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UNLABELLED: Piscine lactococcosis is a significant threat to cultured and wild fish populations worldwide. The disease typically presents as a per-acute to acute hemorrhagic septicemia causing high morbidity and mortality, recalcitrant to antimicrobial treatment or management interventions. Historically, the disease was attributed to the gram-positive pathogen Lactococcus garvieae. However, recent work has revealed three distinct lactococcosis-causing bacteria (LCB)-L. garvieae, L. petauri, and L. formosensis-which are phenotypically and genetically similar, leading to widespread misidentification. An update on our understanding of lactococcosis and improved methods for identification are urgently needed. To this end, we used representative isolates from each of the three LCB species to compare currently available and recently developed molecular and phenotypic typing assays, including whole-genome sequencing (WGS), end-point and quantitative PCR (qPCR) assays, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), API 20 Strep and Biolog systems, fatty acid methyl ester analysis (FAME), and Sensititre antimicrobial profiling. Apart from WGS, sequencing of the gyrB gene was the only method capable of consistent and accurate identification to the species and strain level. A qPCR assay based on a putative glycosyltransferase gene was also able to distinguish L. petauri from L. garvieae/formosensis. Biochemical tests and MALDI-TOF MS showed some species-specific patterns in sugar and fatty acid metabolism or protein profiles but should be complemented by additional analyses. The LCB demonstrated overlap in host and geographic range, but there were relevant differences in host specificity, regional prevalence, and antimicrobial susceptibility impacting disease treatment and prevention. IMPORTANCE: Lactococcosis affects a broad range of host species, including fish from cold, temperate, and warm freshwater or marine environments, as well as several terrestrial animals, including humans. As such, lactococcosis is a disease of concern for animal and ecosystem health. The disease is endemic in European and Asian aquaculture but is rapidly encroaching on ecologically and economically important fish populations across the Americas. Piscine lactococcosis is difficult to manage, with issues of vaccine escape, ineffective antimicrobial treatment, and the development of carrier fish or biofilms leading to recurrent outbreaks. Our understanding of the disease is also widely outdated. The accepted etiologic agent of lactococcosis is Lactococcus garvieae. However, historical misidentification has masked contributions from two additional species, L. petauri and L. formosensis, which are indistinguishable from L. garvieae by common diagnostic methods. This work is the first comprehensive characterization of all three agents and provides direct recommendations for species-specific diagnosis and management.

Background: Linezolid is commonly used to treat severe and/or resistant Gram-positive infections. Few studies have assessed its pharmacokinetic (PK) target attainment in pediatrics. Objective: To evaluate the percentage of pediatrics achieving the PK targets of linezolid with standard dosing regimens and to assess the incidence and risk factors associated with its hematologic toxicity. Methods: This prospective observational study included pediatric patients aged 0–14 who received linezolid for suspected or proven Gram-positive infections. Linezolid trough concentrations and the 24-h area under the curve (AUC24) were estimated, and hematologic toxicity was assessed. Results: Seventeen pediatric patients (5 neonates and 12 older pediatrics) were included. A wide variability was observed in linezolid's trough and AUC24 (ranging from 0.5 to 14.4 mg/L and from 86 to 700 mg.h/L, respectively). The median AUC24 was significantly higher in neonates than older pediatrics (436 [350–574] vs. 200 [134–272] mg,h/L, P = 0.01). Out of all patients, only 41% achieved adequate drug exposure (AUC24 160–300 mg.h/L and trough 2–7 mg/L), with 24% having subtherapeutic, and 35% having higher-than-optimal exposures. Hematological toxicity was observed in 53% of cases. Identified risk factors include treatment duration over 7 days, baseline platelet counts below 150 × 109/L, sepsis/septic shock, and concomitant use of meropenem. Conclusions: Linezolid's standard dosing failed to achieve its PK targets in approximately half of our pediatric cohort. Our findings highlight the complex interplay between the risk factors of linezolid-associated hematological toxicity and underscore the importance of its vigilant use and monitoring, particularly in pediatrics with concomitant multiple risk factors. [ABSTRACT FROM AUTHOR]

Background & objective: The Infectious Disease Society of America guidelines recommend vancomycin trough levels of 15–20 mg/L for severe methicillin-resistant Staphylococcus aureus. However, recent consensus guidelines of four infectious disease organizations no longer recommend vancomycin dosing using minimum serum trough concentrations. Therefore, this study aimed to evaluate the impact of low (< 15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough levels on clinical outcomes in adult patients with sepsis or gram-positive bacterial infections. Method: A systematic literature review from inception to December 2022 was conducted using four online databases, followed by a meta-analysis. The outcomes of interest included clinical response/efficacy, microbial clearance, length of ICU stay, treatment failure, nephrotoxicity, and mortality. Results: Fourteen cohort studies met the inclusion criteria from which vancomycin trough concentration data were available for 5,228 participants. Our analysis found no association between vancomycin trough levels and clinical response [OR = 1.06 (95%CI 0.41–2.72], p = 0.91], microbial clearance [OR = 0.47 (95% CI 0.23–0.96), p = 0.04], ICU length of stay [MD=-1.01 (95%CI -5.73–3.71), p = 0.68], or nephrotoxicity [OR = 0.57 (95% CI 0.31–1.06), p = 0.07]. However, low trough levels were associated with a non-significant trend towards a lower risk of treatment failure [OR = 0.89 (95% CI 0.73–1.10), p = 0.28] and were significantly associated with reduced risk of all-cause mortality [OR = 0.74 (95% CI 0.62–0.90), p = 0.002]. Conclusion: Except for a lower risk of treatment failure and all-cause mortality at low vancomycin trough levels, this meta-analysis found no significant association between vancomycin trough levels and clinical outcomes in adult patients with sepsis or gram-positive bacterial infections. [ABSTRACT FROM AUTHOR]

Background: Aneurysms of the internal iliac artery in infective endocarditis are extremely rare, with few cases reported in the literature, and Rothia dentocariosa infective endocarditis are rare. Analysis: We describe the case of a previously healthy 62-year-old male who presented a Rothia dentocariosa infective endocarditis. Results: Multi-modality imaging revealed an aneurysm of the left internal iliac artery, which was clinically silent. The patient was treated with antibiotics and semi-emergent bioprosthesis aortic valve replacement. Follow-up multi-modality imaging showed the regression of the aneurysm. Conclusion: This case shows that an aneurysm of the internal iliac artery in infective endocarditis can regress under antibiotherapy alone. This case also highlights the ability of PET/CT to identify and follow such an aneurysm. [ABSTRACT FROM AUTHOR]

Introduction: Different initial manifestations of peritoneal dialysis-associated peritonitis (PDAP) may depend on the type of pathogenic organism. We investigated the association between the clinical characteristics of PDAP and susceptibility to vancomycin and investigated the possibility of using vancomycin monotherapy alone as an initial treatment regimen for some PDAP patients to avoid unnecessary antibiotic exposure and secondary infection. Methods: Patients with culture-positive PDAP were retrospectively analyzed and divided into two groups: peritonitis with only cloudy effluent (PDAP-cloudy) or with cloudy effluent, abdominal pain and/or fever (PDAP-multi). The bacterial culture of PD effluent and antibiotic sensitivity test results were compared between groups. Logistic regression was used to investigate factors predicting susceptibility to vancomycin. Results: Of 162 episodes of peritonitis which had a positive bacterial culture of PD fluid, 30 peritonitis were in the PDAP-cloudy group, and 132 peritonitis were in the PDAP-multi group. Thirty (100%) peritonitis in the PDAP-cloudy group had gram-positive bacterial infections, which was significantly greater than that in the PDAP-multi group (51.5%) (P < 0.001). Twenty-nine (96.7%) peritonitis in the PDAP-cloudy group were susceptible to vancomycin, compared to 67 (50.8%) in the PDAP-multi group (P < 0.001). The specificity of PDAP-cloudy for vancomycin-sensitive peritonitis was 98.48%. Only one patient (3.3%) in the PDAP-cloudy group experienced vancomycin-resistant peritonitis caused by Enterococcus gallinarum, which could neither be covered by vancomycin nor by the initial antibiotic regimen recommended by the current ISPD guidelines. The presence of only cloudy effluent was an independent predictor of susceptibility to vancomycin according to multivariate analysis (OR = 27.678, 95% CI 3.191-240.103, p = 0.003), in addition to PD effluent WBC counts (OR = 0.988, 95% CI 0.980–0.996, p = 0.004), diabetes mellitus (OR = 3.646, 95% CI 1.580–8.416, p = 0.002), first episode peritonitis (OR = 0.447, 95% CI 0.207–0.962, p = 0.039) and residual renal creatinine clearance (OR = 0.956, 95% CI 0.918–0.995, p = 0.027). Addition of these characteristics increased the AUC to 0.813 (95% CI 0.0.749–0.878, P < 0.001). The specificity of presenting with only cloudy effluent for vancomycin-sensitive peritonitis was 98.48%. Conclusions: Cloudy dialysate, as the only symptom at PDAP onset, was an independent predictor of vancomycin-sensitive PDAP, which is an important new insight that may guide the choice of initial antibiotic treatment. [ABSTRACT FROM AUTHOR]

