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1.
Eur J Clin Microbiol Infect Dis ; 32(11): 1417-22, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23686506

RESUMEN

Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum fluoroquinolone rather recently introduced in certain European countries. We compared the antimicrobial potency of ulifloxacin with that of other fluoroquinolones against common urinary and respiratory bacterial pathogens. The microbial isolates were prospectively collected between January 2007 and May 2008 from patients with community-acquired infections in Greece. Minimum inhibitory concentrations (MICs) were determined for ciprofloxacin, levofloxacin, moxifloxacin (for respiratory isolates only), and ulifloxacin using the E-test method. The binary logarithms of the MICs [log2(MICs)] were compared by using the Wilcoxon signed-ranks test. A total of 409 isolates were studied. Ulifloxacin had the lowest geometric mean MIC for the 161 Escherichia coli, 59 Proteus mirabilis, and 22 Staphylococcus saprophyticus urinary isolates, the second lowest geometric mean MIC for the 38 Streptococcus pyogenes respiratory isolates (after moxifloxacin), and the third lowest geometric mean MIC for the 114 Haemophilus influenzae and the 15 Moraxella catarrhalis respiratory isolates (after ciprofloxacin and moxifloxacin). Compared with levofloxacin, ulifloxacin had lower log2(MICs) against E. coli (p < 0.001), P. mirabilis (p < 0.001), S. saprophyticus (p < 0.001), and S. pyogenes (p < 0.001). Compared with ciprofloxacin, ulifloxacin had lower log2(MICs) against P. mirabilis (p < 0.001), S. saprophyticus (p = 0.008), and S. pyogenes (p < 0.001), but higher log2(MICs) against H. influenzae (p < 0.001) and M. catarrhalis (p = 0.001). In comparison with other clinically relevant fluoroquinolones, ulifloxacin had the most potent antimicrobial activity against the community-acquired urinary isolates studied and very good activity against the respiratory isolates.


Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Infecciones Bacterianas/microbiología , Infecciones Comunitarias Adquiridas/microbiología , Dioxolanos/farmacología , Fluoroquinolonas/farmacología , Piperazinas/farmacología , Infecciones del Sistema Respiratorio/microbiología , Infecciones Urinarias/microbiología , Adulto , Bacterias/aislamiento & purificación , Femenino , Grecia , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos
2.
Eur J Clin Microbiol Infect Dis ; 32(7): 877-81, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23354677

RESUMEN

This study was conducted to evaluate the association between pneumococcal DNA load and parapneumonic pleural effusion (PPE) in children with community-acquired pneumonia. Bacterial load was quantified and related to the presence of PPE with or without empyema in 72 otherwise healthy children aged ≤5 years who were hospitalised because of radiographically confirmed CAP and showed a real-time polymerase chain reaction that was positive for Streptococcus pneumoniae. The proportion of children with a high bacterial load (i.e. ≥265 DNA copies/mL) was larger among the subjects with PPE than those without it. Multivariate analysis showed that a high bacterial load was significantly associated with PPE (OR 8.65; 95% CI 1.10-67.8 vs a bacterial load of <125 copies/mL). Children with infection due to pneumococcal serotype 19A were at highest risk of developing PPE (OR 7.44; 95% CI 1.10-50.4 vs all other typeable serotypes). The patients with CAP due to pneumococcal serotypes that are not included in the 13-valent conjugate vaccine (PCV13) were more frequently affected by PPE than those with infections associated with serotypes included in the vaccine, except for serotype 19A. Bacterial loads of ≥265 DNA copies/mL are significantly associated with PPE, and serotype 19A is significantly associated with a high bacterial load and the development of PPE. The mean bacterial load of the patients with empyema was higher than that of patients with simple PPE. Although further studies are required, it seems that serotypes not included in PCV13 can play a major role in causing a higher bacterial load and PPE.


