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.

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.

[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.

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.

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.

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.

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.

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.

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.

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.

Clinical characteristics and response to newer quinolones in Legionella pneumonia: a report of 28 cases.

Twenty-eight (11.6%) out of 241 Spanish patients enrolled in an international phase III clinical trial of mild to moderate community-acquired pneumonia (CAP) comparing gemifloxacin vs. trovafloxacin were diagnosed of Legionnaires' disease. A definite diagnosis was established by seroconversion in 13 patients of whom only 2 had a positive Legionella urinary antigen. The remaining 15 patients were possible Legionella infections based on a single elevated IgG titer (> or = 1:512). All patients had a radiologically confirmed diagnosis of pneumonia, 5 (19%) patients were older than 65, comorbidity was present in 9 (33%), and 10 (36%) had to be hospitalized. Fifteen patients were treated with oral gemifloxacin (320 mg/day) and 13 with oral trovafloxacin (200 mg/day). Overall, clinical success occurred in 25 (89.3%) patients after 7 days of treatment and only 1 patient needed a 14-day treatment. There were only one adverse event withdrawal and one clinical failure, and no patients died. In light of the favorable clinical outcome, the use of newer fluoroquinolones seems adequate for the treatment of suspected or proven Legionella pneumonia.

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.

Genetic relatedness of recently collected Spanish respiratory tract Streptococcus pneumoniae isolates with reduced susceptibility to amoxicillin.

Of Streptococcus pneumoniae isolates from 17 hospitals, 9.8% were amoxicillin nonsusceptible (MIC > or = 4 microg/ml). The genetic relatedness of 138 isolates was studied by pulsed-field gel electrophoresis. Although 44 different clones were detected, more than 62% of these isolates were related to four clones (Spain(23F)-1, Spain(6B)-2, Spain(9V)-3, and Spain(14)-5).