Drug Resistance


Nosocomial respiratory tract infections are major cause of excessive morbidity and mortality. Patients with serious underlying diseases have an especially high risk of acquiring these infections and that risk is magnified by exposure to respiratory therapy.

Beta-lactams remain a cornerstone for antimicrobial chemotherapy of a large number of bacterial infections, but their efficacy has been increasingly thwarted by dissemination of acquired resistance determinants among pathogenic bacteria. The exposure of bacterial strains to a multitude of β-lactams has induced a dynamic and continuous production and mutation of β-lactamase in many bacteria, expanding their activity even against later generation cephalosporins 5 and carbapenems by the production of extended-spectrum beta-lactamase (ESBL) and metallo-beta-lactamase (MBL) respectively. Since the genes that code for the production of ESBL are often linked to other resistance genes causing extended spectrum of drug resistance, this will result into fewer therapeutic alternatives.

ESBLs with hydrolytic activity against carbapenems are classified in three groups:

– Class A β-lactamases - Klebsiella pneumoniae carbapenemase (KPC)

– Class B - metallo-beta-lactamase (MBL) which includes New Delhi metallo-β-lactamase (NDM), Verona integron-encoded-metallo-β-lactamase (VIM) and imipenemase-metallo-β-lactamase (IMP)

– Class D - OXA-carbapenemases.


Main ESBL-producing pathogens are:

  • Enterobacteriaceae

o   E. coli

o   K. Pneumoniae

o   K. Oxytoca

o   P. mirabilis

o   Enterobacter

o   Salmonella

  • Non-fermentative Gram-negative

o   A. baumannii

o   P. aeruginosa


Methods of detection of ESBLs:

  • Phenotypic methods (antibiotic susceptibility)

o   Used routinely in clinical laboratories

o   The accuracy of semiautomated microbiology systems is not optimal

  • Genotypic methods (PCR-based amplification)

o   Used in reference laboratories

o   Discriminate between specific types of ESBLs

o   Need shorter time to detection (culture not required)

o   Have ability to detect low level resistance

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