Impact of Extracorporeal Membrane Oxygenation Circuitry on Remdesivir.

OBJECTIVES: This study aimed to determine the oxygenator impact on alterations of remdesivir (RDV) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane -oxygenation (ECMO) circuit including the Quadrox-i oxygenator. METHODS: One-quarter-inch and a 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A 1-time dose of RDV was administered into the circuits and serial preoxygenator and postoxygenator concentrations were obtained at 0 to 5 minutes, and 1-, 2-, 3-, 4-, 5-, 6-, 8-, 12-, and 24-hour time points. The RDV was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. RESULTS: For the 1/4-inch circuits with an oxygenator, there was a 35% to 60% RDV loss during the study period. For the 1/4-inch circuits without an oxygenator, there was a 5% to 20% RDV loss during the study period. For the 3/8-inch circuit with and without an oxygenator, there was a 60% to 70% RDV loss during the study period. CONCLUSIONS: There was RDV loss within the circuit during the study period and the RDV loss was more pronounced with the larger 3/8-inch circuit when compared with the 1/4-inch circuit. The impact of the -oxygenator on RDV loss appears to be variable and possibly dependent on the size of the circuit and -oxygenator. These preliminary data suggest RDV dosing may need to be adjusted for concern of drug loss via the ECMO circuit. Additional single- and multiple-dose studies are needed to validate these findings.

Detention of children and adolescents under mental health legislation: a scoping review of prevalence, risk factors, and legal frameworks.

BACKGROUND: For individuals with severe mental illness, involuntary assessment and/or treatment (hereafter detention) can be a necessary intervention to support recovery and may even be lifesaving. Despite this, little is known about how often these interventions are used for children and adolescents. METHODS: This global scoping review set out to: (1) map the current evidence around mental health detentions of children and adolescents (< 18 years); (2) identify the clinical, sociodemographic, and behavioural factors associated with detention; and (3) document the views of professionals and young people on the implementation of mental health legislation. RESULTS: After searching databases of peer-reviewed literature and citation chaining, 42 articles from 15 jurisdictions were included. About one fifth of psychiatric admissions in national register data were detentions, however trends were only available for a few high-income Western countries. The circumstances justifying detention and the criteria authorising detention varied between studies, with a mix of clinical factors and observed behaviours reported as the reason(s) warranting/precipitating a detention. Particular groups were more likely to experience detention, such as children and adolescents from minority ethnic communities and those with a documented history of abuse. There was a notable absence of qualitative research exploring the views of professionals or children and adolescents on detention. CONCLUSION: Further research is needed to explore the impact of detention on those aged < 18 years, including national register-based studies and qualitative studies. This is particularly relevant in nations currently undergoing legislative reform.

CSI clinical practice guidelines for dyslipidemia management: Executive summary.

Dyslipidemias are the most important coronary artery disease (CAD) risk factor. Proper management of dyslipidemia is crucial to control the epidemic of premature CAD in India. Cardiological Society of India strived to develop consensus-based guidelines for better lipid management for CAD prevention and treatment. The executive summary provides a bird's eye-view of the 'CSI: Clinical Practice Guidelines for Dyslipidemia Management' published in this issue of the Indian Heart Journal. The summary is focused on the busy clinician and encourages evidence-based management of patients and high-risk individuals. The summary has serialized various aspects of lipid management including epidemiology and categorization of CAD risk. The focus is on management of specific dyslipidemias relevant to India-raised low density lipoprotein (LDL) cholesterol, non-high density lipoprotein cholesterol (non-HDL-C), apolipoproteins, triglycerides and lipoprotein(a). Drug therapies for lipid lowering (statins, non-statin drugs and other pharmaceutical agents) and lifestyle management (dietary interventions, physical activity and yoga) are summarized. Management of dyslipidemias in oft-neglected patient phenotypes-the elderly, young and children, and patients with comorbidities-stroke, peripheral arterial disease, kidney failure, posttransplant, HIV (Human immunodeficiency virus), Covid-19 and familial hypercholesterolemia is also presented. This consensus statement is based on major international guidelines (mainly European) and expert opinion of lipid management leaders from India with focus on the dictum: earlier the better, lower the better, longer the better and together the better. These consensus guidelines cannot replace the individual clinician judgement who remains the sole arbiter in management of the patient.

