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Teresa del Rosal,1,2 Ana Méndez-Echevarría,1,2 Cesar Garcia-Vera,3 Luis Escosa-Garcia,1,2 Martin Agud,1 Fernando Chaves,4 Federico Román,5 José Gutierrez-Fernandez,6 Enrique Ruiz de Gopegui,7 Guillermo Ruiz-Carrascoso,8 Maria del Carmen Ruiz-Gallego,9 Albert Bernet,10 Sara Maria Quevedo,11 Ana Maria Fernández-Verdugo,12 Jesús Díez-Sebastian,13 Cristina Calvo1,2 On behalf of the COSACO Study Group1Pediatric Infectious and Tropical Diseases Department, Hospital Universitario La Paz, Madrid, Spain; 2Translational Research Network in Pediatric Infectious Diseases (RITIP), Institute for Health Research IdiPAZ, Madrid, Spain; 3“José Ramón Muñoz Fernández” Health Care Center, Aragón Health Service, Zaragoza, Spain; 4Department of Clinical Microbiology, Hospital Universitario 12 de Octubre, Madrid, Spain; 5Laboratory of Nosocomial Infections, Department of Bacteriology, CNM, Instituto de Salud Carlos III, Madrid, Spain; 6Department of Microbiology, Hospital Virgen de las Nieves, Granada, Spain; 7Department of Clinical Microbiology, Hospital Universitari Son Espases. Servicio de Microbiología, Palma de Mallorca, Spain; 8Department of Clinical Microbiology, Hospital Universitario La Paz, Madrid, Spain; 9Department of Microbiology, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 10Section of Microbiology, Arnau de Vilanova University Hospital, Lleida, Spain; 11Department of Microbiology, Hospital Universitario Severo Ochoa, Leganes, Spain; 12Department of Microbiology, Hospital Universitario Central de Asturias, Oviedo, Spain; 13Department of Preventive Medicine, Hospital Universitario La Paz, Madrid, SpainCorrespondence: Ana Méndez-Echevarría Pediatric Infectious and Tropical Diseases Department. Hospital La Paz-IdiPAZ, Paseo de la Castellana 261, Madrid 28046, SpainTel/Fax +34-917277479Email amendezes@yahoo.esObjective: To assess the prevalence and risk factors for S. aureus and methicillin-resistant S. aureus (MRSA) nasal colonization in Spanish children.Methods: Cross-sectional study of patients < 14 years from primary care centers all over Spain. Clinical data and nasal aspirates were collected from March to July 2018.Results: A total of 1876 patients were enrolled. Prevalence of S. aureus and MRSA colonization were 33% (95% CI 30.9– 35.1) and 1.44% (95% CI 0.9– 2), respectively. Thirty-three percent of the children (633/1876) presented chronic conditions, mainly atopic dermatitis, asthma and/or allergy (524/633). Factors associated with S. aureus colonization were age ≥ 5 years (OR 1.10, 95% CI 1.07– 1.12), male sex (OR 1.43, 95% CI 1.17– 1.76), urban setting (OR 1.46, 95% CI 1.08– 1.97) and the presence of asthma, atopic dermatitis or allergies (OR 1.25; 95% CI: 1.093– 1.43). Rural residence was the only factor associated with MRSA colonization (OR 3.62, 95% CI 1.57– 8.36). MRSA was more frequently resistant than methicillin-susceptible S. aureus to ciprofloxacin [41.2% vs 2.6%; p< 0.0001], clindamycin [26% vs 16.9%; p=0.39], and mupirocin [14.3% vs 6.7%; p=0.18]. None of the MRSA strains was resistant to tetracycline, fosfomycin, vancomycin or daptomycin.Conclusions: The main risk factors for S. aureus colonization in Spanish children are being above five years of age, male gender, atopic dermatitis, asthma or allergy, and residence in urban areas. MRSA colonization is low, but higher than in other European countries and is associated with rural settings.Keywords: S. aureus, MRSA, child, colonization

Summary: The spread of meticillin-resistant Staphylococcus aureus (MRSA) is a major problem for both acute care hospitals and among residents in long term care facilities (LTCFs). We performed a cohort study to assess the natural history of MRSA colonisation in LTCF residents. Two cohorts of residents (231 MRSA carriers and 196 non-carriers) were followed up for an 18 month period, with cultures of nasal and decubitus ulcers performed every six months. In the MRSA carrier cohort, 110 (47.8%) residents had persistent MRSA colonisation for six months or longer, 44 (19.0%) had transient colonisation and nine (3.9%) were intermittently colonised. No risk factors for persistent MRSA colonisation could be determined. The annual incidence of MRSA acquisition was around 20% [95% confidence interval (CI): 14.3–25.5]. Antibiotic treatment was independently associated with MRSA acquisition (odds ratio: 2.27; 95% CI: 1.05–4.88; P =0.03). Just two clones were distinguishable by pulsed-field gel electrophoresis and multilocus sequence typing: CC5-MRSA IV, which is widely disseminated in Spanish hospitals, and ST22-MRSA IV. This study adds to the knowledge of the epidemiology of MRSA in community LTCFs, which are important components of long term care in Spain. [ABSTRACT FROM AUTHOR]

