Juan Frasquet Artés
@gva.es
Generalitat Valencian
Scopus Publications
Scopus Publications
Marta García-Hita, Ignacio Antonio Sigona-Giangreco, Alejandro Rincón-Almanza, and Juan Frasquet-Artes
Elsevier BV
P. Ramírez, M. Gordón, M. Martín-Cerezuela, E. Villarreal, E. Sancho, M. Padrós, J. Frasquet, G. Leyva, I. Molina, M. Barrios,et al.
Elsevier BV
OBJECTIVE
Information from critically ill coronavirus disease 2019 (COVID-19) patients is limited and in many cases coming from health systems approaches different from the national public systems existing in most countries in Europe. Besides, patient follow-up remains incomplete in many publications. Our aim is to characterize acute respiratory distress syndrome (ARDS) patients admitted to a medical critical care unit (MCCU) in a referral hospital in Spain.
DESIGN
Retrospective case series of consecutive ARDS COVID-19 patients admitted and treated in our MCCU.
SETTING
36-bed MCCU in referral tertiary hospital.
PATIENTS AND PARTICIPANTS
SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal/pharyngeal swabs.
INTERVENTIONS
None MAIN VARIABLES OF INTEREST: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality.
RESULTS
Forty-four ARDS COVID-19 patients were included in the study. Median age was 61.50 (53.25 - 67) years and most of the patients were male (72.7%). Hypertension and dyslipidemia were the most frequent co-morbidities (52.3 and 36.4% respectively). Steroids (1mg/Kg/day) and tocilizumab were administered in almost all patients (95.5%). 77.3% of the patients needed invasive mechanical ventilation for a median of 16 days [11-28]. Prone position ventilation was performed in 33 patients (97%) for a median of 3 sessions [2-5] per patient. Nosocomial infection was diagnosed in 13 patients (29.5%). Tracheostomy was performed in ten patients (29.4%). At study closing all patients had been discharged from the CCU and only two (4.5%) remained in hospital ward. MCCU length of stay was 18 days [10-27]. Mortality at study closing was 20.5% (n 9); 26.5% among ventilated patients.
CONCLUSIONS
The seven-week period in which our MCCU was exclusively dedicated to COVID-19 patients has been challenging. Despite the severity of the patients and the high need for invasive mechanical ventilation, mortality was 20.5%.
Alba Ruiz-Gaitán, Héctor Martínez, Ana María Moret, Eva Calabuig, María Tasias, Ana Alastruey-Izquierdo, Óscar Zaragoza, Joan Mollar, Juan Frasquet, Miguel Salavert-Lletí,et al.
Informa UK Limited
ABSTRACT Background: Candida auris is an emerging, multidrug-resistant yeast causing hospital outbreaks. This study describes the first 24 months of the ongoing C. auris outbreak in our hospital and analyzes predisposing factors to C. auris candidemia/colonization. Research design and methods: A 12-month prospective, case-controlled study was performed including a total of 228 patients (114 colonized/candidemia and 114 controls). Data from the first 79 candidemia episodes and 738 environmental samples were also analyzed. Definitive C. auris identification was performed by ITS sequencing. Antifungal susceptibility was carried out by EUCAST methodology. Results: Polytrauma (32%), cardiovascular disease (25%), and cancer (17%) were the most common underlying condition in colonized/candidemia patients. Indwelling CVC (odds ratio {OR}, 13.48), parenteral nutrition (OR, 3.49), and mechanical ventilation (OR, 2.43) remained significant predictors of C. auris colonization/candidemia. C. auris was most often isolated on sphygmomanometer cuffs (25%) patient tables (10.2%), keyboards (10.2%), and infusion pumps (8.2%). All isolates were fully resistant to fluconazole (MICs >64 mg/L) and had significantly reduced susceptibility to voriconazole (GM, 1.8 mg/L). Conclusions: Predictor conditions to C. auris colonization/candidemia are similar to other Candida species. C. auris colonizes multiple patient’s environment surfaces. All isolates are resistant to fluconazole and had significant reduced susceptibility to voriconazole.
