Iodine status and thyroid function among Spanish schoolchildren aged 6-7 years: the Tirokid study.

I deficiency is still a worldwide public health problem, with children being especially vulnerable. No nationwide study had been conducted to assess the I status of Spanish children, and thus an observational, multicentre and cross-sectional study was conducted in Spain to assess the I status and thyroid function in schoolchildren aged 6-7 years. The median urinary I (UI) and thyroid-stimulating hormone (TSH) levels in whole blood were used to assess the I status and thyroid function, respectively. A FFQ was used to determine the consumption of I-rich foods. A total of 1981 schoolchildren (52 % male) were included. The median UI was 173 µg/l, and 17·9 % of children showed UI<100 µg/l. The median UI was higher in males (180·8 v. 153·6 µg/l; P<0·001). Iodised salt (IS) intake at home was 69·8 %. IS consumption and intakes of ≥2 glasses of milk or 1 cup of yogurt/d were associated with significantly higher median UI. Median TSH was 0·90 mU/l and was higher in females (0·98 v. 0·83; P<0·001). In total, 0·5 % of children had known hypothyroidism (derived from the questionnaire) and 7·6 % had TSH levels above reference values. Median TSH was higher in schoolchildren with family history of hypothyroidism. I intake was adequate in Spanish schoolchildren. However, no correlation was found between TSH and median UI in any geographical area. The prevalence of TSH above reference values was high and its association with thyroid autoimmunity should be determined. Further assessment of thyroid autoimmunity in Spanish schoolchildren is desirable.

Exposure-response analysis of tigecycline in pharmacodynamic simulations using different size inocula of target bacteria.

This study explored tigecycline exposure-bacterial responses in pharmacodynamic simulations (in vitro kinetic model) using different inocula. One meticillin-resistant vancomycin-heteroresistant Staphylococcus aureus, one Enterococcus faecium and one extended-spectrum beta-lactamase-producing Escherichia coli with equal tigecycline minimum inhibitory concentrations/minimum bactericidal concentrations (MICs/MBCs) (0.12/0.25 microg/mL) were used. A computerised pharmacodynamic bicompartmental model simulated three tigecycline twice-daily dosing regimens over 48h: 50mg (100mg loading dose); 100mg; and 150 mg. Areas under bacterial growth curves were calculated, and differences between the growth curve used as control and the killing curve of bacteria exposed to tigecycline (ABBC) were determined. With standard inocula [ca. 1 x 10(6)colony-forming units (CFU)/mL], linear increases in area under the concentration-time curve (AUC)/MIC (25.6 for 50mg, 53.76 for 100mg and 79.52 for 150 mg) produced linear increases in activity against Gram-positive organisms (mean ABBCs of 120.60, 143.20 and 195.80 log CFU x h/mL for S. aureus and of 95.75, 172.55 and 216.90 log CFUxh/mL for E. faecium, respectively), with the activity of the 150 mg regimen being significantly higher (P<0.01) than that of the other two regimens. ABBCs obtained with the 100mg regimen using standard inocula were similar to those obtained with the 150 mg regimen when using high inocula (ca. 1 x 10(7)CFU/mL). Against E. coli, the highest dosing regimen was required to obtain significant antibacterial activity compared with control (mean ABBCs of 145.75 log CFU x h/mL with standard inocula and 63.33 log CFU x h/mL with high inocula). An increase in tigecycline dosing appears to be an interesting therapeutic option to maximise antibacterial activity owing to its linear pharmacokinetics and pharmacodynamics, especially when severe infections with high bacterial load are suspected.

Recomendaciones en el tratamiento antibiótico empírico de la infección intraabdominal / No disponible

No disponible

Recomendaciones en el tratamientoantibiótico empírico de la infecciónintraabdominal / Recommendations in the empiric anti-infective agents of intra-abdominal infection

Un número importante de pacientes con infección intraabdominaldesarrollan estados avanzados de la infeccióny la mortalidad es todavía superior al 20%. El fracaso esmultifactorial y se relaciona con el incremento de resistenciasbacterianas, el tratamiento empírico inapropiado, la mayorcomorbilidad de los pacientes y el mal control del foco de infección.Estas guías analizan cada uno de estos problemas yproponen medidas para evitar el fracaso, basadas en la mejorevidencia científica actual (AU)

A significant number of patients with abdominal infectiondevelop advanced stages of infection and mortalityis still above 20%. Failure is multifactorial and isassociated with an increase of bacterial resitance, inappropriateempirical treatment, a higher comorbidity of patientsand poor source control of infection. These guidelinesdiscuss each of these problems and propose measuresto avoid the failure based on the best current scientificevidence (AU)

[Recommendations in the empiric anti-infective agents of intra-abdominal infection]. / Recomendaciones en el tratamiento antibiótico empírico de la infección intraabdominal.

