Related Experiment Video
Updated: Sep 11, 2025
Preparation of Agar Bead Embedded Mycobacterium abscessus to Inoculate Immunocompetent Mice Intratracheally
Published on: April 25, 2025
Sulbactam-Durlobactam Plus Ceftriaxone Dosing and Novel Treatment Regimens for Mycobacterium abscessus Lung Disease
Sanjay Singh1, Avneesh Shrivastava1, Gunavanthi D Boorgula1
1Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Texas at Tyler, Tyler, Texas, USA.
Background:
IDSA guideline-based therapy achieves sputum culture conversion rates in 20-34% of patients with Mycobacterium abscessus (MAB) lung disease (LD). Double-β-lactam combinations have been proposed to improve cure, based on time-kill curves.
Methods:
We performed minimum inhibitory concentrations (MICs) experiments followed by hollow fiber system model of MAB-LD (HFS-MAB) exposure-effect studies with sulbactam-durlobactam administered every 8h (q8h), q12h, and q24h, to identify target exposures. Next, the sulbactam-durlobactam target exposure plus ceftriaxone was administered in the HFS-MAB inoculated with three different MAB isolates, as was the sulbactam-durlobactam-ceftriaxone combination with epetraborole and omadacycline (SDCEO). γ -slopes (kill-speed) were calculated for all regimens. The minimal sulbactam-durlobactam clinical doses that achieved target exposure were identified using Monte Carlo experiments.
Results:
Ceftriaxone reduced sulbactam-durlobactam MICs by 8-tube dilutions. In the HFS-MAB, sulbactam-durlobactam microbial kill and antimicrobial resistance were linked to % time concentration persists above MIC (%TMIC), with target exposure of 50%. Sulbactam-durlobactam killed 3.85 log10 CFU/mL below day 0 burden (B 0 ) with regrowth. Sulbactam-durlobactam plus ceftriaxone killed without regrowth and demonstrated Bliss' additivity. γ of bacterial population in >95% of virtual subjects were 2.28 (0.97-4.80) log10 CFU/mL/day for sulbactam-durlobactam-ceftriaxone and 2.91 (1.65-4.93) log10 CFU/mL/day for SDCEO. The optimal sulbactam-durlobactam dose co-administered with ceftriaxone was 2G q8h for creatinine clearance >90 mL/min, 2G q12h for 60-90 mL/min, 1G q12h for ≥30 to <60 mL/min, and 1G q24h for <30 mL/min.
Conclusion:
Sulbactam-durlobactam-ceftriaxone achieved the highest microbial kill encountered so far in the HFS-MAB. Sulbactam-durlobactam-ceftriaxone should be tested as the backbone for novel treatment shortening regimens.
Related Concept Videos
01:28Pulmonary Tuberculosis V
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
01:28Acute Pyelonephritis II: Diagnostic Studies and Management
01:26Pulmonary Tuberculosis IV
Several diagnostic approaches are used to detect TB. The conventional method is the Tuberculin Skin Test (TST), also known as the Mantoux test. However, this method has...
01:28Pulmonary Tuberculosis II
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
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:
01:20Sputum Studies II: Culture and Sensitivity
Sputum culture and sensitivity is a medical procedure used to diagnose bacterial infections in the respiratory tract and select the most appropriate antibiotics for treatment. This process involves analyzing sputum samples of thick and opaque secretions produced in the lungs and airways. These samples are collected from patients and then sent to the laboratory for analysis.
The test can identify various pathogens responsible for respiratory infections, including Streptococcus,...