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Background: This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn1546-type transposons harboring the vanA operon. Methods: All E. faecium blood isolates were collected from eight general hospitals in South Korea during one-year study period. Antimicrobial susceptibility testing and vanA and vanB PCR were performed. Growth rates of E. faecium isolates were determined. The vanA-positive isolates were subjected to whole genome sequencing and conjugation experiments. Results: Among 308 E. faecium isolates, 132 (42.9%) were positive for vanA. All Tn1546-type transposons harboring the vanA operon located on the plasmids, but on the chromosome in seven isolates. The plasmids harboring the vanA operon were grouped into four types; two types of circular, nonconjugative plasmids (Type A, n = 50; Type B, n = 46), and two types of putative linear, conjugative plasmids (Type C, n = 16; Type D, n = 5). Growth rates of vanA-positive E. faecium isolates were significantly lower than those of vanA-negative isolates (P < 0.001), and reduction in growth rate under vancomycin pressure was significantly larger in isolates harboring putative linear plasmids than in those harboring circular plasmids (P = 0.020). Conclusions: The possession of vanA operon was costly to bacterial hosts in antimicrobial-free environment, which provide evidence for the importance of reducing vancomycin pressure for prevention of VREfm dissemination. Fitness burden to bacterial hosts was varied by type and size of the vanA operon-harboring plasmid. [ABSTRACT FROM AUTHOR]

Introduction: A target trough concentration (Cmin) of teicoplanin ≥ 15–20 mg/L between the fourth and sixth day has been suggested for severe infections or management of febrile neutropenia (FN). Owing to no reports discussing the impact of early target attainment on treatment outcomes, this study aimed to evaluate the dose–Cmin relationship and clinical outcome and estimate the optimal early target Cmin for FN in patients with hematological malignancies. Methods: This single-center, prospective study enrolled patients with hematological malignancies who were treated with teicoplanin either as an empirical antibiotic for FN or as targeted treatment for Gram-positive bacteria. Blood samples were collected on day three (48 h) post-loading doses, day 5 (96 h), and day 8 (when applicable) and determined by ultrahigh-pressure liquid chromatography–triple quadruple mass spectrometry. A total of 117 samples from 47 patients with FN (27 men, 20 women) were consecutively analyzed. A two-tailed α value of 0.05 was considered statistically significant. Results: The mean Cmin values at 48 h, 96 h, and on day 8 were 23.4, 21.4, and 27.8 mg/L, respectively. The patients achieving Cmin ≥ 20 mg/L at 48 h had a higher likelihood of treatment success. The areas under the receiver operating characteristic curves were 0.71 for clinical efficacy and the cutoff value of Cmin at 48 h was 18.85 mg/L (95% confidence interval 0.55–0.87; P = 0.018). Conclusions: The Cmin of teicoplanin after completion of loading doses could predict the treatment response, with a target concentration ≥ 18.85 mg/L. [ABSTRACT FROM AUTHOR]

Abstract Background This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn1546-type transposons harboring the vanA operon. Methods All E. faecium blood isolates were collected from eight general hospitals in South Korea during one-year study period. Antimicrobial susceptibility testing and vanA and vanB PCR were performed. Growth rates of E. faecium isolates were determined. The vanA-positive isolates were subjected to whole genome sequencing and conjugation experiments. Results Among 308 E. faecium isolates, 132 (42.9%) were positive for vanA. All Tn1546-type transposons harboring the vanA operon located on the plasmids, but on the chromosome in seven isolates. The plasmids harboring the vanA operon were grouped into four types; two types of circular, nonconjugative plasmids (Type A, n = 50; Type B, n = 46), and two types of putative linear, conjugative plasmids (Type C, n = 16; Type D, n = 5). Growth rates of vanA-positive E. faecium isolates were significantly lower than those of vanA-negative isolates (P

Abstract Background Many older adult patients receive low-dose teicoplanin with varied regimens, leading to a lack of clarity on its optimal regimens and toxicity profiles in China. This study aimed to clarify these aspects by analyzing teicoplanin treatment concentrations and toxicities. Methods We included older adult patients administered teicoplanin at four tertiary hospitals in Beijing from June 2021 to July 2023, targeting a trough concentration (Cmin) ≥ 10 mg/L. Teicoplanin concentrations and toxicities were monitored dynamically. Results From 204 patients, we obtained 632 teicoplanin concentrations. Most patients (83.3%) received low-dose regimens. Suboptimal concentrations were found in 66.4% of patients within 7 days of treatment and 17.0% after 15 days. Cmin gradually increased with treatment duration and was influenced initially by creatinine and by both body weight and creatinine from days 8 to 14. The target concentration was achieved in 53.1%, 33.9%, 15.6%, and 5.5% of patients at 3, ≤ 7, 8–14, and ≥ 15 days after withdrawal, respectively. Slow elimination was associated with average Cmin and eGFR. Nephrotoxicity, hepatotoxicity, and thrombocytopenia occurred in 12.5%, 4.1%, and 31.5% of patients, respectively, without significant differences between concentrations. Conclusions Most older adult patients were underdosed, indicating a need for dose adjustment. Given the varied risk factors for suboptimal concentrations in different treatment stages, a one-size-fits-all regimen was ineffective. We recommend an initial dose of 400 mg at 12-h intervals for the first three days, with subsequent doses from days 4 to 14 adjusted based on creatinine and body weight; after day 14, a maintenance dose of 200 mg daily is advised. Trial registration ChiCTR2100046811; 28/05/2021.

