PubMed Health⌕ Search

Biomedical subjects

A Fenoll

Publications and source records attributed to A Fenoll.

At least 19 recordsLinked to original sources
PubMed2006

Increase of the M phenotype among erythromycin-resistant Streptococcus pneumoniae isolates from Spain related to the serotype 14 variant of the Spain9V-3 clone.

Between 1998 and 2003 the rate of erythromycin resistance among pneumococci in Spain was 34.4%. Although the MLS(B) phenotype was prevalent (94.7%), the rate of the M phenotype increased from 3.3% to 8.9% (P < 0.01). Clonal dissemination of mef(E)-carrying strains of serotype 14 variant of the Spain(9V)-3 clone was the major contributor to this increase.

Anti-Bacterial Agents↗
PubMed2006

Very high resistance to amoxicillin in Streptococcus pneumoniae: an epidemiological fact or a technical issue?

To explore reproducibility of high amoxicillin minimum inhibitory concentrations (MIC(AMX) ), isolates received during 2002 and 2003 in the National Reference Laboratory of Streptococcus pneumoniae with an amoxicillin MIC of 16 microg/ml (43 strains) and 8 g/ml (12 strains) when singly determined on a routine basis in this center by agar dilution, were retested 10 times by agar dilution and microdilution following NCCLS guidelines, not only using double dilutions but also dilution steps of 2 microg/ml (i.e, 2, 4, 6, 8, 10, 12, 14 and 16 microg/ml). A significant (p<0.05) shift to a higher MIC(AMX )was obtained with microdilution vs. agar dilution. Routine MIC(AMX )of 16 microg/ml were confirmed in 0 strains by agar dilution and in 6 by microdilution, when retested. These 6 strains presented a modal MIC(AMX )value of 10 microg/ml (5 cases) and of 14 micro g/ml (1 case) when using 2 microg/ml microdilution steps. There is low reproducibility of the highest MIC(AMX )values.

Amoxicillin↗
PubMed2006

[Activity of cefpodoxime and other oral beta-lactams against Haemophilus influenzae and Streptococcus pneumoniae with different susceptibilities to penicillin].

This study explores the influence on the intrinsic activity of different oral beta-lactams of beta-lactamase production in Haemophilus influenzae and penicillin resistance in Streptococcus pneumoniae. Three substudies were performed: a) a general susceptibility study, analyzing 550 strains received by the Spanish Laboratorio de Referencia de Neumococos throughout February and March 2005; b) a study on the influence of penicillin resistance on the activity of beta-lactams, analyzing 251 penicillin-susceptible strains (MIC or=2 mg/l) randomly chosen among those received by the Spanish Laboratorio de Referencia de Neumococos throughout 2005; and c) an H. influenzae susceptibility study analyzing 150 strains received by Instituto Valenciano de Microbiologia throughout 2005. A total of 71% of S. pneumoniae strains were susceptible to penicillin, 21% exhibited intermediate resistance and 8% strains presented full resistance. H. influenzae beta-lactamase production rate was 18.6%. Of the non-beta-lactamase-producing strains, 3% were not susceptible to ampicillin. Cefpodoxime and cefixime exhibited the highest intrinsic activity against H. influenzae, while amoxicillin and cefpodoxime were the most active compounds against S. pneumoniae. All H. influenzae strains were susceptible to oral cephalosporins and amoxicillin/clavulanic acid. The increase in penicillin resistance in S. pneumoniae influenced cefixime, cefaclor and cefuroxime to a higher degree than amoxicillin and cefpodoxime.

Ceftizoxime↗
PubMed2004

Effects of amoxicillin subinhibitory concentrations on the cross-protection developed by pneumococcal antibodies in mouse sepsis caused by an amoxicillin-resistant serotype 6B Streptococcus pneumoniae strain.