Asunto(s)
Bacteriemia/microbiología , Carga Bacteriana , Infecciones Comunitarias Adquiridas/microbiología , Neumonía Neumocócica/complicaciones , Streptococcus pneumoniae/aislamiento & purificación , Preescolar , ADN Bacteriano/genética , Empiema/microbiología , Femenino , Humanos , Lactante , Masculino
3.
J Chemother ; 22(5): 345-54, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21123159

RESUMEN

Because of increasing antibiotic resistance in Escherichia coli, the main uropathogen of uncomplicated urinary tract infections (UTIs), updated susceptibility data are vital in guiding the selection of first-line treatment agents. interpretation of these data depends on the breakpoints adopted, that may vary among different guidelines.In this study we report the minimum inhibitory concentrations (MICs) of eight antibiotics and compare antimicrobial susceptibility results obtained in 2315 E. coli strains recently collected during the ARESC survey using EUCAST and CLSI breakpoints. We have also evaluated the clinical impact of breakpoint discrepancies on the overall susceptibility patterns.Fosfomycin, nitrofurantoin and mecillinam showed the highest susceptibility rates in all countries (>92%) according to both CLSI and EUCAST criteria. Minor category shifts were observed for ciprofloxacin, amoxicillin-clavulanic acid, ampicillin and trimethoprim/sulfamethoxazole. A large number of strains classified as intermediate resistant to cefuroxime according to CLSI are included by the EUCAST in the susceptible category.In conclusion, fosfomycin, mecillinam, and nitrofurantoin have preserved their in vitro activity in all countries investigated, regardless of the criteria adopted. They continue to represent effective options for the empiric therapy of female patients with uncomplicated cystitis. The use of different interpretative criteria for E. coli responsible for UTIs therefore has no influence on the decision to be taken by the physicians managing the patients.


Asunto(s)
Antibacterianos/uso terapéutico , Cistitis/tratamiento farmacológico , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Escherichia coli/aislamiento & purificación , Infecciones Urinarias/tratamiento farmacológico , Cistitis/microbiología , Farmacorresistencia Microbiana , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Urinarias/microbiología
4.
J Chemother ; 20(5): 561-9, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19028617

RESUMEN

In this study we evaluated the in vitro activities of cefditoren--a broad-spectrum oral cephalosporin--and other comparator agents against 2,396 fresh isolates from community-acquired respiratory tract infections, collected from 6 clinical Italian microbiology laboratories. On penicillin-susceptible pneumococci and Streptococcus pyogenes, cefditoren demonstrated to be the most active antibiotic (MIC(90)values of 0.03 and 0.06 mg/L respectively), showing only a slight decrease in potency on penicillin-intermediate and resistant pneumococci (MIC(90)value 0.5 mg/L, 1.0 mg/L respectively). All the other comparators displayed MIC(90 )values of 4 - 8 mg/L for penicillins and of 4 to >64 mg/L for the oral cephalosporins. Cefditoren and levofloxacin were the most active against MSSA (MIC(90)0.5 mg/mL). Cefditoren displayed a uniformly potent inhibitory activity (MIC(90)of 0.03 mg/L) against all strains of Haemophilus influenzae, regardless of their ampicillin resistance (mediated or not by beta-lactamase production), while against Moraxella catarrhalis MIC(90)values were higher against beta-lactamase-positive (0.25 mg/L). Cefditoren was active also against Klebsiella pneumoniae and Escherichia coli : in this case its activity was comparable with that of levofloxacin. In conclusion, cefditoren, due to its potent activity, is a new effective therapeutic option for the treatment of respiratory tract infections.


Asunto(s)
Antibacterianos/farmacología , Cefalosporinas/farmacología , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/microbiología , Haemophilus influenzae/efectos de los fármacos , Humanos , Italia , Klebsiella pneumoniae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Infecciones del Sistema Respiratorio/microbiología , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacos
5.
Int J Antimicrob Agents ; 31(4): 321-8, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18201873

