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Clinical Microbiology Reviews Jun 2023Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern... (Review)
Review
Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Significant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis. Therapeutic drug monitoring (TDM) for antimicrobial therapy is evolving for VRE-active agents; however, there are significant gaps in the literature for predicting antimicrobial efficacy for VRE BSIs. To date, TDM has the greatest evidence for predicting drug toxicity for the three main VRE-active antimicrobial agents daptomycin, linezolid, and teicoplanin. This article presents an overview of the treatment options for VRE BSIs, the role of antimicrobial dose optimization through TDM in supporting clinical infection management, and challenges and perspectives for the future.
Topics: Humans; Anti-Bacterial Agents; Vancomycin; Linezolid; Bacteremia; Vancomycin-Resistant Enterococci; Anti-Infective Agents; Sepsis; Gram-Positive Bacterial Infections
PubMed: 37067406
DOI: 10.1128/cmr.00059-22 -
Current Opinion in Critical Care Oct 2023Staphylococcus aureus is a significant human pathogen, causing a variety of infections, from skin and soft tissue infections to endocarditis, bone and joint infections... (Review)
Review
PURPOSE OF REVIEW
Staphylococcus aureus is a significant human pathogen, causing a variety of infections, from skin and soft tissue infections to endocarditis, bone and joint infections and deep tissue abscesses. Mortality from S. aureus bacteraemia remains high, without major therapeutic advances in recent decades.
RECENT FINDINGS
In recent years, optimized dosing of antibiotics is increasingly being recognized as a cornerstone of management for severe infections including S. aureus bacteraemia. This comprehensive review details the pharmacokinetics/pharmacodynamics (PK/PD) targets for commonly used antistaphylococcal antibiotics and the doses predicted to achieve them in clinical practice. Recent advances in dosing of teicoplanin and use of cefazolin in CNS infections and findings from combination therapy studies are discussed. Drug exposure relationships related to toxicity are also detailed.
SUMMARY
This review details the different PK/PD targets for drugs used to treat S. aureus bacteraemia and how to apply them in various scenarios. The drug doses that achieve them, and the risks of toxicity are also provided.
Topics: Adult; Humans; Staphylococcal Infections; Bacteremia; Staphylococcus aureus; Cefazolin; Anti-Bacterial Agents
PubMed: 37641503
DOI: 10.1097/MCC.0000000000001072 -
International Journal of Antimicrobial... Nov 2023Dalbavancin is a lipoglycopeptide with a long elimination half-life and is currently licensed for the treatment of acute bacterial skin and skin structure infections in...
BACKGROUND
Dalbavancin is a lipoglycopeptide with a long elimination half-life and is currently licensed for the treatment of acute bacterial skin and skin structure infections in adults. Dalbavancin's potential in treating off-label complex Gram-positive infections is promising and real-world experience in treating such infections is growing. However, clear guidance on extended dosing regimens is lacking.
OBJECTIVES
This study aimed to provide clear expert opinion based on recent pharmacokinetic literature and expert and real-world experience in infection areas that require > 2 weeks of treatment.
METHODS
A single face-to-face meeting was held in September 2022 to collate expert opinion and present safety data of dalbavancin use in these clinical indications. A survey was completed by all authors on their individual experience with dalbavancin, which highlighted the heterogeneity in the regimens that were used.
RESULTS
After review of the survey data and recent literature, this study presents expert panel proposals that accommodate different healthcare settings and resource availability, and centre around the length of treatment duration including up to or exceeding 6 weeks. To achieve adequate dalbavancin concentrations for up to 6 weeks, 3000 mg of dalbavancin should be given over 4 weeks for the agreed complex infections requiring > 2 weeks of treatment. Therapeutic drug monitoring (TDM) is advised for longer treatment durations and in cases of renal failure. Specific dosing recommendations for other special populations require further investigation.
CONCLUSIONS
These proposals based on expert opinion have been defined to encourage best practice with dalbavancin, to optimise its administration beyond the current approved licenced dose across different healthcare settings.
