Search Results (266)

Background/Objectives: Evidence indicates that aberrant glutamate transporter function and expression are linked to the pathophysiology of comorbid major depressive disorder (MDD) and pain. We have previously reported that cefepime (CFP) attenuates lipopolysaccharide (LPS)-evoked pain and depression by regulating hyperglutamatergic activity in male mice. However, the effects of CFP on LPS-evoked pain, depression-related anxiety, and cognitive impairment in female mice regarding sex-specific glial mechanisms remain unknown. Methods: Using behavioral paradigms, we evaluated the therapeutic potential of CFP in mitigating LPS-evoked pain, depression-related anxiety, and cognitive impairment in female mice. Furthermore, we used Western blot analysis to examine the effects of CFP on ionized calcium-binding adaptor molecule 1 (Iba-1) and glutamate transporter 1 (GLT-1) protein levels in the prefrontal cortex (PFC) and hippocampus (HPC). We also measured tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations in the HPC and PFC after CFP treatment using ELISA. Results: Pretreatment with CFP significantly increased the mechanical threshold and withdrawal latency in female mice. Additionally, systemic treatment with CFP markedly reduced immobility during the forced swim and tail suspension tests. Moreover, pretreatment with CFP remarkably augmented the open arm time during elevated plus maze test and spontaneous alternation between arms during Y-maze test. Western blot analysis indicated that systemic administration of CFP significantly reversed the downregulation of astroglial GLT-1 expression and reduced the microglial Iba-1 protein levels in the HPC and PFC. Furthermore, pretreatment with CFP significantly attenuated the LPS-evoked increase in the production of pro-inflammatory cytokines in the HPC and PFC. Conclusions: These results represent the novel inaugural report of a combined pain-MDD phenotype in female mice. The findings imply that positive glutamate transporter modulator CFP could be a novel treatment for comorbid pain and MDD in female patient population. Full article

Cefepime combined with late-generation β-lactamase inhibitors—enmetazobactam, zidebactam, and taniborbactam—represents a promising strategy to treat multidrug-resistant Gram-negative infections. These combinations expand the therapeutic armamentarium beyond established β-lactam/β-lactamase inhibitor regimens, offering targeted activity against ESBL-, AmpC-, and carbapenemase-producing Enterobacterales, as well as multidrug-resistant Pseudomonas aeruginosa. In vitro studies highlight potent and broad activity, with mechanisms including β-lactamase inhibition and, in the case of zidebactam, dual β-lactam enhancement through PBP2 binding. Clinical evidence demonstrates efficacy in complicated urinary tract infections and suggests potential for treating extensively drug-resistant infections, including those unresponsive to conventional β-lactam/β-lactamase inhibitors. Emerging resistance mechanisms—such as PBP alterations, porin loss, efflux pump overexpression, and evolving KPC or NDM variants—underscore the need for ongoing surveillance and robust susceptibility testing. This review provides a comprehensive overview of the mechanisms of action, in vitro activity, pharmacokinetic/pharmacodynamic properties, clinical outcomes, and resistance patterns of these cefepime-based combinations. It also highlights future directions, including the establishment of clinical breakpoints, evaluation in severe infections, and exploration of combination strategies to counteract complex resistance. Overall, these agents exemplify a strategic evolution in β-lactam therapy, offering versatile options to reduce carbapenem reliance while maintaining high efficacy against multidrug-resistant Gram-negative pathogens. Full article

Background: Empirical antibacterial therapy for febrile neutropenia requires adaptation to local epidemiology, a process that is often complex, time-consuming, and prone to human error. This study aims to address this challenge by developing a practical, data-driven tool to efficiently evaluate and adapt treatment protocols. Methods: We developed a novel, open-source computational script in Python (version 3.10), aided by large language models for code revision, to analyze antibiotic susceptibility data. The script was validated using a retrospective dataset of 237 Gram-negative bloodstream infections (BSIs) from 2015 to 2024 in cancer or hematopoietic stem cell transplant recipients at a tertiary care pediatric hospital in Italy. The script calculates efficacy metrics for both single agents and two-drug combinations. Results: Among the Gram-negative BSI strains analyzed, meropenem monotherapy demonstrated the highest efficacy (median 95.4%). In contrast, piperacillin/tazobactam and cefepime showed lower efficacy (80.3% and 81.8%, respectively). On the contrary, combination therapy, particularly with amikacin, significantly increased the efficacy of beta-lactams, elevating their effectiveness to a level comparable to meropenem. Conclusions: The developed script is a valuable tool for antimicrobial stewardship programs, offering a rapid and accessible method to validate international guidelines against local epidemiological data. While meropenem shows high efficacy, its broad use should be limited to prevent resistance. The combination of piperacillin–tazobactam and amikacin is identified as a robust and effective empirical treatment choice. Full article

