Model-informed precision dosing of antimicrobial drugs in pediatrics: experiences from a pilot scale program.

Antibiotics are among the most utilized drugs in pediatrics. Nonetheless, there is a lack in pharmacokinetics information for this population, and dosing criteria may vary between healthcare centers. Physiological variability associated with maturation in pediatrics makes it challenging to reach a consensus on adequate dosing, which is further accentuated in more vulnerable groups, such as critically ill or oncology patients. Model-informed precision dosing is a useful practice that allows dose optimization and attainment of antibiotic-specific pharmacokinetic/pharmacodynamic targets. The aim of this study was to evaluate the needs of model-informed precision dosing of antibiotics in a pediatrics unit, at a pilot scale. Pediatric patients under antibiotic treatment were monitored with either a pharmacokinetic/pharmacodynamic optimized sampling scheme or through opportunistic sampling. Clindamycin, fluconazole, linezolid, meropenem, metronidazole, piperacillin, and vancomycin plasma concentrations were quantified through a liquid chromatography coupled to mass spectrometry method. Pharmacokinetic parameters were estimated using a Bayesian approach to verify pharmacokinetic/pharmacodynamic target attainment. A total of 23 pediatric patients aged 2 to 16 years were included, and 43 dosing regimens were evaluated; 27 (63%) of them required adjustments as follows: 14 patients were underdosed, 4 were overdosed, and 9 patients needed infusion rate adjustments. Infusion rate adjustments were mostly recommended for piperacillin and meropenem; daily doses were augmented for vancomycin and metronidazole, meanwhile linezolid was adjusted for under- and overdosing. Clindamycin and fluconazole regimens were not adjusted at all.  Conclusion: Results showcase a lack of antibiotic pharmacokinetic/pharmacodynamic target attainment (particularly for linezolid, vancomycin, meropenem, and piperacillin), and the need for model-informed precision dosing in pediatrics. This study provides pharmacokinetic evidence which can further improve antibiotic dosing practices. What is Known: • Model-informed precision dosing is performed in pediatrics to optimize the treatment of antimicrobial drugs such as vancomycin and aminoglycosides, while its usefulness is debated for other groups (beta-lactams, macrolides, etc.). What is New: • Vulnerable pediatric subpopulations, such as critically ill or oncology patients, can benefit the most from model-informed precision dosing of antibiotics. • Model-informed precision dosing of linezolid, meropenem, piperacillin, and vancomycin is particularly useful in pediatrics, and further research may improve dosing practices altogether.

Interesting Cytokine Profile Caused by Clinical Strains of Pseudomonas aeruginosa MDR Carrying the exoU Gene.

Pseudomonas aeruginosa is an opportunistic pathogen in HAIs with two facets: the most studied is the high rate of antimicrobial resistance, and the less explored is the long list of virulence factors it possesses. This study aimed to characterize the virulence genes carried by strains as well as the profile of cytokines related to inflammation, according to the resistance profile presented. This study aims to identify the virulence factors associated with MDR strains, particularly those resistant to carbapenems, and assess whether there is a cytokine profile that correlates with these characteristics. As methodology species were identified by classical microbiological techniques and confirmed by molecular biology, resistance levels were determined by the minimum inhibitory concentration and identification of MDR strains. Virulence factor genotyping was performed using PCR. In addition, biofilm production was assessed using crystal violet staining. Finally, the strains were cocultured with PBMC, and cell survival and the cytokines IL-1ß, IL-6, IL-10, IL-8, and TNF-α were quantified using flow cytometry. Bacteremia and nosocomial pneumonia in adults are the most frequent types of infection. In the toxigenic aspect, genes corresponding to the type III secretion system were present in at least 50% of cases. In addition, PBMC exposed to strains of four different categories according to their resistance and toxicity showed a differential pattern of cytokine expression, a decrease in IL-10, IL-6, and IL-8, and an over-secretion of IL-1b. In conclusion, the virulence genes showed a differentiated appearance for the two most aggressive exotoxins of T3SS (exoU and exoS) in multidrug-resistant strains. Moreover, the cytokine profile displays a low expression of cytokines with anti-inflammatory and proinflammatory effects in strains carrying the exoU gene.