A significant number of patients with abdominal infection develop advanced stages of infection and mortality is still above 20%. Failure is multifactorial and is associated with an increase of bacterial resistance, inappropriate empirical treatment, a higher comorbidity of patients and poor source control of infection. These guidelines discuss each of these problems and propose measures to avoid the failure based on the best current scientific evidence.

Influence of testing methodology on the tigecycline activity profile against presumably tigecycline-non-susceptible Acinetobacter spp.

OBJECTIVES: To compare the tigecycline activity profile against Acinetobacter spp. by Etest versus broth microdilution in isolates with high Etest MIC. METHODS: Acinetobacter spp. isolates with tigecycline MICs of >or=0.5 mg/L determined by commercially developed Etests strips (January 2006 to July 2007) in five Spanish hospitals were considered. Values were rounded to the nearest upper double-dilution. Susceptibility by broth microdilution following CLSI (formerly NCCLS) recommendations, as the reference method, was determined in a central laboratory. BSAC breakpoints were used: susceptible 2 mg/L. RESULTS: One hundred and forty-eight isolates were collected: 12 isolates with a tigecycline Etest MIC of 0.5 mg/L, 14 with 1 mg/L, 86 with 2 mg/L, 31 with 4 mg/L and 5 with 8 mg/L. Isolates with Etest MICs of 0.5-1 mg/L showed the same values by broth microdilution. Among isolates with Etest MICs of 2 mg/L, only 5.8% of strains showed the same value by both methods (88.4% showed values that were one or two dilutions lower by microdilution). None of the 36 isolates with Etest MICs of 4-8 mg/L showed the same value by both methods, with values at least two dilutions lower by microdilution. Weak correlation (R = 0.238; P or=2 mg/L for Acinetobacter spp. since strains with Etest MICs of 2-4 mg/L are susceptible when tested by microdilution. False non-susceptibility by Etest may exclude tigecycline as a therapeutic option in a field where multiresistance is the rule.

[Clinical experience with tigecycline in the treatment of nosocomial infections caused by isolates exhibiting prevalent resistance mechanisms]. / Experiencia clínica con tigeciclina en el tratamiento de infecciones nosocomiales producidas por aislados con mecanismos de resistencia prevalentes.

This article reviews the clinical experience with tigecycline in the treatment of infections caused by microorganisms with prevalent resistance mechanisms among nosocomial microbiota, as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, multidrug- resistant Acinetobacter baumannii and enterobacteria producing extended spectrum beta-lactamases. Most of articles found in the literature describe the use of tigecycline in the treatment of severe infections (sepsis and septic shock, nosocomial pneumonia and ventilator-associated pneumonia...) produced by multidrug-resistant microorganisms, in patients with multiple comorbidities (admitted in ICU, with malignancies, transplants and/or immunodepressed...) and in many occasions after failures of previous antibiotic treatments. Favourable outcomes with tigecycline are reported in most articles. However, an accurate global assessment is difficult since, in addition to the described confounding factors, there are concomitant or sequential antibiotic treatments in several communications, and lack of relevant clinical (as comorbidities), microbiological (as susceptibility) and outcome (different criteria by different authors) data in others. More even, the described series are retrospective and lack of control groups. Nevertheless the usefulness of this revision is based on the fact that in daily clinical practice the use of tigecycline will increase, since epidemiology of specific hospital medical units shows multidrug resistance among nosocomial isolates and tigecycline can be one of the scarce available compounds active against multidrug-resistant strains/clones.

