Pseudomonas aeruginosa Pneumonia: Evolution of Antimicrobial Resistance and Implications for Therapy

Abstract

Pseudomonas aeruginosa (PA), a non–lactose-fermenting gram-negative bacillus, is a common cause of nosocomial infections in critically ill or debilitated patients, particularly ventilator-associated pneumonia (VAP), and infections of urinary tract, intra-abdominal, wounds, skin/soft tissue, and bloodstream. PA rarely affects healthy individuals, but may cause serious infections in patients with chronic structural lung disease, comorbidities, advanced age, impaired immune defenses, or with medical devices (e.g., urinary or intravascular catheters, foreign bodies). Treatment of pseudomonal infections is difficult, as PA is intrinsically resistant to multiple antimicrobials, and may acquire new resistance determinants even while on antimicrobial therapy. Mortality associated with pseudomonal VAP or bacteremias is high (> 35%) and optimal therapy is controversial. Over the past three decades, antimicrobial resistance (AMR) among PA has escalated globally, via dissemination of several international multidrug resistant “epidemic” clones. We discuss the importance of PA as a cause of pneumonia including health care–associated pneumonia, hospital-acquired pneumonia, VAP, the emergence of AMR to this pathogen, and approaches to therapy (both empirical and definitive).

Worldwide Dissemination of blaKPC Gene by Novel Mobilization Platforms in Pseudomonas aeruginosa: A Systematic Review

“…Although there is a wide range of antibiotics used to treat P. aeruginosa infections, such as ß-lactams, fluoroquinolones, aminoglycosides, and polymyxins [ 12 ], carbapenems are currently one of the most commonly used ß-lactam antibiotics for treating complicated P. aeruginosa infections [ 13 , 14 ]; however, the prevalence of carbapenem-resistant P. aeruginosa (CRPA) has increased rapidly, threatening the efficacy of these antibiotics and limiting the effective therapeutic options [ 6 , 15 ]. Due to the above, P. aeruginosa belongs to the “ESKAPE” list of pathogens of the Infectious Disease Society of America, which includes pathogens that represent a great threat to public health due to the ineffectiveness of multiple antibiotics against these bacteria [ 16 ].…”

Molecular pharmacodynamics of meropenem for nosocomial pneumonia caused by Pseudomonas aeruginosa

“…Additionally, the high inoculum burden of HAP infections above the inverse of typical mutation frequency value means that resistance commonly emerges during treatment, either due to de novo mutation or expansion of a pre-existing resistant subpopulation ( 16 , 17 , 19 , 36 ). The high prevalence of P. aeruginosa in HAP, with intrinsic resistance to many antibiotics and a vast repertoire of adaptive mechanisms (with loss of the OprD porin, upregulation of efflux pumps [e.g., MexAB-OprM, MexXY-OprM, or MexCD-OprJ] and overexpression of AmpC being the most relevant clinically [ 37 – 39 ]), further limits successful treatment options ( 40 ). Optimization of antimicrobial dosing to successfully treat HAP and prevent emergence of resistance is clearly needed.…”

Mechanisms of Antibiotic and Biocide Resistance That Contribute to Pseudomonas aeruginosa Persistence in the Hospital Environment

“…Contrary to intrinsic resistance, the development of acquired resistance is highly influenced by external stressors, such as exposure to antibiotics. In the presence of such compounds, resistant bacteria present a selective advantage over susceptible strains; this way, the surviving bacteria will give rise to a resistant population [ 106 , 107 , 108 , 109 ].…”