Background: Postoperative infection after the Latarjet procedure, ranging from 1% to 6%, can compromise the functional outcome of young athletes. Cutibacterium acnes is a main pathogen as a consequence of an intraoperative contamination. Purpose: To evaluate intraoperative contamination with C. acnes and the effectiveness of the local application of vancomycin during the Latarjet procedure. Study Design: Cohort study; Level of evidence, 2. Methods: This was a single-center study including 75 patients (mean age, 26 years; range, 15-55 years) operated on for anterior shoulder instability with the primary open Latarjet procedure; they underwent the same protocol of skin preparation and preoperative prophylactic antibiotics. Three groups of 25 patients were created and divided sequentially, without the results of each group being known before the end of the study: group A (5 mg/mL of vancomycin), group B (20 mg/mL of vancomycin), and group C (control group with no vancomycin). Swab samples of the coracoid were taken before sectioning the coracoid process (time 1) and after its preparation (time 2). The coracoid was then wrapped in gauze impregnated with different concentrations of vancomycin, except for group C. A final sample (time 3) was taken before screwing the bone block onto the glenoid. All samples were cultured for 21 days, and patients underwent clinical and radiological follow-up for 6 months. Results: The C. acnes contamination rates at times 1, 2, and 3 were 25%, 44%, and 45%, respectively, without significant difference. There was no significant difference between groups A and B with respect to the number of positive cultures at each time point. Of 9 positive cultures at time 1, all were still positive at time 3 in group A, whereas 3 of 5 were negative in group B (P =.027). The rate of C. acnes at time 3 in the control group was higher than that in the 2 other groups (68% vs 44% for group A and 20% for group B; P =.003). Body mass index was the only prognostic factor for a C. acnes –positive culture (26.05 ± 3.39 vs 23.34 ± 2.33; P =.018). No clinical infection was reported at the 6-month postoperative follow-up. Conclusion: The rate of C. acnes contamination ranged from 25% to 68% during the open Latarjet procedure in young athletes. Vancomycin reduced the bacterial contamination when it was used at high concentrations in a gauze wrap on the coracoid. The type of C. acnes detected and its clinical implications remain to be studied. [ABSTRACT FROM AUTHOR]

Purpose: The diagnosis of liver abscess (LA) caused by Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB) depends on ultrasonography, but it is difficult to distinguish the overlapping features. Valuable ultrasonic (US) features were extracted to distinguish GPB-LA and GNB-LA and establish the relevant prediction model. Materials and Methods: We retrospectively analyzed seven clinical features, three laboratory indicators and 11 US features of consecutive patients with LA from April 2013 to December 2023. Patients with LA were randomly divided into training group (n=262) and validation group (n=174) according to a ratio of 6:4. Univariate logistic regression and LASSO regression were used to establish prediction models. The performance of the model was evaluated using area under the curve(AUC), calibration curves, and decision curve analysis (DCA), and subsequently validated in the validation group. Results: A total of 436 participants (median age: 55 years; range: 42– 68 years; 144 women) were evaluated, including 369 participants with GNB-LA and 67 with GPB-LA, respectively. A total of 11 predictors by LASSO regression analysis, which included gender, age, the liver background, internal gas bubble, echogenic debris, wall thickening, whether the inner wall is worm-eaten, temperature, diabetes mellitus, hepatobiliary surgery and neutrophil(NEUT). The performance of the Nomogram prediction model distinguished between GNB-LA and GPB-LA was 0.80, 95% confidence interval [CI] (0.73– 0.87). In the validation group, the AUC of GNB was 0.79, 95% CI (0.69– 0.89). Conclusion: A model for predicting the risk of GPB-LA was established to help diagnose pathogenic organism of LA earlier, which could help select sensitive antibiotics before the results of drug-sensitive culture available, thereby shorten the treatment time of patients. [ABSTRACT FROM AUTHOR]

The flora of Azerbaijan is represented by one species of the Macrosciadium genus: Macrosciadium alatum, belonging to the Apiaceae family. It is commonly found in the Greater and Lesser Caucasus regions of Azerbaijan, as part of subalpine meadow plant communities. M. alatum is characterized by its robust, thick, tuberous roots, long-petioled and several times pinnately divided leaves, numerous (30–50) white umbels, and oval-shaped fruits. The primary objective of this research is to determine the antimicrobial potential of the aqueous extract obtained from M. alatum against both Gram-negative and Gram-positive bacteria. The plant preparations utilized in in vitro experiments were in the form of maceration, infusion, and hydrodistillation as aqueous extracts. M. alatum extract exhibited maximum (measuring 22.3 ± 1.4 mm) inhibition zones against bacteria (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus, and Salmonella enteritidis) strains. Following exposure to the M. alatum plant extract, a significant reduction in bacterial cell cytoplasmic pH was observed (p≤0.04). In order to investigate the antimicrobial effects of the plant extract, commonly accepted procedures were followed using well-known bacterial strains, including S. aureus, B. cereus, E. coli, S. enteritis and P. aeruginosa, which are principal causative agents of purulent-inflammatory processes. The 20 % aqueous extract was used. The conducted experiment to determine the impact of the plant extract on microorganisms revealed that the extract significantly affects the bacterial cell membrane. Specifically, there is a decrease in pH, and hyperpolarization of the cell membrane occurs. The efficacy of the preservative effect is highly dependent on the environmental pH. 1. The 20 % aqueous extract from exhibited antimicrobial activity and effectively preventing the development of foodborne pathogens and putrefactive microorganisms. 2. A 20 % aqueous extract of M. alatum exhibits antimicrobial activity, effectively inhibiting the growth of foodborne pathogens and spoilage microorganisms. 3. Extract led to an increase in H+ concentration within bacterial cell cytoplasm, surpassing the OH− concentration. 4. M. alatum species has a significant inhibitory effect on the growth of microorganisms such as S. aureus, E. coli, P. aeruginosa, and S. enteritidis. The results suggest that the extract from M. alatum possesses antimicrobial properties, making it a potential candidate for use as a natural food preservative. The observed hyperpolarization of the cell membrane and pH reduction further support its potential as an effective antibacterial agent. [ABSTRACT FROM AUTHOR]

