Safety and Tolerability of Antimicrobial Agents in the Older Patient

Abstract

Older patients are at high risk of infections, which often present atypically and are associated with high morbidity and mortality. Antimicrobial treatment in older individuals with infectious diseases represents a clinical challenge, causing an increasing burden on worldwide healthcare systems; immunosenescence and the coexistence of multiple comorbidities determine complex polypharmacy regimens with an increase in drug–drug interactions and spread of multidrug-resistance infections. Aging-induced pharmacokinetic and pharmacodynamic changes can additionally increase the risk of inappropriate drug dosing, with underexposure that is associated with antimicrobial resistance and overexposure that may lead to adverse effects and poor adherence because of low tolerability. These issues need to be considered when starting antimicrobial prescriptions. National and international efforts have been made towards the implementation of antimicrobial stewardship (AMS) interventions to help clinicians improve the appropriateness and safety of antimicrobial prescriptions in both acute and long-term care settings. AMS programs were shown to decrease consumption of antimicrobials and to improve safety in hospitalized patients and older nursing home residents. With the abundance of antimicrobial prescriptions and the recent emergence of multidrug resistant pathogens, an in-depth review of antimicrobial prescriptions in geriatric clinical practice is needed. This review will discuss the special considerations for older individuals needing antimicrobials, including risk factors that shape risk profiles in geriatric populations as well as an evidence-based description of antimicrobial-induced adverse events in this patient population. It will highlight agents of concern for this age group and discuss interventions to mitigate the effects of inappropriate antimicrobial prescribing.

The critically ill older patient with sepsis: a narrative review

“…Selecting and dosing antibiotics is challenging due to factors, such as comorbidities, drug pharmacokinetics (PK) and pharmacodynamics (PD), polypharmacy and risk of drug interactions [ 87 , 88 ]. Age-related changes in organ function, body composition, renal clearance, hepatic metabolism, and drug distribution significantly influence antibiotic PK and PD [ 49 , 89 , 90 ]. With aging, the decrease in body water percentage reduces the distribution volume for hydrophilic drugs (e.g., β-lactams, glycopeptides, aminoglycosides, azoles), leading to a faster increase in plasma concentrations.…”

“…With aging, the decrease in body water percentage reduces the distribution volume for hydrophilic drugs (e.g., β-lactams, glycopeptides, aminoglycosides, azoles), leading to a faster increase in plasma concentrations. Conversely, a relative increase in adipose tissue raises the distribution volume for lipophilic drugs (e.g., macrolides, fluoroquinolones), prolonging their half-life and leading to lower tissue concentrations [ 90 ]. Age-related liver and renal declines affect drug half-life and elimination [ 87 , 91 – 94 ].…”

“…Morphological and functional changes such as delayed gastric emptying, reduced splanchnic blood flow and altered gastric pH can affect the bioavailability of orally administered drugs [ 87 , 89 , 90 , 92 ].…”

Feeding Drosophila gut microbiomes from young and old flies modifies the microbiome

“…Secondly in killifish 39 where transplantation of ‘young’ microbiomes into middle aged fish treated with an antibiotic cocktail resulted in an increase in lifespan and fitness. However, such harsh antibiotic treatments can be detrimental for the host 47 , 48 or not a suitable method of intervention 49 , 50 and for this reason it is of great interest to test whether it is possible to shape a naturally existing microbiome by supplementing with differently aged microbiomes, in order to investigate phenotypic effects.…”

Potentially inappropriate prescriptions of antibiotics in geriatric psychiatry—a retrospective cohort study

“…Recent evidence suggests that the majority of antibiotic PIPs occur in the inpatient setting ( 5 ). Older patients in particular are frequently affected by bacterial infections and, consequently, are frequently exposed to antibiotic PIPs, thus representing an at-risk group ( 6 ). In addition, geriatric patients are at particular risk for the occurrence of adverse drug reactions (ADRs) due to physiologically altered pharmacokinetic and pharmacodynamic properties (e.g., lower volume of distribution, increased sensitivity to psychotropic side effects) as well as age-related multimorbidity and associated polypharmacy ( 7 ).…”