Jesus Ruiz, Monica Gordon, Esther Villarreal, Juan Frasquet, María Ángeles Sánchez, María Martín, Álvaro Castellanos, and Paula Ramirez
Springer Science and Business Media LLC
BackgroundThe aim of this study is to evaluate the risk factors for colonisation by multidrug resistant (MDR) K. pneumoniae in a critical care unit and the relationship between colonisation and the antibiotic pressure exerted by the antimicrobial treatments received by patients.MethodsA prospective observational was designed. Patients admitted for more than 48 h to an intensive care unit were included. Samples for surveillance cultures were obtained from all the patients upon admission and once a week. The association between risk factors and colonisation by MDR K. pneumoniae was determined by logistic regression. A Cox regression model was used to evaluate the effect of the use of antimicrobials on the colonisation rate. An ARMIA model was used to investigate the association between the incidence of colonisation by MDR strains and the global consumption of antimicrobials in the unit.ResultsOne thousand seven hundred twenty-five patients were included, from which 308 (17.9%) were positive for MDR K. pneumoniae. In the multivariate analysis, hospitalisation for longer than 7 days together with respiratory infection and administration of any antibiotic was associated with increased MR K. pneumoniae colonisation. Patients who received antibiotics for more than 48 h were colonised earlier than patients who did not receive antibiotic treatment [HR: 2.16 (95%CI:1.55–3.03)]. The ARIMA model found a significant association between the monthly colonisation rate for MR K. pneumoniae and the consumption of cephalosporins and carbapenems in the previous month.ConclusionIndividual antibiotic administration and the global antibiotic pressure of cephalosporins and carbapenems are associated to an increased colonisation by MDR K. pneumoniae strains.
Marta Garrido-Jareño, Juan Frasquet-Artes, María Tasias-Pitarch, and José Luis López-Hontangas
Elsevier BV
Jesus Ruiz, Paula Ramirez, Pablo Concha, Miguel Salavert-Lletí, Esther Villarreal, Monica Gordon, Juan Frasquet, and Álvaro Castellanos-Ortega
Elsevier BV
OBJECTIVES
The aim of this study was to determine the persistence of the adverse prognostic effect of elevated vancomycin minimum inhibitory concentration (MIC) in methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in a setting with low vancomycin use.
METHODS
A retrospective study focusing on episodes of bacteraemia due to MRSA diagnosed from January 2010 through December 2015 was designed. The main outcome measures were 30-day mortality and treatment failure. Multivariate logistic regression analysis was used to identify variables associated with patient mortality and treatment outcome.
RESULTS
In total, 79 MRSA bacteraemia episodes were included. The vancomycin MIC was >1.0μg/mL in 53 episodes (67.1%). The presence of high vancomycin MIC was not associated with a higher mortality rate or treatment success. A daptomycin MIC≥0.5μg/mL was present in 16 (26.2%) of 61 episodes for which the daptomycin MIC was obtained and was associated with 30-day mortality in the multivariate analysis (odds ratio=4.72, 95% confidence interval 1.19-18.71). None of the antimicrobials used were associated with a lower risk of treatment failure or mortality.
CONCLUSIONS
The pernicious effect of high vancomycin MIC disappears in the absence of a predominant use of this antibiotic. However, a high daptomycin MIC in MRSA bacteraemia is associated with higher mortality in patients with bacteraemia, irrespective of antimicrobial treatment choice.
J. Ruiz, P. Ramirez, M. Gordon, E. Villarreal, J. Frasquet, J.L. Poveda-Andres, M. Salavert-Lletí, and A. Catellanos
Elsevier BV
OBJECTIVE
Hospital antimicrobial stewardship programmes have achieved savings and a more rational use of antimicrobial treatments in general wards. The purpose of this report is to evaluate the experience of an antimicrobial stewardship programme in an intensive care unit (ICU).
DESIGN
Prospective interventional, before-and-after study.
SCOPE
24-bed medical ICU in a tertiary hospital.
