scholarly journals Target Attainment and Clinical Efficacy for Vancomycin in Neonates: Systematic Review

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 347
Author(s):  
Marta Mejías-Trueba ◽  
Marta Alonso-Moreno ◽  
Laura Herrera-Hidalgo ◽  
Maria Victoria Gil-Navarro

Vancomycin is commonly used as a treatment for neonatal infections. However, there is a lack of consensus establishing the optimal vancomycin therapeutic regimen and defining the most appropriate PK/PD parameter correlated with the efficacy. A recent guideline recommends AUC–guided therapeutic dosing in treating serious infections in neonates. However, in clinical practice, trough serum concentrations are commonly used as a surrogate PKPD index for AUC24. Despite this, target serum concentrations in a neonatal population remain poorly defined. The objective is to describe the relationship between therapeutic regimens and the achievement of clinical or pharmacokinetic outcomes in the neonatal population. The review was carried out following PRISMA guidelines. A bibliographic search was manually performed for studies published on PubMed and EMBASE. Clinical efficacy and/or target attainment and the safety of vancomycin treatment were evaluated through obtaining serum concentrations. A total of 476 articles were identified, of which 20 met the inclusion criteria. All of them evaluated the target attainment, but only two assessed the clinical efficacy. The enormous variability concerning target serum concentrations is noteworthy, which translates into a difficulty in determining which therapeutic regimen achieves the best results. Moreover, there are few studies that analyze clinical efficacy results obtained after reaching predefined trough serum concentrations, this information being essential for clinical practice.

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 912
Author(s):  
Marta Alonso-Moreno ◽  
Marta Mejías-Trueba ◽  
Laura Herrera-Hidalgo ◽  
Walter Alfredo Goycochea-Valdivia ◽  
María Victoria Gil-Navarro

Vancomycin is used to treat a wide variety of infections within the pediatric population. In adults, continuous infusion of vancomycin (CIV) has been evaluated as an alternative to intermittent infusion of vancomycin (IIV) with potential advantages. In children, the use of CIV is increasing; however, data is currently limited. The objective is to provide efficacy and safety evidence for CIV within this population. The review was carried out following PRISMA guidelines. A bibliographic search was performed for studies on PubMed and EMBASE. Clinical trials and observational studies that reported clinical efficacy and/or target attainment of CIV in pediatrics were included. Articles were reviewed to assess their design and target population, characteristics of vancomycin treatment and the main findings in terms of safety and efficacy. A total of 359 articles were identified, of which seven met the inclusion criteria. All of them evaluated the target attainment, six assessed safety but only three assessed clinical efficacy. The best administration method for this antibiotic within the pediatric population is still unknown due to limited evidence. However, studies conducted thus far suggest pharmacokinetic advantages for CIV. Further investigation is required, in particular for studies comparing IIV with CIV for clinical efficacy and toxicity outcomes.


1993 ◽  
Vol 2 (3) ◽  
pp. 52-55 ◽  
Author(s):  
Michael Collins ◽  
Robert McDonald ◽  
Robert Stanley ◽  
Timothy Donovan ◽  
C. Frank Bonebrake

This report describes an unusual and persistent dysphonia in two young women who had taken a therapeutic regimen of isotretinoin for intractable acne. We report perceptual and instrumental data for their dysphonia, and pose a theoretical basis for the relationship of dysphonia to this drug. We also provide recommendations for reducing the risk of acquiring a dysphonia during the course of treatment with isotretinoin.


1988 ◽  
Vol 59 (02) ◽  
pp. 273-276 ◽  
Author(s):  
J Dawes ◽  
D A Pratt ◽  
M S Dewar ◽  
F E Preston

SummaryThrombospondin, a trimeric glycoprotein contained in the platelet α-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relationship between plasma thrombospondin levels and platelet count in samples from profoundly thrombocytopenic patients with marrow hypoplasia, using the platelet-specific α-granule protein β-thromboglobulin as control. Serum concentrations of both proteins were highly correlated with platelet count, but while plasma β-thromboglobulin levels and platelet count also correlated, there was no relationship between the number of platelets and thrombospondin concentrations in plasma. Serial sampling of patients recovering from bone marrow depression indicated that the plasma thrombospondin contributed by platelets is superimposed on a background concentration of at least 50 ng/ml probably derived from a non-platelet source, and plasma thrombospondin levels do not simply reflect platelet release.