RESUMEN

The aim of this study was to assess whether the novel lipopeptide daptomycin might be capable of disrupting or inhibiting the synthesis of biofilms produced by staphylococci. Fourteen recently isolated slime-producing methicillin-susceptible (MET-S) and methicillin-resistant (MET-R) strains (three MET-S Staphylococcus aureus, three MET-R S. aureus, three MET-S Staphylococcus epidermidis, three MET-R S. epidermidis and two vancomycin-intermediate S. aureus (VISA)) were tested. Slime formation on polystyrene plates was quantified spectrophotometrically. Daptomycin (2-64 mg/L) inhibited slime synthesis by > or =80% in MET-S strains, by 60-80% in MET-R S. aureus and by 70-95% in MET-R S. epidermidis. At 64 mg/L, biofilm synthesis decreased by 80% in the VISA isolates. Daptomycin also disrupted pre-formed biofilm: >50% breakdown of initial biofilm (5h) was observed in all strains. Disruption of mature biofilms (48 h), in terms of percentage, was more variable depending on the strain, ranging from ca. 20% in a MET-R S. epidermidis strain to almost 70% in two MET-S strains (one S. aureus and one S. epidermidis). Daptomycin at concentrations achievable during therapy promoted a statistically significant inhibition of slime synthesis (preventing biofilm building) and induced slime disruption (disaggregating its structure) both in initial and mature biofilms on a plastic support in all staphylococcal strains studied.


Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Daptomicina/farmacología , Staphylococcus/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Recuento de Colonia Microbiana , Resistencia a la Meticilina , Pruebas de Sensibilidad Microbiana , Plásticos , Staphylococcus aureus/efectos de los fármacos
6.
Int J Immunopathol Pharmacol ; 20(3): 607-17, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17880774

RESUMEN

Eight hundred and seventeen patients with upper respiratory tract infections were treated with thiamphenicol glycinate acetylcisteinate (TGA) or other standard antibiotics for 6-10 days in a randomised trial. In 419 out of 817 patients, the symptomatology was severe and they were treated with TGA in sequential therapy (TGA 500 mg- as thiamphenicol- b.i.d. intramuscularly on the first day and TGA 500 mg b.i.d by aerosol during the following days) (n=151), or with antibiotics of comparison (n=268) given intramuscularly. In this group the disappearance of the symptomatology with TGA ranged from 90 percent of the patients with otitis media to 94 percent in pharyngotonsillitis and rhinosinusitis; in this latter group TGA was significantly better than cefazolin. In 398 patients with mild symptomatology TGA (250 mg as thiamphenicol- b.i.d.) was given by aerosol (n=149) and the antibiotics of comparison by oral route (n=249). In TGA patients, the disappearance of symptoms was achieved in 87 percent of those with rhinosinusitis, in 88 percent of those with pharyngotonsillitis and in 91 percent of those with otitis media. S. pyogenes, S. pneumoniae and H. influenzae were the most frequently isolated pathogens, and none of the isolated bacteria proved to be resistant to TGA. Microbiological eradication was obtained in TGA groups in a percentage of patients ranging from 90.2 to 96.0 percent in those with severe forms, and from 86.2 to 91.6 percent in those with a mild clinical picture. Investigators rated the TGA efficacy as excellent in 96-100 percent of the patients with severe forms and in 85.5-100 percent of the patients with mild forms, whereas in the group of patients with rhinosinusitis the comparison of TGA versus other treatment was significantly in favour of TGA. The Investigator rating of treatment tolerability significantly favoured TGA in sequential treatments in comparison to the other antibiotics. No patient dropped out from the trial because of adverse events.


Asunto(s)
Acetilcisteína/uso terapéutico , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Tianfenicol/análogos & derivados , Acetilcisteína/administración & dosificación , Acetilcisteína/efectos adversos , Administración por Inhalación , Adolescente , Adulto , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Infecciones Bacterianas/microbiología , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/microbiología , Tianfenicol/administración & dosificación , Tianfenicol/efectos adversos , Tianfenicol/uso terapéutico , Resultado del Tratamiento
7.
Int J Antimicrob Agents ; 30(5): 415-21, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17768034

