Pharmacological properties of oral antibiotics for the treatment of uncomplicated urinary tract infections

Figures & data

Table 1 National and international guideline recommendation for the treatment of uncomplicated urinary tract infections

Infectious diseases society of America 2011^1	European association of urology guidelines 2017^2
• Nitrofurantoin monohydrate/ macrocrystals 100 mg twice daily for 5 days (A–I) • Trimethoprim-sulfamethoxazole 160/800 mg bid for 3 days^* (A–I) • Fosfomycin trometamol 3 g single dose (A–I) • Pivmecillinam(400 mg bid for 5 days (A–I) • Fluoroquinolones in 3-day regimens^* (A–I) but should be considered alternative antimicrobials for acute cystitis (A–III). • Beta-lactam agents in 3- to 7-day regimens when other recommended agents cannot be used (B–I)	First choice agents
	• Fosfomycin trometamol 3 g single dose • Pivmecillinam 400 mg tid for 3–5 days • Nitrofurantoin macrocrystal 100 mg bid for 5 days
	Alternative agents
	• ^*Cephalosporins (e.g. cefadroxil) 500 mg bid for 3 days

Notes: bid, twice daily; tid, three times daily.

* Only if local resistance rates of uropathogens causing acute uncomplicated cystitis do not exceed 20% or if the infecting strain is known to be susceptible.

Table 2 Characteristics of an ideal drug for treatment of uncomplicated urinary tract infections⁴

• Maximum in vitro activity against prevalent uropathogens • Minimum percentage of resistance • Possibility of overcoming resistance to other molecules • Optimum pharmacokinetic-pharmacodynamic profile • Good tolerability and documented clinical efficacy

Figure 1 Pharmacokinetic-pharmacodynamic parameters for antimicrobial activity of antibiotics.

Table 3 Pharmacokinetic parameters of quinolones indicated for the treatment of uncomplicated UTIs^10,12–19

Quinolones	Dose (mg)	Cmax (mg/L)	t½ß (h)	Bioavailability (%)	Protein binding (%)	Metabolism (%)	Fu (%)	Peak urine concentration (mg/L)
First generation
Nalidixic acid	1000	20–35	1.5	95	90	70	90	150–400
Pipemidic acid	400	3–4	3.5	70	15	<5	50–70	600–900
Second generation
Norfloxacin	400	1–2	3.5–5	40	15	20	30	30
Ofloxacin	300	5–7	6–8	90	25	<10	80	85–95
Ciprofloxacin	250	0.8–1.9	–	–	–	–	–	–
	500	2–3	5–6	70–80	30	35	40–50	200
Prulifloxacin	600	~2	10	–	50	<20	20	110
Third generation
Levofloxacin	500^*	5–7	7–8	99	24–38	–	85	521–771

Notes: C_max, peak plasma concentration; Fu, urinary recovery; t_1/2β, elimination half-life.

* 250 mg dose is recommended for urinary tract infections.

Table 4 Pharmacokinetic parameters after a single oral 800/160 mg dose of co-trimoxazole^30,31

Parameter	Sulfamethoxazole	Trimethoprim
Bioavailability (%)	85–90	85–90
Cmax (mg/L)	35–65	1.2–1.9
Vd (L)	13	100
Protein binding (%)	65	45
Kel (h^−1)	0.060	0.060
t1/2β (h)	10–12	10–12
pKa	5.8	7.3

Notes: C_max, peak plasma concentration; K_el, elimination rate constant; t_1/2β, elimination half-life; pKa, acid dissociation constant; Vd, volume of distribution.

Table 5 Pharmacokinetic parameters of oral beta-lactams^37–44

Beta-lactam	Dose (mg)	Cmax (mg/L)	tmax(h)	t½ß(h)	Bioavailability (%)	Dosing interval (h)	Fu(%)
Amoxicillin/clavulanic acid	875/125	10.4–3.5	1	1.2/1	90/75	12	75/60
Cefuroxime axetil^*	500	4.4–9.9	2.3–3.4	1.3–1.8	36–52	12	32
Cefixime^**	400	4	4	3.8	40–48	24	18
Ceftibuten^**	400	15	2	2.5	80–85	24	70
Cefpodoxime proxetil	200	2.6	2.8	2.7	50	12	46
Pivmecillinam	200	1.7±1.2	1.5	10.0	65–70	24	40

Notes: C_max, peak plasma concentration; Fu, urinary recovery; t_1/2β, elimination half-life; t_max, time to peak plasma concentration.

* Prodrug.

** Intrinsic bioavailability.

Table 6 Pharmacokinetic parameters of nitrofurantoin in healthy subjects^*,52

Parameter	Value
Cmax (mg/L)	0.875–0.963
t1/2β (h)	0.72–0.78
AUC0-∞ (mg·h/L)	2.21–2.42
CLR (L/h)	16.7–19.4
Fu (%)	38.8–44.3

Notes: AUC, area under the concentration-time curve; CL_R, renal clearance; C_max, peak plasma concentration; Fu, urinary recovery; t_1/2β, elimination half-life.

* 36 subjects with different expression of the ABCG2 421 genotype.

Table 7 Pharmacokinetic parameters of fosfomycin trometamol^57,59

Parameter	Value
Cmax (mg/L)	25–30
tmax (min)	45–120
Cmin (mg/L)	~3 mg/l
t1/2β (h)	5–7
Vd (L/kg)	0.3–0.4
CLR (L/h)	~7.8

Notes: CL_R, renal clearance; C_max, peak plasma concentration; C_min, trough concentration; t_1/2β, elimination half-life; t_max, time to peak plasma concentration; Vd, volume of distribution.

Figure 2 Mean serum and urinary drug concentrations after a single oral 3 g dose of fosfomycin trometamol.⁵⁷

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