Dietary management of dyslipidemia.

The rising burden of cardiovascular disease (CVD) has made the achievement of optimal lipoprotein levels a major public health priority. As nearly a fifth of global mortality is associated with dietary factors, and recommendations have been mired in controversy, a fresh look on the available data is attempted. Well established concepts regarding nutrition and cardiometabolic health, role of macronutrients, calories, and controversial foods are discussed followed by recommendations in the Indian context. A healthy dietary pattern rather than individual foods or nutrients is emphasized, and this is generally plant based with optional consumption of dairy, eggs, and meats within the suggested limits. Suggestions/recommendations are given for consumption of individual foods, remembering that choosing appropriate replacement foods is as important as restricting unhealthy foods.

Length and associated characteristics of short-term detentions: an analysis of detentions under the Mental Health Act in Scotland, 2006-2018.

PURPOSE: The Mental Health Act in Scotland is under review. Previous iterations increased patients' rights but the maximum time for short-term detentions remains unchanged, despite evolving psychiatric treatment models. We explored length, mode of ending and factors of influence on the application of short-term detention certificates (STDCs), which can last up to 28 days, across Scotland between 2006 and 2018. METHODS: Data on age, gender, ethnicity, date of commencement and ending of the STDC and detention site from all 42,493 STDCs issued to 30,464 patients over 12 years were extracted from the national repository for detentions under the Mental Health (Care and Treatment) (Scotland) Act 2003 and analysed using mixed models. RESULTS: One in five STDCs lapsed on day 28. Two in five were revoked and the remainder extended to a treatment order. STDCs that were not extended averaged 19 days, and revoked STDCs 14 days. The probability of a detention lapsing varied across hospitals and increased with patient age. The odds of a detention lapsing on day 28 were 62% lower and revoked detentions 10% shorter in 2018 relative to 2006. The odds of a detention extending decreased significantly from 2012 to 2018. Extended STDCs were associated with increased patient age, male gender, and ethnicity other than White Scottish. There was little initiation of or active revocation of STDCs on weekend days. CONCLUSION: The length of STDCs reduced over time, fewer detentions lapsed, and weekday patterning was evident in each year. These data can inform legislative and service reviews.

Oxygenator impact on peramivir in extra-corporeal membrane oxygenation circuits.

INTRODUCTION: This study aims to determine the oxygenator impact on alterations of peramivir (PRV) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extra-corporeal membrane oxygenation (ECMO) circuit including the Quadrox-i® oxygenator. METHODS: 1/4-inch and 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of PRV was administered into the circuits and serial pre- and post-oxygenator concentrations were obtained at 5-min and 1-, 2-, 3-, 4-, 5-, 6-, 8-, 12-, and 24-h time points. PRV was also maintained in a glass vial, and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. RESULTS: For the 1/4-in. circuit with an oxygenator, there was < 15% PRV loss, and for the 1/4-in. circuit without an oxygenator, there was < 3% PRV loss during the study period. For the 3/8-in. circuits with an oxygenator, there was < 15% PRV loss, and for the 3/8-in. circuits without an oxygenator, there was < 3% PRV loss during the study period. CONCLUSION: There was no significant PRV loss over the 24-h study period in either the 1/4-in. or 3/8-in circuit, regardless of the presence of the oxygenator. The concentrations obtained pre- and post-oxygenator appeared to approximate each other, suggesting there may be no drug loss via the oxygenator. This preliminary data suggests PRV dosing may not need to be adjusted for concern of drug loss via the oxygenator. Additional single and multiple dose studies are needed to validate these findings.