RESUMEN

The aim of this study was to assess whether moxifloxacin is able to inhibit the synthesis of and to disrupt biofilms produced in vitro by bacterial pathogens involved in acute bacterial exacerbations of chronic bronchitis. Three strains each of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli recently isolated from clinical respiratory specimens and capable of slime production were used. Biofilm formation on polystyrene plates was quantified spectrophotometrically by established methodologies. Moxifloxacin (0.5 mg/L) inhibited slime synthesis by >70% in S. aureus, H. influenzae and S. pneumoniae, 45-70% in E. coli and 35-70% in M. catarrhalis. Disruption of pre-formed structures was also promoted by moxifloxacin both for initial (5h) and mature (48 h) biofilms. Drug concentrations reached during therapy (0.5-4 mg/L) resulted in a breakdown of initial biofilm of 60-80% in H. influenzae and S. pneumoniae, 48-86% in S. aureus, 37-69% in M. catarrhalis and 51-71% in E. coli. Mature biofilms were less susceptible to degradation. Moxifloxacin at concentrations that can be achieved in the bronchial mucosa during therapy therefore promotes a significant inhibition of biofilm synthesis and induces slime disruption, a feature that may be instrumental in reducing the exacerbations so frequently observed in this condition.


Asunto(s)
Antibacterianos/farmacología , Compuestos Aza/farmacología , Biopelículas/efectos de los fármacos , Bronquitis Crónica/microbiología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Quinolinas/farmacología , Biomasa , Fluoroquinolonas , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/microbiología , Bacterias Grampositivas/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Pruebas de Sensibilidad Microbiana , Moxifloxacino , Espectrofotometría
8.
Int J Antimicrob Agents ; 29(6): 679-87, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17363225

RESUMEN

Minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) of prulifloxacin against 30 strains of Escherichia coli isolated from urinary tract infections as well as the 'biological cost' related to acquisition of resistance to the same drug in 10 uropathogenic E. coli were assessed. In terms of MIC(90), prulifloxacin was more potent than ciprofloxacin and levofloxacin. Prulifloxacin produced lower or equal MPC values than the other two fluoroquinolones (93.3% and 73.3% compared with levofloxacin and ciprofloxacin, respectively). Compared with susceptible strains, prulifloxacin-resistant mutants showed a reduced rate of growth (ranging from 20.0% to 98.0% in different culture media and incubation conditions) and a decreased fitness index (ranging from 0.959 to 0.999). They were also impaired in their ability to adhere to uroepithelial cells and urinary catheters (11.7-66.4% and 16.3-78.3% reduction, respectively) and showed a lower surface hydrophobicity (51.2-76.0%). They were more susceptible to ultraviolet irradiation (30.6-93.8% excess mortality), showed increased resistance to colicins and diminished transfer of plasmids (<1-8.5x10(-8) vs. 3.3x10(-7)-2.4x10(-4)). Synthesis of haemolysin and type I fimbriae and production of flagella were also adversely affected. This study demonstrates a strict relationship between acquisition of prulifloxacin resistance and loss of important virulence traits. In this transition, E. coli pays a severe biological cost that entails a general reduction of fitness, thus compromising competition with susceptible wild-type strains in the absence of the drug.


Asunto(s)
Antiinfecciosos Urinarios/farmacología , Dioxolanos/farmacología , Farmacorresistencia Bacteriana/fisiología , Escherichia coli/efectos de los fármacos , Fluoroquinolonas/farmacología , Piperazinas/farmacología , Quinolonas/farmacología , Infecciones Urinarias/microbiología , Adhesión Bacteriana/fisiología , Ciprofloxacina/farmacología , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Proteínas Hemolisinas/antagonistas & inhibidores , Humanos , Técnicas In Vitro , Levofloxacino , Pruebas de Sensibilidad Microbiana , Ofloxacino/farmacología , Rayos Ultravioleta , Infecciones Urinarias/tratamiento farmacológico
9.
J Chemother ; 19(6): 609-19, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18230541

