Antibiotics For Severe Infections Research Articles

Relationship between nephrotoxicity and area under the concentration-time curve of vancomycin in critically ill patients: a multicenter retrospective study.

Vancomycin (VAN) is a glycopeptide antibiotic and one of the most commonly used antibiotics for severe infections caused by methicillin-resistant Staphylococcus aureus. However, higher VAN concentrations have been associated with an increased risk of acute kidney injury (AKI). Herein, we aimed to assess the frequency of AKI in different areas under the concentration-time curve (AUC) values of VAN using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. We identified an association between AUC on day 2 and the risk of AKI in intensive care unit patients, suggesting that not only AUCs above 600 µg·h/mL but also those between 500 and 600 µg·h/mL pose a risk for AKI. Therefore, individualized dosing is feasible, with pharmacists being able to optimize VAN doses to attain appropriate targets.

Re-evaluating the suitability of using fluoroquinolones in the treatment of infections in the context of FQ consumption and correlating changes to microorganism resistance levels in EU/EEA countries between 2016 and 2021.

The aim of this study was to re-evaluate fluoroquinolone (FQ) use in treatment by analyzing the consumption of FQ and the resistance levels of selected Gram‑negative bacilli, as well as Neisseria gonorrhoeae and Mycobacterium tuberculosis complex in EU/EEA countries and in Poland between 2016 and 2021. Data from ECDC surveillance systems EARS-Net, Euro-GASP, and the European Tuberculosis Surveillance Network were included in the description of pathogen resistance. And the ESAC-Net project for determining FQ consumption. In over half of the EU/EEA countries, the consumption of fluoroquinolones decreased in both the community sector and the hospital sector between 2016 and 2021. The prevalence of FQ-R Escherichia coli, Klebsiella pneumoniae, Acinetobacter spp., Mycobacterium tuberculosis complex, and Neisseria gonorrhoeae exceeded 20%. The prevalence of fluoroquinolone-resistant (FQ-R) Pseudomonas aeruginosa in EU/EEA countries was less than 20% except for 2017. In most EU/EEA countries, the use of FQ has reduced in last years, except for countries like Poland where FQ were an overused group of antibiotics in the treatment of various types of infections. Fluoroquinolones, as life-saving antibiotics in severe infections, should be withdrawn from empirical treatment in Poland and in countries with a high prevalence of FQ-R microorganisms.

European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine)

ScopeThese ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy. MethodsAn expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii. Treatments were classified as head-to-head comparisons between individual antibiotics and between monotherapy and combination therapy regimens, including defined monotherapy and combination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and secondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy and combination therapy regimens was classified by the GRADE recommendations. The strength of the recommendations for or against treatments was classified as strong or conditional (weak). RecommendationsThe guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, β-lactam/β-lactamase inhibitors on infections caused by carbapenem-resistant Gram-negative bacteria. Most recommendations are based on very-low- and low-certainty evidence. A high value was placed on antibiotic stewardship considerations in all recommendations, searching for carbapenem-sparing options for 3GCephRE and limiting the recommendations of the new antibiotics for severe infections, as defined by the sepsis-3 criteria. Research needs are addressed.

Physician administered antibiotics in severe infections in a prehospital setting

Physician administered antibiotics in severe infections in a prehospital setting

Continuous infusion of β-lactam antibiotics in severe infections: a review of its role

Continuous infusion of β-lactam antibiotics has been widely promoted to optimise their time-dependent activity. Increasing evidence is emerging suggesting potential benefits in patient populations with altered pathophysiology, such as seriously ill patients. From a pharmacokinetic viewpoint, much information supports higher trough concentrations of β-lactam antibiotics when administered by continuous infusion. This advantage of continuous infusion translates into a superior ability to achieve pharmacodynamic targets, particularly when the minimum inhibitory concentration (MIC) of the pathogen is ≥4 mg/L. One drawback of continuous infusion may be limited physicochemical stability. This issue exists particularly for carbapenem antibiotics whereby prolonged infusions (i.e. >3 h) can be used to improve the time above the MIC compared with conventional bolus dosing. Few studies have examined clinical outcomes of bolus and continuous dosing of β-lactam antibiotics in seriously ill patients. No statistically significant differences have been shown for: mortality; time to normalisation of leukocytosis or pyrexia; or duration of mechanical ventilation, intensive care unit stay or hospital stay. Some evidence suggests improved clinical cure and resolution of illness with continuous infusion in seriously ill patients. Pharmacoeconomic advantages of continuous infusion of β-lactam antibiotics are well characterised. Available data suggest that seriously ill patients with severe infections requiring significant antibiotic courses (≥4 days) may be the subgroup that will achieve better outcomes with continuous infusion.

Aminoglucósidos

Aminoglycosides remain as a efficacious class of antimicrobials, commonly used in the clinical practice. In spite of the existence of several mechanisms of resistance, they continue being active against most of the aerobic Gram-negative bacilli. Currently, although aminoglycosides may be used as monotherapy in the urinary tract infections, they are mainly used in combination with b-lactam antibiotics in severe infections caused by Gram-negative bacilli. The knowledge about the pharmacokinetic and pharmacodynamic parameters of aminoglycosides has suggested their use in an once-daily dosing regimen. This dosing has shown as efficacious as multiple-daily dosing regimen in several studies, which also have shown a trend toward a lower toxicity. Among the adverse events, nephrotoxicity and ototoxicity require a careful evaluation during its administration.

The efficacy of intravenous immunoglobulin in combination therapy with antibiotics for severe infections

The efficacy of intravenous immunoglobulin in combination therapy with antibiotics for severe infections

脳神経外科領域の難治性感染症におけるpH4処理酸性ヒト免疫グロブリン併用療法

脳外科重症感染症に対するpH4処理酸性ヒト免疫グロブリン(PG4)と抗生物質の併用療法による臨床的・細菌学的効果を検索した.抗生物質の単独投与に抵抗した,脳外科術後重症感染症14例(髄膜炎,肺炎,皮下膿瘍)と非手術患者の重症感染症6例にPG4(5g/回/日,3日間)を点滴静注した.遷延化した重症術後髄膜炎の1例にはPG4の髄注(50mg[1m1]/回/日,3日間)を行った.結果は19例(95%)の症例で臨床的に高い有効性が認められ,細菌学的には5例(25%)で細菌が消失し,10例(50%)で細菌が減少した.髄腔内投与をした髄膜炎症例も速やかに軽快治癒した.全例において副作用は認められなかった.PG4は完全分子型を保持しているためオプソニン効果を発揮しやすく,宿主免疫低下時には抗生物質との併用による受動免疫療法の有効性が示唆された.