INTERVENTION
Prospective audit and feedback antimicrobial stewardship programme.
ENDPOINTS
Antimicrobial consumption, antimicrobial related costs, multi-drug resistant microorganisms (MDRM) prevalence, nosocomial infections incidence, ICU length of stay, and ICU mortality rates were compared before and after one-year intervention.
RESULTS
A total of 218 antimicrobial episodes of 182 patients were evaluated in 61 team meetings. Antimicrobial stewardship suggestions were accepted in 91.5% of the cases. Total antimicrobial DDD/100 patient-days consumption was reduced from 380.6 to 295.2 (-22.4%; p=0.037). Antimicrobial stewardship programme was associated with a significant decrease in the prescription of penicillins plus b-lactamase inhibitors, linezolid, cephalosporins, and aminoglycosides. Overall antimicrobial spending was reduced by €119,636. MDRM isolation and nosocomial infections per 100 patient-days did not change after the intervention period. No changes in length of stay or mortality rate were observed.
CONCLUSIONS
An ICU antimicrobial stewardship programme significantly reduced antimicrobial use without affecting inpatient mortality and length of stay. Our results further support the implementation of an antimicrobial stewardship programme in critical care units.
Jesus Ruiz, Paula Ramirez, María José Company, Mónica Gordon, Esther Villarreal, Pablo Concha, María Aroca, Juan Frasquet, María Remedios-Marqués, and Álvaro Castellanos-Ortega
Elsevier BV
OBJECTIVES
This study evaluated the association between the pharmacokinetic/pharmacodynamic index and treatment response to amikacin in critically ill patients.
METHODS
An observational prospective study was designed. Critically ill adult patients with infection due to amikacin-sensitive Gram-negative bacteria treated with amikacin were included. Amikacin maximum (Cmax) and minimum (Cmin) plasma concentration samples were taken during the first 48-96h after the beginning of treatment. The impact of Cmax/MIC ratio and area under the concentration-time curve (AUC)/MIC ratio on early and final clinical response, microbiological eradication, development of resistant strains and renal toxicity was analysed using a multivariate model.
RESULTS
A total of 85 patients received amikacin treatment, of whom 71 (83.5%) achieved a Cmax/MIC >6, 66 (77.6%) a Cmax/MIC >8, 64 (75.3%) a Cmax/MIC >10 and 72 (84.7%) an AUC/MIC >65. Clinical response at the end of treatment was significantly greater in patients with Cmax/MIC >6 [OR=5.48 (95% CI 1.28-11.40)], Cmax/MIC >8 [OR=6.01 (2.41-12.2)] and Cmax/MIC >10 [OR=8.02 (2.21-14.2)]. Cmax/MIC >10 was associated with a non-significant increase in microbiological eradication [OR=2.84 (0.76-10.61)]. Achieving Cmax/MIC >6 was associated with a lower proportion of patients with selection of resistant strains or with an increase in amikacin MIC (27.8% vs. 10.2%). Amikacin AUC was associated with development of nephrotoxicity [ROC curve 0.77 (0.66-0.87)].
CONCLUSIONS
The Cmax/MIC ratio of amikacin in critically ill patients is directly related to the response to treatment and the selection of resistant strains.