From January 2000 to June 2002, 24 Staphylococcus aureus isolates were recovered from decubitus ulcers of patients in a geriatric institution, of which 17 (70.8%) were methicillin-resistant S. aureus (MRSA). Antibiotic resistance and DNA macrorestriction (pulsed-field gel electrophoresis; PFGE) patterns of the MRSA isolates were compared with a collection of 161 MRSA isolates from patients admitted to the institution's reference hospital. PFGE revealed the presence of five clonal types (found also in hospitalised patients) among the 17 MRSA isolates. The findings suggest nosocomial acquisition of the MRSA strains by five patients, with subsequent dissemination of the strains within the institution. The high rate of MRSA highlights the need for epidemiological analysis to control the dissemination of MRSA in long-term care facilities. [ABSTRACT FROM AUTHOR]

Purpose Describe and quantify the effect of myopic LASIK on corneal biomechanics considering the preoperative hysteresis Methods In 126 eyes with myopia and myopic astigmatism the Ocular Response Analyzer (ORA) was used to measure corneal hysteresis (CH), corneal resistance factor (CRF), Goldman‐correlated intraocular pressure (IOPg), and corneal‐compensated IOP (IOPcc) before and 3 months after LASIK. We divided the sample into three groups based on the values of CH (mmHg) preoperative: G1 (30 eyes) CH 7.5‐9.5, G2 (66 eyes) 9.5‐11.5, G3 (30 eyes) >11.5. Results After LASIK, there was a reduction in mean CH (ΔCH; G1:0.98 G2:1.51 G3: 1.81), CRF (ΔCRF; G1:2.35 G2:2.46 G3:2.83), IOPcc (ΔIOPcc; G1: 3.26 G2:1.74 G3: 1.75) and IOPg (ΔIOPg; G1: 5.01 G2:3.92 G3: 4.31) in three groups. However, there was no statistically significant difference between the groups in the percentage change of CH (G1: 13% G2: 14.6% G3: 15%) and CRF (G1: 25% G2: 23% G3: 24%). While the percentage decrease in IOPcc (G1: 18% G2: 10.5% G3: 11.5%) and IOPg (G1: 31% G2: 25% G3: 27%) was statistically different. Was find a significant correlation between ΔCH and ΔCRF with microns of ablation (r =‐ 0.406, r =‐ 0.616) and spherical equivalent (r = 0.405, r =‐ 0.599). Conclusion LASIK surgery decreases the corneal hysteresis and corneal resistance factor. The percentage decline of corneal hysteresis and corneal resistance factor after LASIK surgery was no different between the three groups based on the preoperative hysteresis. Although there is a correlation between variations of the CH and CRF, with microns of ablation and the refractive error corrected. [ABSTRACT FROM AUTHOR]

Purpose To evaluate by Optical Coherence Tomography (OCT) the presence of peripapillary retinal nerve fiber layer (RNFL) damage in patients suffering from multiple sclerosis (MS). Methods Prospective study of the peripapillary RNFL measured by Stratus OCT in 116 eyes from 58 patients divided in four groups: non optic neuritis MS patients (non ON‐MS): 35 eyes; optic neuritis MS patients (ON‐MS): 20 eyes; fellow eye optic neuritis MS patients (FE‐ON‐MS): 29 eyes; healthy controls (HC): 32 eyes. Results The peripapillary RNFL thickness is lowered not only in eyes from patients with MS and ON (81'6±20'6µm), but also in their fellow eye 92'9±13'6µm), and even in eyes from MS patients without previous history of ON (101'0±11'2µm). p< 0,05, ANOVA test. Conclusion OCT proved to be a useful device in the diagnosis of axonal damage in patients with MS. [ABSTRACT FROM AUTHOR]

Purpose To describe the modifications produced in the anterior segment of the eye after placing an encircling scleral buckling (SB) in terms of corneal morphology, biomechanics and intraocular pressure. Methods A prospective study of 15 eyes with rhegmatogenous retinal detachment who underwent pars plana vitrectomy combined with a scleral buckle (PPV/SB), and 12 eyes with vitreous hemorrhage treated with PPV alone. We measured preoperatively and 1‐month after surgery the corneal biomechanical properties using the Ocular Response Analyzer (ORA), including corneal hysteresis (CH), corneal resistance factor (CRF), intraocular pressure (IOPg), and corneal compensated IOP (IOPcc). Moreover, we defined the corneal morphology by 4 parameters provided by the topographer Orbscan IIz: mean corneal power (dioptres), standard deviation, thinnest point (µm), and anterior chamber depth (ACD) (mm). Results Mean CH values were significantly diminished following PPV/SB (p=0.003). We found no significant changes in CRF. IOPg and IOPcc mean values were significantly increased only in the PPV/SB group (p=0.019 and p=0.010, respectively) but not in PPV group (p=0.715 and p=0.273, respectively). In PPV/SB group, IOPcc mean values were significantly higher than IOPg before (p=0.001) and after surgery (p=0.003), but not in the other group. None of the morphological parameters were modified after surgery in any of the two study groups (p>0.05) Conclusion Anterior segment morphology was not modified after placing a SB. Corneal biomechanical properties showed a reduction in CH, probably due to a vascular constriction and reduction of the eye compliance. PPV might be considered a less invasive approach for the repair of noncomplex retinal detachments than PPV/SB. [ABSTRACT FROM AUTHOR]

