scholarly journals A Proof of Concept of the Role of TDM-Based Clinical Pharmacological Advices in Optimizing Antimicrobial Therapy on Real-Time in Different Paediatric Settings

2021 ◽  
Vol 12 ◽  
Author(s):  
Milo Gatti ◽  
Pier Giorgio Cojutti ◽  
Caterina Campoli ◽  
Fabio Caramelli ◽  
Luigi Tommaso Corvaglia ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Real Time ◽  
Antimicrobial Therapy ◽  
Turnaround Time ◽  
Antimicrobial Treatment ◽  
Therapeutic Drug ◽  
Proof Of Concept ◽  
Paediatric Patients ◽  
Dosing Regimens

Introduction: Antimicrobial treatment is quite common among hospitalized children. The dynamic age-associated physiological variations coupled with the pathophysiological alterations caused by underlying illness and potential drug-drug interactions makes the implementation of appropriate antimicrobial dosing extremely challenging among paediatrics. Therapeutic drug monitoring (TDM) may represent a valuable tool for assisting clinicians in optimizing antimicrobial exposure. Clinical pharmacological advice (CPA) is an approach based on the correct interpretation of the TDM result by the MD Clinical Pharmacologist in relation to specific underlying conditions, namely the antimicrobial susceptibility of the clinical isolate, the site of infection, the pathophysiological characteristics of the patient and/or the drug-drug interactions of cotreatments. The aim of this study was to assess the role of TDM-based CPAs in providing useful recommendations for the real-time personalization of antimicrobial dosing regimens in various paediatric settings.Materials and methods: Paediatric patients who were admitted to different settings of the IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy (paediatric intensive care unit [ICU], paediatric onco-haematology, neonatology, and emergency paediatric ward), between January 2021 and June 2021 and who received TDM-based CPAs on real-time for personalization of antimicrobial therapy were retrospectively assessed. Demographic and clinical features, CPAs delivered in relation to different settings and antimicrobials, and type of dosing adjustments were extracted. Two indicators of performance were identified. The number of dosing adjustments provided over the total number of delivered CPAs. The turnaround time (TAT) of CPAs according to a predefined scale (optimal, <12 h; quasi-optimal, between 12–24 h; acceptable, between 24–48 h; suboptimal, >48 h).Results: Overall, 247 CPAs were delivered to 53 paediatric patients (mean 4.7 ± 3.7 CPAs/patient). Most were delivered to onco-haematological patients (39.6%) and to ICU patients (35.8%), and concerned mainly isavuconazole (19.0%) and voriconazole (17.8%). Overall, CPAs suggested dosing adjustments in 37.7% of cases (24.3% increases and 13.4% decreases). Median TAT was 7.5 h (IQR 6.1–8.8 h). Overall, CPAs TAT was optimal in 91.5% of cases, and suboptimal in only 0.8% of cases.Discussion: Our study provides a proof of concept of the helpful role that TDM-based real-time CPAs may have in optimizing antimicrobial exposure in different challenging paediatric scenarios.

scholarly journals MP13: IMPORTANT ROLE OF PROTHROMBIN TIME (PT) AND PARTIAL THROMBOPLASTIN TIME (PTT) IN PREDICTING TPA-RELATED HEMORRHAGIC TRANSFORMATION

2016 ◽  
Vol 64 (3) ◽  
pp. 810.1-810
Author(s):  
W Deng ◽  
T Wickham ◽  
D McMullin ◽  
K Feeney ◽  
FS Buonanno ◽  
...  
Keyword(s):  
Real Time ◽  
Clinical Utility ◽  
Roc Analysis ◽  
Neurovascular Unit ◽  
Hemorrhagic Transformation ◽  
Proof Of Concept ◽  
Vascular Effects ◽  
D Dimer ◽  
Iv Tpa

Purpose of StudyIV tPA is not routinely followed by blood work due to its reputed short half life. While there has been much focus on tPA's extra-vascular effects on the neurovascular unit in the context of hemorrhagic transformation (HT), little is known about its intravascular efficacy, where it has its intended effect. Emerging data suggest that tPA may be most effective in microvasculature and IV therapy may be a good adjunct to intra-arterial therapy. We previously found that the effect of tPA can last more than 72 hr after stroke onset. Now, we report that even routine blood labs can potentially predict HT.Methods Used72 storke patients with IV tPA were recruited on IRB approval. Clinical coagulation profile (PT, PTT, fibrinogen and D-dimer) were performed at 12, 24, 72 hr post tPA. Patients on medications (e.g. anticoagulants) or with conditions (e.g. liver dysfunction, infection) that may affect these labs were excluded.Summary of ResultsCompared to those without HT, HT patients had significantly higher PT and PTT (Fig A,B) as early as 12 hr post IV tPA and throughout the first 3 days of treatment. ROC analysis suggested PT/PTT at 12 and 24 hr has potential to predict tPA-induced HT (Fig C,D. PT: AUC=0.848, p=0.001; PTT: AUC=0.877; p=0.003).ConclusionsHigher PT/PTT level within 72 hr of IV tPA is early marker of tPA-induced HT. Whether these routine labs have value in symptomatic hemorrhage will require further study in a larger cohort. But this proof-of-concept study suggests that tPA efficacy can potentially be followed in real time. The development of a reliable blood test would be of clinical utility to gauge thrombolytic efficacy in real time to guide and triage adjunct treatments.Abstract MP13 Figure 1

