中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (9): 1221-1230.doi: 10.12092/j.issn.1009-2501.2026.09.008
• 临床药理学 • 上一篇
姜俞濛1(
), 李建中1, 杭永付2, 杨友静3, 陶莎莎3, 胡坤1, 徐德宇1, 卢国元1,*(
)
收稿日期:2025-07-04
修回日期:2025-12-15
出版日期:2026-09-26
发布日期:2026-10-08
通讯作者:
卢国元
E-mail:18151820813@163.com;sdfyylgy@163.com
作者简介:姜俞濛,女,硕士研究生,住院医师,研究方向:血药浓度影响因素。E-mail:基金资助:
Yumeng JIANG1(
), Jianzhong LI1, Yongfu HANG2, Youjing YANG3, Shasha TAO3, Kun HU1, Deyu XU1, Guoyuan LU1,*(
)
Received:2025-07-04
Revised:2025-12-15
Online:2026-09-26
Published:2026-10-08
Contact:
Guoyuan LU
E-mail:18151820813@163.com;sdfyylgy@163.com
摘要:
目的: 分析腹膜透析相关性腹膜炎(peritoneal dialysis-related peritonitis,PDRP)患者腹腔内注射万古霉素后血药浓度的影响因素及与临床疗效的相关性。方法: 回顾性收集2021年1月至2024年8月苏州大学附属第一医院37例接受腹腔1 g万古霉素给药并监测血药浓度的PDRP患者临床资料,于第2次给药前0.5 h采血,测定首次血药浓度(谷浓度)。结果: 17例既往有腹膜炎感染史的PDRP患者首次血药浓度为11.22(9.46,11.93)μg/mL,显著高于20例无感染史的PDRP患者首次血药浓度[8.66(7.84,9.51)μg/mL(P<0.01)];Logistic回归分析提示腹膜炎感染史及给药间隔时长是首次血药浓度的独立影响因素(P<0.01);腹膜炎感染史在任何给药间隔下均能提高浓度,而给药间隔时间仅在无感染史患者中起明显作用;万古霉素治疗前、后,腹透液细胞成分及转阴天数在高浓度组与低浓度组差异无统计学意义(P>0.05);两组治疗后腹透液细胞成分和C反应蛋白(C-reactive protein,CRP)水平均较治疗前下降(P<0.05);高浓度组患者治疗后CRP水平较低浓度组患者高(P<0.05)。结论: 既往腹膜炎感染史和给药间隔时长可显著影响万古霉素首次血药浓度,但首次浓度水平对PDRP患者的临床疗效和转阴天数无显著影响。
中图分类号:
姜俞濛, 李建中, 杭永付, 杨友静, 陶莎莎, 胡坤, 徐德宇, 卢国元. 腹膜透析相关性腹膜炎患者的万古霉素首次血药浓度影响因素分析[J]. 中国临床药理学与治疗学, 2026, 31(9): 1221-1230.
Yumeng JIANG, Jianzhong LI, Yongfu HANG, Youjing YANG, Shasha TAO, Kun HU, Deyu XU, Guoyuan LU. Influencing factors of the first serum concentration of vancomycin in patients with peritoneal dialysis-related peritonitis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(9): 1221-1230.
