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Biomedical subjects

F Baquero

Publications and source records attributed to F Baquero.

At least 19 recordsLinked to original sources
PubMed2002

Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence.

Widespread, increasing antibiotic resistance amongst the major respiratory pathogens has compromised traditional therapy of the major infective respiratory syndromes, including bacterial pneumonia and acute exacerbations of chronic bronchitis. Guidelines for antibiotic prescribing dating from the 1980s to 1990s, which attempted to address such problems, were commonly too prescriptive and difficult to apply, and took little account of end-user practice or locally prevalent resistance levels. Further confusion was caused by conflicting recommendations emanating from differing specialty groups. The evidence that such guidelines benefited either clinical outcomes or treatment costs has been disputed. They have probably had little effect on resistance emergence. We report the recommendations of an independent, multi-national, inter-disciplinary group, which met to identify principles underlying prescribing and guideline formulation in an age of increasing bacterial resistance. Unnecessary prescribing was recognized as the major factor in influencing resistance and costs. Antibiotic therapy must be limited to syndromes in which bacterial infection is the predominant cause and should attempt maximal reduction in bacterial load, with the ultimate aim of bacterial eradication. It should be appropriate in type and context of local resistance prevalence, and optimal in dosage for the pathogen(s) involved. Prescribing should be based on pharmacodynamic principles that predict efficacy, bacterial eradication and prevention of resistance emergence. Pharmacoeconomic analyses confirm that bacteriologically more effective antibiotics can reduce overall management costs, particularly with respect to consequential morbidity and hospital admission. Application of these principles should positively benefit therapeutic outcomes, resistance avoidance and management costs and will more accurately guide antibiotic choices by both individuals and formulary/guideline committees.

Community-Acquired Infections↗
PubMed2002

Multicentre evaluation of the VITEK 2 Advanced Expert System for interpretive reading of antimicrobial resistance tests.

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).

Data Interpretation, Statistical↗
PubMed2001

Comparative genomics of Listeria species.

Listeria monocytogenes is a food-borne pathogen with a high mortality rate that has also emerged as a paradigm for intracellular parasitism. We present and compare the genome sequences of L. monocytogenes (2,944,528 base pairs) and a nonpathogenic species, L. innocua (3,011,209 base pairs). We found a large number of predicted genes encoding surface and secreted proteins, transporters, and transcriptional regulators, consistent with the ability of both species to adapt to diverse environments. The presence of 270 L. monocytogenes and 149 L. innocua strain-specific genes (clustered in 100 and 63 islets, respectively) suggests that virulence in Listeria results from multiple gene acquisition and deletion events.

Adaptation, Physiological↗
PubMed2001

Nontuberculous mycobacteria in patients with cystic fibrosis.

The prevalence and clinical implications of colonization with nontuberculous mycobacteria were prospectively studied in 37 patients who had cystic fibrosis. Sputum samples were cultured on Coletsos and Löwenstein-Jensen selective media after decontamination with sodium hydroxide and oxalic acid. Oxalic acid-decontaminated fractions were also cultured in selective liquid medium. Nontuberculous mycobacteria were isolated from 6 patients (16.1%). Mycobacterium chelonae and Mycobacterium avium-intracellulare complex were the most common species. Three patients with positive results of culture had at least 1 positive result by acid-fast smear. Oxalic acid decontamination and culture in liquid medium had the lowest contamination rate (6.7%). Colonization with nontuberculous mycobacteria was associated with humoral response to mycobacteria (immunoglobulin G titers against antigen A60) in patients with samples that tested positive by acid-fast smear. An improvement in pulmonary function was observed in 2 patients after they received a course of antimycobacterial therapy. Screening for nontuberculous mycobacteria in patients with cystic fibrosis will contribute to understanding the relevance of these pathogens with regard to deterioration of pulmonary function in patients with cystic fibrosis.

Adolescent↗
PubMed2001

Performance of the VITEK2 system for identification and susceptibility testing of routine Enterobacteriaceae clinical isolates.

The VITEK2 system was evaluated with 138 fresh consecutive routine clinical Enterobacteriaceae isolates. Susceptibility results to 10 beta-lactams, three aminoglycosides and a quinolone were compared with those obtained following the NCCLS standard microdilution. API20E was used as reference method for identification. All but three isolates were correctly identified in 3 h at species level (97.8%), two isolates (1.4%) at genus level and only one isolate was misidentified. Overall essential agreement for susceptibility testing was 97.1%. Discrepancies were mainly observed with piperacillin (1.1%), cefuroxime (0.6%) and amoxycillin/clavulanate (0.3%). Discrepancies for aminoglycosides and ciprofloxacin were low (<0.1%). Minor, major and very major errors (NCCLS categories) were 4.1%, 0.2% and 6.1%, respectively. Very major errors were due to piperacillin (4.5%), ampicillin (0.8%) and amoxycillin/clavulanate (0.8%). The VITEK2 system gave accurate identification and susceptibility testing results of routine Enterobacteriaceae clinical isolates.

