BACKGROUND:Acute kidney injury frequently complicates the end stages of liver diseases, worsening the condition of patients waiting for liver transplants. Continuous renal replacement therapy during liver transplant is still a limited experience, with large variability in the indication criteria. The recent KDIGO guidelines on acute kidney injury may help identify patients who could potentially benefit from the procedure. Therefore, close collaboration between intensivists and nephrologists is essential for shared criteria and treatment management. This study aimed to assess the feasibility and safety in clinical practice of a joint intraoperative continuous renal replacement therapy (IO-CRRT) program. Some aspects of clinical impact were analyzed as a secondary outcome. METHODS:A collaborative organization between nephrologists and anesthesiologists was implemented at St. Orsola Hospital of Bologna (Italy) to manage liver transplant candidates with acute kidney injury. Feasibility, the main outcome, was assessed through adherence to clinical indications and operative details. We also compared a group receiving IO-CRRT (n = 20) and a historical control group (n = 13) without replacement therapy. RESULTS:No substantial operative deviations from the program were found, excluding 4 patients mistakenly enrolled. The IO-CRRT group had better control of lactates, serum bicarbonate gain, and smoother acute sodium changes compared to controls. CONCLUSION:The overall organization proved to be feasible and safe, provided a high level of collaboration is guaranteed. The trend of some metabolic parameters appeared to benefit from IO-CRRT, which may reasonably help in balancing metabolism during liver transplant surgery. This strategy could increase the opportunity for transplant for some patients who otherwise would be excluded.

Donation after cardiovascular determination of death (DCD) has expanded the liver donor pool but remains limited by concerns over prolonged donor warm ischemia and inferior outcomes, particularly in countries such as Italy where legally mandated asystolic periods increase donor risk. This study evaluates trends in DCD liver transplantation at a high-volume Italian center, to assess whether accumulated experience and advanced reconditioning strategies influenced outcomes over time. We retrospectively analyzed adult DCD liver transplants performed between 2016 and 2023. Donor characteristics, recipient risk profiles, perfusion strategies, ischemia times, and post-transplant outcomes were compared between an early (2016–2021) and a late (2022–2023) period. Temporal trends were evaluated using linear regression. Seventy-five DCD liver transplants were included. Later-period recipients had more advanced liver disease (39.1

OBJECTIVES:To assess the biliary pharmacokinetic/pharmacodynamic (PK/PD) of continuous infusion (CI) ceftazidime-avibactam in a series of critical orthotopic liver transplant (OLT) recipients having pre-emptive therapy during OLT because of carbapenemase-producing Enterobacterales (CPE) rectal colonization or targeted therapy of CPE intra-abdominal (IAIs) and/or biliary tract infections (BTIs). METHODS:We performed an exploratory, hypothesis-generating prospective case series including critical OLT recipients carrying a Kehr's tube and undergoing therapeutic drug monitoring of ceftazidime and avibactam in both bile and plasma simultaneously while receiving CI ceftazidime-avibactam pre-emptive or targeted therapy. Biliary aggressive joint PK/PD target attainment [defined as a free ceftazidime steady-state concentrations fCss/MIC ratio >4 coupled with an avibactam fCss/target concentration (CT = 4 mg/L) ratio >1] was selected as optimal threshold of ceftazidime-avibactam efficacy, given this was previously shown to be independently associated with lower rates of microbiological failure and resistance development. Bile-to-plasma fCss ratios were calculated. RESULTS:Overall, four critical OLT recipients were included. Aggressive biliary ceftazidime-avibactam joint PK/PD target during treatment with CI 2 g/0.5 g q8 h over 8 h was attained in 2/4 cases (quasi-optimal and suboptimal in one case each). Median (range) fCss bile-to-plasma ratios were 0.28 (0.22-0.38) for ceftazidime and 0.24 (0.11-0.52) for avibactam. CONCLUSIONS:Our limited cases series suggested that both ceftazidime and avibactam showed a moderate and broadly similar biliary penetration. Administration by CI may be helpful in attaining an aggressive biliary joint PK/PD target of ceftazidime-avibactam against pathogens with an MIC up to 8 mg/L.

