Search Results (7,685)

Objective: The aim of this case series was to investigate the safety and efficacy of vancomycin–gentamicin embedded PMMA beads (VGPB) in the setting of acute pyogenic soft tissue infections (STIs) of the extremities. Materials and Methods: A retrospective study of 19 cases diagnosed with pyogenic STIs of the lower or upper extremity in two academic institutions was conducted between January 2017 and December 2023. All patients underwent surgical debridement, systemic antibiotics and intrawound deposition of vancomycin and gentamicin embedded cement beads (2 g of vancomycin plus 1 g of gentamicin diluted in 40 g of PMMA). Upon second look (4th–7th day post-index surgery) the cement beads were removed, serum samples from the surgical site of infection and from peripheral blood were obtained and the concentration of eluted vancomycin and gentamicin was measured. Furthermore, the white blood cell count (WBC), C reactive protein serum levels (CRP) and erythrocyte sedimentation rate (ESR) were measured before the surgical debridement and after the end of the bead therapy. All patients were reevaluated after discharge with a mean follow-up of 4.4 years (range, 1 to 7.6). Results: Wound vancomycin and gentamicin levels were significantly higher than those measured in the serum (34.01 ± 4.47 μg/mL versus 11.96 ± 2.79 μg/mL, p < 0.001 and 5.75 ± 1.22 μg/mL versus 0.51 ± 0.14 μg/mL, p < 0.001 respectively). Serum vancomycin and gentamicin concentrations were below the level of toxicity and no adverse events related to antibiotic-embedded bead treatment were documented. Serum WBC, ESR and CRP levels before debridement (13,446 ± 935.7 c/μL, 42.3 ± 18.7 mm/h and 113.9 ± 20.26 mg/L respectively) were significantly higher than those after the end of treatment (7889 ± 1203.6 c/μL, p < 0.001; 30.3 ± 9.14 mm/h, p = 0.017; and 22.7 ± 6.68 mg/L, p < 0.001 respectively). Two cases (10.5%) had a local recurrence of their STIs. Both of them relapsed within 4 months after their treatment and both had Gram-negative pathogens. Conclusions: Vancomycin–gentamicin PMMA bead pouch therapy appears to be a safe and effective adjuvant treatment for pyogenic soft tissue infections, offering high local antibiotic availability without systemic adverse effects. Full article

Background: Peritoneal dialysis-associated peritonitis (PDAP) remains a major complication of peritoneal dialysis and an important cause of technique failure. Increasing evidence suggests marked inter-center variability in PDAP microbiology, with a growing contribution of Gram-negative pathogens in some settings. Methods: We performed a single-center, retrospective observational study of adult peritoneal dialysis patients with PDAP treated between January 2020 and December 2024. Episodes were defined according to International Society for Peritoneal Dialysis criteria. Clinical, microbiological, and antimicrobial treatment data were analyzed, with particular focus on relapsing peritonitis and treatment complexity. Results: Thirty-three patients were included (median age 59 years; 51.5% male). Gram-negative organisms were the most frequent causative agents (48.5%), followed by Gram-positive bacteria (21.2%), fungal pathogens (6.1%), and culture-negative episodes (6.1%). Relapsing or recurrent peritonitis occurred in 12.1% of cases and was significantly associated with increased antimicrobial treatment complexity, with all relapsing episodes requiring three or more antimicrobial agents (p = 0.02). Conclusions: Gram-negative pathogens predominated in this single-center PDAP cohort and showed trends toward greater antimicrobial treatment complexity and a higher burden of relapsing episodes; however, these findings should be interpreted cautiously due to the limited sample size and lack of statistical significance. These findings nevertheless support the need for center-specific microbiological surveillance and individualized management strategies in peritoneal dialysis-associated peritonitis. Full article