| Baseline characteristics | Dosing interval 48 h group | Dosing interval 72 h group | P |
| Dialysis duration (month) | 38(19,47) | 34(20,98) | 0.673 |
| Scr (μmol/L) | 946.45(783.80, | 0.126 | |
| CysC (mg/L) | 7.12(5.73,8.16) | 7.07(5.57,8.17) | 0.933 |
| Urea (mmol/L) | 24.00(14.85,26.30) | 22.40(16.90,29.20) | 0.768 |
| UA (μmol/L) | 351.00(274.80,464.00) | 327.60(279.28,401.13) | 0.399 |
| Urine volume (mL/24 h) | 0(0,865) | 0(0,125) | 0.418 |
| Kt/V | 1.56(1.44,1.73) | 1.68(1.37,1.88) | 0.593 |
| D/P | 0.68(0.62,0.75) | 0.69(0.61,0.75) | 0.994 |
| Peritoneal dialysate nucleated cell count (109/L) | 1.056(0.423,5.366) | 1.562(0.396,4.712) | 0.978 |
| Percentage of neutrophils in dialysate (%) | 86.0(79.4,90.3) | 83.7(74.4,90.1) | 0.663 |
| Peripheral blood WBC count (109/L) | 7.20(4.57,9.22) | 6.84(5.08,8.72) | 0.966 |
| Peripheral blood neutrophil percentage (%) | 75.4(68.4,83.8) | 78.2(67.0,83.5) | 0.536 |
| CRP (mg/L) | 12.93(10.06,50.34) | 27.38(14.25,49.55) | 0.126 |
| History of peritonitis infection (%) | 0.699 | ||
| No | 7(50.00) | 13(56.52) | |
| Yes | 7(50.00) | 10(43.48) |
表 1
Table 1 Comparison of renal function, peritoneal transport characteristics, and inflammatory status between the 48 h and 72 h dosing interval groups
| Baseline characteristics | Dosing interval 48 h group | Dosing interval 72 h group | P |
| Dialysis duration (month) | 38(19,47) | 34(20,98) | 0.673 |
| Scr (μmol/L) | 946.45(783.80, | 0.126 | |
| CysC (mg/L) | 7.12(5.73,8.16) | 7.07(5.57,8.17) | 0.933 |
| Urea (mmol/L) | 24.00(14.85,26.30) | 22.40(16.90,29.20) | 0.768 |
| UA (μmol/L) | 351.00(274.80,464.00) | 327.60(279.28,401.13) | 0.399 |
| Urine volume (mL/24 h) | 0(0,865) | 0(0,125) | 0.418 |
| Kt/V | 1.56(1.44,1.73) | 1.68(1.37,1.88) | 0.593 |
| D/P | 0.68(0.62,0.75) | 0.69(0.61,0.75) | 0.994 |
| Peritoneal dialysate nucleated cell count (109/L) | 1.056(0.423,5.366) | 1.562(0.396,4.712) | 0.978 |
| Percentage of neutrophils in dialysate (%) | 86.0(79.4,90.3) | 83.7(74.4,90.1) | 0.663 |
| Peripheral blood WBC count (109/L) | 7.20(4.57,9.22) | 6.84(5.08,8.72) | 0.966 |
| Peripheral blood neutrophil percentage (%) | 75.4(68.4,83.8) | 78.2(67.0,83.5) | 0.536 |
| CRP (mg/L) | 12.93(10.06,50.34) | 27.38(14.25,49.55) | 0.126 |
| History of peritonitis infection (%) | 0.699 | ||
| No | 7(50.00) | 13(56.52) | |
| Yes | 7(50.00) | 10(43.48) |
| Variable | Low-serum concentration group | High-serum concentration group | P |
| Sex (%) | 0.742 | ||
| Male | 12(57.14) | 10(62.50) | |
| Female | 9(42.86) | 6(37.50) | |
| Age (years) | 46(37,63) | 48(37,65) | 0.978 |
| BSA (m2) | 1.80(1.70,1.96) | 1.84(1.56,1.94) | 0.391 |
| Dialysis duration (month) | 38(19,61) | 34(22,94) | 0.649 |
| eGFR [mL/(min·1.73 m2)] | 5.00(4.05,5.60) | 4.40(3.60,6.10) | 0.934 |
| Scr (μmol/L) | 955.20(829.43, | 0.772 | |
| CysC (mg/L) | 7.27(5.37,8.22) | 7.12(6.27,7.44) | 0.610 |
| Urea (mmol/L) | 23.40(18.20,26.10) | 20.80(11.80,30.20) | 0.363 |