Experiencia clínica con tigeciclina en el tratamiento de infecciones nosocomiales producidas por aislados con mecanismos de resistencia prevalentes / Clinical experience with tigecycline in the treatment of nosocomial infections caused by isolates exhibiting prevalent resistance mechanisms

Este artículo incluye una revisión de la experiencia clínicacon tigeciclina en infecciones por microorganismos con losfenotipos de resistencia más prevalentes en la microbiotanosocomial, como Staphylococcus aureus resistente a lameticilina y enterococos resistentes a la vancomicina dentrode los gram positivos, y Acinetobacter baumannii multirresistentey enterobacterias productoras de betalactamasasde espectro extendido dentro de los gram negativos nosocomiales.La mayoría de los artículos encontrados en la literaturadescriben la utilización de la tigeciclina en el tratamientode infecciones graves (sepsis y shock séptico,neumonía nosocomial y neumonía asociada a ventilaciónmecánica, etc.) producidas por estos microorganismos multirresistentes,en pacientes que presentan comorbilidadesgraves (pacientes ingresados en la unidad de cuidados intensivos(UCI), oncológicos, inmunodeprimidos, etc.) y enmuchas ocasiones tras el fracaso de otros tratamientos. Apesar de estas circunstancias, tigeciclina presenta unos datosde eficacia favorables. Hacer una evaluación global precisaresultaría muy difícil, ya que aparte de los factores deconfusión descritos, se añade la presencia de tratamientosantibióticos concomitantes o secuenciales, así como la faltaen algunas comunicaciones de datos clínicos (como comorbilidades),microbiológicos (como sensibilidad antibiótica) yde respuesta terapéutica (como criterios de valoración distintospor distintos autores) relevantes. Por otra parte lasseries son retrospectivas sin grupo control (AU)

This article reviews the clinical experience with tigecyclinein the treatment of infections caused by microorganismswith prevalent resistance mechanisms amongnosocomial microbiota, as methicillin-resistant Staphylococcusaureus, vancomycin-resistant enterococci, multidrug-resistant Acinetobacter baumannii and enterobacteriaproducing extended spectrum ß-lactamases. Mostof articles found in the literature describe the use of tigecyclinein the treatment of severe infections (sepsisand septic shock, nosocomial pneumonia and ventilador-associated pneumonia…) produced by multidrug-resistantmicroorganisms, in patients with multiple comorbidities(admitted in ICU, with malignancies, transplantsand/or immunodepressed…) and in many occasions afterfailures of previous antibiotic treatments. Favourableoutcomes with tigecycline are reported in most articles.However, an accurate global assessment is difficult since,in addition to the described confounding factors, thereare concomitant or sequential antibiotic treatments inseveral communications, and lack of relevant clinical (ascomorbidities), microbiological (as susceptibility) andoutcome (different criteria by different authors) data inothers. More even, the described series are retrospectiveand lack of control groups. Nevertheless the usefulnessof this revision is based on the fact that in daily clinicalpractice the use of tigecycline will increase, since epidemiologyof specific hospital medical units shows multidrugresistance among nosocomial isolates and tigecy cline can be one of the scarce available compounds activeagainst multidrug-resistant strains/clones (AU)

Factors impacting on length of stay and mortality of community-acquired pneumonia.

A 1-year retrospective multicentre study was performed to identify factors influencing hospital length of stay (LOS) and mortality of patients (n = 3233) admitted to hospital because of community-acquired pneumonia (CAP). Pneumonia severity index (PSI) high-risk classes (IV and V), positive blood culture, admission to an intensive care unit (ICU), multi-lobar involvement and alcohol consumption were associated independently with prolonged LOS. Tobacco smoking was associated with a reduced LOS. The LOS varied markedly among centres. Only PSI high-risk class, admission to ICU and multi-lobar involvement were associated with early, late and global mortality. Positive blood cultures, antimicrobial therapy according to treatment guidelines and the establishment of an aetiological diagnosis were linked to reduced late and global mortality. These data suggest that early mortality associated with CAP is highly dependent on the clinical status of the patient at presentation. Conversely, late mortality seems to be associated more closely with clinical management factors; hence, an aetiological diagnosis and compliance with appropriate therapeutic guidelines have a significant influence on outcome.

Quinolone resistance in female outpatient urinary tract isolates of Escherichia coli: age-related differences.

