Time to trimethoprim/sulfamethoxazole initiation among patients with rheumatic disease complicated by Pneumocystis jirovecii pneumonia: impact on 90-day mortality

Abstract

Background Pneumocystis jirovecii pneumonia (PJP) is a life-threatening disease with increasing prevalence in patients with rheumatic disease. Trimethoprim/sulfamethoxazole (TMP/SMX) is an effective treatment for patients with rheumatic disease hospitalized for PJP. This study aimed to describe the 90-day mortality of patients with rheumatic disease complicated by PJP and investigate whether the administration of TMP/SMX after 7 days from initial symptoms correlates with 90-day mortality. Methods We enrolled consecutive patients with rheumatic disease complicated with PJP in our center from August 2018 to August 2021. The participants were classified into two groups according to when TMP/SMX was initiated: early (within the first 7 days) and late (after 7 days). The primary outcome was 90-day PJP-related mortality. Multivariate cox regression and Kaplan–Meier survival analyses were conducted to identify the risk factors for mortality and examine differences in survival between early and late use of TMP/SMX. Results Thirty-seven patients with rheumatic disease (median age 50.1 years, 24.3% male) complicated by PJP were enrolled in our study, and 15 (40.5%) patients died at or before 90 days of follow-up. The most common comorbidity was systemic lupus erythematosus (14, 37.8%), followed by inflammatory myopathy (11, 27.9%). Patients in the early group were less likely to require mechanical ventilation (8/27, 29.6% vs. 9/10, 90.0%, P = 0.002), lower doses glucocorticoids (43.2 mg/d vs. 72.2 mg/d, P = 0.039) and had lower mortality (7/27, 25.9% vs. 8/10, 80.0%, P = 0.006) than those in the late group. In the Kaplan–Meier analysis, the survivor probability of the early group was notably higher than that of the late group (P = 0.007). Multivariate cox regression analysis showed that initiation of TMP/SMX after 7 days from admission (hazard ratio [HR]: 5.9, 95% confidence interval [CI]: 1.1–30.4; P = 0.034) and a higher level of lactate dehydrogenase (LDH; HR: 6.0, 95% CI: 1.1–31.8; P = 0.035) were associated with 90-day mortality in patients with rheumatic disease complicated by PJP. Conclusion Patients with rheumatic disease complicated by PJP had poor prognoses, with mortality rates as high as 40.5%. TMP/SMX initiation after 7 days from initial symptoms and a higher level of serum LDH were significantly associated with increased 90-day mortality.

Pneumocystis pneumonia in intensive care: clinical spectrum, prophylaxis patterns, antibiotic treatment delay impact, and role of corticosteroids. A French multicentre prospective cohort study

“…The second unexpected finding was that a non-negligible proportion of patients received the first dose of curative antibiotic treatment for PJP late: among patient not yet treated upon ICU admission, 12.7% received the first dose after the 96th hour. This is in line with what was reported years ago [11,24,[27][28][29], suggesting that the practices of intensivists may not have evolved since then. Despite a rich literature emphasizing the high index of suspicion of PJP when caring for immunocompromised patients with diffuse pneumonia, there still remains a considerable gap between theory and practice.…”

“…Our study further suggests that early treatment is of paramount importance, as it reveals that a delay of 4 days accelerated the time to death by a factor 6.75. This aligns with findings from earlier retrospective studies [24,28,29] and one prospective study, encompassing all PJP cases, whether requiring intensive care admission or not. That study demonstrated an increased risk of mortality of 1.11 for each day of delayed treatment [11].…”

“…The sample size was determined to assess the association of late treatment of PJP on patient mortality 6 months post-admission to the ICU. Given the available literature [11,24,28,29], we opted to compare patients receiving the first dose of curative antibiotic treatment for PJP before or on the fourth day of ICU stay with those treated after the fourth day. Based on an anticipated 55% overall mortality rate at 6 months and a death hazard ratio of 2.4 for the late treatment cohort, a total of 103 patients were required with a type I alpha risk set at 5%, and a 90% statistical power.…”

“…In immunocompromised individuals, PJP should be suspected in cases of diffuse pneumonia, with or without respiratory distress [24][25][26]. However, studies have underscored delays in initiating treatment among a subset of these patients during the initial hospitalization, potentially impacting in-hospital survival rates [11,13,[27][28][29].…”

Clinical course and prognostic factors of Pneumocystis pneumonia with respiratory failure in non-HIV patients

“…Song et al. found that in patients with rheumatic disease and PCP, initiating treatment with TMP-SMX 7 days after the onset of symptoms was significantly linked to a higher 90-day mortality ( Song et al., 2022 ). These findings highlight the fact that delayed diagnosis and treatment are major contributors to increased mortality and the need for mechanical ventilation in PCP patients.…”