Search Results (29)

Cyclic triaxial tests are widely used in laboratory studies to assess the liquefaction susceptibility of soils. Although standardized procedures exist for conducting these tests, there is no universally accepted criterion for defining liquefaction. The choice of a liquefaction criterion significantly influences the interpretation of test results and subsequent engineering analyses. This study evaluates the impact of different liquefaction criteria by analyzing 42 cyclic triaxial tests performed on soil mixtures containing plastic fines. Both stress-based and strain-based liquefaction criteria were applied to assess their influence on test outcomes. The analyses focused on two key parameters: the number of loading cycles required to initiate liquefaction and the normalized dissipated energy per unit volume needed for liquefaction to occur. Results indicate that for soils susceptible to liquefaction failures, these parameters remain relatively consistent across different failure criteria. However, for soils prone to cyclic mobility failures, the number of loading cycles and the dissipated energy required for liquefaction vary significantly depending on the selected failure criterion. These findings highlight the importance of carefully selecting a liquefaction criterion, as it directly affects the assessment of soil behavior under cyclic loading. A better understanding of these variations can improve the accuracy of liquefaction susceptibility evaluations and inform geotechnical design and hazard mitigation strategies. Full article

Background/Objectives: Non-fermenting Gram-negative bacilli (NFGNB) represent a significant clinical challenge due to their intrinsic and acquired resistance, particularly in immunocompromised patients. Infections cause by NFGNB are associated with high morbidity and mortality, especially among patients with cystic fibrosis and hematologic malignancies. This study aimed to assess the in vitro susceptibility of clinically relevant NFGNB isolates to two newer antibiotics, cefiderocol and aztreonam/avibactam, and an established antibiotic, trimethoprim/sulfamethoxazole. Methods: This retrospective, monocentric study analysed 94 NFGNB isolates (30 Pseudomonas aeruginosa, 30 Acinetobacter sp., 24 Stenotrophomonas maltophilia, and 10 Burkholderia cepacia complex). Susceptibility testing for cefiderocol, aztreonam/avibactam, and trimethoprim/sulfamethoxazole was conducted using gradient strip method. MIC values were interpreted using EUCAST breakpoints, ECOFFs, or alternative criteria when necessary. Results: All S. maltophilia isolates were susceptible to cefiderocol (FCR) and aztreonam/avibactam (A/A) based on ECOFFs, with one strain resistant to trimethoprim–sulfamethoxazole (COT). Burkholderia cepacia complex strains also showed high susceptibility to FCR, with only one isolate exceeding the ECOFF for A/A, and 20% resistant to COT. All Acinetobacter sp. isolates were susceptible to FCR; however, most MIC values clustered at or just below the ECOFF value. In P. aeruginosa, one isolate was resistant to FCR, and three isolates (10%) were resistant to A/A. Interestingly, confirmed carbapenemase producers remained susceptible to both FCR and A/A. Most A/A MIC values for P. aeruginosa were just below the ECOFF. Conclusions: Cefiderocol and aztreonam/avibactam demonstrated promising in vitro activity against clinically relevant NFGNB, including carbapenem-resistant strains. These findings support their potential role as therapeutic options for difficult-to-treat infections, particularly in immunocompromised patients. Full article

Background: Cefiderocol (FDC) presents challenges in antimicrobial susceptibility testing (AST). The reference standard is the broth microdilution (BMD) method with iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB). Still, it is cumbersome for routine clinical laboratory use, while variable accuracy has been reported with available commercial systems. Variability in interpretive criteria and areas of technical uncertainty (ATUs) further complicate assessments. Methods: This review and expert opinion presents: (1) an overview of non-susceptibility to FDC and then delves into the performance of current FDC AST methods for Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex; (2) a practical decision framework to guide clinical microbiologists in making informed choices. Results and Conclusions: For Enterobacterales, including carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa, we propose disk diffusion (DD) as a preliminary screening tool to classify isolates as susceptible (S) or resistant (R). Confirmatory testing using the UMIC^® FDC system or the ID-CAMHB BMD method is recommended for R isolates. In cases of discrepancy, repeating the test with ID-CAMHB BMD is advised. Additionally, isolates falling within the ATU during DD testing should be retested using the UMIC^® system or ID-CAMHB BMD. For A. baumannii complex, since EUCAST breakpoints have not been defined yet, we propose a stepwise framework based on the first DD result: isolates with inhibition zones < 17 mm are considered non-susceptible and should be confirmed with standard BMD. Those between 17 and 22 mm require retesting with a commercial BMD method, with further confirmation recommended if S isolates with zones ≥ 23 mm may be considered S without additional testing. Full article

