Background
Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.
Methods
We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.
Results
The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.
Conclusion
The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

/pdf/surviving-sepsis-campaign-international-guidelines-for-1trp1tl9am.pdf

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.

This Position Paper aims to review and discuss the available data on therapeutic drug monitoring (TDM) of antibacterials, antifungals and antivirals in critically ill adult patients in the intensive care unit (ICU). This Position Paper also provides a practical guide on how TDM can be applied in routine clinical practice to improve therapeutic outcomes in critically ill adult patients.
 Literature review and analysis were performed by Panel Members nominated by the endorsing organisations, European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/Pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), International Association for Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) and International Society of Antimicrobial Chemotherapy (ISAC). Panel members made recommendations for whether TDM should be applied clinically for different antimicrobials/classes. TDM-guided dosing has been shown to be clinically beneficial for aminoglycosides, voriconazole and ribavirin. For most common antibiotics and antifungals in the ICU, a clear therapeutic range has been established, and for these agents, routine TDM in critically ill patients appears meritorious. For the antivirals, research is needed to identify therapeutic targets and determine whether antiviral TDM is indeed meritorious in this patient population. The Panel Members recommend routine TDM to be performed for aminoglycosides, beta-lactam antibiotics, linezolid, teicoplanin, vancomycin and voriconazole in critically ill patients. Although TDM should be the standard of care for most antimicrobials in every ICU, important barriers need to be addressed before routine TDM can be widely employed worldwide.

/pdf/antimicrobial-therapeutic-drug-monitoring-in-critically-ill-zs644jfoir.pdf

Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper .

Continuous Renal Replacement Therapy (CRRT) is more and more widely used in patients for various indications recent years. It is still intricate for clinicians to decide a suitable empiric antimicrobial dosing for patients receiving CRRT. Inappropriate doses of antimicrobial agents may lead to treatment failure or drug resistance of pathogens. CRRT factors, patient individual conditions and drug pharmacokinetics/pharmacodynamics are the main elements effecting the antimicrobial dosing adjustment. With the development of CRRT techniques, some antimicrobial dosing recommendations in earlier studies were no longer appropriate for clinical use now. Here, we reviewed the literatures involving in new progresses of antimicrobial dosages, and complied the updated empirical dosing strategies based on CRRT modalities and effluent flow rates. The following antimicrobial agents were included for review: flucloxacillin, piperacillin/tazobactam, ceftriaxone, ceftazidime/avibactam, cefepime, ceftolozane/tazobactam, sulbactam, meropenem, imipenem, panipenem, biapenem, ertapenem, doripenem, amikacin, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, azithromycin, tigecycline, polymyxin B, colistin, vancomycin, teicoplanin, linezolid, daptomycin, sulfamethoxazole/trimethoprim, fluconazole, voriconazole, posaconzole, caspofungin, micafungin, amphotericin B, acyclovir, ganciclovir, oseltamivir, and peramivir.

/pdf/recommendation-of-antimicrobial-dosing-optimization-during-yfcepks27g.pdf

Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy.

Model-informed drug development (MIDD) has a long and rich history in infectious diseases This review describes foundational principles of translational anti-infective pharmacology, including choice of appropriate measures of exposure and pharmacodynamic (PD) measures, patient subpopulations, and drug-drug interactions Examples are presented for state-of-the-art, empiric, mechanistic, interdisciplinary, and real-world evidence MIDD applications in the development of antibacterials (review of minimum inhibitory concentration-based models, mechanism-based pharmacokinetic/PD (PK/PD) models, PK/PD models of resistance, and immune response), antifungals, antivirals, drugs for the treatment of global health infectious diseases, and medical countermeasures The degree of adoption of MIDD practices across the infectious diseases field is also summarized The future application of MIDD in infectious diseases will progress along two planes; "depth" and "breadth" of MIDD methods "MIDD depth" refers to deeper incorporation of the specific pathogen biology and intrinsic and acquired-resistance mechanisms; host factors, such as immunologic response and infection site, to enable deeper interrogation of pharmacological impact on pathogen clearance; clinical outcome and emergence of resistance from a pathogen; and patient and population perspective In particular, improved early assessment of the emergence of resistance potential will become a greater focus in MIDD, as this is poorly mitigated by current development approaches "MIDD breadth" refers to greater adoption of model-centered approaches to anti-infective development Specifically, this means how various MIDD approaches and translational tools can be integrated or connected in a systematic way that supports decision making by key stakeholders (sponsors, regulators, and payers) across the entire development pathway

https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1002/cpt.2198

Model-Informed Drug Development for Anti-Infectives: State of the Art and Future.

The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and to relate observed trough antibiotic concentrations to optimal targets. We performed a prospective, observational, multi-national, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam and vancomycin and related them to high and low target trough concentrations. We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8 fold) in antibiotic dosing regimens; RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/min (interquartile range [IQR] 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (p In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study

Alexander Brinkmann

Papers

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study