Pretreatment parameters associated with hemorrhagic transformation among successfully recanalized medium vessel occlusions.

Although pretreatment radiographic biomarkers are well established for hemorrhagic transformation (HT) following successful mechanical thrombectomy (MT) in large vessel occlusion (LVO) strokes, they are yet to be explored for medium vessel occlusion (MeVO) acute ischemic strokes. We aim to investigate pretreatment imaging biomarkers representative of collateral status, namely the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index, and their association with HT in successfully recanalized MeVOs. A prospectively collected registry of acute ischemic stroke patients with MeVOs successfully recanalized with MT between 2019 and 2023 was retrospectively reviewed. A multivariate logistic regression for HT of any subtype was derived by combining significant univariate predictors into a forward stepwise regression with minimization of Akaike information criterion. Of 60 MeVO patients successfully recanalized with MT, HT occurred in 28.3% of patients. Independent factors for HT included: diabetes mellitus history (p = 0.0005), CBV index (p = 0.0071), and proximal versus distal occlusion location (p = 0.0062). A multivariate model with these factors had strong diagnostic performance for predicting HT (area under curve [AUC] 0.93, p < 0.001). Lower CBV indexes, distal occlusion location, and diabetes history are significantly associated with HT in MeVOs successfully recanalized with MT. Of note, HIR was not found to be significantly associated with HT.

Population-based Influenza and Respiratory Syncytial Virus Hospitalizations and In-hospital Mortality Rates Among Mexican Children Less Than Five Years of Age.

BACKGROUND: Population-based information regarding the impact of respiratory syncytial virus (RSV) and influenza on hospital admissions and mortality is scant for many countries. METHODS: Prospective testing of RSV and influenza virus was undertaken in patients <5 years old admitted to hospital with acute respiratory infection (ARI) between July, 2014 and June, 2015, and mortality rates for children living in 3 municipalities in the state of San Luis Potosí were calculated. RESULTS: During the 12-month study period, 790 children living in these municipalities were admitted with ARI. RSV was detected in 245 (31%) and influenza in 47 (5.9%). History of preterm birth was recorded for 112 children on admission. For children <5 years old, ARI-, RSV- and influenza-associated admission rates were 23.2, 7.2 and 1.4 (per 1000 population), respectively. The corresponding admission rates per 1000 infants <1 year old were 78, 25.2 and 4.4. Preterm infant admission rates were 2 times higher than those of term infants. Six children died; RSV was detected in 4 (66.6%) of the deceased, while no deaths were associated with influenza. ARI and RSV in-hospital mortality rates for children <5 years were 0.18 and 0.12 per 1000 population. ARI and RSV mortality rates in preterm infants were 7 and 14 times higher than in term infants, respectively. CONCLUSIONS: RSV was associated with both high admission and in-hospital mortality rates in children <5 years old. Specific interventions, such as active or passive immunization, to prevent RSV infections are required to reduce ARI-associated infant mortality.

Cranberry Supplements for Urinary Tract Infection Prophylaxis in Pregnant Women: A Systematic Review of Clinical Trials and Observational Studies on Efficacy, Acceptability, Outcomes Measurement Methods, and Studies' Feasibility.

Cranberry supplements are commonly used to prevent urinary tract infections (UTIs). However, their usefulness is uncertain in pregnant women. We aimed to comprehensively summarize the current knowledge on cranberry supplements' efficacy and acceptability during pregnancy in addition to the outcomes measurement methods and studies' feasibility. To achieve it, we searched PubMed, PMC, and Europe PMC databases plus screened citations followed by critical appraisal of included eligible English-written primary studies that (1) focused on pregnant women supplemented with any cranberry supplements; (2) provided data on cranberry supplements' efficacy, acceptability, outcomes measurement methods, and studies' feasibility; (3) included human subjects; and (4) published worldwide. Two randomized clinical trials (RCTs) and one nested cohort study, including 1156 pregnant women in total, contributed to our analysis. A tendency toward UTI reduction was demonstrated, although the results' validity was impacted by significant juice-induced gastrointestinal intolerance (23%; 44 of 188 subjects). Changing the form of supplementation from cranberry juice to capsules reduced the issue, causing side effects in one of 49 subjects (2%). Nevertheless, both RCTs still experienced significant recruitment and retention problems, which were at 33% and 59% on average, respectively. Newly acquired safety data on 919 more subjects suggests no increased risks of all malformations, vaginal bleeding, and neonatal complications. Investigating cranberry capsules' efficacy as a non-antibacterial option for UTI prevention in pregnant women has become a feasible and important direction with the current advancement in understanding cranberry supplements' actions, recommended doses plus regimens, and their safety in the population. We reviewed the challenges and discovered knowledge gaps and the implementation strategies for future studies.

