Caspofungin combined with TMP/SMZ as a first‐line therapy for moderate‐to‐severe PCP in patients with human immunodeficiency virus infection

Abstract

Objectives The effectiveness of trimethoprim/sulfamethoxazole (TMP/SMZ) for pneumocystis pneumonia (PCP) is limited with adverse events. Caspofungin, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, the availability of clinical data about caspofungin combined with TMP/SMZ in the treatment of PCP in HIV‐infected patients is limited. Thus, we aimed to examine the clinical effectiveness and safety of caspofungin combined with TMP/SMZ as a first‐line therapy for moderate‐to‐severe PCP in HIV‐infected patients. Methods From January 2017 to December 2019, data of HIV‐infected patients with moderate‐to‐severe PCP who received either TMP/SMZ alone or caspofungin combined with TMP/SMZ as first‐line therapy were retrospectively reviewed to assess the effectiveness and safety of each regimen. The Kaplan–Meier curve and log‐rank test were used for survival analysis. Results A total of 278 patients met the criteria. The overall positive response rate of PCP treatment was 48.92%, and the overall all‐cause in‐hospital mortality rate was 33.09%. Patients who received combination therapy consisting of caspofungin and TMP/SMZ had a better positive response rate (59.44% vs. 37.78%, P < 0.001) and lower all‐cause in‐hospital mortality rate (24.48% vs. 42.22%, P = 0.003). Also, patients who received combination therapy had higher survival rate during a hospital stay (75.52% vs. 57.78%, P = 0.004), and those who received longer combination therapy were more likely to have higher survival rate (P = 0.042). We found that age (P = 0.019), CD4 cell count (P = 0.001) and therapeutic regimen (P = 0.002) were significant risk factors for all‐cause in‐hospital mortality rate in univariate analysis. In multivariate analysis, only CD4 cell count and therapeutic regimen were statistically significant factors associated with all‐cause in‐hospital mortality rate. Patients with a CD4 count of > 30 cells/µL and patients who received combination therapy consisting of caspofungin and TMP/SMZ were more likely to survive from PCP (P = 0.011 and P = 0.002, respectively). There were no additional severe adverse events caused by adding caspofungin. Conclusions For HIV‐infected patients with moderate‐to‐severe PCP, combination therapy with caspofungin and TMP/SMZ is an effective and promising first‐line therapy with no greater number of adverse events compared with TMP/SMZ monotherapy. Patients who received caspofungin had better positive response rates and lower all‐cause in‐hospital mortality rates. Also, we recommend early initiation of caspofungin.

The Long-Acting Echinocandin, Rezafungin, Prevents Pneumocystis Pneumonia and Eliminates Pneumocystis from the Lungs in Prophylaxis and Murine Treatment Models

“…With the increasing complexity of azole-based prophylaxis (e.g., drug-drug interactions), echinocandins have garnered attention for their potential in antifungal prophylaxis [ 38 , 39 ]. However, despite limited alternatives to standard TMP-SMX, micafungin, anidulafungin and CAS have not been recommended for prophylaxis against PCP based on in vivo efficacy [ 26 , 40 , 41 , 42 ]. The PK profile of rezafungin not only sets it apart from other echinocandins in traditional PK analysis; higher penetration of rezafungin at the infected tissue site, as observed compared with micafungin, may explain observed differences in efficacy compared with other echinocandins [ 23 ].…”

On the Treatment of Pneumocystis jirovecii Pneumonia: Current Practice Based on Outdated Evidence

“…On the basis of bioplausibility [ 50 ] and observational reports [ 51–53 ], there has been interest in the use of the echinocandins as adjunctive agents for the treatment of PCP. There are currently 2 randomized controlled trials in critically ill patients without HIV examining the use of adjunctive caspofungin listed as actively recruiting (ClinicalTrials.gov Identifier NCT03978559 and NCT02603575); however, the use of echinocandins in patients with HIV and/or before critical illness will need to be inferred from those results unless additional trials are conducted.…”

No Statistically Apparent Difference in Antifungal Effectiveness Observed Among Trimethoprim/Sulfamethoxazole Plus Clindamycin or Caspofungin, and Trimethoprim/Sulfamethoxazole Monotherapy in HIV-Infected Patients with Moderate to Severe Pneumocystis Pneumonia: Results of an Observational Multicenter Cohort Study

“…Previous case reports showed that the efficacy of caspofungin was favorable when it was used as a first-line drug or for salvage therapy for PCP [ 19 ]. A trial involving the caspofungin salvage therapy for PCP showed a high success rate (80%) among HIV-infected patients [ 20 ].…”