The effectiveness of colistin/levofloxacin compared to colistin/meropenem in the treatment of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii: a randomized controlled clinical trial

Background and purpose: The treatment of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is still a great challenge. This study evaluated the effectiveness of the colistin/levofloxacin regimen compared to the usual colistin/meropenem regimen in the treatment of patients with VAP caused by CRAB. Experimental approach: The patients with VAP were randomly assigned to experimental (n = 26) and control (n = 29) groups. The first group received IV colistin 4.5 MIU every 12 h + levofloxacin 750 mg IV daily, and the second group received IV colistin with the same dose + meropenem 1 g IV every 8 h for 10 days. The clinical (complete response, partial response, or treatment failure) and microbiological responses at the end of the intervention were recorded and compared between the two groups. Findings/Results: The complete response rate was higher (n = 7; 35%) and the failure rate was lower (n = 4; 20%) in the experimental group than in the control group (n = 2; 8%, and n = 11; 44%, respectively), but the differences were not statistically significant. Even though the microbiological response rate was higher in the experimental group (n = 14; 70%) than in the control group (n = 12; 48%), the difference was not statistically significant. The mortality rate was 6 (23.10%) and 4 patients (13.8%) in the experimental and control groups, respectively (P = 0.490). Conclusion and implication: The levofloxacin/colistin combination can be considered an alternative regimen to meropenem/colistin in the treatment of VAP caused by CRAB.

[1]  Zhenjiang Bai,et al.  Comparison of diagnostic criteria for acute kidney injury in critically ill children: a multicenter cohort study , 2022, Critical Care.

[2]  M. Assefa Multi-drug resistant gram-negative bacterial pneumonia: etiology, risk factors, and drug resistance patterns , 2022, Pneumonia.

[3]  F. Shafiee,et al.  In vitro synergistic effect of colistin and ampicillin/sulbactam with several antibiotics against clinical strains of multi-drug resistant Acinetobacter baumannii. , 2021, Indian journal of medical microbiology.

[4]  L. De Martino,et al.  Acinetobacter baumannii: Its Clinical Significance in Human and Veterinary Medicine , 2021, Pathogens.

[5]  G. Guyatt,et al.  Diagnosis of ventilator-associated pneumonia in critically ill adult patients—a systematic review and meta-analysis , 2020, Intensive Care Medicine.

[6]  Y. Zhong,et al.  Risk Factors of Ventilator-Associated Pneumonia in Critically III Patients , 2019, Front. Pharmacol..

[7]  Junyi Li,et al.  Acinetobacter baumannii Ventilator-Associated Pneumonia: Clinical Efficacy of Combined Antimicrobial Therapy and in vitro Drug Sensitivity Test Results , 2019, Front. Pharmacol..

[8]  Afsaneh Vazin,et al.  In vitro activity of colistin in combination with various antimicrobials against Acinetobacter baumannii species, a report from South Iran , 2018, Infection and drug resistance.

[9]  S. Taheri,et al.  Interim Study: Comparison Of Safety And Efficacy of Levofloxacin Plus Colistin Regimen With Levofloxacin Plus High Dose Ampicillin/Sulbactam Infusion In Treatment of Ventilator-Associated Pneumonia Due To Multi Drug Resistant Acinetobacter , 2018, Iranian journal of pharmaceutical research : IJPR.

[10]  R. Wunderink,et al.  A global priority list of the TOp TEn resistant Microorganisms (TOTEM) study at intensive care: a prioritization exercise based on multi-criteria decision analysis , 2018, European Journal of Clinical Microbiology & Infectious Diseases.

[11]  M. Kollef,et al.  Acinetobacter Pneumonia: Improving Outcomes With Early Identification and Appropriate Therapy , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  A. Abdollahi,et al.  Meropenem/colistin versus meropenem/ampicillin-sulbactam in the treatment of carbapenem-resistant pneumonia. , 2018, Journal of comparative effectiveness research.

[13]  I. Siriopol,et al.  Endotracheal Tube Biofilm and its Impact on the Pathogenesis of Ventilator-Associated Pneumonia , 2018, Journal of critical care medicine.

[14]  Y. Ye,et al.  Activity of levofloxacin in combination with colistin against Acinetobacter baumannii: In vitro and in a Galleria mellonella model. , 2017, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[15]  Eurosurveillance Editorial Team Note from the editors: 10th European Antibiotic Awareness Day (EAAD) – raising awareness about prudent use of antimicrobials to help curb antimicrobial resistance , 2017, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[16]  H. Fazeli,et al.  Isolation of bacteriophages against multidrug resistant Acinetobacter baumannii , 2017, Research in pharmaceutical sciences.

[17]  R. Moniri,et al.  Sensitivity of levofloxacin in combination with ampicillin-sulbactam and tigecycline against multidrug-resistant Acinetobacter baumannii , 2017, Iranian journal of microbiology.

[18]  G. March,et al.  A meta-analysis of in vitro antibiotic synergy against Acinetobacter baumannii. , 2015, Journal of microbiological methods.

[19]  T. Schwartz,et al.  Synergistic Effect of Membrane-Active Peptides Polymyxin B and Gramicidin S on Multidrug-Resistant Strains and Biofilms of Pseudomonas aeruginosa , 2015, Antimicrobial Agents and Chemotherapy.

[20]  E. Giamarellos‐Bourboulis,et al.  Time–kill effect of levofloxacin on multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: synergism with imipenem and colistin , 2015, European Journal of Clinical Microbiology & Infectious Diseases.

[21]  M. Etminan,et al.  Risk of acute kidney injury associated with the use of fluoroquinolones , 2013, Canadian Medical Association Journal.

[22]  S. Sriwiriyajan,et al.  Comparison of the Pharmacodynamics of Meropenem in Patients with Ventilator-Associated Pneumonia following Administration by 3-Hour Infusion or Bolus Injection , 2005, Antimicrobial Agents and Chemotherapy.

[23]  B. Lomaestro Fluoroquinolone-Induced Renal Failure , 2000, Drug safety.

[24]  Jumaa Naser Synergistic Effect of Silver Nanoparticles and Polymyxin B on Multidrug-resistant Acinetobacter baumannii Isolated from Burn Wound Infections , 2018 .