Background: Many older adult patients receive low-dose teicoplanin with varied regimens, leading to a lack of clarity on its optimal regimens and toxicity profiles in China. This study aimed to clarify these aspects by analyzing teicoplanin treatment concentrations and toxicities. Methods: We included older adult patients administered teicoplanin at four tertiary hospitals in Beijing from June 2021 to July 2023, targeting a trough concentration (Cmin) ≥ 10 mg/L. Teicoplanin concentrations and toxicities were monitored dynamically. Results: From 204 patients, we obtained 632 teicoplanin concentrations. Most patients (83.3%) received low-dose regimens. Suboptimal concentrations were found in 66.4% of patients within 7 days of treatment and 17.0% after 15 days. Cmin gradually increased with treatment duration and was influenced initially by creatinine and by both body weight and creatinine from days 8 to 14. The target concentration was achieved in 53.1%, 33.9%, 15.6%, and 5.5% of patients at 3, ≤ 7, 8–14, and ≥ 15 days after withdrawal, respectively. Slow elimination was associated with average Cmin and eGFR. Nephrotoxicity, hepatotoxicity, and thrombocytopenia occurred in 12.5%, 4.1%, and 31.5% of patients, respectively, without significant differences between concentrations. Conclusions: Most older adult patients were underdosed, indicating a need for dose adjustment. Given the varied risk factors for suboptimal concentrations in different treatment stages, a one-size-fits-all regimen was ineffective. We recommend an initial dose of 400 mg at 12-h intervals for the first three days, with subsequent doses from days 4 to 14 adjusted based on creatinine and body weight; after day 14, a maintenance dose of 200 mg daily is advised. Trial registration: ChiCTR2100046811; 28/05/2021. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the impact of three different types of intraoperative antibiotic prophylaxis on the risk of postoperative surgical site infection (SSI). Material and Methods: Single-center retrospective cohort study. Patients who underwent surgery for osteosynthesis of a tibial plateau fracture (January 2009–November 2018) in Hospital Clinic i Provincial de Barcelona were included. Three types of prophylaxis during the study period were used: group A (cefuroxime single-dose treatment), group B (meropenem + teicoplanin), and group C (ceftriaxone + teicoplanin). Demographics, co-morbidity, type of fracture, need for external fixation, microbiology data, surgical time, and outcome were recorded. Failure was defined as the need for reintervention due to postoperative surgical site infection. Results: From a total of 148 patients included, 20 cases developed SSI, 8 from group A, 8 from group B, and 4 from group C. Higher ASA scores, Schatzker II classification, need for external fixation, and a prolonged surgical time were associated with a significantly (p < 0.005) increased incidence of SSI. Group C showed the overall highest survival and lowest cumulative risk, but differences were not statistically significant. Conclusions: Group C showed the lowest incidence of infection in this sample. It is necessary to confirm these findings with larger studies. [ABSTRACT FROM AUTHOR]

Due to the favorable features obtained through the incorporation of fluorine atom(s), fluorinated drugs are a group with emerging pharmaceutical importance. As their commercial availability is still very limited, to expand the range of possible candidates, new fluorinated tryptophan analogs were synthesized. Control of enantiopurity during the synthesis procedure requires that highly efficient enantioseparation methods be available. In this work, the enantioseparation of seven fluorinated tryptophans and tryptophan was studied and compared systematically to (i) develop analytical methods for enantioselective separations and (ii) explore the chromatographic features of the fluorotrytophans. For enantioresolution, macrocyclic glycopeptide-based selectors linked to core-shell particles were utilized, applying liquid chromatography-based methods. Application of the polar-ionic mode resulted in asymmetric and broadened peaks, while reversed-phase conditions, together with mobile-phase additives, resulted in baseline separation for all studied fluorinated tryptophans. The marked differences observed between the methanol and acetonitrile-containing eluent systems can be explained by the different solvation abilities of the bulk solvents of the applied mobile phases. Among the studied chiral selectors, teicoplanin and teicoplanin aglycone were found to work effectively. Under optimized conditions, baseline separations were achieved within 6 min. Ionic interactions were semi-quantitatively characterized and found to not influence enantiorecognition. Interestingly, fluorination of the analytes does not lead to marked changes in the chromatographic characteristics of the methanol-containing eluents, while larger differences were noticed when the polar but aprotic acetonitrile was applied. Experiments conducted on the influence of the separation temperature indicated that the separations are enthalpically driven, with only one exception. Enantiomeric elution order was found to be constant on both teicoplanin and teicoplanin aglycone-based chiral stationary phases (L < D) under all applied chromatographic conditions. [ABSTRACT FROM AUTHOR]

Purpose: In clinical practice, teicoplanin (TEIC) is typically administered at a trough concentration of 15–40 µg/mL. TEIC has a protein binding rate of approximately 90%, and its concentration rarely exceeds 40 µg/ml. Nevertheless, an increase in the free blood trough concentration may result in renal dysfunction. However, the relationship between the free blood trough concentration and the occurrence of renal dysfunction remains unclear. This study aimed to examine the impact of the predicted free blood concentration on the development of renal dysfunction. Methods: This retrospective study included patients who underwent TEIC and had at least one trough concentration measurement. The association between the frequency of renal dysfunction occurrence and the predicted free blood concentration was evaluated using the following equation: free TEIC concentration = total TEIC concentration/(1 + 1.78 × serum albumin level). Results: Of the 170 patients included in this study, 18% (31/170) developed renal dysfunction. The predicted free trough concentration was significantly higher in the renal dysfunction onset group than in the nononset group. However, the total trough concentration was not significantly associated with the development of renal dysfunction. The odds ratio for developing renal dysfunction was 4.5 (95% confidence interval, 1.9–10.5; P < 0.001) when the predicted free trough concentration was > 4.0 µg/mL. Conclusion: Elevated free trough concentrations of TEIC were associated with an increased risk of renal dysfunction. Controlling the increase in the predicted free blood concentration may effectively prevent the development of renal dysfunction. [ABSTRACT FROM AUTHOR]

In patients with normal renal function, significant teicoplanin dose adjustments are often necessary. This study aimed to develop a population pharmacokinetic (PK) model for teicoplanin in healthy adults and use it to recommend optimal dosage regimens for patients with normal renal function. PK samples were obtained from 12 subjects and analyzed using a population approach. The derived parameters informed Monte Carlo simulations for dosing recommendations. The PK profile was best described using a three-compartment model, in which the estimated glomerular filtration rate calculated via the CKD-EPI equation and adjusted for body surface area was identified as a significant covariate affecting total clearance. For pathogens with a minimum inhibitory concentration of 1 mg/L, a loading dose (LD) of 14 mg/kg administered every 12 h for four doses, followed by a maintenance dose (MD) of 16 mg/kg administered every 24 h, is recommended. These findings indicate the need for dosage adjustments, such as increasing the LD and MD or decreasing the dosing interval of MD in patients with normal renal function. Because of the long half-life of teicoplanin and the requirement for long-term administration, therapeutic drug monitoring at strategic intervals is important to avoid nephrotoxicity associated with elevated trough concentrations. [ABSTRACT FROM AUTHOR]

