Although febrile neutropenia (FN) remains a major cause of morbidity and mortality in patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients, the increasing prevalence of antimicrobial resistance necessitates a reassessment of antibiotic prophylaxis and treatment strategies. This review explores the prophylactic and therapeutic use of antibiotics in FN management, with a particular focus on patients with hematologic malignancies - particularly acute leukemia - and HSCT recipients. Challenges in FN management, including antibiotic prophylaxis and treatment optimization, remain due to the complexity of the condition. Pathogens with emerging antibacterial resistance cause significant concern in the management of patients. Particulary due to selection potential of resistant gram-negative bacteria (GNB), fluoroquinolones (FQs) have become less attractive agents for prophylaxis. Whereas, emerging data may help to revitalize long-abandoned aminoglycoside containing combination therapies particulary in high-risk patients with presumed sepsis. With only a few agents available for highly-resistant bacteria alternative treatment strategies including pharmacokinetic/pharmacodynamic (PK/PD) concerning antibiotic applications may be warranted. Carefully-designed, randomized, controlled trials providing large scale data which then can be analyzed with emerging artificial intelligence (AI) technologies are needed. The results from such trials may allow a better, data-driven approaches for management of FN.

Objective: This study aims to assess the impact of hospital-specific guidelines on the optimal utilization of carbapenems and to examine their effects on patient outcomes. Design: Quasi-experimental study. Setting: Tertiary care hospital in Turkey where infectious diseases (IDs) consultation and antibiotic approval are mandatory for carbapenem use. Participants: All inpatients ≥18 years of age who received a carbapenem for at least 24 hours during the study periods were enrolled. Intervention: Hospital-specific treatment guidelines were introduced in April 2019. The control group was the year 2018, when there were no guidelines (pre-GP). The year 2020 was analyzed as the intervention period (post-GP). Results: A total of 678 patients were analyzed, 326 in the pre-GP period and 352 in the post-GP period. Following guideline implementation, there was a significant increase in appropriate carbapenem use (49.1% in pre-GP vs 71.9% in post-GP, P < .001). The duration of carbapenem use decreased significantly (P = .019). However, there was no significant change in the incidence of new infection episodes within the subsequent 30 days (27.6% in pre-GP vs 28.3% in post-GP), or in the length of hospitalization [median (25%–75%) = 28 (16–46) in pre-GP, 28 (15–47.5) in post-GP, P = .678]. Mortality rates were similar at day 7 post-GP (1.7%) compared to pre-GP (0.03%) (P = .125). Conclusions: The implementation of guidelines increased the appropriate utilization of carbapenems, without resulting in extended hospital stays or recurrent episodes. Despite an increased number of patients admitted to the ICU during the latter period, infection-related mortality rates remained comparable.

Objectives: To evaluate the clinical and microbiological factors associated with the failure of levofloxacin prophylaxis in high-risk haematology patients, with a particular focus on the attainment of the pharmacokinetic/pharmacodynamic (PK/PD) target. Methods: This prospective case–control study evaluated adult high-risk haematology patients receiving levofloxacin prophylaxis (750 mg/day) during neutropenia. Analyses were performed at the episode level. Individual levofloxacin exposure was described using a population PK model, with the PK/PD target defined as fAUC0–24/MIC ≥80. Surveillance cultures were used to characterize Gram-negative bacterial (GNB) colonization and resistance profiles. Results: A total of 120 neutropenic episodes were analysed. Profound neutropenia was independently associated with prophylaxis failure (OR: 4.17; 95% CI: 1.70–10.2; P = 0.002], whereas achievement of fAUC/MIC ≥80 was independently associated with a reduced risk of failure (OR: 0.12; 95% CI: 0.02–0.62; P = 0.012). Receiver operating characteristic curve analysis identified fAUC/MIC ≥48.46 as the Youden-optimal cutoff (sensitivity 86.0%, specificity 38.3%; Youden J = 0.243). Achievement of this cutoff was also independently associated with a reduced risk of prophylaxis failure (OR: 0.26; 95% CI: 0.083–0.803; P = 0.019). Target non-attainment was strongly associated with levofloxacin-resistant GNB colonization, indicating that PK/PD failure was predominantly MIC driven. Conclusions: Levofloxacin prophylaxis failure appears to reflect an interplay between host factors and inadequate PK/PD target attainment, which was largely influenced by levofloxacin-resistant GNB colonization. The standard 750 mg dose was insufficient in a significant proportion of patients, supporting the need for prophylaxis strategies that integrate PK/PD targets and local resistance patterns.

Background/Objectives: Cefazolin is commonly administered for surgical antibiotic prophylaxis. This review aims to examine whether target unbound plasma and tissue cefazolin concentrations are reached following prophylactic administration across multiple surgical subtypes. The primary outcome was a lower limit of cefazolin concentration variability (mean–SD, lower quartile, or lower range) in unbound plasma and/or tissue > 2 mg·L⁻¹, the epidemiological cut-off (ECOFF) value for Staphylococcus aureus at skin incision and/or closure. Methods: Prisma 2020 guidelines were followed, and the protocol is registered in PROSPERO (CRD42021080289). A literature search using MEDLINE (PubMed), Embase, CENTRAL, CINAHL, and further databases was performed to identify studies in which prophylactic cefazolin was administered to adult surgical patients (≥18 years old) undergoing elective surgery, and unbound plasma and tissue concentrations were measured at skin incision and closure. Exclusion criteria included languages other than English, emergency surgery, cefazolin being administered for any reason other than surgical site prophylaxis, and whether patients received any cefazolin within the 48 h prior to the prophylactic dose. The search was repeated in August 2025 to ensure currency. A narrative assessment of the methodological quality was performed. The data were synthesised in a narrative and tabular form, and the certainty of the evidence was assessed using the GRADE approach. Results: A total of 37 studies with 1102 patients met the inclusion criteria. Twelve bariatric studies and 378 patients, 9 cardiac studies and 197 patients, 8 obstetric studies and 277 patients, 6 orthopaedic studies and 176 patients, 3 abdominal surgery studies and 62 patients, and 1 vascular study and 12 patients were included. Two studies met the inclusion criteria for both bariatric and abdominal surgery. The lower limit of variability of the unbound plasma concentration was consistently >2 mg·L⁻¹. The reported lower limits of variability in tissue concentrations of bariatric surgery were conflicting. Only one study in cardiac surgery assessed the current dosing regimens. The lower range of variability of tissue concentrations was consistently >2 mg·L⁻¹ in the orthopaedic, obstetric, abdominal, and vascular surgery subtypes. Conclusions: The current dosing approaches in the obstetric, orthopaedic, abdominal, and vascular surgery groups are reassuring for achieving effective concentrations, although the overall data are sparse. It is unclear if increased dosing is warranted in bariatric surgery patients, and further investigations in cardiac surgery with current dosing regimens are required.