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Butranova, O.I.; Ushkalova, E.A.; Zyryanov, S.K.; Chenkurov, M.S.; Baybulatova, E.A. Influencing Factors of Antibiotics Prescribing in the Elderly. Encyclopedia. Available online: https://encyclopedia.pub/entry/45378 (accessed on 23 June 2024).
Butranova OI, Ushkalova EA, Zyryanov SK, Chenkurov MS, Baybulatova EA. Influencing Factors of Antibiotics Prescribing in the Elderly. Encyclopedia. Available at: https://encyclopedia.pub/entry/45378. Accessed June 23, 2024.
Butranova, Olga I., Elena A. Ushkalova, Sergey K. Zyryanov, Mikhail S. Chenkurov, Elena A. Baybulatova. "Influencing Factors of Antibiotics Prescribing in the Elderly" Encyclopedia, https://encyclopedia.pub/entry/45378 (accessed June 23, 2024).
Butranova, O.I., Ushkalova, E.A., Zyryanov, S.K., Chenkurov, M.S., & Baybulatova, E.A. (2023, June 09). Influencing Factors of Antibiotics Prescribing in the Elderly. In Encyclopedia. https://encyclopedia.pub/entry/45378
Butranova, Olga I., et al. "Influencing Factors of Antibiotics Prescribing in the Elderly." Encyclopedia. Web. 09 June, 2023.
Influencing Factors of Antibiotics Prescribing in the Elderly
Edit

Infections are important factors contributing to the morbidity and mortality among elderly patients. High rates of consumption of antimicrobial agents by the elderly may result in increased risk of toxic reactions, deteriorating functions of various organs and systems and leading to the prolongation of hospital stay, admission to the intensive care unit, disability, and lethal outcome. Both safety and efficacy of antibiotics are determined by the values of their plasma concentrations, widely affected by physiologic and pathologic age-related changes specific for the elderly population. Drug absorption, distribution, metabolism, and excretion are altered in different extents depending on functional and morphological changes in the cardiovascular system, gastrointestinal tract, liver, and kidneys. Water and fat content, skeletal muscle mass, nutritional status, use of concomitant drugs are other determinants of pharmacokinetics changes observed in the elderly. The choice of a proper dosing regimen is essential to provide effective and safe antibiotic therapy in terms of attainment of certain pharmacodynamic targets.

elderly pharmacokinetics antibiotics dosing infections

1. Introduction

The global population aging in the 21st century is unprecedented. In the Western world persons over 65 years are the fastest growing cohort [1], which outnumbers the population of children below five years old and attracts the attention of researchers all over the world [2]. It is predicted that by 2100 in Europe people over 65 will make up 31% of the total population, and people over 80 will reach about 15% [3].
Age-related physiological and pathological changes, poor functional status, poor nutrition, and comorbidities predispose older adults to infections and their complications [4][5]. The incidence and severity of infections increase with advancing age [6][7]. Compared to younger age groups, elderly patients are more prone to pneumonia, skin and soft tissue infections, urinary tract infections and septicemia [1][4]. An additional problem is a substantial risk of antibiotic (AB) resistance; its typical risk factors in the elderly include frequent contact with the healthcare system, frequent AB exposure, depressed immune system, frailty, and comorbidity [4]. Elderly patients are considered the high-risk group for the development of healthcare-associated infections caused by multidrug-resistant (MDR) bacteria [8][9][10]. The elderly population has longer hospital stays compared to younger adults and a significantly higher mortality rate (25%) compared to the general population (10%) [6][11][12]. Infections aggravate the course of concomitant chronic diseases, including cardiovascular and cognitive disorders, and contribute to the emergence of a new comorbidity [13].
High infectious morbidity leads to high consumption of antimicrobial agents by the elderly. ABs are among the most frequently prescribed medicines to seniors [14][15][16] and their use is accompanied by a significant rate of side effects and clinically relevant drug-drug interactions compared to younger counterparts [14]. Adverse drug reactions (ADRs) are an important cause of morbidity and mortality in the elderly [17][18][19] and their risk is significantly increased in the presence of comorbidity and polypharmacy [19][20][21][22].
The choice of optimal antimicrobial agent for the elderly is challenging [23]. Finding the right balance between efficacy, safety and tolerability of antibiotics is difficult for several reasons including significant changes in body tissue composition, a progressive physiological decline of organ functions, frailty, comorbidity, and polypharmacy [24]. All these factors can cause significant alterations in antimicrobials pharmacokinetics (PK) and pharmacodynamics (PD) leading to altered efficacy, safety, and tolerance. The problem is compounded by the fact that elderly patients represent a heterogeneous group that should be treated individually [25][26].