Peritoneal dialysis-associated peritonitis (PDAP) is a frequent complication of peritoneal dialysis. The guidelines from the International Society for Peritoneal Dialysis (ISPD) suggest administering teicoplanin through the peritoneal route to treat PDAP, but do not specify the ideal concentration for peritoneal dialysis effluent (PDE). Patients meeting the trial criteria for PDAP in our hospital between July 2022 and December 2023 were enrolled. Data on PDE white blood cell count, PDE neutrophil percentage, clinical symptoms, CRP, and PCT were gathered pre- and post-treatment. Incidences of adverse drug reaction (ADR) and case numbers during treatment were recorded. Subsequently, patients were categorized into cured and uncured groups for evaluating the relationship between PDE teicoplanin concentration and treatment effectiveness. The self-control study results on teicoplanin efficacy indicated intraperitoneal teicoplanin administration achieved an efficacy rate of 88.9% and an ADR incidence of 5.5% in treating PDAP patients. There was no observed correlation between teicoplanin blood concentration and PDE concentration. PDE teicoplanin concentrations on days 1, 3, 5, and 7 post-dosing were higher inthe cured group, with a significant contrast in PDE concentration on day 5 between the 18.98 ± 2.43 mg/L of the cured group and the 12.07 ± 2.68 mg/L of the uncured group. ROC curve revealed a higher likelihood of cure in patients when PDE teicoplanin concentration exceeded 15.138 mg/L on day 5 post-dosing. Univariate and multifactorial studies identified 24-h urine volume and the number of daily abdominal dialysis sessions as influential factors in PDE teicoplanin concentration on day 5. A positive correlation was found between 24-h urine volume and PDE teicoplanin concentration, with PDAP patients having urine volume over 537 mL showing significantly higher drug concentrations. Conversely, the number of daily PDAP sessions was negatively correlated with PDE teicoplanin concentrations, indicating that patients with 1∼3 daily PDAP sessions had notably higher PDE teicoplanin concentrations compared to those with 4∼6 sessions. Therefore, PDAP patients who use intraperitoneal teicoplanin could effectively control infection by monitoring the PDE teicoplanin concentration (>15.138 mg/L) on day 5 after dosing.

Aims: This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. Methods: Nonlinear mixed‐effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. Results: A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non‐complicated methicillin‐resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. Conclusions: Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow‐up therapeutic drug monitoring of teicoplanin at least once every week. [ABSTRACT FROM AUTHOR]

StrR-like pathway-specific transcriptional regulators (PSRs) function as activators in the biosynthesis of various antibiotics, including glycopeptides (GPAs), aminoglycosides, aminocoumarins, and ramoplanin-like lipodepsipeptides (LDPs). In particular, the roles of StrR-like PSRs have been previously investigated in the biosynthesis of streptomycin, novobiocin, GPAs like balhimycin, teicoplanin, and A40926, as well as LDP enduracidin. In the current study, we focused on StrR-like PSRs from the ramoplanin biosynthetic gene cluster (BGC) in Actinoplanes ramoplaninifer ATCC 33076 (Ramo5) and the chersinamycin BGC in Micromonospora chersina DSM 44151 (Chers28). Through the analysis of the amino acid sequences of Ramo5 and Chers28, we discovered that these proteins are phylogenetically distant from other experimentally investigated StrR PSRs, although all StrR-like PSRs found in BGCs for different antibiotics share a conserved secondary structure. To investigate whether Ramo5 and Chers28, given their phylogenetic positions, might influence the biosynthesis of other antibiotic pathways governed by StrR-like PSRs, the corresponding genes (ramo5 and chers28) were heterologously expressed in Actinoplanes teichomyceticus NRRL B-16726 and Nonomuraea gerenzanensis ATCC 39727, which produce the clinically-relevant GPAs teicoplanin and A40926, respectively. Recombinant strains of NRRL B-16726 and ATCC 39727 expressing chers28 exhibited improved antibiotic production, although the expression of ramo5 did not yield the same effect. These results demonstrate that some StrR-like PSRs can "cross-talk" between distant biosynthetic pathways and might be utilized as tools for the activation of silent BGCs regulated by StrR-like PSRs. [ABSTRACT FROM AUTHOR]

Heteroresistance (HR) is an enigmatic phenotype where, in a main population of susceptible cells, small subpopulations of resistant cells exist. This is a cause for concern, as this small subpopulation is difficult to detect by standard antibiotic susceptibility tests, and upon antibiotic exposure the resistant subpopulation may increase in frequency and potentially lead to treatment complications or failure. Here, we determined the prevalence and mechanisms of HR for 40 clinical Staphylococcus aureus isolates, against 6 clinically important antibiotics: daptomycin, gentamicin, linezolid, oxacillin, teicoplanin, and vancomycin. High frequencies of HR were observed for gentamicin (69.2%), oxacillin (27%), daptomycin (25.6%), and teicoplanin (15.4%) while none of the isolates showed HR toward linezolid or vancomycin. Point mutations in various chromosomal core genes, including those involved in membrane and peptidoglycan/teichoic acid biosynthesis and transport, tRNA charging, menaquinone and chorismite biosynthesis and cyclic-di-AMP biosynthesis, were the mechanisms responsible for generating the resistant subpopulations. This finding is in contrast to gram-negative bacteria, where increased copy number of bona fide resistance genes via tandem gene amplification is the most prevalent mechanism. This difference can be explained by the observation that S. aureus has a low content of resistance genes and absence of the repeat sequences that allow tandem gene amplification of these genes as compared to gram-negative species. Heteroresistance is a phenotype where, in a population of susceptible cells, small subpopulations of resistant and often unstable cells exist. This study shows that in the human pathogen Staphylococcus aureus, heteroresistance is widespread and caused by common point mutations in core genes. Examination of 40 isolates reveals that up to 2/3 of all isolates might be heteroresistant to a specific antibiotic, with the potential to cause treatment failure. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a significant cause of morbidity and mortality in humans. Understanding the common pathogens and the antibacterial susceptibility patterns of infections in each region is invaluable for effectively treating this life-threatening condition. Objectives: We studied the etiology and antibiotic susceptibility patterns of community-acquired sepsis in 3 large hospitals in Isfahan, Iran. Methods: Clinical data were extracted from patients' medical files. Bacteria were identified by standard tests, and the data on antimicrobial susceptibility patterns were obtained from the WHONET database software. Results: Among 480 patients, Escherichia coli (26.3%), Klebsiella species (22.7%), and Staphylococcus aureus (14.8%) were the most frequent isolates. The susceptibility patterns of gram-negative isolates to various antibiotics were as follows: Imipenem (92.4%), meropenem (78.6%), amikacin (76.4%), gentamicin (72.2%), and ciprofloxacin (66.5%). The sensitivity of these isolates to meropenem, amikacin, and cefepime was more remarkable in females. The sensitivity patterns of gram-positive organisms were as follows: Linezolid (100%), amikacin (100%), rifampin (100%), teicoplanin (90%), vancomycin (87.5%), gentamicin (81.7%), and trimethoprim-sulfamethoxazole (71.2%). The susceptibility of these organisms to vancomycin was significantly higher in males. Conclusions: Our data suggested that a combination of a carbapenem with linezolid, teicoplanin, or vancomycin is an appropriate empiric therapy in septicemic patients in the area. Besides, in females, linezolid or teicoplanin would be better than vancomycin for inclusion in the initial treatment. [ABSTRACT FROM AUTHOR]

