Serotype distribution and susceptibility of Streptococcus pneumoniae isolates from pleural fluid in Spain from 1997 to 2008.

Trends in serotype incidence and susceptibility (1997 to 2008) of Spanish Streptococcus pneumoniae pleural isolates (n = 831) were explored. Penicillin (oral) nonsusceptibility rates and the incidence of 7-valent pneumococcal conjugate vaccine (PCV-7) serotypes showed decreasing trends (R(2) ≥ 0.600; P ≤ 0.002). The incidence of serotypes 1 and 19A showed increasing trends (R(2) ≥ 0.759; P < 0.001), with no trends for serotype 3. Serotypes 19A, 1, and 3 represented 85% of pediatric isolates in 2008. In serotype 19A, the penicillin nonsusceptibility rate was 82.4% in 2008, associated with amoxicillin and cefotaxime nonsusceptibility in 21.4% of isolates. Inclusion of these serotypes in new vaccines offers the broadest coverage.

Temporal trends of invasive Streptococcus pneumoniae serotypes and antimicrobial resistance patterns in Spain from 1979 to 2007.

Temporal trends of serotypes from invasive pneumococcal disease (IPD) in Spain from 1979 to September 2007 under antibiotic and vaccine pressure were analyzed. A significant trend in pneumococcal conjugate 7-valent vaccine (PCV7) serotypes (except serotype 4) was found, whereby the prevalence increased from the early 1980s and decreased in the 2000s for all but serotype 23F, which began decreasing in the late 1980s. Among the major non-PCV7 serotypes, a significant decrease was observed for serotypes 1, 5, and 7F in the 1980s. From the late 1990s, serotypes 1, 5, 6A, 7F, and 19A increased significantly, while serotypes 3 and 8 showed similar but nonsignificant trends over time. The incidence of IPD cases was 10.7/100,000 for the period 1996 to 2006, with reporting coverage ranging from 18% to 43%. A significant decrease in IPD incidence due to PCV7 serotypes was observed, while the incidence of non-PCV7 serotypes increased, with the consequence that there was no clear pattern in the overall incidence of IPD. Penicillin nonsusceptibility was correlated with the proportion of PCV7 serotypes. Erythromycin nonsusceptibility increased in association with long-half-life macrolide consumption and then decreased in 2004 to 2007. The increase in PCV7 serotypes and antibiotic nonsusceptibility related to antibiotic consumption in the 1980s and 1990s was reversed in the 2000s, probably as a result of PCV7 immunization. The decrease in IPD incidence due to PCV7 serotypes was mirrored by an increase in that of non-PCV7 serotypes. The impact of various preventive/therapeutic strategies on pneumococcal evolution is serotype dependent, and the dynamics remain unpredictable.

Antimicrobial efficacy in vivo of a new formulation of 2-butanone peroxide in n-propanol: comparison with commercial products in a cross-over trial.

The use of hand rub to obtain maximum decrease in bacterial load is important because the reduction needed to avoid transmission is unknown. The monomer of 2-butanone peroxide is a peroxygen derivative with potential biocidal use in hospitals. The aim of this study was to compare the efficacy of hand rub with an alcoholic solution of peroxide 2-butanone versus five antiseptic products, against E. coli K12 (CECT 433) transient flora acquired by hand immersion in a broth culture following the UNE-EN-1500 standard. Isopropanol 60% (control) obtained 99.99% reductions, driving down the bacterial load from 10(6) cfu/mL in the initial inocula to <100 cfu/mL. Products A, B and C (different alcoholic solutions ranging from 65% to 75% with low amounts of biguanidines and/or quaternary ammonium compounds) resulted in significantly lower amounts, reducing initial inocula to approximately 500 cfu/mL. Products D and E (70-75% alcohol solutions containing higher amounts of different quaternary ammonium compounds and triclosan in the case of product E) produced reductions similar to that of isopropanol, with significantly larger reductions than products A, B and C. The product with the solution of 2-butanone peroxide produced the same effect as products D and E with mean reductions of approximately 4log(10) (99.99%), driving the initial inocula down to < or = 100 cfu/mL, despite the low concentration (35%) of propanol in the solution. This novel peroxygen biocide offers high in-vivo cidal activity against acquired E. coli transient flora, offering an alternative to products with higher alcohol concentrations.