The Stability Toolkit for the Appraisal of Bio/Pharmaceuticals’ Level of Endurance (STABLE) is introduced and proposed as a comprehensive tool and software to evaluate the stability of active pharmaceutical ingredients (APIs) under various stress conditions. In the pharmaceutical industry, stability testing is a critical step in the drug development process, ensuring the quality, safety, and efficacy of APIs. Traditional stability tests—such as real-time, accelerated, and forced degradation testing—often face challenges, including inconsistent interpretation and implementation across different regions and organizations. STABLE addresses these challenges by providing a standardized and holistic approach to assessing drug stability across five key stress conditions: oxidative, thermal, acid-catalyzed hydrolysis, base-catalyzed hydrolysis, and photostability. Beyond its role as an evaluation tool, STABLE also serves as a practical guide for chemists, encouraging a more complete and thoughtful approach to stability studies. While many investigations focus solely on acid- and base-catalyzed hydrolysis, other critical conditions—such as photostability—are often underexplored or entirely omitted. By highlighting the importance of evaluating all relevant degradation pathways, STABLE promotes more robust and informed stability testing protocols. The index utilizes a color-coded scoring system to quantify and compare stability, facilitating consistent assessments across different APIs. This paper discusses the methodology of STABLE, including the scoring system and specific criteria applied under each condition. This tool is introduced to reflect intrinsic degradation susceptibility under forced conditions. The software is freely available as an open-source tool at bit.ly/STABLE2025, enabling broader accessibility and implementation across the pharmaceutical research community. Full article

Cyclic triaxial tests are frequently used in the laboratory to assess the liquefaction susceptibility of soils. This paper will serve a two-fold purpose: First, it will serve to explain how the mechanics of the tests represent the stresses that occur in the field. Topics covered include the differences in the stress paths for the soil in the field and in the lab, the differences in the actual stresses applied in the lab and the field, the differences between stress-controlled and strain-controlled tests, and the effects of other aspects of the testing methodology. The development of adjustment factors for converting the laboratory test results to the field is also briefly discussed. The second purpose of the paper is to serve as a guide to interpreting cyclic triaxial test results. The topics covered will include an examination of the two main liquefaction modes and the impact that the failure criteria selected have on the analysis, the differences between stress-controlled and strain-controlled test results, energy dissipation, and pore pressure generation. The author has run more than 1500 cyclic triaxial tests over the course of his career. He has found that, while the test is fairly straightforward to perform, it requires a much deeper understanding of the test mechanics and data interpretation in order to maximize the information gained from performing the test. This paper is intended as a guide, helping engineers to gain further insights into the test and its results. It has a target audience encompassing both those who are running their first tests and those who are looking to increase their understanding of the tests they have performed. Full article

The treatment of Mycobacterium avium complex (MAC) remains a clinical challenge as multidrug regimens are needed and may be limited by treatment-related toxicity. The Clinical and Laboratory Standards Institute (CLSI) endorses breakpoints for several agents used for MAC infection treatment. Amikacin has distinct breakpoints for intravenous (IV) therapy and inhaled therapy using amikacin liposome inhalation suspension (ALIS) for MAC pulmonary disease. The purpose of the present retrospective cohort study of MAC pulmonary isolates was to assess the number of amikacin non-susceptible isolates by the IV breakpoints that remain susceptible to the inhaled breakpoints. One isolate per patient per year was assessed and susceptibility was described for amikacin IV, amikacin inhaled, clarithromycin, moxifloxacin, and linezolid per the CLSI. Of the 218 isolates, 94% [204/218] tested as susceptible to amikacin per the IV breakpoints compared with 99.5% [217/218] to the inhaled breakpoints. Of the amikacin IV non-susceptible isolates, 93% [13/14] were susceptible by the inhaled breakpoints. For comparison, clarithromycin was the next most active agent followed by moxifloxacin and linezolid with 97% [211/218], 82% [178/218], and 66% [143/218] of isolates testing as susceptible to each, respectively. These data highlight the importance of laboratories to report both the IV and inhaled amikacin interpretive criteria so that clinicians do not disregard potential therapeutic options for the treatment of MAC pulmonary disease. Full article

