Sleep variability and fatigue in adolescents: Associations with school-related features.

This study aims to evaluate the influences of sleep duration and sleep variability (SleepV), upon adolescents' school-related situations. The Health Behaviour in School-Aged Children (HBSC) survey is based on a self-completed questionnaire. The participants were 3164 pupils (53.7% girls), attending the 8th and 10th grades, 14.9 years old, and were inquired about subjective sleep duration during the week and weekends, SleepV, fatigue, difficulties in sleep initiation, school achievement, feelings towards schools, pressure with school work and skipping classes. Multiple regression models used, as dependent variables: (a) school achievement, (b) disliking school, (c) pressure with school work and (d) skipping classes, using as independent variables, each of the remaining school-related variables, fatigue, total sleep duration and difficulties in sleep initiation. The average sleep duration in the week and during weekdays was lower than recommended for these age groups, and almost half of students had high SleepV between weekdays and weekends. A logistic model revealed that the absence of SleepV was associated with lower perception of school work pressure, less frequent skipping classes, more infrequent fatigue and more infrequent difficulties in sleep initiation. Poor sleep quality, SleepV and insufficient sleep duration affected negatively school-related variables.

[Multicenter study in southern South America of the in vitro activity of telithromycin in strains with defined resistance phenotypes isolated from community-acquired respiratory infections]. / Estudio multicéntrico en el Cono Sur Americano de la actividad comparativa in vitro de telitromicina en cepas con fenotipos definidos de resistencia asociadas a infecciones respiratorias adquiridas en la comunidad.

Telithromycin was the first ketolide to be approved in Europe and is in the approval process in the United States. It is structurally related to the macrolides; it has a keto group in the C3 position rather than cladinose. A carbamate group is also present at C11-C12. As a result, it has a reduced induction of the MLSB resistance mechanism (erm gene), it is not affected by the flux mechanism (mef gene), it has higher stability at low pH and has increased intrinsic activity compared with clarithromycin and azithromycin. Phase III studies have shown telithromycin to be effective in the treatment of community-acquired upper and lower respiratory tract infections. Its long half-life allows for oral once-daily dosing. From a pharmacokinetic point of view, its activity has been shown to be AUC(24h)/MIC dependent. It is active against bacteria involved in atypical pneumonia. The aim of our study was to determine the activity of telithromycin in isolates with defined resistance phenotypes obtained from community-acquired respiratory tract infections. Twelve centers in Argentina, Chile, Paraguay and Uruguay participated in the study. Each center collected three strains of the following species and resistance patterns: S. pyogenes, S. pneumoniae with resistance or intermediate resistance to oxacillin, erythromycin-resistant S. pneumoniae, clindamycin-resistant S. pneumoniae, oxacillin-susceptible S. aureus, erythromycin-resistant S. aureus, ampicillin-susceptible and -resistant M. catarrhalis and H. influenzae. Agar diffusion susceptibility tests with NeoSensitabs tablets (Rosco, Denmark) were carried out at each center. Isolates were sent to the coordinating center, where MICs were determined using agar microdilution and the Seppala test was used to determine the resistance mechanism to macrolides. The 327 isolates received were susceptible to telithromycin. Eighty percent of the erythromycin-resistant S. pneumoniae isolates were likely resistant due to a flux mechanism, and all those resistant to clindamycin were resistant due to the erm inducible mechanism. Only 20 out of 36 strains of clindamycin-resistant S. pneumoniae and 25 of the 36 ampicillin-resistant H. influenzae strains could be collected, thereby showing that these resistance patterns are less common in the participating South American countries than in other areas. The in vitro activity of telithromycin suggests that it is a promising antibacterial drug for the treatment of community-acquired respiratory tract infections.

Estudio multicéntrico en el Cono Sur Americano de la actividad comparativa in vitro de telitromicina en cepas con fenotipos definidos de resistencia asociadas a infecciones respiratorias adquiridas en la comunidad / Multicenter study in southern South America of the in vitro activity of telithromycin in strains with defined resistance phenotypes isolated from community-acquired respiratory infections