4-Quinolones↗
PubMed2001

Evaluation of the OSIRIS video reader system for disk diffusion susceptibility test reading.

OBJECTIVE: The objective of this study was to compare the performance of the OSIRIS video-assisted reading system for disk diffusion susceptibility testing with conventional manual reading. METHODS: Prospectively collected clinical isolates (n = 119) and isolates with well-characterised resistant mechanisms, including extended-spectrum (ESBL) or inhibitor-resistant TEM (IRT) beta-lactamases producing Enterobacteriaceae (80), methicillin-resistant Staphylococcus aureus (MRSA) (16) and vancomycin-resistant enterococci (14) were studied using the National Committee for Clinical Laboratory Standards disk-diffusion technique. The OSIRIS reading (inhibition zone in mm) was compared with manual reading (reference value). RESULTS: Essential agreement (< or =3 mm discrepancy with manual reading) was 91.6% in routine isolates and 94.8% in those with well-characterised resistant mechanisms, respectively. Overall agreement for susceptibility testing interpretation was slightly higher in the former (95.5%) than in the latter (93.2%) group. The presence of ESBL enzymes enhanced variations of measurements due to synergy among amoxicillin-clavulanate and cephalosporins, as a consequence of closer disk placement. The poor growth characteristic of enterococci affected the video reading; on the other hand, there was a high performance with MRSA isolates. Combining all interpretative results, 4.1% minor, 1.0% major and 2.8% very major errors were observed. CONCLUSION: The OSIRIS system is a useful tool for the reading and interpretation of inhibition zone sizes in disk diffusion susceptibility testing.

Anti-Bacterial Agents↗
PubMed2001

Low-level antibacterial resistance: a gateway to clinical resistance.

The huge amount of antibiotic substances released in the human environment has probably resulted in an acceleration in the rate of bacterial evolution. It is to note that most interactions between chemotherapeutic agents and microbial populations occur at very low antibiotic concentrations. Thus, natural selection is expected to act on very small increases in the bacterial ability to resist to antibiotic inhibitory effects. On the other hand, there is a wealth of mechanisms to resist to these low antibiotic concentrations. The progressive enrichment in low-level resistant populations favours secondary selections for more specific and effective mechanisms of resistance, particularly in treated patients. These adaptations may have a biological cost in the absence of antibiotics, but frequently compensatory mutations occur, minimizing such genetic burden. In this way, a phenomenon of directional selection takes place, with low possibilities of return to susceptibility. Moreover, low antibiotic concentrations are not only able to select low-level antibiotic resistant variants, but may produce a substantial stress in bacterial populations, that eventually influences the rate of genetic variation and the diversity of adaptive responses. More attention should be devoted to the mechanisms of low-level resistance in microorganisms, as they can serve as stepping stones to develop high level, clinically relevant resistance. These mechanisms should be identified early in the development of drugs in order to adapt the therapeutic strategies (for instance dosage) to minimize the selection of low-level resistant variants, as frequently they emerge by means of concentration-specific selection. At the same time, conventional susceptibility testing should probably be able to detect low-level resistance, and not only clinically-relevant resistance. We should be vigilant of the evolutionary trends of microorganisms; for that a purpose, knowledge of the biology and epidemiology of low-level resistance is becoming a real need.

Animals↗
PubMed2001

Evidence to support the rationale that bacterial eradication in respiratory tract infection is an important aim of antimicrobial therapy.

Clinical outcome is dependent upon antibiotic-mediated bacterial eradication in a number of infections. However, in respiratory tract infections, the need for bacterial eradication has been controversial. Clinical data are now available that support the need for active bacterial eradication in otitis media. This may also be the case for other respiratory tract infections. An increase in antimicrobial resistance reduces the probability of achieving eradication. Conversely, failure to eradicate bacteria may promote the emergence and dissemination of antimicrobial-resistant clones. Pharmacokinetic/pharmacodynamic parameters can be used to predict the bacteriological efficacy of antimicrobial therapy. In conclusion, the aim of antimicrobial therapy in respiratory tract infections should be the eradication of the infecting organism.

Anti-Bacterial Agents↗
PubMed2001

Antimicrobial susceptibilities of 1,684 Streptococcus pneumoniae and 2,039 Streptococcus pyogenes isolates and their ecological relationships: results of a 1-year (1998-1999) multicenter surveillance study in Spain.

