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Biomedical subjects

L Aguilar

Publications and source records attributed to L Aguilar.

At least 55 records · Page 3Linked to original sources
PubMed2001

Influence of diminished susceptibility of Streptococcus pneumoniae to ciprofloxacin on the serum bactericidal activity of gemifloxacin and trovafloxacin after a single dose in healthy volunteers.

The serum bactericidal activity against 2 Streptococcus pneumoniae strains (ciprofloxacin MIC 1 and 4 mg/l) was measured in 12 volunteers who received oral single doses of gemifloxacin 320 mg and trovafloxacin 200 mg in a crossover fashion. The 4-fold increase in ciprofloxacin MIC from the susceptible to the resistant strain resulted in a 2-fold increase in MIC (from 0.015 to 0.03 mg/l), a 2-fold decrease in C(max)/MIC (104 vs 52) and in AUC(0-24 h)/MIC (532 vs 266), but a 5.6-fold decrease in area under the bactericidal curve (AUBC: 168 vs 30) for gemifloxacin. Trovafloxacin showed a 4-fold higher MIC (0.25 vs 0.06 mg/l), a 4-fold lower C(max)/MIC (8.6 vs 36), a 4-fold lower AUC(0-24 h)/MIC (85 vs 356) and a 11-fold lower AUBCs (2 vs 22) against the resistant isolate compared with the susceptible one. Trovafloxacin serum bactericidal titres against the ciprofloxacin-resistant strain were measurable generally only at 1 h after dosing (median titre=2). Gemifloxacin showed similar ex vivo bactericidal activity against the ciprofloxacin-resistant strain to that of trovafloxacin against the ciprofloxacin-susceptible strain.

Adult↗
PubMed2001

Frequency of selection of fluoroquinolone-resistant mutants of Neisseria gonorrhoeae exposed to gemifloxacin and four other quinolones.

We studied the frequency of mutation of clinical isolates of Neisseria gonorrhoeae (two nalidixic acid susceptible and two nalidixic acid resistant), and the stability of the mutants obtained, in the presence of three different concentrations of five fluoroquinolones. The frequency of mutation was low for all the quinolones. Only one N. gonorrhoeae mutant, obtained with trovafloxacin at 4 x MIC presented a stable increase in the MIC of this quinolone, not attributable to novel mutation(s), both in the gyrA and parC genes, although not showing any increase in the MIC of the other quinolones tested. In summary, gemifloxacin was the only quinolone tested for which resistant mutants were not obtained.

Anti-Infective Agents↗
PubMed2001

Influence of the decrease in ciprofloxacin susceptibility and the presence of human serum on the in vitro susceptibility of Streptococcus pneumoniae to five new quinolones.

Sixty recent Streptococcus pneumoniae isolates with different susceptibilities to ciprofloxacin (14 with MIC 0.5 mg/L, 10 with MIC 1 mg/L, eight with MIC 2 mg/L, 11 with MIC 4 mg/L and 17 with MIC > or =8 mg/L) were tested against five new quinolones using Todd-Hewitt broth with and without 80% serum. The final inoculum was 5 x 10(5) cfu/mL. Gemifloxacin and clinafloxacin exhibited the lowest MIC90 values and resistance rates (percentage above and defined breakpoint) with and without serum for strains with a ciprofloxacin MIC of > or =4 mg/L. Other quinolones tested were less active against strains with reduced ciprofloxacin susceptibility. The presence of serum did not affect susceptibility to moxifloxacin, but increased the resistance rates to other new quinolones for strains with high ciprofloxacin MICs.

Anti-Infective Agents↗
PubMed2001

Herpes simplex virus type 2 seroepidemiology in Spain: prevalence and seroconversion rate among sexually transmitted disease clinic attendees.

BACKGROUND: Only limited data on the seroprevalence of herpes simplex virus type 2 (HSV-2) are available from European countries. Until recently, serologic tests for HSV-2 serotyping have been hampered by cross-reactivity to type-common antigens. The present study aims at providing data on the prevalence of HSV-2 infection in a group of STD clinic attendees using a reliable type-specific immunoassay. GOAL: To evaluate the seroprevalence of HSV-2 and the accumulated incidence of clinical genital herpes infection in a sample of Spanish sexually transmitted disease (STD) clinic attendees. STUDY DESIGN: The study consisted of two parts. First, a cross-sectional study of HSV-2 seroprevalence was conducted in patients with STDs. Second, a prospective cohort study was undertaken to evaluate the accumulated incidence of infection by HSV-2 and of clinical episodes of genital herpes in HSV-2-negative patients included in the first study during a follow-up period of 6 to 18 months. RESULTS: Of the 374 patients (129 men, 245 women) studied, 25% were seropositive for HSV-2 (12% of men, 30% of women). Antibodies to HSV-2 were related to female gender (odds ratio, 2.7; P < 0.001) and to the number of sexual partners (odds ratio, 4.1; P < 0.001). Fifty-two percent of patients (145 of 281 patients) who were initially seronegative returned to the clinic for a second serologic testing, of whom 1% (2 of 145 patients) had seroconverted. None of the patients developed genital herpes during the follow-up period. CONCLUSION: The relatively high seroprevalence (25%) and the low rate (4%) of HSV-2 previously reported in the general population in Spain suggest that the virus circulation may be restricted to certain risk groups. Therefore, future healthcare measures may target specific groups, such as patients with STDs.