| UA (μmol/L) | 373.15(309.15,416.43) | 291.70(274.20,394.25) | 0.080 |
| ALT (U/L) | 12.70(9.43,19.00) | 8.50(6.80,15.20) | 0.045* |
| AST (U/L) | 12.20(10.30,17.20) | 11.50(9.20,20.40) | 0.895 |
| Urine volume (mL/24 h) | 0(0,200) | 0(0,365) | 0.678 |
| Kt/V | 1.62(1.40,1.88) | 1.57(1.34,1.73) | 0.581 |
| D/P | 0.70(0.61,0.76) | 0.68(0.60,0.73) | 0.349 |
| Peritoneal dialysate nucleated cell count (109/L) | 0.882(0.313,4.832) | 1.182(0.574,5.286) | 0.355 |
| Percentage of neutrophils in dialysate (%) | 85.0(75.0,92.0) | 86.0(76.4,88.4) | 0.783 |
| Peripheral blood WBC count (109/L) | 6.49(5.15,9.22) | 7.20(4.46,8.81) | 0.501 |
| Peripheral blood neutrophil percentage (%) | 79.8(68.2,83.8) | 73.1(63.6,82.5) | 0.214 |
| CRP (mg/L) | 26.16(12.08,85.2) | 15.68(12.45,43.80) | 0.155 |
| Bacterial species (%) | 0.500 | ||
| G+ | 11(52.38) | 11(68.75) | |
| G? | 10(47.62) | 5(31.25) | |
| Dosing interval (h) | 0.015* | ||
| 48 | 4(19.05) | 10(62.50) | |
| 72 | 17(80.95) | 6(37.50) | |
| History of peritonitis (%) | 0.022* | ||
| No | 15(71.43) | 5(31.25) | |
| Yes | 6(28.57) | 11(68.75) |
表 2
Table 2 Comparison of general information and laboratory indicators between the two groups
| Variable | Low-serum concentration group | High-serum concentration group | P |
| Sex (%) | 0.742 | ||
| Male | 12(57.14) | 10(62.50) | |
| Female | 9(42.86) | 6(37.50) | |
| Age (years) | 46(37,63) | 48(37,65) | 0.978 |
| BSA (m2) | 1.80(1.70,1.96) | 1.84(1.56,1.94) | 0.391 |
| Dialysis duration (month) | 38(19,61) | 34(22,94) | 0.649 |
| eGFR [mL/(min·1.73 m2)] | 5.00(4.05,5.60) | 4.40(3.60,6.10) | 0.934 |
| Scr (μmol/L) | 955.20(829.43, | 0.772 | |
| CysC (mg/L) | 7.27(5.37,8.22) | 7.12(6.27,7.44) | 0.610 |
| Urea (mmol/L) | 23.40(18.20,26.10) | 20.80(11.80,30.20) | 0.363 |
| UA (μmol/L) | 373.15(309.15,416.43) | 291.70(274.20,394.25) | 0.080 |
| ALT (U/L) | 12.70(9.43,19.00) | 8.50(6.80,15.20) | 0.045* |
| AST (U/L) | 12.20(10.30,17.20) | 11.50(9.20,20.40) | 0.895 |
| Urine volume (mL/24 h) | 0(0,200) | 0(0,365) | 0.678 |
| Kt/V | 1.62(1.40,1.88) | 1.57(1.34,1.73) | 0.581 |
| D/P | 0.70(0.61,0.76) | 0.68(0.60,0.73) | 0.349 |
| Peritoneal dialysate nucleated cell count (109/L) | 0.882(0.313,4.832) | 1.182(0.574,5.286) | 0.355 |
| Percentage of neutrophils in dialysate (%) | 85.0(75.0,92.0) | 86.0(76.4,88.4) | 0.783 |
| Peripheral blood WBC count (109/L) | 6.49(5.15,9.22) | 7.20(4.46,8.81) | 0.501 |
| Peripheral blood neutrophil percentage (%) | 79.8(68.2,83.8) | 73.1(63.6,82.5) | 0.214 |
| CRP (mg/L) | 26.16(12.08,85.2) | 15.68(12.45,43.80) | 0.155 |
| Bacterial species (%) | 0.500 | ||
| G+ | 11(52.38) | 11(68.75) | |
| G? | 10(47.62) | 5(31.25) | |
| Dosing interval (h) | 0.015* | ||
| 48 | 4(19.05) | 10(62.50) | |
| 72 | 17(80.95) | 6(37.50) | |
| History of peritonitis (%) | 0.022* | ||
| No | 15(71.43) | 5(31.25) | |
| Yes | 6(28.57) | 11(68.75) |
图 1 cP<0.01, compared with previous PDRP group.
