Prolonged Infusion of ß-lactams Decreases Mortality in Patients with Septic Shock: A Retrospective Before-and-after Study

Septic shock substantially alters the pharmacokinetic properties of ß-lactams with a subsequently high risk of insufficiently low serum concentrations and treatment failure. Considering their pharmacokinetic (PK)/pharmacodynamic (PD) index, prolonged infusions (PI) of ß-lactams extend the time that the unbound fraction of the drug remains above the minimal inhibitory concentration MIC (ft >MIC) and may improve patient survival. The present study is a monocentric, retrospective before-and-after analysis of septic shock patients treated with ß-lactams. Patients of the years 2015-2017 received intermittent bolus application whereas patients of 2017-2020 received PI of ß-lactams. The primary outcome was mortality at day 30 and 90 after diagnosis of septic shock. Mortality rates in the PI group were significantly lower on day 30 (PI: 41%, n=119/290 vs. IB: 54.8%, n=68/114; p=0.0097) and day 90 (PI: 47.9%, n=139/290 vs. IB: 62.9%, n=78/124; p=0.005). After propensity-score matching, 30- and 90-day mortality remained lower for the PI group (-10%). PI further reduced duration of invasive ventilation. PI of β-lactam antibiotics led to a stronger decrease in SOFA scores within a 14d-observation period. PI of ß-lactams significantly reduces mortality in patients with septic shock and may have beneficial effects on invasive ventilation and recovery from sepsis-related organ failure.

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Prolonged Infusion of β-Lactams Decreases Mortality in Patients with Septic Shock: A Retrospective Before-and-After Study

Antibiotics ◽

10.3390/antibiotics10060687 ◽

2021 ◽

Vol 10 (6) ◽

pp. 687

Author(s):

Daniel Christoph Richter ◽

Maximilian Dietrich ◽

Lazar Detelinov Lalev ◽

Felix C.F. Schmitt ◽

Mascha Onida Fiedler ◽

...

Keyword(s):

Septic Shock ◽

Invasive Ventilation ◽

Unbound Fraction ◽

Improve Patient Survival ◽

Beneficial Effects ◽

Pharmacokinetic Properties ◽

Before And After ◽

Reduction Of Mortality ◽

Improve Patient ◽

Observation Period

Septic shock substantially alters the pharmacokinetic properties of β-lactams with a subsequently high risk of insufficiently low serum concentrations and treatment failure. Considering their pharmacokinetic (PK)/pharmacodynamic (PD) index, prolonged infusions (PI) of β-lactams extend the time that the unbound fraction of the drug remains above the minimal inhibitory concentration MIC (ft >MIC) and may improve patient survival. The present study is a monocentric, retrospective before-and-after analysis of septic shock patients treated with β-lactams. Patients of the years 2015-2017 received intermittent bolus application whereas patients of 2017–2020 received PI of β-lactams. The primary outcome was mortality at day 30 and 90 after diagnosis of septic shock. Mortality rates in the PI group were significantly lower on day 30 (PI: 41%, n = 119/290 vs. IB: 54.8%, n = 68/114; p = 0.0097) and day 90 (PI: 47.9%, n = 139/290 vs. IB: 62.9%, n = 78/124; p = 0.005). After propensity-score matching, 30- and 90-day mortality remained lower for the PI group (−10%, p = 0.14). PI was further associated with a reduction in the duration of invasive ventilation and a stronger decrease in SOFA scores within a 14d-observation period. PI of β-lactams was associated with a significant reduction of mortality in patients with septic shock and may have beneficial effects on invasive ventilation and recovery from sepsis-related organ failure.

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Common Organisms Responsible for Healthcare-associated Infection (HCAI)

Tutorial Topics in Infection for the Combined Infection Training Programme ◽

10.1093/oso/9780198801740.003.0026 ◽

2019 ◽

Author(s):

George Jacob ◽

Martina N. Cummins

Keyword(s):