Developing a new pediatric extracorporeal membrane oxygenation (ECMO) program.

OBJECTIVES: We aimed to critically evaluate the effectiveness of a designated ECMO team in our ECMO selection process and patient outcomes in the first 3 years of our low-volume pediatric ECMO program. METHODS: We conducted a retrospective chart review of patients who received an ECMO consultation between the start of our program in March 2015 and May 2018. We gathered clinical and demographic information on patients who did and did not receive ECMO, and described our selection process. We reflected on the processes used to initiate our program and our outcomes in the first 3 years. RESULTS: Sixty-nine patients received consultations, and of those, 50 patients were potential candidates. 19 (38%) of the candidates were ultimately placed on ECMO. There were statistically significant differences in oxygen saturation, paO2, oxygenation index, A-aDO2, lactate, and pH between the patients who went on ECMO and who did not. We improved our outcomes from 0% survival to discharge in 2015, to 60% in 2018, with an average of 63% survival to discharge over the first 3 years of our program. CONCLUSIONS: In a low-volume pediatric ECMO center, having a designated team to assist in the patient selection process and management can help provide safe and efficient care to these patients, and improve patient outcomes. Having a strict management protocol and simulation sessions involving all members of the medical team yields comfort for the providers and optimal care for patients. This study describes our novel structure, processes, and outcomes, which we hope will be helpful to others seeking to develop a new pediatric ECMO program.

Experts' Consensus on Use of Long-Acting Nitroglycerine in the Management of Angina and Chronic Coronary Syndrome in India.

AIM: To address the existing gaps in knowledge about long-acting nitroglycerine (LA-NTG) and provide recommendations to address these issues. METHODOLOGY: Approved LA-NTG questionnaire that included 17 questions related to the role of LA-NTG in the management of angina and chronic coronary syndrome (CCS) was shared with 150 expert cardiologists from different regions from India. Results of these survey questionnaires were further discussed in 12 regional level meetings. The opinions and suggestions from all the meetings were compiled and analyzed. Further, recommendations were made with the help of attending national cardiology experts and a consensus statement was derived. RESULTS: This is the first consensus on LA-NTG, summarizing the clinical evidence from India and suggesting recommendations based on these data. The experts recommended early use of LA-NTG as a first-line antianginal therapy in combination with beta-blocker since it improves exercise tolerance in patients with CCS. A strong consensus was observed for using LA-NTG in patients with co-morbid hypertension, diabetes, chronic kidney disease and post-percutaneous coronary intervention angina. As a part of cardiac rehabilitation, LA-NTG allows patients with angina to exercise to a greater functional capacity. CONCLUSIONS: A national consensus was observed for several aspects of LA-NTG in the management of angina and CCS. The clinical experience of the experts confirmed an extremely satisfied patient perception about the efficacy of LA-NTG.

COVID-19 Vaccination in those with mental health difficulties: A guide to assist decision-making in England, Scotland, and Wales.

There is currently no specific guidance addressing vaccine hesitancy in those with mental health difficulties in the United Kingdom. This is particularly problematic when one considers that individuals with serious mental illnesses are at greater risk of infection and have poorer health outcomes for a range of reasons. There are also many individual and system level barriers to vaccination in this group. When an affected adult lacks the capacity to make a decision for themselves, it often falls to healthcare professionals to make a decision on that person's behalf and in their best interests. This article explores this matter with regard to the law in practice in the English and Welsh, and Scottish, jurisdictions and consider this with relevance to the safest approach that doctors and other healthcare professionals should take in working with patients for whom mental disorder may impact on decision-making capacity. The article focuses on psychiatric inpatients, including those who are detained involuntarily, to consider whether, and in what circumstances, COVID-19 vaccination should be given to individuals who cannot or do not consent.

Oxygenator impact on meropenem/vaborbactam in extracorporeal membrane oxygenation circuits.