2. Factors Influencing AB Prescribing in the Elderly

Infections in the elderly may be caused by a more diverse group of pathogens compared to the younger population [6][27][28]. For example, there is a higher prevalence of Gram-negative bacilli in pneumonia and a lower prevalence of E. coli in urinary tract infections [6].
Common infections do not manifest with classic symptoms in the elderly. Aged patients may have neither fever nor leukocytosis [29]. An absence of fever and a lack of respiratory symptoms has been described in 40–60% of elderly patients with community-acquired pneumonia [30]. The only clinical presentation of pneumonia in up to 20–50% of the elderly may be an altered mental status including delirium and confusion, a sudden decline in functional capacity, and worsening of underlying diseases [28]. The high prevalence of unusual and/or multidrug-resistant pathogens in the elderly makes AB susceptibility testing highly desirable, though in the real clinical practice, antibiotics may be prescribed empirically as even subtle clinical manifestations may herald the onset of life-threatening infectious disease and delayed therapy can worsen treatment outcomes [28].
Appropriate AB dosing requires knowledge of the pharmacokinetic and pharmacodynamic properties of AB which are often altered due to aging processes, including age- or disease-related decline of kidney and liver functions. To select an optimal AB for the concrete patient, it is necessary to identify all comorbidities, concomitant drugs, and dietary supplements, and collect the patient’s allergic history. Consideration should be given to the factors associated with poor treatment compliance such as poor vision and/or hearing, physical dexterity, cognitive impairment, or mental illness [21][31][32][33]. These patients require treatment supervision by relatives or caregivers.
Elderly patients are at high risk of potential harm associated both with missed treatment and excessive AB therapy [31][34]. In long-term care facilities 50–75% of residents receive at least one course of AB each year with 30–50% of AB prescriptions being unnecessary or inappropriate in terms of drug choice, dosing regimen and/or duration of treatment [35]. Inappropriate drug selection and use may lead to medication-related problems, including ADRs, therapy failure and withdrawal events alongside the spread of AB resistance [34][36].
Compared to younger counterparts, older patients are more vulnerable to AB side effects and clinically relevant consequences of drug interactions [14]. The risk of ADR development is especially high in patients with comorbidity and polypharmacy [19][20][21][22]. ADRs are an important cause of morbidity and mortality in elderly patients [17][18][19].
Increased risk of AB-induced toxicity, ADRs, and negative outcomes in elderly patients with infectious diseases may be mediated by the changed PK of AB resulting in the changed PD.

3. AB Dosing Regimens in the Elderly

The main aim of AB therapy in elderly patients is to provide a proper balance between efficacy (PK/PD target attainment) and safety. Changed PK parameters may lead both to decreased or increased AB exposure contributing to negative treatment outcomes. Dose adjustment is a typical approach in the management of the elderly with infections. Decreased metabolizing capacity and declined renal clearance result in the need to decrease the standard adult dose of AB, while ARC specific for critically ill patients may dictate the necessity to use a higher dose.
Table 1, Table 2, Table 3, Table 4 and Table 5 include information about the proposed regimens of AB dosing depending on age, renal function, and hepatic function along with data on concentrations reported to cause toxic reactions.
Table 1. Beta-lactam AB dosing depending on age, renal function, and hepatic impairment.
Drug Regimen for Patients with
Different Renal Function
PK/PD Target
in the Elderly
Regimen for Patients with Hepatic Impairment Safety References
Penicillin group
Ampicillin/Sulbactam mean age > 65 years:
2 g of ampicillin/
1 g of sulbactam every 8 h
(normal renal function)
