Rongrong Wang,1 Xiuhua Wu,1 Xishao Xie,2 Chunchun Wei,2 Jianyong Wu,2,* Kuifen Ma1,* 

1Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Kuifen Ma Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China, Email makuifen@zju.edu.cn Jianyong Wu Kidney Disease Center, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, 310003, People’s Republic of China, Email wujianyong1964@zju.edu.cn

Objective: Emerging evidence suggests that low doses of sulfamethoxazole-trimethoprim (TMP-SMX) may offer protection against Pneumocystis jiroveci pneumonia (PJP) in kidney transplant recipients. However, cases of PJP following the withdrawal of prophylaxis have been documented. This study aimed to investigate the relationship between the occurrence of PJP and different regimes of low-dose TMP-SMX prophylaxis.
Methods: This retrospective observational study was conducted in the First Affiliated Hospital of Zhejiang University in China. Recipients diagnosed with PJP were included, and four controls were matched for each case based on transplantation time, age, and sex. Multivariate conditional logistic regression was employed to compare the odds of PJP occurrence among different TMP-SMX regimens.
Results: From January 1, 2017, to December 31, 2020, 1763 patients underwent kidney transplantation at our center. Thirty-one patients developed PJP post-transplantation, and 124 patients without PJP were included as controls. One patient developed PJP during the prophylaxis period, and the others occurred after TMP-SMX discontinuation, resulting in a PJP incidence rate of 1.36% over the follow-up period. Compared to controls, the PJP group received a significantly lower cumulative TMP-SMX dose (median: 57 single-strength dose [SSD] tablets vs 100 tablets; p = 0.001) and had a shorter prophylaxis duration (median: 6.00 months vs 10.00 months; p = 0.004). They also exhibited higher CMV infection rates (29.0% vs 4.8%, p < 0.001), elevated serum creatinine levels at discharge (174.80μmol/L vs 134.58 μmol/L, p = 0.018), and reduced CD 4+ cell counts (354.12/L vs 542.58/L, p = 0.05). Multivariate analysis revealed that a higher cumulative TMP-SMX dose was significantly associated with a lower risk of PJP (p = 0.005). Subgroup analysis indicated that at least 6 months of TMP-SMX prophylaxis is necessary for PJP prevention in recipients on quarter-strength daily (SMX/TMP 100/20 mg, p = 0.022) or half-single strength daily (SMX/TMP 200/40 to 400/80 mg, p = 0.005) regimens.
Conclusion: An adequate prophylactic duration of either quarter-strength daily TMP-SMX or half-single strength daily TMP-SMX may protect kidney transplant recipients from PJP.

Keywords: Pneumocystis jiroveci pneumonia, low dose, sulfamethoxazole-trimethoprim, kidney transplant, anti-Pneumocystis prophylaxis