INTRODUCTION: To determine the oxygenator impact on alterations of meropenem (MEM)/vaborbactam (VBR) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extra corporeal membrane oxygenation (ECMO) circuit including the Quadrox-i® oxygenator. METHODS: 1/4-inch and 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of MEM/VBR was administered into the circuits and serial pre- and post-oxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, 8, 12, and 24-hour time points. MEM/VBR was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. RESULTS: For the 1/4-inch circuit, there was an approximate mean 55% MEM loss with the oxygenator in series and a mean 33%-40% MEM loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was an approximate mean 70% MEM loss with the oxygenator in series and a mean 30%-38% MEM loss without an oxygenator in series at 24 hours. For both the 1/4-inch circuit and 3/8-inch circuits with and without an oxygenator, there was <10% VBR loss for the duration of the experiment. CONCLUSIONS: This ex-vivo investigation demonstrated substantial MEM loss within an ECMO circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and no significant VBR loss. Further evaluations with multiple dose in-vitro and in-vivo investigations are needed before specific MEM/VBR dosing recommendations can be made for clinical application with ECMO.

SIDMA as a criterion for psychiatric compulsion: An analysis of compulsory treatment orders in Scotland.

Scottish mental health legislation includes a unique criterion for the use of compulsion in the delivery of mental health care and treatment. Under the Mental Health (Care and Treatment) (Scotland) Act, 2003, patients must exhibit 'significantly impaired decision-making ability' (SIDMA) in order to be eligible for psychiatric detention or involuntary psychiatric treatment outside the forensic context. The SIDMA requirement represents a distinctive strategy in ongoing international efforts to rethink the conditions under which psychiatric compulsion is permissible. We reconstruct the history of the Scottish SIDMA requirement, analyse its differences from so-called 'fusion law,' and then examine how the SIDMA standard actually functions in practice. We analyse 100 reports that accompany applications for Compulsory Treatment Orders (CTOs). Based on this analysis, we provide a profile of the patient population that is found to exhibit SIDMA, identify the grounds upon which SIDMA is attributed to individual patients, and offer an assessment of the quality of the documentation of SIDMA. We demonstrate that there are systemic areas of poor practice in the reporting of SIDMA, with only 12% of CTOs satisfying the minimum standard of formal completeness endorsed by the Mental Welfare Commission. We consider what lessons might be drawn both for the ongoing review of mental health legislation in Scotland, and for law reform initiatives in other jurisdictions.

Limits of remote working: the ethical challenges in conducting Mental Health Act assessments during COVID-19.

COVID-19 has created additional challenges in mental health services, including the impact of social distancing measures on care and treatment. For situations where a detention under mental health legislation is required to keep an individual safe, psychiatrists may consider whether to conduct an assessment in person or using video technology. The Mental Health (Care and Treatment) (Scotland) Act 2003 does not stipulate that an assessment has to be conducted in person. Yet, the Code of Practice envisions that detention assessments would be conducted face to face in all circumstances. During the pandemic, the Mental Welfare Commission for Scotland, a statutory body with a duty to promote best practice of the Act, has been asked whether it may be acceptable and indeed preferable for some assessments to be conducted via video technology. Where an assessment is needed to determine if a patient needs to be detained, and where there is a need for social distancing or the need for 'shielding', remote assessments may in some circumstances be preferable. In this article, we outline the modification of the Mental Welfare Commission's previous outright rejection of virtual assessments as the pandemic progressed and discuss the ethical and legal issues the possibility of remote assessments has exposed. We also discuss the limits and when a virtual assessment is not considered ethical. As the pandemic moves from a state of emergency into a 'new normal' in psychiatric services during second, or subsequent, waves, the use and place (if any) of remote assessments for detention needs to be considered.

Morbidity of conversion from venovenous to venoarterial ECMO in neonates with meconium aspiration or persistent pulmonary hypertension.