Fig.1 Effect of a history of peritonitis infection on the first serum concentration ($\bar x $±s) cP<0.01, compared with previous PDRP group.
| Variable | Univariate logistic | Multivariate logistic | |||
| OR(95%CI) | P | OR(95%CI) | P | ||
| Sex (%) | |||||
| Male | Reference | ||||
| Female | 1.006(0.296,3.422) | 0.992 | |||
| Age (years) | 0.999(0.963,1.036) | 0.966 | |||
| BSA (m2) | 0.290(0.016,5.194) | 0.400 | |||
| Dialysis duration (month) | 1.003(0.992,1.015) | 0.597 | |||
| Scr (μmol/L) | 1.117(0.677,1.842) | 0.666 | |||
| CysC (mg/L) | 0.943(0.658,1.352) | 0.749 | |||
| Urea (mmol/L) | 0.977(0.921,1.036) | 0.440 | |||
| UA (μmol/L) | 0.996(0.990,1.001) | 0.114 | |||
| ALT (U/L) | 0.961(0.907,1.019) | 0.183 | |||
| AST (U/L) | 1.043(0.980,1.110) | 0.183 | |||
| Urine volume (mL/24 h) | 1.146(0.695,1.891) | 0.593 | |||
| Kt/V | 0.869(0.296,2.546) | 0.798 | |||
| D/P | 0.081(0.000,14.740) | 0.344 | |||
| Peritoneal dialysate nucleated cell count (109/L) | 0.959(0.834,1.102) | 0.552 | |||
| Percentage of neutrophils in dialysate (%) | 0.989(0.947,1.032) | 0.604 | |||
| Peripheral blood WBC count (109/L) | 1.059(0.907,1.237) | 0.470 | |||
| Peripheral blood neutrophil percentage (%) | 0.973(0.927,1.021) | 0.266 | |||
| CRP (mg/L) | 0.986(0.972,1.001) | 0.066 | 0.986(0.969,1.004) | 0.138 | |
| Bacterial species (%) | |||||
| G+ | Reference | ||||
| G? | 0.450(0.160,1.267) | 0.130 | |||
| Dosing interval (h) | |||||
| 48 | Reference | ||||
| 72 | 0.158(0.052,0.485) | 0.001 | 0.092(0.021,0.400) | 0.001 | |
| History of peritonitis (%) | |||||
| No | Reference | ||||
| Yes | 2.719(1.551,4.767) | 0.000 | 3.207(1.568,6.560) | 0.001 | |
表 3
Table 3 Logistic regression analysis of the influencing factors Vancomycin blood concentration
| Variable | Univariate logistic | Multivariate logistic | |||
| OR(95%CI) | P | OR(95%CI) | P | ||
| Sex (%) | |||||
| Male | Reference | ||||
| Female | 1.006(0.296,3.422) | 0.992 | |||
| Age (years) | 0.999(0.963,1.036) | 0.966 | |||
| BSA (m2) | 0.290(0.016,5.194) | 0.400 | |||
| Dialysis duration (month) | 1.003(0.992,1.015) | 0.597 | |||
| Scr (μmol/L) | 1.117(0.677,1.842) | 0.666 | |||
| CysC (mg/L) | 0.943(0.658,1.352) | 0.749 | |||
| Urea (mmol/L) | 0.977(0.921,1.036) | 0.440 | |||
| UA (μmol/L) | 0.996(0.990,1.001) | 0.114 | |||
| ALT (U/L) | 0.961(0.907,1.019) | 0.183 | |||
| AST (U/L) | 1.043(0.980,1.110) | 0.183 | |||
| Urine volume (mL/24 h) | 1.146(0.695,1.891) | 0.593 | |||
| Kt/V | 0.869(0.296,2.546) | 0.798 | |||
| D/P | 0.081(0.000,14.740) | 0.344 | |||
| Peritoneal dialysate nucleated cell count (109/L) | 0.959(0.834,1.102) | 0.552 | |||
| Percentage of neutrophils in dialysate (%) | 0.989(0.947,1.032) | 0.604 | |||
| Peripheral blood WBC count (109/L) | 1.059(0.907,1.237) | 0.470 | |||
| Peripheral blood neutrophil percentage (%) | 0.973(0.927,1.021) | 0.266 | |||
| CRP (mg/L) | 0.986(0.972,1.001) | 0.066 | 0.986(0.969,1.004) | 0.138 | |
| Bacterial species (%) | |||||
| G+ | Reference | ||||
| G? | 0.450(0.160,1.267) | 0.130 | |||
| Dosing interval (h) | |||||
| 48 | Reference | ||||
| 72 | 0.158(0.052,0.485) | 0.001 | 0.092(0.021,0.400) | 0.001 | |
