Doripenem Susceptibility Testing
Doripenem is a carbapenem antibiotic with potent activity against Gram-negative pathogens, including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. It is primarily used for treating complicated intra-abdominal infections (cIAIs), complicated urinary tract infections (cUTIs), and nosocomial pneumonia. Susceptibility testing is essential due to the emergence of carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant (MDR) Pseudomonas aeruginosa.
Testing Methods
Doripenem susceptibility is determined using standardized phenotypic and molecular techniques to ensure accurate resistance detection:
- Broth Microdilution (BMD): CLSI and EUCAST gold-standard method for determining MIC values in Enterobacterales, Pseudomonas spp., and Acinetobacter spp.
- Agar Dilution: Used for precise MIC determination but less commonly applied in clinical settings.
- E-test (Epsilometer Test): Gradient diffusion method for doripenem MIC determination, useful in routine microbiology laboratories.
- Disk Diffusion Assay: Provides zone diameter measurements for qualitative susceptibility interpretation based on CLSI/EUCAST breakpoints.
- Molecular Methods (PCR, Whole Genome Sequencing): Detects resistance genes such as blaKPC, blaNDM, blaVIM, blaOXA-48, which confer carbapenem resistance.
Clinical Applications
Doripenem susceptibility testing is crucial in managing severe Gram-negative infections, particularly in the following cases:
- Complicated Intra-Abdominal Infections (cIAIs): Ensures efficacy against MDR Enterobacterales and Pseudomonas aeruginosa.
- Complicated Urinary Tract Infections (cUTIs): Guides therapy for resistant uropathogens, including ESBL- and carbapenemase-producing Enterobacterales.
- Nosocomial Pneumonia (HAP/VAP): Assesses activity against Pseudomonas aeruginosa and Acinetobacter baumannii, frequent causes of ventilator-associated pneumonia.
- Bacteremia and Sepsis: Determines doripenem effectiveness in bloodstream infections caused by MDR Gram-negative bacteria.
Doripenem susceptibility testing is critical for Gram-negative bacterial infections, particularly in CRE, MDR Pseudomonas aeruginosa, and Acinetobacter baumannii cases. Broth microdilution remains the gold standard, while molecular methods provide rapid resistance detection, supporting antimicrobial stewardship and infection control strategies.
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