Empirical antimicrobials in the intensive care unit

De Bus, L., Arvaniti, K. & Sj?vall, F. Empirical antimicrobials in the intensive care unit. Intensive Care Med (2024). https://doi.org/10.1007/s00134-024-07453-0

Abstract

Critically ill patients in the ICU often present with infections that can lead to sepsis or septic shock, making timely and appropriate antimicrobial treatment essential. This article provides a step-by-step approach for prescribing empirical antimicrobials in ICU patients with suspected infection. It covers the need and urgency of antimicrobial therapy, pathogen profiling, selection of appropriate antimicrobial regimens, and future perspectives. The article emphasizes the importance of a multidisciplinary approach, rapid diagnostics, and individualized assessment to ensure effective and targeted therapy while minimizing the risks associated with antimicrobial overuse.

Introduction

In the ICU, critically ill patients frequently present with infections that can escalate to sepsis or septic shock. Timely and appropriate antimicrobial treatment is crucial in these scenarios. This article outlines a systematic approach for prescribing empirical antimicrobials in ICU patients with suspected infections, addressing the need and urgency of treatment, pathogen profiling, and selecting the right antimicrobial regimen. Additionally, it discusses the importance of individualized care, rapid diagnostics, and future research directions to enhance treatment effectiveness and antimicrobial stewardship.

Assessing the Need and Urgency

The Need Antimicrobial therapy is essential for treating most infections but poses potential harm if overused. Proper diagnostic assessment, including clinical examination, imaging, and laboratory testing, is crucial. Intensivists play a key role in interpreting these results and integrating them into the broader decision-making process. In complex cases, a multidisciplinary strategy involving ICU physicians, surgeons, microbiologists, and infectious disease specialists is often necessary.

Despite extensive research, no gold standard biomarker exists to distinguish infection from other inflammatory states. The 2021 Survival Sepsis Campaign Guidelines (SSCG) advise against using procalcitonin for diagnosing sepsis and initiating antimicrobials, recommending clinical assessment instead. Microbiological sampling is essential for diagnosis and later targeted therapy and should be performed before starting antimicrobials to avoid delays in treatment. Blood cultures and samples from suspected infection sites are the minimum requirements. Rapid microbiological and molecular techniques can support earlier and tailored antimicrobial regimens, although these tests have limitations such as detecting only predefined pathogen panels and being costly.

The Urgency

Sepsis and septic shock are medical emergencies requiring immediate action. The SSCG recommends administering antimicrobials within 1 hour of recognizing septic shock or a high likelihood of sepsis. In patients presenting with possible sepsis without shock, the diagnostic assessment window can be extended for a more thorough evaluation. There is a weak recommendation for deferring antimicrobials in patients with a low likelihood of infection and no shock, with careful observation. In certain well-monitored ICU environments, postponing antimicrobial treatment until preliminary microbiological findings are available may be justifiable in less severely ill patients. The advent of rapid diagnostics is expected to revolutionize this approach.

Pathogen Profiling

Profiling the suspected causative pathogen(s) is essential when determining empirical treatment. This process considers the presumed infection source, underlying comorbidities, local ecology, and the risk of multidrug-resistant (MDR) organisms. ICUs have a high prevalence of MDR infections due to high antimicrobial pressure and extensive interventions. Risk factors include a history of colonization or infection with MDR pathogens, recent hospitalization, and recent antimicrobial treatment. MDR prevalence thresholds guide empirical antimicrobial choice, though these thresholds vary widely.

Selecting the Right Arsenal

No single empirical antimicrobial regimen is recognized as the gold standard. An individualized assessment considering illness severity, infection source, immunosuppressive status, and patient-related MDR risk factors is crucial. Hospital-specific guidelines should be developed to address unique environmental factors. The chosen agent should cover the majority of suspected pathogens, with beta-lactams being commonly used. Combining multiple agents to broaden coverage is generally accepted when necessary, but combination therapy targeting the same pathogen to prevent resistance is controversial. Regular reassessment of treatment spectrum and duration is important to mitigate ecological pressure.

Pharmacokinetic and pharmacodynamic factors must be considered to ensure sufficient antimicrobial concentration at the infection site while minimizing toxicity. Initial dosing should account for larger volumes of distribution and augmented drug clearance in sepsis patients. Therapeutic drug monitoring can help optimize doses and reduce adverse effects.

Future Perspectives

Advancements in diagnosing sepsis and identifying causative microorganisms are key to increasing treatment effectiveness and minimizing antimicrobial exposure. Decision tools incorporating patient, setting, and microbiology data, interpreted by artificial intelligence, represent a promising area of exploration. Well-designed trials are needed to establish optimal timeframes for initiating or deferring empirical therapy, determine the efficacy of combination therapies, and study the ecological impact of various antimicrobial choices at different levels.

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Discussion Questions:

1. How can rapid diagnostic techniques improve the accuracy and timeliness of empirical antimicrobial therapy in the ICU, and what are the potential limitations of these techniques?
2. What factors should be considered when developing hospital-specific guidelines for empirical antimicrobial therapy in the ICU, and how can these guidelines be tailored to address unique environmental factors and patient populations?
3. How can therapeutic drug monitoring be effectively implemented in the ICU to optimize antimicrobial dosing, and what are the challenges associated with this approach?

Javier Amador-Casta?eda, BHS, RRT, FCCM

Interprofessional Critical Care Network (ICCN)

[email protected]

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