J. Ruiz, P. Ramirez, E. Villarreal, M. Gordon, S. Cuesta, M. Piñol, J. Frasquet, and Á. Castellanos
Springer Science and Business Media LLC
The purpose of this study was to assess the effectiveness of silver-embedded surfaces (BactiBlock®) to prevent surface colonization by multi-resistant bacteria (MRB) and to reduce the incidence of MRB colonization and infection in patients admitted to an intensive care unit (ICU). A 6-month prospective observational study in a 24-bed mixed ICU divided into two identical subunits (12 beds each) was designed. Seven solid mobile screens were placed in one of the subunits while in the other cloth screens remained. Solid screens were constructed with high-density polyethylene embedded in Bactiblock®. To evaluate the effectiveness of screens coated with Bactiblock®, number of MRB isolates on screens were compared for 6 months. Likewise, numbers of new patients and ICU-stays with MRB colonization in the two subunits were compared. One hundred forty screen samples were collected in 10-point prevalent days. MRB were detected on 28 (20.0%) samples. Over the 70 samples taken on cloth folding screens, MRB were detected in 25 (35.7%), while only 3 (4.3%) of the 70 samples taken on Bactiblock® screens were positive for MRB (p < 0.001). The unit with Bactiblock® screens presented fewer number of ICU stays with MRB colonization (27.8% vs 47.1%; p < 0.001). No significant differences were found in the global incidence of MRB nosocomial infection. The presence of Bactiblock® embedded in solid folding screens avoided MRB surface colonization and reduced MRB transmission to patients admitted to critical care units, proving to be an useful tool in the control of MRB.
J. Ruíz-Ramos, J. Frasquet, J. L. Poveda-Andrés, E. Romá, M. Salavert-Lletí, Á. Castellanos and P. Ramírez
OBJECTIVE
Antimicrobial Stewardship Programs (ASPs) have appeared as very useful tools in order to improve the use of antimicrobial agents. The objective of this study is to assess the impact of an ASP on haematological patients hospitalized in an Intensive Care Unit (ICU).
METHODS
A quasi-experimental pre-post intervention study, which included haematological patients admitted to an ICU and assessed by the ASP program during 3 years. The impact of the program on patient evolution was assessed by comparison between the previous period and the intervention period in terms of mortality, mean stay, number of re-hospitalizations, and duration of mechanical ventilation for intubated patients.
RESULTS
The ASP team assessed 324 antimicrobial agents in 169 patients; they recommended 121 modifications, including 55 treatment discontinuations. Compared with the pre-intervention period, there were no significant differences in the variables assessed. No variation was observed in colonization by multi-resistant bacteria.
CONCLUSIONS
The implementation of an APS on critical haematological patients will lead to a relevant number of treatment modifications, without any impact on the clinical evolution of patients.
Jesus Ruiz-Ramos, Juan Frasquet, Eva Romá, Jose Luis Poveda-Andres, Miguel Salavert-Leti, Alvaro Castellanos, and Paula Ramirez
Informa UK Limited
Abstract Aims: To evaluate the cost-effectiveness of antimicrobial stewardship (AS) program implementation focused on critical care units based on assumptions for the Spanish setting. Materials and methods: A decision model comparing costs and outcomes of sepsis, community-acquired pneumonia, and nosocomial infections (including catheter-related bacteremia, urinary tract infection, and ventilator-associated pneumonia) in critical care units with or without an AS was designed. Model variables and costs, along with their distributions, were obtained from the literature. The study was performed from the Spanish National Health System (NHS) perspective, including only direct costs. The Incremental Cost-Effectiveness Ratio (ICER) was analysed regarding the ability of the program to reduce multi-drug resistant bacteria. Uncertainty in ICERs was evaluated with probabilistic sensitivity analyses. Results: In the short-term, implementing an AS reduces the consumption of antimicrobials with a net benefit of €71,738. In the long-term, the maintenance of the program involves an additional cost to the system of €107,569. Cost per avoided resistance was €7,342, and cost-per-life-years gained (LYG) was €9,788. Results from the probabilistic sensitivity analysis showed that there was a more than 90% likelihood that an AS would be cost-effective at a level of €8,000 per LYG. Limitations: Wide variability of economic results obtained from the implementation of this type of AS program and short information on their impact on patient evolution and any resistance avoided. Conclusions: Implementing an AS focusing on critical care patients is a long-term cost-effective tool. Implementation costs are amortized by reducing antimicrobial consumption to prevent infection by multidrug-resistant pathogens.
J.M. Sahuquillo-Arce, R. Chouman-Arcas, J.M. Molina-Moreno, A. Hernández-Cabezas, J. Frasquet-Artés, and J.L. López-Hontangas
Elsevier BV
Bacteria use bicarbonate as substrate for crucial metabolic reactions. We report the first case of bacteremia by capnophilic E. coli without the YadF gene (also known as CynT2 or Can2) that needs high concentrations of CO2 to non-enzymatically produce bicarbonate. This lack may also apply to previously reported capnophilic Enterobacteriaceae.
