Clinical significance of plasma peak concentration determination of compound sulfamethoxazole in treatment of Pneumocystis jirovecii pneumonia in patients with non-human immunodeficiency virus infection

doi:10.16138/j.1673-6087.2024.01.09

Abstract

Abstract:

Objective To explore the significance of monitoring the blood peak concentration of sulfamethoxazole (SMZ) to learn the efficacy and safety of compound SMZ (SMZco) tablets in the treatment of Pneumocystis jirovecii pneumonia (PJP) in patients with non-human immunodeficiency virus (HIV). Methods Clinical data of PJP infected patients with non-HIV hospitalized in Ruijin Hospital, from January 2019 to May 2023 were enrollled, and the relationship between the peak plasma concentration of SMZ and the efficacy and occurrence of adverse reactions was retrospectively analyzed. Results A total of 47 patients were included in this study. The peak plasma concentration of SMZ ranged from 87.49 mg/L to 334.31 mg/L, the median (interquartile distance) was 168.62 (79.72) mg/L, and the peak plasma concentration in 64% of patients was >150 mg/L. The 30-day all-cause mortality of the patients was 28%，and the positive response rate was 66%. Among them, there was no statistical difference in 30-day all-cause death and treatment positive response rate between the patients with peak concentration ≤150 mg/L and the patients with peak concentration of SMZ >150 mg/L. In terms of safety, a total of 29 (62%) patients showed adverse reactions. The incidence of thrombocytopenia (40% vs 6%, P=0.025), decreased hemoglobin (37% vs 0, P=0.013) and serious adverse reactions (43% vs 12%, P=0.026) were higher in the patients with SMZ peak concentration >150 mg/L than those in the patients with SMZ peak concentration <150 mg/L. The incidence of serious adverse reactions was higher in the patients with a peak concentration of SMZco >150 mg/L. Conclusions The results of the study showed that as SMZco tablets were used in the treatment of non-HIV patients infected with PJP, those with a peak plasma concentration ≤150 mg/L of SMZ could achieve comparable efficacy, and their risk of serious adverse reactions was less than that of the patients with a peak plasma concentration >150 mg/L. It is suggested that the plasma peak concentration of SMZ should be monitored regularly.

Key words: Pneumocystis yerbii pneumonia, Sulfamethoxazole, Blood concentration monitoring, Adverse reaction

CLC Number:

R519，R563.1

SHU Yang, HE Xiaoshuang, $\boxed{\hbox{CHEN Hong}}$, SHI Guochao, FANG Jie. Clinical significance of plasma peak concentration determination of compound sulfamethoxazole in treatment of Pneumocystis jirovecii pneumonia in patients with non-human immunodeficiency virus infection[J]. Journal of Internal Medicine Concepts & Practice, 2024, 19(01): 51-56.

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References 17

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项目	全部患者(n=47)	SMZ峰浓度≤150 mg/L(n=17)	SMZ峰浓度>150 mg/L(n=30)	t/χ²/Z	P
年龄(岁)	57.62±15.65	58.59±14.88	56.67±15.78	0.622	0.537
男性[n(%)]	24(51)	10(59)	14(47)	0.642	0.423
体质量指数(kg/m²)	21.98±3.68	22.73±4.03	21.54±3.46	1.065	0.992
发热[n(%)]	29(62)	12(71)	13(57)	0.890	0.345
有创机械通气[n(%)]	14(32)	5(29)	9(33)	0.074	0.786
白细胞计数(×10⁹/L)	7.65(5.97)	6.05(5.53)	8.04(4.93)	-1.528	0.127
淋巴细胞计数(×10⁹/L)	0.50(0.48)	0.48(0.63)	0.47(0.46)	-0.833	0.406
乳酸脱氢酶(μmol/L)	458(297.25)	475.00(323.00)	458.00(184.25)	-0.231	0.818
G试验(pg/mL)	194.71(380.39)	260.53(549.06)	199.03(245.77)	-0.764	0.445
CD4⁺T细胞(/μL)	170.00(279.00)	286.00(309.00)	125.00(184.00)	-1.674	0.094
氧分压(mmHg)	71(30.50)	71.00(33.00)	69.00(29)	-0.308	0.758
二氧化碳分压(mmHg)	35(8.00)	35.00(8.00)	34.00(8.00)	-0.915	0.360
自身免疫性疾病[n(%)]	32(68)	13(76)	19(63)	0.862	0.353
恶性肿瘤[n(%)]	18(38)	6(35)	12(40)	0.102	0.750
间质性肺病[n(%)]	10(20)	1(6)	9(30)	2.466	0.116
高血压病[n(%)]	10(20)	2(12)	8(27)	0.687	0.407
糖尿病[n(%)]	9(19)	4(24)	5(17)	0.036	0.850
合并感染[n(%)]	32(68)	11(65)	21(70)	0.140	0.708
合并细菌感染[n(%)]	27(57)	9(53)	18(60)	0.221	0.638
合并其他真菌感染[n(%)]	13(28)	5(29)	8(27)	0.000	1.000
合并使用抗菌药物[n(%)]	46(98)	16(94)	30(100)	0.085	0.771
合并使用卡泊芬净[n(%)]	29(62)	9(53)	20(67)	0.865	0.352

项目	全部患者（n=47）	SMZ峰浓度≤150 mg/L（n=17）	SMZ峰浓度>150 mg/L（n=30）	χ²	P
30 d全因死亡率	13(28)	4(24)	9(30)	0.019	0.891
治疗阳性反应率	31(66)	12(71)	19(63)	0.254	0.614

项目	全部患者（n=47）	SMZ峰浓度≤150 mg/L （n=17）	SMZ峰浓度>150 mg/L （n=30）	t/χ²/Z	P
初始给药剂量[mg/(kg·d)]	61.73±19.02	53.89±17.68	66.17±18.56	-2.215	0.785
SMZ-TMP给药剂量小于说明书推荐下限[n(%)]	37(79)	15(88)	22(73)	0.687	0.407
肾小球滤过率(mL/min)	95.13(52.58)	85.08(70.82)	97.84(49.30)	-1.816	0.069

项目	总例数 (n=47)	SMZ峰浓度 >150 mg/L (n=30)	SMZ峰浓度 ≤150 mg/L (n=17)	χ²	P
不良反应	29(62)	21(70)	8(47)	2.417	0.120
血小板减少	13(28)	12(40)	1(6)	5.025	0.025
血红蛋白下降	11(23)	11(37)	0(0)	6.221	0.013
转氨酶异常	10(21)	7(23)	3(18)	0.008	0.931
胃肠道反应	8(17)	5(17)	3(18)	0.000	1.000
胆红素升高	6(13)	4(13)	2(12)	0.000	1.000
肌酐升高	4(9)	4(13)	0(0)	1.125	0.289
中性粒减少	3(6)	2(7)	1(6)	0.000	1.000
严重不良反应	15(32)	13(43)	2(12)	4.977	0.026
血红蛋白下降	6(13)	6(20)	0(0)	2.309	0.129
血小板减少	5(11)	5(17)	0(0)	1.660	0.198
转氨酶异常	4(9)	4(13)	0(0)	1.061	0.303
胆红素升高	4(9)	2(7)	2(12)	0.003	0.954