Dataset Information

Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment.

ABSTRACT:

Background

Strong evidence suggests a correlation between pharmacodynamics (PD) index and antibiotic efficacy while dose adjustment should be considered in critically ill patients due to modified pharmacokinetic (PK) parameters and/or higher minimum inhibitory concentrations (MICs). This study aimed to assess pharmacodynamic (PD) target attainment considering both antibiotics serum concentrations and measured MICs in these patients.

Method

A multicentric prospective open-label trial conducted in 11 French ICUs involved patients with Gram-negative bacilli (GNB) ventilator-associated pneumonia (VAP) confirmed by quantitative cultures.

Results

We included 117 patients. Causative GNBs were P. aeruginosa (40%), Enterobacter spp. (23%), E. coli (20%), and Klebsiella spp. (16%). Hence, 117 (100%) patients received β-lactams, 65 (58%) aminoglycosides, and two (1.5%) fluoroquinolones. For β-lactams, 83% of the patients achieved a C_min/MIC > 1 and 70% had a C_min/MIC > 4. In the case of high creatinine clearance (CrCL > 100 mL/min/1.73 m²), 70.4% of the patients achieved a C_min/MIC ratio > 1 versus 91% otherwise (p = 0.041), and 52% achieved a C_min/MIC ratio > 4 versus 81% (p = 0.018). For aminoglycosides, 94% of the patients had a C_max/MIC ratio > 8. Neither β-lactams nor aminoglycosides PK/PD parameters were associated clinical outcomes, but our data suggest a correlation between β-lactams C_min/MIC and microbiological success.

Conclusion

In our ICU patients treated for GNB VAP, using recommended antibiotic dosage led in most cases to PK/PD targets attainment for aminoglycosides and β-lactams. High creatinine clearance should encourage clinicians to focus on PK/PD issues.

SUBMITTER: Pajot O

PROVIDER: S-EPMC9686941 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment.

Pajot Olivier O Lakhal Karim K Lambert Jérome J Gros Antoine A Bruel Cédric C Boulain Thierry T Garot Denis D Das Vincent V Timsit Jean François JF Cerf Charles C Souweine Bertrand B Chaffaut Cendrine C Mentec Hervé H Zahar Jean Ralph JR Mira Jean Paul JP Jullien Vincent V

Antibiotics (Basel, Switzerland) 20221119 11

Background: Strong evidence suggests a correlation between pharmacodynamics (PD) index and antibiotic efficacy while dose adjustment should be considered in critically ill patients due to modified pharmacokinetic (PK) parameters and/or higher minimum inhibitory concentrations (MICs). This study aimed to assess pharmacodynamic (PD) target attainment considering both antibiotics serum concentrations and measured MICs in these patients. Method: A multicentric prospective open-label trial conducted ...[more]

PMID: 36421308

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Project description:IntroductionVentilator-associated pneumonias (VAPs) are a complication of mechanical ventilation in the intensive care unit (ICU) that increase length of stay, morbidity, and mortality. While identifying and treating infections early is paramount to improving patient outcomes, more and more data demonstrate limited courses of antibiotics improve outcomes. Prolonged (10-14 day) courses of antibiotics have remained the standard of care for pneumonia due to gram-negative bacilli (GNR). We aimed to review our GNR VAPs to assess risk factors for recurrent GNR infections.MethodsWe reviewed trauma patients who developed VAP from 02/2019 through 05/2022. Demographics, injury characteristics, and outcomes were reviewed with a focus on pneumonia details including the cultured pathogen(s), antibiotic(s) used, treatment duration, and presence of recurrent infections. We then compared single episode VAPs to multiple episode VAPs among patients infected by GNRs.ResultsEleven of the fifty trauma patients admitted to the ICU suffered a VAP caused by a GNR. Of these eleven patients, six experienced a recurrent infection, four of which were caused by Pseudomonas aeruginosa and two of which were caused by Enterobacter aerogenes. Among the patients who received ten days of antibiotic treatment, half suffered a recurrence. Although, there was no difference in the microbiology or antibiotic duration between the recurrences and single episodes.ConclusionDespite prolonged use of antibiotics, we found that the risk of recurrent or persistent infections was high among patients with VAP due to GNB. Further study is needed to determine optimal treatment to minimize the risk of these recurrences.Key messageVentilator-associated pneumonia due to gram-negative bacilli is a rare but high morbidity complication in intensive care units. Despite prolonged duration of therapy, these infections still appear to account for many recurrent infections and further study into optimal therapy is warranted.

Project description:Ventilator-associated pneumonia (VAP) remains an important clinical problem globally, being associated with significant morbidity and mortality. As management of VAP requires adequate and timely antibiotic administration, global emergence of antimicrobial resistance poses serious challenges over our ability to maintain this axiom. Development of antimicrobials against MDR Gram-negative pathogens has therefore emerged as a priority and some new antibiotics have been marketed or approach late stage of development. The aim of this review is to analyse new therapeutic options from the point view of potential treatment of VAP. Among recently developed antimicrobials presented herein, it is obvious that we will have promising therapeutic options against VAP caused by Enterobacteriaceae excluding those producing metallo-β-lactamases, against which only cefiderocol and aztreonam/avibactam are expected to be active. Against infections caused by carbapenem non-susceptible Pseudomonas aeruginosa, ceftolozane/tazobactam and to a lesser extend ceftazidime/avibactam may cover a proportion of current medical needs, but there still remain a considerable proportion of strains which harbor other resistance mechanisms. Murepavadin and cefiderocol hold promise against this particularly notorious pathogen. Finally, Acinetobacter baummannii remains a treatment-challenge. Eravacycline, cefiderocol and probably plazomicin seem to be the most promising agents against this difficult-to treat pathogen, but we have still a long road ahead, to see their position in clinical practice and particularly in VAP. In summary, despite persisting and increasing unmet medical needs, several newly approved and forthcoming agents hold promise for the treatment of VAP and hopefully will enrich our antimicrobial arsenal in the next few years. Targeted pharmacokinetic and clinical studies in real-life scenario of VAP are important to position these new agents in clinical practice, whereas vigilant use will ensure their longevity in our armamentarium.

Dataset Information

Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment.

Background

Method

Results

Conclusion

Publications

Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment.

Similar Datasets

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