The global spread of multidrug-resistant (MDR) Gram-negative bacteria, particularly extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, presents a significant public health challenge by limiting effective antimicrobial treatment options. Cefepime, a fourth-generation cephalosporin with broad-spectrum activity, is increasingly compromised by β-lactamase production, efflux pumps, and porin loss. In response, novel cefepime-based β-lactam/β-lactamase inhibitor (BL/BLI) combinations have been developed to overcome these resistance mechanisms. This review examines preclinical and clinical studies on cefepime-based BL/BLI combinations, specifically cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, and cefepime/nacubactam, as found in the PubMed database. Key findings include the restoration of activity against class A ESBLs with cefepime/enmetazobactam, while cefepime/taniborbactam and cefepime/zidebactam show broader inhibition of serine β-lactamases and selected metallo-β-lactamases. Additionally, zidebactam and nacubactam target penicillin-binding protein 2, enhancing bactericidal potency. Preclinical and early-phase clinical trial data indicate potent in vitro activity and favorable pharmacokinetic/pharmacodynamic (PK/PD) profiles. Specifically, the combination of cefepime with enmetazobactam has demonstrated an optimal Cmax/MIC ratio of 8–10, supporting its efficacy in treating MDR Gram-negative infections. Phase III studies are ongoing to confirm efficacy in complicated infections. Cefepime-based BL/BLI combinations are emerging as promising carbapenem-sparing agents, offering broad-spectrum activity, dual mechanisms of action, and encouraging clinical outcomes. These findings support their inclusion in antimicrobial stewardship strategies aimed at mitigating resistance. Full article

Background: Cefepime/enmetazobactam (FEP/META) is a novel fixed-dose β-lactam/β-lactamase inhibitor combination. The objective was to study the physicochemical stability of the approved daily dose in polypropylene syringes and elastomeric devices over a 24 or 72 h period to understand the feasibility of using FEP/META in prolonged infusions and its use for outpatient parenteral antibiotic therapy (OPAT). Methods: Solutions of FEP/META were prepared in 0.9% NaCl or 5% dextrose (D5W) and stored in syringes (6 g/1.5 g/48 mL) or silicone and polyisoprene elastomeric devices (EDs) at 6 g/1.5 g/120 mL and 6 g/1.5 g/240 mL: syringes were tested at 22–25 °C over a 24 h period, polyisoprene EDs at 2–8 °C over 72 h period, and silicone and polyisoprene EDs at 32 °C over a 24 h period. The solution was considered stable if it retained more than 90% of its initial concentration (Ci), no pH variation (±1 unit), no significant visual change, and with compliant subvisual examination. Liquid Chromatography–Electrospray Ionization–Quadrupole Time-of-Flight–Mass Spectrometry was utilized to identify intermediate degradation products. Results: At the daily dose, FEP/META retained >90% of its Ci up to 12 h in 0.9% NaCl and 24 h in D5W when stored in syringes. In silicone ED, stability was enhanced up to 24 h in D5W at all concentrations. The solution was chemically stable for 24 h when stored in polyisoprene ED in 0.9% NaCl at 2–8 °C. Conclusions: FEP/META combination showed prolonged stability with physicochemical integrity up to 12–24 h in all containers and conditions. It appears to be stable for prolonged infusions and for OPAT. Full article