Topics: Adult; Humans; Anti-Bacterial Agents; Drug Monitoring; Expert Testimony; Teicoplanin
PubMed: 37633424
DOI: 10.1016/j.ijantimicag.2023.106960 -
Expert Review of Anti-infective Therapy 2023is a commensal microorganism that can cause infections such as bacteremia. Incidence of ampicillin-resistant and vancomycin-susceptible (EfARSV) bacteremia is on the... (Review)
Review
INTRODUCTION
is a commensal microorganism that can cause infections such as bacteremia. Incidence of ampicillin-resistant and vancomycin-susceptible (EfARSV) bacteremia is on the rise, and the mortality rate is high. Despite much data, the most appropriate treatment remains a question.
AREAS COVERED
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.
EXPERT OPINION
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.
Topics: Humans; Anti-Bacterial Agents; Vancomycin; Daptomycin; Enterococcus faecium; Treatment Outcome; Bacteremia; Ampicillin; Gram-Positive Bacterial Infections
PubMed: 37294450
DOI: 10.1080/14787210.2023.2223977 -
The Journal of Antimicrobial... Dec 2023Limited pharmacokinetics data support dalbavancin long-term use in off-label indications and the optimal dosing regimen is debated. We aimed to describe dalbavancin... (Observational Study)
Observational Study
OBJECTIVES
Limited pharmacokinetics data support dalbavancin long-term use in off-label indications and the optimal dosing regimen is debated. We aimed to describe dalbavancin concentrations in an observational retrospective multicentre study.
METHODS
Patients from 13 French hospitals, treated with 1500 mg doses of dalbavancin and for whom therapeutic drug monitoring was performed from June 2018 to March 2021 were included. Dalbavancin plasma concentrations were described at peak and 1, 2, 3, 4, 6 and 8 weeks after the last 1500 mg dose. Concentrations in patients weighing more or less than 75 kg and with a GFR greater or less than 60 mL/min were compared. Microbiological data were collected and dalbavancin MIC was measured when possible.
RESULTS
One hundred and thirty-three patients were included (69% treated for bone and joint infections, 16% for endocarditis). Thirty-five patients received a single dose of dalbavancin and 98 received several administrations. Two, 3 and 4 weeks after the last dose, median plasma concentrations were respectively 25.00, 14.80 and 9.24 mg/L for the first doses and 34.55, 22.60 and 19.20 mg/L for the second or subsequent doses. Weight and renal function had an impact on pharmacokinetics. Infection was documented in 105 patients (Staphylococcus spp. in 68% of cases). Staphylococcus aureus was isolated in 32.5% of cases (median MIC: 0.047 mg/L) and Staphylococcus epidermidis in 27% of cases (median MIC of 0.047 mg/L).
CONCLUSIONS
Plasma concentrations of dalbavancin were consistent with those described in clinical trials and those sought during the industrial development of the molecule.
Topics: Humans; Anti-Bacterial Agents; Teicoplanin; Staphylococcal Infections; Staphylococcus aureus
PubMed: 37864551
DOI: 10.1093/jac/dkad331 -
International Journal of Antimicrobial... May 2024Clostridioides difficile (formerly Clostridium difficile) has been regarded as an 'urgent threat' and a significant global health problem, as life-threatening diarrhoea... (Review)
Review
Clostridioides difficile (formerly Clostridium difficile) has been regarded as an 'urgent threat' and a significant global health problem, as life-threatening diarrhoea and refractory recurrence are common in patients with C. difficile infection (CDI). Unfortunately, the available anti-CDI drugs are limited. Recent guidelines recommend fidaxomicin and vancomycin as first-line drugs to treat CDI, bezlotoxumab to prevent recurrence, and faecal microbiota transplantation for rescue treatment. Currently, researchers are investigating therapeutic antibacterial drugs (e.g. teicoplanin, ridinilazole, ibezapolstat, surotomycin, cadazolid, and LFF571), preventive medications against recurrence (e.g. Rebyota, Vowst, VP20621, VE303, RBX7455, and MET-2), primary prevention strategies (e.g. vaccine, ribaxamase, and DAV132) and other anti-CDI medications in the preclinical stage (e.g. Raja 42, Myxopyronin B, and bacteriophage). This narrative review summarises current medications, including newly marketed drugs and products in development against CDI, to help clinicians treat CDI appropriately and to call for more research on innovation.