75–100
% T > MIC
(MIC90 = 1 mg/L)
NA Transient low-level elevations of ALT or AST in serum indicating transient liver damage [37][38]
mean age > 75 years:
1 g of ampicillin/
0.5 g of sulbactam every 6 h
(10 ≤ CLCR < 50 mL/min)
40% T > MIC
(MIC = 8 μg/mL)
 
Piperacillin/Tazobactam mean age 85 (82–87) years:
4.5 g every 24 h
(CLCR 0–19 mL/min/1.73 m2)
fCss/MIC ≥ 1
MIC ≤ 8 mg/L
4.5 g every 4–6 h
(loading dose)
4.5 g every 6 h
(maintenance dose)
Plasma concentration ≥ 157.2 μg/mL—risk of neurotoxicity [39][40][41]
mean age 85 (82–87) years:
9 g every 24 h
(CLCR 20–39 mL/min/1.73 m2)
mean age 85 (82–87) years:
11.25 g every 24 h
(CLCR 40–59 mL/min/1.73 m2)
mean age 85 (82–87) years:
13.5 g every 24 h
(CLCR 60–79 mL/min/1.73 m2)
Cephalosporins
Cefepime frail patients:
1 g every 12 h
(CLCR = 30 mL/min)
fT > 50% MIC
(susceptible strains)
1–2 g every 8–12 h (loading dose)
1–2 g every 8–12 h (maintenance dose)
Plasma concentration ≥ 38.1 mg/L—risk of neurotoxicity [40][42][43]
frail patients:
1 g every 8 h
(CLCR 30–60 mL/min)
frail patients:
2 g every 8 h
(normal renal function)
fT > 80% MIC
(susceptible strains)
Ceftriaxone mean age > 65 years:
1 g every 48 h
(eGFRcys 10 mL/min/1.73 m2) [41]
unbound fraction of ceftriaxone >MIC
(MIC = 0.5–1 mg/L) [41]
1–2 g every 12 h
(loading dose)
1–2 g every 12 h
(maintenance dose)
[37]
Plasma concentration ≥ 22 mg/L—risk of neurotoxicity and ceftriaxone-induced encephalopathy
[42]
[44][45]
mean age > 65 years:
2 g every 48 h
(eGFRCR-cys 40 mL/min/1.73 m2) [41]
Ceftazidime/avibactam age 66 years
(clinical case):
0.94 g every 12 h
(CLCR 30–40 mL/min)
100% fT > 4 × MIC for ceftazidime
99% fT > 4 mg/L for avibactam
(MIC = 1.5/4 mg/L)
2.5 g every 8 h
(loading dose)
2.5 g every 8 h
(maintenance dose)
Concentration in cerebrospinal fluid ≥ 9.4 mg/L—risk of neurotoxicity [40][46][47]
Ceftobiprole CLCR < 50 mL/min:
0.5 g as a 2-h intravenous infusion every 12 h
30–40% T > MIC
MIC = 2 mg/L
NA NA [48]
CLCR < 30 mL/min:
0.25 g as a 2-h intravenous infusion every 12 h
Carbapenems
Doripenem mean age > 60 years, mean CLCR = 53.0 mL/min:
0.5 g every 8 h [49]
40% fT > MIC
(MIC = 2 μg/mL)
[49]
NA NA [49]
Ertapenem mean age
73.1 ± 4.8 years:
1 g every 24 h
(normal renal function)
AUC0-24 746.1 ± 79.4 μg·h/mL at 1 day
AUC0-24
681.9 ± 47.0 μg·h/mL at 7 day
1 g every 12 h
(loading dose)
1 g every 12 h
(maintenance dose)
Plasma concentration > 79.2 µg/mL—risk of neurotoxicity [40][50][51]
Meropenem mean age > 65 years,
CLCR ≤ 50 mL/min:
1 g every 8 h;
40% fT> MIC
(MIC≤ 2–8 mg/L)
2 g every 8 h
(loading dose)
1 g every 8 h
(maintenance dose)
Plasma concentration ≥ 64.2 μg/mL—risk of neurotoxicity
Cmin ≥ 44.45 μg/mL—risk of nephrotoxicity
[52][53]
mean age > 65 years,
CLCR > 100 mL/min:
2 g every 8 h
40% T > MIC
(MIC > 8 mg/L)
Biapenem mean age > 65 years:
0.3 g every 8 h
40% T > MIC
(MIC = 2 μg/mL)
NA NA [54]
ALT—Alanine transaminase; AST—Aspartate transaminase; AUC0-24—Area under the plasma concentration-time curve over the last 24-h dosing interval; CLCR—Creatinine clearance; Cmin—Minimum concentration; eGFRcys—Glomerular filtration rate estimated from cystatin C; MIC—Minimum inhibitory concentration; %T > MIC—Percent of time for total drug concentration remains above the minimum inhibitory concentration; fT > MIC—Percent of time for free drug concentration remains above the minimum inhibitory concentration; AUC—Area under curve; fCss > MIC—Free plasma steady-state concentration above the MIC.
Table 2. Aminoglycosides dosing depending on age, renal function, and hepatic impairment.
Drug Regimen for Patients with
Different Renal Function
PK/PD Target
in the Elderly
Regimen for Patients with Hepatic Impairment Safety References
Amikacin mean age > 70 years:
1.8 g every 72 h
(CLCR = 40–50 mL/min)
1.8 g every 48 h
(CLCR = 60–90 mL/min)
Cmax >
MIC
(MIC ≤ 8 mg/L)
NA Cmin > 4 μg/mL—risk of nephrotoxicity [55]
Gentamicin Geriatric population, CLCR > 60 mL/min:
3 mg/kg every 24 h
Cmax > MIC
(MIC = 1 μg/mL)
NA Cmin > 2 μg/mL—risk of nephrotoxicity [56]
CLCR—Creatinine clearance; Cmin—Minimum concentration; Cmax—Maximum concentration; MIC—Minimum inhibitory concentration.