Listeria monocytogenes is a high-risk pathogenic bacterium associated with ready-to-eat foods and poses a potential threat to consumer health. This study aimed to investigate the prevalence, characterization and genetic diversity of L. monocytogenes in ready-to-eat raw salmon and trout products obtained from physical stores and online stores in China. Out of 150 samples analyzed, 23 (15.3%) were positive for L. monocytogenes. Among these positive samples, three (12%) were from Japanese restaurants, four (16%) from farmers markets, one (2.9%) from large supermarkets and fifteen (30%) from e-commerce platforms, and only one sample showed a contamination level exceeding 100 most probable number (MPN)/g. The isolates from positive samples demonstrated a concrete public health risk through several findings: twenty-three L. monocytogenes exhibited varying degrees of cytotoxicity, ranging from 7.6% to 71.8%. Compared with the reference strain ATCC 19115, five of these isolates were highly cytotoxic, a result that was validated by mouse survival rate experiment, which also confirmed their high virulence at tested dose. All isolates were resistant to cefuroxime sodium, ceftriaxone, cefepime and nalidixic acid, and 13% showed resistance to sulphamethoxazole-trimethoprim. Three serogroups were identified, with serogroup Ⅰ.1 (1/2a, 3a) being the most prevalent (65.2%). These isolates were grouped into eight sequence types, with ST8 (34.8%) and ST87 (30.4%) dominating. All isolates carried virulence genes associated with LIPI-1 andmultiple internalin genes (inlA, inlB, inlJ and inlK), confirming their potential pathogenicity. Additionally, the isolates harbored antimicrobial resistance genes lin and FosX. The five highly virulent isolates exhibited the highest genetic similarity to J2-031 (GCA_000438645.1) and C1-387 (GCA_000438605.1). The results provided valuable information for Chinese regulatory authorities to strengthen the risk monitoring of L. monocytogenes in ready-to-eat raw salmon and trout products. Full article

Background/Objectives: Sepsis is a life-threatening condition associated with high mortality. Optimal dosing strategies for β-lactam antibiotics in sepsis remain controversial, particularly in patients with renal impairment. Cefepime (CFPM) is widely used as empiric therapy; however, its appropriate initial dosing in critically ill patients is unclear. This study aimed to evaluate whether high-dose CFPM administration during the first 48 h improves survival in patients with sepsis, irrespective of renal function. Methods: This single-center, retrospective, observational study included adult intensive care unit (ICU) patients with sepsis who received CFPM as initial therapy between January 2017 and December 2024. Patients were categorized into High-dose (12 g within 48 h; 2 g every 8 h) and Low-dose (<12 g/48 h) groups. The primary outcome was ICU survival. To address confounding, inverse probability of treatment weighting (IPTW) based on serum creatinine was applied, with sensitivity analyses using 1% trimmed and stabilized IPTW. Results: Of 122 eligible patients, 84 were analyzed (High-dose: n = 27; Low-dose: n = 57). After IPTW adjustment, high-dose CFPM was significantly associated with improved ICU survival (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.60–18.39, p = 0.0066). This association remained consistent in the 1% trimmed IPTW analysis (OR 4.07, 95% CI 1.19–13.97, p = 0.0256). Stabilized IPTW yielded a similar effect estimate, though without statistical significance (OR 5.43, 95% CI 0.72–41.16, p = 0.1017). Overall, results were consistent in direction and magnitude across models. Conclusions: High-dose CFPM administration during the initial 48 h was associated with improved ICU survival in patients with sepsis, independent of renal function. Full article

Background/Objectives: Healthcare-associated infections (HAIs), particularly those caused by multidrug-resistant (MDR) bacteria, remain a major challenge for Romanian hospitals. This study aimed to evaluate the epidemiological burden of MDR-related HAIs and to characterize the distribution of MDR bacterial isolates and their antimicrobial resistance patterns over four consecutive semesters in a Romanian tertiary care hospital. Methods: A retrospective study was conducted using data from the Electronic Registry of HAIs, clinical observation sheets, and microbiology laboratory records. An epidemiological analysis was performed on patients diagnosed with MDR-related HAIs, while a separate microbiological analysis included all MDR bacterial isolates identified during the study period. Descriptive and comparative statistical analyses were applied to assess temporal trends, pathogen distribution, and resistance profiles. Results: Of the 327 HAIs identified, 56 cases (17.13%) were caused by MDR bacteria. Most MDR-HAIs originated from the Intensive Care Unit (≈60%), with Acinetobacter baumannii and Klebsiella spp. as the predominant pathogens. Overall mortality among patients with MDR-HAIs was high (51.79%), particularly in infections caused by A. baumannii and K. pneumoniae. Microbiological analysis of MDR isolates (n = 406) revealed consistently high resistance rates to ciprofloxacin, cefepime, and ceftazidime, exceeding 95% in 2023–2024, while resistance to carbapenems surpassed 90% by the end of the study period. Temporal variability in MDR burden was observed across semesters, suggesting an influence of clinical and institutional factors. Conclusions: MDR-related HAIs represent a significant and persistent problem in Romanian acute-care hospitals, particularly in Intensive Care Units. The dominance of carbapenem-resistant A. baumannii and extended-spectrum beta-lactamase-producing and carbapenem-resistant Klebsiella spp. highlights the urgent need for strengthened antimicrobial stewardship, enhanced microbiological surveillance, and reinforced infection prevention strategies. Full article