A model of mouse sepsis caused by a serotype 6B Streptococcus pneumoniae strain (amoxicillin MIC of 8 microg/ml) was developed to investigate the therapeutic effect of an amoxicillin dose (3.12 mg/kg of body weight three times daily for 48 h) producing, over the whole treatment period, subinhibitory concentrations in serum (peak concentration [C(max)]: 6.1 microg/ml) in animals that prior to infection had been passively immunized with a 6B or 23F hyperimmune serum (obtained by immunization with a whole-cell heat-inactivated inoculum and diluted to produce no protective effect by itself). Mortality in nonimmunized animals treated with antibiotic (3.12 mg/kg) was 90%, and mortality in animals immunized but not treated with the antibiotic was 100%. Antibiotic treatment in immunized animals produced mortality rates </=20% when the hyperimmune serum was used, thus showing cross-protection and synergism (defined as the situation in which there is no response to the single agents [no differences versus placebo] while the combination exhibits significant activity) with subinhibitory concentrations of the antibiotic. The presence of antipneumococcal antibodies allowed antibiotic efficacy with negligible values of pharmacodynamic parameters (C(max)/MIC ratio of <1 and thus a null value for the time that serum levels exceed the MIC). This in vivo synergism offers a potential therapeutic strategy against resistant strains.

Amoxicillin↗
PubMed2003

Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae isolated in four southern European countries (ARISE project) from adult patients: results from the cefditoren surveillance program.

From four southern European countries (Spain, Italy, Portugal, and Greece) 877 Streptococcus pneumoniae isolates were recovered from adult patients with respiratory tract infections between September 2000 and March 2001. The antimicrobial susceptibility to 11 antibiotics was determined in a central laboratory. Penicillin resistance was high in Greece (47.1%) and Spain (25.1%) but much lower in Portugal (7.9%) and Italy (4.8%). On the other hand, erythromycin resistance was high in Italy (38.5%) and Spain (36.2%) with no statistical difference with Greece (29.4%) but reaching significance (p <0.01) with Portugal (15.7%). Resistance to levofloxacin was low (1.5%) but present in Spanish and Italian isolates. Cefditoren, a new cephem antibiotic tested, was the most potent compound (MIC90 = 0.5 microg/ml) followed by levofloxacin and cefotaxime (MIC90 = 1 microg/ml). Given the high rates of penicillin and macrolide resistance reported, there is an evident need for new drugs and continued antimicrobial surveillance of S. pneumoniae.

Adolescent↗
PubMed2002

Modification of bacteraemia by specific antibodies and relation with mortality in a pneumococcal mouse sepsis model.

The relationship between mortality and the bacteraemic profile was investigated in a pneumococcal (serotype 6B) sepsis BALB/c mouse model where animals received protection by specific hyperimmune serum. A single intraperitoneal dose of hyperimmune serum obtained from mice immunized with the heat-inactivated strain was administered (non-diluted or diluted to 1/4 or to 1/16) to 5-mice study groups 1 h prior to intraperitoneal inoculation with the infective inoculum (3.57 x 108 cfu/ml). Blood cultures were performed daily over 15 days, with 8 microl of blood being collected from the tail vein; the samples were resuspended in Todd-Hewitt broth containing 10% trisodium citrate and plated onto blood agar for colony counting. Animals included in the control group received placebo (PBS). Mortality was 100% in control animals within the first 48 h. Hyperimmune serum decreased and delayed mortality in a dose-related trend, producing 100%, 80%, 60% and 40% survival rates at 72, 96, 144 and 360 h, with non-diluted serum. Bacteraemic profiles with maximum colony counts > or =5 x 107 cfu/ml in blood during the follow-up period were related to > or =65% probability of death, regardless of the serum dilution administered.

Animals↗
PubMed2002

Beta-lactam modification of the bacteraemic profile and its relationship with mortality in a pneumococcal mouse sepsis model.

