A Pilot Study of Echinocandin Combination with Trimethoprim/Sulfamethoxazole and Clindamycin for the Treatment of AIDS Patients with Pneumocystis Pneumonia

Abstract

Background and Objectives Pneumocystis pneumonia (PCP) is a common opportunistic infection in acquired immune deficiency syndrome (AIDS) patients that continues to result in a high mortality rate. To develop a better treatment strategy and improve PCP prognosis, a cohort study was conducted to evaluate the therapeutic potential of echinocandin treatment for AIDS patients with PCP (AIDS-PCP). Methods The AIDS-PCP patients were analyzed in our retrospective cohort study that were hospitalized in The First Affiliated Hospital of Zhejiang University during 2013–2018. The antifungal effects of echinocandins were evaluated in two subgroups that were classified by oxygenation as a proxy for the disease state: PaO2/FiO2 > 200 mmHg and PaO2/FiO2 ≤ 200 mmHg. Intergroup comparisons and survival curves were used to evaluate the effectiveness of the two AIDS-PCP treatment regimens. Results During the follow-up, 182 AIDS-PCP patients were diagnosed and analyzed in the study. After excluding 55 patients with other superinfections and five patients that were treated with HAART, the remaining 122 patients were enrolled in the study. The group treated with echinocandins combined with trimethoprim-sulfamethoxazole (TMP-SMZ) and clindamycin exhibited a lower mortality rate (9.62%, 5/52) than did the group with TMP-SMZ and clindamycin treatment (20%, 14/70). For AIDS-PCP patients in the PaO2/FiO2 > 200 mmHg subgroup, treatment with echinocandins combined with TMP-SMZ and clindamycin significantly reduced their mortality rate (4.44% (2/45) vs. 18.18% (10/55), P = 0.035). Conclusion The results of this study indicate that treatment with echinocandins in combination with the standard TMP-SMZ and clindamycin regimen can improve the prognosis and reduce the mortality rate in patients with mild to moderate AIDS-PCP disease.

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 ].…”

Efficacy of Trimethoprim–Sulfamethoxazole in Combination with an Echinocandin as a First-Line Treatment Option for Pneumocystis Pneumonia: A Systematic Review and Meta-Analysis

“…Subsequently, the full-text review of 22 articles was performed. Of these, 18 articles were further excluded on the basis of the exclusion criteria listed in Figure 1 , leaving four studies that met eligibility for the meta-analysis [ 11 , 12 , 13 , 14 ].…”

“…The characteristics of these four studies, all of which were conducted at single centers, are summarized in Table 1 . One was a case-control study conducted in Taiwan [ 11 ], and the other three were cohort studies undertaken in China [ 12 , 13 , 14 ]. The participants reported by Lu et al [ 11 ] were heart transplant recipients, whereas those in the cohort studied by Jin et al [ 12 ] were non-HIV-infected patients.…”

“…To date, there is only one case-control study with available clinical data on the effects of TMP–SMX in combination with echinocandins on PCP [ 11 ]. Recently, several retrospective cohort studies comparing TMP–SMX monotherapy with the combination therapy for PCP have been published [ 12 , 13 , 14 ]. Although each study showed a tendency of the combination therapy to improve the PCP mortality rate, they did not provide obvious evidence for its use as the preferred treatment strategy.…”

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

“…However, it is believed at present that caspofungin alone should not be used for the treatment of PCP (especially in moderate to severe PCP), as it is unlikely to completely clear Pneumocystis , and may allow PCP recurrence after drug withdrawal [ 12 ]. TMP-SMX exerts its effects on trophic forms of P. jirovecii , while caspofungin primarily acts on cystic forms of P. jirovecii [ 13 ], and the combination of caspofungin and TMP-SMX thus has the potential to inhibit the entire life cycle of the Pneumocystis organism [ 14 ]. Case reports have described the clinical success of caspofungin when used in combination with TMP-SMX in treating moderate to severe PCP in immunocompromised hosts [ 15 ].…”