Safety profile of cefditoren. A pooled analysis of data from clinical trials in community-acquired respiratory tract infections.

INTRODUCTION: A high number of individuals in the population are exposed to antibiotics for the treatment of respiratory tract infections. It is important to review the adverse events profile related to antibiotic exposure during the clinical development of drugs that are or have been recently included in the therapeutic armamentarium. MATERIAL AND METHODS: Safety data from all 13 clinical trials of cefditoren on community acquired respiratory infections were reviewed. Safety population was defined as all randomized patients with at least one dose intake. Adverse events considered by investigators as related during antibiotic exposure were considered. RESULTS: The overall safety population consisted in 4,592 patients for cefditoren and 2,784 for comparators. Overall reported diarrhoea related to cefditoren administration was significantly higher (p < or = 0.001) than comparators (9.9% vs 6.9%) due to the significant difference in the pooled pharyngotonsillitis studies (8.3% vs 3.2%), while no significant differences in others pathologies were found, with 9.4% (with cefditoren) vs 10.3% (with comparators) in the case of community-acquired pneumonia (CAP). Dyspepsia and abdominal pain were reported as adverse events in < 2.7% patients regardless the treated disease. In females population lower related vaginosis rate was found in cefditoren vs comparators, mainly due to differences among patients treated for sinusitis (4.5% vs 8.1%) and CAP (2.3% vs 5.5%) although differences were not significant (p = 0.017 and p = 0.008, respectively). CONCLUSION: This study analysing reported adverse events from clinical trials showed an adverse events profile of cefditoren similar to those of standard antibiotics used in the treatment of respiratory tract infections.

[Tinidazole: a classical anaerobical drug with multiple potential uses nowadays]. / Tinidazol: un anaerobicida clásico con múltiples usos potenciales en la actualidad.

Tinidazole is a 5-nitroimidazole active in vitro against a wide variety of anaerobic bacteria and protozoa. Tinidazole is an effective treatment against anaerobic microorganisms based on its pharmacokinetic characteristics (C(max) 51 microg/ml, t(1/2) 12.5 h) and its excellent in vitro activity. Its long half-life allows once a day regimens. Tinidazole is as effective as metronidazole in the treatment of infections caused by T. vaginalis, giardiasis and amebiasis and bacterial vaginosis, malaria, odontogenic infections, anaerobic bacterial infections (pelvic inflammatory disease, diabetic foot), surgical prophylaxis (abdominal and hysterectomy) and Helicobacter pylori eradication. Tinidazole was recently approved by the Food and Drug Administration (FDA) for the treatment of infections caused by Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia.

Factors associated with development of nephrotoxicity in patients treated with vancomycin versus daptomycin for severe Gram-positive infections: A practice-based study.

