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.
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) |
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mean age 85 (82–87) years: 11.25 g every 24 h (CLCR 40–59 mL/min/1.73 m2) |
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mean age 85 (82–87) years: 13.5 g every 24 h (CLCR 60–79 mL/min/1.73 m2) |
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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 |
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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] |
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] |
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] |
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] |
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] |
This entry is adapted from the peer-reviewed paper 10.3390/biomedicines11061633