A sepsis BALB/c mice model was used to investigate the relationship between mortality and the bacteraemic profile produced by a serotype 6B Streptococcus pneumoniae clinical isolate (MIC/MBC of amoxicillin 4/4 mg/L and of cefotaxime 2/4 mg/L). Animals were treated subcutaneously with doses of amoxicillin or cefotaxime ranging from 6.25 to 50 mg/kg tds for 48 h, starting 1 h after intraperitoneal inoculation (2 x 10(7) cfu/mouse). Blood cultures were carried out daily over 15 days. A survival rate of 100% was obtained with amoxicillin 25 mg/kg and of 60% with cefotaxime 50 mg/kg. A statistically significant (P = 0.012) relationship was found between the maximum cfu/mL in blood and mortality. A maximum log cfu/mL of 6.5 was associated with an 84% probability of death.

Animals↗
PubMed2002

Beta-lactam activity against resistant pneumococcal strains is enhanced by the immune system.

Pandemic resistance in Streptococcus pneumoniae is compromising antibiotic activity. Antibiotics that act on the cell wall, such as beta-lactams, may have a combined effect with the immune system against S. pneumoniae, since both act on the bacterial envelope. This combined effect can be studied in vitro or in vivo with respect to bacterial killing, since lysis is the end-point of both beta-lactams and the immune system. We review here the in vitro increase in the bactericidal activity of aminopenicillins by non-specific immunity (complement and polymorphonuclear leucocytes). Few data are available on the collaboration of specific immunity and beta-lactams. We also review the effect of the presence of specific antibodies on the in vivo T > MIC needed for the therapeutic efficacy of amoxicillin, and on blood bacterial clearance in animal models. The effect that immunity has on pharmacodynamic parameters, such as T > MIC, in non-human studies may be used as a tool to predict the effect of these pharmacodynamic variations in overcoming resistance and its selection, in the context of increasing the use of pneumococcal conjugated vaccines.

Animals↗
PubMed2002

Antimicrobial susceptibility and pneumococcal serotypes.

The increase in antibiotic resistance and the possible changes in serotype prevalence as a consequence of a new conjugated vaccine have contributed to renewed interest in the study of pneumococcal serotypes and their antibiotic resistances. Spain still has one of the highest penicillin resistance rates, but in the past 4-5 years a slight decrease has been observed. The level of resistance has not increased either, 12.7% of the 11 165 isolates studied showed high-level penicillin resistance but 94% of these had an MIC of only 2 mg/L. Serotypes 6, 9, 14, 19 and 23 included 83% of the penicillin-resistant pneumococci; the remaining 17% belonged to 18 different serotypes. We analysed these minor penicillin-resistant serotypes in view of their potential increase following a possible child vaccination programme. Four of these serotypes (11, 15, 21 and 35) were the most prevalent, and among them serotype 15 was particularly frequent with >50% of its strains resistant. The effective control of these minor penicillin-resistant serotypes should be based on continuous surveillance of pneumococcal epidemiology.

Drug Resistance, Bacterial↗
PubMed2002

Effects of specific antibodies against Streptococcus pneumoniae on pharmacodynamic parameters of beta-lactams in a mouse sepsis model.

A dose-ranging study to investigate the in vivo effects of the presence of specific antibodies on the efficacy of beta-lactam treatment of sepsis caused by Streptococcus pneumoniae (non-beta-lactam-susceptible serotype 6B isolate) was performed with a BALB/c mouse model. Hyperimmune serum was obtained from mice immunized with the heat-inactivated strain. The rate of mortality was 100% in nontreated animals in the absence of specific antibodies. A single injection of a one-half or one-quarter dilution of hyperimmune serum produced 60 to 40% survival rates. In the absence of specific antibodies, the minimal effective doses of amoxicillin and cefotaxime that produced survival rates of 100 and 80% were 25 and 50 mg/kg of body weight (three times a day for up to six doses), respectively. These doses produced times that the levels in serum remained above the MIC (deltaT > MICs) approximately 30% of the dosing interval. When specific antibodies were present (by administration of a one-half or one-quarter dilution of hyperimmune serum), the minimal effective doses of the antibiotics were 3.12 and 6.25 mg/kg ( approximately 8 times lower), with the deltaT > MICs being approximately 3 and 5% of the dosing interval for amoxicillin and cefotaxime, respectively. This in vivo combined pharmacodynamic effect offers possibilities that can be used to address penicillin resistance.