Purpose To describe a persistent entrapment of triamcinolone acetonide behind the crystalline lens (Berger´s space), a rare complication of intravitreal triamcinolone acetonide (IVTA) injection, and its successful drainage using a Nd:YAG laser anterior hyaloidotomy. Methods A case report providing a new indication of Nd:YAG laser, performing an anterior hyaloidotomy to release triamcinolone acetonide entrapped between the crystalline lens and the anterior hyaloids membrane following an IVTA injection. Results A 66‐year‐old male suffering from diffuse diabetic macular edema in his left eye was treated with an IVTA injection. The following day he complained from sudden loss of vision. Visual acuity dropped from 20/80 to "hand motion", and biomicroscopy showed a drug entrapment in the Berger´space. After a couple of weeks of observation treatment, Nd:YAG laser anterior hyaloidotomy was performed. One week later, slit lamp examination of the retrolental space revealed the complete disappearance of triamcinolone, visual acuity recovered to 20/50, remaining the means transparent. Conclusion We describe a minimally invasive, quick, simple and effective outpatient procedure to release rests of triamcinolone acetonide entrapped behind the crystalline lens. This indication of Nd:YAG laser has never been described before. [ABSTRACT FROM AUTHOR]

Purpose To determine in vivo corneal biomechanical properties in patients without refractive errors and patients with moderate‐high myopic and hyperopic spherical refractive errors. Methods A comparative study was carried out to measure Corneal Hysteresis (CH, mmHg) and Corneal Resistance Factor (CRF, mmHg) of 384 eyes of 201 patients classified in four groups. Moderate myopia (< 6 D, n=203), high myopia (> 6 D, n=43), moderate‐high hyperopia (> 2 D, n=62), and emetropic group (n=76). Corneal compensated intraocular pressure (IOPcc),and Goldman correlated intraocular pressure (IOPg) were also studied. Central corneal thickness (CCT, microns) was measured by ultrasonic pachymetry. Patients with ocular pathology or astigmatism greater than the spherical refractive error were not considered. A multiple‐comparison analysis was made to establish differences among the groups. Results Mean values were: CH= 10.59±1.52, CRF= 10.52±1.69 and CCT= 556.3 for the moderate myopia group, CH=10.04 ±1.55, CRF=10.23 ±1.82 and CCT=543.75 for the high myopia group, CH=11.16 ±1.88, CRF=10.69 ±2.07 and CCT=555.43 for the hyperopia group, CH=10.66 ±1.30 , CRF=10.48±1.14 and CCT=558.10 for the control group. Although these results of the biomechanical parameters showed higher values corresponding to the hyperopia group and lower to the myopia group, these differences were not statistically significant. Conclusion CH and CRF are greater in hyperopic patients in comparison with myopic and emetropic eyes. We do not find statistical significant differences between moderate myopia and high myopia. There are significant differences in CH between the high myopia and the hyperopia groups. [ABSTRACT FROM AUTHOR]

