Search

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 selfcontrol 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. [ABSTRACT FROM AUTHOR]

Teicoplanin has been banned in the veterinary field due to the drug resistance of antibiotics. However, teicoplanin residue from the antibiotic abuse of humans and animals poses a threat to people's health. Therefore, it is necessary to develop an efficient way for the highly accurate and reliable detection of teicoplanin from humans, food, and water. In this study, novel imprinted quantum dots of teicoplanin were prepared based on boronate affinity-based precisely controlled surface imprinting. The imprinting factor (IF) for teicoplanin was evaluated and reached a high value of 6.51. The results showed excellent sensitivity and selectivity towards teicoplanin. The relative fluorescence intensity was inversely proportional to the concentration of teicoplanin, in the range of 1.0–17 μM. And its limit of detection (LOD) was obtained as 0.714 μM. The fluorescence quenching process was mainly controlled by a static quenching mechanism via the non-radiative electron-transfer process between QDs and the five-membered cyclic boronate esters. The recoveries for the spiked urine, milk, and water samples ranged from 95.33 to 104.17%, 91.83 to 97.33, and 94.22 to 106.67%, respectively. [ABSTRACT FROM AUTHOR]

Introduction: According to the World Health Organization, the likelihood of mortality due to MRSA infections is estimated to be 64% higher compared to that caused by susceptible Staphylococcal isolates. In India, the prevalence of MRSA is considerable and varies across regions. Western India has reported a 25% MRSA prevalence, while Southern India has reported a higher rate of 50%. Aims & Objectives: To find out the invitro susceptibility pattern of MRSA and the susceptibility of fluoroquinolone-resistant Staphylococcal isolates (including MRSA) against Levonadifloxacin along with other antibiotics within formulary. Material & Methods: This was a prospective, descriptive study carried out in the Department of Microbiology, Central Laboratory School of Medical Science and Research (SMS&R), Sharda Hospital, Sharda University Greater Noida. For in-vitro susceptibility of MRSA, isolates positive for catalase and coagulase test (Staphylococcus aureus) were subjected for Antibiotic sensitivity testing along with cefoxitin disc and results were interpreted according to CLSI guidelines. Results: In the present study Gram positive isolates were found to be highly sensitive for Vancomycin (100%) followed by Linezolid (98%), Teicoplanin (92.8%), nitrofurantoin (83.14%) and Fosfomycin (88.37%) whereas, Cefipime was the least sensitive (1.2%) drug among all the antibiotics tested. MRSA was found to be highly sensitive for Vancomycin (100%) followed by Linezolid (96.8%), Teicoplanin (96.8%), Levonadiflocxacin (89.1%) and Gentamicin (67.4%) whereas, Cefoxitin was the least sensitive (0%) drug among all the antibiotics tested. Conclusion: As the antibiotic resistance is on the rise nowadays, updating the strategies to overcome the growing antibiotic resistance like selection of narrow spectrum antibiotics with low resistance properties and antibiotic resistance surveillance is need of the hour. [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: 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]

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]

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]

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.

Teicoplanin has been banned in the veterinary field due to the drug resistance of antibiotics. However, teicoplanin residue from the antibiotic abuse of humans and animals poses a threat to people’s health. Therefore, it is necessary to develop an efficient way for the highly accurate and reliable detection of teicoplanin from humans, food, and water. In this study, novel imprinted quantum dots of teicoplanin were prepared based on boronate affinity-based precisely controlled surface imprinting. The imprinting factor (IF) for teicoplanin was evaluated and reached a high value of 6.51. The results showed excellent sensitivity and selectivity towards teicoplanin. The relative fluorescence intensity was inversely proportional to the concentration of teicoplanin, in the range of 1.0–17 μM. And its limit of detection (LOD) was obtained as 0.714 μM. The fluorescence quenching process was mainly controlled by a static quenching mechanism via the non-radiative electron-transfer process between QDs and the five-membered cyclic boronate esters. The recoveries for the spiked urine, milk, and water samples ranged from 95.33 to 104.17%, 91.83 to 97.33, and 94.22 to 106.67%, respectively.

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.

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 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]

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]

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.

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.

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.

