Normal aging results in subtle changes both in ACTH and cortisol secretion. Most notable is the general increase in mean daily serum cortisol levels in the elderly, without a noteworthy alteration in the normal circadian rhythm pattern. Glucocorticoid excess seen in the elderly population can have serious consequences in both the structural and functional integrity of various key areas in the brain, including the hippocampus, amygdala, prefrontal cortex, with consequent impairment in normal memory, cognitive function, and sleep cycles. The chronically elevated glucocorticoid levels also impinge on the normal stress response in the elderly, leading to an impaired ability to recover from stressful stimuli. In addition to the effects on the brain, glucocorticoid excess is associated with other age-related changes, including loss of muscle mass, hypertension, osteopenia, visceral obesity, and diabetes, among others. In contrast to the increase in glucocorticoid levels, other adrenocortical hormones, particularly serum aldosterone and DHEA (the precursor to androgens and estrogens) show significant decreases in the elderly. The underlying mechanisms for their decrease remain unclear. While the adrenomedullary hormone, norephinephrine, shows an increase in plasma levels, associated with a decrease in clearance, no notable changes observed in plasma epinephrine levels in the elderly. The multiplicity and complexity of the adrenal hormone changes observed throughout the normal aging process, suggests that age-related alterations in cellular growth, differentiation, and senescence specific to the adrenal gland must also be considered.

Antibacterial activity can be classified as either bactericidal or bacteriostatic, using methods such as the MBC/MIC ratio and time–kill curves. However, such categorization has proven challenging in clinical practice, as these definitions only apply under specific laboratory conditions, which may differ from clinical settings. Several factors, such as the specific bacteria or infectious medium, can affect the action of antibiotics, with many antibacterials exerting both activities. These definitions have also led to the belief that bactericidal antibacterials are superior to bacteriostatic, especially in more severe cases, such as endocarditis, neutropenia and bacteraemia. Additionally, current dogma dictates against the combination of bactericidal and bacteriostatic antibacterials in clinical practice, due to potential antagonism. This review aimed to assess the differences in antibacterial activity of bactericidal and bacteriostatic antibacterials based on in vitro and in vivo studies and examine their antagonistic or synergistic effects. Our findings show that specific bacteriostatic agents, such as linezolid and tigecycline, are clinically non-inferior to bactericidals in multiple infections, including pneumonia, intra-abdominal infections, and skin and soft tissue infections. Studies also support using several bacteriostatic agents as salvage therapies in severe infections, such as neutropenic fever and endocarditis. Additionally, not all combinations of bacteriostatic and bactericidal agents appear to be antagonistic, with many combinations, such as linezolid and rifampicin, already being used. The findings should be interpreted with caution, as most evidence is from observational studies and there is a need for randomized controlled trials to assess their effectiveness and combinations, especially within the context of rising antimicrobial resistance.

To identify the roles of various antibiotics as risk factors for carbapenem-resistant extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) infection (ESBL-KP infection). Data were collected over 26 months in a tertiary care university hospital with established endemicity of carbapenem-resistant ESBL-KP (ESBL-CRKP). Using a case–case–control design, patients who presented an infection caused by carbapenem-susceptible ESBL-KP (ESBL-CSKP) and patients with ESBL-CRKP infection were compared with a common control group of hospitalized patients. Effects of treatment and duration of treatment with antibiotics were examined, adjusting for major non-antibiotic risk factors and controlling for confounding effects among the antibiotics via logistic regression models. Ninety-six ESBL-CRKP cases, 55 ESBL-CSKP cases and 151 controls were analysed. Multivariate analysis, adjusting for major non-antibiotic risk factors, showed that the risk of ESBL-CRKP infection rose with increasing duration of prior treatment with β-lactam/β-lactamase inhibitor combinations [odds ratio (OR) 1.15 per day increase; P = 0.001] and revealed that increased duration of treatment with fluoroquinolones amplified the impact of exposure to carbapenems (and vice versa) on ESBL-CRKP infection risk (OR 1.02 for interaction term; P = 0.009). Duration of prior treatment with fluoroquinolones was also associated with increased risk of ESBL-CSKP infection (OR 1.07 per day increase; P = 0.028), while prior receipt of carbapenems presented a protective effect against ESBL-CSKP infection (OR 0.21; P = 0.003). This study highlights the major role of treatment and duration of treatment with β-lactam/β-lactamase inhibitor combinations and combinations of carbapenems with fluoroquinolones. Clinicians should counterweight the potential benefits of administering these antibiotics against the increased risk of ESBL-CRKP infection.

To develop a consensus-based set of generic competencies in antimicrobial prescribing and stewardship for European prescribers through a structured consensus procedure. The RAND-modified Delphi procedure comprised two online questionnaire rounds, a face-to-face meeting between rounds, and a final review. Our departure point was a set of competencies agreed previously by consensus among a UK multi-disciplinary panel, and which had been subsequently revised through consultation with ESCMID Study Group representatives. The 46 draft competency points were reviewed by an expert panel consisting of specialists in infectious diseases and clinical microbiology, and pharmacists. Each proposed competency was assessed using a nine-point Likert scale, for relevance as a minimum standard for all independent prescribers in all European countries. A total of 65 expert panel members participated, from 24 European countries (one to six experts per country). There was very high satisfaction (98%) with the final competencies set, which included 35 competency points, in three sections: core concepts in microbiology, pathogenesis and diagnosing infections (11 points); antimicrobial prescribing (20 points); and antimicrobial stewardship (4 points). The consensus achieved enabled the production of generic antimicrobial prescribing and stewardship competencies for all European independent prescribers, and of possible global utility. These can be used for training and can be further adapted to the needs of specific professional groups.