Abstract Background The loading dose of teicoplanin (TEIC) is recommended for implementation. However, there is significant discrepancy between the dose settings in the package insert and, in the guidelines, and the actual status of loading doses in Japan is unclear. Furthermore, TEIC causes liver injury as side effect. Although the risk of developing liver injury has not been reported to be increased following a loading dose based on the guidelines, there is a lack of reports in large populations. Therefore, we evaluated the trend in the loading dose and factors affecting the efficacy and safety of TEIC administration. Methods A Japanese administrative claims database was used in this study. Trends in loading doses were evaluated in target populations administered TEIC between 2010 and 2019. Patient characteristics were adjusted by propensity score matching based on the guideline group (total dose of 3 days > 1,600 mg) and non-guideline group (≤ 1,600 mg) of the loading dose. Finally, univariable and multivariable conditional logistic regression analysis was performed to evaluate factors affecting 30-day mortality and liver injury. Results A total of 10,030 patients were selected based on these criteria. The proportion of loading doses based on the recommended guidelines showed an increase over time, regardless of the implementation of therapeutic drug monitoring (TDM), but especially so in cases where TDM was implemented, the loading doses were administered in accordance with the recommendations of the guidelines. Conditional logistic regression analysis showed a relationship between drug management and guidance fees (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.36‒0.55), a reimbursement indicating pharmacist intervention, and a reduction in 30-day mortality. In addition, loading doses based on the recommended guidelines had no influence on liver injury, and other factors were not significantly associated with increased incidence of liver injury. Conclusion Thus, this study implies the benefits of pharmacological management as indicated by drug management and guidance fee and supports the implementation of loading doses based on the guideline on TEIC administration.

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Nonomuraea gerenzanensis (N. gerenzanensis) is known for its ability to biosynthesize A40926, the precursor of the glycopeptide antibiotic (GPA) Dalbavancin. However, challenges and uncertainties related to the genetic manipulation of the rare actinomycetes remain. In order to improve the conjugation transfer of N. gerenzanensis, the crucial factors affecting conjugal transfer were evaluated, including agar medium, mycelial state, donor-recipient ratio, magnesium ion concentration, and antibiotic coverage time firstly. Additionally, γ-butyrolactone (GBL) for quorum sensing (QS) and antibiotics targeting bacterial walls were applied to evaluate their effects on conjugation transfer. As a result, the optimal conditions of 5%TSB of liquid medium, 24 h of the period time, V0.1 of agar medium, 30 mM of magnesium ion, the ratio 10:1 of donor-to-recipient, and 27 h of the overlaying time of antibiotic were determined. Furthermore, the results showed that autoinducer GBL and GPA teicoplanin had a synergetic effect on the conjugation transfer of N. gerenzanensis at a working concentration of 60 µM and 0.5 µg mL−1, respectively. The highest conjugation efficiency could reach about 1.3 depending on the optimal process conditions and the interference of QS and antibiotics. [ABSTRACT FROM AUTHOR]

Teicoplanin can cause acute kidney injury, but little is known about the risk of acute kidney injury when teicoplanin is co-administered with loop diuretics (a powerful diuresis), which can alter renal hemodynamics and glomerular filtration rate. We performed a signal detection analysis using a Japanese adverse event database to determine the additive impact of loop diuretics on acute kidney injury associated with teicoplanin. The dataset originated between April 2004 and August 2022. Disproportionality analysis was performed to detect the signals for acute kidney injury (the Standardized MedDRA Query) when co-administered teicoplanin or vancomycin (a positive control) with individual diuretics, including loop diuretics. Multivariate logistic regression analysis was tested to estimate the adjusted reporting odds ratio (aROR) and 95% confidence interval (95% CI). There were 147 and 515 events of acute kidney injury associated with teicoplanin and vancomycin, respectively. A significant positive signal for acute kidney injury when teicoplanin was co-administered with loop diuretics was present (aROR 4.83, 95% CI 3.52–6.61, p < 0.0001). Contrastingly, no significant signals were observed when vancomycin was co-administered with any diuretics. These findings suggest that co-administered loop diuretics may have an unfavorable effect on acute kidney injury while undertaking teicoplanin but not vancomycin. [ABSTRACT FROM AUTHOR]

Background: Foot ulcers are high-morbidity and debilitating complications of diabetes mellitus, and carry significantly increased rates of associated major amputations. They contribute to significantly worse quality of life. Osteomyelitis is a frequent complication of diabetic foot ulcers, since bacteria can contiguously spread from soft tissues to the bone, involving the cortex first and then the bone marrow. Unfortunately, clinically unsuspected osteomyelitis is frequent in persisting diabetic foot ulcers. It is associated with limb amputations and increased mortality. Case Report: We describe a 76-year-old man with long-standing insulin-treated type 2 diabetes, who experienced extensively drug-resistant Enterococcus faecalis diabetic foot myositis and osteomyelitis associated with sepsis. He was successfully treated with surgical debridement combined with the administration of teicoplanin plus rifampicin in the outpatient setting, completing, in total, a twelve-week course of antibiotic therapy. Conclusions: Clinically unsuspected osteomyelitis in patients with persisting diabetic foot ulcers has been associated with infections from highly resistant bacteria. Early and accurate diagnosis of diabetic foot osteomyelitis, as well as proper therapeutic approach (antimicrobial and surgical), is of great importance to reduce the risk of minor and major amputations, septic shock leading to multiple organ failure, and overall mortality. [ABSTRACT FROM AUTHOR]