Accurate antimicrobial susceptibility testing (AST) of cefiderocol remains a diagnostic challenge, especially in infections caused by metallo-β-lactamase (MBL)-producing Klebsiella pneumoniae. While disk diffusion offers a cost-effective alternative to broth microdilution, it is highly sensitive to factors such as media composition and the presence of atypical colony morphology. The objective of this study was to evaluate how different agar media and interpretations of isolated colonies affect the performance and reliability of cefiderocol AST by disk diffusion. A total of 50 clinical K. pneumoniae MBL isolates were tested using disk diffusion on Columbia with blood, MacConkey, and chromogenic agars from three manufacturers. Inhibition zones were compared with MICs from broth microdilution. Statistical analyses included paired t-tests and Spearman correlation to assess media effects and zone morphology impact. Variability in inhibition zone diameters was observed between media, notably with chromogenic agar. The most consistent results were obtained using Graso Biotech and Thermo Fisher Columbia with blood agar. Isolated colonies were observed in over half the samples and, depending on how they were interpreted, led to major changes in classification accuracy. Up to 64% of results fell into the EUCAST area of technical uncertainty (ATU), and categorical agreement varied across media and interpretive criteria. Disk diffusion for cefiderocol may be used in resource-limited settings but only if rigorously standardized using validated media, consistent zone reading, and ATU-aware interpretive strategies. In borderline cases or when morphological anomalies are present, broth microdilution should be considered the sole reliable method. Clinical microbiologists are advised to exercise caution with ambiguous results and seek expert or confirmatory testing when needed. Full article

Since the 1960s, cyclic triaxial tests have been utilized to assess the liquefaction susceptibility of cohesionless soils. While standardized procedures exist for conducting cyclic triaxial tests, there remains no universally accepted criterion for defining liquefaction in a laboratory test. The selection of a liquefaction criterion significantly impacts the interpretation of the test results and subsequent analyses. To quantify these effects, more than 250 cyclic triaxial tests were evaluated using both stress-based and strain-based liquefaction criteria. The analyses performed focused on two aspects of the liquefaction behavior: the number of cycles of loading required to initiate liquefaction and the amount of normalized dissipated energy per unit volume that must be absorbed into the specimen in order for it to liquefy. The findings indicate that for soils susceptible to flow liquefaction failures, the number of loading cycles required to induce liquefaction decreases. They also show that the amount of energy dissipation required to trigger liquefaction remains largely consistent across different failure criteria. However, for soils prone to cyclic mobility failures, both the number of loading cycles and the amount of dissipated energy required to cause liquefaction were found to vary significantly depending on the failure criterion applied. Full article

Ceftazidime–avibactam (CZA) is a potent broad-spectrum drug combination covering extended-spectrum β-lactamases, AmpC, and carbapenemases of class A and D, OXA-48-type producers. Rapid antimicrobial susceptibility testing is crucial for the timely de-escalation/escalation of therapy. We evaluate CZA susceptibility using the CE-IVD FASTgramneg kit (FASTinov^®), a ground-breaking 2 h assay, based on flow cytometry technology for antimicrobial susceptibility testing. The assay involved rapid bacterial extraction and purification from positive blood cultures (PBCs), followed by a 1 h 37 °C incubation and flow cytometry analysis (Cytoflex, Beckman-Coulter). The susceptibility report was generated using a proprietary software and interpreted using EUCAST and CLSI 2024 criteria. Sensitivity and specificity were calculated against a reference standardized method (disk diffusion) according to ISO20776-2:2021. Overall, 135 Enterobacterales and 73 Pseudomonas aeruginosa isolates were studied. Thirty-four isolates were resistant to CZA, including six P. aeruginosa and 28 Enterobacterales (24 metallo-beta-lactamase producers, three KPC variants, and one co-producing KPC+NDM). Sensitivity and specificity reached 100% when using EUCAST and CLSI criteria compared with the reference method. The FASTinov ultra-rapid susceptibility assay for CZA demonstrated excellent results, potentially enabling de-escalation/escalation even before the second dose. Combining the speed of a molecular assay with the comprehensive information of a phenotypic test offers valuable insights for treatment decisions. Full article

