Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review

Abstract

Introduction: Not enough data exist to inform the optimal duration and type of antimicrobial therapy against GN infections in critically ill patients. Methods: Narrative review based on a literature search through PubMed and Cochrane using the following keywords: “multi-drug resistant (MDR)”, “extensively drug resistant (XDR)”, “pan-drug-resistant (PDR)”, “difficult-to-treat (DTR) Gram-negative infection,” “antibiotic duration therapy,” “antibiotic combination therapy” “antibiotic monotherapy” “Gram-negative bacteremia”, “Gram-negative pneumonia”, and “Gram-negative intra-abdominal infection”. Results: Current literature data suggest adopting longer (≥10–14 days) courses of synergistic combination therapy due to the high global prevalence of ESBL-producing (45–50%), MDR (35%), XDR (15–20%), PDR (5.9–6.2%), and carbapenemases (CP)/metallo-β-lactamases (MBL)-producing (12.5–20%) Gram-negative (GN) microorganisms (i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii). On the other hand, shorter courses (≤5–7 days) of monotherapy should be limited to treating infections caused by GN with higher (≥3 antibiotic classes) antibiotic susceptibility. A general approach should be based on (i) third or further generation cephalosporins ± quinolones/aminoglycosides in the case of MDR-GN; (ii) carbapenems ± fosfomycin/aminoglycosides for extended-spectrum β-lactamases (ESBLs); and (iii) the association of old drugs with new expanded-spectrum β-lactamase inhibitors for XDR, PDR, and CP microorganisms. Therapeutic drug monitoring (TDM) in combination with minimum inhibitory concentration (MIC), bactericidal vs. bacteriostatic antibiotics, and the presence of resistance risk predictors (linked to patient, antibiotic, and microorganism) should represent variables affecting the antimicrobial strategies for treating GN infections. Conclusions: Despite the strategies of therapy described in the results, clinicians must remember that all treatment decisions are dynamic, requiring frequent reassessments depending on both the clinical and microbiological responses of the patient.

Association of Inappropriate Initial Antibiotic Treatment with 30-Day Mortality in Hematological Malignancies Patients with Klebsiella pneumoniae Bloodstream Infection: A Single-Centre Retrospective Study

“…Regarding treatment strategies, current literature suggests a preference for longer courses of synergistic treatment (≥ 10 to 14 days) for more resistant infections, while shorter courses (≤ 5 to 7 days) may be reserved for less resistant Gram-negative bacterial infections (32). However, our study did not nd a signi cant difference in mortality between monotherapy and combination therapy in HM patients with KP BS.…”

Synergism Activity of Pyoluteorin with Some Antibiotic Against Urinary Tract Infections Pathogens

“…While the combination of PLT with Amoxicillin clavulanic acid had the lower activity on bacterial isolates (7 mm) on Enterobacter cloacae. Many studies reveld that randomly used of common antibiotics made it useless against numerous bacteria and development several mechanisums of resistance, so new antibacterial agent are required for treatment such infection [3]. in his report pointed that they could treatment of MDR gram negative bacteria (Acinetobacter spp., Pseudomonas spp., Klebsiella spp.)…”

The antibacterial activity and mechanism of a novel peptide MR-22 against multidrug-resistant Escherichia coli

“…For instance, colistin, carbapenems, and carbapenem derivatives were frequently employed in the therapeutic management of infections arising from drug-resistant bacterial strains ( Karaiskos et al., 2019 ). Inaddition, the third- or fourth-generation cephalosporins represent the prevailing choice for the multi-drug resistant Gram-negative infections ( Corona et al., 2023 ). Polymyxin and tigecycline are regarded as viable alternatives against MDR Gram-negative bacterial.…”