| History of peritonitis (%) | |||||
| No | Reference | ||||
| Yes | 2.719(1.551,4.767) | 0.000 | 3.207(1.568,6.560) | 0.001 | |
| Variable | Unstandardized coefficients | Standardized coefficients | T | P | Collinearity diagnostics | ||
| B | Standard error | Beta | VIF | ||||
| CRP | ?0.002 | 0.001 | ?0.194 | ?1.881 | 0.065 | 1.039 | |
| Dosing interval | ?0.408 | 0.103 | ?0.400 | ?3.954 | <0.001 | 1.007 | |
| History of peritonitis | 0.383 | 0.103 | 0.393 | 3.815 | <0.001 | 1.044 | |
| R2 | 0.399 | ||||||
| Adjusted R2 | 0.369 | ||||||
表 4
Table 4 Multiple linear regression analysis of factors influencing the first serum concentration of vancomycin
| Variable | Unstandardized coefficients | Standardized coefficients | T | P | Collinearity diagnostics | ||
| B | Standard error | Beta | VIF | ||||
| CRP | ?0.002 | 0.001 | ?0.194 | ?1.881 | 0.065 | 1.039 | |
| Dosing interval | ?0.408 | 0.103 | ?0.400 | ?3.954 | <0.001 | 1.007 | |
| History of peritonitis | 0.383 | 0.103 | 0.393 | 3.815 | <0.001 | 1.044 | |
| R2 | 0.399 | ||||||
| Adjusted R2 | 0.369 | ||||||
图 3
Fig.3 Stratified analysis of the impact of dosing interval and peritonitis history on the first serum concentration of vancomycin ($\bar x$±s) bP<0.05, cP<0.01, compared with previous PDRP; eP<0.05, compared with previous 72 h.
| Group | Peritoneal dialysate nucleated cell count (109/L) | P | Percentage of neutrophils in dialysate (%) | P | Days to negative conversion (d) | ||
| Before treatment | After treatment | Before treatment | After treatment | ||||
| Low-serum concentration group (n=11) | 0.396(0.226,6.238) | 0.020(0.007,0.026) | <0.001 | 80.7(75.0,90.9) | 10.0(6.4,22.7) | <0.001 | 5(2,8) |
| High-serum concentration group (n=11) | 1.182(0.574,6.285) | 0.011(0.004,0.43) | <0.001 | 86.4(78.0,87.2) | 9.3(0.0,18.0) | <0.001 | 5(3,7) |
| P | 0.158 | 0.641 | 0.821 | 0.373 | 0.798 | ||
表 5
Table 5 Comparison of cell components in peritoneal dialysis fluid before and after treatment in two groups
| Group | Peritoneal dialysate nucleated cell count (109/L) | P | Percentage of neutrophils in dialysate (%) | P | Days to negative conversion (d) | ||
| Before treatment | After treatment | Before treatment | After treatment | ||||
| Low-serum concentration group (n=11) | 0.396(0.226,6.238) | 0.020(0.007,0.026) | <0.001 | 80.7(75.0,90.9) | 10.0(6.4,22.7) | <0.001 | 5(2,8) |
| High-serum concentration group (n=11) | 1.182(0.574,6.285) | 0.011(0.004,0.43) | <0.001 | 86.4(78.0,87.2) | 9.3(0.0,18.0) | <0.001 | 5(3,7) |
| P | 0.158 | 0.641 | 0.821 | 0.373 | 0.798 | ||
| Group | CRP (mg/L) | P | |
| Before treatment | After treatment | ||
| Low-serum concentration group (n=11) | 20.41(15.60,44.55) | 4.89(3.00,7.70) | 0.001 |
| High-serum concentration group (n=11) | 16.44(12.93,43.80) | 6.56(5.59,7.72) | <0.001 |
| P | 0.598 | 0.045 | |
表 6
Table 6 Comparison of CRP before and after treatment in two groups
| Group | CRP (mg/L) | P | |
| Before treatment | After treatment | ||
| Low-serum concentration group (n=11) | 20.41(15.60,44.55) | 4.89(3.00,7.70) | 0.001 |
| High-serum concentration group (n=11) | 16.44(12.93,43.80) | 6.56(5.59,7.72) | <0.001 |