PubMed: 38734214
DOI: 10.1016/j.ijantimicag.2024.107198 -
Clinical Therapeutics Sep 2023Vancomycin and linezolid are first-line drugs used for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Vancomycin is well...
PURPOSE
Vancomycin and linezolid are first-line drugs used for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Vancomycin is well known as the best alternative drug when linezolid-induced thrombocytopenia occurs. However, several cases with vancomycin-induced thrombocytopenia, especially with bleeding complications, have been reported recently, which has attracted attention. The objective of this study is to assess the potential relevance between vancomycin and bleeding complications in thrombocytopenia.
METHODS
This is a real-world pharmacovigilance study conducted in October 2022 using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We performed a disproportional analysis to assess the risk of bleeding complications in vancomycin-induced thrombocytopenia by calculating reporting odds ratios (RORs) and information components (ICs), with a weak signal defined as a lower limit of the IC 95% CI of 0 to 1.5, a middle signal defined as a lower limit of the IC 95% CI of 1.5 to 3.0, and a strong signal defined as a lower limit of the IC 95% CI of >3.0.
FINDINGS
There were 21,854 cases in the FAERS database that listed vancomycin as a suspected drug from quarter 1 of 2004 to quarter 2 of 2022. There were 800 cases of vancomycin-induced thrombocytopenia and 125 cases of bleeding complications in vancomycin-induced thrombocytopenia. Teicoplanin, tigecycline, and vancomycin (3 middle signals) were sequentially less associated with thrombocytopenia than linezolid (strong signal). However, bleeding complications in thrombocytopenia were significant associated with vancomycin (ROR = 9.641; 95% CI, 8.105-11.468; IC = 3.184; 95% CI, 2.929-3.440 [middle signal]), followed by linezolid (ROR = 9.350; 95% CI, 7.318-11.947; IC = 3.106; 95% CI, 2.745-3.466 [middle signal]), teicoplanin (ROR = 6.399; 95% CI, 2.869-14.272; IC = 2.059; 95% CI, 0.881-3.283 [weak signal]), and daptomycin (ROR = 2.784; 95% CI, 1.496-5.180; IC = 1.287; 95% CI, 0.374-2.201 [weak signal]). Tigecycline and daptomycin were the least likely anti-MRSA drug to cause thrombocytopenia (middle signal and weak signal, respectively) and bleeding complications in thrombocytopenia (no signal and weak signal, respectively). Middle signals of bleeding complication in vancomycin-induced thrombocytopenia were found in all group except those <45 to ≥80 years of age (weak signal).
IMPLICATIONS
Bleeding complications in thrombocytopenia were significantly associated with vancomycin use, and the risk was highest among all the anti-MRSA drugs. Physicians should be aware of this possible serious adverse reaction.
Topics: Humans; Vancomycin; Linezolid; Daptomycin; Tigecycline; Teicoplanin; Methicillin-Resistant Staphylococcus aureus; Pharmacovigilance; Thrombocytopenia; Anti-Bacterial Agents
PubMed: 37640615
DOI: 10.1016/j.clinthera.2023.06.022 -
The Journal of Antimicrobial... Nov 2023The glycopeptide teicoplanin is considered first-line treatment for severe infections caused by Gram-positive bacteria. Individualized treatment of teicoplanin is...
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.