Correction: Cranberry Supplements for Urinary Tract Infection Prophylaxis in Pregnant Women: A Systematic Review of Clinical Trials and Observational Studies on Efficacy, Acceptability, Outcomes Measurement Methods, and Studies' Feasibility.

[This corrects the article DOI: 10.7759/cureus.46738.].

Plasmid Carrying bla CTX-M-15, bla PER-1, and bla TEM-1 Genes in Citrobacter spp. From Regional Hospital in Mexico.

INTRODUCTION: Citrobacter spp. is an opportunistic bacteria that have been recognized as significant pathogens in patients with underlying diseases or immunocompromised status. The aim of this study was to identify extended-spectrum ß-lactamases in clinical isolates of Citrobacter spp. METHODS: This cross-sectional study was conducted at Hospital Central "Dr. Ignacio Morones Prieto" in San Luis Potosi, Mexico. Nineteen isolates of Citrobacter spp. were obtained from clinical specimens between April to December 2015. Four isolates were resistant to third-generation cephalosporins. The presence of genes encoding ESBL (bla CTX-M-15, bla TEM-1, bla VEB-1, bla SHV, and bla PER-1) was analyzed by PCR. For this purpose, plasmid DNA was extracted and horizontally transferred to recipient E. coli Top 10. RESULTS: bla CTX-M-15 and bla VEB-1 genes were detected in Citrobacter freundii and Citrobacter sedlakii, whereas bla PER-1 gene was identified in 1 isolate of Citrobacter freundii. In contrast, bla SHV gene was not detected in any isolate. One strain carried bla CTX-M-15, bla TEM-1, bla VEB-1, and bla PER-1 genes, most in a 275-kb plasmid. CONCLUSION: This study shows the presence of different types of ESBL in clinical isolates of Citrobacter freundii and Citrobacter sedlakii, which confer resistance to broad-spectrum ß-lactams. The plasmid identified in this study harboring ESBL genes could play an important role in the dissemination of antibiotic resistance.

Nosocomial bacteremia in children: a 15-year experience at a general hospital in Mexico.

OBJECTIVE: To describe the incidence and etiology of nosocomial bloodstream infections in children at a general hospital. DESIGN: Review of nosocomial bloodstream infections detected in children during 1991-2005. Data were prospectively gathered through active surveillance. Annual rates of infection were compared. SETTING: A public general hospital in San Luis Potosi, Mexico. PATIENTS: Children younger than 15 years of age admitted to pediatric wards and subjected to prospective surveillance for nosocomial infection. INTERVENTIONS: Measures instituted to decrease the incidence of hospital-acquired infection during the 15-year study period included establishing active surveillance for hospital-acquired infection, reinforcing compliance with handwashing recommendations, decreasing the degree of crowding on wards, establishing guidelines for the management of intravenous catheters and solutions, preparing parenteral nutrition and intravenous solutions under a laminar air-flow hood, and increasing nursing personnel. RESULTS: There were 868 nosocomial bloodstream infections detected in 29,273 subjects (overall rate, 2.94 episodes per 100 discharges). Infection rates were greatest among children admitted to the neonatal intensive care unit and lowest for those admitted to the school-age ward and the infectious diseases ward. There was a significant decrease in rates of nosocomial bacteremia in all of the wards. The organisms isolated most commonly were Klebsiella pneumoniae, Candida species, and coagulase-negative staphylococci. Mortality rates were higher for children with a gram-negative bacterial bloodstream infection (45.2%) and lower for children with a gram-positive bacterial infection (19.2%).Conclusions. Rates of nosocomial bloodstream infection decreased over the past 15 years at our hospital but continue to cause significant mortality. Continuing efforts to decrease the frequency of and mortality due to bloodstream infection are warranted.