Background The glycopeptide teicoplanin is considered first-line treatment for severe infections caused by Gram-positive bacteria. Individualized treatment of teicoplanin is gaining interest. As only protein-unbound drug is pharmacologically active, a sensitive assay measuring unbound and total teicoplanin is indispensable for pharmacological research and dose optimization. Objectives To develop and validate a UPLC-MS/MS method to quantify unbound and total teicoplanin in human serum. Methods The developed assay was validated according to the ICH guideline M10 on Bioanalytical Method Validation and study sample analysis. Unbound teicoplanin was obtained by ultrafiltration. The assay was cross-validated with a quantitative microsphere (QMS) immunoassay in a side-by-side comparison using 40 patient samples. Results With the developed and validated method, all main teicoplanin components (A2-1, A2-2/A2-3, A2-4/A2-5 and A3-1) can be quantified. Total run time was 5.5 min. Concentration range was 2.5–150 mg/L for total and 0.1–25 mg/L for unbound teicoplanin. Precision (coefficient of variation) and accuracy (bias) of total teicoplanin were 5.97% and 107%, respectively, and 7.17% and 108%, respectively, for unbound teicoplanin. Bland–Altman analysis showed total concentrations measured with the UPLC-MS/MS method were equivalent to the results of the QMS immunoassay. A total of 188 samples from 30 patients admitted to the ICU and haematology department were measured; total concentrations ranged between 2.92 and 98.5 mg/L, and unbound concentrations ranged between 0.37 and 30.7 mg/L. Conclusions The developed method provided rapid, precise and accurate measurement of unbound and total teicoplanin. The developed method is now routinely applied in pharmacological research and clinical practice. [ABSTRACT FROM AUTHOR]

Background: The loading dose of teicoplanin (TEIC) is recommended for implementation. However, there is significant discrepancy between the dose settings in the package insert and, in the guidelines, and the actual status of loading doses in Japan is unclear. Furthermore, TEIC causes liver injury as side effect. Although the risk of developing liver injury has not been reported to be increased following a loading dose based on the guidelines, there is a lack of reports in large populations. Therefore, we evaluated the trend in the loading dose and factors affecting the efficacy and safety of TEIC administration. Methods: A Japanese administrative claims database was used in this study. Trends in loading doses were evaluated in target populations administered TEIC between 2010 and 2019. Patient characteristics were adjusted by propensity score matching based on the guideline group (total dose of 3 days > 1,600 mg) and non-guideline group (≤ 1,600 mg) of the loading dose. Finally, univariable and multivariable conditional logistic regression analysis was performed to evaluate factors affecting 30-day mortality and liver injury. Results: A total of 10,030 patients were selected based on these criteria. The proportion of loading doses based on the recommended guidelines showed an increase over time, regardless of the implementation of therapeutic drug monitoring (TDM), but especially so in cases where TDM was implemented, the loading doses were administered in accordance with the recommendations of the guidelines. Conditional logistic regression analysis showed a relationship between drug management and guidance fees (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.36‒0.55), a reimbursement indicating pharmacist intervention, and a reduction in 30-day mortality. In addition, loading doses based on the recommended guidelines had no influence on liver injury, and other factors were not significantly associated with increased incidence of liver injury. Conclusion: Thus, this study implies the benefits of pharmacological management as indicated by drug management and guidance fee and supports the implementation of loading doses based on the guideline on TEIC administration. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is part of normal human flora and is widely associated with hospital-acquired bacteremia. S. aureus has shown a diverse array of resistance to environmental stresses and antibiotics. Methicillin-resistant S. aureus (MRSA) is on the high priority list of new antibiotics discovery and glycopeptides are considered the last drug of choice against MRSA. S. aureus has developed resistance against glycopeptides and the emergence of vancomycin-intermediate-resistant, vancomycin-resistant, and teicoplanin-resistant strains is globally reported. Teicoplanin-associated genes tcaR-tcaA-tcaB (tcaRAB) is known as the S. aureus glycopeptide resistance operon that is associated with glycopeptide resistance. Here, for the first time, the role of tcaRAB in S. aureus persister cells formation, and ΔtcaA dependent persisters’ ability to resuscitate the bacterial population was explored. We recovered a clinical strain of MRSA from a COVID-19 patient which showed a high level of resistance to teicoplanin, vancomycin, and methicillin. Whole genome RNA sequencing revealed that the tcaRAB operon expression was altered followed by high expression of glyS and sgtB. The RNA-seq data revealed a significant decrease in tcaA (p =  0.008) and tcaB (p =  0.04) expression while tcaR was not significantly altered. We knocked down tcaA, tcaB, and tcaR using CRISPR-dCas9 and the results showed that when tcaA was suppressed by dCas9, a significant increase was witnessed in persister cells while tcaB suppression did not induce persistence. The results were further evaluated by creating a tcaA mutant that showed ΔtcaA formed a significant increase in persisters in comparison to the wild type. Based on our findings, we concluded that tcaA is the gene that increases persister cells and glycopeptide resistance and could be a potential therapeutic target in S. aureus. [ABSTRACT FROM AUTHOR]

Yifan Wang,1,2,&ast; Fen Yao,2,&ast; Shenglong Chen,3 Xin Ouyang,4 Jinhua Lan,5 Zheng Wu,2 Yirong Wang,2 Jingchun Chen,2 Xipei Wang,6,7 Chunbo Chen1 1Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of China; 2School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, People’s Republic of China; 3Department of Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 4Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 5Department of Pharmacy, General Hospital of Southern Theatre Command, Guangzhou, 510010, People’s Republic of China; 6Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunbo Chen, Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of China, Email gghccm@163.com Xipei Wang, Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Email xipei_wang@163.comPurpose: To develop a population pharmacokinetic model describing teicoplanin concentrations in patients hospitalized in intensive care unit (ICU) and to perform Monte Carlo simulations to provide detailed dosing regimens of teicoplanin.Methods: This single-center, prospective, observational study was conducted on 151 patients in ICU with 347 plasma samples. The population pharmacokinetics model was established and various covariates were evaluated. The probability of target attainment (PTA) of various proposal dosing regimens was calculated by Monte Carlo simulations.Results: The two-compartment model adequately described teicoplanin concentration-time data. The estimated glomerular filtration rate (eGFR) associated with systemic clearance (CL) was the only covariate included in the final model. The estimate of CL was 0.838 L/h, with the eGFR adjustment factor of 0.00823. The volume of the central compartment (Vc), inter-compartmental clearance (Q) and volumes of the peripheral compartments (Vp) were 14.4 L, 3.08 L/h and 51.6 L, respectively. The simulations revealed that the standard dosage regimen was only sufficient for the patients with severe renal dysfunction (eGFR ≤ 30 mL/min/1.73 m2) to attain target trough concentration (Cmin, PTA 52.8%). When eGFR > 30 mL/min/1.73 m2, increasing dose and the administration times of loading doses were the preferred options to achieve target Cmin based on the renal function and types of infection.Conclusion: The most commonly used standard dosage regimen was insufficient for all ICU patients. Our study provided detailed dosing regimens of teicoplanin stratified by eGFR and types of infection for ICU patients.Keywords: teicoplanin, pharmacokinetics, Monte Carlo simulation, intensive care unit, renal function

