Colours of Sepsis 2023: Antimicrobial Stewardship is a Necessity. The Spectrum of Effective Antimicrobial Modalities has Expanded to Include Another Combination

How to Maintain Sustainable and Effective Treatment?

Dr. Václava Adámková, Ph.D., from the Institute of Medical Biochemistry and Laboratory Diagnostics at the 1st Faculty of Medicine, Charles University and General University Hospital in Prague, referred to antibiotics as a rare, non-renewable natural resource. Coordinated intervention known as antibiotic stewardship (ABS) aims to improve their use by supporting the selection of appropriate antibiotics, including dosage, duration, and administration route. ABS is defined as a comprehensive, possibly unified set of procedures across society that leads to using anti-infectives in such a way that treatment is sustainable and effective for everyone who needs it.

However, it focuses only on individual antibiotic prescription and, according to Dr. Adámková, overlooks other participants in the entire process. The term stewardship cannot be limited to the concept of conservation used as a synonym, as preserving the effectiveness of antibiotics is a much broader term than ABS and includes other strategies not directly related to antibiotic use (vaccination, infection prevention and control, including hygiene measures).

ABS exclusively addresses how to use antibiotics specifically, and thus improving diagnostics is also an integral part. It is important to balance the needs of the patient and society when choosing antibiotic treatment. To understand the broader context of antibiotic use, i.e., in various components of society, less emphasis should be placed on the prescriber's actions. Among the most important and at the same time hardest-to-obtain parameters are data on the quality of antibiotic use. The mere information on the recommended daily dose is not sufficient.

Prudence in Indicating Biomarker Testing

Biomarkers, as an integral part of ABS, were addressed by Dr. Helena Lahoda Brodská, Ph.D., from the same workplace. Inflammatory markers are expected to answer questions about the identification of inflammation, estimation of severity, cause, etiology, and potential suitability of antibiotic deployment as well as response to therapy. Each has its advantages and limitations. For example, biological treatment or liver damage can limit the interpretation of C-reactive protein (CRP) tests. For procalcitonin (PCT), it is the presence of localized infections or nonspecific elevation, and for presepsin, renal failure. The speaker emphasized the need for prudence in indicating inflammatory marker tests and the necessity of clinical correlation certainty. She recommended combining markers and monitoring their dynamics. The importance of testing directly in the practitioner's office (POCT – point-of-care testing) was highlighted.

She also pointed out a prospective multicenter cohort study that assessed the differentiation of viral and bacterial infections using a combination of 3 proteins – TRAIL, IP-10, and CRP in a cohort of 1140 pediatric patients due to antibiotic overuse in children. This test achieved sensitivity of 93.7%, specificity of 94.2%, positive predictive value (PPV) of 73%, and negative predictive value (NPV) of 98.9%.

Effective Combinations Against Resistant Strains

Dr. Vojtěch Vodička from KARIM LF OU and FN Ostrava reminded that the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC) consider multidrug-resistant enterobacteria and resistant strains of Pseudomonas aeruginosa the greatest risk or serious threat. The efficacy against P. aeruginosa has been demonstrated by the third-generation cephalosporin ceftazidime, for example.

The combination of ceftazidime with the beta-lactamase inhibitor avibactam has expanded the spectrum of antimicrobial modalities. It is indicated for complicated intra-abdominal infections, complicated urinary tract infections, nosocomial pneumonia including ventilator-associated, in adults with bacteremia related to these infections (or if such a relationship is suspected), and in adults and children older than 3 months who have limited treatment options for infections caused by gram-negative aerobic microorganisms. It targets mainly multi-resistant microorganisms, being effective against 95% of P. aeruginosa isolates and more than 99% of enterobacteria. Naturally resistant to it are Enterococcus spp., Acinetobacter spp., Stenotrophomonas maltophilia and Staphylococcus aureus. It is administered by slow infusion (120 min.) at a dose of 2/0.5 g (1 vial) every 8 hours in adults, 50/12.5 mg/kg every 8 hours in children older than 6 months, and 40/10 mg/kg in children aged 3–6 months. In the case of renal insufficiency, the dose is reduced according to creatinine clearance. The treatment is well tolerated and has not been shown to have serious toxicity so far.

“Given the challenges that resistant pathogens present for modern medicine, it is necessary to use antimicrobial therapy rationally and according to ABS rules,” the speaker concluded.

Eva Srbová
Editorial Board of MeDitorial

Sources:
1. Adámková V. AMS – State of the Art. 25th Annual Colours of Sepsis, Ostrava, January 25, 2023.
2. Lahoda Brodská H. Laboratory Markers as Part of AMS (limitations, interpretation). 25th Annual Colours of Sepsis, Ostrava, January 25, 2023.
3. Papan C., Argentiero A., Porwoll M. et al. A host signature based on TRAIL, IP-10, and CRP for reducing antibiotic overuse in children by differentiating bacterial from viral infections: a prospective, multicentre cohort study. Clin Microbiol Infect 2022; 28 (5): 723–730, doi: 10.1016/j.cmi.2021.10.019. 
4. Vodička V. Clinical Use of Zavicefta in Intensive Medicine. 25th Annual Colours of Sepsis, Ostrava, January 25, 2023.
5. SPC Zavicefta. Available at: www.ema.europa.eu/en/documents/product-information/zavicefta-epar-product-information_cs.pdf