Model-informed precision dosing of vancomycin in clinical practice: an intervention development study.

Background: Current guidelines recommend dosing vancomycin based on the area under the concentration time curve (AUC) to maximise efficacy and minimise the risk of nephrotoxicity. The preferred approach to AUC-guided therapy is to apply model-informed precision dosing (MIPD). However, the adoption in clinical practice has been slow.

Swedish multicentre study of target attainments with β-lactams in the ICU: which MIC parameter should be used?

Background: Therapeutic drug monitoring (TDM) has been suggested to optimize antimicrobial target attainment, typically using 100%T>MIC, in β-lactam treatment in the ICU. The MIC parameter used in this equation is mostly the worst case scenario MIC (MICWCS)-the highest MIC the empirical treatment should cover. However, the impact of the MIC parameter used in pharmacokinetic/pharmacodynamic calculations has been poorly investigated.

Semi-Conservative Treatment Versus Radical Surgery in Abdominal Aortic Graft and Endograft Infections.

Objective: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft preserving strategy is possible.

Invasive fungal infection by in an immunocompromised patient.

We report for the first time a case of disseminated infection caused by , a mold not previously associated with invasive infections in humans. occurs in natural and sterilized soil and may cause hypersensitivity pneumonitis in greenhouse workers. The immunocompromised patient presented with neutropenic fever that did not respond to broad-spectrum antibiotics and developed multiple skin and lung lesions.

Low attainment to PK/PD-targets for β-lactams in a multi-center study on the first 72 h of treatment in ICU patients.

Severe infections are life-threatening conditions commonly seen in the intensive care units (ICUs). Antibiotic treatment with adequate concentrations is of great importance during the first days when the bacterial load is the highest. Therapeutic drug monitoring (TDM) of β-lactam antibiotics has been suggested to monitor target attainment and to improve the outcome.

Urine Hydrogen Peroxide Levels and Their Relation to Outcome in Patients with Sepsis, Septic Shock, and Major Burn Injury.

Hydrogen peroxide (H2O2) and oxidative stress have been suggested as possible instigators of both the systemic inflammatory response and the increased vascular permeability associated with sepsis and septic shock. We measured H2O2 concentrations in the urine of 82 patients with severe infections, such as sepsis, septic shock, and infections not fulfilling sepsis-3 criteria, in patients with major burn injury with associated systemic inflammation, and healthy subjects. The mean concentrations of H2O2 were found to be lower in patients with severe infections compared to burn injury patients and healthy subjects.

Editor's Choice - Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study.

Objective: Abdominal aortic graft and endograft infection (AGI) is primarily treated by resection of the infected graft and restoration of distal perfusion through extra-anatomic bypass (EAB) or in situ reconstruction/repair (ISR). The aim of this study was to compare these surgical strategies in a nationwide multicentre retrospective cohort study.

Methods: The Swedish Vascular Registry (Swedvasc) was used to identify surgically treated abdominal AGIs in Sweden between January 1995 and May 2017.

Human plasma protein levels alter the in vitro antifungal activity of caspofungin: An explanation to the effect in critically ill?

Background: Recent studies have shown low caspofungin concentrations in critically ill patients. In some patients, the therapeutic target, area under the total plasma concentration curve in relation to the minimal inhibition concentration (AUC /MIC), seems not to be achieved and therapeutic drug monitoring (TDM) has been proposed. Caspofungin is highly protein-bound and the effect of reduced plasma protein levels on pharmacodynamics has not been investigated.

Population pharmacokinetics of cefotaxime in intensive care patients.

Purpose: To characterise the pharmacokinetics and associated variability of cefotaxime in adult intensive care unit (ICU) patients and to assess the impact of patient covariates.

Methods: This work was based on data from cefotaxime-treated patients included in the ACCIS (Antibiotic Concentrations in Critical Ill ICU Patients in Sweden) study. Clinical data from 51 patients at seven different ICUs in Sweden, given cefotaxime (1000-3000 mg given 2-6 times daily), were collected from the first day of treatment for up to three consecutive days.

The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting.

Objective: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs).

Methods: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.

Branched Endovascular Aortic Plug in Patients With Infrarenal Aortic Graft Infection and Hostile Anatomy.