Table 3. Glycopeptides and Lipopeptides dosing depending on age, renal function, and hepatic impairment.
Drug Regimen for Patients with
Different Renal Function
PK/PD Target
in the Elderly
Regimen for Patients with Hepatic Impairment Safety References
Glycopeptides
Vancomycin mean age ≥ 65 years:
1.0 g every 8 (CLCR > 50 mL/min)
1.0 g every 12 h (CLCR ≤ 50 mL/min)
Cmin, ss
> MIC
NA Cmin > 20 mg/L—risk of nephrotoxicity [57]
Lipopeptides
Daptomycin eGFRcys = 20 mL/min:
age 65 years:
600 mg (loading dose)
350 mg (maintenance dose)
every 24 h
age 75 years:
550 mg (loading dose)
300 mg (maintenance dose)
every 24 h
age 85 years:
500 mg (loading dose)
250 mg (maintenance dose)
every 24 h
age 95 years:
450 mg (loading dose)
200 mg (maintenance dose)
every 24 h
(fAUCss)/MIC ≥ 66.6 NA Risk of toxic reactions at Cmin > 24 mg/L and Cmax > 60 mg/L [58][59]
CLCR—Creatinine clearance; Cmin—Minimum concentration; Cmin, ss—Minimum plasma concentration at up to 24 h after administration; Cmax—Maximum concentration; eGFRcys—Glomerular filtration rate estimated from cystatin C; MIC—Minimum inhibitory concentration; (fAUCss)/MIC—Ratio of the area under the unbound concentration from 0 to 24 h at steady state time curve to the MIC.
Table 4. Fluoroquinolones dosing depending on age, renal function, and hepatic impairment.
Drug Regimen for Patients with
Different Renal Function
PK/PD Target
in the Elderly
Regimen for Patients with Hepatic Impairment Safety References
Levofloxacin mean age 81 years:
CLCR 0–19 mL/min:
125 mg every 48 h (MIC = 0.125 mg/L)
250 mg every 48 h (MIC = 0.25 mg/L)
500 mg every 48 h (MIC = 0.5 mg/L)
CLCR 20–39 mL/min:
500 mg every 48 h (MIC = 0.125 mg/L)
500 mg every 48 h (MIC = 0.25 mg/L)
750 mg every 48 h (MIC = 0.5 mg/L)
CLCR 40–59 mL/min:
500 mg every 48 h (MIC = 0.125 mg/L)
500 mg every 48 h (MIC = 0.25 mg/L)
500 mg every 24 h (MIC = 0.5 mg/L)
CLCR 60–79 mL/min:
500 mg every 48 h (MIC = 0.125 mg/L)
750 mg every 48 h (MIC = 0.25 mg/L)
750 mg every 24 h (MIC = 0.5 mg/L)
CLCR > 80 mL/min:
750 mg every 48 h (MIC = 0.125 mg/L)
750 mg every 24 h (MIC = 0.25 mg/L)
500 mg every 12 h (MIC = 0.5 mg/L)
AUC0-24/MIC ratio (≥95.7) NA NA [60]
Moxifloxacin No age adjustment
400 mg every 24 h per os
AUC0-24ss
46.67 µg·h/mL
NA NA [61]
CLCR—Creatinine clearance; MIC—Minimum inhibitory concentration; AUC0-24/MIC—Ratio of area under the concentration-time curve during a 24-h period to minimum inhibitory concentration; AUC0-24ss—Area under the baseline-corrected plasma concentration versus time curve from time 0 to 24 h at steady state.
Table 5. Linezolid and polymyxin B dosing depending on age, renal function, and hepatic impairment.
Drug Regimen for Patients with
Different Renal Function
PK/PD Target
in the Elderly
Regimen for Patients with Hepatic Impairment Safety References
Tedizolid No age adjustment
200 mg every 24 h
fAUC/MIC
(MIC ≤0.5 μg/mL)
NA NA [62]
Polymyxin B Median age 68 years (IQR: 63–73), median CRCL 89 (IQR: 68–106) mL/min, bloodstream infection caused by carbapenem-resistant Klebsiella pneumoniae:
1.25 mg/kg every 12 h
AUC0-24ss/MIC ≥ 54.4 NA Risks of nephrotoxicity (manifesations may vary from proteinuria to acute kidney injury) and neurotoxicity [63][64]
fAUC/MIC—The ratio of the area under the bound (unbound) concentration time curve to the MIC; MIC—Minimum inhibitory concentration; AUC0-24ss/MIC—Area under the baseline-corrected plasma concentration versus time curve from time 0 to 24 h at steady state.

References

  1. Chinzowu, T.; Roy, S.; Nishtala, P.S. Antimicrobial-associated organ injury among the elderly: A systematic review and meta-analysis protocol. BMJ Open 2022, 11, e055210.