During a 1-year period, from November 2003 to October 2004, urinary Escherichia coli isolates were collected from 20 clinical microbiology laboratories across Spain. The main objective was to assess the resistance of E. coli to the antimicrobials most commonly prescribed for community-acquired urinary tract infections depending on the patient's age. A total of 2,230 valid E. coli strains from female outpatients were isolated and sent to a single central reference laboratory for confirmation and susceptibility testing using an agar dilution method. A two-sided chi-squared test was used to assess the differences in resistance between age groups (< or =65 and >65 years). E. coli resistance was found to be more common to ampicillin (52.1%), cotrimoxazole (26%) and quinolones (18%), whereas resistance to amoxicillin-clavulanic acid, cefuroxime axetil and fosfomycin were below 3%. In women older than 65 years, resistance to ciprofloxacin reached up to 29% compared with 13% of those in the under 65 age group (p <0.001). For cotrimozaxole, rates were 32% vs. 23% (p <0.001) and for ampicillin 56% vs. 50% (p=0.02), respectively. It was concluded that fosfomycin, amoxicillin-clavulanic acid and cefuroxime axetil are the most suitable antimicrobials for empirical treatment in Spain given the high 18% and 26% resistance rates to quinolones and cotrimoxazole, respectively. Being older than 65 years of age was associated with higher resistance rates to ciprofloxacin (29%). These results should be considered when recommending empirical therapy for acute cystitis in women.

Quinolone resistance in female outpatient urinary tract isolates of Escherichia coli: age-related differences

Se recogieron a lo largo de un año (noviembre de 2003 a octubre de 2004) 2230 aislamientos de Escherichia coli de pacientes con infección urinaria adquirida en la comunidad procedentes de 20 laboratorios microbiológicos de toda España, que fueron enviados a un laboratorio central de referencia para realizar la confirmación del patógeno y las pruebas de sensibilidad antibacteriana, mediante el método de dilución en agar. El principal objetivo fue evaluar la resistencia a los antimicrobianos más prescritos en las cistitis agudas, en relación con la edad. Se utilizó el test de χ2 bilateral para valorar las diferencias de la resistencia entre los dos grupos de edad (≤65 años y ≥65 años). E. coli mostró una elevada resistencia a la ampicilina (52,1%), el cotrimoxazol (26%) y las quinolonas (18%), mientras que a amoxicilina-ácido clavulánico, cefuroxima-axetilo y fosfomicina fue inferior al 3%. En las mujeres mayores de 65 años, la resistencia al ciprofloxacino alcanzó el 29%, frente al 13% en las mujeres por debajo de esa edad (p 65 años se asoció con mayores tasas de resistencia al ciprofloxacino (29%). Estos resultados deberían tenerse en cuenta cuando se recomienda un tratamiento antimicrobiano empírico en mujeres con cistitis aguda comunitaria

During a 1-year period, from November 2003 to October 2004, urinary Escherichia coli isolates were collected from 20 clinical microbiology laboratories across Spain. The main objective was to assess the resistance of E. coli to the antimicrobials most commonly prescribed for community- acquired urinary tract infections depending on the patient’s age. A total of 2,230 valid E. coli strains from female outpatients were isolated and sent to a single central reference laboratory for confirmation and susceptibility testing using an agar dilution method. A two-sided chi-squared test was used to assess the differences in resistance between age groups (≤65 and >65 years). E. coli resistance was found to be more common to ampicillin (52.1%), cotrimoxazole (26%) and quinolones (18%), whereas resistance to amoxicillin-clavulanic acid, cefuroxime axetil and fosfomycin were below 3%. In women older than 65 years, resistance to ciprofloxacin reached up to 29% compared with 13% of those in the under 65 age group (p <0.001). For cotrimozaxole, rates were 32% vs. 23% (p <0.001) and for ampicillin 56% vs. 50% (p=0.02), respectively. It was concluded that fosfomycin, amoxicillin-clavulanic acid and cefuroxime axetil are the most suitable antimicrobials for empirical treatment in Spain given the high 18% and 26% resistance rates to quinolones and cotrimoxazole, respectively. Being older than 65 years of age was associated with higher resistance rates to ciprofloxacin (29%). These results should be considered when recommending empirical therapy for acute cystitis in women

Antimicrobial susceptibility of clinical Escherichia coli isolates from uncomplicated cystitis in women over a 1-year period in Spain.