Background: cultivated and wild plants are used to treat different ailments. The Astragalus genus is found in temperate and dry climates; thus, it is found in Egypt and the arab world. Astragalus caprinus has a good amount of bioactive chemicals, which may help explain its therapeutic effects in reducing the risk of consequences from disease. Method: The phytochemical investigation of the herb and roots of Astragalus caprinus L. included the analytical characterization for the petroleum ether components by GC/MS, unsaponifiable matter (unsap. fraction), and fatty acids (FAME) investigation by GLC analysis. Main flavonoids were chromatographically isolated from ethyl acetate and n-butanol extracts. In vitro antimicrobial activity has been tested against the Gram-positive bacteria Staphylococcus aureus and Streptococcus mutans for different plant extracts, the Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumonia, the fungus Candida albicans and Aspergillus niger, and the Escherichia coli bacterium. Metabolite cytotoxicity was examined using the MTT assay against HepG-2 (human liver carcinoma) and MCF-7 (breast carcinoma). Results: Identifying the important components of the herb and root petroleum ether extracts was achieved. Using column chromatography, luteolin, cosmosiin (apigenin-7-O-glucoside), and cynaroside (luteolin-7-O-glucoside) were separated and identified using UV, NMR, and Mass Spectroscopy. Root extracts displayed potential antimicrobial activity against most of the tested pathogens. Both extracts (herb and roots) were active against the MCF-7 cell line and HepG-2 cell line with IC50 62.5 ± 0.64 and 72.4 ± 2.3 µg/ml, and 75.9 ± 2.5 and 96.8 ± 4.2 µg/ml, respectively. Conclusion: Astragalus caprinus seems to be a promising source of bioactive compounds that could potentially aid in preventing disease complications and address common health issues in developing countries. Moreover, the various parts of this plant could be utilized as natural raw materials for producing health-boosting products that could address common health issues in developing countries. [ABSTRACT FROM AUTHOR]

Gram-positive bacterial infections present a major clinical challenge, with methicillin- and vancomycin-resistant strains continuing to be a cause for concern. In recent years, semisynthetic vancomycin derivatives have been developed to overcome this problem as exemplified by the clinically used telavancin, which exhibits increased antibacterial potency but has also raised toxicity concerns. Thus, glycopeptide antibiotics with enhanced antibacterial activities and improved safety profiles are still necessary. We describe the development of a class of highly potent semisynthetic glycopeptide antibiotics, the guanidino lipoglycopeptides, which contain a positively charged guanidino moiety bearing a variable lipid group. These glycopeptides exhibited enhanced in vitro activity against a panel of Gram-positive bacteria including clinically relevant methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant strains, showed minimal toxicity toward eukaryotic cells, and had a low propensity for resistance selection. Mechanistically, guanidino lipoglycopeptides engaged with bacterial cell wall precursor lipid II with a higher binding affinity than vancomycin. Binding to both wild-type d-Ala-d-Ala lipid II and the vancomycin-resistant d-Ala-d-Lac variant was confirmed, providing insight into the enhanced activity of guanidino lipoglycopeptides against vancomycin-resistant isolates. The in vivo efficacy of guanidino lipoglycopeptide EVG7 was evaluated in a S. aureus murine thigh infection model and a 7-day sepsis survival study, both of which demonstrated superiority to vancomycin. Moreover, the minimal to mild kidney effects at supratherapeutic doses of EVG7 indicate an improved therapeutic safety profile compared with vancomycin. These findings position guanidino lipoglycopeptides as candidates for further development as antibacterial agents for the treatment of clinically relevant multidrug-resistant Gram-positive infections. Editor's summary: Vancomycin and its second-generation lipoglycopeptide derivatives work mainly by binding the peptidoglycan precursor lipid II to inhibit cell wall synthesis in Gram-positive bacteria. However, antibiotic resistance and safety concerns remain, and improved antibiotics are still needed. Van Groesen et al. report the optimization of a series of vancomycin-derived antibiotic compounds: lipoglycopeptides that bear a guanidino lipid group. This modification promoted stronger binding to the cell wall precursor lipid II, resulting in potent antibacterial activity while also showing less toxicity to mammalian cells than second-generation vancomycin derivatives. The lead candidate compound outperformed vancomycin in improving therapeutic outcome in mouse models of S. aureus thigh infection and sepsis, suggesting that guanidino lipoglycopeptides may benefit from further development. —Catherine Charneski [ABSTRACT FROM AUTHOR]

Introduction: This study aims to investigate the changing epidemiology and antimicrobial susceptibility of bacteria isolated from cerebrospinal fluid (CSF) in the Shandong region. Methodology: We conducted a retrospective analysis of bacterial distribution and resistance patterns in CSF samples, utilizing data from the SPARSS network and analyzed with WHONET 5.6 software. Results: A total of 3968 pathogenic bacterial strains were isolated, consisting of 70.6% Gram-positive bacteria, 27.2% Gram-negative bacteria, and 0.2% fungi. The six most commonly detected bacteria were coagulase-negative staphylococcus, Acinetobacter baumannii, Klebsiella pneumoniae, Streptococcus pneumoniae, Escherichia coli, and staphylococcus aureus. Analysis revealed gender and seasonal variations in the distribution of CSF pathogens, with a higher incidence observed in males and during autumn compared to other seasons. The susceptibility profiles of these bacterial species varied significantly, with many exhibiting multidrug resistances. A. baumannii showed a high resistance rate to cephalosporins and carbapenems but was sensitive to tigecycline and polymyxins. For treating multidrug-resistant A. baumannii infections, polymyxin-based combinations with tigecycline or sulbactam are recommended for adults, while tigecycline combined with meropenem is suggested for children. Enterobacteriaceae species were generally sensitive to carbapenems, such as meropenem and other carbapenems that can penetrate the blood-brain barrier can be recommended. Linezolid and vancomycin are the first choice for treating common gram-positive bacterial infections. Conclusions: The high resistance rates observed among common CSF isolates and their varied distributions across different demographics highlight the necessity for customized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Marginal zone lymphomas of mucosa-associated lymphatic tissues (MZL of MALT) are a group of indolent B-cell neoplasms, which are thought to arise from chronic antigenic stimulation of B-cells either due to underlying chronic infection or autoimmune disease. Little is known about potential causative pathogens in pulmonary MZL (PMZL), although some data suggests a potential role of Achromobacter (A.) xylosoxidans. Methods: An index case of chronic pulmonary colonisation with Tropheryma (T.) whipplei and subsequent development of PMZL was identified by T. whipplei specific PCR and metagenomic next genome sequencing (mNGS). This case prompted a retrospectively conducted analysis of T. whipplei-specific PCRs in lung tissue from PMZL patients (n = 22), other pulmonary lymphomas, and normal controls. Positive results were confirmed by mNGS. A systematic search for T. whipplei and A. xylosoxidans in our in-house mNGS dataset comprising autopsy lungs, lung biopsies and lung resection specimens (n = 181) was subsequently performed. Results: A 69-year-old patient presented with weight loss and persistent pulmonary consolidation. Subsequent mNGS analysis detected T. whipplei in the resected lung specimen. An antibiotic regimen eventually eliminated the bacterium. However, the consolidation persisted, and the diagnosis of PMZL was made in a second lung resection specimen. A second case of T. whipplei-associated PMZL was subsequently detected in the retrospectively analysed PMZL cohort. Both cases showed comparatively few mutations and no mutations in genes encoding for NF-κB pathway components, suggesting that T. whipplei infection may substitute for mutations in these PMZL. None of the samples in our in-house dataset tested positive for T. whipplei. In contrast, A. xylosoxidans was frequently found in both autopsy lungs and lung biopsy / resection specimens that were not affected by PMZL (> 50%). Conclusions: Our data suggests that T. whipplei colonisation of lungs may trigger PMZL as a potential driver. Systematic analyses with larger cohorts should be conducted to further support this hypothesis. The frequent detection of A. xylosoxidans in lung tissue suggests that it is a common component of the pulmonary microbiome and therefore less likely to trigger lymphomas. [ABSTRACT FROM AUTHOR]