  2. Sabri, S.M.; Annuar, N.; Rahman, N.L.A.; Musairah, S.K.; Mutalib, H.A.; Subagja, I.K. Major Trends in Ageing Population Research: A Bibliometric Analysis from 2001 to 2021. Proceedings 2022, 82, 19.
  3. Veimer Jensen, M.L.; Aabenhus, R.M.; Holzknecht, B.J.; Bjerrum, L.; Jensen, J.N.; Siersma, V.; Córdoba, G. Antibiotic prescribing in Danish general practice in the elderly population from 2010 to 2017. Scand. J. Prim. Health Care 2021, 39, 498–505.
  4. Petrosillo, N.; Cataldo, M.A.; Pea, F. Treatment options for community-acquired pneumonia in the elderly people. Expert Rev. Anti-Infect. Ther. 2015, 13, 473–485.
  5. Bradley, S.F. Principles of Antimicrobial Therapy in Older Adults. Clin. Geriatr. Med. 2016, 32, 443–457.
  6. Bouza, E.; Brenes, F.J.; Díez Domingo, J.; Eiros Bouza, J.M.; González, J.; Gracia, D.; Juárez González, R.; Muñoz, P.; Petidier Torregrossa, R.; Casado, J.M.R.; et al. The situation of infection in the elderly in Spain: A multidisciplinary opinion document. Rev. Española Quimioter. 2020, 33, 327–349.
  7. Barber, K.E.; Bell, A.M.; Stover, K.R.; Wagner, J.L. Intravenous Vancomycin Dosing in the Elderly: A Focus on Clinical Issues and Practical Application. Drugs Aging 2016, 33, 845–854.
  8. Giarratano, A.; Green, S.E.; Nicolau, D.P. Review of antimicrobial use and considerations in the elderly population. Clin. Interv. Aging 2018, 13, 657–667.
  9. Pagani, L. Appropriate antimicrobial therapy in the elderly: When half-size does not fit all frail patients. Clin. Microbiol. Infect. 2015, 21, 1–2.
  10. Cristina, M.L.; Spagnolo, A.M.; Giribone, L.; Demartini, A.; Sartini, M. Epidemiology and Prevention of Healthcare-Associated Infections in Geriatric Patients: A Narrative Review. Int. J. Environ. Res. Public Health 2021, 18, 5333.
  11. Sanz, F.; Morales-Suarez-Varela, M.; Fernandez, E.; Force, L.; Perez-Lozano, M.J.; Martin, V.; Egurrola, M.; Castilla, J.; Astray, J.; Toledo, D.; et al. A Composite of Functional Status and Pneumonia Severity Index Improves the Prediction of Pneumonia Mortality in Older Patients. J. Gen. Intern. Med. 2018, 33, 437–444.
  12. Zhang, Z.X.; Yong, Y.; Tan, W.C.; Shen, L.; Ng, H.S.; Fong, K.Y. Prognostic factors for mortality due to pneumonia among adults from different age groups in Singapore and mortality predictions based on PSI and CURB-65. Singap. Med. J. 2018, 59, 190–198.
  13. Torres, A.; Cilloniz, C.; Niederman, M.S.; Menéndez, R.; Chalmers, J.D.; Wunderink, R.G.; van der Poll, T. Pneumonia. Nat. Rev. Dis. Prim. 2021, 7, 25.
  14. Galimberti, F.; Casula, M.; Olmastroni, E.; Catapano, A.L.; Tragni, E.; On Behalf Of Edu Re Drug Group. Antibiotic Prescription in the Community-Dwelling Elderly Population in Lombardy, Italy: A Sub-Analysis of the EDU.RE.DRUG Study. Antibiotics 2022, 11, 1369.
  15. Kusuma, I.Y.; Matuz, M.; Bordás, R.; Juhasz Haverinen, M.; Bahar, M.A.; Hajdu, E.; Visnyovszki, Á.; Ruzsa, R.; Doró, P.; Engi, Z.; et al. Antibiotic use in elderly patients in ambulatory care: A comparison between Hungary and Sweden. Front. Pharmacol. 2022, 13, 1042418.
  16. Cruz, S.P.; Cebrino, J. Prevalence and Determinants of Antibiotic Consumption in the Elderly during 2016–2017. Int. J. Environ. Res. Public Health 2020, 17, 3243.
  17. Insani, W.N.; Whittlesea, C.; Alwafi, H.; Man, K.K.C.; Chapman, S.; Wei, L. Prevalence of adverse drug reactions in the primary care setting: A systematic review and meta-analysis. PLoS ONE 2021, 16, e0252161.
  18. Vrdoljak, D.; Borovac, J.A. Medication in the elderly—Considerations and therapy prescription guidelines. Acta Med. Acad. 2015, 44, 159–168.
