High initial (1, 3) Beta-d-Glucan concentration may be a predictor of satisfactory response of c aspofungin combined with TMP/SMZ for HIV-negative patients with moderate to severe Pneumocystis jirovecii pneumonia.

The aim of this study was to investigate the efficacy of combination therapy of caspofungin and TMP/SMZ (trimethoprim/sulfamethoxazole) in moderate to severe pneumocystis jirovecii pneumonia (PJP) in patients without human immunodeficiency virus infection (HIV) and the relationship between therapeutic effect and plasma (1, 3) Beta-d-Glucan (BDG) levels. We retrospectively reviewed HIV-negative patients with PJP diagnosed in our department, who were treated with combination therapy of caspofungin and TMP/SMZ or monotherapy of TMP/SMZ during a six and a half year period. A total of 126 moderate to severe PJP patients were enrolled in the study. In the multivariate analysis, low lymphocyte counts, high serum lactate dehydrogenase levels at the diagnosis of PJP and progression to shock were significant risk factors for death. In all patients, there was no significant difference in risk of death at 3 months. In the group of BDG≥800pg/m, patients receiving combination therapy was associated with a significantly decreased risk of death at 3 months, whereas in the group of BDG<800pg/ml, there were no statistically significant difference in survival rate between the two treatment regimens. High initial plasma (1, 3) Beta-d-Glucan concentration may be a predictor of satisfactory caspofungin response to HIV-negative patients with PJP. Based on our findings, we suggest the choice of combination therapy with caspofungin and TMP/SMZ as the initial treatment when BDG≥800pg/ml in moderate to severe HIV-negative patients with PJP.

Jin F ，Liu XH ，Chen WC ，Fan ZL ，Wang HL ... -  《-》

A regimen based on the combination of trimethoprim/sulfamethoxazole with caspofungin and corticosteroids as a first-line therapy for patients with severe non-HIV-related pneumocystis jirovecii pneumonia: a retrospective study in a tertiary hospital.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening and severe disease in immunocompromised hosts. A synergistic regimen based on the combination of sulfamethoxazole-trimethoprim (SMX-TMP) with caspofungin and glucocorticosteroids (GCSs) may be a potential first-line therapy for PJP. Therefore, it is important to explore the efficacy and safety of this synergistic therapy for treating non-HIV-related PJP patients. We retrospectively analysed the data of 38 patients with non-HIV-related PJP at the First Affiliated Hospital of Xi'an Jiaotong University. Patients were divided into two groups: the synergistic therapy group (ST group, n = 20) and the monotherapy group (MT group, n = 18). All patients were from the ICU and were diagnosed with severe PJP. In the ST group, all patients were treated with SMX-TMP (TMP 15-20 mg/kg per day) combined with caspofungin (70 mg as the loading dose and 50 mg/day as the maintenance dose) and a GCS (methylprednisolone 40-80 mg/day). Patients in the MT group were treated only with SMX-TMP (TMP 15-20 mg/kg per day). The clinical response, adverse events and mortality were compared between the two groups. The percentage of patients with a positive clinical response in the ST group was significantly greater than that in the MT group (100.00% vs. 66.70%, P = 0.005). The incidence of adverse events in the MT group was greater than that in the ST group (50.00% vs. 15.00%, P = 0.022). Furthermore, the dose of TMP and duration of fever in the ST group were markedly lower than those in the MT group (15.71 mg/kg/day vs. 18.35 mg/kg/day (P = 0.001) and 7.00 days vs. 11.50 days (P = 0.029), respectively). However, there were no significant differences in all-cause mortality or duration of hospital stay between the MT group and the ST group. Compared with SMZ/TMP monotherapy, synergistic therapy (SMZ-TMP combined with caspofungin and a GCS) for the treatment of non-HIV-related PJP can increase the clinical response rate, decrease the incidence of adverse events and shorten the duration of fever. These results indicate that synergistic therapy is effective and safe for treating severe non-HIV-related PJP.

Li H ，Lu Y ，Tian G ，Wu Y ，Chen T ，Zhang J ，Hu N ，Wang X ，Wang Y ，Gao L ，Yan J ，Zhou L ，Shi Q ... -  《BMC INFECTIOUS DISEASES》

Combination of Echinocandins and Trimethoprim/Sulfamethoxazole for the Treatment of Pneumocystis jiroveci Pneumonia After Heart Transplantation.

