An Evidence-Based Multidisciplinary Approach Focused at Creating Algorithms for Targeted Therapy of BSIs, cUTIs, and cIAIs Caused by Enterobacterales in Critically Ill Adult Patients

Abstract

Prompt implementation of appropriate targeted antibiotic therapy represents a valuable approach in improving clinical and ecological outcome in critically septic patients. This multidisciplinary opinion article focused at developing evidence-based algorithms for targeted antibiotic therapy of bloodstream (BSIs), complicated urinary tract (cUTIs), and complicated intrabdominal infections (cIAIs) caused by Enterobacterales . The aim was to provide a guidance for intensive care physicians either in appropriately placing novel antibiotics or in considering strategies for sparing the broadest-spectrum antibiotics. A multidisciplinary team of experts (one intensive care physician, one infectious disease consultant, one clinical microbiologist and one MD clinical pharmacologist), performed several rounds of assessment to reach agreement in developing six different algorithms according to the susceptibility pattern (one each for multi-susceptible, extended-spectrum beta-lactamase-producing, AmpC beta-lactamase-producing, Klebsiella pneumoniae carbapenemase (KPC)-producing, OXA-48-producing, and Metallo-beta-lactamase (MBL)-producing Enterobacterales ). Whenever multiple therapeutic options were feasible, a hierarchical scale was established. Recommendations on antibiotic dosing optimization were also provided. In order to retrieve evidence-based support for the therapeutic choices proposed in the algorithms, a comprehensive literature search was performed by a researcher on PubMed-MEDLINE from inception until March 2021. Quality and strength of evidence was established according to a hierarchical scale of the study design. Only articles published in English were included. It is expected that these algorithms, by allowing prompt revision of antibiotic regimens whenever feasible, appropriate place in therapy of novel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and pharmacokinetic/pharmacodynamic optimization of antibiotic dosing regimens, may be helpful either in improving clinical outcome or in containing the spread of antimicrobial resistance.

Clinical outcomes in elderly patients with infections caused by NDM-producing Klebsiella pneumoniae. Results from a real-life retrospective single center study in an endemic area

“…Pending data from RCTs, optimal management of infections caused by NDM-Kp remains uncertain, and recommendations are mainly moved by small observational studies and expert opinions [12][13][14][15][18][19][20][21].…”

Cefiderocol, a Siderophore Cephalosporin, as a Treatment Option for Infections Caused by Carbapenem-Resistant Enterobacterales

“…This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. [63,64]. Further clinical evidence on the latest antibiotics is needed to strengthen the recommendations.…”

A Proposal for a Classification Guiding the Selection of Appropriate Antibiotic Therapy for Intra-Abdominal Infections

“…Although piperacillin/tazobactam is not considered the first-choice antibiotic to treat ESBL-producing Enterobacterales [ 43 ], it may still be considered a valuable carbapenem-sparing agent in the management of ESBLs in IAIs treated with adequate source control when dealing with fully susceptible bacteria (MIC ≤ 8 mg/L). A high dose (18 g) should be prescribed to optimise PK/PD targeting in critically ill patients [ 44 ].…”

“…Finally, ceftolozane/tazobactam and ceftazidime/avibactam have shown efficacy in treating patients with IAIs caused by ESBL-producing Enterobacterales [ 50 , 51 ]. They may be especially useful in critically ill patients when dealing with isolates exhibiting high MIC values [ 44 ]. In settings with a high prevalence of carbapenem-resistant Enterobacterales (CRE), ceftazidime/avibactam should be reserved for the treatment of CRE.…”