Background: The selection of patients in whom endoscopic third ventriculostomy (ETV) can be effective remains poorly defined. The ETV success score (ETVSS) and the presence of bowing of the third ventricle have been identified as independent factors for predicting success, each with limitations. The objective of this study is to elaborate a combined predictive model to predict ETV success in a mixed cohort of patients., Methods: Demographic, intraoperative, postoperative, and radiologic variables were analyzed in all ventriculostomies performed consecutively at a single institution from December 2004 to December 2022. Qualitative and quantitative measurements of preoperative, immediate, and late postoperative magnetic resonance imaging were conducted. Univariate analysis and logistic regression models were performed., Results: 118 ETVs were performed in the selected period. Of these procedures, 106 met the inclusion criteria. The overall success rate was 71.7%, with a median follow-up of 3.64 years (interquartile range, 1.06-5.62). The median age was 36.1 years (interquartile range, 11.7-53.5). 35.84% were children (median, 7.81 years). Among the 80 patients with third ventricle bowing, the success rate was 88.8% (P < 0.001). Larger third ventricle dimensions on preoperative mid-sagittal magnetic resonance imaging were associated with increased ETV success. The model with the best receiver operating characteristic curves, with an area under the curve of 0.918 (95% confidence interval, 0.856-0.979) includes sex, ETVSS, presence of complications, and third ventricle bowing., Conclusions: The presence of bowing of the third ventricle is strongly associated with a higher ETV success rate. However, a combined predictive model that integrates it with the ETVSS is the most appropriate approach for selecting patients for ETV., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In December 2022, an alert was published in the UK and other European countries reporting an unusual increase in the incidence of Streptococcus pyogenes infections. Our aim was to describe the clinical, microbiological, and molecular characteristics of group A Streptococcus invasive infections (iGAS) in children prospectively recruited in Spain (September 2022-March 2023), and compare invasive strains with strains causing mild infections. One hundred thirty isolates of S. pyogenes causing infection (102 iGAS and 28 mild infections) were included in the microbiological study: emm typing, antimicrobial susceptibility testing, and sequencing for core genome multilocus sequence typing (cgMLST), resistome, and virulome analysis. Clinical data were available from 93 cases and 21 controls. Pneumonia was the most frequent clinical syndrome (41/93; 44.1%), followed by deep tissue abscesses (23/93; 24.7%), and osteoarticular infections (11/93; 11.8%). Forty-six of 93 cases (49.5%) required admission to the pediatric intensive care unit. iGAS isolates mainly belonged to emm 1 and emm 12; emm 12 predominated in 2022 but was surpassed by emm 1 in 2023. Spread of M1 UK sublineage (28/64 M1 isolates) was communicated for the first time in Spain, but it did not replace the still predominant sublineage M1 global (36/64). Furthermore, a difference in emm types compared with the mild cases was observed with predominance of emm 1, but also important representativeness of emm 12 and emm 89 isolates. Pneumonia, the most frequent and severe iGAS diagnosed, was associated with the spe A gene, while the ssa superantigen was associated with milder cases. iGAS isolates were mainly susceptible to antimicrobials. cgMLST showed five major clusters: ST28-ST1357/ emm 1, ST36-ST425/ emm 12, ST242/ emm 12.37, ST39/ emm 4, and ST101-ST1295/ emm 89 isolates., Importance: Group A Streptococcus (GAS) is a common bacterial pathogen in the pediatric population. In the last months of 2022, an unusual increase in GAS infections was detected in various countries. Certain strains were overrepresented, although the cause of this raise is not clear. In Spain, a significant increase in mild and severe cases was also observed; this study evaluates the clinical characteristics and the strains involved in both scenarios. Our study showed that the increase in incidence did not correlate with an increase in resistance or with an emm types shift. However, there seemed to be a rise in severity, partly related to a greater rate of pneumonia cases. These findings suggest a general increase in iGAS that highlights the need for surveillance. The introduction of whole genome sequencing in the diagnosis and surveillance of iGAS may improve the understanding of antibiotic resistance, virulence, and clones, facilitating its control and personalized treatment., Competing Interests: The authors declare no conflict of interest.

Objectives: To assess the microbiological characteristics of Escherichia coli causing healthcare-associated bacteraemia of urinary origin (HCA-BUO) in Spain (ITUBRAS-2 project), with particular focus on ESBL producers and isolates belonging to ST131 high-risk clone (HiRC). Clinical characteristics and outcomes associated with ST131 infection were investigated., Methods: A total of 222 E. coli blood isolates were prospectively collected from patients with HCA-BUO from 12 tertiary-care hospitals in Spain (2017-19). Antimicrobial susceptibility and ESBL/carbapenemase production were determined. ST131 subtyping was performed. A subset of 115 isolates were selected for WGS to determine population structure, resistome and virulome. Clinical charts were reviewed., Results: ESBL-producing E. coli prevalence was 30.6% (68/222). ST131 represented 29.7% (66/222) of E. coli isolates and accounted for the majority of ESBL producers (46/68, 67.6%). The C2/H30-Rx subclone accounted for most ST131 isolates (44/66) and was associated with CTX-M-15 (37/44) and OXA-1 enzymes (27/44). Cluster C1-M27 was identified in 4/10 isolates belonging to subclade C1/H30-R1 and associated with CTX-M-27. Additionally, ST131 isolates showed a high content of other acquired resistance genes, and clade C/ST131 isolates carried characteristic QRDR mutations. They were categorized as uropathogenic E. coli and had higher aggregate virulence scores. ST131 infection was associated with more complex patients, prior use of cephalosporins and inadequate empirical treatment but was not associated with worse clinical outcomes., Conclusions: ST131 HiRC is the main driver of ESBL-producing E. coli causing HCA-BUO in Spain, mainly associated with the expansion of subclade CTX-M-15-C2/H30-Rx and the emergence of CTX-M-27-C1/H30-R1 (Cluster C1-M27)., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: To evaluate the effect of fingolimod in visual function and neuroretinal structures in patients with multiple sclerosis (MS) for a period of 1 year., Methods: This longitudinal and observational cohort study included 78 eyes of 78 patients with MS treated with fingolimod. All subjects were evaluated every 3 months during 12 months and compared with 32 patients treated with interferon beta. All patients were examined for high-contrast and low-contrast (2.5% and 1.25%) visual acuity (VA), contrast sensitivity vision (CSV) (using Pelli-Robson and CSV-1000E tests), color vision (Farnsworth D-15 and L'Anthony D-15 desaturated tests), and retinal structural measurements (retinal nerve fiber layer [RNFL] and ganglion cell layer [GCL] thickness) using optical coherence tomography (OCT) technology., Results: Patients with MS treated with fingolimod for a period of 1 year showed significant reduction in 100% and 1.25% contrast VA (P = 0.009 and 0.008, respectively), an alteration of contrast sensitivity and color perception (Pelli-Robson test, CSV-1000E test, Farnsworth D-15 desaturated test, and L'Anthony D-15 desaturated test; P < 0.001), GCL thickness reduction (P = 0.007), and an average macular central thickness increase of 2.6 μm (P = 0.006). Patients with MS treated with interferon beta did not show significant changes in visual function tests neither in macular thickness measurements, but they showed a significant reduction in GCL and RNFL thicknesses. The reduction in neuroretinal structures observed by OCT was significantly higher in the interferon-beta group, but patients treated with fingolimod showed a significant increase in macular central thickness and a reduction in low contrast vision (P < 0.001)., Conclusions: Patients with MS treated with fingolimod and with no clinically observable macular edema show a significant change in visual function parameters and average macular central thickness increase compared with those treated with interferon beta. These findings are probably due to subclinical macular edema produced by fingolimod, which might be considered as an indicator for pharmacovigilance of sphingosine-1-phosphate inhibitors to be improved., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