Risk Assessment ◽

High Risk ◽

Local Policy ◽

Healthcare Associated Infection ◽

Beta Lactam ◽

Beta Lactam Antibiotics ◽

Patient Admissions ◽

Before And After ◽

Control And Prevention ◽

Infectious Waste

MRSA are S. aureus which become methicillin resistant by the acquisition of the mec A gene which is on a mobile chromosomal determinant called staphylococcal cassette chromosome mec (SCC mec). The mec A gene encodes for a penicillin- binding protein (PBP2a) which has a low affinity for isoxazolyl-penicillins (MICs to oxacillin/ meticillin ≥ 4μg/ ml) and is resistant to all classes of beta-lactam antibiotics. Current Department of Health (DOH) guidance (2014) recommends that mandatory MRSA screening be streamlined to include only: ● All patient admissions to high- risk units; ● Healthcare workers; and ● All patients previously identified as colonized or infected with MRSA. The guidance also advises Trusts to follow local risk assessment policies to identify other potential high- risk units or units with a history of high endemicity of MRSA; and The guidance also recommends regular auditing of compliance with MRSA screening policy. The 2006 guideline for the control and prevention of MRSA in healthcare facilities recommends the following four measures. ● Isolation MRSA- positive patients should be nursed in a single room or if none is available, cohorting into a bay after risk assessment. Patient movement, and the number of staff and visitors looking after the patient, should be minimized. ● Hand hygiene and use of personal protective equipment (PPE) All staff and visitors should decontaminate their hands with soap and water/or an alcohol rub before and after contact with the patient or their immediate surroundings. Single-use disposable gloves and aprons/non- permeable gowns should be used by staff and visitors if there is a risk of contamination with body fluids. ● Disposal of waste and laundry All waste from colonized/ infected patients should be placed in the infectious waste stream. All linen and bedding from patients colonized/infected with MRSA should be considered as contaminated and processed as infected linen. ● Cleaning and decontamination The patient’s room should be cleaned/disinfected daily with an appropriate detergent/disinfectant as per local policy. On discharge of the patient, the room needs to be terminally cleaned before it is reused. All patient equipment should either be single-patient use or be cleaned, disinfected, and sterilized.

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29: IMPACT OF DELAYS IN SECOND-DOSE BETA-LACTAM ANTIBIOTICS ON MORTALITY IN SEPSIS AND SEPTIC SHOCK

Critical Care Medicine ◽

10.1097/01.ccm.0000618616.87511.12 ◽

2020 ◽

Vol 48 (1) ◽

pp. 15-15

Author(s):

John Hammer ◽

Shelby Merchant ◽

Jing Zhao ◽

William Anderson ◽

Erin Roach

Keyword(s):

Septic Shock ◽

Beta Lactam ◽

Beta Lactam Antibiotics ◽

Sepsis And Septic Shock

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Effects of High Volume Haemodiafiltration on Inflammatory Response Profile and Microcirculation in Patients with Septic Shock

BioMed Research International ◽

10.1155/2015/125615 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Kadri Tamme ◽

Liivi Maddison ◽

Rein Kruusat ◽

Hans-Erik Ehrlich ◽

Mirjam Viirelaid ◽

...

Keyword(s):

Septic Shock ◽

Kidney Injury ◽

High Volume ◽

Target Range ◽

Sublingual Microcirculation ◽

Cytokine Levels ◽

Before And After ◽

Single Centre Study ◽

The Mean ◽

Improve Patient

Background. High volumes of haemofiltration are used in septic patients to control systemic inflammation and improve patient outcomes. We aimed to clarify if extended intermittent high volume online haemodiafiltration (HVHDF) influences patient haemodynamics and cytokines profile and/or has effect upon sublingual microcirculation in critically ill septic shock patients.Methods. Main haemodynamic and clinical variables and concentrations of cytokines were evaluated before and after HVHDF in 19 patients with septic shock requiring renal replacement therapy due to acute kidney injury. Sublingual microcirculation was assessed in 9 patients.Results. The mean (SD) time of HVHDF was 9.4 (1.8) hours. The median convective volume was 123 mL/kg/h. The mean (SD) dose of norepinephrine required to maintain mean arterial pressure at the target range of 70–80 mmHg decreased from 0.40 (0.43) μg/kg/min to 0.28 (0.33) μg/kg/min (p= 0.009). No significant changes in the measured cytokines or microcirculatory parameters were observed before and after HVHDF.Conclusions. The single-centre study suggests that extended HVHDF results in decrease of norepinephrine requirement in patients with septic shock. Haemodynamic improvement was not associated with decrease in circulating cytokine levels, and sublingual microcirculation was well preserved.

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The Kinetics of Ampicillin Release from Hydroxyapatite for Bones Regeneration

International Journal of Chemical Engineering ◽

10.1155/2009/273808 ◽

2009 ◽

Vol 2009 ◽

pp. 1-5

Author(s):

Giovanilton Ferreira da Silva ◽

José Sílvio Veras Albuquerque ◽

Caroliny Gomes de Oliveira ◽

Ricardo Emilio Ferreira Quevedo Nogueira ◽

Andrea Lopes de Oliveira Ferreira

Keyword(s):

Human Medicine ◽

Beta Lactam ◽

Adsorption Experiment ◽

Beta Lactam Antibiotics ◽

High Release ◽

Before And After ◽

Dose Control ◽

Low Toxicity ◽

The Difference ◽

Kinetics Of

Semisynthetic beta-lactam antibiotics are among the most used pharmaceuticals. Their use in veterinary and human medicine is in continuous expansion. There is a growing need for developing bioactive implants. Advantages of implantable drug delivery tools can include high release efficiency, precise dose control, low toxicity, and allow to overcome disadvantages connected with conventional methods. In this respect, hydroxyapatite (HA) is an elective material. It enables to produce architectures similar to those of real bones. Here we studied a kinetic model to describe ampicillin release from HA. In the course of adsorption experiment, ampicillin was dissolved, maintained at and shaken at 60 strokes/minute. Samples were withdrawn periodically for analysis and then returned to the mixture. Adsorbed amounts were measured by the difference of the concentration of the antibiotics before and after adsorption using UV adsorption at 225 nm. The aim of this work was to evaluate its application as ampicillin delivery carrier.

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