Background and Aims: Severe alcohol-associated hepatitis (SAH) can trigger unstable decompensations in cirrhosis patients. They experience high rates of emergency department visits and hospitalization. We evaluated real-world clinical outcomes following palliative-faecal microbiota transplantation (pFMT) compared to best supportive care (BSC) in this critically ill population. Patients and Methods: From July 2021 to April 2024, 28 patients on pFMT were compared with 37 on BSC. Patients on pFMT received nasoduodenal healthy donor stool infusion daily for 5-days. Patients were followed up for portal hypertension-related events, infections, hospitalizations, extrahepatic organ failure and 6- and 12-months survival. 16S rRNA sequencing on stool samples collected at baseline and on follow up were analysed for changes in relative abundance (RA) of bacterial communities. Results: Patients were matched for age, type of decompensation and liver disease severity at enrolment. Twelve-month survival was 64.3% in pFMT versus 51.4% in BSC groups. pFMT dramatically reduced hospital readmissions (mean 0.76 ± 0.76 vs. 2.29 ± 1.27, p < 0.001). Unstable decompensations beyond 3 months occurred in 14.3% of pFMT versus 64.9% of BSC (p < 0.001). Organ failures were lesser with pFMT: acute kidney injury 7.7% versus 93.8% (p < 0.001), hepatic encephalopathy 7.1% versus 68.2% (p < 0.001). Infection burden was significantly lower (53.6% vs. 83.8%, p = 0.008), particularly infections requiring admission (17.4% vs. 66.7%, p < 0.001) with pFMT. Microbiome analysis revealed progressive expansion of Gram-negative genera in BSC, and beneficial Actinobacteria in pFMT-treated patients at 3, 6, and 12 months. Conclusions: Palliative FMT represents a unique disease-modifying intervention in end-stage alcohol-related cirrhosis, preventing organ failure progression, reducing healthcare utilization, and improving survival trajectories. Full article

Background: Klebsiella pneumoniae is a Gram-negative bacterium that is found in human microbiota and in diverse environments. This opportunistic pathogen exhibits a highly variable genetic background and is responsible for a broad range of hospital- and community-acquired, multidrug-resistant infections worldwide. To track transmission pathways and understand genetic diversity, single-nucleotide polymorphism (SNP) clustering has become an essential tool. Methods: This study examines data from 2018 to 2024 in the NCBI Pathogen Detection database to determine the temporal and spatial distribution of SNP clusters in clinical K. pneumoniae across Middle East and North Africa (MENA) countries. Results: Among 1858 isolates, a heterogeneous population structure was observed. Of the 478 identified SNP clusters, a few dominant clusters accounted for 37% of the isolates, and numerous low-frequency lineages were detected. The descriptive yearly snapshot revealed a diverse representation of top clusters. Geographical analysis showed the presence of both localized and limited cross-border distribution patterns. Countries with diverse clusters also exhibit higher diversity of carbapenem- and ESBL-resistant genes. Conclusions: These findings provide valuable insights into the dominant, regionally concentrated K. pneumoniae lineage across MENA countries, assisting future genomic surveillance and efforts to combat clinical K. pneumoniae infections in this region. Full article

Background: To evaluate the potential of cefiderocol as a topical ophthalmic antibiotic by determining the susceptibility of keratitis isolates from an extensive panel of Gram-negative bacterial species to this siderophore-cephalosporin class antibiotic. Methods: Minimum Inhibitory Concentrations (MICs) of cefiderocol were determined by the broth dilution method using iron-depleted, cation-adjusted Mueller–Hinton broth. The following Gram-negative bacteria were included: Acinetobacter baumannii (n = 13), Achromobacter xylosoxidans (n = 14), Escherichia coli (n = 15), Klebsiella aerogenes (n = 14), Klebsiella pneumoniae (n = 13), Klebsiella oxytoca (n = 14), Moraxella spp. (n = 15), Proteus mirabilis (n = 13), Pseudomonas aeruginosa (n = 17), Serratia marcescens (n = 14) and Stenotrophomonas maltophilia (n = 12). MIC₉₀ values were calculated for each of the species. Results: MIC₉₀ values (µg/mL): A. baumannii (0.5), A. xylosoxidans (0.25), E. coli (0.5), K. aerogenes (1.0), K. oxytoca (0.5), K. pneumoniae (0.5), Moraxella spp. (0.5), P. mirabilis (0.25), P. aeruginosa (0.5), S. marcescens (0.5), and S. maltophilia (0.25). In total, 100% of the isolates were determined to be susceptible to cefiderocol in vitro except for A. xylosoxidans and Moraxella spp., for which there are no established breakpoints for cefiderocol. Conclusions: Cefiderocol demonstrated in vitro activity against the tested panel of Gram-negative keratitis isolates. The results of this study suggest cefiderocol may be useful for the treatment of keratitis caused by numerous Gram-negative pathogens. Further development of cefiderocol for the topical treatment of Gram-negative keratitis is indicated. Full article

