Beta-Lactam Antibiotics Can Be Measured in the Exhaled Breath Condensate in Mechanically Ventilated Patients: A Pilot Study.

Different techniques have been proposed to measure antibiotic levels within the lung parenchyma; however, their use is limited because they are invasive and associated with adverse effects. We explore whether beta-lactam antibiotics could be measured in exhaled breath condensate collected from heat and moisture exchange filters (HMEFs) and correlated with the concentration of antibiotics measured from bronchoalveolar lavage (BAL). We designed an observational study in patients undergoing mechanical ventilation, which required a BAL to confirm or discard the diagnosis of pneumonia. We measured and correlated the concentration of beta-lactam antibiotics in plasma, epithelial lining fluid (ELF), and exhaled breath condensate collected from HMEFs. We studied 12 patients, and we detected the presence of antibiotics in plasma, ELF, and HMEFs from every patient studied. The concentrations of antibiotics were very heterogeneous over the population studied. The mean antibiotic concentration was 293.5 (715) ng/mL in plasma, 12.3 (31) ng/mL in ELF, and 0.5 (0.9) ng/mL in HMEF. We found no significant correlation between the concentration of antibiotics in plasma and ELF (R2 = 0.02, p = 0.64), between plasma and HMEF (R2 = 0.02, p = 0.63), or between ELF and HMEF (R2 = 0.02, p = 0.66). We conclude that beta-lactam antibiotics can be detected and measured from the exhaled breath condensate accumulated in the HMEF from mechanically ventilated patients. However, no correlations were observed between the antibiotic concentrations in HMEF with either plasma or ELF.

[Severe metabolic disorder associated with an enterovesical fistula. Report of one case]. / Trastorno grave del medio interno por fístula enterovesical, a propósito de un caso clínico.

Enterovesical fistula (EVF) is a fistulous communication between the intestine and the bladder. It is uncommon and its classic clinical manifestations are the presence of pneumaturia, fecaluria, suprapubic pain and recurrent urinary infections. Surgical repair of EVF leads to rapid correction of both diarrhea and metabolic abnormalities. We report a 73-year-old diabetic woman with a neurogenic bladder secondary to a spine meningioma. She presented with diarrhea, vomiting, impaired consciousness and metabolic acidosis. She developed hypernatremia, hypokalemia, hypocalcemia, and hypophosphatemia, which were successfully corrected.

Trastorno grave del medio interno por fístula enterovesical, a propósito de un caso clínico / Severe metabolic disorder associated with an enterovesical fistula: report of one case

Enterovesical fistula (EVF) is a fistulous communication between the intestine and the bladder. It is uncommon and its classic clinical manifestations are the presence of pneumaturia, fecaluria, suprapubic pain and recurrent urinary infections. Surgical repair of EVF leads to rapid correction of both diarrhea and metabolic abnormalities. We report a 73-year-old diabetic woman with a neurogenic bladder secondary to a spine meningioma. She presented with diarrhea, vomiting, impaired consciousness and metabolic acidosis. She developed hypernatremia, hypokalemia, hypocalcemia, and hypophosphatemia, which were successfully corrected.

[Neurology and COVID-19: Case Series of Neurological Complications in 96 patients Admitted at a University Hospital]. / Neurología hospitalaria y COVID-19: serie de 96 pacientes evaluados en un hospital universitario.

BACKGROUND: There are multisystemic consequences secondary to SARS- CoV-2 infection. AIM: To characterize neurological complications in patients admitted due to SARS-CoV-2 infection. METHODS: Review of medical records of patients aged over 15 years with COVID-19 evaluated by the neurology team between April and August 2020 at a university hospital. Severity of the infection, referral reasons, neurological diagnoses and laboratory results were registered. The diagnoses were defined by consensus among the members of the hospital neurology group. Cerebrovascular and inflammatory diseases of the central and peripheral nervous system were defined as "probably associated" or "possibly associated" to COVID-19. RESULTS: Ninety-six patients had at least 1 new neu- rological complication. 74% were admitted due to pneumonia and 20% due to a neurological disease. The most common reasons for neurological referral were impaired consciousness (39%), focal neurological deficit (24%), headache (9%) and seizures (5%). The most relevant neurological diagnoses were delirium in 48 patients, stroke in 24, critical illness polyneuropathy and myopathy in 17, seizures in 14, brachial plexopathy in 3, compressive neuropathies in 5, encephalitis in 1, possible vasculitis in 1 and Guillain-Barré syndrome in 1. Stroke and epilepsy were associated with increased length of hospital stay, but without differences in mortality. CONCLUSIONS: The spectrum of neurological complications of COVID-19 is wide. There are clinical entities typical of critically ill patients and also diseases associated directly and indirectly with the SARS-CoV2 infection.