BACKGROUND: Outcomes in neonates receiving extracorporeal membrane oxygenation (ECMO) for meconium aspiration syndrome (MAS) and/or persistent pulmonary hypertension (PPHN) are favorable. Infants with preserved perfusion are often offered venovenous (VV) support to spare morbidities of venoarterial (VA) ECMO. Worsening perfusion or circuit complications can prompt conversion from VV-to-VA support. We examined whether outcomes in infants requiring VA ECMO for MAS/PPHN differed if they underwent VA support initially versus converting to VA after a VV trial, and what factors predicted conversion. METHODS: We reviewed the Extracorporeal Life Support Organization registry from 2007 to 2017 for neonates with primary diagnoses of MAS/PPHN. Propensity score analysis matched VA single-runs (controls) 4:1 against VV-to-VA conversions based on age, pre-ECMO pH, and precannulation arrests. Primary outcomes were complications and survival. Data were analyzed using Mann-Whitney U and Fisher's exact testing. Multivariate regression identified independent predictors of conversion for VV patients. RESULTS: 3831 neonates underwent ECMO for MAS/PPHN, including 2129 (55%) initially requiring VA support. Of 1702 patients placed on VV ECMO, 98 (5.8%) required VV-to-VA conversion. Compared with 364 propensity-matched isolated VA controls, conversion runs were longer (190 vs. 127 h, P < 0.001), were associated with more complications, and decreased survival to discharge (70% vs. 83%, P = 0.01). On multivariate regression, conversion was more likely if neonates on VV ECMO did not receive surfactant (OR = 1.7;95%CI = 1.1-2.7;P = 0.03) or required high-frequency ventilation (OR = 1.9;95%CI = 1.2-3.3;P = 0.01) before ECMO. CONCLUSION: Conversion from VV-to-VA ECMO in infants with MAS/PPHN conveys increased morbidity and mortality compared to similar patients placed initially onto VA ECMO. VV patients not receiving surfactant or requiring high-frequency ventilation before cannulation may have increased risk of conversion. While conversions remain rare, decisions to offer VV ECMO for MAS/PPHN must be informed by inferior outcomes observed should conversion be required. LEVEL OF EVIDENCE: Level of evidence 3 Retrospective comparative study.

Characteristics of Hospitalized Children With SARS-CoV-2 in the New York City Metropolitan Area.

OBJECTIVES: To describe the characteristics of hospitalized children with severe acute respiratory syndrome coronavirus 2 in New York City metropolitan area. PATIENTS AND METHODS: This was a multicenter, retrospective cohort study at 4 hospitals comprising 82 hospitalized children (0-21 years) who tested positive for severe acute respiratory syndrome coronavirus 2 after symptoms and risk screening between March 1 and May 10, 2020. We subdivided patients on the basis of their admission to acute or critical care units and by age groups. Further subanalyses were performed between patients requiring respiratory support or no respiratory support. RESULTS: Twenty-three (28%) patients required critical care. Twenty-nine (35%) patients requiring respiratory support, with 9% needing mechanical ventilation, and 1 required extracorporeal support. All patients survived to discharge. Children with any comorbidity were more likely to require critical care (70% vs 37%, P = .008), with obesity as the most common risk factor for critical care (63% vs 28%, P = .02). Children with asthma were more likely to receive respiratory support (28% vs 8%, P = .02), with no difference in need for critical care (P = .26). Children admitted to critical care had higher rates of renal dysfunction at presentation (43% vs 10%, P = .002). CONCLUSIONS: Children with comorbidities (obesity and asthma in particular) were at increased risk for critical care admission and/or need for respiratory support. Children with renal dysfunction at presentation were more likely to require critical care.

Oxygenator impact on voriconazole in extracorporeal membrane oxygenation circuits.

