Antibiotic Resistance Mechanisms in the Intensive Care Unit

Abstract

Antibiotic resistance is increasingly recognised as a major threat to global health, with few new antimicrobial agents in development. The intensive care unit provides a unique environment for the growth and spread of drug-resistant organisms. Knowledge of the pathogenesis and mechanisms of resistance of drug-resistant organisms provides a conceptual framework which underpins the clinical manifestation of infections caused by these organisms, and is crucial for the intensivist to understand. Particular importance lies in the prevention of infection and the control of drug-resistant pathogens. The major resistance mechanisms of these organisms will be highlighted, focusing on specific gram-positive (meticillin-resistant Staphylococcus aureus and glycopeptide-resistant Enterococci), gram-negative ( Pseudomonas aeruginosa, Acinetobacter baumannii and multi-drug resistant Enterobacteriaceae) organisms, and then placed in historical and clinical context.

Terminalia bellirica fruit extracts: in-vitro antibacterial activity against selected multidrug-resistant bacteria, radical scavenging activity and cytotoxicity study on BHK-21 cells

“…Jinukti and Giri [ 33 ] report that an aqueous extract of T. bellirica fruits at 0.5 mg/mL inhibits drug-sensitive strains of both Gram-negative ( K. pneumoniae MTCC 3384, E. coli MTCC 7410, P. aeruginosa MTCC 2295, Proteus mirabilis MTCC 425, Salmonella typhimurium MTCC 98 and Proteus vulgaris MTCC 744) and Gram-positive ( S. aureus MTCC 7443 and Bacillus sphaericus MTCC 511) bacteria in an agar well-diffusion assay and that, among these microbial strains, P. mirabilis and K. pneumoniae have been the most sensitive. Thus, the relatively low susceptibility of MDR K. pneumoniae and MDR E. coli to T. bellirica aqueous extracts, compared to other organisms in the current study, may be attributed to the presence of multiple resistant mechanisms in the same isolate [ 4 , 34 ] found in MDR lactose-fermenting Gram-negative bacteria. The non-lactose fermenters MDR Acinetobacter spp.…”

“…Infection by MDR bacteria increases morbidity and mortality and requires increased expenditure to manage patients and implement infection control measures [ 3 ]. All current antibiotics available in clinical practice experience antibiotic resistance and none of them are effective against all MDR pathogens [ 4 ]. The World Health Organization (WHO) has prepared a priority list of antibiotic-resistant bacteria to guide research, discovery and development of new antibiotics and this list includes MDR Staphylococcus aureus , Pseudomonas aeruginosa , Acinetobacter baumannii , Klebsiella pneumoniae and Escherichia coli [ 5 ].…”

“…K. pneumoniae , a Gram-negative bacterium present in the normal flora of the intestines, can cause bloodstream, urinary and respiratory infections and has emerged as a cause of MDR infections worldwide [ 1 ]. Several MDR mechanisms are known for Gram-negative bacteria such as P. aeruginosa , A. baumannii , K. pneumoniae and E. coli [ 4 , 6 ].…”

Bloodstream infections in intensive care unit patients: distribution and antibiotic resistance of bacteria

“…Antibiotic resistance is a complex phenomenon that encompasses recognized in vitro mechanisms and their phenotypic expression, but also – at the clinical level – infection site, pharmacodynamic/pharmacokinetic properties of the specific antibiotic, modification of these pharmacological profiles in the critically ill patient, and immune status. 30 , 31 Resistance patterns of bacteria at a cellular level may be generally classified as follows: altered target site, namely modification of the molecule that is the target of the antimicrobial action; decreased antimicrobial uptake through decreased permeability to the antimicrobial or its elimination by efflux pumps; bypass pathways, which overcome the inhibition caused by the antibiotic molecule; and inactivation of the antimicrobial molecule through the production of enzymes that inactivate the drug. 31 Antibiotic resistance may represent an intrinsic property of different bacteria (eg, low permeability to some molecules), or rather may be acquired as a consequence of antibiotic pressure or mobile genetic element transmission.…”

“… 80 A. baumannii worldwide shows high-level resistance to all aminoglycosides by decreased outer-membrane permeability, active efflux pumps, and amino acid substitutions in ribosomal proteins. 31 In P. aeruginosa and A. baumannii , a single mutation in the gyrA gene encoding DNA gyrase is sufficient to confer clinically high-level resistance to fluoroquinolones. Of note, decreased susceptibility to this class of molecules is also due to low permeability and efflux-pump activity.…”