Pharmacokinetic and pharmacodynamic principles of antimicrobials

2016 ◽  
Author(s):  
Menino Osbert Cotta ◽  
Jason Roberts
Keyword(s):  
Antimicrobial Resistance ◽  
Protein Binding ◽  
Clinical Outcomes ◽  
Antimicrobial Therapy ◽  
Potential Role ◽  
Volume Of Distribution ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Dosing Regimens ◽  
Dosing Strategies

The continual threat of antimicrobial resistance means that optimizing current antimicrobial therapy is of paramount importance. Antimicrobial pharmacokinetics and pharmacodynamics (PK/PD) play a central role in developing dosing regimens that target maximal clinical outcomes and microbiological eradication. This chapter describes the three main PK/PD indices into which current antimicrobials are categorized. Elements of PK that require due consideration when optimizing antimicrobial therapy, including volume of distribution, antimicrobial clearance, and protein binding, are also discussed. Finally, specific attention is paid to antimicrobial dosing among challenging populations, namely the critically ill and obese, and the potential role of alternative dosing strategies, such as use of loading doses and extended/continuous infusions, is also outlined.

scholarly journals Neuroischeminės pėdos infekcija ir revaskuliarizacijos galimybės

2003 ◽  
Vol 1 (1) ◽  
pp. 0-0
Author(s):  
Vytautas Triponis ◽  
Dalia Triponienė ◽  
Birutė Vaišnytė ◽  
Stanislovas Ščerbinskas
Keyword(s):  
Diabetes Mellitus ◽  
Antimicrobial Therapy ◽  
Antimicrobial Treatment ◽  
Arterial Occlusive Disease ◽  
Keywords Diabetes Mellitus ◽  
Keywords Diabetes ◽  
Sensitivity Tests ◽  
Foot Function ◽  
Reconstructive Arterial Surgery

Vytautas Triponis, Dalia Triponienė, Birutė Vaišnytė, Stanislovas ŠčerbinskasVilniaus universiteto Bendrosios ir kraujagyslių chirurgijos klinika Įvadas / tikslas Požiūris, kad sergančiajam cukralige, kai pakinklio arterijos pulsas gerai užčiuopiamas, o pėdos ischemija progresuoja, geriau atlikti amputaciją, dabar laikomas klaidingu. Tačiau, jeigu yra pado tarpo infekcija, galūnę išsaugoti beveik niekada nepavyksta. Šio darbo tikslas – išanalizuoti rekonstrukcinių arterijų operacijų, atliktų sergantiesiems cukralige, rezultatus ir juos įvertinti atsižvelgiant į arterijų patologijos pobūdį ir pėdos infekciją. Metodai Operuota 1211 cukriniu diabetu sergančių ligonių. Pagal galūnių kraujotakos sutrikimo stadijas ligoniai pasiskirstė taip: šlubavimas – 36 (3,0 %), nuolatiniai skausmai – 368 (30,4 %), gangrena – 807 (66,6 %). Pėdos infekcija buvo 239 (29,6 %) ligoniams, iš jų 77 (9,5 %) infekcija išplito. Atliktos arterijų rekonstrukcinės operacijos: aortos ir klubinių arterijų rekonstrukcija – 71, šlaunies ir pakinklio arterijų endarterektomija ir šuntavimas – 409, blauzdos arterijų šuntavimas – 451, pėdos arterijų šuntavimas – 188, perkutaninė transliuminalinė angioplastika – 92 ligoniams. Rezultatai Nustatyta, kad veiksmingiausi antibiotikai buvo: cefoperazonas – 23 (10,4), ceftazidimas – 23 (10,4 %), gentamicinas – 26 (11,8 %), ampicilinas-sulbaktamas – 20 (9,1 % ), amoksicilinas-klavulano rūgštis – 20 (9,1 %) ligonių. Penicilinams flora buvo jautri 0,5–4,1 % pasėlių. Iš 239 ligonių 124 (51,9 %) gydyti penicilinais (penicilinu arba ampicilinu). Antibiotikais, kuriems buvo jautrūs identifikuoti mikrobai, dažniausiai cefalosporinais arba cefalosporinų ir gentamicino deriniu, buvo gydyta 115 (48,1 %) ligonių. Iš 1211 ligonių 942 (77,8 %) pėdos funkcija išliko nepakitusi arba šiek tiek sutriko. Pėdos nepavyko išsaugoti 181 (14,9 %) ligoniui. Iš 181 ligonio 70 (38,6 %) amputacija buvo atlikta dėl užleistos ir netinkamai gydytos infekcijos: gydyta tik penicilinais ir neatsižvelgiant į bakterijų jautrumo antibiotikams duomenis. Kitos amputacijos buvo susijusios su nesėkminga rekonstrukcine arterijų operacija. 88 ligoniams, kuriems buvo atlikta sritinė pėdos amputacija, infekciją pavyko nugalėti mechaniškai pašalinant infekcijos židinį ir gydant antibiotikais pagal bakterijų jautrumą. Išvados Dažniausias kraujotakos atkūrimo metodas buvo šuntavimas autovena tiesiai į blauzdos arba pėdos arterijas. Kraujotakos atkūrimo efektas mažai tesiskyrė, kai buvo operuojamos blauzdos ir pėdos arterijos ir kai buvo rekonstruojama šlaunies arterija. Aterosklerozės pažeistos blauzdos ir pėdos arterijos bei pėdos infekcija buvo pats svarbiausias kliuvinys išsaugoti pėdą. Prasminiai žodžiai: cukrinis diabetas, arterijų užakimas, pėdos infekcija, rekonstrukcinės arterijų operacijos. Neuroischemic foot infection and revascularisation possibilities Vytautas Triponis, Dalia Triponienė, Birutė Vaišnytė, Stanislovas Ščerbinskas Background / objective The aim of the study was to analyze the results of the treatment of neuroischemic foot and to assess the role of foot infection. Methods In 1211 patients reconstructive arterial surgery was performed combining the procedure with foot regional amputations and antimicrobial therapy. The following reconstructions were performed: aortoiliac 71, femoropopliteal 409, tibial 451, bypass to the dorsalis pedis 188, and PTA 92. Results / conclusions The most effective antibiotics were cephoperazone 23 (10.4%), ceftazidime 23 (10.4%), gentamicin 26 (11.8%), ampicillin-sulbactam 20 (9.1% ), amoxycillin-clavulanic acid 20 (9.1%). Microbes were sensitive to penicillin in 0.5–4.1% cases. Of 239 patients, 124 (51.9%) were treated with penicillin. Cephalosporins in combination with aminoglycosides were used in 115 (48.1%) patients. The foot function was saved in 942 (77.8%). Foot salvage procedures were not successful in 181 (14.9%) patients. In this group, 70 (38.6%) amputations were done because of progressing infection and inadequate antimicrobial treatment. The rest of amputations were conditioned by bad runoff. In 88 patients in whom the regional amputations were performed infection was overcome by using antibiotics according to the sensitivity tests. Keywords: diabetes mellitus, arterial occlusive disease, foot infection, reconstructive arterial surgery.