  19. Lexow, M.; Wernecke, K.; Schmid, G.L.; Sultzer, R.; Bertsche, T.; Schiek, S. Considering additive effects of polypharmacy: Analysis of adverse events in geriatric patients in long-term care facilities. Wien. Klin. Wochenschr. 2021, 133, 816–824.
  20. Dovjak, P. Polypharmacy in elderly people. Wien. Med. Wochenschr. 2022, 172, 109–113.
  21. Kim, J.; Parish, A.L. Polypharmacy and Medication Management in Older Adults. Nurs. Clin. N. Am. 2017, 52, 457–468.
  22. Ye, L.; Yang-Huang, J.; Franse, C.B.; Rukavina, T.; Vasiljev, V.; Mattace-Raso, F.; Verma, A.; Borrás, T.A.; Rentoumis, T.; Raat, H. Factors associated with polypharmacy and the high risk of medication-related problems among older community-dwelling adults in European countries: A longitudinal study. BMC Geriatr. 2022, 22, 841.
  23. Corsonello, A.; Abbatecola, A.M.; Fusco, S.; Luciani, F.; Marino, A.; Catalano, S.; Maggio, M.G.; Lattanzio, F. The impact of drug interactions and polypharmacy on antimicrobial therapy in the elderly. Clin. Microbiol. Infect. 2015, 21, 20–26.
  24. Pea, F. Pharmacokinetics and drug metabolism of antibiotics in the elderly. Expert Opin. Drug Metab. Toxicol. 2018, 14, 1087–1100.
  25. Hoff, B.M.; Maker, J.H.; Dager, W.E.; Heintz, B.H. Antibiotic Dosing for Critically Ill Adult Patients Receiving Intermittent Hemodialysis, Prolonged Intermittent Renal Replacement Therapy, and Continuous Renal Replacement Therapy: An Update. Ann. Pharmacother. 2020, 54, 43–55.
  26. Tannenbaum, C.; Day, D.; on behalf of the Matera Alliance. Age and sex in drug development and testing for adults. Pharmacol. Res. 2017, 121, 83–93.
  27. Appaneal, H.J.; Shireman, T.I.; Lopes, V.V.; Mor, V.; Dosa, D.M.; LaPlante, K.L.; Caffrey, A.R. Poor clinical outcomes associated with suboptimal antibiotic treatment among older long-term care facility residents with urinary tract infection: A retrospective cohort study. BMC Geriatr. 2021, 21, 436.
  28. Simonetti, A.F.; Viasus, D.; Garcia-Vidal, C.; Carratalà, J. Management of community-acquired pneumonia in older adults. Ther. Adv. Infect. Dis. 2014, 2, 3–16.
  29. Compté, N.; Dumont, L.; Bron, D.; De Breucker, S.; Praet, J.P.; Bautmans, I.; Pepersack, T. White blood cell counts in a geriatric hospitalized population: A poor diagnostic marker of infection. Exp. Gerontol. 2018, 114, 87–92.
  30. Chong, C.P.; Street, P.R. Pneumonia in the elderly: A review of the epidemiology, pathogenesis, microbiology, and clinical features. South Med. J. 2008, 101, 1141–1145; quiz 1132, 1179.
  31. Davies, E.A.; O’Mahony, M.S. Adverse drug reactions in special populations—The elderly. Br. J. Clin. Pharmacol. 2015, 80, 796–807.
  32. Völter, C.; Götze, L.; Dazert, S.; Wirth, R.; Thomas, J.P. Impact of Hearing Loss on Geriatric Assessment. Clin. Interv. Aging 2020, 15, 2453–2467.
  33. Kim, L.D.; Koncilja, K.; Nielsen, C. Medication management in older adults. Clevel. Clin. J. Med. 2018, 85, 129–135.
  34. Zullo, A.R.; Gray, S.L.; Holmes, H.M.; Marcum, Z.A. Screening for Medication Appropriateness in Older Adults. Clin. Geriatr. Med. 2018, 34, 39–54.
  35. Morrill, H.J.; Caffrey, A.R.; Jump, R.L.; Dosa, D.; LaPlante, K.L. Antimicrobial Stewardship in Long-Term Care Facilities: A Call to Action. J. Am. Med. Dir. Assoc. 2016, 17, 183.e1–183.e16.
  36. Janssen, M.W.H.; de Bont, E.G.P.M.; Hoebe, C.J.P.A.; Cals, J.W.L.; den Heijer, C.D.J. Trends in antibiotic prescribing in Dutch general practice and determinants of nonprudent antibiotic prescriptions. Fam. Pract. 2023, 40, 61–67.