Purpose: Bacterial biofilms create a challenge in the treatment of prosthetic joint infection (PJI), and failure to eradicate biofilms is often implicated in the high rates of recurrence. In this study, we aimed to compare the effectiveness of a novel nanoparticle ultrasonication technology on Staphylococcus aureus biofilm eradication compared to commonly used orthopedic irrigation solutions. Methods: Twenty-four sterile, titanium alloy discs were inoculated with a standardized concentration of methicillin-resistant S. aureus and cultured for seven days to allow for biofilm formation. Discs were then treated with either ultrasonicated nanoparticle therapy or irrigation with chlorhexidine gluconate, povidone-iodine or normal saline. The remaining bacteria on each surface was subsequently plated for colony-forming units of S. aureus. Bacterial eradication was reported as a decrease in CFUs relative to the control group. Mann–Whitney U tests were used to compare between groups. Results: Treatment with ultrasonicated nanoparticles resulted in a significant mean decrease in CFUs of 99.3% compared to controls (p < 0.0001). Irrigation with povidone-iodine also resulted in a significant 77.5% reduction in CFUs compared to controls (p < 0.0001). Comparisons between ultrasonicated nanoparticles and povidone-iodine demonstrated a significantly higher reduction in bacterial CFUs in the nanoparticle group (p < 0.0001). Conclusion: Ultrasonicated nanoparticle were superior to commonly used bactericidal irrigation solutions in the eradication of S. aureus from a titanium surface. Future clinical studies are warranted to evaluate this ultrsonication technology in the treatment of PJI. [ABSTRACT FROM AUTHOR]

• LPS and PAM3CSK4 which mimic gram-negative and gram-positive bacterial infection in neonates, respectively, leads to metabolic alterations and impairment in respiratory chemoreflexes. • LPS induces a robust neuroinflammation in brainstem tissue and brainstem enriched astrocytes, microglia, and neurons. • PAM3CSK4 induces to a smaller degree of inflammatory changes in brainstem without resulting in gene expression changes of enriched GLAST-1 positive astrocytes. • PAM3CSK4 leads to impaired anoxic chemoreflex and neurotransmission between preBötzinger complex and hypoglossal. • Machine learning analysis suggests IL6 as a potential mechanism for hypothermia-hypometabolic changes in neonatal sepsis through LPS. Neonatal sepsis remains one of the leading causes of mortality in newborns. Several brainstem-regulated physiological processes undergo disruption during neonatal sepsis. Mechanistic knowledge gaps exist at the interplay between metabolism and immune activation to brainstem neural circuits and pertinent physiological functions in neonates. To delineate this association, we induced systemic inflammation either by TLR4 (LPS) or TLR1/2 (PAM3CSK4) ligand administration in postnatal day 5 mice (PD5). Our findings show that LPS and PAM3CSK4 evoke substantial changes in respiration and metabolism. Physiological trade-offs led to hypometabolic-hypothermic responses due to LPS, but not PAM3CSK4, whereas to both TLR ligands blunted respiratory chemoreflexes. Neuroinflammatory pathways modulation in brainstem showed more robust effects in LPS than PAM3CSK4. Brainstem neurons, microglia, and astrocyte gene expression analyses showed unique responses to TLR ligands. PAM3CSK4 did not significantly modulate gene expression changes in GLAST-1 positive brainstem astrocytes. PD5 pups receiving PAM3CSK4 failed to maintain a prolonged metabolic state repression, which correlated to enhanced gasping latency and impaired autoresuscitation during anoxic chemoreflex challenges. In contrast, LPS administered pups showed no significant changes in anoxic chemoreflex. Electrophysiological studies from brainstem slices prepared from pups exposed to either TLR4 or PAM3CSK4 showed compromised transmission between preBötzinger complex and Hypoglossal as an exclusive response to the TLR1/2 ligand. Spatial gene expression analysis demonstrated a region-specific modulation of PAM3CSK4 within the raphe nucleus relative to other anatomical sites evaluated. Our findings suggest that metabolic changes due to inflammation might be a crucial tolerance mechanism for neonatal sepsis preserving neural control of breathing. [ABSTRACT FROM AUTHOR]

Introduction: Extracorporeal membrane oxygenation (ECMO) is an increasingly used modality of life support with high risk for nosocomial infections. The accuracy of sepsis prediction tools in identifying blood stream infections (BSI) in this population is unknown as measurement of multiple variables commonly associated with infection are altered by the circuit. Methods: This study compares all blood stream infections for patients receiving ECMO between January 2012 and December 2020 to timepoints when blood cultures were negative using the Sequential Organ Failure Assessment (SOFA), Logistic Organ Dysfunction Score (LODS), American Burn Association Sepsis Criteria (ABA), Systemic Inflammatory Response Syndrome (SIRS) scores. Results: Of the 220 patients who received ECMO during the study period, 40 (18%) had 51 blood stream infections and were included in this study. Gram-positive infections composed 57% (n = 29) of infections with E. faecalis (n = 12, 24%) being the most common organism isolated. There were no significant differences in sepsis prediction scores at the time of infection compared to infection-free time points for SOFA (median (IQR) 7 (5–9) vs. 6 (5–8), p = 0.22), LODS (median (IQR) 12 (10–14) vs. 12 (10–13), p = 0.28), ABA (median (IQR) 2 (1–3) vs. 2 (1–3) p = 0.75), or SIRS (median (IQR) 3 (2–3) vs. 3 (2–3), p = 0.20). Conclusions: Our data shows that previously published sepsis scores are elevated throughout a patient's ECMO course, and do not correlate with bacteremia. Better predictive tools are needed to determine the appropriate timing for blood cultures in this population. [ABSTRACT FROM AUTHOR]

Background Daptomycin is widely used in critically ill patients for Gram-positive bacterial infections. Extracorporeal membrane oxygenation (ECMO) is increasingly used in this population and can potentially alter the pharmacokinetic (PK) behaviour of antibiotics. However, the effect of ECMO has not been evaluated in daptomycin. Our study aims to explore the effect of ECMO on daptomycin in critically ill patients through population pharmacokinetic (PopPK) analysis and to determine optimal dosage regimens based on both efficacy and safety considerations. Methods A prospective, open-label PK study was carried out in critically ill patients with or without ECMO. The total concentration of daptomycin was determined by UPLC-MS/MS. NONMEM was used for PopPK analysis and Monte Carlo simulations. Results Two hundred and ninety-three plasma samples were collected from 36 critically ill patients, 24 of whom received ECMO support. A two-compartment model with first-order elimination can best describe the PK of daptomycin. Creatinine clearance (CLCR) significantly affects the clearance of daptomycin while ECMO has no significant effect on the PK parameters. Monte Carlo simulations showed that, when the MICs for bacteria are  ≥1 mg/L, the currently recommended dosage regimen is insufficient for critically ill patients with CLCR > 30 mL/min. Our simulations suggest 10 mg/kg for patients with CLCR between 30 and 90 mL/min, and 12 mg/kg for patients with CLCR higher than 90 mL/min. Conclusions This is the first PopPK model of daptomycin in ECMO patients. Optimal dosage regimens considering efficacy, safety, and pathogens were provided for critical patients based on pharmacokinetic-pharmacodynamic analysis. [ABSTRACT FROM AUTHOR]

Objective Late-onset sepsis (LOS) is a substantial contributor to morbidity and mortality among neonates. The use of nonculture-based tools for early diagnosis is an area of active investigation. Therefore, we aimed to evaluate the diagnostic value of serum interleukin-27 (IL-27) and mean platelet volume (MPV) in full-term neonates with LOS. Study Design In this single-center, cross-sectional study, 90 full-term newborns were assigned to two equal-matched groups as follows: (1) culture-proven sepsis and (2) control groups. Clinical data and laboratory findings as complete blood pictures, including MPV, highly sensitive C-reactive protein, and blood culture results, were recorded. Moreover, IL-27 levels were measured using enzyme-linked immunosorbent assay. Results IL-27 levels (median = 4,364 pg/mL) and MPV (mean = 12.02 ± 1.54 FL) were significantly higher in the culture-proven sepsis group than in the control group (p < 0.001). For IL-27, the optimum cut-off value for the diagnosis of LOS was 283.8 pg/mL with sensitivity and specificity of 97.8 and 100%, respectively. For MPV, the optimum cut-off value was 11.6 FL, with diagnostic sensitivity and specificity of 77.8 and 97.8%, respectively. Conclusion IL-27 and MPV are promising markers for the diagnosis of LOS in full-term neonates. The diagnostic performance of IL-27 was superior to MPV. Key Points Late-onset neonatal sepsis diagnosis is time consuming. Nonculture-based rapid diagnostic tests are much needed. IL-27 is superior in LOS diagnosis to MPV. [ABSTRACT FROM AUTHOR]