OBJECTIVE:To assess whether attaining an aggressive joint pharmacokinetic/pharmacodynamic (PK/PD) target of therapeutic drug monitoring (TDM)-guided continuous infusion (CI) meropenem-vaborbactam monotherapy may be a valuable strategy for maximizing the microbiological outcome of documented KPC-producing Enterobacterales infections. METHODS:This retrospective cohort study was performed in patients receiving CI meropenem-vaborbactam monotherapy for KPC-producing Enterobacterales infections and undergoing real-time TDM. Free fractions of plasma steady-state concentrations (fCss) of meropenem and vaborbactam were calculated according to a protein binding of 2% and 33%, respectively. Aggressive joint PK/PD target attainment was defined as a meropenem fCss/MIC ratio >4 coupled with a vaborbactam free area under time-to-concentration curve (fAUC)/target concentration (CT) ratio >24. Multivariate analysis was performed for assessing potential independent predictors of microbiological failure. RESULTS:Overall, 55 patients were included. Aggressive joint PK/PD target of meropenem-vaborbactam was attained in 96.3% (53/55) of cases. Among 44/55 patients having follow-up cultures (80.0%), 9 experienced microbiological failure (20.5%), and 2 developed 90-day resistance (4.5%). Continuous renal replacement therapy (OR, 15.00; 95% CI: 1.75-128.40; P = 0.013) and intrabdominal infection (OR, 10.00; 95% CI: 1.36-73.33; P = 0.024) emerged as independent predictors of microbiological failure. Aggressive joint PK/PD target was non-attained more frequently among patients having microbiological failure than in those having microbiological eradication (22.2% vs. 0.0%; P = 0.038), although not statistically significant at multivariate analysis. CONCLUSIONS:Our findings suggest that a TDM-guided monotherapy of documented KPC-producing Enterobacterales infections focused on aggressive joint PK/PD target attainment with CI meropenem-vaborbactam could represent a valuable strategy either for granting microbiological cure and for counteracting resistance development.

Background Extended criteria donors (ECDs) have become an important source of organs, but their association with infection risk remains unclear. This systematic review assessed the impact of ECD versus standard criteria donors (SCDs) on infection rates in kidney and liver transplant recipients and analyzed the variability of ECD definitions.Methods Three different literature databases were searched up to June 2024 for randomized controlled trials or observational studies comparing infection rates between ECD and SCD recipients. Studies without quantitative data or comparator groups were excluded. Outcomes were measured at 30-180 days and 1, 3, and 5 years posttransplant, evaluating both bacterial and viral infections.Results A total of 11 119 articles were screened and 131 studies included. At 30 days, bacterial infections occurred at similar rates between ECD and SCD recipients (odds ratio [OR] 1.15, 95% confidence interval [CI] .86-1.53, P = .36). However, liver transplant recipients from ECDs had a higher infection risk (OR 1.73, 95% CI 1.12-2.68, P = .01). Definitions of ECD varied notably, especially in liver transplantation, while kidney transplantation criteria were more consistent.Conclusions Current evidence does not definitively establish a link between ECD and infection risk, highlighting the need for standardized donor definitions and routine reporting of infections as ECD outcomes.