Determinación de factores de riesgo a reacciones adversas a medicamentos mediante farmacovigilancia intensiva en UCI / Risk factors for adverse drug reactions in patients admitted to intensive care units

Background: Patients hospitalized in intensive care units (ICU) are at higher risk of having adverse drug reactions (ADR). Aim: To determine risk factors for ADR, through intensive pharmacological surveillance at the ICU. Patients and Methods: An observational, descriptive and prospective study was made, determining risk parameters in patients who experienced ADR. Results: Eighty-five patients were surveilled and 24 (28%) had an ADR. A total of 48 drugs responsible for at least one ADR were identified. Seventy-three percent ADR were moderate and 27% were severe. The clinical variables significantly associated with ADR were a history of allergies, a high body mass index, the reason for admission, an APACHE II score ≥ 14 points, the use of invasive mechanical ventilation and more than seven days of hospitalization. The pharmacological variables associated with ADR were polypharmacy and medication associations and combinations. Conclusions: The identified risk factors have a great impact on pharmacokinetic and pharmacodynamic parameters, and should be considered to avoid the appearance of ADR.

Characterization of the Modulatory Effect of Hydroxychloroquine on ACE2 Activity: New Insights in relation to COVID-19.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown the ability to inhibit in vitro viral replications of coronaviridae viruses such as SARS-CoV and SARS-CoV-2. However, clinical trial outcomes have been disparate, suggesting that CQ and HCQ antiviral mechanisms are not fully understood. Based on three-dimensional structural similarities between HCQ and the known ACE2 specific inhibitor MLN-4760, we compared their modulation on ACE2 activity. Here we describe, for the first time, in a cell-free in vitro system that HCQ directly and dose-dependently inhibits the activity of recombinant human ACE2, with a potency similar to the MLN-4760. Further analysis suggests that HCQ binds to a noncompetitive site other than the one occupied by MLN-4760. We also determined that the viral spike glycoprotein segment that comprises the RBD segment has no effect on ACE2 activity but unexpectedly was able to partially reverse the inhibition induced by HCQ but not that by MLN-4760. In summary, here we demonstrate the direct inhibitory action of HCQ over the activity of the enzyme ACE2. Then, by determining the activity of ACE2, we reveal that the interaction with the spike protein of SARS-CoV-2 leads to structural changes that at least partially displace the interaction of the said enzyme with HCQ. These results may help to explain why the effectiveness of HCQ in clinical trials has been so variable. Additionally, this knowledge could be used for to develop techniques for the detection of SARS-CoV-2.

Central catheter-associated deep vein thrombosis in cancer: clinical course, prophylaxis, treatment.

The adequate handling of central venous catheters is a key element in the management of patients with cancer. Catheter-associated deep vein thrombosis is frequently observed in patients with malignant diseases; however, despite being a common complication among these patients, objective information concerning its epidemiology, clinical course, prophylaxis and treatment strategies is very limited. The reported incidence of catheter-related thrombosis (CRT) is highly variable, depending on symptomatic events, or if patients are screened for asymptomatic thrombosis. Several factors have been identified as potential predisposing factors for CRT, both technical and pathological aspects. The anticoagulant of choice is still unclear; while low-molecular-weight heparin is most commonly used, recent studies assessing the role of direct oral anticoagulants in the treatment of CRT show promise as an alternative, but the evidence remains insufficient and the decision must be made on a case-by-case basis.