Introduction: Healthcare-associated (HCA) infections represent a growing public health problem. The aim of this study was to compare community-onset healthcare associated (CO-HCA) bacteremic urinary tract infections (BUTI) and hospital-acquired (HA)-BUTI with special focus on multidrug resistances (MDR) and outcomes., Methods: ITUBRAS-project is a prospective multicenter cohort study of patients with HCA-BUTI. All consecutive hospitalized adult patients with CO-HCA-BUTI or HA-BUTI episode were included in the study. Exclusion criteria were: patients < 18 years old, non-hospitalized patients, bacteremia from another source or primary bacteremia, non-healthcare-related infections and infections caused by unusual pathogens of the urinary tract. The main outcome variable was 30-day all-cause mortality with day 1 as the first day of positive blood culture. Logistic regression was used to analyze factors associated with clinical cure at hospital discharge and with receiving inappropriate initial antibiotic treatment. Cox regression was used to evaluate 30-day all-cause mortality., Results: Four hundred forty-three episodes were included, 223 CO-HCA-BUTI. Patients with CO-HCA-BUTI were older (p < 0.001) and had more underlying diseases (p = 0.029) than those with HA-BUTI. The severity of the acute illness (Pitt score) was also higher in CO-HCA-BUTI (p = 0.026). Overall, a very high rate of MDR profiles (271/443, 61.2%) was observed, with no statistical differences between groups. In multivariable analysis, inadequate empirical treatment was associated with MDR profile (aOR 3.35; 95% CI 1.77-6.35), Pseudomonas aeruginosa (aOR 2.86; 95% CI 1.27-6.44) and Charlson index (aOR 1.11; 95% CI 1.01-1.23). Mortality was not associated with the site of acquisition of the infection or the presence of MDR profile. However, in the logistic regression analyses patients with CO-HCA-BUTI (aOR 0.61; 95% CI 0.40-0.93) were less likely to present clinical cure., Conclusion: The rate of MDR infections was worryingly high in our study. No differences in MDR rates were found between CO-HCA-BUTI and HA-BUTI, in the probability of receiving inappropriate empirical treatment or in 30-day mortality. However, CO-HCA-BUTIs were associated with worse clinical cure., (© 2021. The Author(s).)