BACKGROUND:To assess the true prevalence and the risk factors of augmented renal clearance (ARC) in critical orthotopic liver transplant (OLT) recipients and its impact on early aggressive pharmacokinetic/pharmacodynamic (PK/PD) target non-attainment of continuous infusion (CI) beta-lactams. METHODS:OLT recipients without renal dysfunction and undergoing one or more measured creatinine clearance (mCLCr) assessments in the first 30 days posttransplant were retrospectively included. Reliability of three different eGFR formulas (Cockcroft-Gault, 2021, CKD-EPI, and MDRD) in estimating mCLCr was tested. Univariate analyses compared the clinical features of ARC versus non-ARC patients and the severity of the clinical conditions during ARC versus non-ARC episodes in the whole cohort. In patients receiving CI beta-lactam therapy, risk factors for early aggressive PK/PD target non-attainment were investigated. RESULTS:Among 450 critical OLT recipients, 112 were included. The true prevalence of ARC was 23.2%. ARC versus non-ARC patients were younger (p = 0.003), had lower MELD score (p = 0.001), received lower number of intraoperative blood transfusions (p = 0.007), and had a lower need for venovenous bypass technique (p = 0.024). ARC episodes occurred more frequently in patients having lower SOFA score (p = 0.005) and lower median serum creatinine levels (p < 0.001). None of the eGFR formulas properly estimated mCLCr. In the subset of 50 OLT recipients receiving 60 CI beta-lactam treatment courses, ARC was the only factor associated with early aggressive PK/PD target non-attainment (p = 0.018). CONCLUSIONS:ARC is a quite prevalent condition among critical OLT recipients, which may hinder early aggressive PK/PD target attainment when using standard beta-lactams dosing regimens, regardless of delivery by CI.

Normothermic regional perfusion (NRP) is increasingly implemented to optimize the outcome of transplantation from donors undergoing circulatory determination of death. NRP shortens the duration of warm ischemia, allowing splanchnic reperfusion with oxygenated blood. This supports the abdominal organs throughout recovery, allowing for their thorough assessment, avoids the need for rapid recovery, and restores a near physiological environment. However, after NRP, the grafts are exposed to a period of cold ischemia preceding further evaluation and reconditioning through ex situ machine perfusion or direct transplantation. The duration of cold ischemic time may be extremely variable. During cold ischemic time, the liver and the kidneys are indirectly protected by a decrease in metabolic demands induced by deep hypothermia. To optimize protection, the hypothermic state is initiated in situ, immediately after extracorporeal blood flow interruption, via topical cooling with sterile ice and intravascular cooling. The latter is usually induced by the administration of cold preservation solution (CPS) by gravity. We performed an observational study to assess the feasibility, safety, and effectiveness of a controlled strategy of CPS administration and oxygenation employing the NRP circuit and cannulae in controlled circulatory determination of death undergoing abdominal NRP. This approach provided a controlled, fast, and consistent flow, ensuring a prompt induction of hypothermia. Moreover, during CPS administration, the delivery of a fresh gas flow through the membrane lung resulted effective in significantly increasing the oxygen tension in the CPS. The hyperoxygenation of the blood-free perfusate might provide a metabolic substrate to the cells, preconditioning the grafts before cold ischemia.

BACKGROUND:The advent of machine perfusion (MP) has significantly improved post-liver transplantation (post-LT) outcomes, potentially enabling the use of increasingly marginal grafts and expanding the organ donor pool. METHODS:We present a retrospective cohort study of consecutive adult patients who underwent LT between 2018 and 2023 at a leading Italian institution. The objective was to evaluate outcomes following the use of hypothermic oxygenated perfusion (HOPE) in high-risk grafts. RESULTS:A total of 507 patients were included in the final analysis, of whom 420 (83%) received extended criteria donor (ECD) grafts. Among ECD grafts, 62 (15%) were from donation after circulatory death (DCD) donors, and 64 (15%) were previously discarded by other centers. HOPE was applied in 248 (49%) cases. Recipients in the HOPE group experienced significantly lower rates of early allograft dysfunction (EAD) (20% vs. 32%, p = 0.007), primary nonfunction (2% vs. 7%, p = 0.017), and severe postoperative complications (Clavien-Dindo grade ≥ 3b) (19% vs. 28%, p = 0.026). Notably, marginal grafts treated with HOPE achieved survival outcomes comparable to those of standard risk. CONCLUSIONS:HOPE is associated with improved outcomes in LT using ECD grafts and can enable the safe use of higher-risk organs with acceptable results when performed in experienced centers.