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]

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 < 0.001). Around 26% of the patients in the PD group and 50% of the patients in the NPD group met the composite endpoint during their hospital stay (p = 0.002). The PD group exhibited a significantly lower incidence of sepsis or septic shock, shorter hospital stays, reduced drug costs, and lower total expenses. Conclusions: Our study demonstrates that pharmacist-driven teicoplanin therapy can improve the clinical and economic outcomes for non-critically ill patients. Trial registration: https://www.chictr.org.cn; identifier, ChiCTR2000033521. [ABSTRACT FROM AUTHOR]

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. [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.

Lipoglycopeptide antibiotics are semi-synthetic derivatives of glycopeptides and are characterized by a pronounced bactericidal activity against gram-positive pathogens. The aim of the study was comparative assessment of the sensitivity of gram-positive clinical isolates to lipoglycopeptide antibiotics (telavancin, dalbavancin, oritavancin). The following isolates were included in the work: methicillin-resistant Staphylococcus aureus (MRSA, n=780), methicillin-resistant coagulase-negative Staphylococcus spp. (MRCoNS, n=163), and vancomycin-resistant Enterococcus faecium (VREf, n=93). Serial dilutions were used to assess sensitivity with the addition of 0.002% polysorbate 80 to the medium. Lipoglycopeptides showed more pronounced antibacterial activity against MRSA compared to vancomycin, teicoplanin, and daptomycin, and had a MIC₅₀/MIC₉₀ (µg/ml): for telavancin — 0.06 /0.125, for dalbavancin — 0.016/0.06, and for oritavancin — 0.06/0.125. A trend towards an increase in the MIC of lipoglycopeptides and daptomycin was established in MRSA with the MIC of 2 µg/ml for vancomycin, the proportion of which was 13%. For MRCoNS, MIC₅₀ and MIC₉₀ of lipoglycopeptides did not exceed 0.06 µg/ml and 0.125 µg/ml, respectively. Oritavancin showed strong activity against VREf at MIC range of 0.03 µg/ml to 0.5 µg/ml, and at MIC₉₀ of 0.25 µg/ml. Thus, lipoglycopeptide antibiotics are a plausible alternative to vancomycin and daptomycin; they are characterized by pronounced activity and can be used to treat severe forms of staphylococcal infections.

This paper provides a review of the largest studies (over the period of 2017 to 2022) on cost-effectiveness analysis of the recommended treatment algorithms for Clostridioides difficile infection in patients with antibiotic-associated diarrhea (AAD), including pseudomembranous colitis. The review showed that professional medical societies in Russia, EU and US as well as meta-analyses consistently consider vancomycin as the most important treatment option for AAD and pseudomembranous colitis. The role of metronidazole and fidaxomicin in the treatment of AAD is considered ambiguous. Teicoplanin is recommended for using more commonly based on cost-effectiveness analysis.

Patients with severe coronavirus disease 2019 (COVID-19) receiving ventilation or pulmonary support via veno-venous extracorporeal membrane oxygenation (VV-ECMO) can be infected with drug-resistant bacteria. When introducing VV-ECMO, the changes in serum antibiotic concentration should be considered due to an increased volume of distribution (Vd). However, no pharmacokinetic study has assessed teicoplanin (TEIC) treatment in patients with COVID-19 receiving VV-ECMO.

ABSTRACT: Objective: To evaluate the cost-effectiveness of dalbavancin compared with standard of care (SoC) treatment as daptomycin or teicoplanin in patients with sternal wound infections (SWI). Methods: Multicentre retrospective study of patients diagnosed with SWI from January 2016 to December 2019 at two cardiac surgery facilities treated with dalbavancin, teicoplanin or daptomycin. Patients with SWI treated with dalbavancin were compared with SoC to evaluate resolution of infection at 90 and 180 days from infection diagnosis, length of stay (LoS) and management costs. Results: 48 patients with SWI were enrolled, 25 (50%) male, median age 67 (60–73) years, Charlson index score 5 (4–7). Fifteen patients were treated with dalbavancin (31%) and 33 with SoC (69%): teicoplanin in 21 (63%), and daptomycin in 12 (37%). Staphylococcus species were the most frequent isolates (44, 92%), mostly (84%) resistant to methicillin. All patients were treated with surgical debridement followed by negative pressure wound therapy. Wound healing at day 90 and 180 was achieved in 46 (95.8%) and 34 (82.9%) of patients, respectively. A shorter length of hospitalization in patients treated with dalbavancin compared with SoC [12 (7–18) days vs 22 (12–36) days, p:0.009] was found. Treatment with dalbavancin resulted in total cost savings of €16 026 (95% CI 5976–26 076, P < 0.001). Savings were mainly related to the LoS that was significantly shorter in the dalbavancin group, generating significantly lower cost compared to SoC group. Conclusion: Dalbavancin treatment of sternal wound infections is effective and seems to reduce hospitalization length, leading to significantly lower costs.