INTRODUCTION: To determine the oxygenator impact on alterations of voriconazole in a contemporary neonatal/pediatric (1/4 inch) and adolescent/adult (3/8 inch) extracorporeal membrane oxygenation circuit including the Quadrox-i® oxygenator. METHODS: Simulated closed-loop extracorporeal membrane oxygenation circuits (1/4 and 3/8 inch) were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. In addition, 1/4- and 3/8-inch circuits were also prepared without an oxygenator in series. A one-time dose of voriconazole was administered into the circuits, and serial pre- and post-oxygenator concentrations were obtained at 5 minutes, 1, 2, 3, 4, 5, 6, and 24 hour time points. Voriconazole was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation. RESULTS: For the 1/4-inch circuit, there was an approximate mean of 64-67% voriconazole loss with the oxygenator in series and mean of 15-20% voriconazole loss without an oxygenator in series at 24 hours. For the 3/8-inch circuit, there was an approximate mean of 44-51% voriconazole loss with the oxygenator in series and a mean of 8-12% voriconazole loss without an oxygenator in series at 24 hours. The reference voriconazole concentrations remained relatively constant during the entire study period demonstrating that the drug loss in each size of the extracorporeal membrane oxygenation circuit with or without an oxygenator was not a result of spontaneous drug degradation. CONCLUSION: This ex vivo investigation demonstrated substantial voriconazole loss within an extracorporeal membrane oxygenation circuit with an oxygenator in series with both sizes of the Quadrox-i oxygenator at 24 hours and no significant voriconazole loss in the absence of an oxygenator. Further evaluations with multiple dose in vitro and in vivo investigations are needed before specific voriconazole dosing recommendations can be made for clinical application with extracorporeal membrane oxygenation.

Ceftaroline Cerebrospinal Fluid Penetration in the Treatment of a Ventriculopleural Shunt Infection: A Case Report.

Pharmacokinetic data regarding ceftaroline fosamil (CPT) penetration into cerebrospinal fluid (CSF) are limited to a rabbit model (15% inflamed) and adult case reports. We describe serum and CSF CPT concentrations in a 21-year-old, 34.8 kg female, medically complex patient presented with a 4-day history of fevers (Tmax 39.2°C), tachypnea, tachycardia, fatigue, and a 1-week history of pus and blood draining from the ventriculopleural (VPL) shunt. A head CT and an ultrasound of the neck revealed septated complex fluid collection surrounding the shunt. Therapy was initiated with vancomycin and ceftriaxone. Blood and CSF cultures from hospital day (HD) 1 were positive for methicillin-resistant Staphylococcus aureus with a CPT MIC of 0.5 mg/L and a vancomycin MIC range of 0.5 to 1 mg/L. On HD 3, CPT was added. On HD 7, simultaneous serum (69.4, 44, and 30.2 mg/L) and CSF (1.7, 2.3, and 2.3 mg/L) concentrations were obtained at 0.25, 1.5, and 4.75 hours from the end of an infusion. Based on these concentrations, CPT CSF penetration ratio ranged from 2.4% to 7.6%. After addition of CPT, the blood and CSF cultures remained negative on a regimen of vancomycin plus CPT. On HD 14, a new left-sided VPL shunt was placed. The patient continued on CPT for a period of 7 days after the new VPL shunt placement. This case demonstrated CPT CSF penetration in a range of 2.4% to 7.6%, approximately half of the rabbit model. This allowed for CSF concentrations at least 50% free time > 4 to 6× MIC of the dosing interval with a dosing regimen of 600 mg IV every 8 hours in a 34.8 kg chronic patient and resulted in a successful clinical outcome with no identified adverse outcomes.

Therapeutic Drug Monitoring of Levoffoxacin in an Obese Adolescent: A Case Report.