Ceftolozane/tazobactam is widely used against extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, yet FDA-approved dosing relies on intermittent infusion and a fixed 2:1 ratio that assumes adequate β-lactamase inhibition. Tazobactam's faster and variable clearance raises concerns for subtherapeutic exposure. This study evaluated whether continuous infusion (CI) improves pharmacokinetic target attainment and whether current dosing adequately covers both components. We conducted an analysis of 139 hospitalized adults receiving CI ceftolozane/tazobactam with therapeutic drug monitoring (TDM). Free steady-state concentrations (fCss) and observed clearance were calculated and assessed across kidney function strata. Population pharmacokinetic modeling and Monte Carlo simulations evaluated the probability of target attainment (PTA) for each drug. Despite kidney function-adjusted CI, 38.1% of patients had tazobactam fCss <4 mg/L, a threshold linked to reduced efficacy and resistance emergence, while only 2.5% had ceftolozane fCss <8 mg/L (namely 4× MIC the Enterobacterales clinical breakpoint for susceptibility). Tazobactam clearance (mean 7.41 L/h) was 2.5-fold higher than ceftolozane and highly variable (CV 115%). Kidney function explained only 23% of clearance variability. The cohort's older age (median 66 years; 26.6% ≥75 years) likely led to lower tazobactam clearance, suggesting even greater underexposure in younger patients. Simulations showed standard dosing achieved only 29%-54% cumulative response against ESBL-producing Enterobacterales, versus 73%-82% with optimized regimens using 2-3× higher ceftolozane/tazobactam doses of magnitude similar to those licensed for pneumonia. Current ceftolozane/tazobactam dosing, even with CI, is often subtherapeutic for tazobactam. These findings challenge fixed-ratio formulations and support individualized, component-guided dosing to preserve efficacy and suppress resistance.

Background/Objectives: Lung ultrasound (LUS) has emerged as a crucial bedside tool for evaluating and managing patients with respiratory failure, particularly those receiving mechanical ventilation (MV). Its ability to rapidly characterise lung pathology, including extent, severity, and progression, has established LUS as a key diagnostic and monitoring modality in both hospital and home-care settings. Methods: This narrative review analyses the specific applications of LUS in the assessment and management of patients undergoing MV, aiming to optimise ventilatory strategies. Results: We examine the role of LUS in (1) identifying patients requiring MV; (2) guiding ventilator settings (Positive End Expiratory Pressure selection, inspiratory pressure adjustment, and patient-ventilator synchrony optimisation); (3) performing and monitoring recruitment manoeuvres; (4) assessing parenchymal damage and evaluating the response to medical and ventilatory therapies; (5) detecting ventilation-associated complications; (6) facilitating weaning from MV; and (7) assisting with airway management procedures, specifically tracheostomy. The utility of Transesophageal Lung Ultrasound (TELU) is also briefly discussed. Conclusions: This review highlights the potential of LUS to improve clinical decision making and patient outcomes in the context of MV.

BACKGROUND:To assess the impact of attaining aggressive β-lactam (BL) pharmacokinetic-pharmacodynamic (PK/PD) targets on clinical efficacy in critically ill orthotopic liver transplant (OLT) recipients with documented early gram-negative infections. METHODS:The study prospectively enrolled OLT recipients admitted to the posttransplant intensive care unit between June 2021 and May 2024; they had documented gram-negative infections treated with targeted therapy continuous infusion (CI) BLs and underwent therapeutic drug monitoring (TDM)-guided BL dosing adjustment within the first 72 hours. Aggressive PK/PD target attainment was measured. Multivariate logistic regression analyses were performed to test independent variables associated with 30-day resistance occurrence. RESULTS:Fifty critically ill OLT recipients were treated with CI BL in monotherapy (n = 34) or combination (n = 16) therapy for documented gram-negative infections No significant difference in clinical/microbiological outcome emerged between monotherapy and combination therapy. In 4 patients (8.0%), resistance developed within 30 days. At multivariate analysis, failure in attaining an aggressive BL PK/PD target emerged as the only independent predictor of 30-day resistance development (odds ratio, 14.33 [95% confidence interval, 1.46-140.53]; P = .02). CONCLUSIONS:Attaining an aggressive PK/PD target with CI BLs in critically ill OLT recipients with documented gram-negative infections could represent an effective strategy for minimizing resistance occurrence to the selected BL.