High usage of antibiotics in Spain has led to an increase in resistance in urinary Escherichia coli isolates in different geographic regions. The problem of resistance in urinary E. coli in Spain was investigated by gathering a large number of isolates from 20 different sites nationwide over a 1-year period from November 2003 to October 2004 in a large population of women. The objectives of this study were to assess the resistance to the antibiotics most commonly prescribed for community-acquired urinary tract infections (UTIs), according to age and different geographical areas of Spain, and to evaluate the potential association between geographical differences in quinolone consumption and resistance to E. coli. A total of 2,292 valid E. coli strains from female outpatients were isolated and sent to a single central reference laboratory for confirmation and susceptibility testing. Of these, 2,230 isolates were available for the age analysis. A two-sided chi2 test was used to identify differences in resistance between age groups. Antibiotic units per province were purchased from IMS and consumption was expressed in units per 1,000 people per year. Univariate correlation (Pearson coefficient) between resistance to ciprofloxacin and quinolone consumption was calculated using a two-sided p-value. Resistance shown by E. coli was more common to ampicillin (52.1%) and cotrimoxazole (26%), followed by quinolones (18%), whereas resistance to amoxicillin-clavulanic acid, cefuroxime-axetil and fosfomycin was less than 3%. In the subgroup of women aged >65 years, resistance to ciprofloxacin was 29% compared to 13% for the subgroup of women <65 years (p<0.001). For these same subgroups, resistance rates were 32% vs. 23% for cotrimoxazole (p<0.001) and 56% vs. 50% for ampicillin (p=0.02), respectively. Statistically significant correlations were found between consumption of quinolones and E. coli resistance to ciprofloxacin (r=0.5; p=0.025). Resistance of E. coli isolates to quinolones varied significantly according to geographical areas, ranging from a high of 16.5% and 16.6% in the southern and eastern regions of Spain, respectively, to a low of 8% in the north in women aged <65 years. Additionally, the susceptibility to quinolones of E. coli isolates recovered from women aged >65 years was significantly lower across all regions of Spain than that of isolates recovered from younger women. Fosfomycin, amoxicillin/clavulanic acid and cefuroxime-axetil are the most suitable antibiotics for empirical treatment in Spain given the high 18% and 26% resistance rates to quinolones and cotrimoxazole, respectively. Higher resistance rates to ciprofloxacin were associated with being aged 65 years and over. These data need to be considered when recommending empirical therapy for acute cystitis.

Antimicrobial susceptibility of clinical Escherichia coli isolates from uncomplicated cystitis in women over a 1-year period in Spain

La frecuente utilización de antibióticos en España ha permitido la aparición de resistencias en las cepas de E. coli urinarias aisladas en distintas regiones geográficas. Nosotros hemos analizado el problema de las resistencias de E. coli urinaria en España recogiendo un gran número de muestras en 20 centros distintos de todo el país durante un periodo de un año (noviembre de 2003 a octubre de 2004), procedentes de una gran población de mujeres. Los objetivos de este estudio fueron valorar las resistencias a los antibióticos que con más frecuencia se prescriben como tratamiento de las infecciones de vías urinarias adquiridas en la comunidad, así como según la edad de las pacientes y las distintas regiones geográficas de España, y valorar una posible asociación entre las diferencias geográficas en la utilización de quinolonas y las resistencias de E. coli. Se aislaron en total 2292 cepas de E. coli válidas de mujeres en régimen ambulatorio y se remitieron a un único laboratorio de referencia central para la confirmación del diagnóstico y la realización de las pruebas de sensibilidad. De todas estas muestras, 2230 estuvieron disponibles para el análisis por edad. Se realizó una prueba de χ2 de dos colas para analizar las diferencias de las resistencias entre los grupos de edad. La información sobre unidades de antibióticos en cada provincia se obtuvo del IMS y el consumo se expresó en unidades por mil personas-año. Se realizó una correlación univariable (coeficiente de Pearson) entre la resistencia al ciprofloxacino y el consumo de quinolonas usando un valor de p bilateral. Las resistencias que mostró E. coli fueron principalmente frente a ampicilina (52,1%), cotrimoxazol (26%) y después quinolonas (18%), mientras que las resistencias a amoxicilina-ácido clavulánico, cefuroxima axetilo y fosfomicina fueron inferiores al 3%. En el grupo de mujeres mayores de 65 años, las resistencias al ciprofloxacino alcanzaron el 29%, lo que contrasta con el 13% en las de menor edad (p <0.001). En el caso del cotrimoxazol estos valores fueron del 32% y el 23% (p <0.001), y para ampicilina del 56% y el 50% (p=0.02). Se encontró una correlación estadísticamente significativa entre el consumo de quinolonas y la resistencia de E. coli al ciprofloxacino (r=0.5; p=0.025). Las resistencias a las quinolonas de los aislamientos de E. coli variaron de forma significativa en función de las regiones geográficas, oscilando entre una elevada frecuencia, del 16,5% y 16,6%, en las regiones sur y este de España, hasta otras bajas como el 8% descrito en la zona norte del país en mujeres menores de 65 años. Además, la sensibilidad a las quinolonas de las cepas de E. coli aisladas en mujeres mayores de 65 años fue significativamente menor en todas las regiones de España en comparación con las aisladas de mujeres más jóvenes. Fosfomicina, amoxicilina-ácido clavulánico y cefuroxima axetilo son los antibióticos más adecuados para el tratamiento empírico en España, dadas las elevadas frecuencias de resistencia a las quinolonas y el cotrimoxazol, del 18% y el 26%, respectivamente. La edad mayor de 65 años se asoció a una frecuencia de resistencias al ciprofloxacino superior a la observada en mujeres más jóvenes. Esta información se debe tener en cuenta a la hora de recomendar un tratamiento empírico para la cistitis aguda