Topics: Humans; Teicoplanin; Chromatography, Liquid; Tandem Mass Spectrometry; Glycopeptides
PubMed: 37757461
DOI: 10.1093/jac/dkad290 -
Orvosi Hetilap Jun 2023Anaphylaxis is a generalized, severe, life-threatening reaction, mostly with an allergic origin. Triggers are usually drugs, insect bites, poisons, contrast material and...
Anaphylaxis is a generalized, severe, life-threatening reaction, mostly with an allergic origin. Triggers are usually drugs, insect bites, poisons, contrast material and food. It is caused by various mediators (histamine, prostaglandins, leukotrienes etc.) released from mast cells, basophilic granulocytes. Histamine plays a central role in its creation. Immediate recognition and specific treatment instantaneously are essential for successful treatment. In severe conditions, the clinical features are very similar, regardless of their allergic/non-allergic origin. The incidence can vary over time and between patient populations. Its incidence is extremely variable, approximately 1/10 000 anaesthesia. Most studies cite neuromuscular blocking agents as the most common causative factor. In England, the results of the 6th National Audit Project revealed that the most common causes were antibiotics (1/26 845), followed by neuromuscular junction blocking drugs (1/19 070), chlorhexidine (1/127 698), and Patent Blue paint (1/6863). It occurs within 5 minutes in 66% of cases, 6-10 minutes in 17%, 11-15 minutes in 5%, 16-30 minutes in 2%, but usually within 30 minutes. Antibiotic allergy is a growing problem, especially to teicoplanin (16.4/100 000) and co-amoxiclav (8.7/100 000). The risk of anaphylactic shock should not be a determining factor in choosing the type of muscle relaxant drug. The patient's anaesthesia classification, physical condition, obesity, use of beta-blockers and ACE inhibitors influence the clinical characteristics. The initial symptoms can be extremely varied in terms of the effectiveness of the treatment, early recognition and commencement of therapy are the keys to success. Asking about a preoperative allergy history can reduce the risk and incidence of anaphylaxis. Orv Hetil. 2023; 164(22): 871-877.
Topics: Humans; Anaphylaxis; Histamine; Drug Hypersensitivity; Anesthesia; Anesthesiology
PubMed: 37270773
DOI: 10.1556/650.2023.32789 -
Journal of Chromatography. A Aug 2023Retention and separation of enantiomers of amine derivatives of indane and tetralin (rasagiline and its analogues) on chiral stationary phases (CSPs) Chiral-T and... (Review)
Review
Retention and separation of enantiomers of amine derivatives of indane and tetralin (rasagiline and its analogues) on chiral stationary phases (CSPs) Chiral-T and Chiral-V with teicoplanin and vancomycin antibiotics grafted onto superficially porous silica particles under conditions of reversed-phase and polar organic chromatography were studied. The mobile phases (MP) were water-methanol and acetonitrile-methanol solvents modified with triethylamine-acetic acid buffer. The effects of molecular structure and physical properties of the analytes on enantioselective retention are discussed. The retention mechanism is hypothesized to involve the ion-ion attraction between the positively charged amino group of an analyte and the carboxylate anion of either antibiotic. The binding occurs outside of the antibiotic's aglycon basket that accounts for relatively low enantioselectivity observed. The presence of a large substitute at the analyte's amino group complicates enantiorecognition. The effect of the MP solvent composition on retention and enantioseparation was investigated. It is a complex phenomenon combined of different oppositely directed influences that resulted in different shapes, increasing, decreasing, or U-shaped, of the retention factor vs. composition dependences. A model taking into account the interaction of both solvents of a binary MP with both an analyte and an adsorption site was successfully applied to approximate a majority of the studied systems. Pros and cons of the model are discussed.
Topics: Vancomycin; Teicoplanin; Porosity; Methanol; Anti-Bacterial Agents; Solvents; Stereoisomerism; Indicators and Reagents; Chromatography, High Pressure Liquid
PubMed: 37315444
DOI: 10.1016/j.chroma.2023.464120