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

Abstract

Purpose: Severe Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic therapy may impact survival in these severe forms of PJP. The impact of corticosteroid therapy combined with antibiotics is also unclear.

Methods: This multicentre, prospective observational study involving 49 adult intensive care units (ICUs) in France was designed to evaluate the severity, the clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality.

Results: We included 158 patients with PJP from September 2020 to August 2022. Their main reason for admission was acute respiratory failure (n = 150, 94.9%). 12% of them received antibiotic prophylaxis for PJP before ICU admission. The ICU, hospital, and 6-month mortality were 31.6%, 35.4%, and 40.5%, respectively. Using time-to-event analysis with a propensity score-based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96 h of ICU admission was associated with faster occurrence of death [time ratio: 6.75; 95% confidence interval (95% CI): 1.48-30.82; P = 0.014]. The use of corticosteroids for PJP was associated with faster occurrence of death (time ratio: 2.48; 95% CI 1.01-6.08; P = 0.048).

Conclusion: This study showed that few patients with PJP admitted to intensive care received prophylactic antibiotic therapy, that delay in curative antibiotic treatment was common and that both delay in curative antibiotic treatment and adjunctive corticosteroids for PJP were associated with accelerated mortality.

Keywords: Pneumocystis jirovecii; Adjunctive corticosteroid therapy; Delayed treatment; Intensive care; Mortality; Prophylaxis.

Fig. 1

Flow chart. ARDS acute respiratory distress syndrome, ICU intensive care unit, IQR interquartile range, LOS length of stay, PCR polymerase chain reaction (either conventional i.e., not quantitative or quantitative), PJP Pneumocystis jirovecii pneumonia, qPCR quantitative PCR. ARDS was defined according to the Berlin definition [47]. ^aDiagnostic of PJP made by the pathologist using microscopy and specific staining (modified Toluidine Blue O, Grocott-Gomori methenamine silver, or Immunofluorescent-antibody staining). ^bIn every case, the diagnosis of PJP was based on a positive quantitative or non-quantitative PCR test performed on oral wash (%) or on lower respiratory tract sample, and serum (1–3)-b-d-glucan positivity (threshold for positivity left to the appreciation of the attending intensivist) [48], but also on the presence of bilateral interstitial pneumonia and a diagnostic workup that ruled out other diagnoses. ^cIn every case, the diagnosis of PJP was based on a positive quantitative PCR test with sufficiently low cycle threshold (Ct) (left to the appreciation of the attending intensivist), but also on the presence of bilateral interstitial pneumonia and a diagnostic workup that ruled out other diagnoses. ^dIn every case, the diagnosis of PJP was based on a positive non-quantitative PCR test performed on oral wash (%) or on lower respiratory tract sample, but also on the presence of either bilateral interstitial infiltrates on chest X-ray or bilateral ground glass opacities on high-resolution lung computed tomography and a diagnostic workup that ruled out other diagnoses. ^eAmong the 36 participating ICUs, 18 were in university affiliated hospitals. ^f13 ICUs, including 6 ICUs in university affiliated hospitals, did not admit any patient with PJP during the study period

Fig. 2

Survival probability according to early or late (after the 96th hour of ICU) curative antibiotic treatment of PJP. The upper panel shows the weighted Kaplan–Meier curves for each group obtained by propensity score-based inverse probability of treatment weighting (PS-IPW, see “Methods” for details). In contrast, the risk table (lower panel) shows raw numbers at risk for each group (i.e., not in the weighted population constructed by PS-IPW for statistical analysis). The P value is the one obtained by accelerated failure time modeling (see “Methods”) for the comparison of late versus early treatment. Time zero was the time of ICU admission

Fig. 3

Survival probability according to the use of adjunctive corticosteroid therapy for PJP in the whole study population (N = 158). The upper panel shows the weighted Kaplan–Meier curves for each group obtained by propensity score-based inverse probability of treatment weighting (PS-IPW, see “Methods” for details). In contrast, the risk table (lower panel) shows raw numbers at risk for each group (i.e., not in the weighted population constructed by PS-IPW for statistical analysis). The P value is the one obtained by accelerated failure time modeling (see “Methods”) for the comparison of use of adjunctive corticosteroid therapy versus no use. Time zero was the time at which curative antibiotic treatment for PJP was started. Patients were right censored at Day 180 after the beginning of curative treatment. Note that one patient of the no corticosteroids group could be followed up only until the 178th day