumoniae: a link with long-acting macrolide consumption?

The Alexander Project indicates an increase in the prevalence of S. pneumoniae resistance to macrolide antibiotics. In some centers, the prevalence of S. pneumoniae macrolide resistance exceeds that of penicillin resistance. Centers with a high level of macrolide resistance tend to also have high levels of penicillin resistance. Antimicrobial use may be an important driver of resistance. The application of pharmacodynamic concepts suggests that bacterial exposure to low and prolonged concentrations of macrolides may have a role in the selection of resistance. Analysis of macrolide prescribing and resistance patterns indicates a correlation between increasing macrolide resistance and the increased use of newer, long-acting macrolides, although further study is required to investigate the causality of this correlation. In order to attempt to prevent the further spread of resistance, antibiotic choice should maximize the opportunity for bacterial eradication.

Adolescent↗