Approach to the Treatment of Patients with Serious Multidrug‐Resistant Pseudomonas aeruginosa Infections

Abstract

Multidrug resistance(MDR) among Pseudomonas aeruginosa (PSA) isolates presents a significant clinical challenge and can substantially complicate the approach to selection of optimal antibiotic therapy. This review addresses major considerations in antibiotic selection for patients with suspected or documented serious MDR‐PSA infections. Common mechanisms contributing to MDR among clinical PSA isolates are summarized. Empiric and definitive therapy considerations are addressed including the potential role of combination therapy. Newer agents with in vitro activity against MDR‐PSA (e.g., ceftolozane‐tazobactam, ceftazidime‐avibactam, imipenem‐relebactam, and cefiderocol) and their potential roles in clinical settings are discussed. Although these newer agents are promising options for the treatment of MDR‐PSA, clinical data remain generally limited. Future studies are needed to determine optimal agents for the empiric and definitive treatment of MDR‐PSA.

Diagnosis and Stratification of Pseudomonas aeruginosa Infected Patients by Immunochemical Quantitative Determination of Pyocyanin From Clinical Bacterial Isolates

“…In the same line, the ineffectiveness of classic antibiotics as a consequence of their inappropriate use has resulted in the rise of P. aeruginosa multidrug-resistant strains. However, patients are still treated with the same classical antibiotics, especially β-lactam antibiotics alone and in combination with other families of these compounds due to the lack of new therapeutic approaches ( O'Donnell et al., 2020 ). Among the new emerging therapeutic techniques, mAbs are gaining importance as a consequence of their high affinity and specificity, which minimize possible side effects ( Ducancel and Muller, 2012 ; Khan et al., 2017 ).…”

Population Pharmacokinetics and Dose Optimization of Ceftazidime and Imipenem in Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease

“…We performed simulations with conventional daily doses of 2 to 6 g for CAZ and 2 to 4 g for IMI. Higher doses of CAZ (2 g q8h and 3h EI) were also applied to increase the likelihood to cover P. aeruginosa strains with reduced susceptibility [ 55 ]. According to CLSI, CAZ intermediate resistant P. aeruginosa exhibits a MIC value of 16 mg/L.…”

“…In contrast, for IMI the target of 40% f T>MIC could be achieved with a dose as low as 0.5 g q6h EI for susceptible pathogens, and 4 g q24h for a pathogen with a MIC equal or greater than 8 mg/L when the patient had normal renal function. Therefore, the dose of 1 g q8h previously suggested to cover MDR P. aeruginosa might not be appropriated for all situation s [ 55 ]. A more aggressive target of 100% f T>MIC was also investigated as it is sometimes suggested for critically-ill patients [ 39 ].…”

Clinical Pharmacology of Bacteriophage Therapy: A Focus on Multidrug-Resistant Pseudomonas aeruginosa Infections

“…In fact, hospital-acquired infections may be more frequent due to increased exposure within hospitals, where drains and sinks serve as natural reservoirs for P. aeruginosa [ 25 ]. Though some infections caused by relatively susceptible P. aeruginosa phenotypes can be treated quite straightforwardly, this pathogen has a unique capability of developing antimicrobial resistance to commonly used broad-spectrum antibiotics (such as beta-lactams, aminoglycosides, and fluoroquinolones) through numerous mechanisms that can be concurrently expressed [ 26 ].…”

“…The clinical significance of this increased prevalence of MDR/XDR P. aeruginosa is evident, which, coupled with the already high rate of intrinsic resistance to many commonly used antibiotics, has led to many challenging clinical scenarios. Though beta-lactamases are arguably the most clinically relevant resistance mechanism amongst MDR Gram-negative pathogens, the more common resistance mechanisms displayed by P. aeruginosa involve porin mutations (e.g., loss of OprD) and the upregulation of efflux pumps (e.g., MexAB-OprM) (although beta-lactamases may be expressed and overexpressed, particularly AmpC) [ 23 , 26 ]. This poses an obvious problem, as most of the recent novel antimicrobials developed to combat MDR Gram-negative bacteria are either primarily targeted to overcome beta-lactamases (e.g., ceftazidime/avibactam and meropenem/vaborbactam) or lack in vitro activity against P. aeruginosa (e.g., tigecycline and eravacycline).…”