OBJECTIVE: To evaluate nephrotoxicity development in patients treated with vancomycin (VAN) and daptomycin (DAP) for proven severe Gram-positive infections in daily practice. METHODS: A practice-based, observational, retrospective study (eight Spanish hospitals) was performed including patients ≥18 years with a baseline glomerular filtration rate (GFR)>30 mL/min and/or serum creatinine level<2 mg/dL treated with DAP or VAN for >48h. Nephrotoxicity was considered as a decrease in baseline GRF to <50 mL/min or decrease of >10 mL/min from a baseline GRF<50 mL/min. Multivariate analyses were performed to determine factors associated with 1) treatment selection, 2) nephrotoxicity development, and 3) nephrotoxicity development within each antibiotic group. RESULTS: A total of 133 patients (62 treated with DAP, 71 with VAN) were included. Twenty-one (15.8%) developed nephrotoxicity: 4/62 (6.3%) patients with DAP and 17/71 (23.3%) with VAN (p=0.006). No differences in concomitant administration of aminoglycosides or other potential nephrotoxic drugs were found between groups. Factors associated with DAP treatment were diabetes mellitus with organ lesion (OR=7.81, 95%CI:1.39-4.35) and basal creatinine ≥0.9 mg/dL (OR=2.53, 95%CI:1.15-4.35). Factors associated with VAN treatment were stroke (OR=7.22, 95%CI:1.50-34.67), acute myocardial infarction (OR=6.59, 95%CI:1.51-28.69) and primary bacteremia (OR=5.18, 95%CI:1.03-25.99). Factors associated with nephrotoxicity (R2=0.142; p=0.001) were creatinine clearance<80 mL/min (OR=9.22, 95%CI:1.98-30.93) and VAN treatment (OR=6.07, 95%CI:1.86-19.93). Factors associated with nephrotoxicity within patients treated with VAN (R2=0.232; p=0.018) were congestive heart failure (OR=4.35, 95%CI:1.23-15.37), endocarditis (OR=7.63, 95%CI:1.02-57.31) and basal creatinine clearance<80 mL/min (OR=7.73, 95%CI:1.20-49.71). CONCLUSIONS: Nephrotoxicity with VAN was significantly higher than with DAP despite poorer basal renal status in the DAP group.

Has the licensing of respiratory quinolones for adults and the 7-valent pneumococcal conjugate vaccine (PCV-7) for children had herd effects with respect to antimicrobial non-susceptibility in invasive Streptococcus pneumoniae?

OBJECTIVES: The aim of the study was to analyse the evolution of antibiotic non-susceptibility in Spanish invasive Streptococcus pneumoniae after licensure of respiratory-quinolones for adults and 7-valent pneumococcal conjugate vaccine (PCV-7) for immunization of children. METHODS: All invasive pneumococci received in the Reference Laboratory (January 2000-August 2007; n = 12 957 isolates) were serotyped, and susceptibility to penicillin/erythromycin/levofloxacin was determined. Antibiotic consumption and PCV-7 doses/year were provided by IMS and the manufacturer, respectively. RESULTS: In 2000-07, PCV-7 distribution (doses/1000 inhabitants

Efficacy of cefditoren in the treatment of upper respiratory tract infections: a pooled analysis of six clinical trials.

OBJECTIVE: A pooled analysis of all upper respiratory tract infection studies performed with cefditoren (CDN) was performed. METHODS: Studies were prospective, comparative, multicentre and randomised. Comparators were penicillin V (pharyngitis) and cefuroxime or amoxicillin/clavulanate (sinusitis). A total of 1,322 patients were randomized, 1,241 included in intention-to-treat (ITT) and 1,010 in per-protocol populations (PP) in pharyngotonsillitis studies, and 1,819 randomized, 1,726 included in ITT and 1,589 in PP in acute sinusitis studies. RESULTS: No significant differences in pharyngitis clinical response were found (success rates: 89.4 % to 95.3 %). S. pyogenes eradication was higher with cefditoren at end of therapy (EOT) (90.4% vs. 82.7%; p=0.002) and follow-up (84.7% vs. 76.7%; p=0.008), although no statistically significant (p<0.001). In both groups, clinical failures were significantly higher (p<0.001) in patients showing S. pyogenes persistence than in those showing eradication (> or =98.5% vs. 51.4 %). No differences in sinusitis clinical response were found between CDN and comparators both at EOT (80.2% vs. 84.8%) and at end of follow-up (71.2% vs. 77.4%). CONCLUSION: Cefditoren had similar point estimates of clinical efficacy to comparators in pharyngotonsillitis and sinusitis, and a tendency to higher S. pyogenes eradication in pharyngotonsillitis.

