Table 2.

Summary of vancomycins’ PK parameters in adults affected with ventriculitis and meningitis. n represents the number of participants.

Type of Infection	Study Design (n)	Dose	Route	Blood and CSF Sampling	Plasma (mg/L)	CSF (mg/L)	CSF Penetration	PK Model	Age	Treatment Outcome/Remarks	Ref.
Proven or suspected EVD- associated ventriculitis	Prospective observational (21)	Prolonged infusion (over 4 h) median daily dose 2500 (500–4000) mg in two divided doses, targeted trough concentrations in serum 10–15 mg/L	IV	Serum and CSF both just before start of infusion (Cmin) and at end of infusion (Cmax), Source of CSF samples: intraventricular (EVD)	Cmax = 25.67 (10.60–50.78) Cmin = 9.60 (4.46–23.56)	Cmax = 0.65 (<0.24–3.83) Cmin = 0.59 (<0.24–3.95)	Cumulative AUCCSF/CumulativeAUCSerum 0.03 (0.01–0.18)	Yes	52 (46–80) years	30 days mortality: 0	[36]
EVD- associated ventriculitis	Retrospective (29)	Daily dose of 2–4 g, depending on creatinine clearance, either via continuous infusion (initial bolus of 1 g over 1 h) or as intermittent infusion (q6h over 1 h), depending on physician, Doses adjusted to TDM (target plasma trough levels of 15–20 mg/L with bolus infusions, plasma levels of 20–25 mg/L with continuous infusion)	IV	Mostly trough samples, no CSF samples for 3 patients, Source of CSF samples NS	17.7 (IQR 13.00, 23.02)	2.9 (IQR 1.76, 4.2)	0.13 (IQR 0.07; 0.24) under bolus therapy 0.08 (IQR 0.05; 0.12) under continuous therapy	Yes	52 (IQR 44; 61) years	NS	[20]
Ventriculitis	Retrospective(22 for vancomycin and meropenem)	Continuous infusion of 30 mg/kg/day after initial bolus of 30 mg/kg of adjusted body weight, Serum target concentration of 20–30 mg/L, CSF target concentration of 2 mg/L, Dosage adjusted according to TDM results	IV	Samples from 15 patients, timepoints NS, Source of CSF samples: NS	22 ± 814 values (33%) below and two values,(5%) above the targeted concentration	4.5 ± 2.6Above the breakpoint for susceptibility of S. aureus in 30 cases (70%), above the breakpoint for susceptibility of other Gram-positive cocci in 21 cases (49%)	20% ± 11% (3–48%)	No	57 ± 12 years	Death of 7 out of 22 patients, for the remaining patients GOS 2–4	[11]
Healthcare- associated meningitis	Retrospective (6)	15 mg/kg loading dose, followed by continuous infusion of 60 mg/kg/day	IV	First measurements (day 1–5 of treatment); when antibiotics administration discontinuous right before following administration Second measurements (day 2–11, 4 patients), Source of CSF samples: NS	36.1 ± 19.2 (A)(15.4–66.4) 34.9 ± 22.1 (A)(17.2–71.4)	3 patients < 1.1,2 patients 1.5 1 patient < 1.1 3 patients: 1.2, 2.6, 2.2	ND	No	43.2± 13.0 (28–64) years (A)	Treatment regimen was changed to other antibiotics	[47]
Suspected and provenbacterial meningitis	Retrospective (7)	2–4 times/day, Dose adjusted to TDMto achieve serum trough concentrations of 15–20 mg/L	IV	Blood samples measured just before vancomycin infusion when steady-state concentrations were achieved and after at least 2 days of the dosing regimen, CSF measured retrospectively using residual CSF, Source of CSF samples: intraventricular (EVD) or lumbar, after achievement of steady-state serum concentrations	17.6 ± 7.2	3.31 ± 3.14	0.180 ± 0.152 (0.010–0.431)	No	41.7 ± 19.2 (17–70) years (A)	Vancomycin treatment ineffective in 2 patients, for 2 patients clinical efficacy was undeterminable	[48]
Proven or highly suspectedpostsurgical meningitis	Prospective (22)	500 mg over 1 h, q6h(for at least 5 days)	IV	Serum and CSF both measured 5 h after the end of infusion (Cmin) on day 3 or 4, Source of CSF samples: lumbar (puncture or drainage)	Cmin = 13.38 ± 5.36 (5.07–28.6)	Cmin = 3.63 ± 1.64 (1.44–8.51)	0.291 ± 0.118 (0.163–0.570)	No	52.6 ± 12.1 (25–74) years	12 patients were cured, 10 patients improved after 3–5 days, no vancomycin-induced nephrotoxicity	[49]
Postneuro- surgical meningitis	Randomized clinical trial (20) (10 for each infusion group)	Intermittent infusion: Initial dose of 25 mg/kg over 2 h, then 25 mg/kg over 2 h q12h Continuous infusion: Initial dose of 25 mg/kg over 2 h, then 50 mg/kg/day	IV IV	Serum samples measured 30 min before (Ctrough) and 1 h after each maintenance dose (Cpeak), CSF samples measured at days 4 and 8, concomitantly with serum trough samples, Source of CSF samples: NS “-“	Ctrough = 17.49 ± 2.46 Cpeak = 41.33 ± 2.73 24.76 ± 2.02	Ctrough = 4.83 ± 1.05 6.20 ± 1.31	CSF/trough ratio 27.39% ± 2.43% 24.84% ± 3.54%	No	49 ± 7.25 years 48 ± 8.02 years	Recovery of all patients, Therapy was well-tolerated	[50]
Community-acquired Meningitis Postoperative intracranial infection	Prospective (22) (10 community-acquired meningitis, 12 postoperative intracranial infection)	Initial treatment 1 g over more than 1 h, q12h; regimen adjusted according to signs and symptoms “-“	IV IV	Serum and CSF 0.5 h before fifth dose (Ctrough) “-“ Source of CSF samples: lumbar (puncture) or intraventricular (ventricle drainage tube)	Ctrough = 9.81 ± 1.89 (6.90~13.00) Ctrough = 9.74 ± 3.04 (5.01~13.90)	Ctrough = 2.47 ± 1.15 (0.80~4.03) Ctrough = 1.90 ± 1.29 (0.42~4.40)	0.26 ± 0.12 (0.11~0.47) 0.19 ± 0.12(0.06~0.45)	No	36.2 ±14.3 years 51.2 ± 9.9 years	NS	[51]
Meningitis	Case report	1 g, q12h	IV	Blood and serum samples measured during treatment, NS, Source of CSF samples: lumbar (puncture)	Ctrough = 11–18 Cpeak(day 26) = 28.6	Ctrough = 9.4 C(1 h after infusion) = 12.8	ND	No	47 years	Successfully treated	[52]

Abbreviations: C_max: maximum concentration, C_min: minimum concentration, C_peak: peak concentration, C_trough: trough concentration, GOS: Glasgow Outcome Scale, IQR: interquartile range, IV: intravenous, NS: not specified, ND: no data, q12h: every 12 h, TDM: therapeutic drug monitoring (A) not reported in study, calculated from individual patient data, “-“: same as above.