RESUMEN

This article critically evaluates the main in vitro and in vivo studies published which compare generic with the original molecules, both those administered orally and parenterally. The authors indicate that caution should be used in assuming bioequivalence of the generic drug with its clinical efficacy in clinical practice. In fact, mild differences in the content of the active ingredient, less relevant in healthy volunteers, may have an impact in the actual population, which is heterogeneous for age, sex, weight, concomitant risk factors and severity of the underlying disease, as in critically ill patients, with consequences for the patient and ecosystem. Nowadays the requirements for authorization to commercialize a generic antimicrobial agent are focused on demonstration of bioequivalence to the original molecule, with a range variability of +/-20%. However this kind of trial is not sufficient to predict the actual profile in clinical practice, particularly in critically ill patients. Thus while generics can represent an opportunity for physicians, patients and healthcare systems the regulatory procedures do not seem exhaustive, and it is probably necessary to define an ad hoc technical standard of quality before their commercialization and to perform adequate clinical trials regarding efficacy and safety of the "equivalent molecule", especially for drugs used in critically ill patients.


Asunto(s)
Antibacterianos/uso terapéutico , Medicamentos Genéricos/normas , Antibacterianos/farmacología , Antibacterianos/normas , Ensayos Clínicos como Asunto , Aprobación de Drogas , Farmacorresistencia Bacteriana , Medicamentos Genéricos/farmacología , Medicamentos Genéricos/uso terapéutico , Ecología , Humanos , Equivalencia Terapéutica
11.
J Chemother ; 18(5): 507-13, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17127228

RESUMEN

A total of 102 patients with recurrent upper respiratory tract infections underwent microbiological exploration with appropriate sampling and direct biopsies of the infected sites. Therapy was then started and on day 1 each patient received two intramuscular injections of thiamphenicol glycinate acetylcysteinate (TGA). From day 2 to 10 sequential therapy with the same drug was continued employing TGA administered by aerosol. All putative etiologic agents recovered were susceptible to thiamphenicol and only 24 demonstrated the ability to produce in vitro biofilms. The organisms comprised 10 Staphylococcus aureus, 6 Streptococcus pyogenes, 4 Streptococcus pneumoniae and 3 Haemophilus influenzae. Of the 24 subjects in whom biofilms were demonstrated to be present in vivo by Scanning Electron Microscopy, clinical and bacteriological cure was obtained in 21 cases (87.5%) following sequential therapy with TGA. Failures were considered to be persistent signs and symptoms at day 15 after initiation of treatment and lack of eradication of 3 S. aureus strains, despite their in vitro susceptibility to thiamphenicol. Very few adverse events attributable to TGA were reported in this cohort of patients. In no case was discontinuation of treatment deemed necessary by the attending physician.


Asunto(s)
Acetilcisteína/administración & dosificación , Fenómenos Fisiológicos Bacterianos/efectos de los fármacos , Biopelículas/efectos de los fármacos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Tianfenicol/análogos & derivados , Acetilcisteína/efectos adversos , Adolescente , Adulto , Aerosoles/uso terapéutico , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Vías de Administración de Medicamentos , Combinación de Medicamentos , Expectorantes/administración & dosificación , Expectorantes/efectos adversos , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/microbiología , Tianfenicol/administración & dosificación , Tianfenicol/efectos adversos , Resultado del Tratamiento
12.
Clin Microbiol Infect ; 12 Suppl 1: 3-8, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16445718

