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

Abstract

Abstract:

ObjectiveTo 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 ofPneumocystis jiroveciipneumonia (PJP) in patients with non-human immunodeficiency virus (HIV).MethodsClinical 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.ResultsA 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%vs6%,P=0.025), decreased hemoglobin (37%vs0,P=0.013) and serious adverse reactions (43%vs12%,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.ConclusionsThe 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 yerbiipneumonia,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 ofPneumocystis jiroveciipneumonia in patients with non-human immunodeficiency virus infection[J]. Journal of Internal Medicine Concepts & Practice, 2024, 19(01): 51-56.

Figures/Tables5

Tab 1

Basic data of non-HIV infected patients with PJP [$\bar{x} \pm s$/n(%)/M(IQR)]

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

Tab 1

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

Tab 2

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

Fig 1

Tab 4

Relationship between peak concentration of SMZ and incidence of adverse reactions [n(%)]

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

Tab 4

References17

[1]	Tokuda H, Sakai F, Yamada H, et al. Clinical and radiological features ofPneumocystispneumonia in patients with rheumatoid arthritis, in comparison with methotrexatePneumonitisandPneumocystispneumonia in acquired immunodeficiency syndrome[J].Intern Med,2008,47(10):915-923. doi:10.2169/internalmedicine.47.0702 URL
[2]	Thomas CF Jr, Limper AH.Pneumocystispneumonia[J].N Engl J Med,2004,350(24):2487-2498. doi:10.1056/NEJMra032588 URL
[3]	Maschmeyer G, Helweg-Larsen J, Pagano L, et al. ECIL guidelines for treatment ofPneumocystis jiroveciipneumonia in non-HIV-infected haematology patients[J].J Antimicrob Chemother,2016,71(9):2405-2413. doi:10.1093/jac/dkw158pmid:27550993
[4]	Fishman JA, Gans H.Pneumocystis jiroveciin solid organ transplantation[J].Clin Transplant,2019,33(9):e13587.
[5]	Chang HM, Tsai HC, Lee SS, et al. High daily doses of trimethoprim/sulfamethoxazole are an independent risk factor for adverse reactions in patients withPneumocystispneumonia and AIDS[J].J Chin Med Assoc,2016,79(6):314-319. doi:10.1016/j.jcma.2016.01.007 URL
[6]	Hughes WT, Feldman S, Chaudhary SC, et al. Comparison of pentamidine isethionate and trimethoprim-sulfamethoxazole in the treatment ofPneumocystis cariniipneumonia[J].J Pediatr,1978,92(2):285-291. doi:10.1016/S0022-3476(78)80028-6 URL
[7]	Chin TW, Vandenbroucke A, Fong IW. Pharmacokinetics of trimethoprim-sulfamethoxazole in critically ill and non-critically ill AIDS patients[J].Antimicrob Agents Chemother,1995,39(1):28-33. doi:10.1128/AAC.39.1.28pmid:7695325
[8]	Kim T, Hong HL, Lee YM, et al. Is caspofungin really an effective treatment forPneumocystis jiroveciipneumonia in immunocompromised patients without human immunodeficiency virus infection?[J].Scand J Infect Dis,2013,45(6):484-488. doi:10.3109/00365548.2012.760842 URL
[9]	潘欢妍, 祁慧, 梁培, 等. 重症耶氏肺孢子菌肺炎患者复方磺胺甲噁唑血药浓度监测的临床研究[J].中南药学,2023,21(6):1653-1658.
[10]	Kosaka M, Ushiki A, Ikuyama Y, et al. A four-center retrospective study of the efficacy and toxicity of low-dose trimethoprim-sulfamethoxazole for the treatment ofPneumocystispneumonia in patients without HIV infection[J].Antimicrob Agents Chemother,2017,61(12):e01173-e01217.
[11]	Nakashima K, Aoshima M, Nakashita T, et al. Low-dose trimethoprim-sulfamethoxazole treatment forPneumocystispneumonia in non-human immunodeficiency virus-infected immunocompromised patients[J].J Microbiol Immunol Infect,2018,51(6):810-820. doi:S1684-1182(17)30147-0pmid:28779879
[12]	Ohmura SI, Naniwa T, Tamechika SY, et al. Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim therapy forPneumocystis jiroveciipneumonia in patients with systemic rheumatic diseases[J].J Infect Chemother,2019,25(4):253-261. doi:10.1016/j.jiac.2018.11.014 URL
[13]	Chin TW, Vandenbroucke A, Fong IW. Pharmacokinetics of trimethoprim-sulfamethoxazole in critically ill and non-critically ill AIDS patients[J].Antimicrob Agents Chemother,1995,39(1):28-33. doi:10.1128/AAC.39.1.28pmid:7695325
[14]	Hall RG Nd, Pasipanodya JG, Meek C, et al. Fractal geometry-based decrease in trimethoprim-sulfamethoxazole concentrations in overweight and obese people[J].CPT Pharmacometrics Syst Pharmacol,2016,5(12):674-681. doi:10.1002/psp4.v5.12 URL
[15]	Reeves DS, Wilkinson PJ. The pharmacokinetics of trimethoprim and trimethoprim/sulphonamide combinations, including penetration into body tissues[J].Infection,1979,7 Suppl 4:S330-S341.
[16]	Kagaya H, Miura M, Niioka T, et al. Influence of NAT2 polymorphisms on sulfamethoxazole pharmacokinetics in renal transplant recipients[J].Antimicrob Agents Chemother,2012,56(2):825-829. doi:10.1128/AAC.05037-11pmid:22106207
[17]	Kavanagh ON. Alkalising agents in urinary tract infections: theoretical contraindications, interactions and synergy[J].Ther Adv Drug Saf,2022,13:20420986221080794.

Clinical significance of plasma peak concentration determination of compound sulfamethoxazole in treatment ofPneumocystis jiroveciipneumonia in patients with non-human immunodeficiency virus infection

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