Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006–May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 10⁹ cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006–2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01–2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27–0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76–2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.

Few studies have evaluated the efficacy of ceftazidime–avibactam (CA) for Klebsiella pneumoniae carbapenemase-producing Enterobacterales bacteremia (KPC-PEB) in high-risk neutropenic patients. This is a prospective multicenter observational study in high-risk neutropenic patients with multi-drug resistant Enterobacterales bacteremia. They were compared according to the resistance mechanism and definitive treatment provided: KPC-CPE treated with CA (G1), KPC-CPE treated with other antibiotics (G2), and patients with ESBL-producing Enterobacterales bacteremia who received appropriate definitive therapy (G3). Thirty-day mortality was evaluated using a logistic regression model, and survival was analyzed with Kaplan–Meier curves. A total of 238 patients were included: 18 (G1), 52 (G2), and 168 (G3). Klebsiella spp. (60.9%) and Escherichia coli (26.4%) were the Enterobacterales most frequently isolated, and 71% of the bacteremias had a clinical source. The resistance profile between G1 and G2 was colistin 35.3% vs. 36.5%, amikacin 16.7% vs. 40.4%, and tigeclycline 11.1% vs. 19.2%. The antibiotics prescribed in combination with G2 were carbapenems, colistin, amikacin, fosfomycin, tigecycline, and fluoroquinolones. Seven-day clinical response in G1 vs. G2 vs. G3 was 94.4% vs. 42.3% vs. 82.7%, respectively (p < 0.001). Thirty-day overall mortality in G1 vs. G2 vs. G3 was 22.2% vs. 53.8% vs. 11.9%, respectively (p < 0.001), and infection-related mortality was 5.5% vs. 51.9% vs. 7.7% (p < 0.001). The independent risk factors for mortality were Pitt score > 4: OR 3.63, 95% CI, 1.18–11.14 (p = 0.025) and KPC-PEB treated with other antibiotics: OR 8.85, 95% CI, 2.58–30.33 (p = 0.001), while 7-day clinical response was a protective factor for survival: OR 0.02, 95% CI, 0.01–0.08 (p < 0.001). High-risk neutropenic patients with KPC-CPE treated with CA had an outcome similar to those treated for ESBL-producing Enterobacterales, with higher 7-day clinical response and lower overall and infection-related mortality than those treated with other antibiotics. In view of these data, CA may be considered the preferred therapeutic option for KPC-PEB in high-risk neutropenic patients.

Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88–8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29–9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74–93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80–0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia.

The epidemiology of bacteremia and the antibiotic resistance profile (ARP) of Gram-negative bacilli (GNB) in hematological malignancies (HM) and hematopoietic stem cell transplant (HSCT) patients may differ according to geographic region. In addition, multidrug-resistant organisms (MDROs) may impact mortality. This is a prospective, observational, and multicenter study. The first episodes of bacteremia in adult patients with HM or HSCT were included. The risk factors for 30-day mortality were identified. One thousand two hundred and seventy-seven episodes were included (HM: 920; HSCT: 357). GNB were isolated in 60.3% of episodes, with Enterobacterales (46.9%) and P. aeruginosa (8.5%) being the most frequent. Gram-positive cocci were isolated in 41.9% of episodes, with coagulase-negative staphylococci (19.8%) and S. aureus (10.4%) being the most frequent. MDROs were isolated in 40.2% (24.4% GNB). The ARP of GNB in patients with HM vs. HSCT was cefepime: 36.8% vs. 45.7% (p = 0.026); piperacillin–tazobactam: 31.05% vs. 45.2% (p < 0.0001); carbapenems: 18.9% vs. 27.3% (p = 0.012); and aminoglycosides: 9.3% vs. 15.4% (p = 0.017), respectively. Overall mortality between patients with HM and HSCT was 17.5% vs. 17.6% (p = 0.951), respectively. The risk factors for mortality were relapsed and refractory underlying disease, corticosteroids use, respiratory source, septic shock, and GNB resistant to meropenem, while 7-day clinical response was a protective factor for survival. Bacteremia was frequently caused by GNB, with a large proportion of MDROs and a high level of antibiotic resistance, especially in patients with HSCT. Carbapenem-resistant GNB bacteremia was associated with a significant increase in mortality.