RESUMEN

Hospital- and community-acquired Staphylococcus aureus infections pose a substantial burden in terms of morbidity, mortality and health care costs. The introduction of new antibiotics to counter this pathogen has frequently been closely followed by the emergence of resistant strains. Most significantly, S. aureus isolates resistant to beta-lactams have become common, and many of these are also resistant to beta-lactamase-resistant penicillins. The rapid spread of methicillin-resistant S. aureus (MRSA) clones across the world often results in hospital outbreaks, but implementation of appropriate control measures usually reduces prevalence to sporadic levels. However, the recent emergence of MRSA infections in the community, affecting patients with no established risk factors for MRSA acquisition, is likely to impact significantly on future strategies for control of nosocomial MRSA. In contrast to other antibiotic classes, S. aureus resistance to glycopeptides did not emerge until nearly 40 years after their clinical introduction, and as a result this drug class has remained the mainstay of treatment for MRSA infections. However, a number of vancomycin-intermediate S. aureus isolates have emerged worldwide and four fully resistant S. aureus isolates have been reported in the USA. This raises the concern that the current first-line treatment for MRSA infection may become ineffective in an increasing proportion of cases in the near future. New classes of antibiotic are urgently needed to treat infections with this growing population of multidrug-resistant S. aureus, and the recently introduced oxazolidinone linezolid and the cyclic lipopeptide daptomycin are welcome additions to the ever-narrowing range of therapies effective against this pathogen.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Aminoglicósidos/farmacología , Glicopéptidos/farmacología , Humanos , Macrólidos/farmacología , Quinolonas/farmacología , Infecciones Estafilocócicas/microbiología , Estreptograminas/farmacología , Resistencia betalactámica
13.
J Chemother ; 17 Suppl 2: 33-40, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16315582

RESUMEN

Time above MIC (T>MIC) is regarded as the best pharmacokinetic/pharmacodynamic (PK/PD) parameter for predicting the clinical efficacy of cephalosporins. The concentration of non-protein-bound proprietary ceftriaxone (Rocephin, Roche) in body fluids exceeds this PK/PD criterion for the treatment of Streptococcus pneumoniae respiratory infections. However, the pharmaceutical quality of several generic products may be inferior to Rocephin. We have calculated the variations in fluid concentrations of 34 generic formulations of ceftriaxone and, by mathematical modelling, the implications for attainment of recommended PK/PD criteria, specifically: Treatment of S. pneumoniae infections based on the time that non-protein-bound ceftriaxone concentration in pleural fluid exceeds the CLSI (NCCLS) breakpoint of 4 mg/L for identification of resistant isolates. Impact upon Monte Carlo simulations in plasma for the treatment of S. pneumoniae infections based on T>MIC for 50% dosing interval. Rocephin exceeded the required PK/PD parameters at the mean and two standard deviation levels in both investigations. In contrast, most generic products failed to achieve required PK/PD levels in both investigations. As a consequence, some generic formulations of ceftriaxone may increase risks of clinical failure and/or emergence of resistant isolates.


Asunto(s)
Antibacterianos/farmacología , Antibacterianos/farmacocinética , Ceftriaxona/farmacología , Ceftriaxona/farmacocinética , Modelos Teóricos , Infecciones Neumocócicas/tratamiento farmacológico , Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Farmacorresistencia Bacteriana , Predicción , Humanos , Pruebas de Sensibilidad Microbiana , Método de Montecarlo , Factores de Riesgo , Streptococcus pneumoniae/efectos de los fármacos , Equivalencia Terapéutica , Resultado del Tratamiento
14.
Int J Antimicrob Agents ; 26(6): 479-85, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16289710

RESUMEN

Isolates of Streptococcus pneumoniae collected over the first 4 years of the PROTEKT study were tested for susceptibility to penicillin, azithromycin and telithromycin. A total of 20,750 isolates were collected from 39 countries. Penicillin non-susceptibility rates were stable over the study period; overall, 21.8% of isolates were resistant. Azithromycin resistance increased from 31.0% in Year 1 to 36.3% in Year 4. Resistance rates for penicillin and azithromycin varied between countries and were highest in France, Spain, South Africa, USA and the Far East. Multidrug resistance in S. pneumoniae did not change significantly over the 4 years, with an overall rate of 38.6%. Telithromycin retained good activity against S. pneumoniae (0.1% of isolates resistant), including multidrug-resistant isolates.