Dependence of correlations between antibody titres and opsonophagocytosis on pneumococcal serotype and patient morbidity in pre- and post-pneumococcal vaccination states.

Pre- vs. post-vaccination changes in correlations between IgG concentrations (ELISA titres) and opsonophagocytic activity (OPA) against Streptococcus pneumoniae serotypes 6B, 14 and 23F induced by the 23-valent polysaccharide vaccine were studied in paired serum samples received from elderly individuals, haemodialysed patients and kidney transplant recipients by the Spanish Pneumococcal Reference Laboratory. The pre- and post-vaccination parameters considered were: ELISA and OPA titres and the percentage of subjects with post-vaccination OPA values above the cut-off levels; the correlations between OPA and ELISA (Spearman correlation coefficient, r); and the amount of IgG needed to obtain OPA (beta coefficient). Non-significant pre-vaccination correlations between OPA and ELISA were found. Vaccination increased the correlation coefficient between OPA and ELISA to a statistically significant level for serotypes 6B, 14 and 23F in samples from haemodialysed patients, for serotypes 14 and 23F in samples from elderly individuals, and for none of the serotypes in samples from transplant recipients. In all cases, except for serotype 23 in transplant recipients, vaccination increased the beta coefficient, indicating that lower amounts of IgG were needed to obtain high OPA titres. A globally lower response was obtained for serotype 23 and/or transplant recipients.

In-vitro evaluation of the adhesion to polypropylene sutures of non-pigmented, rapidly growing mycobacteria.

The ability of non-pigmented, rapidly growing mycobacteria (NPRGM) to attach to polypropylene sutures was evaluated using an in-vitro assay. Thirty clinical isolates and five culture collection strains of NPRGM, together with Staphylococcus epidermidis ATCC 35983, were tested. Mycobacterium fortuitum and Mycobacterium chelonae showed the highest attachment ability, which differed significantly from the results obtained with Mycobacterium peregrinum. According to these results, NPRGM are able to attach to polypropylene sutures, and the species implicated most frequently in human infection showed increased levels of attachment in comparison with the other mycobacteria studied.

Wound infections due to Mycobacterium fortuitum after polypropylene mesh inguinal hernia repair.

Mycobacterium fortuitum complex is a group of rapidly growing mycobacteria (RGM). These opportunistic pathogens are frequently associated with infections related to surgical procedures involving biomaterials. Two cases of Mycobacterium fortuitum infection occurred in a prospective study of inguinal hernia prosthesis repairs. These infections differed from those caused by other bacteria in terms of pathogenic mechanisms, clinical manifestation and resistance to both prophylactic and therapeutic antibiotics.

Isolation of Legionella species/serogroups from water cooling systems compared with potable water systems in Spanish healthcare facilities.

Surveillance of Legionella spp. in hospital water systems was performed in forty-four inpatient healthcare facilities in Spain during 2005-2006. A total of 2,341 samples were collected: 470 from cooling systems (cooling towers) and 1,871 from potable water systems. The latter included 211 from cold-water tanks and 260 from hot-water tanks, totalling 471 from central water reservoirs 136 from showers, 1,172 from unfiltered taps and 92 from filtered taps, totalling 1,400 from peripheral points. Temperature, chlorine levels and the presence of Legionella spp. were determined. In all, 373 (15.9%) samples yielded Legionella spp. Significantly higher isolation rates were obtained from cooling towers (23.8%) versus cold- and hot-water tanks (approximately 4.7%), due to the significantly higher number of samples positive for serogroup 1 (19.4 vs 0.9-3.5%). In potable water systems, no differences were found between central water tanks and showers, but significant differences in isolation rates between central water tanks and unfiltered taps were observed (4.7 vs 19.6%) due to differences in non-serogroup 1 L. pneumophila. Filters significantly decreased isolation rates of these serotypes (11 vs 0%). Some seasonal differences were noted, with higher isolation rates in summer for legionella serogroup 1 in cooling systems and for L. pneumophila serogroups 2-14 in potable water systems. In regression models, higher temperatures were associated with colonisation in cooling systems, while lower chlorine levels were associated with colonisation in potable water systems.