In recent years, glycopeptide antibiotics have been widely used to treat severe bacterial infections. The long-term use of first-generation antibiotics of this group (vancomycin, teicoplanin) has contributed to the emergence of bacteria resistant to them. The problem of resistance has motivated the development of three new glycopeptide antibiotics: dalbavancin, telavancin, and oritavancin. The aim of this study was to consolidate and analyse the data from literature and current quality standards related to glycopeptide antibiotics. The article presents basic information about the discovery of glycopeptide antibiotics of natural origin (vancomycin, teicoplanin) and their derivatives (telavancin, oritavancin, dalbavancin). It briefly characterises the structures of the glycopeptide antibiotics under consideration and describes their main properties, application, and distribution in the pharmaceutical market. The article also gives information on the spectra of antibacterial activity of vancomycin, teicoplanin, and their semi-synthetic derivatives. It considers approaches to vancomycin and teicoplanin standardisation and covers the main requirements of leading pharmacopoeias for the quality of vancomycin, teicoplanin, and the corresponding medicinal products. According to the study results, glycopeptide antibiotics are still widely prescribed because of their high effectiveness in diseases caused by Gram-positive bacteria. However, at present, leading pharmacopoeias have developed and implemented quality standards only for two antibiotics of the group: vancomycin and teicoplanin. According to the results of literature consolidation, further modification of glycopeptide antibiotics is aimed at creating compounds characterised by prolonged action and greater effectiveness against pathogenic microorganisms. Thus, the attention of researchers should be directed to further standardisation of the newest derivatives of glycopeptide antibiotics: telavancin, oritavancin, and dalbavancin.

In patients with normal renal function, significant teicoplanin dose adjustments are often necessary. This study aimed to develop a population pharmacokinetic (PK) model for teicoplanin in healthy adults and use it to recommend optimal dosage regimens for patients with normal renal function. PK samples were obtained from 12 subjects and analyzed using a population approach. The derived parameters informed Monte Carlo simulations for dosing recommendations. The PK profile was best described using a three-compartment model, in which the estimated glomerular filtration rate calculated via the CKD-EPI equation and adjusted for body surface area was identified as a significant covariate affecting total clearance. For pathogens with a minimum inhibitory concentration of 1 mg/L, a loading dose (LD) of 14 mg/kg administered every 12 h for four doses, followed by a maintenance dose (MD) of 16 mg/kg administered every 24 h, is recommended. These findings indicate the need for dosage adjustments, such as increasing the LD and MD or decreasing the dosing interval of MD in patients with normal renal function. Because of the long half-life of teicoplanin and the requirement for long-term administration, therapeutic drug monitoring at strategic intervals is important to avoid nephrotoxicity associated with elevated trough concentrations.

Abstract Introduction Pharmacist-driven (PD) dosing and monitoring services have been shown to improve the clinical and economic outcomes in patients treated with different antibiotics, other than teicoplanin. This study investigates the impact of PD dosing and monitoring services on the clinical and economic outcomes of non-critically ill patients receiving teicoplanin treatment. Methods A single-center retrospective study was conducted. Patients were divided into the PD group and the non-PD (NPD) group. Primary outcomes included the achievement of target serum concentration, and a composite endpoint of all-cause mortality, intensive care unit (ICU) admission, and sepsis or septic shock development during hospitalization or within 30 days of hospital admission. The cost of teicoplanin, overall medication cost, and total cost during hospital stay were also compared. Results A total of 163 patients from January to December 2019 were included and assessed. Seventy patients were assigned to the PD group and 93 to the NPD group. The PD group had a higher percentage of patients reaching the target trough concentration (54% versus 16%, p

An Enterococcus faecium strain was obtained from a paraprostatic cyst of a 17-year-old dog in Greece. Antibiotic susceptibility testing (AST) was accomplished by disc diffusion and MIC methods, and the isolate demonstrated a multidrug-resistant (MDR) phenotype against a great variety of antibiotics, such as β-Lactams, Quinolones, Macrolides, Tetracyclines, Rifampin, Nitrofurantoin, and surprisingly, Glycopeptides, Fosfomycin and Gentamicin (high-level). Molecular screening for Vancomycin resistance genes was carried out, and a vanA gene cluster was identified. To our knowledge, this is the first report of a vanA-positive E. faecium strain isolated from a companion animal in Greece. Importantly, this strain was related with the presence of paraprostatic cysts, a pathological condition requiring treatment. The presence of a highly resistant isolate in a canine clinical sample and the consequent need for treatment constitutes a new challenge for veterinarians due to the lack of available treatment options. Our findings indicate the occurrence of respective bacteria in companion animals, which could act as a reservoir of epidemic MDR strains or relevant mobile genetic elements (MGE) in the community, constituting a threat for public health.

Background: The effectiveness, safety, and cost of vancomycin and linezolid for managing gram-positive bacterial infections in Kuwait are unknown. This study assessed the effectiveness, safety, and cost of vancomycin, teicoplanin and linezolid for managing gram-positive bacterial infections in Kuwait. Research design and methods: This retrospective study included adult patients who were prescribed antibiotics (vancomycin, teicoplanin, and linezolid) for the treatment of gram-positive infections at five hospitals in Kuwait. Descriptive statistics were used to assess the effectiveness and safety outcomes. A cost analysis was performed on the patients hospitalised for gram-positive infections. Results: Among 116 patients, 42.2 % (n = 49) received glycopeptides (vancomycin [n = 45] and teicoplanin [n = 4]) or linezolid (n = 67). Clinical cure was achieved in 100 patients without significant intergroup differences (p = 0.34). Thrombocytopenia and acute kidney injury occurred in 19 and 20 patients (p = 0.82 and 0.96), respectively, and their incidence was similar with all the studied agents. The average cost per patient was USD 983.70. The estimated total direct medical costs were USD 894,570.6, the cost was highest for linezolid (USD 469,682.30) and vancomycin (USD 370,342.5), and lowest for teicoplanin (USD 20,799.9). Conclusions: Glycopeptides and linezolid were highly effective. Linezolid was the most frequently prescribed agent; its effectiveness and safety were similar according to the antibiotic class. However, treatment with linezolid and vancomycin were associated with considerable costs.