High usage of antibiotics in Spain has led to an increase in resistance in urinary Escherichia coli isolates in different geographic regions. The problem of resistance in urinary E. coli in Spain was investigated by gathering a large number of isolates from 20 different sites nationwide over a 1-year period from November 2003 to October 2004 in a large population of women. The objectives of this study were to assess the resistance to the antibiotics most commonly prescribed for community-acquired urinary tract infections (UTIs), according to age and different geographical areas of Spain, and to evaluate the potential association between geographical differences in quinolone consumption and resistance to E. coli. A total of 2,292 valid E. coli strains from female outpatients were isolated and sent to a single central reference laboratory for confirmation and susceptibility testing. Of these, 2,230 isolates were available for the age analysis. A two-sided χ2 test was used to identify differences in resistance between age groups. Antibiotic units per province were purchased from IMS and consumption was expressed in units per 1,000 people per year. Univariate correlation (Pearson coefficient) between resistance to ciprofloxacin and quinolone consumption was calculated using a two-sided p-value. Resistance shown by E. coli was more common to ampicillin (52.1%) and cotrimoxazole (26%), followed by quinolones (18%), whereas resistance to amoxicillin-clavulanic acid, cefuroxime-axetil and fosfomycin was less than 3%. In the subgroup of women aged >65 years, resistance to ciprofloxacin was 29% compared to 13% for the subgroup of women 65 years was significantly lower across all regions of Spain than that of isolates recovered from younger women. Fosfomycin, amoxicillin/clavulanic acid and cefuroxime-axetil are the most suitable antibiotics for empirical treatment in Spain given the high 18% and 26% resistance rates to quinolones and cotrimoxazole, respectively. Higher resistance rates to ciprofloxacin were associated with being aged 65 years and over. These data need to be considered when recommending empirical therapy for acute cystitis

Prophylaxis versus pre-emptive treatment for infective and inflammatory complications of surgical third molar removal: a randomized, double-blind, placebo-controlled, clinical trial with sustained release amoxicillin/clavulanic acid (1000/62.5 mg).

The most common complications after surgical extraction of the third mandibular molar are trismus, oedema or swelling, local pain, dysphagia and infection. The aim of this comparative, double-blind, randomized clinical trial was to evaluate the efficacy of two sustained release amoxicillin/clavulanate regimens in the reduction of infection after third molar extractive surgery. A total of 225 patients were randomized into three equal groups: placebo, prophylaxis with single pre-surgical dose of two tablets amoxicillin/clavulanate 1000/62.5 mg, and pre-emptive post-surgery therapy with two tablets amoxicillin/clavulanate 1000/62.5 mg BID for 5 days. A higher rate of infection (P=0.006) was found among patients receiving placebo (16%) than those receiving single-dose prophylaxis (5.3%) or 5-day pre-emptive therapy (2.7%). A relationship between both the duration (13.8% for long versus 7.4% for medium versus 1.6% for short) and difficulty (12.7% with ostectomy versus 3.5% without ostectomy; P=0.011) of surgical procedure and incidence of subsequent infection was also observed. Both prophylactic and therapeutic regimens versus placebo achieved greater reduction of pain after surgery on day 3 (P=0.001). Logistic regression analysis revealed a risk of infection of 24%, 9% and 4% for ostectomy with placebo, prophylaxis and pre-emptive treatment, respectively, whereas it was 7%, 2% and 1% if ostectomy was not performed. Pre-emptive therapy with the oral sustained release amoxicillin/clavulanate formulation reduced the rate of subsequent infection in patients undergoing ostectomy. Prophylaxis was beneficial in simpler procedures and may be indicated in cases where ostectomy is not performed.