Bacterial urinary tract infections (UTIs) are common in dogs and cats. This study examined the correlations between routine urinalysis and culture-confirmed infections and described the etiologic agents and antimicrobial susceptibility to support stewardship. In 2023, 1787 urine samples (854 dogs, 933 cats) underwent urinalysis, aerobic culture with species identification, and disk-diffusion testing per Clinical and Laboratory Standards Institute standards; non-parametric statistics with effect sizes were applied. Pyuria was the strongest correlate of infection in both species. Low urine specific gravity was associated with infection and crystal detection, and urine pH correlated weakly with growth in dogs. Nitrite positivity was strongly associated with infection in dogs but showed no diagnostic value in cats. Hematuria showed a weak inverse association in dogs and no association in cats. Females and older animals were more frequently infected, and infections were slightly more common in summer. Most episodes were monomicrobial (85%), predominantly caused by Escherichia coli (48.4% of dogs; 51.5% of cats). E. coli remained broadly susceptible to nitrofurantoin and aminoglycosides. Fluoroquinolone activity was variable. Pseudomonas spp. showed the highest susceptibility to ceftazidime, cefepime, and aminoglycosides. These findings support culture when pyuria, dilute urine, or nitrite positivity is detected and favour short, targeted empiric therapy pending results, guided by a stepwise clinical decision pathway. Full article

Background/objectives: Studies evaluating the longitudinal impact (beyond a decade) of antibiotic stewardship programs (ASPs) on the volume/quality of antibiotic prescriptions, as well as the impact on antibiotic resistance, are lacking. Since 2008, the ASP at Singapore General Hospital has implemented various strategies in the following phases: (1) initiation, (2) expansion, (3) optimisation, and (4) innovation. In this study, we aim to evaluate the volume/quality of antibiotic prescribing and susceptibility trends of clinically significant Gram-negative bacilli (GNBs), along with the evolution of ASP strategies over time. Methods: We conducted a single-centre, retrospective observational study from 2011 to 2024. Antibiotic consumption, appropriateness, and susceptibility trends of six GNBs to seven commonly used antibiotics were analysed using the Kendall tau test to identify potential monotonic trends based on aggregated rather than patient-level data. Results: We demonstrated sustained improvement in appropriateness of seven broad-spectrum IV antibiotics, accompanied by significant reductions in IV ciprofloxacin, cefepime, and ertapenem use (p < 0.05). Hospital-wide susceptibility of six GNBs to all evaluated antibiotics improved significantly (p < 0.05), except for E. coli’s susceptibility to ertapenem and Enterobacterales’s susceptibility to ciprofloxacin. Conclusions: With an evolving, multi-pronged stewardship approach, antibiotic prescribing and GNB susceptibility to most antibiotics have improved. In a rapidly evolving healthcare landscape, ASPs must remain agile, continually refining priorities and employing innovative strategies. Full article

