Pneumocystis jirovecii pneumonia (PJP) remains a severe disease associated with high rates of invasive mechanical ventilation (MV) and mortality. The objectives of this study were to assess early risk factors for severe PJP and 90-day mortality, including the broncho-alveolar lavage fluid cytology profiles at diagnosis. We prospectively enrolled all patients meeting pre-defined diagnostic criteria for PJP admitted at Nantes university hospital, France, from January 2012 to January 2017. Diagnostic criteria for PJP were typical clinical features with microbiological confirmation of P. jirovecii cysts by direct examination or a positive specific quantitative real-time polymerase chain reaction (PCR) assay. Severe PJP was defined as hypoxemic acute respiratory failure requiring high-flow nasal oxygen with at least 50% FiO2, non-invasive ventilation, or MV. Of 2446 respiratory samples investigated during the study period, 514 from 430 patients were positive for P. jirovecii. Of these 430 patients, 107 met criteria for PJP and were included in the study, 53 (49.5%) patients had severe PJP, including 30 who required MV. All patients were immunocompromised with haematological malignancy ranking first (n = 37, 35%), followed by solid organ transplantation (n = 27, 25%), HIV-infection (n = 21, 20%), systemic diseases (n = 13, 12%), solid tumors (n = 12, 11%) and primary immunodeficiency (n = 6, 8%). By multivariate analysis, factors independently associated with severity were older age (OR, 3.36; 95% CI 1.4–8.5; p < 0.05), a P. jirovecii microscopy-positive result from bronchoalveolar lavage (BAL) (OR, 1.3; 95% CI 1.54–9.3; p < 0.05); and absence of a BAL fluid alveolitis profile (OR, 3.2; 95% CI 1.27–8.8; p < 0.04). The 90-day mortality rate was 27%, increasing to 50% in the severe PJP group. Factors independently associated with 90-day mortality were worse SOFA score on day 1 (OR, 1.05; 95% CI 1.02–1.09; p < 0.001) whereas alveolitis at BAL was protective (OR, 0.79; 95% CI 0.65–0.96; p < 0.05). In the subgroup of HIV-negative patients, similar findings were obtained, then viral co-infection were independently associated with higher 90-day mortality (OR, 1.25; 95% CI 1.02–1.55; p < 0.05). Older age and P. jirovecii oocysts at microscopic examination of BAL were independently associated with severe PJP. Both initial PJP severity as evaluated by the SOFA score and viral co-infection predicted 90-day mortality. Alveolitis at BAL examination was associated with less severe PJP. The pathophysiological mechanism underlying this observation deserves further investigation.

Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality and the impact of immunocompromising underlying disease on the clinical presentation, severity and mortality of PcP has not been adequately evaluated. Does the underlying disease and immunosuppression causing Pneumocystis jirovecii pneumonia (PcP) impact the outcome and clinical presentation of the disease? In this multicentre retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to The European Organization for Research and Treatment of Cancer (EORTC) consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality. Overall, 481 patients were included in the study, 180 (37.4%) were defined as proven PcP and 301 (62.6%) as probable PcP. Patients with immune-mediated inflammatory diseases (IMID) or solid tumors had a statistically poorer prognosis than other patients with PcP at D90. In multivariate analysis, among HIV-negative population, solid tumor underlying disease (OR 5.47, 2.16-14.1; p<0.001), IMID (OR 2.19, 1.05-4.60; p=0.037), long term corticosteroid exposure (OR 2.07, 1.03-4.31; p=0.045), cysts in sputum/BAL smears (OR 1.92, 1.02-3.62; p=0.043), and SOFA score at admission (OR 1.58, 1.39-1.82; p<0.001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR 1.67, 1.03-2.71; p=0.035), especially for a prednisone daily dose ≥ 10 mg (OR 1.80, 1.14-2.85; p=0.010). Among HIV-negative patients, long term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in IMID patients. These results highlight both the needs for PcP prophylaxis in IMID patients as well as to early consider PcP curative treatment in severe pneumonia among IMID patients.

It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90–1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.

Background: K. pneumoniae is one of the bacteria most frequently causing health care-associated urinary tract infections, and increasingly incriminating Klebsiella pneumoniae carbapenemase producers (KPCp). Most infections caused by KPCp are nosocomial and might cause serious issues, even leading to death in half of the reported cases. Our aim was to identify the best strategy, based on available scientific data, for the use of new antibiotic treatments to manage KPCp UTIs. Methods: this narrative review of the literature was performed according to the criteria of preferred reporting items for systematic review and meta-analyses statement (PRISMA) (2020). Results and Conclusions: KPCp-UTIs are a real challenge for physicians. While cefiderocol, meropenem-vaborbactam, ceftazidim-avibactam, and imipenem-relebactam represent a major step forward in the treatment of these UTIs, no guidelines are currently available, in view of choosing the most appropriate treatment, in each specific case.

Early antibiotic discontinuation according to the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations is not systematically applied in high-risk neutropenic patients with haematological malignancies. A retrospective multicentre observational study was conducted over 2 years to evaluate the safety of early antibiotic discontinuation for fever of unknown origin (FUO) during neutropenia after induction chemotherapy or HSCT, in comparison with a historical cohort. We used Cox proportional hazards models, censored on neutropenia resolution, to analyse factors associated with febrile recurrence. Among 147 included patients in the ECIL-4 cohort, mainly diagnosed with acute leukaemia (n = 104, 71%), antibiotics were discontinued during 170 post-chemotherapy neutropenic episodes. In comparison with the historical cohort of 178 episodes of neutropenia without antibiotic discontinuation, no significant differences were observed regarding febrile recurrences [71.2% (121/170) versus 71.3% (127/178), P = 0.97], admission in ICUs [6.5% (11/170) versus 11.2% (20/178), P = 0.17], septic shock [0.6% (1/170) versus 3.9% (7/178), P = 0.07] and 30 day mortality [1.4% (2/147) versus 2.7% (4/150), P = 0.084]. In the ECIL-4 cohort, the rate of bacteraemia in case of febrile recurrence was higher [27.1% (46/170) versus 11.8% (21/178), P < 0.01] and antibiotic consumption was significantly lower (15.5 versus 19.9 days, P < 0.001). After early antibiotic discontinuation according to ECIL-4 recommendations, enterocolitis was associated with febrile recurrence [HR = 2.31 (95% CI = 1.4–3.8), P < 0.001] and stage III–IV oral mucositis with bacteraemia [HR = 2.26 (95% CI = 1.22–4.2), P = 0.01]. After an FUO episode in high-risk neutropenia, compliance with ECIL-4 recommendations for early antibiotic discontinuation appears to be safe and mucosal damage was associated with febrile recurrence and bacteraemia. Prospective interventional studies are warranted to assess this strategy in high-risk neutropenic patients.