Antibodies, Viral↗
PubMed2001

Antimicrobial susceptibilities of 1,730 Haemophilus influenzae respiratory tract isolates in Spain in 1998-1999.

A beta-lactamase prevalence of 23% was found among 1,730 Haemophilus influenzae isolates. Ampicillin susceptibility was 70%, and 12% of beta-lactamase-negative strains presented diminished susceptibility to ampicillin (BLNAR phenotype). Susceptibility of 90% was found for cefaclor and clarithromycin, whereas it was nearly 100% for cefotaxime, cefixime, azithromycin, and cefuroxime. Ciprofloxacin-resistant (0.1%) and beta-lactamase-positive amoxicillin/clavulanate-resistant (BLPACR) phenotypes (0.1%) are anecdotal so far.

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

Effects of single oral doses of gemifloxacin (320 milligrams) versus trovafloxacin (200 milligrams) on fecal flora in healthy volunteers.

Gemifloxacin and trovafloxacin were administered to 12 volunteers in a randomized crossover trial with a 2-week washout period. Stool samples were collected predose and 1, 2, and 3 days postdose. Both quinolones reduced the number of organisms of the family Enterobacteriaceae and aerobic gram-positive organisms. Escherichia coli reduction was greater with gemifloxacin than with trovafloxacin, with postdose isolation of quinolone-resistant strains for which MICs of trovafloxacin were higher than those of gemifloxacin.

Anti-Infective Agents↗
PubMed2001

Antibacterial properties of gemifloxacin and trovafloxacin in urine ex vivo: phase I study.

Urine bactericidal titers (UBTs) against Escherichia coli ATCC 25922 and Staphylococcus saprophyticus ATCC 1970 were determined after the administration of single oral doses of gemifloxacin at 320 mg and trovafloxacin at 200 mg to healthy volunteers. Gemifloxacin presented significantly lower experimental versus mathematically predicted UBTs over 72 h, due to the effect of urine on the susceptibility of the E. coli strain. Experimental UBTs were significantly higher for gemifloxacin than trovafloxacin against both strains over 72 h.

Administration, Oral↗
PubMed2001

Differences between two new quinolones (gemifloxacin and trovafloxacin) and ciprofloxacin in their concentration-dependent killing of Streptococcus pneumoniae.

BACKGROUND: Ciprofloxacin resistance influences the in vitro effect of new quinolones on Streptococcus pneumoniae. METHODS: The early (over 3 h) in vitro bactericidal activity of gemifloxacin, trovafloxacin and ciprofloxacin was explored by time-kill tests against two ciprofloxacin-susceptible (MIC = 0.5 and 1 microg/ml) and two ciprofloxacin-resistant (MIC = 16 microg/ml) S. pneumoniae strains. RESULTS: At subinhibitory concentrations (0.5 x MIC) and inhibitory concentrations (1 x MIC), only gemifloxacin exhibited significant bactericidal activity with, respectively, approximately 85 and approximately 95% decrease in the initial inoculum of the two ciprofloxacin-resistant strains. At concentrations similar to peak serum concentrations (1.5, 3 and 2.5 microg/ml for gemifloxacin, trovafloxacin and ciprofloxacin, respectively) after standard doses, only gemifloxacin exhibited an approximately 99.9% (3 log(10)) reduction in the initial inoculum for the four strains tested, regardless of their susceptibility to ciprofloxacin. No bactericidal activity was exhibited for the other two quinolones against the ciprofloxacin-resistant strains. CONCLUSIONS: Gemifloxacin offers high early bactericidal activity at concentrations similar to peak and trough levels, theoretically preventing regrowth over the dosing interval, and thus dealing with the problem of ciprofloxacin resistance in S. pneumoniae.

Anti-Infective Agents↗
PubMed2001

Prediction of in-vivo efficacy by in-vitro early bactericidal activity with oral beta-lactams, in a dose-ranging immunocompetent mouse sepsis model, using strains of Streptococcus pneumoniae with decreasing susceptibilities to penicillin.