Asunto(s)
Antibacterianos/farmacología , Azitromicina/farmacología , Cetólidos/farmacología , Penicilinas/farmacología , Streptococcus pneumoniae/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Salud Global , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Neumocócicas/microbiología
15.
J Chemother ; 17(3): 251-7, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16038517

RESUMEN

During 2004 four Italian Laboratories assessed the prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in female out-patients. A total of 600 urine samples from individuals aged 18-65 were studied. The overall prevalence of Escherichia coli was 85.3%. Klebsiella pneumoniae, Staphylococcus saprophyticus, Proteus mirabilis, Enterococcus faecalis and other rarer species were far less represented. Determination of the antibiotic susceptibility pattern of the entire collection of E. coli (512 organisms) revealed that among the drugs analyzed ampicillin was the least active molecule with only 62.5% of the strains being inhibited. Amoxicillin-clavulanate and cefuroxime displayed a higher potency (87.7% and 89.2% respectively). Cotrimoxazole inhibited only 70.1% of the uropathogens. The three fluoquinolones tested had comparable activity ranging from 83.0% for ciprofloxacin, to 83.6% for levofloxacin and 84.9% for prulifloxacin, indicating an identical spectrum of cross resistance. Nitrofurantoin (96.7%) and fosfomycin (98.6%) were the most potent drugs. Against the whole collection of uropathogens, only cefuroxime, nitrofurantoin and fosfomycin overcame the threshold of 90% activity, with the fluoroquinolones and amoxicillin-clavulanate suffering from about 15% resistance. The results of this survey strongly support the conclusions of recent Italian guidelines concerning the best empiric treatment of UTI in this country today.


Asunto(s)
Cistitis/tratamiento farmacológico , Cistitis/microbiología , Farmacorresistencia Bacteriana , Guías de Práctica Clínica como Asunto , Adolescente , Adulto , Anciano , Femenino , Encuestas Epidemiológicas , Humanos , Italia/epidemiología , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Prevalencia
16.
Int J Antimicrob Agents ; 26(2): 138-45, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16024234

RESUMEN

During 2000-2002, 20 clinical microbiology centres collected 1623 Streptococcus pneumoniae isolates. Susceptibility to penicillin, amoxicillin, amoxicillin/clavulanic acid, cefaclor, cefuroxime, cefotaxime, clarithromycin, ciprofloxacin, levofloxacin, rifampicin and teicoplanin was determined locally by the Etest and/or by the microdilution method by three co-ordinating centres. Total resistance to penicillin increased from 15.2% to 16.1% and macrolide resistance increased from 37.9% to 43.7%. Overall, the most effective drugs (>99% susceptible strains) were amoxicillin, amoxicillin/clavulanic acid, levofloxacin and rifampicin. The most frequent serotypes were: 23F (15.8%), 3 (10.8%) 14 (9.1%), 19F (9.1%), 6B (7.2%), 19A (6.9%) and 6A (4.8%). In conclusion, penicillin and macrolide resistance is increasing in Italy, whilst fluoroquinolone currently remains active. The most common serotypes circulating are included in the heptavalent conjugate vaccine, with the exception of type 3.


Asunto(s)
Antibacterianos/farmacología , Infecciones Neumocócicas/microbiología , Serotipificación , Streptococcus pneumoniae/efectos de los fármacos , Humanos , Italia/epidemiología , Pruebas de Sensibilidad Microbiana , Infecciones Neumocócicas/epidemiología , Streptococcus pneumoniae/clasificación
17.
Int J Antimicrob Agents ; 26(1): 8-12, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15967638

RESUMEN

A total of 460 Streptococcus pneumoniae and Haemophilus spp. collected from respiratory infections during 2000 was tested for their susceptibility to 15 selected antibiotics. Overall, penicillin resistance among pneumococci was 10.5%, while lack of susceptibility to macrolides, co-trimoxazole, tetracycline and chloramphenicol reached 35.2%, 26.2%, 22.6% and 6.0%, respectively. Amoxicillin/clavulanic acid and levofloxacin were the most potent compounds (100% and 99.9% susceptible strains, respectively). Among isolates of Haemophilus influenzae and Haemophilus parainfluenzae, beta-lactamase production (12.5% and 10%, respectively), and co-trimoxazole (19.9% and 40.0%) and clarithromycin (11.2% and 40.0%) resistance were the prevalent threats. This study confirms the trend observed in Italy since 1992: macrolide resistance among respiratory microorganisms is increasing, while several drugs including amoxicillin/clavulanic acid, third generation injectable cephalosporins and fluoroquinolones remain active on the great majority of these pathogens.