Odontogenic bacteria in periodontal disease and resistance patterns to common antibiotics used as treatment and prophylaxis in odontology in Spain.

Resistance in streptococci or Gram-negative bacteria is associated with antibiotic consumption. Scarce information exists on the antibiotic susceptibility of bacterial isolates from patients with periodontitis in countries with high antibiotic consumption, as this is an area in which microbiological testing is not performed in daily practice. The present study was undertaken to explore the susceptibility of bacterial isolates in periodontitis to antibiotics prescribed in odontology in Spain as treatment for local infections or prophylaxis for distant focal infections. Periodontal samples were prospectively collected in 48 patients classified by pocket depth of <4 mm and >or=4 mm. Species were identified by culture, selecting the five most frequent morphotypes per sample, and polymerase chain reaction (PCR). Susceptibility was determined by E-test. A total of 261 isolates were identified: 72.9% patients had Streptococcus oralis; 70.8% Streptococcus mitis; 60.4% Prevotella buccae; 39.6% Prevotella denticola; 37.5% Fusobacterium nucleatum; 35.4% Prevotella intermedia; 25% Capnocytophaga spp.; 23% Veillonella spp.; 22.9% Prevotella melaninogenica and Streptococcus sanguis; and <20% other species. Streptococcus viridans resistance rates were 0% for amoxicillin, approximately 10% for clindamycin, 9-22% for tetracycline, and for azithromycin ranged from 18.2% for S. sanguis to 47.7% for S. mitis. Prevotella isolates were susceptible to amoxicillin-clavulanic acid, with amoxicillin resistance ranging from 17.1% in P. buccae to 26.3% in P. denticola. Metronidazole resistance was <6% in all Prevotella species, while clindamycin resistance ranged from 0 to 21.1%. beta-Lactamase production was positive in 54.1% Prevotella spp., 38.9% F. nucleatum, 30% Capnocytophaga spp., and 10% Veillonella spp. In this study, amoxicillin-clavulanic acid was the most active antibiotic against all species tested, followed by metronidazole in the case of anaerobes.

Reliability of a simple fluoroscopic method to study sagittal plane femorotibial contact changes in total knee arthroplasties during flexion.

Clinical interest in sagittal plane kinematic analysis of the knee undergoing total knee replacement fosters the development of simple, reliable methods to estimate femorotibial contact in a regular clinical setting. In this study, the sagittal femorotibial contact was analysed in lateral X-rays and lateral fluoroscopic views, from extension to knee flexion. Quantitative and categorical data were obtained from these views by two different observers, and compared with data from direct views of the components. Interobserver and intermethod errors for quantitative and categorical data were evaluated based on correlation, kappa coefficient, and Bland-Altman graphs. Interobserver reproducibility of quantitative measurement from fluoroscopic views was r=0.96 while categorical assignment exhibited a kappa coefficient of 0.95. Reproducibility from plain radiographs was not so high, with a kappa coefficient of 0.64. High concordance was also obtained when the method was compared with the direct view of the implant, supporting these measurement techniques. Bland-Altman graphs confirmed the absence of bias in the intermethod comparison. Therefore, with the obvious limitation of rotational assessment, lateral fluoroscopic evaluation enhanced by a simple fitting technique can be used as a valuable tool for clinical evaluation of knee kinematics in the sagittal plane.

[A comparative study of aggression towards Primary Care and Hospital Health professionals in a Madrid health area (2009-2014)]. / Estudio comparativo de las agresiones a sanitarios entre Atención Primaria y Atención Especializada en una zona de Madrid (2009-2014).