J. Ruiz, E. Villarreal, M. Gordon, J. Frasquet, A. Castellanos, and P. Ramirez
Elsevier BV
Juan S. Frasquet-Artés, Javier Pemán, Marino Blanes, Miriam Hernández-Porto, Josep Cano, Enrique Jiménez-Herrero, and José Luis López-Hontangas
Elsevier BV
Cerebral phaeohyphomycosis is a rare invasive fungal infection with very few cases referenced in the literature. There is no standardized treatment, and it is associated with poor outcomes. Cladophialophora bantiana, a fungus with special tropism for the central nervous system, is one of the causal agents of phaeohyphomycosis. The case presented here deals with a brain abscess by C. bantiana in an adult with Crohn's disease had beed being treated with immunosuppressive drugs. Despite the correct etiological diagnosis, surgical and pharmacological treatments, the patient died 32 days after surgery. A description of the case is followed by a review of all cerebral C. bantiana phaeohyphomycosis cases published in the last 10 years. Regardless of the use of advanced new imaging techniques in the diagnosis and treatment with new antifungal agents, cerebral phaeohyphomycosis by C. bantiana continues to have very poor prognosis. While new more successful therapeutic treatments appear, a combined surgical and pharmacological approach seems to be more appropriate for this severe mycosis.
A.G. Núñez Ramiro, A. Adell Sales, R.J. Calderón Fernández, J. Frasquet, and A. Pérez Tamarit
Elsevier BV
El Streptococcus pyogenes, también llamado Streptococcus -hemolítico del grupo A, es un coco grampositivo causante de gran variedad de patologías, ya sean frecuentes (faringoamigdalitis o infecciones de la piel) o no tan frecuentes, como infecciones osteoarticulares, neumonía, meningitis o sepsis. Durante la última década se ha observado un aumento de la incidencia y gravedad de las infecciones invasoras causadas por Streptococcus pyogenes. Describimos un caso de meningitis aguda por Streptococcus pyogenes. El paciente era un varón de 4 años que acudió a urgencias de nuestro centro por fiebre de 24 h de evolución, máxima 39,5 ◦C, cefalea y decaimiento. Se trataba de un exprematuro de 33 semanas, segundo gemelo de una gestación múltiple, vacunado correctamente, incluyendo antineumocócica heptavalente, sin otros antecedentes de interés. Presentaba regular estado general, con constantes normales excepto T. de 38,1 ◦C, orofaringe muy hiperémica, soplo sistólico II/VI en el borde esternal izquierdo, signos meníngeos: Kernig negativo y Brudzinski positivo, con el resto de exploración física normal. Se solicitó una analítica general, con los siguientes resultados: leucocitos 35.400/ l (91% neutrófilos), proteína C reactiva 134 mg/l, procalcitonina 2,3 ng/ml, glucemia 130 mg/dl, fibrinógeno 757 mg/dl y ASLO 1.400 U/ml. Se realizó un test rápido de estreptococos en orofaringe, que resultó positivo. Se realizó una punción lumbar, obteniéndose un LCR claro a presión normal, con una glucorraquia de 56 mg/dl, una proteinorraquia de 96 mg/dl y una celularidad de 425/mmc, con un 80% de polinucleares y un 20% de mononucleares. Los antígenos capsulares fueron negativos. El score de Boyer fue de 4. Se ingresó y se inició antibioterapia por vía intravenosa empírica con ceftriaxona a 100 mg/kg/día. A las 24 h se aislaron en el cultivo de LCR 4-6 colonias que aglutinaban a Streptococcus pyogenes, con cultivo faríngeo puro del mismo, por lo que se decidió añadir clindamicina, dada la acción supresora de la síntesis de las toxinas bacterianas de Streptococcus pyogenes, manteniéndose durante 48 h. El hemocultivo fue negativo. Se realizó un estudio de contactos familiar que resultó negativo. El estudio cardiológico (ECG, ecocardiograma) fue normal. Se solicitaron RM cerebral y cervical en las que no se encontró ningún hallazgo significativo. A las 48 