Current treatment of pseudomonal infections in the elderly

Abstract

Pseudomonas aeruginosa infections have emerged as a major infectious disease threat in recent decades as a result of the significant mortality of pseudomonal pneumonia and bacteraemia, and the evolving resistance exhibited by the pathogen to numerous antibacterials. Pseudomonas possesses a large genome; thus, the pathogen is environmentally adaptable, metabolically flexible, able to overcome antibacterial pressure by selecting for resistant strains and even able to accumulate resistance mechanisms, leading to multidrug resistance (MDR), an increasingly recognized therapeutic challenge. In fact, most research currently does not focus on maximizing the efficacy of available antibacterials; rather, it focuses on maximizing their ecological safety. The elderly population may be particularly prone to pseudomonal infection as a result of increased co-morbidities (such as diabetes mellitus and structural lung disease), the presence of invasive devices such as urinary catheters and feeding tubes, polypharmacy that includes antibacterials, and immune compromise related to age. However, age per se, as well as residence in nursing homes, may not predispose individuals to an increased risk for pseudomonal infection. On the other hand, age has been repeatedly outlined as a risk factor for MDR pseudomonal infections. The severity of pseudomonal infections necessitates prompt administration of appropriate antibacterials upon suspicion. Progress has been made in recognizing risk factors for P. aeruginosa infections both in hospitalized and community-residing patients. Antimicrobial therapy may be instituted as a combination or monotherapy: the debate cannot be definitively resolved since the available data are extracted from studies with varying targeted populations and varying definitions of response, adequacy and MDR. Empirical combination therapy maximizes the chances of bacterial coverage and exerts a lower resistance selection pressure. Although associated with increased percentages of adverse events, mainly as a result of the included aminoglycosides, empirical combination therapy seems a reasonable choice. Upon confirmation of Pseudomonas as the causative agent and awareness of its susceptibility profile, monotherapy is advocated by many, but not all, experts. Infections involving MDR strains can be treated with colistin, which has adequate efficacy and few renal adverse events, or doripenem. In the elderly, in addition to making dose modifications that are needed because of loss of renal function, the prescriber should be more cautious about the use of aminoglycoside-containing regimens, possibly replacing them with a combination of quinolone and a beta-lactam, notwithstanding the possible increased pressure for selection of resistance with the latter combination.