Due to bacterial resistance to antimicrobials, antibiotic therapy for urinary tract infections (UTIs) has become a major challenge for clinicians. The present work aimed to compare the antimicrobial susceptibility profiles of 53 uropathogenic Escherichia coli (UPEC) isolates, assessed using the disk diffusion method and two automated systems (PHOENIX BD™ and VITEK2), with interpretations based on CLSI and BrCAST guidelines. Twenty-five antibiotics were tested to assess differences in susceptibility profiles. Statistical tools, including Kappa coefficient analysis and chi-square tests, were applied to assess concordance and significance between methods. Among the main discrepancies found, BrCAST has classified a greater number of UPEC isolates as resistant to more than half of the antibiotics tested by the disk diffusion method, when compared to CLSI. Although faster, the PHOENIX BD and VITEK2 automated systems exhibited significant discrepancies, with divergences observed for half of the antimicrobials tested. Both automated methods showed discrepancies compared to the disk diffusion method under CLSI and BrCAST guidelines. PHOENIX BD classified some isolates resistant by DD/CLSI as susceptible, while VITEK2 misclassified 25% to 50% of the antimicrobials tested. Conversely, VITEK2 also classified some isolates susceptible to DD/CLSI as resistant to 25% of the antimicrobials tested. Regarding DD/BrCAST, PHOENIX BD classified resistant isolates as susceptible (to 50% of the antimicrobials tested). In comparison, VITEK2 classified resistant isolates as susceptible and susceptible isolates as resistant (25% of the antimicrobials for both). These findings highlight the need for careful selection of susceptibility testing methods, as variations in interpretive criteria between CLSI and BrCAST could impact clinical decision-making. This study underscores the importance of methodological consistency in accurately informing antibiotic therapy in UTI management, especially in the face of rising resistance. Full article

Pregnant ewes are susceptible to hypoglycemia and ketosis; therefore, monitoring glycemic status is extremely important. Portable blood glucose meters (PBGMs) can assist in quickly and conveniently identifying glycemic disturbances in this species, provided that they meet the criteria of analytical accuracy. This study evaluated the performance of a human PBGM (Accu-Chek Performa^®, Roche Diagnostics, Basel, Switzerland) in the glycemic evaluation of 34 pregnant ewes at days 90 and 120 of pregnancy in comparison with the results of glycemia determination by a reference method (RM). The device showed a high positive correlation (r = 0.71, 95%CI = 0.57–0.82, p < 0.0001) with the RM; however, 96.6% of the PBGM results (58.5 ± 9.82 mg/dL) were higher (p < 0.0001) than those obtained in the laboratory (48.6 ± 9.31 mg/dL). The PBGM tested was considered analytically inaccurate according to ISO 15197:2013, which states that when glucose levels are below 100 mg/dL, 95% of the measurements should deviate by no more than 15 mg/dL from the RM value, and 1/3 of the PBGM results were above this limit. Hypoglycemia (<50 mg/dL) was documented in 60.29% of samples tested on with the RM, but only 17.64% of results were below 50 mg/dL using the PBGM. Due to these limitations, Accu-Check Performa^® results should be interpreted cautiously in pregnant sheep suspected of hypoglycemia. Full article

Background: Fosfomycin (FOS) is an older antimicrobial agent newly rediscovered as a possible treatment for infections with limited therapeutic options (e.g., Gram-negative bacteria with difficult-to-treat resistance, DTR), especially in intravenous form. However, for correct usage of FOS, it is necessary to have a reliable susceptibility testing method suitable for routine practice and robust interpretation criteria. Results: The results were interpreted according to 2023 interpretation criteria provided by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). DTR Gram-negatives were more likely to be resistant to FOS (45% in Enterobacterales and 20% in P. aeruginosa) than non-DTR (10% and 6.7%, resp.). All isolates of S. aureus were susceptible to FOS. In Gram-negatives, all agreement values were unacceptable. Etest^® performed better in the DTR cohort (categorical agreement, CA, 80%) than in the non-DTR cohort (CA 45.7%). There were no very major errors (VREs) observed in P. aeruginosa. S. aureus had surprisingly low essential agreement (EA) rates (53% for MRSA and 47% for MSSA) for Etest^®, but categorical agreement was 100%. Methods: A total of 130 bacterial isolates were tested and compared using the disc diffusion method (DD) and gradient strip method (Etest^®) with the reference method (agar dilution, AD). The spectrum of isolates tested was as follows: 40 Enterobacterales (20 DTR vs. 20 non-DTR), 30 Pseudomonas aeruginosa (15 DTR vs. 15 non-DTR), and 60 Staphylococcus aureus (30 methicillin-susceptible, MSSA, vs. 30 methicillin-resistant, MRSA). Conclusions: Neither one of the tested methods was identified as a suitable alternative to AD. It would be beneficial to define more interpretation criteria, at least in some instances. Full article