Objectives. To identify the current practices with long half-life lipoglycopeptides (LGPs) and potential use/position of oritavancin. Results. Despite their indication being limited to skin and soft tissue infections (SSTIs), long half-life lipoglycopeptides are mainly used off-label to treat bone and joint infections (BJIs) and infective endocarditis. Oritavancin and dalbavancin are both semisynthetic lipoglycopeptide antibiotics with activity against Gram-positive organisms. The game-changing property of these two antibiotics is their one-time dosing. Due to its shorter half-life, oritavancin might have an advantage over dalbavancin for a treatment duration of less than 2 weeks, as it could be used both in prolonged treatments of complicated patients in BJIs or administered as a single-dose treatment for Gram-positive cocci infections usually treated by a 5- to 10-day antibiotic course. These infections include urinary tract infections, bacteremias, catheter-related infections, etc. In addition to the possibility of being used as an end-of-treatment injection, oritavancin could be used as an empiric therapy treatment in the postoperative period in the context of device-associated especially prosthetic joint infections to allow for the early discharge of the patient. Methods. A qualitative survey was conducted in March 2022 including sixteen infectiologists, one internist, five hospital pharmacists, and one pharmacologist. Conclusion. Long half-life lipoglycopeptides contribute to changing the paradigm in the management of acute bacterial infections, as infectiologists now consider a range of indications and patient profiles for one single drug. Oritavancin strengthens the therapeutic arsenal in numerous infections from BJIs to urinary tract infections and could help to manage specific clinical situations, on top of providing potential benefits for the hospital's budget. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the prevalence of Tropheryma whipplei (TW) infection in the population and to investigate the clinical symptoms, as well as the laboratory and imaging characteristics of patients testing positive for TW using next-generation sequencing (NGS). Methods: A retrospective review was conducted on 1346 bronchoalveolar lavage fluid (BALF) samples collected between January 2021 and September 2023. The case group comprised patients with TW detected using NGS while the control group included 65 randomly chosen Gram-positive bacterial infection patients without TW. Comparative analyses were carried out on the basic demographics, laboratory parameters, and imaging findings between the two groups. Additionally, the case group underwent an in-depth examination of underlying diseases, pathogens, final diagnoses, treatment strategies. Results: The case group comprised of 51 patients with TW, constituting 3.8% of the total. There was no significant difference in gender and age between the case and control groups (P = 0.84, P = 0.07). Symptoms such as coughing, expectoration, wheezing, fever, and hemoptysis are less commonly detected in the case group with a higher incidence of chest pain when compared to the control group (P > 0.05). The case group exhibited decreased albumin levels and increased C-reactive protein and D-dimer levels compared to normal levels. Imaging findings in the case group commonly included nodules, patchy images, and interstitial changes, the most common underlying disease is cardiovascular disease, and the most frequently co-occurring pathogen is the human herpesvirus. Among the case group, 27 patients received a final diagnosis of pneumonia, and 3 patients clinically diagnosed with Whipple's disease demonstrated improvement in both symptoms and imaging after treatment. Conclusion: NGS revealed a relatively low overall detection rate of TW-positive patients using BALF. TW was more prevalent in middle-aged and elderly male patients characterized by symptoms such as cough, expectoration, shortness of breath, and fever. Chest imaging in these cases typically showed nodules and interstitial changes. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot osteomyelitis (DFO) commonly occurs secondary to ulcerations of the skin. Empirical antibiotic agents are a key element of treatment and their use is dependent on local knowledge of the microbial spectrum of diabetic foot infections. This study aimed to retrospectively analyze the local microbiological profile, including bacterial culture/sensitivity results of DFO, and compare findings with literature. This study also aimed to review the concordance of microbiology results with national guidelines for the future treatment of DFO. Methods: A retrospective review of clinical records was performed on patients who presented to the high-risk foot clinic, Townsville University Hospital, between 2018 and 2022. All patients older than 18 years and diagnosed with DFO were included. Our exclusion criteria included all other foot presentations, including trauma, vasculitis, and neoplasms. Results: On the basis of the inclusion and exclusion criteria, 124 patients with DFO were selected. Most patients in the cohort were males (70.2%), non-Indigenous (68.5%), aged 50-69 years (55.6%), and with elevated HbA1c levels (>8.6). Chronic kidney disease (39.5%) and ischemic heart disease (41.9%) were common comorbidities. Of the pertinent microbial results, Staphylococcus aureus (~76%) was the most commonly isolated Gram-positive organism. Gram-positive bacteria were significantly increased in the elderly population with DFO (P <.05). All methicillin-resistant S aureus isolates were vancomycin- and cotrimoxazole-sensitive. Pseudomonas aeruginosa was the predominant Gram-negative organism isolated (39.3%). P aeruginosa exhibited low sensitivity to ciprofloxacin. Conclusion: This study has enhanced our understanding of the various microbial species underlying DFO at our center and may be generalizable. Level of Evidence: Level IV, retrospective case series. [ABSTRACT FROM AUTHOR]

The fight against infectious disease has remained an ever-evolving challenge in the landscape of healthcare. The ability of pathogens to develop resistance against conventional drug treatments has decreased the effectiveness of therapeutic interventions, and antibiotic resistance is recognized as one of the main challenges of our time. The goal of this systematic review paper is to provide insight into the research papers published on innovative nanosized drug delivery systems (DDSs) based on gentamycin and vancomycin and to discuss the opportunity of their repurposing through nano DDS formulations. These two antibiotics are selected because (i) gentamicin is the first-line drug used to treat suspected or confirmed infections caused by Gram-negative bacterial infections and (ii) vancomycin is used to treat serious Gram-positive bacterial infections. Moreover, both antibiotics have severe adverse effects, and one of the purposes of their formulation as nanosized DDSs is to overcome them. The review paper includes an introduction focusing on the challenges of infectious diseases and traditional therapeutic treatments, a brief description of the chemical and pharmacological properties of gentamicin and vancomycin, case studies from the literature on innovative nanosized DDSs as carriers of the two antibiotic drugs, and a discussion of the results found in the literature. [ABSTRACT FROM AUTHOR]

Objectives: Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of linezolid are often overlooked. This manuscript aims to review the medications that affect the pharmacokinetics of linezolid. Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the PubMed, Embase, and Cochrane Library for publications from database establishment to November 3, 2023, using the search terms: "Linezolid" and "interaction," or "interact," or "drug-drug interaction," or "co-treatment," or "cotreatment," or "combined," or "combination." Results: A total of 24 articles were included. Among the reported medication interactions, rifampicin, levothyroxine, venlafaxine, and phenobarbital could reduce the concentration of linezolid; clarithromycin, digoxin, cyclosporine, proton pump inhibitors, and amiodarone could increase the concentration of linezolid, while aztreonam, phenylpropanolamine, dextromethorphan, antioxidant vitamins, and magnesium-containing antacids had no significant effects on linezolid pharmacokinetics. The ratio of mean (ROM) of linezolid AUC in co-treatment with rifampicin to monotherapy was 0.67 (95%CI 0.58–0.77) and 0.63 (95%CI 0.43–0.91), respectively, in 2 studies, and co-treatment with 500 mg clarithromycin to monotherapy was 1.81 (95%CI 1.49–2.13). Conclusions: This systematic review found that numerous drugs have an impact on the pharmacokinetics of linezolid, and the purported main mechanism may be that linezolid is the substrate of P-glycoprotein. In clinical practice, it is prudent to pay attention to the changes in linezolid pharmacokinetics caused by interactions. Conducting therapeutic drug monitoring (TDM) is beneficial to improve efficacy and reduce adverse reactions of linezolid. [ABSTRACT FROM AUTHOR]