  37. Majcher-Peszynska, J.; Loebermann, M.; Klammt, S.; Frimmel, S.; Mundkowski, R.G.; Welte, T.; Reisinger, E.C.; Drewelow, B.; CAPNETZ Study Group. Ampicillin/sulbactam in elderly patients with community-acquired pneumonia. Infection 2014, 42, 79–87.
  38. Suzuki, T.; Sugiyama, E.; Nozawa, K.; Tajima, M.; Takahashi, K.; Yoshii, M.; Suzuki, H.; Sato, V.H.; Sato, H. Effects of dosing frequency on the clinical efficacy of ampicillin/sulbactam in Japanese elderly patients with pneumonia: A single-center retrospective observational study. Pharmacol. Res. Perspect. 2021, 9, e00746.
  39. Cojutti, P.G.; Morandin, E.; Baraldo, M.; Pea, F. Population pharmacokinetics of continuous infusion of piperacillin/tazobactam in very elderly hospitalized patients and considerations for target attainment against Enterobacterales and Pseudomonas aeruginosa. Int. J. Antimicrob. Agents. 2021, 58, 106408.
  40. Ulldemolins, M.; Roberts, J.A.; Lipman, J.; Rello, J. Antibiotic dosing in multiple organ dysfunction syndrome. Chest 2011, 139, 1210–1220.
  41. Quinton, M.C.; Bodeau, S.; Kontar, L.; Zerbib, Y.; Maizel, J.; Slama, M.; Masmoudi, K.; Lemaire-Hurtel, A.S.; Bennis, Y. Neurotoxic Concentration of Piperacillin during Continuous Infusion in Critically Ill Patients. Antimicrob. Agents Chemother. 2017, 61, e00654-17.
  42. Ruiz-Ramos, J.; Herrera-Mateo, S.; López-Vinardell, L.; Juanes-Borrego, A.; Puig-Campmany, M.; Mangues-Bafalluy, M.A. Cefepime Dosing Requirements in Elderly Patients Attended in the Emergency Rooms. Dose Response 2022, 20, 15593258221078393.
  43. Boschung-Pasquier, L.; Atkinson, A.; Kastner, L.K.; Banholzer, S.; Haschke, M.; Buetti, N.; Furrer, D.I.; Hauser, C.; Jent, P.; Que, Y.A.; et al. Cefepime neurotoxicity: Thresholds and risk factors. A retrospective cohort study. Clin. Microbiol. Infect. 2020, 26, 333–339.
  44. Tan, S.J.; Cockcroft, M.; Page-Sharp, M.; Arendts, G.; Davis, T.M.E.; Moore, B.R.; Batty, K.T.; Salman, S.; Manning, L. Population Pharmacokinetic Study of Ceftriaxone in Elderly Patients, Using Cystatin C-Based Estimates of Renal Function To Account for Frailty. Antimicrob. Agents Chemother. 2020, 64, e00874-20.
  45. Jadot, L.; Judong, A.; Canivet, J.L.; Lorenzo-Villalba, N.; Damas, P. Ceftriaxone-induced Encephalopathy: A Pharmacokinetic Approach. Eur. J. Case Rep. Intern. Med. 2021, 8, 003011.
  46. Veillette, J.J.; Truong, J.; Forland, S.C. Pharmacokinetics of Ceftazidime-Avibactam in Two Patients with KPC-Producing Klebsiella pneumoniae Bacteremia and Renal Impairment. Pharmacotherapy 2016, 36, e172–e177.
  47. Pingue, V.; Penati, R.; Nardone, A.; Franciotta, D. Ceftazidime/avibactam neurotoxicity in an adult patient with normal renal function. Clin. Microbiol. Infect. 2020.
  48. Aloy, B.; Launay-Vacher, V.; Bleibtreu, A.; Bortolotti, P.; Faure, E.; Filali, A.; Gauzit, R.; Gilbert, M.; Lesprit, P.; Mahieu, R.; et al. Antibiotics and chronic kidney disease: Dose adjustment update for infectious disease clinical practice. Med. Mal. Infect. 2020, 50, 323–331.
  49. Harada, M.; Inui, N.; Suda, T.; Nakamura, Y.; Wajima, T.; Matsuo, Y.; Chida, K. Pharmacokinetic analysis of doripenem in elderly patients with nosocomial pneumonia. Int. J. Antimicrob. Agents 2013, 42, 149–154.
  50. Musson, D.G.; Majumdar, A.; Holland, S.; Birk, K.; Xi, L.; Mistry, G.; Sciberras, D.; Muckow, J.; Deutsch, P.; Rogers, J.D. Pharmacokinetics of total and unbound ertapenem in healthy elderly subjects. Antimicrob. Agents Chemother. 2004, 48, 521–524.
