Related Experiment Video
Updated: Jul 18, 2025
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review
Alberto Corona1, Vincenzo De Santis2, Andrea Agarossi3
1Accident, Emergency and ICU Department and Surgical Theatre, ASST Valcamonica, University of Brescia, 25043 Breno, Italy.
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.
Insights
For difficult-to-treat Gram-negative infections in critically ill patients, longer courses of combination therapy are recommended due to rising antimicrobial resistance. Shorter monotherapy courses are suitable only for susceptible infections, with treatment dynamically adjusted based on patient response.
Area of Science:
- Infectious Diseases
- Critical Care Medicine
- Antimicrobial Stewardship
Background:
- Optimal antimicrobial therapy for Gram-negative (GN) infections in critically ill patients lacks sufficient evidence.
- Rising antimicrobial resistance necessitates updated treatment guidelines.
Purpose of the Study:
- To review current literature on antimicrobial therapy duration and type for difficult-to-treat Gram-negative infections.
- To provide evidence-based recommendations for managing these challenging infections.
Main Methods:
- A narrative review of literature from PubMed and Cochrane.
- Keywords included multi-drug resistant (MDR), extensively drug resistant (XDR), pan-drug-resistant (PDR), difficult-to-treat (DTR) Gram-negative infections, and various antibiotic therapy strategies.
Main Results:
- Longer courses (≥10-14 days) of synergistic combination therapy are suggested due to high prevalence of MDR, XDR, PDR, and carbapenemase-producing GN organisms.
- Shorter courses (≤5-7 days) of monotherapy are reserved for infections with higher antibiotic susceptibility.
- Treatment strategies involve specific antibiotic classes based on resistance patterns, with therapeutic drug monitoring and resistance predictors influencing decisions.
Conclusions:
- Treatment decisions for Gram-negative infections are dynamic.
- Frequent reassessment based on clinical and microbiological responses is crucial for optimizing patient outcomes.
More Related Videos
12:03Antimicrobial Synergy Testing by the Inkjet Printer-assisted Automated Checkerboard Array and the Manual Time-kill Method
Published on: April 18, 2019
11:15Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
Related Concept Videos
01:28Acute Pyelonephritis II: Diagnostic Studies and Management
01:28Pneumonia IV: Management
Bacterial Pneumonia Treatment
For bacterial pneumonia, antibiotics serve as the cornerstone of therapy. Initial treatment often begins with empirical antibiotics, tailored to the anticipated causative organism and adjusted based on culture results. Key antibiotic choices include:
01:27Combined Effects of Drugs: Synergism
Such synergistic combinations...
01:30Urinary Tract Infection III: Diagnostic Studies and Interprofessional Care
01:26Urine Studies II: Urine Culture and Sensitivity Test
01:17Urinary Tract Infection IV: Nursing Management