Risk factors and biofilm detection on central venous catheters of patients attended at tertiary hospital.

AIM: To determinate the significance of risk factors with the presence of biofilm on catheters of patients attended at tertiary hospital cares. MATERIAL AND METHODS: A total of 126 patients were included, data collection by observing the handling of the CVC, clinical history and microbiological isolation methods of CVCs tips (Roll-plate, sonication and scanning electron microscopy) were evaluated. RESULTS: Certain factors, such as the lack of proper hand washing, the use of primary barriers and preparing medications in the same hospital service, showed an important relationship between biofilm formation in CVCs. The sonication method presented that most of the samples had isolation of multispecies 29 samples (64%); in contrast with the roll-plate method, just one sample (3%) was isolated. CONCLUSIONS: The importance of the strict aseptic techniques of insertion and of the handlings of CVC was highlighted, the failure of both techniques was related to the biofilm formation and was evidenced using the scanning electron microscopy. Since this tool is not available in most hospitals, we present the correlation of those evidences with other standard microbiological methods and risk factors, which are necessary for the sensible detection of the different steps of the biofilm formation on CVC and their correct interpretation with clinical evidences.

Endovascular treatment of cerebral dural and pial arteriovenous fistulas.

Dural arteriovenous fistulas (DAVFs) are arteriovenous shunts from a dural arterial supply to a dural venous channel, typically supplied by pachymeningeal arteries and located near a major venous sinus. Pial arteriovenous fistulas (PAVFs) are composed of one or more arterial feeders draining into a single vein in the absence of an intervening nidus. Fistulas manifesting features of high risk for rupture should be treated aggressively, the spectrum of treatment varies from endovascular, surgical resection, and stereotactic radiosurgery. This article describes the natural history, clinical presentation, and treatment of dural and pial fistulas, with emphasis on endovascular treatment.

Successful treatment of a traumatic carotid pseudoaneurysm with the Pipeline stent: Case report and review of the literature.

BACKGROUND: Traumatic intracranial pseudoaneurysms remain one of the most difficult vascular lesions to treat. In the case of traumatic pseudoaneurysms that may not be treated with parent vessel sacrifice, some flow diversion strategy such as stent-assistance or use of a flow diversion device is usually necessary. CASE DESCRIPTION: In this study we describe endovascular parent vessel wall-remodeling/endoluminal reconstruction and traumatic pseudoaneurysm thrombosis through the use of the Pipeline stent and review recent reports concerning indications, safety, and efficacy for alternative pathology. CONCLUSION: Although currently not routinely employed in the treatment of traumatic pseudoaneurysms, the Pipeline stent may represent a safe and effective treatment alternative achieving complete endoluminal reconstruction of the damaged vessel wall.

Perfil microbiológico de los pacientes con diagnóstico de neumonía asociada a ventilación mecánica en el servicio de medicina 4, hospital general del Instituto Salvadoreño del Seguro Social, año 2015 / Microbiological profile of patients diagnosed with pneumonia associated with mechanical ventilation in the medical service 4, general hospital of the "Instituto Salvadoreño del Seguro Social", year 2015