Killing curves and a sepsis model were performed with Streptococcus pneumoniae strains (MICs of penicillin = 0.01, 1, 2 and 4 mg/L) to assess the in vivo effect of in vitro early bactericidal activity. Optimal bactericidal concentration (OBC) was defined as the minimal concentration needed to obtain the maximal bactericidal activity during the sampling time for colony counting in killing curves. Animals were treated with amoxycillin, cefuroxime or cefpodoxime every 8 h for 48 h, with doses ranging from 2.5 to 50 mg/kg. ED100 (minimal antibiotic dose obtaining a 100% survival) was used as efficacy endpoint. Cmax/MIC, AUC/MIC and deltaT >MIC did not accurately predict efficacy against the most resistant strains, deltaT >OBC being the most predictive efficacy parameter indicating the in vivo effect of early bactericidal activity. Lower deltaT >OBC values for amoxycilin vs oral cehalosporins were needed for efficacy. The higher early bactericidal activity of amoxycillin may explain its higher in vivo efficacy.

Amoxicillin↗
PubMed2000

Seroepidemiology of Bordetella pertussis infections in the Spanish population: a cross-sectional study.

A study was conducted on a representative sample (n=4084) of the Spanish population to assess the prevalence of antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA). A total of 1982 men and 2102 women aged 5-59 years were stratified by sex and age (5-12, 13-19, 20-29, 30-39, 40-49 and 50-59 years). Antibodies to PT were found in 46% samples and to FHA in 74% and increased with age (p<0.0001), ranging from 35% in the 5-12 year age group to 52% in the 50-59 year age group for anti-PT and from 65 to 80% for anti-FHA, respectively. As vaccine induced-immunity wanes over time, the observed age distribution of antibodies suggests that Bordetella pertussis infection is widespread in the Spanish population and that pertussis booster vaccination in adolescents and adults with the newly developed acellular vaccines, should be considered if it is deemed necessary to control the circulation of the organism.

Adhesins, Bacterial↗
PubMed2000

In vitro susceptibility to gemifloxacin and trovafloxacin of Streptococcus pneumoniae strains exhibiting decreased susceptibility to ciprofloxacin.

The in vitro susceptibility to trovafloxacin and gemifloxacin of Streptococcus pneumoniae strains exhibiting decreased susceptibility to ciprofloxacin (MIC > or =2 microg/ml; 30 strains with intermediate resistance [MIC 2 microg/ml] and 43 strains with complete resistance [MIC > or =4 microg/ml]) was determined. Seventy-three strains collected in a surveillance study carried out from May 1996 to April 1997 in Spain (prior to commercialisation of trovafloxacin and gemifloxacin) from patients with respiratory tract infections were tested. The antibacterial activity of gemifloxacin was affected to a lesser extent than that of trovafloxacin by the increase in the MIC of ciprofloxacin, with gemifloxacin showing significantly (P< or =0.001) better antibacterial activity than trovafloxacin in all ciprofloxacin MIC categories (MIC50/MIC90 values of 0.015/0.03, 0.015/0.06, 0.03/0.06 and 0.12/0.25 microg/ml for gemifloxacin vs. 0.12/0.12, 0.12/1, 0.25/0.5 and 2/4 microg/ml for trovafloxacin in the 2, 4, 8 and > or =16 microg/ml ciprofloxacin MIC categories, respectively). Nine (12.3%) of these 73 strains exhibited decreased susceptibility to trovafloxacin (> or =2 microg/ml), whereas all strains were inhibited by 0.25 microg/ml of gemifloxacin.

Anti-Infective Agents↗
PubMed2000

Ex vivo bactericidal activity against group C Neisseria meningitidis in seronegative subjects.

BACKGROUND: To determine the anti-meningococcal C immunological activity by adding functional tests (opsonophagocytosis) to the classical serology techniques. SUBJECTS AND METHODS: 42 adult volunteers were screened using serological methods (determination of total and bactericidal antibodies). Seronegative subjects were tested by opsonophagocytosis. RESULTS: 24 subjects (57%) showed serological evidence of previous contact with Neisseria meningitidis group C antigens: 19 subjects had both total and bactericidal antibodies, two subjects had only total antibodies and three subjects had only bactericidal antibodies. Of the 18 seronegative subjects, five showed ex vivo activity in killing curves with or without polymorphonuclear cells: two subjects exhibited only complement-mediated bactericidal activity, one subject only opsonophagocytosis, and two subjects exhibited both activities. CONCLUSION: The addition of functional tests to the classical serological determination increases the evidence of previous contact with N. meningitidis antigens by 12%.

Adult↗
PubMed2000

Role of Streptococcus pneumoniae and Haemophilus influenzae in the development of acute otitis media and otitis media with effusion in a gerbil model.