Objective: To characterize the Staphylococcus aureus strains colonizing healthy Spanish children., Methods: Between March and July 2018, 1876 Spanish children younger than 14 years attending primary healthcare centers were recruited from rural and urban areas. Staphylococcus aureus colonization of the anterior nostrils was analyzed. MecA and mecC genes, antibiotic susceptibility, and genotyping according to the spa were determined in all strains, and the following toxins were examined: Panton-Valentine leucocidin (pvl), toxic shock syndrome toxin (tst), and exfoliative toxins (eta, etb, etd). Multilocus sequence typing (MLST) and staphylococcal cassette chromosome (SCCmec) typing were performed on methicillin-resistant Staphylococcus aureus (MRSA) strains, as well as pulsed-field gel electrophoresis (PFGE)., Results: 619 strains were isolated in 1876 children (33%), and 92% of them were sent for characterization to the Spanish National Centre of Microbiology (n = 572). Twenty (3.5%) of these strains were mecA-positive. Several spa types were detected among MRSA, being t002 the most frequently observed (30%), associating with SCCmec IVc. Among MSSA, 33% were positive for tst, while only 0.73% were positive for pvl. The 20 MRSA strains were negative for pvl, and 6 (30%) harbored the tst gene., Conclusions: methicillin-resistant Staphylococcus aureus nasal colonization in Spanish children is rare, with t002 being the most observed spa type, associated with SCCmec IVc. None of the MRSA strains produced pvl, but up to 30% of S. aureus strains were positive for tst., (© 2021 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Background: Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality., Methods: This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009-15. We evaluated the association between β-lactam plus aminoglycoside or quinolone combination therapy versus β-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy., Results: Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64-1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens., Conclusions: In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although β-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy., Methods: A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with β-lactam monotherapy during 2009-2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable., Results: Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52-2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67-2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007)., Conclusions: No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to evaluate the effects of deep brain stimulation of the subthalamic nucleus (DBS-SN) on cognitive function in patients with Parkinson's disease (PD) 5 years after surgery., Material and Methods: We conducted a prospective study including 50 patients with PD who underwent DBS-SN (62.5% were men; mean age of 62.2±8.2 years; mean progression time of 14.1±6.3 years). All patients were assessed before the procedure and at one year after surgery; 40 patients were further followed up until the 5-year mark. Follow-up assessments included the following neuropsychological tests: Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (MDRS), letter-number sequencing of the WAIS-III (WAIS-III-LN), clock-drawing test, Rey auditory verbal learning test (RAVLT), Benton Visual Retention Test (BVRT), Judgment of Line Orientation (JLO) test, FAS Phonemic Verbal Fluency Test, Stroop test, and the Montgomery-Asberg Depression Rating Scale (MADRS)., Results: Patients were found to score lower on the MMSE (-0.89%), clock-drawing test (-2.61%), MDRS (-1.72%), and especially phonemic (-13.28%) and sematic verbal fluency tests (-12.40%) at one year after surgery. Delayed recall on the RAVLT worsened one year after the procedure (-10.12%). At 5 years, impairment affected mainly verbal fluency; scores decreased an additional 16.10% and 16.60% in semantic and phonemic verbal fluency, respectively. Moderate decreases were observed in immediate recall (-16.87%), WAIS-III-LN (-16.67%), and JLO test (-11.56%)., Discussion: In our sample, DBS-SN did not result in global cognitive impairment 5 years after surgery. Verbal function was found to be significantly impaired one year after the procedure. Impaired learning and visuospatial function may be attributed to degeneration associated with PD., (Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most important markers for the follow-up of patients infected with these viruses. Microbiology laboratories have a variety of tools to ensure the accuracy of the results obtained, including external quality control programmes such as that of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). This article summarises the results of the 2016 SEIMC External Quality Control Programme for HIV-1, HCV, and HBV viral loads., Methods and Results: In the HIV-1 programme, a total of 5 standards were sent. One standard consisted of seronegative human plasma, while the remaining 4 contained plasma from 3 different viremic patients, in the range of 2-5 log 10 copies/mL. A significant proportion of the laboratories (40% on average) obtained values out of the accepted range (mean ± 0.25 log 10 copies/mL), depending on the standard and on the method used for quantification. The HBV and HCV programme consisted of 2 standards with different viral load contents. Most of the participants, 86.5% in the case of HCV and 85.6% in the case of HBV, obtained results that were all within the accepted range (mean ± 1.96 SD log 10 UI/mL)., Conclusions: Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory. Due to the marked interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow-up. Supplement information: This article is part of a supplement entitled «SEIMC External Quality Control Programme. Year 2016», which is sponsored by Roche, Vircell Microbiologists, Abbott Molecular and Francisco Soria Melguizo, S.A. © 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

Staphylococcus aureus bacteremia (SAB) is associated with high morbidity and mortality, which varies depending on the source of infection. Nevertheless, the global molecular epidemiology of SAB and its possible association with specific virulence factors remains unclear. Using DNA microarrays, a total of 833 S. aureus strains (785 SAB and 48 colonizing strains) collected in Spain over a period of 15 years (2002-2017) were characterized to determine clonal complex (CC), agr type and repertoire of resistance and virulence genes in order to provide an epidemiological overview of CCs causing bloodstream infection, and to analyze possible associations between virulence genes and the most common sources of bacteremia. The results were also analyzed by acquisition (healthcare-associated [HA] and community-acquired [CA]), methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains, and patient age (adults vs. children). Our results revealed high clonal diversity among SAB strains with up to 28 different CCs. The most prevalent CCs were CC5 (30.8%), CC30 (20.3%), CC45 (8.3%), CC8 (8.4%), CC15 (7.5%), and CC22 (5.9%), which together accounted for 80% of all cases. A higher proportion of CC5 was found among HA strains than CA strains (35.6 vs. 20.2%, p < 0.001). CC5 was associated with methicillin resistance (14.7 vs. 79.4%, p < 0.001), whereas CC30, CC45, and CC15 were correlated with MSSA strains ( p < 0.001). Pathogen-related molecular markers significantly associated with a specific source of bacteremia included the presence of sea, undisrupted hlb and isaB genes with catheter-related bacteremia; sed, splE , and fib genes with endocarditis; undisrupted hlb with skin and soft tissue infections; and finally, CC5, msrA resistance gene and hla gene with osteoarticular source. Our study suggests an association between S. aureus genotype and place of acquisition, methicillin resistance and sources of bloodstream infection, and provides a valuable starting point for further research insights into intrinsic pathogenic mechanisms involved in the development of SAB.

Objective: To assess changes in the retinal nerve fiber layer (RNFL) and macula in subjects with cardiovascular risk factors or subclinical ischemia., Design: Prospective and observational study., Methods: A total of 152 healthy men underwent cardiovascular examination, including quantification of subclinical atheroma plaques by artery ultrasound scans, blood analysis, and a complete ophthalmic evaluation, including spectral-domain optical coherence tomography. The variables registered in cardiovascular examination were quantification of classic major risk factors, subclinical atheroma plaques by artery ultrasound scans, and analytical records. The ophthalmic evaluation registered RNFL and macular thickness., Results: Mean subject age was 51.27±3.71 years. The 40 subjects without classic cardiovascular risk factors did not show differences in RNFL and macular thicknesses compared with the 112 subjects with at least one risk factor (except in sector 9 that showed higher thicknesses in subjects with ≥1 risk factor). Comparison between the group of subjects with and without atheroma plaques revealed no differences in RNFL and macular thicknesses. The sub-analysis of subjects with subclinical atheroma plaques in the common carotid artery revealed a significant reduction in central macular thickness in the left eye compared with the right eye (p = 0.016), RNFL in the superior quadrant (p = 0.007), and the 11 o'clock sector (p = 0.020). Comparison between smokers and nonsmokers revealed that smokers had significant thinning of the central macular thickness (p = 0.034), the nasal RNFL quadrant (p = 0.006), and the 3 and 5 o'clock sectors (p = 0.016 and 0.009)., Conclusions: Classic cardiovascular risk factors do not cause RNFL or macular thickness reduction, but tobacco smoking habit reduces nasal RNFL thickness. Subclinical atherosclerosis in the common carotid artery associates a reduction in central macular and nasal RNFL quadrant thicknesses in the left eye compared with the right eye.