OBJECTIVES: To describe the pharmacokinetics of levofloxacin in an obese adolescent patient in the pediatric intensive care unit. METHODS: A single-patient medical record review was conducted. RESULTS: A 168-kg, 15-year-old female with past medical history of Prader-Willi syndrome and asthma initially presented with respiratory distress secondary to asthma exacerbation. She failed non-invasive ventilation and was subsequently intubated for respiratory failure and progressed to high-frequency oscillatory ventilation. On hospital day 1 (HD 1) an infectious workup was begun because of a fever, worsening clinical status, and initiation of vasopressors and an empiric antimicrobial regimen of cefepime and clindamycin. The urine culture subsequently grew Escherichia coli and the respiratory culture grew Pseudomonas aeruginosa. She continued to be febrile, which was thought to be due to an intra-abdominal abscess. On HD 14, the antimicrobial regimen was changed to levofloxacin because of continued fevers and no significant clinical improvement. Levofloxacin was initiated at 1000 mg IV every 24 hours. Levofloxacin serum levels were obtained at 0.5, 3.5, and 11.5 hours after infusion, which were 8.61, 5.76, and 2.7 mg/L, respectively. These concentrations translated into a peak level of 8.79 mg/L, a half-life of 6.4 hours, and an AUC of 80 mg·hr/L, which are discordant from the expected peak of 16 mg/L, a half-life of 8 hours, and an AUC of 120 mg·hr/L. Based on these values, the levofloxacin regimen was adjusted to 1000 mg IV every 12 hours, and repeat levels 0.5, 3.5, and 11.5 hours after infusion were 9.91, 6.56, and 3.27 mg/L, respectively, corresponding to a peak of 10.5 mg/L, a half-life of 5.18 hours, and an AUC of 200 mg·hr/L. After the adjustment in levofloxacin regimen, she became afebrile, WBC resolution and improvement in her overall clinical status, and she received a total duration for levofloxacin of 21 days. CONCLUSION: A levofloxacin regimen of 1000 mg IV every 12 hours was successful in providing for an appropriate AUC exposure and was associated with a successful clinical outcome in this morbidly obese adolescent.

Targeted Multidrug Resistant Organism Antimicrobial Prophylaxis and Postoperative Infections in Pediatric Cardiothoracic Surgical Patients.

BACKGROUND: To determine if receiving targeted antimicrobial (AM) prophylaxis has an effect on the rate of postoperative infections in patient's colonized with a multidrug resistant organism (MDRO) undergoing cardiothoracic surgery (CTS). METHODS: Single-center, retrospective medical record review of pediatric patients from birth to 18 years of age undergoing CTS from January 2013 to September 2018. Demographic data collected included age, specific MDRO, site of MDRO colonization, type of surgery, perioperative AM agent and type of infection. Patients were stratified into 2 groups, MDRO+ and MDRO-. Demographic and clinical characteristics were compared between groups with a Student's t test for continuous variables and a χ2, Fisher exact test or Mann-Whitney U test for noncontinuous variables. A 2-sided significance level of α = 0.05 was used to determine statistical significance. All analyses were performed using IBM SPSS Version 24 (SPSS Inc., Chicago, IL). RESULTS: Fifty patients (26 males/24 females) were included in the MDRO (+) group and 295 patients (168 males/127 females) in the MDRO (-) group. The median age was 0.48 years (interquartile range 0.24-1 year) and 0.9 years (interquartile range 0.19-8 years) in the MDRO (+) and MDRO (-) groups, P = 0.003. 2 of 50 (4%) MDRO (+) patients and 15 of 295 (5.1 %) MDRO (-) patients developed an infection, P = 1. 10 of 50 (20%) MDRO (+) patients received targeted AM toward the MDRO and none developed an infection. Of the 2 MDRO (+) patients with infection, 1 was infected with the MDRO. For MDRO (+) patients, there was no difference in the rate of infection whether targeted AM therapy was received, P = 1. CONCLUSIONS: There was no difference in the rate of postoperative infection between MDRO (+) and MDRO (-) patients. Additionally, these preliminary pediatric data suggest targeting AM agents to a specific MDRO does not impact the rate of postoperative infection in children undergoing CTS. Larger studies are warranted to confirm these findings.