Pseudomonas Aeruginosa

P. aeruginosa is a common podocytic, rod-shaped, gram-negative bacterium that is the most common strain causing human infections. Due to its prevalence and intrinsically advanced antibiotic resistance mechanisms, it is a multi-drug resistant pathogen that is a very challenging organism to treat in modern medicine.

Approximately more than 10% of P. aeruginosa infections are multi-drug resistant. Mild infections may occur in healthy individuals, but severe infections usually occur in seriously ill patients. P. aeruginosa is capable of causing a wide range of infections in immunologically active and immunocompromised hosts. It is an important cause of nosocomial infections such as ventilator-associated pneumonia and catheter-associated urinary tract infections.

Methicillin-resistant Staphylococcus aureus

Epidemiology

Antibiotic Resistance

Treatment Options

Epidemiology

Multidrug-resistant P. aeruginosa infection

P. aeruginosa infections are common in immunocompromised individuals. Populations at greatest risk for infection include those using medical equipment such as ventilators and catheters.

P. aeruginosa is a common cause of hospital-acquired infections that manifest as pneumonia, surgical site infections, urinary tract infections, and bacteremia.
Individuals using invasive devices are also at risk due to their unique ability to form undetectable biofilms.

Antibiotic Resistance

Pseudomonas aeruginosa exhibits resistance to a wide range of antibiotics. In general, the main mechanisms used by P. aeruginosa to fight antibiotics can be classified as intrinsic resistance, acquired and adaptive resistance. P. aeruginosa can have high levels of intrinsic resistance to most antibiotics by limiting outer membrane permeability, by pumping antibiotics out of the cellular efflux system and by producing antibiotic inactivating enzymes. In addition to the high level of intrinsic antibiotic resistance in P. aeruginosa, acquired resistance greatly contributes to the development of multi-drug resistant strains. It can acquire antibiotic resistance either through mutational changes or through horizontal gene transfer to acquire resistance genes. In P. aeruginosa, the mechanisms characterizing adaptive resistance are biofilm formation and production of persistent cells.

Resistance to Quinolones

Nalidixic acid, ciprofloxacin, ofloxacin, etc.

Resistance to Aminoglycosides

Gentamicin, tobramycin, amikacin, plazomicin, etc.

Resistance to β-Lactams

Cephamycins, carbapenems, etc.

Treatment Options

Prospective Treatment Options

Antibiotic therapy

Conventional antibiotic therapy against P. aeruginosa infections is becoming increasingly ineffective due to the increase in multi-drug resistant strains. The main current therapeutic options are the use of different combinations of antibiotics and the development of new antibiotics. Because of their novel mode of action, efficient drug delivery and resistance to bacterial enzymatic modifications, new antibiotics may be more effective in killing P. aeruginosa and reduce the frequency of resistance development compared to existing antibiotics.

Non-antibiotic therapy

Quorum sensing inhibition
Phage therapy
Vaccine strategy
Antimicrobial peptides

The treatment of Pseudomonas aeruginosa infections remains a major challenge. The development of new antimicrobial agents and alternative strategies for the prevention and treatment of P. aeruginosa infections is a long and winding road. In short, we need to discover new classes of antibiotics. We can successfully control P. aeruginosa infections if we continue to make every effort to maintain the effectiveness of antibiotics and develop novel antibiotics.

At Ace Therapeutics, we discuss some new therapeutic approaches that deserve further study. We look forward to having you on board to develop the next generation of antimicrobial treatments for P. aeruginosa.

References

Pang Z, et al. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnology advances, 2019, 37(1): 177-192.
Reynolds D and Kollef M. The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update. Drugs, 2021,81(18):2117-2131.

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