Neurología hospitalaria y COVID-19: serie de 96 pacientes evaluados en un hospital universitario / Neurology and COVID-19: Case Series of Neurological Complications in 96 patients Admitted at a University Hospital

Background: There are multisystemic consequences secondary to SARS- CoV-2 infection. Aim: To characterize neurological complications in patients admitted due to SARS-CoV-2 infection. Methods: Review of medical records of patients aged over 15 years with COVID-19 evaluated by the neurology team between April and August 2020 at a university hospital. Severity of the infection, referral reasons, neurological diagnoses and laboratory results were registered. The diagnoses were defined by consensus among the members of the hospital neurology group. Cerebrovascular and inflammatory diseases of the central and peripheral nervous system were defined as "probably associated" or "possibly associated" to COVID-19. Results: Ninety-six patients had at least 1 new neu- rological complication. 74% were admitted due to pneumonia and 20% due to a neurological disease. The most common reasons for neurological referral were impaired consciousness (39%), focal neurological deficit (24%), headache (9%) and seizures (5%). The most relevant neurological diagnoses were delirium in 48 patients, stroke in 24, critical illness polyneuropathy and myopathy in 17, seizures in 14, brachial plexopathy in 3, compressive neuropathies in 5, encephalitis in 1, possible vasculitis in 1 and Guillain-Barré syndrome in 1. Stroke and epilepsy were associated with increased length of hospital stay, but without differences in mortality. Conclusions: The spectrum of neurological complications of COVID-19 is wide. There are clinical entities typical of critically ill patients and also diseases associated directly and indirectly with the SARS-CoV2 infection.

[Risk factors for adverse drug reactions in patients admitted to intensive care units]. / Determinación de factores de riesgo a reacciones adversas a medicamentos mediante farmacovigilancia intensiva en UCI.

BACKGROUND: Patients hospitalized in intensive care units (ICU) are at higher risk of having adverse drug reactions (ADR). AIM: To determine risk factors for ADR, through intensive pharmacological surveillance at the ICU. PATIENTS AND METHODS: An observational, descriptive and prospective study was made, determining risk parameters in patients who experienced ADR. RESULTS: Eighty-five patients were surveilled and 24 (28%) had an ADR. A total of 48 drugs responsible for at least one ADR were identified. Seventy-three percent ADR were moderate and 27% were severe. The clinical variables significantly associated with ADR were a history of allergies, a high body mass index, the reason for admission, an APACHE II score ≥ 14 points, the use of invasive mechanical ventilation and more than seven days of hospitalization. The pharmacological variables associated with ADR were polypharmacy and medication associations and combinations. CONCLUSIONS: The identified risk factors have a great impact on pharmacokinetic and pharmacodynamic parameters, and should be considered to avoid the appearance of ADR.

Experiencia del internado de medicina durante la pandemia por Covid-19 / Medical internship experience during the Covid-19 pandemic

Introducción: la pandemia por SARS-CoV-2 ha causado cambios en la formación médica a nivel mundial. Se han suspendido todas las actividades presenciales buscando reducir el contagio y, además, dada la creciente demanda hospitalaria, ha generado la necesidad de buscar nuevas formas de mantener la docencia y a la vez, balancear ésta con las necesidades hospitalarias. Desarrollo: revisamos la experiencia de estudiantes de medicina en otros países, tanto las similitudes como diferencias respecto a lo vivido en Chile, bajo nuestra formación. El interno de medicina, a diferencia del estudiante o del médico, se encuentra en un rol intermedio como práctica profesional y consideramos que tiene un rol positivo en el apoyo a los servicios de salud durante la crisis actual. Presentamos nuestra experiencia como internos de medicina voluntarios en los distintos campos clínicos que se encuentran bajo el alero de nuestra universidad y como hemos experimentado la creciente sobrecarga hospitalaria, incertidumbre, soledad y experiencia con la muerte en nuestra práctica. Conclusión: la experiencia como internos durante esta pandemia y como voluntarios en los distintos servicios de nuestros campos clínicos ha alterado profundamente nuestra formación médica. Nos ha permitido interiorizarnos no solo en aspectos técnicos, sino también en el área más humana de la medicina, en aprender sobre trabajo en equipo, la incertidumbre y el fin de la vida. Creemos que todo esto nos ha preparado y nos ha dado una experiencia invaluable para nuestra futura práctica médica.

