Meropenem extended infusion against nosocomial MIC 4 mg/L strains to guarantee drug effectiveness in burn patients at the earlier period of septic shock

<p>A bioanalytical method was developed and applied to quantify the free imipenem concentrations for pharmacokinetics and PK/PD correlation studies of the dose adjustments required to maintain antimicrobial effectiveness in pediatric burn patients. A reverse-phase Supelcosil LC18 column (250 x 4.6 mm 5 micra), binary mobile phase consisting of 0.01 M, pH 7.0 phosphate buffer and acetonitrile (99:1, v/v), flow rate of 0.8 mL/min, was applied. The method showed good absolute recovery (above 90%), good linearity (0.25-100.0 µg/mL, r<sup>2</sup>=0.999), good sensitivity (LLOQ: 0.25 µg/mL; LLOD: 0.12 µg/mL) and acceptable stability. Inter/intraday precision values were 7.3/5.9%, and mean accuracy was 92.9%. A bioanalytical method was applied to quantify free drug concentrations in children with burns. Six pediatric burn patients (median 7.0 years old, 27.5 kg), normal renal function, and 33% total burn surface area were prospectively investigated; inhalation injuries were present in 4/6 (67%) of the patients. Plasma monitoring and PK assessments were performed using a serial blood sample collection for each set, totaling 10 sets. The PK/PD target attained (40%T>MIC) for each minimum inhibitory concentration (MIC: 0.5, 1.0, 2.0, 4.0 mg/L) occurred at a percentage higher than 80% of the sets investigated and 100% after dose adjustment. In conclusion, the purification of plasma samples using an ultrafiltration technique followed by quantification of imipenem plasma measurements using the LC method is quite simple, useful, and requires small volumes for blood sampling. In addition, a small amount of plasma (0.25 mL) is needed to guarantee drug effectiveness in pediatric burn patients. There is also a low risk of neurotoxicity, which is important because pharmacokinetics are unpredictable in these critical patients with severe hospital infection. Finally, the PK/PD target was attained for imipenem in the control of sepsis in pediatric patients with burns.</p>

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Vancomycin dose adjustment in severe burn patients based on trough level for drug effectiveness against pathogens at 1 mg/l minimum inhibitory concentration

Critical Care ◽

10.1186/cc12645 ◽

2013 ◽

Vol 17 (S3) ◽

Cited By ~ 2

Author(s):

JM Silva ◽

AM Oliveira ◽

EV Campos ◽

DS Gomez ◽

MC Ferreira ◽

...

Keyword(s):

Minimum Inhibitory Concentration ◽

Dose Adjustment ◽

Inhibitory Concentration ◽

Trough Level ◽

Burn Patients ◽

Severe Burn ◽

Vancomycin Dose ◽

Drug Effectiveness

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Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria

Annals of Intensive Care ◽

10.1186/s13613-019-0622-8 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 4

Author(s):

Amol T. Kothekar ◽

Jigeeshu Vasishtha Divatia ◽

Sheila Nainan Myatra ◽

Anand Patil ◽

Manjunath Nookala Krishnamurthy ◽

...

Keyword(s):