To present a novel 4-branched endovascular aortic plug (BEVAP) for treatment of patients with infrarenal aortic graft infection. Two polymorbid male patients with aortic graft infections and an unsuturable diseased paravisceral aorta were treated under compassionate use with a custom-made stent-graft. The BEVAP is a factory-modified Zenith t-Branch thoracoabdominal endovascular graft with the distal tubular main graft portion removed, creating an aortic plug that excludes the abdominal aorta while maintaining perfusion to the visceral organs.

Nationwide Study of the Treatment of Mycotic Abdominal Aortic Aneurysms Comparing Open and Endovascular Repair.

Background: No reliable comparative data exist between open repair (OR) and endovascular aneurysm repair (EVAR) for mycotic abdominal aortic aneurysms (MAAAs). This nationwide study assessed outcomes after OR and EVAR for MAAA in a population-based cohort.

Methods: All patients treated for MAAAs in Sweden between 1994 and 2014 were identified in the Swedish vascular registry.

[Cross allergy between penicillins and other beta lactam antibiotics--the risk is much less than previously thought].

Severe IgE-mediated allergic reactions to penicillins are rare but might be fatal. Because some studies demonstrated a high risk of cross-sensitivity to cephalosporins and carbapenems it has been recommended to avoid these antibiotics in patients with suspected hypersensitivity to penicillins. However, recent studies and analyses conclude that the risk of cross-reactivity was overestimated in the earlier studies and that it is in fact very low for parenteral cephalosporins and perhaps even negligible for carbapenems.

Rational use of aminoglycosides--review and recommendations by the Swedish Reference Group for Antibiotics (SRGA).

The Swedish Reference Group for Antibiotics (SRGA) has carried out a risk-benefit analysis of aminoglycoside treatment based on clinical efficacy, antibacterial spectrum, and synergistic effect with beta-lactam antibiotics, endotoxin release, toxicity, and side effects. In addition, SRGA has considered optimal dosage schedules and advice on serum concentration monitoring, with respect to variability in volume of drug distribution and renal clearance. SRGA recommends that aminoglycoside therapy should be considered in the following situations: (1) progressive severe sepsis and septic shock, in combination with broad-spectrum beta-lactam antibiotics, (2) sepsis without shock, in combination with broad-spectrum beta-lactam antibiotics if the infection is suspected to be caused by multi-resistant Gram-negative pathogens, (3) pyelonephritis, in combination with a beta-lactam or quinolone until culture and susceptibility results are obtained, or as monotherapy if a serious allergy to beta-lactam or quinolone antibiotics exists, (4) serious infections caused by multi-resistant Gram-negative bacteria when other alternatives are lacking, and (5) endocarditis caused by difficult-to-treat pathogens when monotherapy with beta-lactam antibiotics is not sufficient.

Significant differences when using creatinine, modification of diet in renal disease, or cystatin C for estimating glomerular filtration rate in ICU patients.

Background: Renal dysfunction is associated with increased morbidity and mortality in intensive care patients. In most cases the glomerular filtration rate (GFR) is estimated based on serum creatinine and the Modification of Diet in Renal Disease (MDRD) formula, but cystatin C-estimated GFR is being used increasingly. The aim of this study was to compare creatinine and MDRD and cystatin C-estimated GFR in intensive care patients.

Subcellular localization and mobilization of carcinoembryonic antigen-related cell adhesion molecule 8 in human neutrophils.

The subcellular localization and mobilization of carcinoembryonic antigen-related cell adhesion molecule 8 (CEACAM8) was investigated quantitatively in human neutrophils. In resting neutrophils the majority of CEACAM8 was present in the secondary granules, and a small amount of CEACAM8 was present in a light membrane fraction. Stimulation of the neutrophils with phorbol 12-myristate 13-acetate caused a dramatic increase in the content of CEACAM8 in the light membrane fraction, suggesting a translocation of CEACAM8 to the plasma membrane from intracellular pools.

Expression of the C5a receptor (CD88) on granulocytes and monocytes in patients with severe sepsis.

Introduction: Treatment of patients with severe sepsis with agents antagonising the effects of C5a has been proposed based on beneficial effects in animal experiments and in vitro studies demonstrating upregulation of the C5a receptor (CD88) on granulocytes by endotoxin.

Materials And Methods: CD88 expression on leukocytes from 12 patients with severe sepsis or septic shock was analysed by flow cytometer, and serum complement factors C3a and C5b-9 were measured by enzyme immunoassay techniques.

Results: The granulocyte CD88 expression on day 1 was lowered (36; range, 2-59) in comparison with controls (63; range, 25-88) (P < 0.