Introduction: The SARS-Cov-2 pandemic has changed medical training worldwide. All face-to-face activities have been suspended seeking to reduce contagion, and also, given the growing hospital demand, it has generated the need to find new ways to keep tea-ching and, at the same time, balance it with hospital needs. Body: We review the experience of medical students in other countries, both similarities and differences from what has been experienced in Chile under our training. Medical interns, unlike other students or physicians, are in an intermediate role in their professional practice, and we consider that we have a positive role in supporting health services during the current crisis. We present our experience as volunteer medical interns in the different clinical facilities that are as-sociated with our university and how we have experienced the increasing hospital overload, uncertainty, loneliness, and experience with death in our practice. Conclusion: The experience as interns during this pandemic and as volunteers in the different departments from our clinical facilities has profoundly affected our medical training. It has allowed us to understand not only technical aspects but also the most humanitarian areas of medicine, by learning about teamwork, living with uncertainty, and the end of life. We believe that all of this has prepared us and given us invaluable experience for our future medical practice.

La criticidad de las Unidades de Intensivo. Ampliando las Unidades en tiempos de pandemia / Expanding ICU facilities in a pandemic scenario

Our country is suffering the effects of the ongoing pandemic of coronavirus disease (COVID-19). Because the vulnerability of healthcare systems, especially the intensive care areas they can rapidly be overloaded. That challenge the ICUs simultaneously on multiple fronts making urgent to increase the number of beds, without lowering the standards of care. The purpose of this article is to discuss some aspects of the national situation and to provide recommendations on the organizational management of intensive care units such as isolation protocols, surge in ICU bed capacity, ensure adequate supplies, protect and train healthcare workers maintaining quality clinical management.

[Expanding ICU facilities in a pandemic scenario]. / La criticidad de las Unidades de Intensivo. Ampliando las Unidades en tiempos de pandemia.

Our country is suffering the effects of the ongoing pandemic of coronavirus disease (COVID-19). Because the vulnerability of healthcare systems, especially the intensive care areas they can rapidly be overloaded. That challenge the ICUs simultaneously on multiple fronts making urgent to increase the number of beds, without lowering the standards of care. The purpose of this article is to discuss some aspects of the national situation and to provide recommendations on the organizational management of intensive care units such as isolation protocols, surge in ICU bed capacity, ensure adequate supplies, protect and train healthcare workers maintaining quality clinical management.

Plasma and Renal Cortex Meropenem Concentrations in Patients Undergoing Percutaneous Renal Biopsy.

BACKGROUND: Urinary tract infection (UTI) is the most common bacterial infection in the world. Some cases can have serious complication as death by septic shock. With the increasing spread of multidrug-resistant bacteria, the therapeutic possibilities against the complicated UTI are exhausted, forcing the use of broad-spectrum antibiotics such as meropenem. OBJECTIVES: To evaluate the penetrating ability of meropenem to renal tissue using an enzymatic biosensor in samples of renal cortex and its correlation with plasma levels. METHOD: We conducted a descriptive study in humans with indication of kidney biopsy. Meropenem was administered 1 hour before performing the biopsy, and the concentrations of meropenem in a series of samples of plasma and renal biopsy were determined. RESULTS: Renal biopsy and plasma samples of 14 patients, 64% women with body mass index of 26.3 kg/m2 (SD ± 2.9) and estimated glomerular filtration rate of 57.5 mL/min/1.73 m2 (SD ± 44.1), were examined. Renal biopsy was done at 68.9 minutes (SD ± 20.3), and the second plasma sample was obtained at 82.1 minutes (SD ± 21.2) and the third at 149.6 minutes (SD ± 31.5). The mean kidney meropenem concentration was 3.1 µg/mL (SD ± 1.9). For each patient, a decay curve of plasma meropenem concentration was constructed. The proportion of meropenem concentrations in renal tissue and plasma at biopsy moment was 14% (SD ± 10) with an interquartile range of 5.5-20.3%. With normal renal function, meropenem can achieve a bactericidal effect towards bacteria with MIC-90 < 0.76 µg/mL in the renal parenchyma. CONCLUSIONS: Meropenem is effective to treat the most frequent uropathogens with the bactericidal effect. Nevertheless, for resistant bacteria, it is necessary to adjust the dose to achieve adequate parenchymal concentration.

Effect of Lactamase Inhibitors on the Biosensor Penp during the Measurement of Lactam Antibiotics Concentration.