Septic Shock ◽

Severe Sepsis ◽

Modeling And Simulation ◽

Empirical Therapy ◽

Gram Negative Bacteria ◽

Clinical Pharmacokinetics ◽

Gram Negative ◽

Arterial Blood ◽

Days Of Therapy ◽

Extended Infusion

Abstract Background Optimal anti-bacterial activity of meropenem requires maintenance of its plasma concentration (Cp) above the minimum inhibitory concentration (MIC) of the pathogen for at least 40% of the dosing interval (fT > MIC > 40). We aimed to determine whether a 3-h extended infusion (EI) of meropenem achieves fT > MIC > 40 on the first and third days of therapy in patients with severe sepsis or septic shock. We also simulated the performance of the EI with respect to other pharmacokinetic (PK) targets such as fT > 4 × MIC > 40, fT > MIC = 100, and fT > 4 × MIC = 100. Methods Arterial blood samples of 25 adults with severe sepsis or septic shock receiving meropenem 1000 mg as a 3-h EI eight hourly (Q8H) were obtained at various intervals during and after the first and seventh doses. Plasma meropenem concentrations were determined using a reverse-phase high-performance liquid chromatography assay, followed by modeling and simulation of PK data. European Committee on Antimicrobial Susceptibility Testing (EUCAST) definitions of MIC breakpoints for sensitive and resistant Gram-negative bacteria were used. Results A 3-h EI of meropenem 1000 mg Q8H achieved fT > 2 µg/mL > 40 on the first and third days, providing activity against sensitive strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. However, it failed to achieve fT > 4 µg/mL > 40 to provide activity against strains susceptible to increased exposure in 33.3 and 39.1% patients on the first and the third days, respectively. Modeling and simulation showed that a bolus dose of 500 mg followed by 3-h EI of meropenem 1500 mg Q8H will achieve this target. A bolus of 500 mg followed by an infusion of 2000 mg would be required to achieve fT > 8 µg > 40. Targets of fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 may be achievable in two-thirds of patients by increasing the frequency of dosing to six hourly (Q6H). Conclusions In patients with severe sepsis or septic shock, EI of 1000 mg of meropenem over 3 h administered Q8H is inadequate to provide activity (fT > 4 µg/mL > 40) against strains susceptible to increased exposure, which requires a bolus of 500 mg followed by EI of 1500 mg Q8H. While fT > 8 µg/mL > 40 require escalation of EI dose, fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 require escalation of both EI dose and frequency.

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Severe Altered Immune Status After Burn Injury Is Associated With Bacterial Infection and Septic Shock

Frontiers in Immunology ◽

10.3389/fimmu.2021.586195 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hélène Moins-Teisserenc ◽

Debora Jorge Cordeiro ◽

Vincent Audigier ◽

Quentin Ressaire ◽

Mourad Benyamina ◽

...

Keyword(s):

Septic Shock ◽

Innate Immunity ◽

Bacterial Infection ◽

Adaptive Immunity ◽

Bacterial Infections ◽

Burn Injury ◽

Inflammatory Responses ◽

Burn Patients ◽

Down Regulation ◽

Risk Of Death

Introduction: Burn injury is associated with a high risk of death. Whether a pattern of immune and inflammatory responses after burn is associated with outcome is unknown. The aim of this study was to explore the association between systemic immune and inflammatory responses and outcome in severely-ill burn patients.Materials and Methods: Innate immunity, adaptive immunity, activation and stress and inflammation biomarkers were collected at admission and days 2, 7, 14, and 28 in severely-ill adult burn patients. Primary endpoint was mortality at day 90, secondary endpoint was secondary infections. Healthy donors (HD) served as controls. Multiple Factorial Analysis (MFA) was used to identify patterns of immune response.Results: 50 patients were included. Age was 49.2 (44.2–54.2) years, total burn body surface area was 38.0% (32.7–43.3). Burn injury showed an upregulation of adaptive immunity and activation biomarkers and a down regulation of innate immunity and stress/inflammation biomarkers. High interleukin-10 (IL-10) at admission was associated with risk of death. However, no cluster of immune/inflammatory biomarkers at early timepoints was associated with mortality. HLA-DR molecules on monocytes at admission were associated with bacterial infections and septic shock. Later altered immune/inflammatory responses in patients who died may had been driven by the development of septic shock.Conclusion: Burn injury induced an early and profound upregulation of adaptive immunity and activation biomarkers and a down regulation of innate immunity and stress/inflammation biomarkers. Immune and inflammatory responses were associated with bacterial infection and septic shock. Absence of immune recovery patterns was associated with poor prognosis.

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Effect of Preinjury Statin Use on Mortality and Septic Shock in Elderly Burn Patients

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0b013e3181df61b1 ◽

2010 ◽

Vol 69 (1) ◽

pp. 99-103 ◽

Cited By ~ 21

Author(s):

Mary D. Fogerty ◽

David Efron ◽

Alessandro Morandi ◽

Jeffrey S. Guy ◽

Naji N. Abumrad ◽

...

Keyword(s):

Septic Shock ◽

Burn Patients ◽

Statin Use

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Coupled-plasma filtration and adsorption for severe burn patients with septic shock and acute kidney injury treated with renal replacement therapy

Burns ◽

10.1016/j.burns.2019.05.017 ◽

2020 ◽

Vol 46 (1) ◽

pp. 190-198 ◽

Cited By ~ 1

Author(s):

Filippo Mariano ◽

Zsuzsanna Hollo’ ◽

Nadia Depetris ◽

Valeria Malvasio ◽

Alberto Mella ◽

...