The echinocandins have shown anti-Pneumocystis jiroveci activity in nonhuman animal models; however, the corresponding human clinical experience has been rarely reported. We report a clinical picture of P jiroveci pneumonia (PJP) and determine the effects of concomitant therapy with echinocandins and trimethoprim (TMP)-sulfamethoxazole (SMZ). We investigated a retrospective case series of heart transplantation (HT) recipients with PJP from July 1988 to December 2015. Recipient charts were reviewed for their demographic characteristics, underlying conditions, concomitant infections, PJP prophylaxis, TMP-SMZ dosages, adverse events, echinocandin use, oxygenation, and outcomes. Eleven of 451 HT recipients developed PJP after a median duration of 2.8 years after transplantation. All 11 were treated with TMP-SMZ; 5 of them were treated with echinocandins added to the standard TMP-SMZ regimen. The longest interval between transplantation and PJP development was 16.3 years. The mortality rate was 33.3% in recipients receiving TMP-SMZ alone, whereas it was 20% in those receiving echinocandins as well. The most common side effects of TMP-SMZ include nausea and vomiting, metabolic acidosis, and hyperkalemia. Five recipients developed acute psychosis after a median duration of 6 days of TMP-SMZ therapy. The incidence of psychosis increased from 25% in recipients receiving TMP at ≤15 mg/kg/d to 100% in those receiving TMP at >15 mg/kg/d. Echinocandins along with the standard TMP-SMZ regimen may effectively alleviate PJP developed after HT. The ideal prophylaxis duration is lifelong owing to the late onset of PJP. The typically intolerable adverse effects of TMP-SMZ therapy for PJP may necessitate dosage adjustments in some cases.

Lu YM ，Lee YT ，Chang HC ，Yang HS ，Chang CY ，Huang CM ，Wei J ... -  《-》

Combination of caspofungin and low-dose trimethoprim/sulfamethoxazole for the treatment of severe Pneumocystis jirovecii pneumonia in renal transplant recipients.

Pneumocystis jirovecii pneumonia (PJP) is a severe and life-threatening complication in immunocompromised patients. Trimethoprim/sulfamethoxazole (TMP-SMZ) is well known for its effectiveness as prophylaxis of PJP. However, the use of TMP-SMZ is associated with various adverse effects that may not be tolerated by critically ill patients. Caspofungin is recommended for invasive fungal infections, but the treatment of PJP after solid organ transplantation (SOT) is an off-label use of this drug. In this study, three cases of severe PJP in renal transplant recipients treated with a combination of caspofungin and low-dose TMP-SMZ were presented. Initial findings indicated that the combined treatment may be beneficial for the treatment of PJP and decrease the incidence of TMP-SMZ-related adverse effects.

Tu GW ，Ju MJ ，Xu M ，Rong RM ，He YZ ，Xue ZG ，Zhu TY ，Luo Z ... -  《-》

Efficacy of initial caspofungin plus trimethoprim/sulfamethoxazole for severe PCP in patients without human immunodeficiency virus infection.

The number of pneumocystis pneumonia (PCP) cases is increasing in immunocompromised patients without human immunodeficiency virus infection (HIV), causing serious morbidity with high mortality. Trimethoprim/sulfamethoxazole (TMP/SMZ) monotherapy has limited effectiveness in the treatment of PCP. Clinical data on whether initial caspofungin plus TMP/SMZ for this disease is superior to monotherapy in non-HIV-infected patients are limited. We aimed to compare the clinical effectiveness of these regimens for severe PCP in non-HIV patients. A retrospective study reviewed 104 non-HIV-infected patients with confirmed PCP in the intensive care unit between January 2016 and December 2021. Eleven patients were excluded from the study because TMP/SMZ could not be used due to severe hematologic disorders or clinical data were missing. All enrolled patients were divided into three groups according to different treatment strategies: Group 1 received TMP/SMZ monotherapy, Group 2 received caspofungin combined with TMP/SMZ as first-line therapy, and Group 3 initially received TMP/SMZ monotherapy and later received caspofungin as salvage therapy. The clinical characteristics and outcomes were compared among the groups. A total of 93 patients met the criteria. The overall positive response rate of anti-PCP treatment was 58.06%, and the overall 90-day all-cause mortality rate was 49.46%. The median APACHE II score was 21.44. The concurrent infection rate was 74.19%, among whom 15.05% (n = 14) of those patients had pulmonary aspergillosis, 21.05% (n = 20) had bacteremia, and 23.65% (n = 22) had CMV infections. The patients who received initial caspofungin combination with TMP/SMZ had the best positive response rate (76.74%) compared to others (p = 0.001). Furthermore, the group that received initial caspofungin combined with TMP/SMZ had a 90-day all-cause mortality rate (39.53%) that was significantly different from that of the shift group (65.51%, p = 0.024), but this rate showed no statistically significant difference compared with that in the monotherapy group (48.62%, p = 0.322). None of the patients had serious adverse events from caspofungin therapy. For non-HIV-infected patients with severe PCP, initial combination therapy with caspofungin and TMP/SMZ is a promising first-line treatment option compared with TMP/SMZ monotherapy and combination therapy as salvage therapy.

Qi H ，Dong D ，Liu N ，Xu Y ，Qi M ，Gu Q ... -  《BMC INFECTIOUS DISEASES》