Background/Objectives: Urine samples are the most frequently analyzed specimens in clinical microbiology laboratories. Although urine culture remains the gold standard for diagnosing urinary tract infections, it is time-consuming and resource-intensive. Therefore, reliable screening methods capable of predicting urine culture positivity are needed to optimize laboratory workflow. Automated urine analysis based on flow cytometry enables efficient screening and identification of samples with a low probability of bacterial infection, thereby rationalizing microbiological testing. This study evaluated the usefulness of a multivariable approach to support interpretation of flow cytometry results following the implementation of the Sysmex UF-4000 urine flow cytometer. Methods: Routinely collected urine samples from outpatients and hospitalized patients were analyzed using the UF-4000 flow cytometer, with a positivity threshold of ≥100 leukocytes/µL. Urinary parameters were compared between samples with positive and negative cultures. Multivariable logistic regression was applied to identify independent predictors of a positive urine culture. Urinary sediment parameters, including leukocyte, bacterial, fungal, and squamous epithelial cell counts, were assessed as covariates. Results: Urine samples with positive cultures showed significantly higher leukocyte counts (median 355.0, IQR 146.5–1429.4) and bacterial counts (median 9805.2, IQR 1134.3–45,011.5). Fungal and squamous epithelial cell counts differed only slightly between groups, although the differences were statistically significant (p < 0.001). Leukocyte counts were higher in urine samples from which Gram-negative bacteria were isolated compared with samples containing Gram-positive bacterial isolates (p < 0.001). The multivariable model demonstrated the most favorable overall performance, combining high sensitivity with improved specificity and the highest negative predictive value (AUC = 0.927). Optimal cut-off values were 70 leukocytes/µL and 105 bacteria/µL. Conclusions: Leukocyte and bacterial counts were the strongest predictors of positive urine culture results. A multivariable model including only these two parameters demonstrated high diagnostic accuracy and may serve as a practical screening tool to identify urine samples with a low probability of bacterial infection. The implementation of this approach could support more efficient use of urine cultures and help optimize laboratory workflow. Full article

The translation of nucleic acid amplification into practical point-of-care and biosensor-integrated diagnostics is still significantly impeded by the necessity for rapid sample preparation. For this reason, a broad comparison of seven commercially available kits for DNA/RNA extraction containing their temperature-related adjustments was performed. Extracts isolated from SARS-CoV-2-positive nasopharyngeal swabs, viral stocks, as well as laboratory-prepared suspensions of clinically relevant Gram-positive and Gram-negative bacteria were evaluated by recombinase polymerase amplification (RPA) and real-time PCR. In addition, the impact of transport media for SARS-CoV-2 samples was investigated. Extraction performance varied markedly according to the kit, pathogen, sample background. For SARS-CoV-2, rapid extraction was more effective for samples collected in viral transport medium than in inactivation buffer. Across bacterial targets, performance was species dependent, highlighting substantial differences in compatibility between simplified extraction workflows and downstream amplification. Among the rapid methods tested, a simplified QuickExtract protocol (95 °C, 5 min) provided the most consistent overall results, although it did not uniformly match the reference silica-based method for all targets. In conclusion, these results demonstrate that rapid nucleic acid extraction must be thoroughly evaluated as an essential element of the entire sample-to-answer workflow, rather than being chosen as a standalone preprocessing step for point-of-care molecular diagnostics. Full article

Klebsiella species, particularly Klebsiella pneumoniae, are among the most frequently isolated Gram-negative pathogens in surgical departments, associated with a growing trend in multidrug resistance. To identify the types of infections caused by Klebsiella spp. in a general surgery department and to analyze their antimicrobial susceptibility patterns. This retrospective observational study includes bacteriological cultures collected from surgical inpatients between October 2016 and December 2024. Only cases with confirmed Klebsiella spp. isolation were included. Specimen types, infection categories, and antibiotic susceptibility profiles were extracted and analyzed. A total of 138 Klebsiella-positive cultures were identified. Clinical characteristics were analyzed in 38 patients with complete records. The most common infection types included surgical site infections (SSIs), intra-abdominal infections, and biliary tract infections. Sensitivity was highest to carbapenems, while marked resistance was observed to ampicillin-sulbactam and third-generation cephalosporins. Some isolates exhibited ESBL or carbapenemase-producing phenotypes. Reported colistin non-susceptibility was elevated in our cohort; however, these results should be interpreted cautiously because the reference broth microdilution method was not systematically documented. The findings underscore the importance of local surveillance of Klebsiella spp. in surgical settings to info rm empirical treatment and control the spread of multidrug-resistant organisms. Full article