The efficacy of amoxicillin/clavulanate and cefuroxime was determined in a gerbil model of otitis media with a mixed Streptococcus pneumoniae plus Haemophilus influenzae middle ear (ME) infection. Results were compared with those obtained in a previous single H. influenzae model. All untreated animals inoculated with the mixed inoculum developed acute otitis media (AOM), whereas 86.7% of those inoculated with H. influenzae developed otitis media with effusion (OME). Antibiotics eradicated H. influenzae from the ME more efficiently in AOM than in OME, and this difference was highly significant (P</=.001) after administration of 5 mg/kg of either drug (amoxicillin/clavulanate, 100% vs. 10%; cefuroxime, 73.3% vs. 10%). Efficacy was predicted by the relation of in vitro susceptibility and ME antibiotic concentration, which was 2.7 times higher in AOM than in OME. In the mixed otitis model, the most efficacious antibiotic was able to prevent AOM, but >80% of animals developed culture-negative OME.

Acute Disease↗
PubMed2000

Streptococcus pneumoniae in community-acquired respiratory tract infections in Spain: the impact of serotype and geographical, seasonal and clinical factors on its susceptibility to the most commonly prescribed antibiotics. The Spanish Surveillance Group for Respiratory Pathogens.

Resistance of Streptococcus pneumoniae to antimicrobial agents shows geographical variation and also depends on serotype, patient age and sample origin. Factors affecting antibiotic resistance in S. pneumoniae were studied from results of a multicentre susceptibility study of 12 antimicrobial agents, carried out in 14 Spanish hospitals between May 1996 and April 1997. The most frequent serotypes were serotypes 6 (14.8%), 19 (11.8%), 23 (10.5%), 3 (9.9%), 9 (8.0%), 14 (8.0%), 15 (3.9%) and 11 (3.2%); 9.6% of isolates were not typeable. The remaining 25 serotypes constituted 20.2% of strains. Penicillin resistance was more prevalent in serotypes 14 (88%), 23 (66%), 9 (62%) and 6 (57%), whereas erythromycin resistance was more prevalent in serotypes 6 (68.5%), 15 (61.4%), 14 (49.5%), 19 (42.7%) and 23 (39.3%). Serotypes 6 and 19 were the serotypes most commonly isolated from both children and adults, although with different proportions (24.0% and 19.2% of isolates from children were serotype 6 and 19, respectively, with the corresponding figures for isolates from adults being 13.6% and 11.5%, respectively). The rates of resistance of pneumococcal strains to penicillin and cefuroxime were significantly higher in strains from children than in those from adults (resistance to penicillin, 50.4% in children and 37.0% in adults; resistance to cefuroxime, 62.4% in children and 45.6% in adults). There was significantly more resistance to erythromycin in middle ear isolates (48.9%) than in blood isolates (27%). The prevalence of resistance to beta-lactams showed a seasonal pattern, with higher rates in summer and winter, proportional to the magnitude of resistance. Susceptibility to macrolides did not vary seasonally. Our results stress the relative importance that geographical, temporal (seasonality), patient (sample type, origin, age group) and bacterium-related (serotype) factors have on the variations in susceptibility observed among different pneumococcal clinical isolates.

Adult↗
PubMed2000

Streptococcus pneumoniae resistance to erythromycin and penicillin in relation to macrolide and beta-lactam consumption in Spain (1979-1997).

Streptococcus pneumoniae resistance to penicillin and erythromycin in relation to beta-lactam and macrolide consumption in Spain over 19 years (1979-1997) was studied from resistance data collected by a search of the literature. Antibiotic consumption was expressed in defined daily dosage (DDD)/1000 inhabitants/day. A significant relationship (P: < 0.001) between erythromycin resistance (MIC >/= 1 mg/L) and global macrolide consumption (r = 0.942), as well as between high-level penicillin resistance (MIC >/= 2 mg/L) and global beta-lactam consumption (r = 0.948) was observed. The relationship between erythromycin resistance and macrolide consumption was due mainly to consumption of macrolides taken twice a day (adjusted r(2) = 0.886). Prevalence of high-level penicillin resistance correlated with consumption of oral cephalosporins (adjusted r(2) = 0.877); however, there appeared to be no correlation of consumption of oral or parenteral aminopenicillins, narrow-spectrum penicillins or cephalosporins with intermediate-level penicillin resistance (MIC 0. 12-1 mg/L). The prevalence of high-level penicillin and of erythromycin resistance were also strongly correlated with each other (r = 0.903, P: < 0.001). In addition to global consumption, different categories of resistance (high or intermediate), and the differential capability of antibiotics to select resistance, must be taken into account when studying antibiotic impact on bacterial populations. Although this ecological analysis is not able to demonstrate a causal relationship between antibiotic consumption and development of resistance, it suggests that overuse of certain specific antibiotics is more likely to be related to the increase in drug-resistant strains of S. pneumoniae.

Anti-Bacterial Agents↗