Introduction
Table of Contents
- Organism: Gram-negative, encapsulated, facultative anaerobic, rod-shaped bacterium.
- Epidemiology: Major cause of healthcare-associated infections (HAIs) like pneumonia, bloodstream infections, and UTIs.
- PDR Definition: Non-susceptible to all antimicrobial agents across all clinical categories (beta-lactams, carbapenems, aminoglycosides, fluoroquinolones, polymyxins, and tigecycline).
Pathogenicity & Virulence Factors
- Capsular Polysaccharide (CPS): Inhibits phagocytosis and complement-mediated killing.
- Lipopolysaccharide (LPS): Acts as an endotoxin, triggering severe inflammatory responses.
- Fimbriae (Types 1 & 3): Mediate adherence to host tissues and synthetic surfaces for biofilm formation.
- Siderophores: Scavenge iron from host proteins to support bacterial metabolism.
- Resistance Drivers: Driven by carbapenemase production (KPC, NDM, OXA-48), porin loss (OmpK35/36), and mgrB gene mutations (colistin resistance).
Laboratory Diagnosis
- Microscopy: Gram-negative bacilli.
- Culture: Large, pink, characteristically mucoid colonies on MacConkey agar due to lactose fermentation.

- Biochemical Profile: Catalase-positive, oxidase-negative, indole-negative, citrate-positive, and urease-positive.
- Susceptibility Testing: Handled via automated systems or broth microdilution (essential for colistin).
- Molecular Diagnostics: PCR and Next-Generation Sequencing (NGS) for the isolation of specific carbapenemase genes.
Therapeutic Management Strategies
- High-Dose Synergy: Combining maximal drug doses via prolonged infusions (e.g., double carbapenems).
- Novel Inhibitors: Aztreonam-avibactam or ceftazidime-avibactam combos (targeted to specific enzyme profiles).
- Salvage Therapies: Use of novel agents like Cefiderocol or experimental bacteriophage therapy.
Prevention and Infection Control
- Hand Hygiene: Compliance with standard alcohol-based hand rub protocols.
- Contact Isolation: Mandatory single-room isolation with dedicated gowns and gloves.
- Decontamination: Intensive environmental disinfection of high-touch clinical surfaces.
- Stewardship: Strict management of broad-spectrum and last-resort antibiotics.
- Active Surveillance: Routine rectal swab screening to identify and isolate asymptomatic carriers.
Keynotes
- PDR vs. XDR: Extensive drug resistance (XDR) leaves a few options; PDR leaves zero conventional choices.

- Testing Pitfall: Disk diffusion is invalid for colistin testing; always request broth microdilution.
- Hypervirulent Shift: Watch for “convergent” strains combining PDR with hypervirulence (hvKP), affecting healthy individuals.
Further Readings
- https://www.researchgate.net/publication/389770138_Mechanisms_of_Antimicrobial_Resistance_in_Klebsiella_Advances_in_Detection_Methods_and_Clinical_Implications
- https://pmc.ncbi.nlm.nih.gov/articles/PMC10886558/
- https://www.tandfonline.com/doi/full/10.2147/IJGM.S548733
- https://www.dovepress.com/mechanisms-of-antimicrobial-resistance-in-klebsiella-advances-in-detec-peer-reviewed-fulltext-article-IDR
- https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1691215/full
- https://pubmed.ncbi.nlm.nih.gov/36912811/
- https://www.clinicalmicrobiologyandinfection.org/article/S1198-743X(17)30499-8/fulltext
- https://academic.oup.com/jac/article/81/3/dkag064/8496198