2020 ◽  
Vol 22 (3) ◽  
pp. 341-361
Author(s):  
Gonzalo Grau-Pérez ◽  
J. Guillermo Milán

In Uruguay, Lacanian ideas arrived in the 1960s, into a context of Kleinian hegemony. Adopting a discursive approach, this study researched the initial reception of these ideas and its effects on clinical practices. We gathered a corpus of discursive data from clinical cases and theoretical-doctrinal articles (from the 1960s, 1970s and 1980s). In order to examine the effects of Lacanian ideas, we analysed the difference in the way of interpreting the clinical material before and after Lacan's reception. The results of this research illuminate some epistemological problems of psychoanalysis, especially the relationship between theory and clinical practice.


Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 155-165 ◽  
Author(s):  
Laurence A. Harker ◽  
Ulla M. Marzec ◽  
Andrew B. Kelly ◽  
Ellen Cheung ◽  
Aaron Tomer ◽  
...  

Abstract This report examines the effects on hematopoietic regeneration of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF ) (2.5 μg/kg/d) alone and in combination with recombinant human granulocyte colony stimulating factor (rHu-GCSF ) (10 μg/kg/d) for 21 days in rhesus macaques receiving intense marrow suppression produced by single bolus injections of hepsulfam (1.5 g/m2). In six hepsulfam-only control animals thrombocytopenia (platelet count <100 × 109/L) was observed between days 12 and 25 (nadir 39 ± 20 × 109/L on day 17), and neutropenia (absolute neutrophil count <1 × 109/L) occurred between days 8 and 30 (nadir 0.167 ± 0.120 × 109/L on day 15). PEG-rHuMGDF (2.5 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.9 ± 0.2 ng/mL and increased the platelet count twofold over basal prechemotherapy levels (856 ± 594 × 109/L v baseline of 416 ± 88 × 109/L; P = .01). PEG-rHuMGDF alone also shortened the period of posthepsulfam neutropenia from 22 days to 12 days (P = .01), although the neutropenic nadir was not significantly altered (neutrophil count 0.224 ± 0.112 × 109/L v 0.167 ± 0.120 × 109/L; P < .3). rHu-GCSF (10 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.4 ± 1.1 ng/mL, and reduced the time for the postchemotherapy neutrophil count to attain 1 × 109/L from 22 days to 4 days (P = .005). The postchemotherapy neutropenic nadir was 0.554 ± 0.490 × 109neutrophils/L (P = .3 v hepsulfam-only control of 0.167 ± 0.120 × 109/L). However, thrombocytopenia of <100 × 109 platelets/L was not shortened (persisted from day 12 to day 25), or less severe (nadir of 56 ± 32 × 109 platelets/L on day 14; P = .7 compared with untreated hepsulfam animals). The concurrent administration of rHu-GCSF (10 μg/kg/d) and PEG-rHuMGDF (2.5 μg/kg/d) in four animals resulted in postchemotherapy peripheral platelet counts of 127 ± 85 × 109/L (P = .03 compared with 39 ± 20 × 109/L for untreated hepsulfam alone, and P = .02 compared with 856 ± 594 × 109/L for PEG-rHuMGDF alone), and shortened the period of neutropenia <1 × 109/L from 22 days to 4 days (P = .8 compared with rHu-GCSF alone). Increasing PEG-rHuMGDF to 10 μg/kg/d and maintaining the 21-day schedule of coadministration with rHu-GCSF (10 μg/kg/d) in another four animals produced postchemotherapy platelet counts of 509 ± 459 × 109/L (P < 10−4compared with untreated hepsulfam alone, and P = .04 compared with 2.5 μg/kg/d PEG-rHuMGDF alone), and 4 days of neutropenia. Coadministration of rHu-GCSF and PEG-rHuMGDF did not significantly alter the pharmacokinetics of either agent. The administration of PEG-rHuMGDF (2.5 μg/kg/d) from day 1 through day 22 and rHu-GCSF (10 μg/kg/d) from day 8 through day 22 in six animals produced peak postchemotherapy platelet counts of 747 ± 317 × 109/L (P < 10−4 compared with untreated hepsulfam alone, and P = .7 compared with PEG-rHuMGDF alone), and maintained the neutrophil count < 3.5 × 109/L (P = .008 v rHu-GCSF therapy alone). Thus, both thrombocytopenia and neutropenia are eliminated by initiating daily PEG-rHuMGDF therapy on day 1 and subsequently adding daily rHu-GCSF after 1 week in the rhesus model of hepsulfam marrow suppression. This improvement in platelet and neutrophil responses by delaying the addition of rHu-GCSF to PEG-rHuMGDF therapy demonstrates the importance of optimizing the dose and schedule of cytokine combinations after severe myelosuppressive chemotherapy.