PenP is a fluorescent biosensor of lactam antibiotics (LA). It is structurally derived from the mutant lactamase TEM-1 comprising the substitution E166C, where fluorescein is covalently linked to cysteine. The presence of LA in the medium produces a change in the intrinsic fluorescence level of the biosensor, and the integral of the fluorescence level over time correlates directly with the LA concentration. Previously, we have successfully used PenP to determine the concentration of lactam antibiotics in clinical samples. The use of lactamase inhibitors (LI) is a common strategy to enhance the effect of LA due to the inhibition of an important resistance mechanism of pathogenic microorganisms. Structurally, LI and LA share the common element of recognition of lactamases (the lactam ring), but they differ in the reversibility of the mechanism of interaction with said enzyme. Because the biological recognition domain of PenP is derived from a lactamase, LI is expected to interfere with the PenP detection capabilities. Surprisingly, this work provides evidence that the effect of LI is marginal in the determination of LA concentration mediated by PenP.

Evaluation of Meropenem Pharmacokinetics in an Experimental Acute Respiratory Distress Syndrome (ARDS) Model during Extracorporeal Membrane Oxygenation (ECMO) by Using a PenP ß-Lactamase Biosensor.

INTRODUCTION: The use of antibiotics is mandatory in patients during extracorporeal membrane oxygenation (ECMO) support. Clinical studies have shown high variability in the antibiotic concentrations, as well as sequestration of them by the ECMO circuit, suggesting that the doses and/or interval administration used during ECMO may not be adequate. Thus, a fast response sensor to estimate antibiotic concentrations in this setting would contribute to improve dose adjustments. The biosensor PenP has been shown to have a dynamic range, sensitivity and specificity useful for pharmacokinetic (PK) tests in healthy subjects. However, the use of this biosensor in the context of a complex critical condition, such as ECMO during acute respiratory distress syndrome (ARDS), has not been tested. OBJECTIVES: To describe, by using PenP Biosensor, the pharmacokinetic of meropenem in a 24-h animal ARDS/ECMO model. METHODS: The PK of meropenem was evaluated in a swine model before and during ECMO. RESULTS: The PK parameters such as maximum concentration (Cmax), elimination rate constant (Ke), and cleareance (Cl), were not significantly altered during ECMO support. CONCLUSIONS: (a) ECMO does not affect the PK of meropenem, at least during the first 24 h; and (b) PenP has the potential to become an effective tool for making medical decisions associated with the dose model of antibiotics in a critical patient context.

Características y evolución de los pacientes que ingresan a una Unidad de Cuidados Intensivos de un hospital público / Characteristics and evolution of patients admitted to a public hospital intensive care unit

Background: The epidemiology of critical patients in Chile could differ from that reported in international studies. Aim: To describe the causes of admission and evolution of patients who were admitted to the ICU (Intensive Care Unit) of a general hospital in Chile in a two-year period (2012-2013). Patients and Methods: A retrospective study was carried out using the ICU database. The following variables were registered: admission diagnosis, APACHE II (Acute Physiology and Chronic Health Evaluation), days of mechanical ventilation (MV), ICU length of stay and ICU and hospital survival. Results: We analyzed data from 1075 aged 54 ± 18 years (55% males), representing 75% of the admissions during the study period. The median ICU and MV lengths were 5 and 3 days respectively (92% of patients required MV). APACHE II was 20.5 ± 8.2. The ICU and hospital mortality rate were 19.4% and 31%, respectively. Critical neurological diseases were the most common diagnoses requiring ICU, representing 26.8% of the admissions. No differences were found between 2012 and 2013 in age, APACHE II, ICU or hospital survival. A longer post ICU length of stay was found during 2013, both for patients who survived and those who died at the hospital. Conclusions: This study highlights the high percentage of patients that required MV and the high percentage critical neurological conditions requiring ICU admission. The characteristics and evolution of patients admitted to the ICU did not differ during 2012 and 2013.

[The impact of a better coordination between emergency and intensive care units in the care of critically ill patients]. / Medicina de urgencia y unidades de cuidados intensivos: Una alianza necesaria en busca de la mejoría de la atención de pacientes críticos.

The need for critical care services is increasing in Chile. Critical care beds and specialists in this area are scarce. In this article we discuss some aspects that hamper the care of critically ill patients from their arrival to the emergency department to their transfer to the ICU. Special emphasis is given to system saturation and its multiple causes. The benefits of an integrative approach between emergency medicine and critical care specialists are highlighted and some solutions are proposed to strengthen this partnership.