Background: Colorectal liver metastases (CRLM) occur in up to 50% of colorectal cancer with a significant impact on patient survival, of whom only 20-30% will be considered suitable for surgical treatment. Despite the progress in systemic therapies, palliative chemotherapy alone results in a 5-year overall survival (OS) < 10%. Recently, liver transplantation (LT) has been reconsidered as an option and demonstrates improved survival in highly selected patients. This study assessed the impact of implementing a standardised patient selection protocol (LITORALE) on post-transplant outcomes for unresectable CRLM (uCRLM) at a high-volume single centre. Methods: This is a prospective observational study including all consecutive patients transplanted for uCRLM at our institution between July 2015 and September 2024. This prospective observational study evaluated the impact of the LITORALE protocol on post-transplant outcomes in uCRLM patients at a single centre. Patients who underwent LT between July 2015 and September 2024 were grouped into pre-LITORALE (2015-2021) and LITORALE (post-2021) cohorts. Recipient profiles, transplant variables, and post-transplant outcomes were compared. Results: Twenty-one patients were included (eight pre-LITORALE, thirteen LITORALE). The LITORALE group had a lower median number of lesions (4 vs. 17.5, p = 0.004), a smaller major lesion size (3 cm vs. 5.5 cm, p = 0.082), and a significantly lower tumour burden score (6.32 vs. 18.02, p = 0.002). Similar to recent major clinical trials, one- and three-years OS were 100% and 83%, respectively, after protocol introduction; recurrence patterns were significantly different, with reduced multi-site recurrences (7.7% vs. 50%, p = 0.048) and a higher incidence of lung-only recurrences in the LITORALE group (50% vs. 0%, p = 0.033). Conclusions: The introduction of the LITORALE protocol significantly influenced patient selection and recurrence patterns in LT for uCRLM. Although the limited number of patients and the short study timespan highlight the need for future validation, these preliminary results support the adoption of structured, multidisciplinary criteria to optimise oncologic outcomes.

Ceftolozane/tazobactam is a key antibiotic for Pseudomonas aeruginosa infections. Our objective was to determine whether continuous infusion (CI) of ceftolozane/tazobactam can achieve aggressive pharmacokinetic/pharmacodynamic (PK/PD) targets that suppress resistance and improve outcomes in severe Pseudomonas aeruginosa infections. A retrospective analysis of adult patients receiving CI ceftolozane/tazobactam and therapeutic drug monitoring (TDM) of both compounds was performed. Population PK/PD modeling identified the most accurate method for estimating ceftolozane/tazobactam clearance based on kidney function and Monte Carlo simulations investigated the relationship between various CI dosing regimens and aggressive PK/PD target attainment of ceftolozane/tazobactam. The 2021 non-race-based Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) equation with body surface area indexation provided the most reliable clearance estimates. Simulations showed that CI regimens of 4-6 g/2-3 g daily achieved optimal target attainment (≥90%) across all kidney function strata for MICs up to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint. Cumulative fraction of responses remained robust against key resistance phenotypes: MDR (12.6%; 83.8%), pan-beta-lactam-nonsusceptible (8.2%; 78.2%), and difficult-to-treat resistant (6.7%; 71.7%). Even among isolates with MIC >4 mg/L, aggressive target attainment was reached in 15%-40% of cases. This study suggests that CI ceftolozane/tazobactam, informed by TDM and optimized for aggressive PK/PD targets, offers a promising strategy to maximize efficacy and suppress resistance in severe Pseudomonas aeruginosa infections. These findings warrant prospective clinical trials of CI-based, exposure-guided therapy.