Background: The rise of multi-drug-resistant Gram-negative bacteria necessitates the development of new antimicrobial agents. Cefiderocol shows promising activity by exploiting bacterial iron transport systems to penetrate the outer membranes of resistant pathogens. Objectives: This study evaluates the efficacy of cefiderocol testing methods and trailing effect impact using a ComASP^® Cefiderocol panel, disk diffusion (DD), and MIC test strips (MTS) compared to iron-depleted broth microdilution (ID-BMD). Methods: A total of 131 Gram-negative strains from clinical samples was tested by commercial methods and the gold standard. Results were interpreted as per 2024 and 2023 EUCAST guidelines. Results: ID-BMD revealed high cefiderocol susceptibility among Enterobacterales and Pseudomonas aeruginosa, with one Klebsiella pneumoniae isolate being resistant. Acinetobacter baumannii exhibited higher MIC values, particularly considering trailing effects that complicated MIC readings. ComASP^® showed 97% categorical agreement (CA) and 66% essential agreement (EA) with ID-BMD for Enterobacterales but failed to detect the resistant K. pneumoniae. DD tests demonstrated variable CA (72% or 93%), and 38% or 34% of strains within the ATU according to EUCAST Breakpoint Tables v13.0 and 14.0, respectively, with major errors only. MTS for P. aeruginosa had 100% CA but 44% EA, and often underestimated MIC values. Conclusions: The study emphasizes the need for standardized criteria to address trailing effects and ATU and highlights the discrepancies between testing methods. While cefiderocol resistance remains rare, accurate susceptibility testing is crucial for its effective clinical use. The findings suggest that current commercial tests have limitations, necessitating careful interpretation and potential supplementary testing to guide appropriate antibiotic therapy. Full article

Background: The treatment of non-tuberculous mycobacterial (NTM) infections is challenging because of the difficulty in obtaining phenotypic (pDST) and/or molecular (mDST) drug susceptibility testing and the need of a multi-drug regimen. Objectives: The objective was to describe the in vitro susceptibility patterns of various NTM species through an analysis of susceptibility results obtained on isolates collected between 2018 and 2023. Methods: Species identification and mutations in rrs or rrl genes (mDST) were identified by a line probe assay, while the pDST was performed by broth microdilution and interpreted according to CLSI criteria. Results: We analysed 337 isolates of NTM belonging to 15 species/subspecies. The Mycobacterium avium complex (MAC) was the most common (62%); other species identified included M. gordonae (11%), M. kansasii (5%), the M. abscessus complex (8%), M. chelonae (6%), and M. fortuitum (2%). The results of pDST (claritromycin and amikacin) and mDST (rrl and rrs genes) on 66 NTM strains showed that while wild-type rrl and rrs occurred in 86.3% and 94% strains, respectively, the pDST showed 88% sensitivity for clarithromycin and 57.5% for amikacin. The main incongruity was observed for macrolides. Conclusions: Most NTM are likely to be susceptible to macrolides and aminoglycosides. The molecular identification of resistant genotypes is accurate and strongly recommended for optimal patient management. Full article

Background/Objectives: Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) commonly found on human skin. Unlike other CoNS, S. lugdunensis has a notable potential to cause severe infections comparable to Staphylococcus aureus. This study aimed to characterize the clinical and microbiological profile of patients with S. lugdunensis skin infections at a single center. Methods: We conducted a retrospective analysis of patient records from the Dermatology Department of the University Hospital of Heraklion, Greece, covering the period from January 2014 to January 2024. Patients’ clinical presentations, demographics, infection sites, comorbidities, prior infections, antimicrobial treatments, and therapeutic responses were examined. Specimens were collected, transported, and processed according to standardized microbiological protocols. Bacterial identification and antibiotic susceptibility testing were performed using the Vitek 2 automated system and MALDI-TOF MS, with results interpreted according to Clinical and Laboratory Standards Institute (CLSI) criteria. Results: A total of 123 skin specimens positive for S. lugdunensis were analyzed. The cohort comprised 62 males (50.4%) and 61 females (49.6%), with a mean age of 40.24 ± 20.14 years. Most specimens were collected from pus (84%), primarily from below the waist (66.7%). Hidradenitis suppurativa (26%) was the most common condition associated with S. lugdunensis, followed by folliculitis, abscesses, ulcers, cellulitis, and acne. Co-infections with other bacteria were noted in 49.6% of cases, and 25.2% of infections were nosocomially acquired. The majority of patients (65%) received systemic antibiotics, predominantly amoxicillin/clavulanic acid, cefuroxime axetil, and doxycycline, with a cure rate of 100%. All isolates were susceptible to several antibiotics, though resistance to penicillin (28.5%) and clindamycin (36%) was observed. Conclusions: S. lugdunensis is a significant pathogen in skin infections, capable of causing severe disease. The high cure rate demonstrates the effectiveness of appropriate antibiotic therapy. Continued monitoring and antimicrobial stewardship are essential to manage resistance and ensure effective treatment. Full article