INTRODUCTION: The aim of this paper is perform an analysis on the incidents and attacks against medical personnel that occurred in the area covered by the Prevention Service Group, comparing the results in Primary Care (PC) with Hospital Care (HC). MATERIAL AND METHODS: The information available in the database of the regional Madrid Register of Aggressions Conflict Health Worker between 2009 and 2014 was analysed. This included a total of 8,056 workers, of whom 1,605 were from PC. RESULTS: A total of 1,262 incidents have been reported, of which 61.2% took place in HC and 38.8% in PC (32.2 notifications/100,000 inhabitants, or 12.88 incidents/100 hospital workers compared to 168.98 notifications/100,000 inhabitants, or 30.53 incidents/100 PC workers). Nurses in CP have a higher incidence of assaults (47.4%), while in HC it is the physicians (53.1%) (P<.001). In PC the aggressor is usually the patient (56.9%), while in HC it is the relative or companion (45.3%) (P<.001). HC aggressions occur more frequently in emergency departments (35.5%) compared with 63.9% in PC, where they occur in the consulting room (P<.001). CONCLUSIONS: Although it is difficult to make comparisons with previous studies due to methodological differences, a higher incidence of aggression in PC is observed compared with HC. It is necessary to establish improvements in Madrid Register of Aggressions and Conflicts, designed to optimise data quality and use them for preventive purposes.

Infections of implantable cardioverter-defibrillators: frequency, predisposing factors and clinical significance.

The prognosis for patients with ventricular arrhythmias has improved dramatically with the aid of implantable cardioverter-defibrillators (ICDs). Although infection is a serious complication that frequently causes dysfunction and loss of ICDs, the frequency, predisposing risk-factors, and clinical and microbiological features are only partially understood. This study describes a retrospective review of 423 procedures in 278 patients with ICD primary implants and replacements performed at a tertiary-care hospital. Generators were placed in either a pectoral (68%) or abdominal (32%) site, and electrodes were placed transvenously in 97% of the patients. Most (95%) interventions were performed in a one-stage procedure. Infection developed with ten (2.4%) implanted devices. Four cases occurred within 30 days of surgery ('early infections') and six occurred > 1 month after surgery ('late infections'). In univariate analysis, factors associated with the development of an early infection were: two-stage surgery, a sub-costal approach, and abdominal generator placement. In patients with late infections, a significant association was found with trauma or decubitus ulcer in the generator area. Infection presented with local signs without systemic complications. Seven of the ten patients required complete removal of the system.

Criteria for arthroscopic treatment of anterior instability of the shoulder: a prospective study.

We prospectively evaluated 61 patients treated arthroscopically for anterior instability of the shoulder at a mean follow-up of 44.5 months (24 to 100) using the Rowe scale. Those with post-operative dislocation or subluxation were considered to be failures. Logistic regression analysis was used to identify patients at increased risk of recurrence in order to develop a suitable selection system. The mean Rowe score improved from 45 pre-operatively to 86 at follow-up (p < 0.001). At least one episode of post-operative instability occurred in 11 patients (18%), although their stability improved (p = 0.018), and only three required revision. Subjectively, eight patients were dissatisfied. Age younger than 28 years, ligamentous laxity, the presence of a fracture of the glenoid rim involving more than 15% of the articular surface, and post-operative participation in contact or overhead sports were associated with a higher risk of recurrence, and scored 1, 1, 5 and 1 point, respectively. Those patients with a total score of two or more points had a relative risk of recurrence of 43% and should be treated by open surgery.

Diagnostic and prognostic significance of flow cytometry immunophenotyping in patients with leptomeningeal carcinomatosis.