Objectives: To compare clinical and microbiological characteristics, treatment and outcomes of MRSA bacteraemia among elderly and younger patients., Material and Methods: Prospective study conducted at 21 Spanish hospitals including patients with MRSA bacteraemia diagnosed between June/2008 and December/2009. Episodes diagnosed in patients aged 75 or more years old (≥75) were compared with the rest of them (<75)., Results: Out of 579 episodes of MRSA bacteraemia, 231 (39.9%) occurred in patients ≥75. Comorbidity was significantly higher in older patients (Charlson score ≥4: 52.8 vs. 44%; p = .037) as was the severity of the underlying disease (McCabe ≥1: 61.9 vs. 43.4%; p < .001). In this group the acquisition was more frequently health-care related (43.3 vs. 33.9%, p = .023), mostly from long-term care centers (12.1 vs. 3.7%, p < .001). An unknown focus was more frequent among ≥75 (19.9 vs. 13.8%; p = .050) while severity at presentation was similar between groups (Pitt score ≥3: 31.2 vs. 27.6%; p = .352). The prevalence of vancomycin resistant isolates was similar between groups, as was the appropriateness of empirical antibiotic therapy. Early (EM) and overall mortality (OM) were significantly more frequent in the ≥75 group (EM: 12.1 vs. 6%; p = .010 OM: 42.9 vs. 23%; p < .001). In multivariate analysis age ≥75 was an independent risk factor for overall mortality (aOR: 2.47, CI: 1.63-3.74; p < .001)., Conclusion: MRSA bacteraemia was frequent in patients aged ≥75 of our cohort. This group had higher comorbidity rates and the source of infection was more likely to be unknown. Although no differences were seen in severity or adequacy of empiric therapy, elderly patients showed a higher overall mortality., (Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of the study was to determine clinical and microbiological differences between patients with methicillin-resistant Staphylococcus aureus (MRSA) catheter-related bacteraemia (CRB) undergoing or not undergoing haemodialysis, and to compare outcomes., Methods: Prospective multicentre study conducted at 21 Spanish hospitals of patients with MRSA bacteraemia diagnosed between June 2008 and December 2009. Patients with MRSA-CRB were selected. Data of patients on haemodialysis (HD-CRB) and those not on haemodialysis (non-HD-CRB) were compared., Results: Among 579 episodes of MRSA bacteraemia, 218 (37.7%) were CRB. Thirty-four (15.6%) were HD-CRB and 184 (84.4%) non-HD-CRB. All HD-CRB patients acquired the infection at dialysis centres, while in 85.3% of the non-HD-CRB group the infection was nosocomial (p < .001). There were no differences in age, gender or severity of bacteraemia (Pitt score); comorbidities (Charlson score ≥ 4) were higher in the HD-CRB group than in the non-HD-CRB group (73.5% vs. 46.2%, p = .003). Although there were no differences in VAN-MIC ≥ 1.5 mg/L according to microdilution, using the E-test a higher rate of VAN-MIC ≥ 1.5 mg/L was observed in HD-CRB than in non-HD-CRB patients (63.3% vs. 44.1%, p = .051). Vancomycin was more frequently administered in the HD-CRB group than in the non-HD-CRB group (82.3% vs. 42.4%, p = <.001) and therefore the appropriate empirical therapy was significantly higher in HD-CRB group (91.2% vs. 73.9%, p = .029). There were no differences with regard to catheter removal (79.4% vs. 84.2%, p = .555, respectively). No significant differences in mortality rate were observed between both groups (Overall mortality: 11.8% vs. 27.2%, p = .081, respectively), but there was a trend towards a higher recurrence rate in HD-CRB group (8.8% vs. 2.2%, p = .076)., Conclusions: In our multicentre study, ambulatory patients in chronic haemodialysis represented a significant proportion of cases of MRSA catheter-related bacteraemia. Although haemodialysis patients with MRSA catheter-related bacteraemia had significantly more comorbidities and higher proportion of strains with reduced vancomycin susceptibility than non-haemodialysis patients, overall mortality between both groups was similar.

Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarized the results obtained from the 2013 SEIMC External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted in seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 2-5 log10 copies/mL; two of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (25% on average) obtained values out of the accepted range (mean ± 0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 98.9% of laboratories reporting results within the limits (D < 0.5 log10 copies/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 82% in the case of HCV and 78% in the HBV, obtained all the results within the accepted range (mean ± 1.96 SD log10 UI/mL). Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up., (Copyright © 2015 Elsevier España, S.L.U. All rights reserved.)

Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarized the results obtained from the 2012 SEIMC External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted in seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 2-5 log10 copies/mL; two of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (22.3% on average) obtained values out of the accepted range (mean±0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 98.9% of laboratories reporting results within the limits (Δ < 0.5 log10 copias/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 84% in the case of HCV and 88% in the HBV, obtained all the results within the accepted range (mean±1.96 SD log10 UI/mL). Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up., (Copyright © 2014 Elsevier España, S.L. All rights reserved.)

Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most important markers in the follow-up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of the results obtained by microbiology laboratories. This article summarizes the results of the 2011 SEIMC External Quality Control Program for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients in the range of 2-5 log10 copies/mL; to determine repeatability, two of these standards were identical. A significant proportion of the laboratories (52.1% on average) obtained values outside the accepted range (mean ± 0,25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was very good, with up to 94.9% of laboratories reporting results within the accepted range (Δ<0,5 log10 copies/ mL). The HBV and HCV program consisted of two standards with different viral load contents. In most of the participating laboratories (90% in the case of HCV and 86% in that of HBV), all the results were within the accepted range (mean ± 1.96 SD log10UI/mL). Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to the marked interlaboratory variability found, use of the same method and the same laboratory for patient follow-up is advisable., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

Objective: Since March 2008, several linezolid and teicoplanin-resistant Staphylococcus hominis (S. hominis) isolates have been recovered from patients admitted to the two major hospitals on the island of Majorca, Spain. For this reason, a study was conducted to determine the molecular epidemiology of these isolates and the mechanism of linezolid resistance., Methods: The molecular epidemiology study was performed by pulsed-field gel electrophoresis (PFGE) analysis, after digestion with ApaI. Linezolid resistance mechanisms were evaluated by PCR amplification of a fragment of the domain V of the 23S rRNA gene (followed by sequencing) and cfr gene., Results: From March 2008 to February 2009, 15 linezolid and teicoplanin-resistant S. hominis isolates were recovered from 14 patients. All of them, except one, were hospitalised in the intensive care units of either of the two institutions. Isolates were obtained mainly from blood cultures (9). The majority of infected patients (12 of 15 infectious episodes, 80.0%) had received courses of linezolid prior to detection of the resistant isolate. PFGE analysis revealed the presence of a unique clone among linezolid resistant S. hominis isolates. The G2576T mutation was detected in all the linezolid resistant strains. None of the resistant isolates showed a positive PCR for the cfr gene. All of the isolates were also resistant to penicillin, oxacillin, trimethoprim-sulfamethoxazole, ciprofloxacin, levofloxacin, and tobramicin; whereas all of them were susceptible to erythromycin, tetracycline, gentamicin, and daptomycin. The MIC of vancomycin was 4μg/ml for all the strains., Conclusions: The detection of linezolid resistant Staphylococci highlights the need to rationalise the use of linezolid, and maintain an active surveillance of its resistance to preserve the clinical usefulness of this antimicrobial., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Introduction: Spontaneous cerebrospinal fluid otorrhea is a relatively rare entity and can be easily missed in adults. Every adult older than 50 years with a negative history of otologic disease who has recurrent serous otitis media should be evaluated for this pathology. Meningitis is the most serious complication, so there is no doubt that the condition needs immediate attention and correction., Objective: We present two patients who were diagnosed with spontaneous CSF otorrhea and make a review of what is reported about this topic., Conclusion: Surgical repair is mandatory to seal these nontraumatic CSF leaks. There are two main surgical approaches, the middle fossa craniotomy and the transmastoid approach. A multilayered closure technique in which autologous and artificial materials are combined is considered to result in the highest rate of success.

Recently, methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a cause of community-acquired (CA) infections among patients without established risk factors for MRSA. CA-MRSA strains mainly cause mild skin and soft tissue infections in otherwise healthy children and young adults, but can also cause severe necrotizing fasciitis and pneumonia. In contrast to nosocomial MRSA, CA-MRSA are, in general, susceptible to multiple antimicrobials and present a different genotype. Most CA-MRSA strains share the staphylococcal chromosomal cassette (SCCmec) type IV and produce Panton-Valentine leukocidin (PVL), a cytotoxin that causes leukocyte destruction and tissue necrosis. At present, the predominant clone is the USA300 clone, which is widely disseminated in the United States, Europe and Australia. In Spain, the predominant clone is related to the USA300 clone. The main mechanism of transmission is close person-to-person contact, although household pets and farm animals have also been implicated. In patients with purulent skin and soft tissue infections, the mainstay of treatment is incision and drainage. Antimicrobials are indicated in patients not responding to appropriate drainage. Clindamycin, trimethoprimsulfamethoxazole or tetracyclines can be administered, while the use of fluoroquinolones should be avoided due to the rapid emergence of resistance. For severe infections, vancomycin should be used. Other alternatives are linezolid or daptomycin (only if there is no pulmonary involvement). Adequate hygiene practices are the most efficient measure to prevent spread.