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.

There are no data available on the effectiveness and safety of isavuconazole (ISA) for treating breakthrough invasive fungal infections (bIFIs). A retrospective and prospective cohort study was conducted between January 2020 and March 2025 in 13 centers in Argentina. Hematologic diseases (HD) and hematopoietic cell transplantation (HCT) patients who received ISA for IFI were included and followed for 12 weeks. Patients with proven and probable bIFIs and non-bIFIs were compared. One hundred and sixty-three patients were included. IFIs were classified as proven (13.5%), probable (26.9%) and possible (59.5%). Among 66 proven and probable IFIs, 53% were bIFIs, with aspergillosis and mucormycosis being the most common. Twenty-three (34.8%) patients had acute myelogenous leukemia, and 40.9% had received HCT. Forty-eight (72.7%) patients experienced neutropenia, with a median duration of 26 days (interquartile range [IQR] 16–44). Fluconazole and posaconazole were the most frequently received antifungal prophylaxis. ISA was prescribed as first-line therapy in 31 (46.9%) patients. The other 35 received ISA as a continuation therapy, mainly as a step-down therapy after liposomal amphotericin B. Four (6.1%) patients developed adverse effects, and one discontinued ISA. The 90-day overall clinical response between patients with bIFI vs. non-bIFI was 91.4% vs. 70.9% (p = 0.052). The 90-day overall and IFI-related mortality rates were, respectively, 11.4% vs. 32.3% (p = 0.068) and 5.7% vs. 9.7% (p = 0.659). The study data evidence ISA effectiveness and safety for the treatment of HD and HCT patients with and without bIFIs.

There are no data available on the effectiveness and safety of isavuconazole (ISA) for treating breakthrough invasive fungal infections (bIFIs). A retrospective and prospective cohort study was conducted between January 2020 and March 2025 in 13 centers in Argentina. Hematologic diseases (HD) and hematopoietic stem cell transplant (HSCT) patients who received ISA for IFI were included and followed for 12 weeks. Patients with proven and probable bIFIs and non-bIFIs were compared. One hundred and sixty-three patients were included. IFIs were classified as proven (13.50%), probable (26.99%) and possible (59.51%). Among 66 proven and probable IFIs, 53.03% were bIFIs, with aspergillosis and mucormycosis being the most common. Twenty-three (34.85%) patients had acute myelogenous leukemia, and 40.91% had received HSCT. Forty-eight (72.73%) patients experienced neutropenia, with a median duration of 26 days (interquartile range [IQR] 16-44). Fluconazole and posaconazole were the antifungal prophylaxis most frequently received. ISA was prescribed as first-line therapy in 31 (46.97%) patients. The other 35 received ISA as a continuation therapy, mainly as a step-down therapy after liposomal amphotericin B. Four (6.06%) patients developed adverse effects, and one discontinued ISA. The 90-day overall clinical response between patients with bIFI vs. non-bIFI was 91.4% vs. 70.9% (p=0.052). The 90-day overall and IFI-related mortality rates were, respectively, 11.4% vs. 32.3% (p = 0.068) and 5.7% vs. 9.7% (p = 0.659). The study data evidence ISA effectiveness and safety for the treatment of HD and HSCT patients with and without bIFIs.