Objectives: To investigate the phenotypic and genotypic changes of Acinetobacter baumannii collected from the tertiary oncology setting in Lithuania. Methods:A. baumannii isolates (n = 61) were collected in the years 2013–2014 (n = 28) and 2017–2019 (n = 33) from a tertiary care cancer center in Lithuania. Antimicrobial susceptibility was determined according to EUCAST and for piperacillin/tazobactam and cefepime, according to CLSI guidelines. PCR, pulsed-field gel-electrophoresis, and multi-locus sequence typing were used for resistance gene detection and genotyping. The biofilm formation ability was determined by a microtiter plate assay. Results: Of 61 A. baumannii isolates obtained, 84% (51/61) and 71% (43/61) were multi-(MDR) and extensively (XDR) drug-resistant, respectively. Carbapenem-resistant isolates comprised 77% (47/61); of these, 92% (43/47) harbored genes encoding the OXA-23-like, and 4% (2/47) OXA-24-like carbapenemases. All isolates were susceptible to colistin. Genotyping analysis revealed six groups with the highest prevalence of international clones 1 (IC1) and 2 (IC2), which dominated during 2013–2014 and 2017–2019, respectively. Notably, the A. baumannii diversity increased in 2017–2019 with the emergence of 3-LST groups G4, G8, G12, and G14, which included isolates of ST276, ST78, ST1463, and ST1336 sequence types, respectively. The IC1 and IC2 isolates displayed characteristic gene profiles aacC1, aacC2, aphA6, sul1, and armA, strA-strB, bla_TEM, respectively, whereas isolates from other groups had lesser resistance gene content. Isolates from IC2, G12, and G14 groups were strong biofilm producers; IC1, G4, and G8 isolates displayed no/weak biofilm formation capacity. Conclusions: A. baumannii from the cancer center showed a high prevalence of MDR and XDR phenotypes. Clonal dominance and diversity changed during the surveillance periods with the replacement of IC1 by IC2 clone isolates and the emergence of higher clonal diversity of isolates with stronger biofilm-forming capacity. The observed changes indicate a concerning trend of the establishment of a more virulent A. baumannii in the cancer setting. Full article

Klebsiella pneumoniae (K. pneumoniae) is a major nosocomial pathogen with increasing antibiotic resistance. Treatment failures and high mortality rates in sepsis caused by K. pneumoniae are associated with difficulties in choosing an adequate antibacterial therapy in the presence of resistance to all available antibiotics, based on the results of susceptibility tests. This study aimed to identify “weak points” in the metabolism of K. pneumoniae, to be able to use these features in the future. Ten nosocomial K. pneumoniae strains were incubated with fourteen broad-spectrum antibiotics representing major drug classes. Aromatic metabolites were analyzed using gas chromatography–mass spectrometry after 24 h exposure. Phenyllactic acid (PhLA), comprising 86% of detected phenylcarboxylic acids, served as the metabolic activity marker. Antibiotics demonstrated multidirectional effects on aromatic compound metabolism. Doxycycline, nitrofurantoin, rifampicin, and tigecycline significantly suppressed metabolic activity, confirmed by decreased PhLA levels. Conversely, meropenem, cephalosporins (ceftriaxone, cefepime, cefotaxime, and ceftazidime), ciprofloxacin, and amikacin stimulated PhLA production, suggesting that bacterial metabolic activity was maintained despite the presence of antibiotics. PhLA is a promising biomarker for quantifying K. pneumoniae’s metabolic response to antibiotics. This potentially introduces a novel approach for future investigations into resistance mechanisms and has the potential to increase the effectiveness of therapies for multidrug-resistant K. pneumoniae infections by providing an additional analytical tool to traditional susceptibility testing methodologies. Full article

Background/Objectives: Multidrug-resistant (MDR) Escherichia coli is a critical One Health challenge, with rising resistance in both humans and animals. The present study aimed to compare antimicrobial resistance (AMR) profiles of E. coli isolates from hospitalized patients and food-producing animals in Satu Mare, a county located in northwestern Romania. Methods: Between 2022–2023, 701 samples were collected, leading to 571 non-duplicate E. coli isolates (420 human, 151 animal). Human strains were recovered from 21 hospital departments and originated from feces, urine, blood, sputum, ear secretions, cerebrospinal fluid, purulent wound secretions, and puncture fluids. Animal isolates were obtained from ceca collected at local slaughterhouses serving farms in north-west Romania, including samples from turkeys, broilers, and pigs. Antimicrobial susceptibility testing was performed against eight antimicrobials (amikacin, ampicillin, cefotaxime, ceftazidime, cefepime, ciprofloxacin, gentamicin, sulfamethoxazole/trimethoprim) using standardized methods. Resistance classification followed international definitions of MDR. Statistical associations between host species and resistance were assessed with chi-square tests. Results: Resistance levels were consistently higher in E. coli strains isolated from animals compared with those from humans (p < 0.05). Among human isolates, resistance to ampicillin (41.9%), ciprofloxacin (41.4%), and sulfamethoxazole/trimethoprim (45.7%) approached, but did not exceed 50%. In contrast, E. coli strains recovered from animals showed markedly higher resistance, exceeding 50% for ampicillin (78.8%), ciprofloxacin (65.6%), and cefotaxime (55.0%). Amikacin retained full activity against all animal isolates, whereas 2.8% of human strains were resistant. Overall, multidrug resistance (MDR) was observed in 70.0% of E. coli isolates from humans and 79.7% from animals, with the highest resistance burden in pig-derived isolates. Conclusions: The study underscores the veterinary sector as a key contributor to the maintenance and spread of MDR E. coli. Even in clinically healthy animals, resistance levels exceeded those observed in human isolates. These findings emphasize the need for coordinated One Health monitoring and stricter antimicrobial use policies in livestock to reduce transmission risks across human and animal populations. Full article

