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AbstractPharmacokinetic/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 pneumoniaeand Haemophilus influenzaewere 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. pneumoniaeand H. influenzaein 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.

AbstractTwenty-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 Legionellaurinary antigen. The remaining 15 patients were possible Legionellainfections based on a single elevated IgG titer (≥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 Legionellapneumonia.

Selection of antibiotic-resistant Streptococcus pneumoniae is an inescapable consequence of antibiotic use. The correlation between antibiotic consumption and selection of resistant organisms can be shown at every ecological level: patient, community, region or country. In the case of multiple resistance, the intensity of antibiotic selection is increased. However, different antibiotics may exert different selective powers. Because of this, co-selection of macrolide and β-lactam resistance is an asymmetrical phenomenon: macrolides select more efficiently strains resistant to both macrolides and β-lactams than aminopenicillins. The difference in rates of antibiotic resistance is also influenced by the local spread of susceptible or resistant clones; it is suggested that under mild antibiotic selection, the susceptible organisms that are more fit for host-to-host transmission could be favoured. Subsequent acquisition of resistance in these clones may rapidly increase the prevalence of resistance, and that may lead to an increase in the use of antibiotics. The reasons for antibiotic resistance are mainly the reasons explaining antibiotic consumption. A number of possible sociobiological determinants of antibiotic consumption can be identified: genetic factors in the human populations (for instance, involving different symptomatic types of infection), cultural factors and attitudes of patients towards antibiotics, sociological factors or public health factors, including incidence of other infectious diseases in the human population. Only 'excess' in the use of antibiotics should be controlled; for such a purpose, the concept, 'appropriate demand for antibiotics' (ADA) is proposed.

Multicentre surveillance is essential in order to monitor the prevalence of certain resistance phenotypes and to identify rapidly the emergence of new ones. However, many surveillance studies are based either on a relatively small number of isolates from a single country, or on a large number of isolates from many different countries and so are not equally meaningful. Extensive national multicentre surveillance would provide a more reliable strategy for assessing the extent of antimicrobial resistance in individual countries. This article describes Spanish experience with the surveillance network SAUCE, and summarizes the main results on antimicrobial resistance in the three key bacterial pathogens involved in community-acquired respiratory tract infections in Spain: Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes.

Multicentre surveillance is essential in order to monitor the prevalence of certain resistance phenotypes and to identify rapidly the emergence of new ones. However, many surveillance studies are based either on a relatively small number of isolates from a single country, or on a large number of isolates from many different countries and so are not equally meaningful. Extensive national multicentre surveillance would provide a more reliable strategy for assessing the extent of antimicrobial resistance in individual countries. This article describes Spanish experience with the surveillance network SAUCE, and summarizes the main results on antimicrobial resistance in the three key bacterial pathogens involved in community-acquired respiratory tract infections in Spain: Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes.

Selection of antibiotic-resistant Streptococcus pneumoniae is an inescapable consequence of antibiotic use. The correlation between antibiotic consumption and selection of resistant organisms can be shown at every ecological level: patient, community, region or country. In the case of multiple resistance, the intensity of antibiotic selection is increased. However, different antibiotics may exert different selective powers. Because of this, co-selection of macrolide and β-lactam resistance is an asymmetrical phenomenon: macrolides select more efficiently strains resistant to both macrolides and β-lactams than aminopenicillins. The difference in rates of antibiotic resistance is also influenced by the local spread of susceptible or resistant clones; it is suggested that under mild antibiotic selection, the susceptible organisms that are more fit for host-to-host transmission could be favoured. Subsequent acquisition of resistance in these clones may rapidly increase the prevalence of resistance, and that may lead to an increase in the use of antibiotics. The reasons for antibiotic resistance are mainly the reasons explaining antibiotic consumption. A number of possible sociobiological determinants of antibiotic consumption can be identified: genetic factors in the human populations (for instance, involving different symptomatic types of infection), cultural factors and attitudes of patients towards antibiotics, sociological factors or public health factors, including incidence of other infectious diseases in the human population. Only ‘excess’ in the use of antibiotics should be controlled; for such a purpose, the concept, ‘appropriate demand for antibiotics’ (ADA) is proposed.

Streptococcus pneumoniae resistance to penicillin and erythromycin in relation to β-lactam and macrolide consumption in Spain over 19 years (1979-1997) was studied from resistance data collected by a search of the literature. Antibiotic consumption was expressed in defined daily dosage (DDD)/1000 inhabitants/day. A significant relationship (P < 0.001) between erythromycin resistance (MIC ≥ 1 mg/L) and global macrolide consumption (r = 0.942), as well as between high-level penicillin resistance (MIC ≥ 2 mg/L) and global β-lactam consumption (r = 0.948) was observed. The relationship between erythromycin resistance and macrolide consumption was due mainly to consumption of macrolides taken twice a day (adjusted r² = 0.886). Prevalence of high-level penicillin resistance correlated with consumption of oral cephalosporins (adjusted r² = 0.877); however, there appeared to be no correlation of consumption of oral or parenteral aminopenicillins, narrow-spectrum penicillins or cephalosporins with intermediate-level penicillin resistance (MIC 0.12-1 mg/L). The prevalence of high-level penicillin and of erythromycin resistance were also strongly correlated with each other (r = 0.903, P < 0.001). In addition to global consumption, different categories of resistance (high or intermediate), and the differential capability of antibiotics to select resistance, must be taken into account when studying antibiotic impact on bacterial populations. Although this ecological analysis is not able to demonstrate a causal relationship between antibiotic consumption and development of resistance, it suggests that overuse of certain specific antibiotics is more likely to be related to the increase in drug-resistant strains of S. pneumoniae.

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

ABSTRACTOf Streptococcus pneumoniaeisolates from 17 hospitals, 9.8% were amoxicillin nonsusceptible (MIC ≥ 4 μg/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 (Spain23F-1, Spain6B-2, Spain9V-3, and Spain14-5).

ABSTRACTSix quinolones were tested on 817 consecutive pneumococcal isolates for which ciprofloxacin MICs were high (≥2 μg/ml); the isolates had been collected during two recent Spanish surveillance studies. For strains for which the ciprofloxacin MIC was ≥4 μg/ml, the MICs at which 90% of the isolates tested against gemifloxacin, moxifloxacin, gatifloxacin, sparfloxacin, levofloxacin, and ofloxacin were inhibited were 0.25, 1, 1, 1, 4 and 16 μg/ml, respectively, and the corresponding prevalences of resistance were 0, 1, 4.5, 9.5, 8.4 and 23%. The proportion of isolates for which the ciprofloxacin MIC is high has increased over time.