El presente trabajo recoge los datos de aislamiento microbiológico en las secreciones bronquiales recolectadas tanto por aspirado bronquial, entendido como aspiración de secreciones mediante una sonda de aspiración con vacío a través de tubo orotraqueal; como por fibrobroncoscopía, utilizando el fibrobroncoscopio flexible mediante toma de lavado bronquioalveolar, en aquellos pacientes con diagnóstico de neumonía asociada a ventilación mecánica, que estando ingresados en el servicio de Medicina 4 del Hospital General del Instituto Salvadoreño del Seguro Social (ISSS), desarrollaron insuficiencia respiratoria por causa no infecciosa y se colocaron en ventilación mecánica, con la posterior complicación infecciosa, que sucedieron durante el período del año 2015. Se contó con una identificación de las principales características clínicas y demográficas de los pacientes y la situación epidemiológica de pacientes que asistieron a este servicio, además de caracterizar el aislamiento bacteriológico de dichas patologías, pudiendo identificar los patógenos y la expresión fenotípica de resistencia antibiótica de las bacterias que afectan a la población de derechohabientes del instituto. Así, tener información de la flora predominante del servicio durante el período de investigación, lograr adecuar proyectos de seguimiento, y poder respaldar medidas de prevención y pautas terapéuticas en base a la evidencia encontrada en el servicio de hospitalización

Funcionamiento sexual después de la histerectomía / Sexual function after a hysterectomy

Objetivo: describir el funcionamiento sexual después de la histerectomía. Método: a 147 pacientes a quienes se les practicó histerectomía, se les entrevistó para evaluar el funcionamiento sexual por medio de la Escala de Experiencia Sexual de Arizona (EESA). Esta consta de 5 ítems que evalúan diferentes aspectos de la respuesta sexual humana. Cada ítem fue calificado desde 1 (no disfunción) hasta 6 (disfunción en grado extremo), a mayor puntuación , mayor disfunción sexual...

Sistemas de soporte hepático extracorpóreo: [revisión] / Extracorporeal liver support systems: [review]

Introducción. Los sistemas de soporte hepático extracorpóreo (SHE) surgen como una alternativa al trasplante hepático (TH), dado el incremento en la incidencia de falla hepática aguda (FHA), falla hepática crónica agudizada (FHCA), así como las restricciones en la oferta de órganos. Objetivo. Revisión de la literatura de los sistemas de soporte hepático extracorporeo. Metodología. Búsqueda de la literatura publicada entre julio de 1990 y noviembre de 2010 en las principales bases de datos médicas que incluyeron MEDLINE, SciELO y EMBASE, de artículos que analizaran tecnologías relacionadas con sistemas de soporte hepático en cuanto a sus especificaciones técnicas, sus usos y la evidencia respecto a su efectividad en pacientes con algún tipo de falla hepática que requirieran soporte.Resultados. Estos sistemas pueden dividirse en artificiales (hemofiltración, sistema MARS) y bioartificiales (como el Hepatassist™). Su fundamento consiste en reemplazar los procesos de destoxificación relacionados específicamente con el sistema de bilirrubinas, la eliminación de aminoácidos aromáticos, agentes inflamatorios y el manejo de los productos de degradación del sistema de la coagulación. Los recientes avances en bioingeniería y biogenética han hecho que estas tecnologías se acerquen cada vez más a una forma ideal, permitiendo que sean utilizados con relativo éxito en humanos. Los SHE, en su gran mayoría en desarrollo, pretenden no solo actuar como puente al TH, sino que, en casos puntuales, pueden llegar a ser la piedra angular del tratamiento mientras la FHA logra resolverse.

Background. Extracorporeal liver support systems (ELS) have emerged as an alternative to liver transplant (LT), given the growing incidence of acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and the limited organ supply. Objective. Review of literature about Extracorporeal Liver Support Systems. Methodology. A literature search was conducted on the main medical databases including MEDLINE, SciELO and EMBASE for papers published between July 1990 and November 2010 looking at technologies associated with liver support systems, their technical specifications, their use, and evidence regarding their effectiveness in patients with some forms of liver failure requiring support. Results. These systems may be divided into artificial (hemofiltration, MARS) and bioartificial (such as the Hepatassist™). They work by replacing detoxification processes associated specifically with bilirubins, aromatic aminoacids, and inflammatory agents, and the elimination of breakdown products of coagulation. Recent advances in bioengineering and biogenetics have brought these technologies closer to hetheideal, enabling their use in humans with a relative degree of success. ELS systems, most of them still under development, are designed not only to act as a bridge for LT but may also become the cornerstone of treatment in specific cases while the ALF resolves.