Sepsis is characterized by a dysfunctional host response to infection culminating in life-threatening organ failure that requires complex patient management and rapid intervention. Timely diagnosis of the underlying cause of sepsis is crucial, and identifying those at risk of complications and death is imperative for triaging treatment and resource allocation. Here, we explored the potential of explainable machine learning models to predict mortality and causative pathogen in sepsis patients. By using a modelling pipeline employing multiple feature selection algorithms, we demonstrate the feasibility of identifying integrative patterns from clinical parameters, plasma biomarkers, and extensive phenotyping of blood immune cells. While no single variable had sufficient predictive power, models that combined five and more features showed a macro area under the curve (AUC) of 0.85 to predict 90-day mortality after sepsis diagnosis, and a macro AUC of 0.86 to discriminate between Gram-positive and Gram-negative bacterial infections. Parameters associated with the cellular immune response contributed the most to models predictive of 90-day mortality, most notably, the proportion of T cells among PBMCs, together with expression of CXCR3 by CD4+ T cells and CD25 by mucosal-associated invariant T (MAIT) cells. Frequencies of Vδ2+ γδ T cells had the most profound impact on the prediction of Gram-negative infections, alongside other T-cell-related variables and total neutrophil count. Overall, our findings highlight the added value of measuring the proportion and activation patterns of conventional and unconventional T cells in the blood of sepsis patients in combination with other immunological, biochemical, and clinical parameters. This study explores the potential of explainable machine learning models to predict mortality and causative pathogen in sepsis patients and demonstrates the feasibility to identify integrative patterns from clinical parameters, plasma biomarkers, and phenotyping of blood cells. While no single variable had sufficient predictive power, models that combined five and more features were able to predict 90-day mortality after sepsis diagnosis, and discriminate between Gram-positive and Gram-negative bacterial infections. Overall, our findings highlight the added value of measuring the proportion and activation patterns of conventional and unconventional T cells in the blood of sepsis patients in combination with other immunological, biochemical, and clinical parameters. Graphical Abstract [ABSTRACT FROM AUTHOR]

Isoflavones are a class of natural products that exhibit a wide range of interesting biological properties, including antioxidant, hepatoprotective, antimicrobial, and anti-inflammatory activities. Scandenone (1), osajin (2), and 6,8-diprenylgenistein (3) are natural prenylated isoflavones that share the same polyphenol framework. In this research, the key intermediate 15 was used for the synthesis of the natural isoflavones 1–3, establishing a stereoselective synthetic method for both linear and angular pyran isoflavones. The antibacterial activities of 1–3 were also evaluated, and all of them displayed good antibacterial activity against Gram-positive bacteria. Among them, 2 was the most potent one against MRSA, with a MIC value of 2 μg/mL, and the SEM assay indicated that the bacterial cell membranes of both MRSA and E. faecalis could be disrupted by 2. These findings suggest that this type of isoflavone could serve as a lead for the development of novel antibacterial agents for the treatment of Gram-positive bacterial infections. [ABSTRACT FROM AUTHOR]

Purpose Persons who inject drugs (PWID) are at risk for severe gram-positive infections and may require prolonged hospitalization and intravenous (IV) antibiotic therapy. Dalbavancin (DBV) is a long-acting lipoglycopeptide that may reduce costs and provide effective treatment in this population. Methods This was a retrospective review of PWID with severe gram-positive infections. Patients admitted from January 1, 2017, to November 1, 2019 (standard-of-care [SOC] group) and from November 15, 2019, to March 31, 2022 (DBV group) were included. The primary outcome was the total cost to the healthcare system. Secondary outcomes included hospital days saved and treatment failure. Results A total of 87 patients were included (37 in the DBV group and 50 in the SOC group). Patients were a median of 34 years old and were predominantly Caucasian (82%). Staphylococcus aureus (82%) was the most common organism, and bacteremia (71%) was the most common type of infection. Compared to the SOC group, the DBV group would have had a median of 14 additional days of hospitalization if they had stayed to complete their therapy (P = 0.014). The median total cost to the healthcare system was significantly lower in the DBV group than in the SOC group ($31,698.00 vs $45,093.50; P = 0.035). The rate of treatment failure was similar between the groups (32.4% in the DBV group vs 36% in the SOC group; P = 0.729). Conclusion DBV is a cost-saving alternative to SOC IV antibiotics for severe gram-positive infections in PWID, with similar treatment outcomes. Larger prospective studies, including other patient populations, may demonstrate additional benefit. [ABSTRACT FROM AUTHOR]

Purpose: The principal objective of this project was to review and thoroughly examine the chemical characteristics, pharmacological activity, and quantification methods associated with contezolid. Methods: The article was based on published and ongoing preclinical and clinical studies on the application of contezolid. These studies included experiments on the physicochemical properties of contezolid, in vitro antimicrobial research, in vivo antimicrobial research, and clinical trials in various phases. There were no date restrictions on these studies. Results: In June 2021, contezolid was approved for treating complicated skin and soft tissue infections. The structural modification of contezolid has resulted in better efficacy compared to linezolid. It inhibits bacterial growth by preventing the production of the functional 70S initiation complex required to translate bacterial proteins. The current evidence has indicated a substantial decline in myelosuppression and monoamine oxidase inhibition without impairing its antibacterial properties. Contezolid was found to have a more significant safety profile and to be metabolised by flavin monooxygenase 5, reducing the risk of harmful effects due to drug–drug interactions. Adjusting doses is unnecessary for patients with mild to moderate renal or hepatic insufficiency. Conclusion: As an oral oxazolidinone antimicrobial agent, contezolid is effective against multi-drug resistant Gram-positive bacteria. The introduction of contezolid provided a new clinical option. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) in diagnosis and treatment of intracranial infection. Methods A retrospective analysis of 117 patients with intracranial infection were admitted to Shenzhen Second People's Hospital from January 2020 to December 2022. Before initiating empirical broad-spectrum antibiotic treatment, CSF samples were collected for microbial culture (conventional culture group, n = 58) and/or mNGS (mNGS group, n = 59). The results were used to adjust the antibiotic treatment plan, and the study compared the pathogen detection rates and result reporting times of the two testing methods, as well as the antibiotic intensity grading, the intensive care unit (ICU) stay, total hospital stay, and mortality rate. Results A total of 65 pathogens were detected from the CSF samples of all the patients through microbial culture and/or mNGS, with viruses being the most prevalent, accounting for 49.23% (32/65), followed by Gram-negative bacteria (24.62%, 16/65), Gram-positive bacteria (18.46%, 12/65) and fungi (7.69%, 5/65). The pathogen detection rate of CSF mNGS was higher than that of CSF microbial culture (χ² = 22.781, P = 0.000), and the results were reported earlier (t = - 32.588, P = 0.000). Based on the results, 20 cases (33.90%) in the mNGS group adjusted antibiotic treatment plan, with 5 cases downgrading and 15 cases upgrading the intensity of antibiotic application. In the conventional culture group, 30 cases (51.72%) adjusted their antibiotic treatment plan, with 17 cases downgrading and 13 cases upgrading the intensity of antibiotic application. There was no significant difference between the 2 groups (Z = -1.917, P = 0.055). And there was no statistically significant difference in ICU stay (Z = -0.716, P = 0.474), total hospital stay (Z = -0.933, P = 0.351) and mortality rate (Fisher's exact probability: P = 0.496) between the 2 groups. Conclusions The application of mNGS can effectively improve the detection rate of intracranial infection pathogens, which may shorten the duration of antibiotic use and reduce the intensity of broad-spectrum antibiotics, so as to help clinical effective judgment and treatment decision. [ABSTRACT FROM AUTHOR]