Background and Objectives: Odontogenic infections are common emergencies in oral and maxillofacial surgery. They are typically polymicrobial, with aerobes guiding initial empirical therapy. However, regional data on their microbiology and resistance patterns in Romania are limited. This study aimed to characterize the aerobic microbial profile of odontogenic infections in Southwestern Romania and assess the antimicrobial susceptibility of isolated pathogens. Materials and Methods: A prospective observational study was conducted over 12 months at a tertiary referral hospital. Pus samples collected intraoperatively were cultured aerobically. Bacterial identification used biochemical methods and the VITEK 2 system. Antimicrobial susceptibility was determined by disk diffusion and automated MIC testing, interpreted according to EUCAST v13.0 (2023). Results: Of 110 patients, 96 (87.3%) yielded positive aerobic cultures, producing 97 isolates. Streptococcus spp. were predominant (49.5%), followed by coagulase-negative staphylococci (24.7%), Staphylococcus aureus (14.4%), Enterobacterales (7.2%), and Pseudomonas aeruginosa (3.1%). Streptococcus spp. remained susceptible to penicillin G (82.3%), amoxicillin–clavulanate (76.4%), and clindamycin (70.5%), but only 55.0% to erythromycin. Most S. aureus isolates were methicillin-susceptible (92.9%), while coagulase-negative staphylococci showed high methicillin resistance (59.3%) yet full susceptibility to linezolid, vancomycin, and teicoplanin. Enterobacterales were resistant to ampicillin (90%) and amoxicillin–clavulanate (65%) but remained susceptible to ceftriaxone (80%) and ciprofloxacin (85%). P. aeruginosa isolates were fully susceptible to piperacillin–tazobactam, ceftazidime, cefepime, and meropenem. Conclusions: This study provides regional data on aerobic pathogens in odontogenic infections. High resistance to penicillin and macrolides limits empirical use. Amoxicillin–clavulanate and clindamycin retain moderate activity, while glycopeptides, linezolid, and carbapenems preserved full efficacy. Surgical drainage remains central to management, and antibiotic therapy should be guided by local susceptibility patterns. These data provide baseline information to inform empirical therapy and stewardship efforts and highlight the need for multicenter studies including anaerobic and molecular analyses. Full article

Sepsis-associated acute kidney injury (SA-AKI) often requires renal replacement therapy (RRT), which markedly alters antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations broaden options against multidrug-resistant Gram-negative bacteria, but dosing during RRT remains uncertain. This review summarizes PK/PD features, extracorporeal clearance, and practical dosing considerations about ceftolozane–tazobactam, ceftazidime–avibactam, aztreonam–avibactam, cefiderocol, meropenem–vaborbactam, imipenem–relebactam, and newer agents including sulbactam–durlobactam, cefepime–enmetazobactam, and cefepime–taniborbactam. Pharmacokinetic data, RRT impact, PK/PD targets, pediatric aspects, and clinical outcomes were extracted from experimental models, case reports, and clinical studies. Drug exposure varies with RRT modality, effluent flow, membrane properties, and patient-specific factors such as augmented renal clearance, hypoalbuminemia, and fluid overload. Standard renal-adjusted dosing often yields subtherapeutic concentrations in critically ill patients. Pediatric data remain scarce and largely limited to case reports. Optimal BL/BLI use in septic patients with SA-AKI on RRT requires individualized dosing that accounts for PK/PD variability and dialysis settings. Full-dose initiation during the first 24–48 h, followed by careful adjustment, appears prudent. Therapeutic drug monitoring should be used when available, and institution-specific protocols should be integrated into stewardship programs to improve efficacy and minimize resistance. Full article