A nationwide multicenter susceptibility surveillance study which included 1,684 Streptococcus pneumoniae and 2,039 S. pyogenes isolates was carried out over 1 year in order to assess the current resistance patterns for the two most important gram-positive microorganisms responsible for community-acquired infections in Spain. Susceptibility testing was done by a broth microdilution method according to National Committee for Clinical Laboratory Standards M100-S10 interpretative criteria. For S. pneumoniae, the prevalences of highly resistant strains were 5% for amoxicillin and amoxicillin-clavulanic acid; 7% for cefotaxime; 22% for penicillin; 31% for cefuroxime; 35% for erythromycin, clarithromycin, and azithromycin; and 42% for cefaclor. For S. pyogenes, the prevalence of erythromycin resistance was 20%. Efflux was encountered in 90% of S. pyogenes and 5% of S. pneumoniae isolates that exhibited erythromycin resistance. Erythromycin resistance was associated with clarithromycin and azithromycin in both species, regardless of phenotype. Despite the different nature of the mechanisms of resistance, a positive correlation (r = 0.612) between the two species in the prevalence of erythromycin resistance was found in site-by-site comparisons, suggesting some kind of link with antibiotic consumption. Regarding ciprofloxacin, the MIC was >or=4 microg/ml for 7% of S. pneumoniae and 3.5% of S. pyogenes isolates. Ciprofloxacin resistance (MIC, >or=4 microg/ml) was significantly (P < 0.05) associated with macrolide resistance in both S. pyogenes and S. pneumoniae and with penicillin nonsusceptibility in S. pneumoniae.

Drug Prescriptions↗
PubMed2001

Nucleotide sequence and characterization of a novel cefotaxime-hydrolyzing beta-lactamase (CTX-M-10) isolated in Spain.

A cefotaxime-resistant, ceftazidime-susceptible Escherichia coli isolate was obtained from a patient with sepsis in 1997, from which a beta-lactamase with a pI of 8.1 was cloned. Cephaloridine and cefotaxime relative hydrolysis rates were 167 and 81, respectively (penicillin G rate = 100), whereas ceftazidime hydrolysis was not detected. The nucleotide sequence revealed a bla gene related to that coding for CTX-M-3. Despite 21 nucleotide substitutions, only 2 determined amino acid changes (Ala27Val and Arg38Gln). The amino acid sequence identity between this enzyme, designated CTX-M-10, and the chromosomal beta-lactamase of Kluyvera ascorbata was 81%.

Cefotaxime↗
PubMed2001

Macrolide resistance in Peptostreptococcus spp. mediated by ermTR: possible source of macrolide-lincosamide-streptogramin B resistance in Streptococcus pyogenes.

Eighty percent (21 of 26) of macrolide-resistant Peptostreptococcus strains studied harbored the ermTR gene. This methyltransferase gene is also the most frequently found gene among macrolide-lincosamide-streptogramin B-resistant Streptococcus pyogenes strains. Transfer of the ermTR gene from Peptostreptococcus magnus to macrolide-susceptible S. pyogenes strains indicates that this resistance determinant may circulate among gram-positive aerobic and anaerobic species of the oropharyngeal bacterial flora.

Anti-Bacterial Agents↗
PubMed2001

Bacteriocin production in vancomycin-resistant and vancomycin-susceptible Enterococcus isolates of different origins.

Bacteriocin production was determined for 218 Enterococcus isolates (Enterococcus faecalis [93] and E. faecium [125]) obtained from different origins (human clinical samples [87], human fecal samples [78], sewage [28], and chicken samples [25]) and showing different vancomycin susceptibility patterns (vancomycin resistant, all of them vanA positive [56], and vancomycin susceptible [162]). All enterococcal isolates were randomly selected except for the vancomycin-resistant ones. A total of 33 isolates of eight different bacterial genera were used as indicators for bacteriocin production. Forty-seven percent of the analyzed enterococcal isolates were bacteriocin producers (80.6% of E. faecalis and 21.6% of E. faecium isolates). The percentage of bacteriocin producers was higher among human clinical isolates (63.2%, 81.8% of vancomycin-resistant isolates and 60.5% of vancomycin-susceptible ones) than among isolates from the other origins (28 to 39.3%). Only one out of the 15 vancomycin-resistant isolates from human fecal samples was a bacteriocin producer, while 44.4% of fecal vancomycin-susceptible isolates were. The bacteriocin produced by the vanA-containing E. faecium strain RC714, named bacteriocin RC714, was further characterized. This bacteriocin activity was cotransferred together with the vanA genetic determinant to E. faecalis strain JH2-2. Bacteriocin RC714 was purified to homogeneity and its primary structure was determined by amino acid sequencing, showing an identity of 88% and a similarity of 92% with the previously described bacteriocin 31 from E. faecalis YI717. The presence of five different amino acids in bacteriocin RC714 suggest that this could be a new bacteriocin. The results obtained suggest that the epidemiology of vancomycin resistance may be influenced by different factors, including bacteriocin production.