La telitromicina es el primer cetólido aprobado en Europa y en vías de aprobación en Estados Unidos. Su estructura deriva de los macrólidos. Presenta en C3 un grupo ceto en lugar de cladinosa y un sustituyente unido a carbamato en C11-C12. Como consecuencia, tiene menor capacidad de inducción del mecanismo de resistencia MLSB (gen erm), no resulta afectado por el mecanismo de flujo (gen mef), tiene mayor estabilidad en el medio ácido gástrico y presenta una acción intrínseca aumentada en relación a claritromicina y azitromicina. La telitromicina ha demostrado su eficacia en estudios de fase III en infecciones respiratorias de vías altas y bajas adquiridas en la comunidad. Su larga vida media le permite ser administrada por vía oral en una sola dosis diaria. Bajo el punto de vista farmacodinámico se ha demostrado que su actividad es dependiente del cociente AUC24h/CMI. Tiene actividad frente a bacterias productoras de neumonías atípicas. Nuestro interés fue determinar su actividad en cepas seleccionadas según su fenotipo de resistencia, aisladas de infecciones respiratorias. El estudio incluyó 12 centros del Cono Sur Americano. Cada uno de ellos recolectó tres cepas de cada una de las siguientes especies y resistotipos: S. pyogenes, S. pneumoniae resistente o con resistencia intermedia a oxacilina, S. pneumoniae resistente a eritromicina, S. pneumoniae resistente a clindamicina, S. aureus sensible a oxacilina, S. aureus resistente a eritromicina, M. catarrhalis y H. influenzae sensible y resistente a ampicilina. En cada centro se determinó la sensibilidad a diversos antibacterianos por el método de difusión con tabletas NeoSensitabs (Rosco, Dinamarca), y en el Centro Coordinador se determinó la CMI por macrodilución en agar, así como el mecanismo de resistencia a macrólidos por el test de Seppala. Las 327 cepas recibidas fueron sensibles a telitromicina. El 80 por ciento de las cepas de S. pneumoniae resistentes a eritromicina fue resistente, probablemente debido al mecanismo de flujo, y todas las resistentes a la clindamicina lo fueron por erm inducible. Sólo 20 de 36 cepas de S. pneumoniae resistentes a clindamicina pudieron ser recuperadas, así como 25 de 36 H. influenzae resistentes a ampicilina, demostrando que estos resistotipos son menos frecuentes en el Cono Sur Americano que en otras áreas. La telitromicina se presenta como un antibacteriano prometedor para el tratamiento de las infecciones respiratorias adquiridas en la comunidad (AU)

[Escherichia coli eradication from the blader urine by amoxicillin-sulbactam. Intrinsic activity of the inhibitor]. / Erradicación de Escherichia coli de la orina vesical por amoxicilina-sulbactam. Actividad intrínseca del inhibidor.

RATIONALE: At urine concentrations obtained after the oral administration of amoxicillin-sulbactam (500/500 mg) this combination inhibits roughly 90% of Escherichia coli and Proteus mirabilis strains. AIMS: To administer amoxicilin-sulbactam 875/125 mg and to determine: a) minimum inhibitory concentration (MIC) of sulbactam for E. coli and P. mirabilis; b) urine inhibitory titres power (UIT) against amoxicillin-resistant E. coli or P. mirabilis; c) urine concentrations of sulbactam; and to verify whether sulbactam 125 mg as single drug, attains a high enough UIT to support the intrinsic action of the inhibitor; and to compare the activity of amoxicillin-sulbactam and amoxicillin-clavulanate and that of sulbactam and clavulanate. METHODS: Twelve healthy volunteers received a single oral dose of amoxicillin-sulbactam 875/125 mg or amoxicillin-clavulanate 875/125 mg, according to a randomized cross-over design. Urine samples were drawn at: 0 (basal), 2, 4, and 6 hours after dosing. Urine pH, specific gravidity and UIP were assessed. Thirty nine strains isolated from urine samples were used: 30 TEM-1 producing E. coli strains and 3 extended spectrum CTX-M-2 betalactamase-producing E. coli; and 6 P. mirabilis resistant to both combinations. In 6 healthy volunteers, sulbactam 125 mg was administered orally and UIT against E. coli (MIC amoxicillin > 2048 mg/l) was assessed. RESULTS AND DISCUSSION: MIC-90 for amoxicillin plus sulbactam or clavulanate were similar to those for sulbactam or clavulanate alone, without any difference attributable to the chemical composition of the urine. The activity of amoxicillin plus the inhibitors could be due, not only to the inhibition of betalactamase but also to the intrinsic effect of the inhibitor. Both combinations showed an equivalent inhibitory activity. Two-hour UIT remained high for the entire 6-h evaluation period. Sulbactam concentration far exceed sulbactam MIC for the 6h-period, inhibiting urine E. coli. We disagree with the cut-off limit proposed for intermediate values of NCCLS, which, for these antimicrobial are 16/8, a value lower than those obtained in urine samples after the administration of betalactamase inhibitors. This may be an explanation for the beneficial effect of amoxicillin-sulbactam in the recovery of uncomplicated lower urinary tract infections in women when the involved strains were considered resistant by diffusional methods.

Comparative in-vitro activity of levofloxacin against isolates of bacteria from adult patients with community-acquired lower respiratory tract infections.