Insect host defense comprises two complementary dimensions, microbial killing-mediated resistance and microbial toxin neutralization-mediated resilience, both jointly providing protection against pathogen infections. Insect defensins are a class of effectors of innate immunity primarily responsible for resistance to Gram-positive bacteria. Here, we report a newly originated gene from an ancestral defensin via genetic deletion following gene duplication in Drosophila virilis, which confers an enhanced resilience to Gram-positive bacterial infection. This gene encodes an 18-mer arginine-rich peptide (termed DvirARP) with differences from its parent gene in its pattern of expression, structure and function. DvirARP specifically expresses in D. virilis female adults with a constitutive manner. It adopts a novel fold with a 310 helix and a two CXC motif-containing loop stabilized by two disulfide bridges. DvirARP exhibits no activity on the majority of microorganisms tested and only a weak activity against two Gram-positive bacteria. DvirARP knockout flies are viable and have no obvious defect in reproductivity but they are more susceptible to the DvirARP-resistant Staphylococcus aureus infection than the wild type files, which can be attributable to its ability in neutralization of the S. aureus secreted toxins. Phylogenetic distribution analysis reveals that DvirARP is restrictedly present in the Drosophila subgenus, but independent deletion variations also occur in defensins from the Sophophora subgenus, in support of the evolvability of this class of immune effectors. Our work illustrates for the first time how a duplicate resistance-mediated gene evolves an ability to increase the resilience of a subset of Drosophila species against bacterial infection. [ABSTRACT FROM AUTHOR]

The recently updated Society for Healthcare Epidemiology of America, the Infectious Diseases Society of America, and the Association of Professionals in Infection Control practice recommendations for methicillin-resistant Staphylococcus aureus (MRSA) prevention in acute care facilities list contact precautions (CPs) for patients known to be infected or colonized with MRSA as an "essential practice," meaning that it should be adopted in all acute care facilities. We argue that existing evidence on benefits and harms associated with CP do not justify this recommendation. There are no controlled trials that support broad use of CP for MRSA prevention. Data from hospitals that have discontinued CP for MRSA have found no impact on MRSA acquisition or infection. The burden and harms of CP remain concerning, including the environmental impact of increased gown and glove use. We suggest that CP be included among other "additional approaches" to MRSA prevention that can be implemented under specific circumstances (eg outbreaks, evidence of ongoing transmission despite application of essential practices). [ABSTRACT FROM AUTHOR]

Key Clinical Message: Linezolid is a potent oxazolidinone for the treatment of various gram‐positive bacterial infections. However, the drug can cause potential adverse reactions such as thrombocytopenia, hyperlactacidemia and serotonin syndrome, which warrant consideration by the medical team when planning treatment. The existing literature has reported some adverse reactions caused by linezolid, but most of these are based on clinical characteristics and simple treatment measures. Two cases of linezolid overdose resulting in thrombocytopenia, hyperlactacidemia and serotonin syndrome are presented, which were successfully managed with therapeutic drug monitoring. A dose adjustment strategy was adopted to safely and effectively mitigate linezolid‐related adverse events. [ABSTRACT FROM AUTHOR]

Background: Linezolid is used for Gram-positive bacterial infections. Thrombocytopenia is one of its main adverse effects resulting from myelosuppression. Several studies have assessed risk factors that may increase the risk of this adverse effect. However, most studies included patients with hemato-oncologic diseases, which may confound such assessments. This study aimed to investigate risk factors for linezolid-associated thrombocytopenia in patients without hemato-oncologic diseases. Methods: This was a multicenter retrospective case-control study of adult patients treated with linezolid twice daily for ≥3 days. Patients with hemato-oncologic diseases, active dengue fever, active COVID-19, baseline platelet count <100 × 103/mm3, concurrent therapy with trimethoprim/sulfamethoxazole or valproic acid, and a recent platelet transfusion within 7 days were excluded. Thrombocytopenia was defined as a drop in platelet count below 100 × 103/mm3. Results: Out of 158 evaluated patients, 33 developed thrombocytopenia, indicating an incidence rate of 20.9%. Of all the risk factors assessed, creatinine clearance of <60 mL/min and bacteremia/infective endocarditis were significantly associated with linezolid-associated thrombocytopenia (adjusted odds ratios, 3.25 and 5.95; 95% CI 1.12–9.45 and 1.23–28.66; p = 0.031 and 0.026, respectively). End of therapy platelet counts were significantly lower in the cases than in the controls (79 vs. 243 × 103/mm3; p < 0.001). Similarly, the percentage of platelet count change was significantly different (−55.1% vs. −10.2%; p < 0.001). Conclusions: In our study, the incidence rate of linezolid-associated thrombocytopenia was 20.9%, and we found that patients with renal impairment and bacteremia may need close monitoring of platelet counts. Prospective studies are warranted to evaluate the potential need for renal dose adjustment. [ABSTRACT FROM AUTHOR]

Background: Chrysomycin A (CA) is a promising antibiotic for treatment of Gram-positive bacterial infections and cancers. In order to enhance CA yield, optimization of fermentation conditions and medium components was carried out on strain Streptomyces sp. 891-B6, an UV-induced mutant with improved CA titer compared with its wide-type marine strain 891. Results: Using one-way experiment, the optimal fermentation conditions for CA production in 1-L shake flask were obtained as follows: 12 days of fermentation time, 5 days of seed age, 5% of inoculum volume ratio, 200 mL of loading volume and 6.5 of initial pH. By response surface methodology, the optimal medium components determined as glucose (39.283 g/L), corn starch (20.662 g/L), soybean meal (15.480 g/L) and CaCO3 (2.000 g/L). Conclusion: Validation tests showed that the maximum yield of CA reached 1601.9 ± 56.7 mg/L, which was a 60% increase compared to the initial yield (952.3 ± 53.2 mg/L). These results provided an important basis for scale-up production of CA by strain 891-B6. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis, a syndrome of organ dysfunction caused by an unregulated host response to infection. This study aimed to develop a novel sepsis diagnostic model of hematological parameters and evaluate its effectiveness in the early identification and prognosis of sepsis in emergency departments. Methods: A retrospective study was conducted in Emergency Department. Cell population data parameters related to monocytes and neutrophils were obtained using the Mindary BC‐6800 plus hematology analyzer. Receiver operating characteristic (ROC) curve analysis, logistic regression analysis was performed to assess the performance of the parameters and establish a diagnostic and prognostic model of sepsis, which was then verified with a validation cohort. Results: Mon_XW exhibited the best diagnostic performance (area under the ROC curve [AUC] = 0.848, 95% confidence interval [CI]: 0.810–0.885, p < 0.001), followed by Neu_Y and Neu_YW (AUC = 0.777 95% CI: 0.730–0.824, p < 0.001). Logistic regression analysis identified Mon_XW and Neu_Y as independent predictors, which were used to establish a diagnostic model named hematological parameter for sepsis (HPS). HPS demonstrated the best diagnostic performance with an AUC of 0.862 (95% CI: 0.826–0.898, p < 0.001), sensitivity of 70.0%, and specificity of 87.1%, compared to C‐reactive protein (CRP) and procalcitonin (PCT). The validation cohort also found that the positive predictive value of HPS was 70.4% and the negative predictive value was 92.2%. Conclusion: The developed HPS model showed promising diagnostic efficacy for sepsis in the emergency department, which outperformed CRP and PCT in terms of sensitivity and specificity. By enabling early identification and prognosis of sepsis, that contributes to reducing sepsis‐related mortality. [ABSTRACT FROM AUTHOR]

Purpose: Dalbavancin, approved in 2014 for Gram-positive acute bacterial skin and skin structure infections (ABSSSI), has pharmacokinetics enabling treatment with one or two doses. Dalbavancin might be useful in outpatient parenteral antibiotic therapy (OPAT) of deep-seated infections, otherwise requiring inpatient admission. We documented our experience with pragmatic dalbavancin use to assess its effectiveness for varied indications, on- and off-label, as primary or sequential consolidation therapy. Methods: Patients prescribed dalbavancin between 1 December 2021 and 1 October 2022 were screened for demographics of age, sex, Charlson comorbidity index (CCI), allergies, pathogens, doses of dalbavancin, other antibiotics administered and surgery. Where available, infection markers were recorded. The primary outcome was a cure at the end of treatment. Secondary outcomes included any adverse events and for those with treatment failures, response to salvage antibiotics. Results: Sixty-seven per cent of patients were cured. Cure rates by indication were 93% for ABSSSI, 100% for bacteraemia, 90% for acute osteomyelitis, 0% for chronic osteomyelitis, 75% for native joint septic arthritis and 33% for prosthetic joint infection. Most bone and joint infections that were not cured did not have source control, and the goal of treatment was suppressive. Successful suppression rates were greater at 48% for chronic osteomyelitis and 66% for prosthetic joint infections. Adverse events occurred in 14 of 102 patients. Conclusion: This report adds to clinical experience with dalbavancin for off-label indications whilst further validating its role in ABSSSI. Dalbavancin as primary therapy in deep-seated infections merits investigation in formal clinical trials. [ABSTRACT FROM AUTHOR]