Background: Hospital wastewater (HWW) is a critical reservoir for carbapenem-resistant Gram-negative bacteria. Methods: Between November 2024 and August 2025, sixty 24 h composite wastewater samples were collected from five tertiary hospitals. Of the 244 carbapenem-resistant isolates recovered, 34 bla_NDM-1-positive Acinetobacter isolates were subjected to phenotypic, genotypic, and plasmid analyses. Results: Eleven species were identified among the 34 carbapenem-resistant Acinetobacter isolates, predominantly non-baumannii Acinetobacter (NBA). All isolates were carbapenem-resistant (34/34, 100%) with high-level MICs (meropenem MIC_50/90, 32/64 mg/L; imipenem MIC_50/90, >128/>128 mg/L); 21% (7/34) of isolates were resistant to colistin, and resistance to ceftazidime, cefepime, and trimethoprim-sulfamethoxazole was 100%, 94%, and 76%, respectively. Core-genome SNP analysis revealed highly similar isolates across hospitals within the same season (1-2 SNPs) or within the same hospital across seasons (19 SNPs). Genomic analysis showed that bla_NDM-1 was present in all isolates (34/34, 100%), with plasmid carriage in 85.3% (29/34); bla_OXA-58 co-occurred in 62.1% (18/29), mainly on Rep_3 plasmids (19/29), especially R3-T28 (15/29) that frequently carried bla_OXA-58 (10/15). Two unclassified plasmids co-harboring bla_NDM-1 and bla_OXA-23 were detected in Acinetobacter tandoii isolates. The bla_NDM-1 gene was embedded in a conserved Tn125-like structures with variable flanks. Conclusions: Overall, carbapenem-resistant Acinetobacter from hospital wastewater frequently carried Rep_3 plasmid-borne bla_NDM-1, especially R3-T28 and often co-occurring with bla_OXA-58, within a conserved Tn125-like core structures. These findings highlight HWW as a potential hotspot for dissemination of carbapenem resistance and support routine genomic surveillance under a One Health framework. Full article

This study reports the synthesis, spectroscopic characterization, and biological evaluation of a novel moxifloxacin hydrazide derivative (MOX-H) and its metal complexes with Co(II), Ni(II), Cu(II), VO(IV), and Gd(III). The ligand was synthesized by hydrazinolysis of moxifloxacin hydrochloride, and the resulting hydrazide was subsequently complexed with the respective metal salts. The interaction between MOX-H and the metal ions yielded the corresponding complexes, formulated as [Co(H₂O)Cl(MOX-H)₂]Cl·2.5H₂O, [Ni(H₂O)Cl(MOX-H)₂]Cl.4.5H₂O, [VO(MOX-H)₂]SO₄.3.5H₂O, [Gd (H₂O)(MOX-H)₂(NO₃)₂]NO₃.2H₂O, and [Cu(MOX-H)₂(H₂O)Cl]Cl·xH₂O (where x = 2, 2.5, 0.5, for products synthesized via template, microwave-assisted, and hydrothermal methods, respectively). The synthesized analogues were characterized by elemental analysis (CHN), FT-IR, UV-visible, and ¹H NMR spectroscopy, and mass spectrometry, as well as thermogravimetric (TG/DTG) and magnetic measurements. FT-IR spectra confirmed coordination through the hydrazide carbonyl and amine groups, while UV–visible and magnetic data indicated predominantly octahedral geometries. The thermal behavior exhibited multistep decomposition with activation parameters supporting exothermic processes. When compared to the free ligand, the metal complexes showed increased antimicrobial activity against both Gram-positive and Gram-negative bacteria and fungus species, particularly for the Co(II) and Cu(II) complexes, which showed the largest inhibition zones. The Cu(II)–MOX-H complex exhibited the lowest MIC values (4.88–9.76 µg/mL) among all tested compounds, confirming its outstanding antibacterial potency and high sensitivity compared to the free ligand and standard drug. Cytotoxicity assays demonstrated selective anticancer activity, with the Cu(II)–MOX-H complex showing the highest potency (IC₅₀ ≈ 2.95 µM against MCF-7 and IC₅₀ ≈ 0.98 µM against HepG-2), while maintaining minimal toxicity toward normal cells. These findings were corroborated by molecular docking investigations, which showed that the MOX-H complexes had substantial binding affinities (−9 to −10 kcal/mol) toward DNA topoisomerase II, consistent with their observed biological effects. Full article