  51. Lee, K.H.; Ueng, Y.F.; Wu, C.W.; Chou, Y.C.; Ng, Y.Y.; Yang, W.C. The recommended dose of ertapenem poses a potential risk for central nervous system toxicity in haemodialysis patients—Case reports and literature reviews. J. Clin. Pharm. Ther. 2015, 40, 240–244.
  52. Usman, M.; Frey, O.R.; Hempel, G. Population pharmacokinetics of meropenem in elderly patients: Dosing simulations based on renal function. Eur. J. Clin. Pharmacol. 2017, 73, 333–342.
  53. Steffens, N.A.; Zimmermann, E.S.; Nichelle, S.M.; Brucker, N. Meropenem use and therapeutic drug monitoring in clinical practice: A literature review. J. Clin. Pharm. Ther. 2021, 46, 610–621.
  54. Karino, F.; Deguchi, N.; Kanda, H.; Ohe, M.; Kondo, K.; Tada, M.; Kuraki, T.; Isobe, T.; Nishimura, N.; Moriyama, H.; et al. Evaluation of the efficacy and safety of biapenem against pneumonia in the elderly and a study on its pharmacokinetics. J. Infect. Chemother. 2013, 19, 98–102.
  55. Kato, H.; Parker, S.L.; Roberts, J.A.; Hagihara, M.; Asai, N.; Yamagishi, Y.; Paterson, D.L.; Mikamo, H. Population Pharmacokinetics Analysis of Amikacin Initial Dosing Regimen in Elderly Patients. Antibiotics 2021, 10, 100.
  56. Bourguignon, L.; Goutelle, S.; De Saint-Martin, J.B.; Maire, P.; Ducher, M. Evaluation of various gentamicin dosage regimens in geriatric patients: A simulation study. Fundam. Clin. Pharmacol. 2010, 24, 109–113.
  57. Zhou, Y.; Gao, F.; Chen, C.; Ma, L.; Yang, T.; Liu, X.; Liu, Y.; Wang, X.; Zhao, X.; Que, C.; et al. Development of a Population Pharmacokinetic Model of Vancomycin and its Application in Chinese Geriatric Patients with Pulmonary Infections. Eur. J. Drug Metab. Pharmacokinet. 2019, 44, 361–370.
  58. Samura, M.; Takada, K.; Yamamoto, R.; Ito, H.; Nagumo, F.; Uchida, M.; Kurata, T.; Koshioka, S.; Enoki, Y.; Taguchi, K.; et al. Population Pharmacokinetic Analysis and Dosing Optimization Based on Unbound Daptomycin Concentration and Cystatin C in Nonobese Elderly Patients with Hypoalbuminemia and Chronic Kidney Disease. Pharm. Res. 2021, 38, 1041–1055.
  59. Balice, G.; Passino, C.; Bongiorni, M.G.; Segreti, L.; Russo, A.; Lastella, M.; Luci, G.; Falcone, M.; Di Paolo, A. Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update. Antibiotics 2022, 11, 914.
  60. Cojutti, P.G.; Ramos-Martin, V.; Schiavon, I.; Rossi, P.; Baraldo, M.; Hope, W.; Pea, F. Population Pharmacokinetics and Pharmacodynamics of Levofloxacin in Acutely Hospitalized Older Patients with Various Degrees of Renal Function. Antimicrob. Agents Chemother. 2017, 61, e02134-16.
  61. Ito, F.; Ohno, Y.; Toyoshi, S.; Kaito, D.; Koumei, Y.; Endo, J.; Kamamiya, F.; Mori, H.; Mori, M.; Morishita, M.; et al. Pharmacokinetics of consecutive oral moxifloxacin (400 mg/day) in patients with respiratory tract infection. Ther. Adv. Respir. Dis. 2016, 10, 34–42.
  62. Flanagan, S.D.; Minassian, S.L.; Prokocimer, P. Pharmacokinetics, Safety, and Tolerability of Tedizolid Phosphate in Elderly Subjects. Clin. Pharmacol. Drug Dev. 2018, 7, 788–794.
  63. Yu, Z.; Liu, X.; Du, X.; Chen, H.; Zhao, F.; Zhou, Z.; Wang, Y.; Zheng, Y.; Bergen, P.J.; Li, X.; et al. Pharmacokinetics/pharmacodynamics of polymyxin B in patients with bloodstream infection caused by carbapenem-resistant Klebsiella pneumoniae. Front. Pharmacol. 2022, 13, 975066.
  64. Qu, J.; Qi, T.T.; Qu, Q.; Long, W.M.; Chen, Y.; Luo, Y.; Wang, Y. Polymyxin B-Based Regimens for Patients Infected with Carbapenem-Resistant Gram-Negative Bacteria: Clinical and Microbiological Efficacy, Mortality, and Safety. Infect. Drug Resist. 2022, 15, 1205–1218.
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