Clinical experience in the management of community-acquired pneumonia: lessons from the use of fluoroquinolones.

Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality worldwide. The treatment of CAP has been complicated by several factors, including the expanding spectrum of causative organisms and the rising prevalence of antibiotic resistance among respiratory pathogens. Initial antimicrobial treatment for patients with CAP is usually selected empirically and should provide appropriate coverage against the most common causative organisms, including resistant strains. Respiratory fluoroquinolones, such as levofloxacin, are the only antimicrobials that are highly active against the pathogens most frequently implicated in CAP, including macrolide-resistant and penicillin-resistant pneumococci, Haemophilus influenzae, Legionella spp., and atypical agents. This paper reviews recent studies involving adult patients with CAP that suggest that levofloxacin, as compared with other conventional antibiotic treatments, may be associated with better clinical outcomes.

Antibiotic consumption and generation of resistance in Streptococcus pneumoniae: the paradoxical impact of quinolones in a complex selective landscape.

The development of resistance to the different antibiotics by the majority of bacterial species of clinical importance seems unavoidable. However, not all drugs have the same efficiency to select for resistance. Large differences in the qualitative and quantitative consumption of antibiotics among countries are known to exist and several authors have consistently reported the direct relationship between consumption and selection of resistance for Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Escherichia coli and beta-lactams and macrolides use. In Spain, extensive surveillance started in 1996, and the Willow (SAUCE) Project, to monitor and update resistance in respiratory pathogens and to couple those data with data concerning national antibiotic consumption (IMS) from both a temporal and geographical approach. Temporally, despite a continuous increase of 16% in quinolone consumption from 1997 to 2001, basically due to the arrival of respiratory quinolones, levofloxacin and moxifloxacin, a continuous linear increase in the resistance rates to ciprofloxacin in S. pneumoniae was not observed. There also was an inverse correlation between provincial consumption of quinolones and resistance to ciprofloxacin. Several hypotheses are proposed and discussed to explain these apparent paradoxical observations, such as the replacement of ciprofloxacin by more potent antipneumococcal quinolones, the possibility of an antibiotic pressure threshold, the influence of other nonquinolone drugs on the expression of ciprofloxacin-resistance biological costs, and the influence of changes in temporal or spatial prevalence of particular clones.

Evaluation of antimicrobial treatments in children with acute otitis media in Spain: a pharmacokinetic-pharmacodynamic (PK/PD) approach.

Pharmacokinetic/pharmacodynamic (PK/PD) principles are priceless tools for evaluating the effectiveness of different antimicrobial treatments for different infections. However, very few studies deal with pediatric dosages and take into account the unbound drug serum levels. Our study is focused on the most frequent antibiotic dosing schedules used in Spain for the treatment of acute otitis media (AOM) in children, where high rates of penicillin and macrolide resistance exist among pneumococcal isolates. Pharmacokinetic parameters of antibiotics in children where obtained from the literature. The minimum inhibitory concentrations (MIC90) of antibiotics for pediatric strains of Streptococcus pneumoniae and Haemophilus influenzae were obtained from the SAUCE 2 project. Only ceftriaxone (50 mg/kg single intramuscular dose) and high doses of co-amoxiclav (27-33 mg/kg q8h) provided adequate efficacy indexes (tss(%)>MIC) for both S. pneumoniae and H. influenzae in AOM in children. These results are consistent with MEF (medium ear fluid) levels obtained from the literature. Our results confirm the utility of serum unbound levels to predict efficacy of antibiotics in children with AOM.

Evolution of penicillin and erythromycin co-resistance in Streptococcus pneumoniae in Spain.

The temporal dynamics of penicillin and erythromycin co-resistance in Streptococcus pneumoniae based on two extensive multicentre Spanish surveillance SAUCE studies (1996-1997 and 1998-1999) is presented. Erythromycin resistance among penicillin non-susceptible isolates seems to have reached a limit as evidenced by a null increase between the two surveys, whereas it is growing among penicillin-susceptible pneumococci.