piperacillin (piperacillin, KRKA / Isipen)

Prospective evaluation of therapeutic target attainment with a beta-lactam dosing nomogram in critically ill adult patients.

Williams Paul P, Cotta Menino Osbert MO, Abdul-Aziz Mohd H MH, Wilks Kathryn K et al.

Therapeutic drug monitoring (TDM) individualises antibiotic dosing, aiming for therapeutic exposures and minimising toxicity. However, TDM cannot always be performed due to resource requirements, and clinicians often dose according to guidelines. This study aimed to quantify the achievement of therapeutic exposures (concentrations) in a heterogeneous cohort of critically ill adults using nomogram-based antibiotic dosing. This was a prospective, single-centre, cohort study of nomogram-based dosing of beta-lactams in critically ill adults. The primary outcome was the proportion of patients with therapeutic exposures, that is those above the efficacy threshold but below the toxic threshold. Secondary endpoints were exposures associated with toxicity, and the relationship between exposure and clinical outcomes. In 79 patients, therapeutic beta-lactam exposure was achieved in 82% (63/77) and 81% (35/43) of patients at days 1 to 3 and days 4 to 6, respectively. Piperacillin yielded the lowest therapeutic attainment, with 75% (24/32) and 71% (12/17) at days 1 to 3 and days 4 to 6, respectively, and the highest proportion of sub-therapeutic exposures: 25% (8/32) and 29% (5/17), respectively. Therapeutic tazobactam trough concentrations were achieved in 66% (21/32) and 65% (11/17) of patients at days 1 to 3 and days 4 to 6, respectively. In a single-centre heterogeneous population of critically ill adults with infection, initial dosing informed by a dosing nomogram for beta-lactams resulted in a high proportion of patients achieving therapeutic exposures.

Audit of the prescription of antimicrobials using the four moments of decision tool in a university hospital.

Cambiais Amanda Magalhães Vilas Boas AMVB, Pinto Vanusa Barbosa VB, Sforsin Andréa Cassia Pereira ACP, Malbouisson Luiz Marcelo Sa LMS et al.

Antimicrobial resistance is a growing global threat driven by inappropriate antimicrobial use. The Four Moments of Antibiotic Decision Making is a stewardship framework that promotes rational antibiotic use. This study applied this framework to audit antimicrobial prescribing, assess adherence, and measure antimicrobial use. We conducted a retrospective, cross-sectional audit of patients who received systemic antimicrobials between October and November 2023. The four audited moments included: (1) indication, suspected site, and clinical evidence of infection; (2) antimicrobial selection and culture collection; (3) reassessment between days 3 and 5 based on clinical response and culture results; and (4) treatment duration. Antimicrobial consumption was measured using days of therapy (DOT), length of therapy (LOT) and the WHO AWaRe classification. A total of 228 patients (53.5% male; mean age 57 years) received 304 antimicrobial treatments, including 129 intensive care units (ICU) admissions. 75.0% were fully adherent to all Four Moments. Adherence rates across moments 1 to 4 were 97%, 88.8%, 89.3%, and 87.1%, respectively. In moment 2, cultures were indicated in 201 treatments but not requested in 15% of cases. Vancomycin was the most prolonged treatment, followed by ceftriaxone, piperacillin-tazobactam, and meropenem. Antimicrobial use was higher in ICUs, with DOT and LOT reaching 739 and 706 per 1,000 patient-days, respectively, compared with 496 and 319 in the wards. Most antimicrobial consumption corresponded to WHO AWaRe Watch antibiotics. Adherence to stewardship principles was high, although opportunities for improvement remain, particularly regarding culture collection and treatment duration optimization.

Vancomycin-piperacillin/tazobactam and acute kidney injury: a genuine clinical risk or an overstated association.

Mehta Ankit A

Cefoperazone-sulbactam versus cefepime and piperacillin-tazobactam for initial empiric treatment of febrile neutropenia in patients with hematologic malignancies: A retrospective matched-cohort study.

Tsai Ming-Tao MT, Chuang Yu-Chung YC

Empiric antipseudomonal β-lactams are the standard of care for febrile neutropenia (FN), but comparative data for cefoperazone-sulbactam are limited. We compared cefoperazone-sulbactam with cefepime and piperacillin-tazobactam as initial empiric therapies for FN in adults with hematologic malignancies. We conducted a retrospective matched-cohort study at a tertiary center in Taiwan (2021-2023). Adults with hematologic malignancies who received cefoperazone-sulbactam, cefepime, or piperacillin-tazobactam as the initial empiric therapy for FN were included (53 episodes/regimen). The episodes were matched by calendar time to reduce confounding factors related to changes in empiric antibiotic use. The primary outcome was treatment success, defined as defervescence without modification of the initial empiric β-lactam regimen and day 5 survival. Among the 159 included episodes, treatment success occurred in 120/159 (75.5%) episodes and did not differ across regimens (cefoperazone-sulbactam, 79.2%; cefepime, 71.7%; piperacillin-tazobactam, 75.5%; P = 0.70). Neutrophil recovery by day 5 independently predicted treatment success (adjusted odds ratio, 3.32; 95% confidence interval, 1.15-9.63; P = 0.027), but empiric β-lactam selection did not. The median duration of empiric β-lactam therapy was similar across regimens. Bleeding (3/159, 1.9%) and prothrombin time/international normalized ratio prolongation (2/46, 4.3%) were uncommon and similar across regimens. No significant differences in early clinical effectiveness or overall safety were observed among the three regimens. Neutrophil recovery, rather than empiric regimen, independently predicts treatment success. These retrospective findings should be interpreted cautiously given potential residual confounding by indication and warrant confirmation in larger studies.