Objectives: Vancomycin and teicoplanin are glycopeptides with activity against Enterococcus faecium. However, studies on the clinical efficacy of teicoplanin are limited. This study aimed to compare the therapeutic efficacy of teicoplanin and vancomycin in E. faecium bacteremia. Methods: We identified patients with bloodstream infections prospectively from July 2015 to December 2016 in 14 hospitals as part of a multicenter nationwide surveillance. Patients with E. faecium monomicrobial bacteremia were selected. Teicoplanin and vancomycin groups included patients treated with either agent for ≥48 hours. The primary outcome was 30-day all-cause in-hospital mortality. The Cox proportional hazards model with inverse probability weighting was used to account for the imbalance in baseline characteristics between the two groups. Results: Among 97 patients with E. faecium bacteremia, 33 (34%) were treated with teicoplanin and 64 (66%) with vancomycin. There were no significant differences in 30-day in-hospital mortality (18.2% vs 26.6%, P = 0.358) and 7-day mortality (6.1% vs 15.6%, P = 0.212). Furthermore, multivariable analysis confirmed that the use of teicoplanin was not significantly associated with mortality (adjusted odds ratio, 0.72; 95% confidence interval, 0.28-1.86; P = 0.494). Conclusion: We found no significant differences in the clinical outcomes. These findings suggest teicoplanin as a useful alternative to vancomycin.

Objectives: Teicoplanin has been extensively used in the treatment for infections caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). However, current teicoplanin treatment is challenging due to relatively low and variable concentrations under standard dosage regimens. This study aimed to investigate the population pharmacokinetics (PPK) characteristics of teicoplanin in adult sepsis patients and provide recommendations for optimal teicoplanin dosing regimens. Methods: A total of 249 serum concentration samples from 59 septic patients were prospectively collected in the intensive care unit (ICU). Teicoplanin concentrations were detected, and patients’ clinical data were recorded. PPK analysis was performed using a non-linear, mixed-effect modeling approach. Monte Carlo simulations were performed to evaluate currently recommended dosing and other dosage regimens. The optimal dosing regimens were defined and compared by different pharmacokinetic/pharmacodynamic parameters, including trough concentration (Cmin), the ratio of 24-h area under the concentration-time curve to the minimum inhibitory concentration (AUC0-24/ MIC), as well as the probability of target attainment (PTA) and the cumulative fraction of response (CFR) against MRSA. Results: A two-compartment model adequately described the data. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance and peripheral compartment volume were 1.03 L/h, 20.1 L, 3.12 L/h and 101 L, respectively. Glomerular filtration rate (GFR) was the only covariate that significantly affected teicoplanin clearance. Model-based simulations revealed that 3 or 5 loading doses of 12/15 mg/kg every 12 h followed by a maintenance dose of 12/15 mg/kg every 24 h–72 h for patients with different renal functions were required to achieve a target Cmin of 15 mg/L and a target AUC0-24/MIC of 610. For MRSA infections, PTAs and CFRs were not satisfactory for simulated regimens. Prolonging the dosing interval may be easier to achieve the target AUC0-24/MIC than reducing the unit dose for renal insufficient patients. Conclusion: A PPK model for teicoplanin in adult septic patients was successfully developed. Model-based simulations revealed that current standard doses may result in undertherapeutic Cmin and AUC, and a single dose of at least 12 mg/kg may be needed. AUC0-24/MIC should be preferred as the PK/PD indicator of teicoplanin, if AUC estimation is unavailable, in addition to routine detection of teicoplanin Cmin on Day 4, follow-up therapeutic drug monitoring at steady-state is recommended. [ABSTRACT FROM AUTHOR]