Amino Acid Sequence↗
PubMed2001

Antimicrobial susceptibilities of unique Stenotrophomonas maltophilia clinical strains.

Susceptibility to 41 antimicrobials was studied with 99 Stenotrophomonas maltophilia strains, and different pulsed-field gel electrophoresis profiles were identified among 130 prospectively collected isolates. Moxalactam, doxycycline, minocycline, and clinafloxacin displayed the highest activity (> or = 98% susceptibility). Ticarcillin resistance (75%) was reverted by clavulanate in 25% of strains. Trimethoprim-sulfamethoxazole resistance was 26.2% (> or = 4 [trimethoprim]/76 [sulfamethoxazole] microg/ml) and dropped to 11.1% when an 8/152-microg/ml breakpoint was applied based on its bimodal MIC distribution. Resistance was lower when unique strains were considered, because clonal organisms contribute to resistance.

Anti-Bacterial Agents↗
PubMed2001

In vitro activities of ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia.

Ertapenem (MK-0826, L-749,345) is a 1-beta-methyl carbapenem with a long serum half-life. Its in vitro activity was determined by broth microdilution against 3,478 bacteria from 12 centers in Europe and Australia, with imipenem, cefepime, ceftriaxone, and piperacillin-tazobactam used as comparators. Ertapenem was the most active agent tested against members of the family Enterobacteriaceae, with MICs at which 90% of isolates are inhibited (MIC(90)s) of < or =1 microg/ml for all species. Ertapenem also was more active than imipenem against fastidious gram-negative bacteria and Moraxella spp.; on the other hand, ertapenem was slightly less active than imipenem against streptococci, methicillin-susceptible staphylococci, and anaerobes, but its MIC(90)s for these groups remained < or =0.5 microg/ml. Acinetobacter spp. and Pseudomonas aeruginosa were also much less susceptible to ertapenem than imipenem, and most Enterococcus faecalis strains were resistant. Ertapenem resistance, based on a provisional NCCLS MIC breakpoint of > or =16 microg/ml, was seen in only 3 of 1,611 strains of the family Enterobacteriaceae tested, all of them Enterobacter aerogenes. Resistance was also seen in 2 of 135 anaerobes, comprising 1 Bacteroides fragilis strain and 1 Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of < or =2 microg/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 microg/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 microg/ml and one required an MIC of 4 microg/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 microg/ml. These streptococci also had diminished susceptibilities to other beta-lactams, including imipenem as well as ertapenem. The Etest and disk diffusion gave susceptibility test results in good agreement with those of the broth microdilution method for ertapenem.

Anti-Bacterial Agents↗
PubMed2001

In vitro activity of telithromycin against Spanish Streptococcus pneumoniae isolates with characterized macrolide resistance mechanisms.

The susceptibilities to telithromycin of 203 Streptococcus pneumoniae isolates prospectively collected during 1999 and 2000 from 14 different geographical areas in Spain were tested and compared with those to erythromycin A, clindamycin, quinupristin-dalfopristin, penicillin G, cefotaxime, and levofloxacin. Telithromycin was active against 98.9% of isolates (MICs, < or =0.5 microg/ml), with MICs at which 90% of isolates are inhibited being 0.06 microg/ml, irrespective of the resistance genotype. The corresponding values for erythromycin were 61.0% (MICs, < or =0.25 microg/ml) and >64 microg/ml. The erm(B) gene (macrolide-lincosamide-streptogramin B resistance phenotype) was detected in 36.4% (n = 74) of the isolates, which corresponded to 93.6% of erythromycin-intermediate and -resistant isolates, whereas the mef(A) gene (M phenotype [resistance to erythromycin and susceptibility to clindamycin and spiramycin without blunting]) was present in only 2.4% (n = 5) of the isolates. One of the latter isolates also carried erm(B). Interestingly, in one isolate for which the erythromycin MIC was 2 microg/ml, none of these resistance genes could be detected. Erythromycin MICs for S. pneumoniae erm(B)-positive isolates were higher (range, 0.5 to >64 microg/ml) than those for erm(B)- and mef(A)-negative isolates (range, 0.008 to 2 microg/ml). The corresponding values for telithromycin were lower for both groups, with ranges of 0.004 to 1 and 0.002 to 0.06 microg/ml, respectively. The erythromycin MIC was high for a large number of erm(B)-positive isolates, but the telithromycin MIC was low for these isolates. These results indicate the potential usefulness of telithromycin for the treatment of infections caused by erythromycin-susceptible and -resistant S. pneumoniae isolates when macrolides are indicated.

Anti-Bacterial Agents↗