To validate a predictive risk score of early aggressive pharmacokinetic/pharmacodynamic (PK/PD) target non-attainment with continuous infusion (CI) piperacillin/tazobactam or meropenem in a retrospective cohort of critically ill patients having documented Gram-negative infections. Critically ill adult patients receiving treatment of documented Gram-negative infections with CI piperacillin-tazobactam or meropenem and undergoing first real-time beta-lactam therapeutic drug monitoring (TDM) instance within 72 h from starting standard dosing regimens were retrospectively included. A receiving operating characteristic (ROC) curve analysis was performed by using the proposed predictive score as the test variable and early aggressive PK/PD target non-attainment as the state variable. Area under the curve (AUC) and 95

Objectives: To assess the role of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program of isavuconazole in preventing under- or overexposure with the intent of improving efficacy and safety outcomes in the critically ill patients. Methods: This retrospective study included critical patients receiving intravenous isavuconazole for prophylaxis or treatment of invasive fungal infections (IFI) and undergoing at least one TDM-guided ECPA in the period 1 March 2021-31 March 2025. Desired isavuconazole exposure was defined as trough concentrations (Cmin) of 1.0-5.1 mg/L. Efficacy outcome was assessed by means of bronchoalveolar (BAL) galactomannan (GM) index, breakthrough IFI, and 30-day mortality rate, whereas safety was assessed by means of hepatic test disturbances (HTD). Univariate analysis was carried out for assessing potential variables associated with isavuconazole under- or overexposure and for comparing features of solid organ transplant (SOT) recipients vs. non-SOT patients. Proportions of isavuconazole Cmin underexposure, desired exposure, and overexposure were assessed at different timepoints from starting therapy. Trends over time of HTD in relation to isavuconazole exposure were assessed separately in patients having HTD or not at baseline. Results: Overall, 32 critical patients were included. A total of 166 TDM-guided ECPAs were provided. Median (IQR) average isavuconazole Cmin was 3.5 mg/L (2.1-4.6 mg/L). Proportions of ECPAs with isavuconazole Cmin under- and overexposure were 4.2% (7/166) and 16.3% (27/166), respectively. Patients experiencing underexposure had higher body mass index (30.1 vs. 25.5 kg/m2; p < 0.001). Trends of isavuconazole Cmin under- and overexposure changed over time, significantly decreasing the former (10.5% <7 days vs. 4.3% 7-28 days vs. 0.0% >28 days; p < 0.001) and increasing the latter (5.3% <7 days vs. 12.8% 7-28 days vs. 29.3% >28 days; p < 0.001). HTD occurred in 15/32 patients, most of whom (10/15) were affected just at baseline. Patients with transient or persistent overexposure trended toward a higher risk of HTD compared to those without (33.3% vs. 8.3%; p = 0.11). Conclusions: A real-time TDM-guided approach could be a valuable tool for optimizing isavuconazole exposure, especially whenever dealing with obese patients or with prolonged treatment.