h se repitió la punción lumbar, no encontrándose cambios en la bioquímica del LCR y siendo ya el cultivo negativo. Se continuó tratamiento con ceftriaxona. La evolución fue favorable, quedando afebril a los 6 días del ingreso, con bioquímica de LCR y analítica general normal previo al alta (16 días), por lo que se suspendió antibioterapia. En el seguimiento posterior en la consulta externa, se observa ASLO en descenso y cultivos faríngeos seriados negativos. Como hemos dicho anteriormente, la incidencia de infección invasora por Streptococcus pyogenes se está viendo incrementada en los últimos años y, aunque produce con mayor frecuencia infecciones leves (faringoamigdalitis, infecciones cutáneas...), no hay que olvidar que puede producir infecciones de mayor gravedad, como artritis, fascitis necrotizante, síndrome de shock tóxico o, en nuestro caso, meningitis. El Streptococcus pyogenes es un raro agente productor de meningitis y representa del 0,2-1% de los casos y se presenta frecuentemente como infección de contigüidad de procesos infecciosos del tracto respiratorio superior, tales como otitis complicada, sinusitis, mastoiditis complicada. Sin embargo, y como ocurre en este caso, también se presenta en individuos sanos que no tienen factores predisponentes y que no presentan clara evidencia de foco contiguo, por lo que debe ser considerado como causa de meningitis en niños previamente sanos. Aunque en general siempre se debe modificar el tratamiento antibiótico cuando los resultados del cultivo del LCR y el antibiograma están disponibles, en nuestro caso, a pesar de conocer los resultados, se decidió continuar el tratamiento con ceftriaxona porque tendríamos que haber administrado dosis muy altas de penicilina para asegurar el paso a través de la barrera hematoencefálica. Además, también por la pauta posológica, ya que la ceftriaxona se puede administrar cada 1224 h y la penicilina presenta un intervalo de dosis menor.
J. Pemán, I. Jarque, J. Frasquet, C. Alberola, M. Salavert, J. Sanz, B. Gomila, and G. Esteban
Wiley
Meningoencephalitis caused by pathogenic free‐living amebas is usually fatal. Only a few cases of Acanthamoeba meningoencephalitis, diagnosed at autopsy, have been reported following hematopoietic stem cell transplantation. We here report a case of Acanthamoeba meningoencephalitis following allogeneic peripheral blood stem cell transplantation with rapidly evolving neurologic symptoms that remained unexplained. Magnetic resonance imaging failed to show brain lesions and cerebrospinal fluid was negative for microbiological cultures. Definite diagnosis was an unexpected autopsy finding. As overall and teaching hospital autopsy rates are declining worldwide, we must emphasize the need of autopsy exams if we want to improve our knowledge as the best way to care for our patients.
Javier Pemán, Rebeca Ortiz, Faisa Osseyran, Carmen Pérez-Bellés, Marisa Crespo, Melitina Chirivella, Juan Frasquet, Anastasio Quesada, Emilia Cantón, and Miguel Gobernado
Elsevier BV
Native valve endocarditis caused by Aspergillus spp. is an uncommon disease with a high mortality rate. Generally, Aspergillus is isolated from affected valve in post-mortem or biopsy specimens. However, its isolation from blood cultures is exceedingly rare. We report a case of fungal endocarditis in a native mitral valve with the isolation of Aspergillus fumigatus both in valve vegetation and in blood culture bottles. The patient underwent valve replacement and antifungal treatment with voriconazole and caspofungin, but he died on post-operative day 45 with disseminated aspergillosis confirmed by necropsy. Paradoxically, galactomannan antigen detection in serum was negative. This is the third case of Aspergillus endocarditis with positive blood culture reported in the literature.