Introduction: Bacterial multidrug resistance (MDR) drives treatment with expensive, toxic, or pharmacokinetically suboptimal antibiotics. Objectives: To assess the prevalence of MDR Gram-positive cocci among isolates from cardiac implantable electronic device (CIED) infections at a Polish reference center. Methods: Data come from the “EXTRACT” registry (ClinicalTrials.gov ID NCT05775783), which covers 702 transvenous lead extraction procedures. Blood samples and intraoperative swabs were collected from participants with CIED infection. Results: From 209 cases with isolated pocket infection (PI) (107, 51.2%) or systemic infections (102, 48.8%), 263 Gram-positive cocci were cultured. They were: coagulase-negative staphylococci (CoNS) (177, 67.3%), Staphylococcus aureus (62, 23.6%), enterococci (15, 5.7%), streptococci (8, 3.0%), and others (1, 0.4%). The highest MDR rate was among CoNS (46.9%). CoNS exhibited methicillin resistance (MR-CoNS) in 55.9% with co-resistance to macrolides (73.2%), lincosamides (51.0%), fluoroquinolones (56.1%), aminoglycosides (41.4%), tetracyclines (29.6%), and co-trimoxazole (29.3%). Resistance to daptomycin (5.3%) and linezolid (2.0%) in MR-CoNS was rare. The frequency of MDR S. aureus was 8.1%. Methicillin resistance in S. aureus (MRSA, 6.5%) co-occurred with resistance to macrolides/lincosamides and fluoroquinolones (100% for both) or linezolid (25.0%). All MDR staphylococci were vancomycin-susceptible. High-level aminoglycoside resistance (HLAR) in Enterococcus faecalis (53.8%) was accompanied by levofloxacin co-resistance (66.7%). Conversely, E. faecium HLAR (50.0%) strains showed 100.0% β-lactam resistance. Vancomycin-resistant enterococci (VRE) accounted for 6.7%; the VRE E. faecium strain was tigecycline- and linezolid-susceptible. Among viridans group streptococci, β-lactam and lincosamides resistance was common (40.0% for both), with 50.0% of co-resistance. Conclusions: Epidemiological data may improve the effectiveness of empirical antibiotic therapy for CIED-related infections. Full article

Despite the importance of surface microbiota in postharvest quality, the effects of mechanical damage on microbial succession in Hypsizygus marmoreus during refrigerated storage remain insufficiently understood. In this study, 16S rRNA gene and ITS amplicon sequencing were used to characterize the bacterial and fungal communities on intact and mechanically damaged H. marmoreus during 15 days of storage at 4 °C. Storage time, rather than mechanical damage, was the main driver of whole-community variation, although mechanical damage accelerated visible spoilage assessed qualitatively. Bacterial communities showed pronounced temporal turnover, shifting from early Firmicutes-rich assemblages to late-stage Proteobacteria-dominated communities, especially Pseudomonas. In contrast, fungal communities remained largely dominated by Ascomycota throughout storage, although mechanically damaged mushrooms showed a greater late-stage occurrence of opportunistic yeasts such as Candida. Predicted functional and phenotypic analyses further suggested late-stage increases in Gram-negative, aerobic, biofilm-forming, stress-tolerant, and potentially pathogenic bacterial traits. Because these traits were inferred from 16S rRNA gene-based prediction rather than measured directly, they should be interpreted cautiously. Overall, the results suggest that maintaining the physical integrity of H. marmoreus during postharvest handling may help preserve quality and delay the emergence of spoilage-associated microbial traits during refrigerated storage. Full article

Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric mucosa, with a global prevalence in humans of approximately 40%. It is likely the cause of 90% of gastric cancer (GC) cases and thus considered the most prominent driver of GC development. However, during gastric mucosal atrophy, other bacteria such as nitrate-reducing bacteria (NRB) also proliferate. In this study, we isolated NRB from patients with gastritis and GC to examine their effects on the epithelial cell cycle and production of various cytokines in monocytic cell lines. Bacterial counts (excluding H. pylori and NRB) increased with the progression of gastric mucosal atrophy and were significantly higher in patients with GC. Gastric epithelial cell lines were stimulated with isolated NRB, and the proportion of cells in each cell cycle was measured. Strains from patients with open-type gastritis progressed more rapidly through cell cycles than those from patients with GC. NRB isolated from gastric cancer had high nitrate-reducing activity. Thus, NRB may contribute to GC progression during H. pylori-induced carcinogenesis. Therefore, evaluating gastric atrophy and microbiota may be important for managing the risk of GC. Full article

Background: Infections caused by multidrug-resistant bacteria and inadequate vaccine coverage against opportunistic pathogens highlight the need for interventions that broadly and durably enhance host defense beyond antigen-specific adaptive immunity. Trained immunity, driven by metabolic and epigenetic reprogramming of innate immune cells, has been predominantly characterized using Bacille Calmette–Guérin and β-glucan, whereas its induction by Gram-negative bacteria remains poorly defined. To address this gap, we aimed to determine whether heat-killed Klebsiella pneumoniae (HK Kp) induces trained immunity through metabolic and hematopoietic reprogramming to confer heterologous antibacterial protection. Methods: HK Kp-trained murine bone marrow-derived macrophages and HK Kp-immunized C57BL/6 mice were employed to interrogate functional, metabolic, and transcriptomic reprogramming in vitro, hematopoietic progenitor remodeling in vivo, and protective efficacy against systemic Salmonella Typhimurium and Staphylococcus aureus infection. Results: HK Kp-trained macrophages showed markedly enhanced IL-1β secretion across all restimulation conditions, stimulus-dependent amplification of TNF-α responses, increased phagocytosis, and improved intracellular control of S. typhimurium, together with sustained upregulation of the glycolytic enzymes-encoding genes Hk2 and Pfkfb3. Transcriptomic profiling revealed extensive reprogramming enriched in glycolysis/gluconeogenesis and hematopoietic cell lineage pathways. In vivo, HK Kp immunization shifted bone marrow stem/progenitor compartments toward a myeloid-biased state. HK Kp-trained mice challenged with lethal S. typhimurium or S. aureus exhibited less weight loss, improved survival rates, and reduced bacterial burdens. Conclusions: Inactivated K. pneumoniae orchestrates metabolic and hematopoietic reprogramming to establish enhanced innate immune responsiveness and confer heterologous protection in murine S. typhimurium and S. aureus sepsis models, supporting its potential as a potent inducer of trained immunity. These findings establish HK Kp-based trained immunity as a promising strategy for combating multidrug-resistant and vaccine-evading pathogens. Full article

Background/Objectives: To prevent surgical site infections, it is important to consider the concentration of the administered antibiotic in the target compartment. We measured the concentrations of cefuroxime and metronidazole in peritoneal fluid with the microdialysis technique in patients undergoing surgery for secondary peritonitis (7 patients) and for inflammatory bowel disease (11 patients). Methods: All patients received 1.5 g of cefuroxime and 0.5 g of metronidazole every 8 h during the postoperative period for at least 72 h. Microdialysates covering 8-h intervals were collected, and the concentration of cefuroxime and metronidazole was measured using liquid chromatography–mass spectrometry. Results: For metronidazole, a concentration of ≥4 μg/mL was reached in all but one sample, corresponding to the minimal inhibitory concentration (MIC) for most anaerobic bacteria strains. For cefuroxime, a value of ≥4 μg/mL was reached in 88% and 93% of the samples in the peritonitis group and the IBD group, respectively, corresponding to the MIC values for most Gram-negative bacteria, and a value of ≥16 μg/mL, corresponding to the MIC value for more resistant bacteria, was reached in only 40% and 23% of the samples, respectively. Conclusions: Our results show that the peritoneal microdialysis method is feasible for studying the diffusion of antibiotics into the peritoneal cavity. Measuring the accumulative concentration of antibiotics in the peritoneal fluid corresponding to the drug administration interval may provide important information to consider alongside traditional pharmacodynamic parameters and may be relevant to achieving an optimal therapeutic effect. Full article