The rising prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Hepatocellular Carcinoma in the elderly population has increased the demand for liver transplantation (LT) in patients over 70 years. Advanced age, however, is still considered an independent risk factor. This study aims to evaluate post-transplant oucomes in patients aged over 70 years, traditionally viewed as an age limit for transplant. We retrospectively analyzed 584 LT recipients (36 aged ≥70, 548 aged <70). Viral cirrhosis was more frequent in the younger group (36.1% vs. 13.1%), while MASLD was more common in those over 70 (25% vs. 13.1%) (p = 0.013). Model for End-Stage Liver Disease (MELD) scores were lower in patients over 70 (13, IQR 9–17) compared to the younger group (15, IQR 10–23) (p = 0.032). Propensity score matching (3:1 ratio, without replacement) was performed based on MELD and cirrhosis etiology. After matching, no significant differences were found in postoperative outcomes, overall survival, or graft survival. Our findings demonstrate that carefully selected patients over 70 can achieve post-transplant outcomes comparable to younger patients. Advanced age alone should not be considered an absolute contraindication; instead, a comprehensive, multidimensional assessment is essential to identify suitable candidates.

Appropriate fluid management is crucial in anesthesiologic management during kidney transplantation (KT). Traditional parameters such as blood pressure and central venous pressure are unreliable and weakly supported by guidelines. Goal-directed fluid therapy (GDT) has emerged as a technique for administering fluids and vasoactive drugs based on algorithms to ensure adequate tissue perfusion. Current data suggest GDT may reduce tissue edema and respiratory complications in KT recipients. This multicenter, single-blind randomized controlled trial compared conventional fluid management strategies with a GDT algorithm using non-invasive pulse pressure contour analysis monitoring (ClearSight (R)) in KT patients. The primary outcome was the hospital length of stay. Secondary outcomes included postoperative complications, delayed graft function, 90-day graft loss, and intensive care unit (ICU) length of stay. Patients and postoperative care physicians were blinded to group assignments. The study enrolled 181 KT recipients over 32 months. The hospital length of stay did not significantly differ between the groups, with a difference of 0.5 days (95% CI: -2.5 to 5 days). No significant differences were found in surgical and medical complications, delayed graft function, graft loss, or ICU length of stay. In KT recipients, using a GDT algorithm did not result in clinically meaningful differences in hospital stay, complications, or graft dysfunction/loss.

To assess the impact of a multidisciplinary approach aimed at attaining aggressive joint pharmacokinetic/pharmacodynamic (PK/PD) target with ceftazidime/avibactam on treatment outcome of KPC-Klebsiella pneumoniae (Kp) infections and prevention of ceftazidime/avibactam resistance development, a pre-post quasi-experimental study on adult patients with documented KPC-Kp who were treated with ceftazidime/avibactam according to a multidisciplinary approach in the period 1 March 2021-31 October 2024 and patients receiving standard management with ceftazidime/avibactam in the period 1 January 2018-28 February 2021 was performed. Multivariate analysis was performed to identify variables associated with microbiological failure and 90-day resistance development to ceftazidime/avibactam in both pre- and post-intervention phases. A total of 116 and 102 patients in pre- and post-intervention phases were included. A significantly lower microbiological eradication rate (53.0% vs. 81.0%; P < 0.001), a lower clinical cure rate (48.3% vs. 70.6%; P < 0.001), and a higher rate of 90-day resistance development (15.5% vs. 5.9%; P = 0.02) were found in the pre-intervention phase. Continuous renal replacement therapy (odds ratio [OR] 5.20; 95% confidence interval [CI] 1.21-22.34) and a ceftazidime/avibactam MIC value ≥ 4 mg/L (OR 3.08; 95% CI 1.10-8.64) emerged as independent predictors of microbiological failure in the pre-intervention phase. Conversely, attaining aggressive joint PK/PD target (OR 0.03; 95% CI 0.005-0.20) and bloodstream infections (OR 0.09; 95% CI 0.02-0.53) resulted in protection against microbiological failure in the post-intervention phase. Attaining aggressive joint PK/PD targets resulted in protection against 90-day resistance development in the post-intervention phase (OR 0.07; 95% CI 0.01-0.69). Implementing a multidisciplinary approach for maximizing the attainment of aggressive joint PK/PD targets of ceftazidime/avibactam could represent an effective strategy for preventing resistance development to ceftazidime/avibactam in KPC-Kp infections.