This study was conducted to evaluate the activity of levofloxacin in comparison with a range of antibacterial agents against recent isolates obtained consecutively from patients with community-acquired pneumonia (CAP) or acute exacerbation of chronic bronchitis (AECB) during the period 1995 to 1996. Susceptibility testing was carried out by either microdilution or the Etest, and interpreted according to NCCLS breakpoints. The activity of levofloxacin was compared with that of amoxycillin, amoxycillin-clavulanate, cefuroxime, cefixime, erythromycin, roxithromycin, clarithromycin, azithromycin, ofloxacin and ciprofloxacin. Clinically significant numbers of bacteria were recovered from 31 CAP and 94 AECB specimens. The predominant bacterial species in the CAP specimens were Streptococcus pneumoniae (21 isolates) and Haemophilus influenzae (four isolates). The AECB isolates mainly consisted of S. pneumoniae (38%), Moraxella catarrhalis (26%), H. influenzae (19%) and Pseudomonas aeruginosa (10%). The overall percentage susceptible of the isolates for each antibiotic was: amoxycillin, 64%; amoxycillin-clavulanate, 89%; cefuroxime, 87%; cefixime, 78%; erythromycin, 85%; roxithromycin, 87%; clarithromycin, 87%; azithromycin, 85%; ofloxacin, 95%; ciprofloxacin, 95%; and levofloxacin, 97%. The activities of levofloxacin and the other agents were also compared against 40 S. pneumoniae isolates, of which 20 were penicillin-non-susceptible, recovered from CAP and AECB specimens during the period 1994 to 1996. These strains were all susceptible to levofloxacin, but only 50% were susceptible to ciprofloxacin and 80% to ofloxacin. Twenty M. catarrhalis, 20 H. influenzae and 20 methicillin-susceptible S. aureus isolates were also all susceptible to levofloxacin. Furthermore, 20 community-acquired P. aeruginosa isolates showed similar percentage susceptible rates to levofloxacin and ciprofloxacin. These in-vitro results suggest that levofloxacin may be useful in the treatment of community-acquired lower respiratory tract infections.

Serum and urinary cefpodoxime levels and time killing curves performed in the urine of children presenting urinary tract infections.

Since resistance to several oral antimicrobials useful for the treatment of pediatric urinary tract infections (UTI) is overwhelming in Argentina, an in vitro investigation was performed testing 400 isolates obtained from urines of children suffering UTI's, 200 collected in 1990 and 200 in 1991. Their susceptibility against oral antimicrobials marketed in Argentina and appropriate for the treatment of UTI was determined by the agar dilution methods. An increase of the resistance to aminopenicillin combined with beta-lactamase inhibitors and to fluoroquinolones was observed comparing the two periods. Cefpodoxime (CPD), cefixime and fluoroquinolones except norfloxacin were the sole oral antimicrobials showing in vitro activity at the 90 per cent level. Unfortunately fluoroquinolones are not yet approved for pediatric use. Consequently we realized an in vitro and in vivo pharmacokinetic study in order to determine CPD activity against E. coli isolated in UTI cases. Five children (6-10 y) showing E. coli UTI infections received 10 mg/kg/d CPD in a single oral daily dose and were treated up to 10 days, 3 had lower UTI and 2 upper UTI. All patients were clinical and bacteriologically cured. Cultures obtained up to 4 weeks after treatment were negative. CPD serum levels at 2 hours after the first dose of treatment showed a median of 2.7 mg/l (2.3-3.4 range). Bactericidal serum titers at the same time against the patients own strain and an E. coli TEM-1 hyperproducer strain (MIC 4,096 mg/l for ampicillin and 0.5 mg/l for CPD) showed a median value of 1/8 against patients strains and 1/2 against the THP strain.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ambulatory esophageal pH monitoring: critical review of methodology: (equipment, reproducibility, standards), clinical importance and personal experience]. / pH-métrie ambulatoire de l'oesophage: revue critique de la méthodologie (appareillage, reproductibilité, normes), intérêt clinique et expérience personnelle.

The authors review the recent literature about the methodology of oesophageal pH monitoring, which has a high sensitivity and a high specificity for assessing gastro-oesophageal reflux. Combined electrodes offer most advantages. Ambulatory recording should be done in hospital under standard conditions (meals), particularly for clinical studies. The best clinical indication is to detect pathological reflux in case of atypical symptoms with negative oesophagoscopy. The authors give their normal values in a series of measurements with two systems as well as their results in a series of cases of oesophagitis of various grades.

Effect of a 2 g cimetidine infusion on twenty-four-hour intragastric pH in critically ill patients.

We evaluated the effect of a cimetidine continuous infusion (2 g in 24 h) on the intragastric pH of 16 critically ill patients (11 men, 5 women, mean age 45 years). During the 24 h pre-trial period and the subsequent 24 h cimetidine infusion, an intragastric combined electrode was placed in the fundus and the pH recorded with a portable pH module and data collection unit. In each patient, the cimetidine infusion induced a prolonged rise of intragastric pH. For all patients the mean percentage of readings above pH 4.0 was 11% pre-trial and 75% during the cimetidine 24 h infusion (p less than 0.001). The percentages of readings above 5.0, 6.0, 7.0 were also significantly higher during infusion than pre-trial in the 16 patients. After starting the cimetidine infusion, there was a concomitant rise of median plasma cimetidine and median intragastric pH in the 7 patients studied. After 6 h, median plasma cimetidine remained above 1 mcg/ml. These results and recent data from the literature suggest that in critically ill patients a continuous infusion of cimetidine might prevent stress ulcerations better than bolus injections by maintaining intragastric pH above 4.0 during longer time intervals.