Amoxicillin↗
PubMed2002

[Pneumococcal meningitis in Spanish children: incidence, serotypes and antibiotic resistance. Prospective and multicentre study].

OBJECTIVE: To determine the incidence, as well as the implicated serotypes and patterns of antibiotic resistance of Streptococcus pneumoniae meningitis in Spanish children. MATERIAL AND METHOD: We performed a prospective, multicenter study in five Autonomous Communities (Catalonia, Galicia, Madrid, Navarre and the Basque Country) for 1 year (1 February 2000 31 January 2001). All children aged 0-14 years with pneumococcal meningitis from all the hospitals in the Autonomous Communities studied were included. Diagnosis was based on clinical findings and isolation of S. pneumoniae in the cerebrospinal fluid/blood using routine methods or polymerase chain reaction. Serotyping was performed using the guellung reaction and/or immunoblotting and susceptibility to antibiotics was evaluated by the technique of agar dilution. The pediatric population aged 0-14 years in the Autonomous Communities studied comprises 2,290,304 children. RESULTS: Fifty-two cases were identified. One patient was aged less than 2 months old, 25 (48 %) were aged 2-12 months, and 12 patients (23 %) were aged 12-24 months. The annual incidence per 100,000 children aged between 1 and 2 years was 17.75 cases (95 % CI: 11.59 26.01) and 8.39 cases (95 % CI: 4.67 15.79) respectively, and that for children in the first 2 and 5 years of life was 13.13 (95 % CI: 9.29 18.02) and 6.29 (95 % CI: 4.57 8.,45) cases respectively. Nearly half the strains isolated (47.6 %) showed reduced sensitivity to penicillin. The most frequent serotype was 19F (12 cases [28.6 %]). Eighty percent of the isolated serotypes were included in the formula of the heptavalent conjugate vaccine. CONCLUSIONS: The incidence of pneumococcal meningitis in children from five Spanish Autonomous Communities is high, nearly twice that found in a prior retrospective studied performed in the same population 1-3 years previously. Almost all the isolated serotypes were included in the heptavalent conjugate vaccine. Half the strains showed reduced sensitivity to penicillin.

Adolescent↗
PubMed2001

Distribution of resistance genes tet(M), aph3'-III, catpC194 and the integrase gene of Tn1545 in clinical Streptococcus pneumoniae harbouring erm(B) and mef(A) genes in Spain.

The most prevalent macrolide resistance phenotype and genotype among pneumococcal isolates was the cMLSB phenotype [erm(B) or erm(B)/mef(A)] (91.3%). We studied the distribution of other resistance genes, tet(M), catpC194, aph3'-III, in these strains, seeing evolution at work in that some strains carried different combinations of resistance determinants. The most prevalent patterns associated with resistance to erythromycin [erm(B)] were resistance to tetracycline [tet(M)] and chloramphenicol (catpC194) (48.2%) or resistance to tetracycline [tet(M)] alone (42.2%). In our isolates of Streptococcus pneumoniae there was a strong association of the erm(B) and tet(M) genes with Tn1545-related elements.

Anti-Bacterial Agents↗
PubMed2001

Identification of the psaA gene, coding for pneumococcal surface adhesin A, in viridans group streptococci other than Streptococcus pneumoniae.