The role of real-time PCR testing in the investigation of paediatric patients with community-onset osteomyelitis and septic arthritis

2019 ◽  
Vol 188 (4) ◽  
pp. 1289-1295
Author(s):  
Sadhbh O’Rourke ◽  
Mary Meehan ◽  
Désirée Bennett ◽  
Nicola O’Sullivan ◽  
Robert Cunney ◽  
...  
Keyword(s):  
Septic Arthritis ◽  
Real Time ◽  
Real Time Pcr ◽  
Paediatric Patients ◽  
Community Onset

scholarly journals Clinical Use and Monitoring of Antiepileptic Drugs

2018 ◽  
Vol 3 (1) ◽  
pp. 115-127 ◽  
Author(s):  
Claire E Knezevic ◽  
Mark A Marzinke
Keyword(s):  
Drug Interactions ◽  
Antiepileptic Drugs ◽  
Neurological Disorders ◽  
Genetic Factors ◽  
Patient Specific ◽  
Therapeutic Drug ◽  
Clinical Tests ◽  
Blood Concentrations ◽  
Specific Factors

Abstract Background Antiepileptic drugs (AEDs) have been used for the treatment of epilepsy and other neurological disorders since the late 19th century. There are currently several classes of AEDs available for epilepsy management, many of which are also used to treat migraines, bipolar disorder, schizophrenia, depression, and neuropathic pain. Because of their molecular and mechanistic diversity, as well as the potential for drug–drug interactions, AEDs are prescribed and monitored in a highly personalized manner. Content This review provides a general overview of the use of AEDs with a focus on the role of therapeutic drug monitoring. Discussed topics include mechanisms of action, guidelines on the clinical applications of AEDs, clinical tests available for AED monitoring, and genetic factors known to affect AED efficacy. Summary Implementation of AED therapies is highly individualized, with many patient-specific factors considered for drug and dosage selection. Both therapeutic efficacy and target blood concentrations must be established for each patient to achieve seizure mitigation or cessation. The use of an AED with any additional drug, including other AEDs, requires an evaluation of potential drug–drug interactions. Furthermore, AEDs are commonly used for nonepilepsy indications, often in off-label administration to treat neurological or psychiatric disorders.

Drug Interactions with Angiotensin Receptor Blockers: Role of Human Cytochromes P450

2016 ◽  
Vol 17 (7) ◽  
pp. 681-691 ◽  
Author(s):  
Ruirui Yang ◽  
Zhiqiang Luo ◽  
Yang Liu ◽  
Mohan Sun ◽  
Ling Zheng ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Cytochromes P450 ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Receptor ◽  
Receptor Blockers
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