Introduction: We aimed to investigate the efficacy of local boric acid (BA) and teicoplanin in prosthetic vascular graft infection (PVGI) caused by methicillin-resistant Staphylococcus aureus (MRSA) in a rat model. Methodology: Fourty rats were divided into five groups. Group 1 received no treatments (control group); group 2 was uncontaminated polytetrafluoroethylene (PTFE) graft group; group 3 was untreated and the PTFE graft was contaminated with 2×107 CFU/mL MRSA; group 4 received local BA (8 mg/kg) and was contaminated with with 2×107 CFU/mL MRSA; group 5 received local BA (8 mg/kg) and intraperitoneal teikoplanin (10 mg/kg), and was contaminated with 2×107 CFU/mL MRSA; On the 3rd day, grafts and serums were removed for microbiological, histological and serological tests. Results: The amounts of culture growth in groups 4 and 5 were significantly lower compared to group 3 (p < 0.001). TNF-a was significantly higher in Group 3 than the other groups (p = 0.001). There was no significant difference between the groups in serum IL-1 levels (p = 0.138). Monocyte chemotactic protein-1 (MCP-1) was not significantly different between groups 3, 4, and 5, but it was significantly higher than groups 1 and 2 (p < 0.001). The severity of inflammation was significantly higher in group 3 than the other groups, and fibroblastic proliferation, granulation tissue and collagen synthesis were significantly lower (p < 0.05). Conclusions: Our study showed that local BA and combined teicoplanin treatment is effective in preventing PVGI. [ABSTRACT FROM AUTHOR]

Purpose: The parenteral antibiotic therapies have always been associated with several limitations that could be overcome by nano-based drug delivery systems. In this study, we aimed to fabricate teicoplanin-loaded zein-chitosan (CS)-zein sandwich-like electrospun nanofibers for targeted drug delivery. Methods: The sandwich-like structures of zein-CS/teicoplanin-zein nanofibers were fabricated by the electrospinning process. Nanofiber membranes were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), drug encapsulation efficiency, in vitro release profile, and tensile strength studies. Finally, the antibacterial activity of the neat teicoplanin and zein-CS/teicoplanin-zein nanofibers was evaluated in static and dynamic conditions. Results: SEM images demonstrated the use of suitable electrospinning conditions that led to the fabrication of the smooth and bead-free nanofibers with nanoscale diameter formation. FTIR and DSC analysis confirmed the presence and uniform distribution of the drug and also the interaction between the teicoplanin and chitosan in the formulation. The concentration of teicoplanin has a direct effect on the increase of mechanical tensile properties of sandwich-like nanofibers. In vitro release profile assay showed a burst release of teicoplanin during the first 24 h followed by a slow-release profile for 19 days. Finally, zein-CS/teicoplanin-zein nanofiber membranes showed significantly higher antibacterial activity compared with neat zein-CS-zein nanofibers and teicoplanin alone at the same concentration. Conclusion: These results indicate that zein-CS-zein nanofibers would be a prospective candidate for targeted drug delivery in the treatment of local infections. [ABSTRACT FROM AUTHOR]

Glycopeptide antibiotics (vancomycin and teicoplanin) are usually used for the treatment of Staphylococcus epidermidis infections owing to their increased oxacillin resistance. However, S. epidermidis strains with decreased susceptibility to teicoplanin have become increasingly incident in recent years. We aimed to identify the characteristics of teicoplanin-non-susceptible (Teico-NS) S. epidermidis isolated at our hospital and analyze its relationship with teicoplanin usage. We retrospectively evaluated 328 S. epidermidis strains isolated from clinical isolates between January 2016 and December 2021. All strains were susceptible to vancomycin (minimal inhibitory concentration (MIC) ≤ 4 mg/L). The annual incidence for S. epidermidis strains with an elevated teicoplanin MIC of 8 mg/L ranged from 22.2 to 28.9%. In addition, in 2021, the number of S. epidermidis strains with teicoplanin MIC ≥ 16 mg/L rapidly increased (n = 13, 32.5%). Furthermore, teicoplanin use increased annually until 2019; however, in 2020, it decreased abruptly due to the COVID 19 pandemic. Thus, we could not confirm the existence of a clear correlation between teicoplanin usage and increased incidence of S. epidermidis with reduced teicoplanin-susceptibility. We showed the increased incidence of Teico-NS S. epidermidis in recent years. Further studies are needed to identify the mechanisms and risk factors for teicoplanin-resistance in S. epidermidis. [ABSTRACT FROM AUTHOR]

D‐amino acids and epimeric peptides/proteins can play crucial biological roles and adversely affect protein folding and oligopeptide aggregation in age‐related pathologies in humans. This has ignited interest in free D‐amino acids as well as those incorporated in peptides/proteins and their effects in humans. However, such stereoisomeric analytes are often elusive and in low abundance with few existing methodologies capable of scouting for and identifying them. In this work, we examine the feasibility of using teicoplanin aglycone, a macrocyclic antibiotic, which has been reported to strongly retain D‐amino acids and peptides with a D‐amino acid on the C‐terminus, for use as a solid phase extraction (SPE) medium. The HPLC retention factors of L‐/D‐amino acids and C‐terminus modified D‐amino acid‐containing peptides and their L‐amino acid exclusive counterparts on teicoplanin aglycone are presented. Retention curve differences between amino acids and peptides highlight regions of solvent composition that can be utilized for their separation. This approach is particularly useful when coupled with enzymatic hydrolysis via carboxypeptidase Y to eliminate all L‐amino acid exclusive peptides. The remaining peptides with carboxy‐terminal D‐amino acids are then more easily concentrated and identified. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is considered a serious threat to public health, besides is one of the most common causes of subclinical mastitis in dairy cows. Therefore, especially methicillin-resistant Staphylococcus aureus (MRSA) is among the most critical reasons for antibiotic treatment. Monitoring the antibiotic resistance of MRSA from livestock animals and foods is of great significance. This study aimed to detect vancomycin, teicoplanin, and linezolid resistance of bulk tank milk-borne 34 MRSA isolates by the E-test method to determine MIC values. In the study, it was determined that 8.8% of MRSA isolates were also resistant to vancomycin, and 11.7% to linezolid, while none of the isolates were determined to be resistant to teicoplanin. Data from the study reveal the status of the efficacy of the commonly used antibiotics vancomycin and linezolid against MRSA infections. Especially before MRSA treatment, MIC values of antibiotics should be determined, and appropriate antibiotics should be used in effective doses. [ABSTRACT FROM AUTHOR]