The gene encoding the pneumococcal surface adhesin A (PsaA) protein has been identified in three different viridans group streptococcal species. Comparative studies of the psaA gene identified in different pneumococcal isolates by sequencing PCR products showed a high degree of conservation among these strains. PsaA is encoded by an open reading frame of 930 bp. The analysis of this fragment in Streptococcus mitis, Streptococcus oralis, and Streptococcus anginosus strains revealed a sequence identity of 95, 94, and 90%, respectively, to the corresponding open reading frame of the previously reported Streptococcus pneumoniae serotype 6B strain. Our results confirm that psaA is present and detectable in heterologous bacterial species. The possible implications of these results for the suitability and potential use of PsaA in the identification and diagnosis of pneumococcal diseases are discussed.

Adhesins, Bacterial↗
PubMed2000

Streptococcus pneumoniae in children in Spain: 1990-1999.

UNLABELLED: This study analyses the serogroups/types (SGTs) and resistance to penicillin and erythromycin of 3921 strains isolated from 1990 to 1999 in children aged 0-14 y in Spanish hospitals of all the autonomous communities. Based on the age of the children, strains have been divided into five groups: 0-6 mo, > 6-1 y, > 1-2 y, > 2-5 y and > 5 y. While only eight SGTs were responsible for 80% of the infections in children from 6 mo to 2 y of age, this number increased to 11 and 16 for the groups > 2-5 y and > 5-14 y, respectively. SGTs 6, 14 and 19 were prevalent in blood and otic exudates. SGTs 1, 4, 5, 12 and 18 were more frequent in invasive disease but serotype 3 was clearly associated with otitis. Serotypes I and 5 were quite significant in children of over 2 y of age, and this should be taken into account in future vaccine formulations. CONCLUSION: Although high, the rate of penicillin resistance in the paediatric population has remained stable in recent years. Conversely, erythromycin resistance is still increasing in our country. Coverage by the 7-valent vaccine was 78 and 81% for blood and otic isolates, respectively. These coverage levels would be increased by 9% and 3% if 9-valent (plus 1 + 5 serotypes) were used and by an additional 2.6% and 7.6% using the 11-valent (plus 3 + 7) formulation.

Adolescent↗
PubMed2000

Horizontal transfer of parC and gyrA in fluoroquinolone-resistant clinical isolates of Streptococcus pneumoniae.

We have analyzed genetically three clinical isolates (3180, 3870, and 1244) of Streptococcus pneumoniae with high-level ciprofloxacin resistance. Isolates 3180 and 3870 were atypical because of their insolubility in deoxycholate. However, they hybridized specifically with pneumococcal autolysin and pneumolysin gene probes and have typical pneumococcal atpC and atpA gene sequences. Analysis of the complete sequences of the parC and gyrA genes revealed total variations of 8 and 8.7% (isolate 3180) and 7.4 and 3.6% (isolate 3870), respectively, compared to the wild-type strain R6 sequence. The variations observed between the sequences of R6 and isolate 1244 were less than 0.9%. The structure of the gyrA and parC genes from isolates 3180 and 3870 was organized in sequence blocks that show different levels of divergence, suggesting a pattern of recombination. These results are evidence for recombination at the fluoroquinolone target genes in clinical isolates of S. pneumoniae. The genetically related viridans group streptococci could act as a reservoir for fluoroquinolone resistance genes.

Amino Acid Sequence↗
PubMed2000

Short-term bactericidal activity of amoxicillin and cefotaxime against penicillin-susceptible and -resistant pneumococcal strains: an in vitro pharmacodynamic simulation.

The 8-hour in vitro activity of serum-simulated concentrations of amoxicillin (obtained after 875 mg oral dose) and cefotaxime (obtained after a 1 g i.v. dose), against 20 strains of the 5 Streptococcus pneumoniae serotypes most prevalent in Spain, was explored. Despite a greater initial inocula decrease observed with cefotaxime against the resistant strains at the first sampling time, a decrease > or =99.9% was obtained with both beta-lactams from 6h onwards against the penicillin-susceptible strains; the same was observed for the penicillin-resistant strains with amoxicillin but not with cefotaxime.

Administration, Oral↗