Neumonía eosinofílica crónica en un paciente con artritis reumatoide en tratamiento con sulfasalazina / Chronic eosinophilic pneumonia in a patient with rheumatoid arthritis on treatment with sulfasalazine

La neumonía eosinofílica crónica es una enfermedad poco conocida, caracterizada por un deterioro respiratorio progresivo mayor de un mes de evolución, con presencia de infiltrados pulmonares y eosinofília. Se han reportado varios casos de asociación con sulfasalazina en enfermedad inflamatoria intestinal. Describimos un caso de neumonía eosinofílica crónica en un paciente con antecedente de artritis reumatoide en tratamiento con sulfasalazina.

Craneotomia con paciente despierto para resección de tumores cerebrales / Craneotomy in awake patient for ablation of tumoral masses brain

La craneotomía realizada bajo bloqueo de los nervios del escalpe junto con sedación conciente, busca mantener las funciones de áreas elocuentes mientras se realiza intervención para resección de masas vecinas o mapeo epileptogénico. Se revisó nuestra base de datos en búsqueda de pacientes llevados a craneotomía en estado de vigilia durante los últimos 10 años. Esta serie de casos pretende comentar la experiencia acumulada, los principales inconvenientes observados durante su implementación y cómo estos fueron solucionados a través del tiempo. Se encontraron 9 pacientes, todos programados para resección de tumores de la glía, quienes fueron previamente instruidos sobre lo que se esperaba durante el intraoperatorio. Las cirugías fueron realizadas sin requerir cambios en la técnica anestésica en tanto que no se presentaron complicaciones mayores.

Craniotomy with the patient under conscious sedation and blockade of the scalp nerves, aims to preserve functionality of eloquent cortex areas while resection of tumors or epilepsy mapping are achieved. We reviewed our institutional database, looking for patients who underwent to awake craniotomy in the last 10 years. This case report resumes the accumulated experience, main observed problems during its implementation and how these were resolved through time. We found 9 patients, all of them scheduled to glial brain tumor resections, whom where previously instructed in the preanesthetic assessment about the different intraoperative situations. Procedures were doing without changes in the anesthetic technique or major events.

Síndrome hepatopulmonar y trasplante hepático / Hepatopulmonary syndrome and liver transplantation

El síndrome hepatopulmonar es una entidad clínica que compromete seseramente el estado funcional de los pacientes con enfermedad hepática en estado terminal. No se puede predecir con exactitud la historia natural de este esndrome una veZ ha sido diagnosticado. Sin embargo se reconoce que queronóstico es grave, lentamente progresivo y aunque la causa de muerte suele estar relacionada a la enfermedad depática, la calidad de vida de estos pacientes se se notablemente alterada por el trastornoventilatorio asoccado. Se considera que el trasplante hepático, en casos bien seleccionados, puede logralla completa resolución de este síndrome y el éxito en elmanejo perioperatorioestá directamente relacionado con el cococimiento de la fisiopatología.

Hepatopulmonary syndrome is a clinical entiy that severely impairs functional status of patients with end stage liver disease. Natural lourse of this syndrome is unpredictable once ii has beeeniagnosed. Hotuevev it is known that its prognosisis seúous, slowly progressive and although cause of death is often related to liver disease, quality of Ufe in these patients ii significantly impaired by yhe additional ventilatory disorder. It is actually considered that liver transplantation, in selected cases, can lead to complete tesolution on this syndrome and so soccess in the peúoperative management is tisectly related to the knotuledge of the pathophysiology process.

Broncoaspiración en el paciente pediátrico / Bronchiaspiration in the pediatric patient

Discusión de 7 eventos de broncoaspiración en paciente pediátrico

Absceso Epidural Lumbar: Una rara complicación posterior a analgesia epidural continua / Abscess Lumbar Epidural: A rare complication after analgesia continuous epidural

El absceso epidural es una rara pero grave complicación de la anestesia y analgesia epidural; el cuál puede llevar a serias lesiones neurológicas cuya severidad y pronóstico depende de un diagnóstico y tratamiento temprano. Nuestro objetivo es crear nuevas expectativas con respecto al manejo y evaluación de los pacientes que reciben estas técnicas para lograr un óptimo resultado...