Teicoplanin is a glycopeptide antibiotic used to treat severe staphylococcal infections. It has been claimed that teicoplanin possesses ototoxic potential, although its toxic effects on cochlear hair cells (HCs) remain unknown. The TP53-induced glycolysis and apoptosis regulator (TIGAR) plays a crucial role in promoting cell survival. Prior research has demonstrated that TIGAR protects spiral ganglion neurons against cisplatin damage. However, the significance of TIGAR in damage to mammalian HCs has not yet been investigated. In this study, firstly, we discovered that teicoplanin caused dose-dependent cell death in vitro in both HEI-OC1 cells and cochlear HCs. Next, we discovered that HCs and HEI-OC1 cells treated with teicoplanin exhibited a dramatically decrease in TIGAR expression. To investigate the involvement of TIGAR in inner ear injury caused by teicoplanin, the expression of TIGAR was either upregulated via recombinant adenovirus or downregulated by shRNA in HEI-OC1 cells. Overexpression of TIGAR increased cell viability, decreased apoptosis, and decreased intracellular reactive oxygen species (ROS) level, whereas downregulation of TIGAR decreased cell viability, exacerbated apoptosis, and elevated ROS level following teicoplanin injury. Finally, antioxidant therapy with N-acetyl-L-cysteine decreased ROS level, prevented cell death, and restored p38/phosphorylation-p38 expression levels in HEI-OC1 cells injured by teicoplanin. This study demonstrates that TIGAR may be a promising novel target for the prevention of teicoplanin-induced ototoxicity. [ABSTRACT FROM AUTHOR]

Enterococcus faecium is a commensal microorganism that can cause infections such as bacteremia. Incidence of ampicillin-resistant and vancomycin-susceptible E. faecium (EfARSV) bacteremia is on the rise, and the mortality rate is high. Despite much data, the most appropriate treatment remains a question. This article mostly reviews the relevant aspects of EfARSV bacteremia: microbiology, gastrointestinal tract colonization and invasion, antibiotic resistance, epidemiology, risk factors, mortality, and treatment, including pharmacologic components of employed agents and related clinical evidence. A literature search was conducted on PubMed on 31 July 2022, which was updated on 15 November 2022. EfARSV bacteremia presents high mortality. However, it is uncertain whether mortality is attributable to or a marker of severity/comorbidities. Considering its antibiotic resistance pattern, EfARSV is considered a difficult-to-treat microorganism. Glycopeptides have been used to treat EfARSV, with linezolid and daptomycin serving as potential alternative agents. Yet, the use of daptomycin is controversial due to a higher risk of treatment failures. Clinical evidence on this issue is scarce, unfortunately, and subject to many limitations. Despite increased incidence and mortality, EfARSV bacteremia presents multiple aspects to be addressed in well-conducted studies. [ABSTRACT FROM AUTHOR]

Abstract Background Enterococcus faecalis remains one of the most common pathogens causing infection in surgical patients. Our goal was to evaluate the antibiotic resistance of E. faecalis, causing infections in a surgical clinic, against two antibacterial drugs, ampicillin and teicoplanin. One commonly administered in the past for such infections, ampicillin, and another newer, teicoplanin, which demonstrated exceptionally good efficacy. Methods Data from 1882 isolates were retrieved from the microbiology department database during two 5-year periods. Standard biochemical methods were employed for the identification of the isolates. The prevalence of E. faecalis among patients with clinical evidence of infection in a surgical oncology ward was assessed. Confidence interval (CI) as well as standard error (SE) were calculated. Moreover, the annual incidence of E. faecalis infections in this surgical ward was recorded. The susceptibility of E. faecalis to ampicillin and teicoplanin was studied and compared using Fisher’s exact test. Results and conclusion Results showed that the incidence of E. faecalis infections in the surgical clinic was increasing. Ampicillin, in the later year period, was not statistically different from teicoplanin in treating E. faecalis infections. Consequently, ampicillin seems currently to be an effective antibiotic against such infections that could be used as empiric therapy.

StrR-like pathway-specific transcriptional regulators (PSRs) function as activators in the biosynthesis of various antibiotics, including glycopeptides (GPAs), aminoglycosides, aminocoumarins, and ramoplanin-like lipodepsipeptides (LDPs). In particular, the roles of StrR-like PSRs have been previously investigated in the biosynthesis of streptomycin, novobiocin, GPAs like balhimycin, teicoplanin, and A40926, as well as LDP enduracidin. In the current study, we focused on StrR-like PSRs from the ramoplanin biosynthetic gene cluster (BGC) in Actinoplanes ramoplaninifer ATCC 33076 (Ramo5) and the chersinamycin BGC in Micromonospora chersina DSM 44151 (Chers28). Through the analysis of the amino acid sequences of Ramo5 and Chers28, we discovered that these proteins are phylogenetically distant from other experimentally investigated StrR PSRs, although all StrR-like PSRs found in BGCs for different antibiotics share a conserved secondary structure. To investigate whether Ramo5 and Chers28, given their phylogenetic positions, might influence the biosynthesis of other antibiotic pathways governed by StrR-like PSRs, the corresponding genes (ramo5 and chers28) were heterologously expressed in Actinoplanes teichomyceticus NRRL B-16726 and Nonomuraea gerenzanensis ATCC 39727, which produce the clinically-relevant GPAs teicoplanin and A40926, respectively. Recombinant strains of NRRL B-16726 and ATCC 39727 expressing chers28 exhibited improved antibiotic production, although the expression of ramo5 did not yield the same effect. These results demonstrate that some StrR-like PSRs can “cross-talk” between distant biosynthetic pathways and might be utilized as tools for the activation of silent BGCs regulated by StrR-like PSRs.