| P | 0.598 | 0.045 | |
| Author (Year) | Country | Case number | Dosage regimen | Serum concentration target | Main conclusions |
| Xie Jing et al.(2024)[ | China | 40 | 0.5 g vancomycin, administered qd, qod and q2d; Adjusting dosing regimens based on the serum concentration. | 15 μg/mL (ISPD guideline) | First serum concentration is difficult to achieve target; Clinical efficacy correlates with concentrations ≥10 μg/mL but not with 15 μg/mL. |
| Cai Le et al.(2021)[ | China | 24 | 1 g vancomycin, administered qd, qod and q2d. | 15 μg/mL (ISPD guideline) | First serum concentration is difficult to achieve target. |
| Hang Yong Fu et al.(2019)[ | China | 41 | 1 g vancomycin, administered q3d, q4d and q5d. | 15 μg/mL (ISPD guideline) | First serum concentration is difficult to achieve target. No correlation between serum concentration and clinical efficacy at 10 or 15 μg/mL. |
| Ma Ying et al.(2023)[ | China | 56 | 15 mg/kg vancomycin, administered on Day1, re-dose 0.5 g on Day3 if serum concentration <15 μg/mL; Adjusting dosing regimens based on the serum concentration on Day5. | 15 μg/mL (ISPD guideline) | No correlation between serum concentration and clinical efficacy. |
| Sarah Stevenson et al.(2015)[ | Australia | 34 | 30 mg/kg vancomycin (max 2.0 g), check serum concentration every 2-3 days and re-dose 30 mg/kg vancomycin (max 2.0 g) if <15 μg/mL. | 15 μg/mL (ISPD guideline) | No correlation between serum concentration and clinical efficacy. |
表 7
Table 7 Overview of domestic and international studies on vancomycin serum concentrations in peritoneal dialysis–related peritonitis
| Author (Year) | Country | Case number | Dosage regimen | Serum concentration target | Main conclusions |
| Xie Jing et al.(2024)[ | China | 40 | 0.5 g vancomycin, administered qd, qod and q2d; Adjusting dosing regimens based on the serum concentration. | 15 μg/mL (ISPD guideline) | First serum concentration is difficult to achieve target; Clinical efficacy correlates with concentrations ≥10 μg/mL but not with 15 μg/mL. |
| Cai Le et al.(2021)[ | China | 24 | 1 g vancomycin, administered qd, qod and q2d. | 15 μg/mL (ISPD guideline) | First serum concentration is difficult to achieve target. |
| Hang Yong Fu et al.(2019)[ | China | 41 | 1 g vancomycin, administered q3d, q4d and q5d. | 15 μg/mL (ISPD guideline) | First serum concentration is difficult to achieve target. No correlation between serum concentration and clinical efficacy at 10 or 15 μg/mL. |
| Ma Ying et al.(2023)[ | China | 56 | 15 mg/kg vancomycin, administered on Day1, re-dose 0.5 g on Day3 if serum concentration <15 μg/mL; Adjusting dosing regimens based on the serum concentration on Day5. | 15 μg/mL (ISPD guideline) | No correlation between serum concentration and clinical efficacy. |
| Sarah Stevenson et al.(2015)[ | Australia | 34 | 30 mg/kg vancomycin (max 2.0 g), check serum concentration every 2-3 days and re-dose 30 mg/kg vancomycin (max 2.0 g) if <15 μg/mL. | 15 μg/mL (ISPD guideline) | No correlation between serum concentration and clinical efficacy. |
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