Cardiac implantable electronic devices (CIED) are increasingly used worldwide, and infection of these devices remains one of the most feared complications. CIED infections (CDIs) represent a challenge for physicians and the healthcare system in general as they require prolonged hospitalization and antibiotic treatment and are burdened by high mortality and high costs, so management of CDIs must be multidisciplinary. The exact incidence of CDIs is difficult to define, considering that it is influenced by various factors mainly represented by the implanted device and the type of procedure. Risk factors for CDIs could be divided into three categories: device related, patient related, and procedural related and the etiology is mainly sustained by Gram-positive bacteria; however, other etiologies cannot be underestimated. As a matter of fact, the two cornerstones in the treatment of these infections are device removal and antimicrobial treatment. Finally, therapeutic drug monitoring and PK/PD correlations should be encouraged in all patients with CDIs receiving antibiotic therapy and may result in a better clinical outcome and a reduction in antibiotic resistance and economic costs. In this narrative review, we look at what is new in the management of these difficult-to-treat infections. [ABSTRACT FROM AUTHOR]

Paeniclostridium sordellii, a spore-forming anaerobic Gram-positive rod commonly found in soil samples, is rarely associated with human disease. The authors report a rare case of P. sordelli osteomyelitis of the left distal femur in a young male patient, which is the first reported case of P. sordelli from Pakistan. A 21-year-old male, laborer by profession, presented with low-grade fever, fatigue and lethargy since more than a month, which progressed in severity over the last 2 weeks. On CT scan, abnormal thickening of the cortical bone along with encroachment of the medullary cavity was observed in the left distal femur. A diagnosis of acute osteomyelitis was made and surgical intervention was performed to remove infected bone and soft tissue, which were sent for culture to the Microbiology laboratory. Bone and soft tissue cultures yielded no growth after 72 hours of aerobic incubation. However, bacterial growth was observed after anaerobic incubation, in bone culture, which was identified as P. sordellii using Vitek® 2 automated system. Penicillin, piperacillin-tazobactam, meropenem, vancomycin and metronidazole were susceptible whereas, clindamycin was resistant in the isolate. The patient was started on metronidazole and after he remained stable with a clean surgical wound and symptomatic management, was discharged on regular follow-up as an out-patient. Since, P. sordelli is rare and highly fatal in most cases, prompt reporting and insights from treated infections could pave the way for successful management. [ABSTRACT FROM AUTHOR]

To investigate the etiological characteristics of wound infection in severe trauma patients and logistic regression analysis of the influencing factors of infection. The 116 patients with severe trauma who were intervened in our hospital from 22 October 2017 to 9 September 2019 were selected as the subjects of this retrospective study and divided into a control group and an observation group according to whether they were infected or not, 58 cases each. Observe and compare the pathogenic characteristics (pathogen distribution and drug resistance) of the two groups of patients and logistic regression analysis of the influencing factors of infection. The gram‐positive bacteria in the observation group were mainly Staphylococcus aureus, accounting for 17.20%; the fungi were mainly Candida tropicalis, accounting for 17.20%; and the gram‐negative bacteria were mainly Acinetobacter baumannii, accounting for 20.39%; the control group was gram‐positive. The main bacteria are S. aureus, accounting for 8.60%; the fungi are mainly Candida albicans, accounting for 4.3%; and the gram‐negative bacteria, which are mainly Pseudomonas aeruginosa, accounting for 14.56%. Gram‐positive bacteria Enterococcus faecium, S. aureus, Enterococcus faecalis, Staphylococcus epidermidis. The highest drug resistance of other gram‐positive bacteria is penicillin and erythromycin at 85.00% and above. Fungi C. tropicalis, Candida parapsilosis, C. albicans, fluconazole and amphotericin B have the highest resistance to 80.00% and above. Gram‐negative bacteria A. baumannii, Ps. aeruginosa, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Enterobacter cloacae and other gram‐negative bacteria are the most resistant to ampicillin, and Piperacillin was 70.00% and above. The combined primary diseases of the two groups of patients, ventilator use ≧3 days, long‐term use of glucocorticoids, catheter use days ≧5 days, fever days ≧3 days and long‐term use of broad‐spectrum antimicrobial drugs, the difference is statistically significant academic significance (p < 0.05). Logistic analysis showed that combined with underlying diseases, fever days ≥3 days, long‐term use of glucocorticoids and catheter use days ≥5 days are the influencing factors for the occurrence of wound infections in patients with severe trauma. Trauma patients are prone to wound infections, and there are many influencing factors. Close observation of patients should be strengthened. Effective prevention and control measures should be taken for related influencing factors to reduce the incidence of infection. [ABSTRACT FROM AUTHOR]

The article highlights reports on the epidemiology of persistent enterococcal bacteremia. Topics discussed include selected reports describing patients with enterococcal bacteremia and including data on bacteremia duration, clinical relevance of persistent enterococcal bacteremia, and commonly used antimicrobials effective against susceptible enterococcus species.

Background: Therapeutic drug monitoring (TDM) of vancomycin is widely recommended for clinical treatment. Due to the complexity of 24-h area under the curve (AUC) guided vancomycin monitoring in clinical practice, the vancomycin trough level remains the most common and practical method. The purpose of this study was designed to investigate the differences in the safety and efficacies of vancomycin TDM based on the two different monitoring methods, and further explore the clinical application of trough-guided vancomycin monitoring in patients with gastrointestinal cancer requiring mechanical ventilation. Methods: We included a total of 78 gastrointestinal cancer patients who required mechanical ventilation due to various diseases. All patients included in this study were aged 18 years or older and were treated with intravenous vancomycin therapy for more than 2 days due to documented or suspected Gram-positive bacterial infections, and have at least one available vancomycin plasma concentration. First, we compared the safety and efficacies of vancomycin TDM based on different monitoring methods as trough-guided monitoring or AUC-guided monitoring. Then, based on whether the initial vancomycin concentration achieving the target trough concentration (less than 48 h), patients were divided into early and delayed groups, and the clinical factors were compared between them. The primary endpoints include the incidence of new-onset acute kidney injury (AKI) or renal replacement therapy (RRT), clinical success rate and 28-day all-cause mortality. Finally, the overall relationship between trough concentration and potential covariates is screened by univariate and multivariate analysis to explore potential information covariates. Results: The research revealed that patients with gastrointestinal cancer exhibited significantly lower initial vancomycin trough concentrations (median [interquartile range (IQR)]: 6.90[5.28-11.20] mg/L). And there were no statistically significant differences in the safety and efficacies of vancomycin TDM based on the two different monitoring methods for the primary endpoint. Moreover, base on trough-guided vancomycin monitoring, the early group demonstrated a notably shorter duration of mechanical ventilation compared with the delayed group (χ2 = 4.532; p < 0.05; Fig. 2E). Propensity score weighting further confirmed that the duration of mechanical ventilation (χ2 = 6.607; p < 0.05; Fig. 2F) and duration of vasoactive agent (χ2 = 6.106; p < 0.05; Fig. 2D) were significantly shorter in the early group compared with delayed group. Multivariate regression analysis revealed that Cystatin C (Cys-C) was the most important variable for vancomycin target trough achievement (odds ratio, 5.274; 95% CI, 1.780 to 15.627; p = 0.003). Conclusions: Trough-guided vancomycin monitoring is a simple and effective marker of TDM for ventilated patients with gastrointestinal cancer. Timely achievement of target trough concentrations for vancomycin can improve partial clinical outcomes in Gram-positive bacterial infections. Cys-C level is a potentially valuable parameter for predicting the vancomycin concentration. [ABSTRACT FROM AUTHOR]