Keyword(s):

Septic Shock ◽

Acute Kidney Injury ◽

Renal Replacement Therapy ◽

Replacement Therapy ◽

Kidney Injury ◽

Burn Patients ◽

Severe Burn ◽

Plasma Filtration

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Long-Term Preservation of Renal Function in Septic Shock Burn Patients Requiring Renal Replacement Therapy for Acute Kidney Injury

Journal of Clinical Medicine ◽

10.3390/jcm10245760 ◽

2021 ◽

Vol 10 (24) ◽

pp. 5760

Author(s):

Filippo Mariano ◽

Consuelo De Biase ◽

Zsuzsanna Hollo ◽

Ilaria Deambrosis ◽

Annalisa Davit ◽

...

Keyword(s):

Septic Shock ◽

Acute Kidney Injury ◽

Renal Function ◽

Renal Replacement Therapy ◽

Kidney Injury ◽

Burn Patients ◽

Urine Protein ◽

Urine Albumin

Background. The real impact of septic shock-associated acute kidney injury (AKI) on the long-term renal outcome is still debated, and little is known about AKI-burn patients. In a cohort of burn survivors treated by continuous renal replacement therapy (CRRT) and sorbent technology (CPFA-CRRT), we investigated the long-term outcome of glomerular and tubular function. Methods. Out of 211 burn patients undergoing CRRT from 2001 to 2017, 45 survived, 40 completed the clinical follow-up (cumulative observation period 4067 months, median 84 months, IR 44-173), and 30 were alive on 31 December 2020. Besides creatinine and urine albumin, in the 19 patients treated with CPFA-CRRT, we determined the normalized GFR by 99mTc-DTPA (NRI-GFR) and studied glomerular and tubular urine protein markers. Results. At the follow-up endpoint, the median plasma creatinine and urine albumin were 0.99 (0.72–1.19) and 0.0 mg/dL (0.0–0.0), respectively. NRI-GFR was 103.0 mL/min (93.4–115). Four patients were diabetic, and 22/30 presented at least one risk factor for chronic disease (hypertension, dyslipidemia, and overweight). Proteinuria decreased over time, from 0.47 g/day (0.42–0.52) at 6 months to 0.134 g/day (0.09–0.17) at follow-up endpoint. Proteinuria positively correlated with the peak of plasma creatinine (r 0.6953, p 0.006) and the number of CRRT days (r 0.5650, p 0.035) during AKI course, and negatively with NRI–GFR (r −0.5545, p 0.049). In seven patients, urine protein profile showed a significant increase of glomerular marker albumin and glomerular/tubular index. Conclusions. Burn patients who experienced septic shock and AKI treated with CRRT had a long-term expectation of preserved renal function. However, these patients were more predisposed to microalbuminuria, diabetes, and the presence of risk factors for intercurrent comorbidities and chronic renal disease.

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Sepsis in Burns—Lessons Learnt from Developments in the Management of Septic Shock

Medicina ◽

10.3390/medicina58010026 ◽

2021 ◽

Vol 58 (1) ◽

pp. 26

Author(s):

Dorothee Boehm ◽

Henrik Menke

Keyword(s):

Septic Shock ◽

Screening Tool ◽

Scientific Basis ◽

Antimicrobial Treatment ◽

Burn Patients ◽

Surviving Sepsis Campaign ◽

Effective Screening ◽

Burn Care ◽

The Past ◽

Sepsis Therapy

After surviving the acute phase of resuscitation, septic shock is the cause of death in the majority of burn patients. Therefore, the management of septic shock is a cornerstone in modern burn care. Whereas sepsis therapy in general has undergone remarkable developments in the past decade, the management of septic shock in burn patients still has a long way to go. Instead, the differences of burn patients with septic shock versus general patients have been emphasized and thus, burn patients were excluded in every sepsis study which are the basis for modern sepsis therapy. However, due to the lack of evidence in burn patients, the standards of procedure for general sepsis therapy have been adopted in burn care. This review identifies the differences of burn patients with sepsis versus other septic patients and summarizes the scientific basis for modern sepsis therapy in general ICU patients and burn patients. Consequently, the results in general sepsis research should be transferred to burn care, which means the implementation of effective screening, early resuscitation, and efficient antimicrobial treatment. Therefore, on the basis of past developments and in the light of the current update of the Surviving Sepsis Campaign guidelines, this review introduces the “Burn SOFA score” and the “3 H’s of burn sepsis” as a screening tool for early sepsis recognition in burn patients.

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