Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review
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)”, “exten...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/12/8/1262 |
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| author | Alberto Corona Vincenzo De Santis Andrea Agarossi Anna Prete Dario Cattaneo Giacomina Tomasini Graziella Bonetti Andrea Patroni Nicola Latronico |
| author_facet | Alberto Corona Vincenzo De Santis Andrea Agarossi Anna Prete Dario Cattaneo Giacomina Tomasini Graziella Bonetti Andrea Patroni Nicola Latronico |
| author_sort | Alberto Corona |
| collection | DOAJ |
| description | 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., <i>Klebsiella pneumoniae, Pseudomonas aeruginosa,</i> and <i>Acinetobacter baumanii</i>). 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. |
| first_indexed | 2024-03-11T00:11:06Z |
| format | Article |
| id | doaj.art-ffe22d86b7a14f27b3b386839940c113 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-11T00:11:06Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-ffe22d86b7a14f27b3b386839940c1132023-11-18T23:59:11ZengMDPI AGAntibiotics2079-63822023-07-01128126210.3390/antibiotics12081262Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative ReviewAlberto Corona0Vincenzo De Santis1Andrea Agarossi2Anna Prete3Dario Cattaneo4Giacomina Tomasini5Graziella Bonetti6Andrea Patroni7Nicola Latronico8Accident, Emergency and ICU Department and Surgical Theatre, ASST Valcamonica, University of Brescia, 25043 Breno, ItalyAUSL Romagna, Umberto I Hospital, 48022 Lugo, ItalyAccident, Emergency and ICU Department, ASST Santi Paolo Carlo, 20142 Milan, ItalyAUSL Romagna, Umberto I Hospital, 48022 Lugo, ItalyUnit of Clinical Pharmacology, ASST Fatebenefratelli Sacco University Hospital, Via GB Grassi 74, 20157 Milan, ItalyUrgency and Emergency Surgery and Medicine Division ASST Valcamonica, 25123 Brescia, ItalyClinical Pathology and Microbiology Laboratory, ASST Valcamonica, 25123 Brescia, ItalyMedical Directorate, Infection Control Unit, ASST Valcamonica, 25123 Brescia, ItalyDepartment of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, ItalyIntroduction: 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., <i>Klebsiella pneumoniae, Pseudomonas aeruginosa,</i> and <i>Acinetobacter baumanii</i>). 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.https://www.mdpi.com/2079-6382/12/8/1262antibiotic therapyGram-negativeinfectioncritically ill patientsstrategycombination |
| spellingShingle | Alberto Corona Vincenzo De Santis Andrea Agarossi Anna Prete Dario Cattaneo Giacomina Tomasini Graziella Bonetti Andrea Patroni Nicola Latronico Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review Antibiotics antibiotic therapy Gram-negative infection critically ill patients strategy combination |
| title | Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review |
| title_full | Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review |
| title_fullStr | Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review |
| title_full_unstemmed | Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review |
| title_short | Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review |
| title_sort | antibiotic therapy strategies for treating gram negative severe infections in the critically ill a narrative review |
| topic | antibiotic therapy Gram-negative infection critically ill patients strategy combination |
| url | https://www.mdpi.com/2079-6382/12/8/1262 |
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