Asunto(s)
Farmacorresistencia Bacteriana , Infecciones por Haemophilus/microbiología , Infecciones Neumocócicas/microbiología , Infecciones del Sistema Respiratorio/microbiología , Vigilancia de Guardia , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Infecciones por Haemophilus/tratamiento farmacológico , Infecciones por Haemophilus/epidemiología , Humanos , Italia/epidemiología , Pruebas de Sensibilidad Microbiana , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones Neumocócicas/epidemiología , Prevalencia , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiología
18.
Int J Antimicrob Agents ; 24(5): 515-8, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15519488

RESUMEN

Here we report the results of the Sentinel Project 2000 and give the susceptibility to selected antibiotics of 108 Pseudomonas aeruginosa and 108 Staphylococcus aureus strains isolated from patients with hospital-acquired lower respiratory tract infections. In P. aeruginosa, susceptibility to aztreonam and ciprofloxacin was lower than 50%. The resistance rate to beta-lactams was up to 25% and to amikacin 15.7%. Blood isolates showed 80-90% susceptibility to all antibiotics tested except for aztreonam and tobramycin. Overall, oxacillin resistance in S. aureus was 45%, reaching 64.3% among the bronchoalveolar lavage isolates, and 42.9% among the blood isolates. These worrying results confirm the need for continuous monitoring of bacterial resistance trends in the hospitals, mainly in ICUs.


Asunto(s)
Antibacterianos/farmacología , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana , Pseudomonas aeruginosa/efectos de los fármacos , Infecciones del Sistema Respiratorio/microbiología , Staphylococcus aureus/efectos de los fármacos , Humanos , Italia , beta-Lactamas/farmacología
19.
J Antimicrob Chemother ; 54(5): 944-51, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15472001

RESUMEN

OBJECTIVES: The in vitro activity of ertapenem was evaluated in comparison to 21 selected agents against a large collection of recently isolated respiratory tract pathogens including: 180 Streptococcus pneumoniae, 100 Streptococcus pyogenes, 70 Haemophilus influenzae, 70 Moraxella catarrhalis, 100 methicillin-susceptible Staphylococcus aureus and 30 Klebsiella pneumoniae. Additional in vitro tests (time-kill curves with ertapenem alone and in combination with four other agents) for S. pneumoniae were carried out. METHODS: MIC determinations and time-kill curves were carried out following the procedures suggested by the NCCLS. RESULTS: According to NCCLS susceptibility breakpoints, ertapenem was comparable to the most potent compounds tested for all pathogens studied. Ertapenem was 100% active against penicillin-susceptible and -intermediate S. pneumoniae and against 60% of penicillin-resistant strains. Time-kill tests at 4x MIC confirmed a pronounced bactericidal potency of ertapenem against these organisms. Interactions of ertapenem with several other agents against pneumococci resulted in clear synergic interactions (98.4%). Indifference was extremely rare and antagonism was not observed. All S. pyogenes strains tested were inhibited by ertapenem, irrespective of their macrolide resistance phenotypes. Ertapenem was also fully active against H. influenzae (100% susceptible) and M. catarrhalis (MIC90 0.015-0.03 mg/L) even when capable of synthesizing beta-lactamases. Methicillin-susceptible S. aureus and K. pneumoniae, including extended-spectrum beta-lactamase-producing strains, were 100% susceptible to ertapenem. CONCLUSIONS: Our results indicate that ertapenem has a suitable spectrum of activity against organisms encountered in community-acquired bacterial respiratory tract infections.


Asunto(s)
Bacterias/efectos de los fármacos , Lactamas/farmacología , Infecciones del Sistema Respiratorio/microbiología , Ertapenem , Humanos , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacos , beta-Lactamas
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