How to Manage Pseudomonas aeruginosa Infections

Abstract

Infections with Pseudomonas aeruginosa have become a real concern in hospital-acquired infections, especially in critically ill and immunocompromised patients. The major problem leading to high mortality lies in the appearance of drug-resistant strains. Therefore, a vast number of approaches to develop novel anti-infectives is currently pursued. Diverse strategies range from killing (new antibiotics) to disarming (antivirulence) the pathogen. In this review, selected aspects of P. aeruginosa antimicrobial resistance and infection management will be addressed. Many studies have been performed to evaluate the risk factors for resistance and the potential consequences on mortality and attributable mortality. The review also looks at the mechanisms associated with resistance -P. aeruginosa is a pathogen presenting a large genome, and it can develop a large number of factors associated with antibiotic resistance involving almost all classes of antibiotics. Clinical approaches to patients with bacteremia, ventilator-associated pneumonia, urinary tract infections and skin soft tissue infections are discussed. Antibiotic combinations are reviewed as well as an analysis of pharmacokinetic and pharmacodynamic parameters to optimize P. aeruginosa treatment. Limitations of current therapies, the potential for alternative drugs and new therapeutic options are also discussed.

Antimicrobial Activity Test of Black Tea Ethanol Extract (Camellia sinensis) against Pseudomonas aeruginosa

“…Key features of bacteria related to their virulence genes and their regulation, antibiotic resistance and future trends of anti-Pseudomonas approaches are discussed (Wu et al, 2015). P. aeruginosa is intrinsically resistant to many structurally unrelated antimicrobial agents due to the low permeability of the outer membrane (Papadimitriou-Olivgeris et al, 2022;Strateva & Yordanov, 2009).…”

Risk Factors and Clinical Characteristics of Pandrug-Resistant Pseudomonas aeruginosa

“…First-line treatment often includes antipseudomonal penicillin, carbapenems, fluoroquinolones, cephalosporins with antipseudomonal activity, and monobactams, as guided by in vitro testing on isolates to determine susceptibility [ 7 , 8 ]. Unfortunately, P. aeruginosa has demonstrated marked resistance to many antibiotics and has been included in the “critical” category in the World Health Organization’s global list of priority pathogens for investigation [ 9 ].…”

“…Other risk factors include length of ICU stay, prolonged bedridden status, surgery, certain implantable devices, and if the previous room occupant was colonized by the same infectious pathogen [ 15 , 16 ]. Given the organism’s high levels of resistance, along with its high variability of the resistance patterns among regions, targeted antimicrobial therapy is heavily preferred for management [ 7 , 8 ].…”

“…In more serious infections or suspected MDR infections, combination therapies are used empirically while awaiting susceptibility testing results, since a delay in treatment is associated with increased mortality [ 7 , 8 ]. If there is resistance to first-line agents, combination drugs such as ceftolozane-tazobactam and ceftazidime-avibactam, which have shown benefit in some studies, may be used [ 7 ].…”

“…If there is further resistance to these medications, other alternatives, which are still yet to be extensively studied, include cefiderocol and imipenem-cilastatin-relebactam [ 7 ]. Newer β-lactams/β-lactamase inhibitor combinations are also being developed as treatment options, as well as a novel antibiotic, murepavadin, which has showcased encouraging clinical outcomes [ 8 ].…”