Some patients with epithelial-cell cancers develop leptomeningeal carcinomatosis (LC), a severe complication difficult to diagnose and with an adverse prognosis. This study explores the contribution of flow cytometry immunophenotyping (FCI) to the diagnosis and prognosis of LC. Cerebrospinal fluid (CSF) samples from patients diagnosed with LC were studied using FCI. Expression of the epithelial-cell adhesion molecule (EpCAM) was the criterion used to identify the epithelial cells. To test the diagnostic precision, 144 patients (94 diagnosed with LC) were included. The prognostic value of FCI was evaluated in 72 patients diagnosed with LC and eligible for therapy. Compared with cytology, FCI showed greater sensitivity and negative predictive value (79.79 vs. 50%; 68.85 vs. 51.55%, respectively), but lower specificity and positive predictive value (84 vs. 100%; 90.36 vs. 100%, respectively). The multivariate analysis revealed that the percentage of CSF EpCAM+ cells predicted an increased risk of death (HR: 1.012, 95% CI 1.000-1.023; p=0.041). A cut-off value of 8% EpCAM+ cells in the CSF distinguished two groups of patients with statistically significant differences in overall survival (OS) (p=0.018). This cut-off value kept its statistical significance regardless of the absolute CSF cell-count. The FCI study of the CSF improved the sensitivity for diagnosing LC, but refinement of the technique is needed to improve specificity. Furthermore, quantification of CSF EpCAM+ cells was revealed to be an independent prognostic factor for OS in patients with LC eligible for therapy. An 8% cut-off value contributed to predicting clinical evolution before initiation of therapy.

Glucocorticoid replacement is permissive for rapid eye movement sleep and sleep consolidation in patients with adrenal insufficiency.

There is a well described temporal relation between hormonal secretion and sleep phase, with hormones of the hypothalamic-pituitary-adrenal (HPA) axis possibly playing a role in determining entry into and duration of different sleep stages. In this study sleep features were studied in primary Addison's patients with undetectable levels of cortisol treated in a double blind, randomized, cross-over fashion with either hydrocortisone or placebo supplementation. We found that REM latency was significantly decreased in Addison's patients when receiving hydrocortisone at bedtime, whereas REM sleep time was increased. There was a trend toward an increase in the percentage of time in REM sleep and the number of REM sleep episodes. Waking time after sleep onset was increased, whereas no differences were observed between the two conditions when total sleep time or specific non-REM sleep parameters were evaluated. Our results suggest that in Addison's patients, cortisol plays a positive, permissive role in REM sleep regulation and may help to consolidate sleep. These effects may be mediated either directly by the central effects of glucocorticoids and/or indirectly through CRH and/or ACTH.

Stimulant and anticataplectic effects of reboxetine in patients with narcolepsy: a pilot study.

STUDY OBJECTIVES: To investigate potential stimulant and anticataplectic effects of 10 mg reboxetine in patients diagnosed with narcolepsy. DESIGN: 12 patients were treated for a 2-week period with 10 mg reboxetine under open conditions. The dosage of reboxetine was gradually increased between Day 1 and Day 9. Outcome parameters consisted of nightime polysomnography (PSG), Multiple Sleep Latency Test (MSLT), Epworth Sleepiness Scale (ESS), Visual Analog Scale for Sleepiness (VAS), Ullanlinna Narcolepsy Scale (UNS), and the Beck Depression Inventory (BDI). SETTING: Sleep Disorders Clinic at a University Hospital. PATIENTS: 12 patients meeting ICSD-criteria for narcolepsy. INTERVENTIONS: Pharmacological treatment with reboxetine. RESULTS: Following treatment for two-weeks, a significant improvement in daytime sleepiness could be observed, as reflected by a mean decrease of 48.6% on the Epworth Sleepiness Scale and a mean increase of 54.7% in sleep latency on the MSLT. Furthermore, a significant reduction in the cataplexy subscore of the Ullanlinna Narcolepsy Scale and in REM-sleep was found. CONCLUSIONS: Our results suggest that reboxetine exerts stimulant and anticataplectic effects in narcolepsy. Contrary to previous thinking, by which stimulant action would require dopaminergic facilitation, noradrenergic mechanisms might be relevant to the control of wakefulness.