2021 ◽  
Vol 49 (2) ◽  
pp. 030006052199096
Author(s):  
Xiwen Sun ◽  
Jiayu Shen ◽  
Liquan Wang

The placenta is a transitory organ indispensable for normal fetal maturation and growth. Recognition of abnormal placental variants is important in clinical practice, and a broader understanding of the significance of placental variants would help clinicians better manage affected pregnancies. Increased thickness of the placenta is reported to be a nonspecific finding but it is associated with many maternal and fetal abnormalities, including preeclampsia and abnormal fetal growth. In this review, we address the questions regarding the characteristics of placenta thickness and the relationship between thickened placenta and poor pregnancy outcomes.


2020 ◽  
Vol 8 (1) ◽  
pp. 1
Author(s):  
Giacomo Riggio ◽  
Chiara Mariti ◽  
Valeria Sergi ◽  
Silvana Diverio ◽  
Angelo Gazzano

In mammals, serotonin (5-HT) levels depend on the availability of tryptophan (TRP). Low 5-HT concentrations have been linked to behavioural disorders in dogs. This study aimed at investigating possible differences in dogs’ serum TRP and 5-HT concentrations according to their behavioural response to a potentially stressful procedure. Thirty-nine physically healthy shelter dogs, 15 females and 24 males, mean age = 5.6 years, were categorized by a certified veterinary behaviourist according to their behavioural response to medical examination and blood collection, in: relaxation, stress signals, tension without growling, tension with growling, escape attempts, and aggression attempts. Extraction and quantification of 5-HT and TRP were performed using a HLPC method. Data were statistically analysed, applying Chi-square and Spearman tests. Results showed no significant difference in TRP (χ2 = 2.084, p = 0.555) nor 5-HT (χ2 = 0.972, p = 0.808) serum concentrations among different categories of dogs; however, some categories were underrepresented (relaxation = 20.5%, stress signals = 30.8%, tension without growling = 43.6%, tension with growling = 5.1%, escape attempts = 0%, aggression attempts = 0%). No correlation between serum TRP and 5-HT concentrations was found (ρ = 0.086, p = 0.602). Serum 5-HT levels do not seem to be associated with dogs’ behavioural response to a stressful situation nor with serum TRP concentrations. The relationship between serum TRP and 5-HT concentrations and behaviour needs further research.


2017 ◽  
Vol 24 (6) ◽  
pp. 805-810 ◽  
Author(s):  
Zoé LE van Kempen ◽  
Cyra E Leurs ◽  
Birgit I Witte ◽  
Annick de Vries ◽  
Mike P Wattjes ◽  
...  

Background: Natalizumab is efficacious in the treatment of relapsing-remitting multiple sclerosis. All patients receive the same treatment regimen of 300 mg every 4 weeks, despite differences in pharmacokinetics between individual patients. Objective: To give neurologists insight into natalizumab concentrations at time of re-dosing, we investigated longitudinal natalizumab concentrations in 80 patients in relation to disease activity, with possible influencing factors. Methods: In a prospective observational cohort study, natalizumab trough serum concentrations were measured in 80 patients. Data on demographics, duration of treatment, Expanded Disability Status Scale, clinical exacerbations, brain magnetic resonance imaging (MRI), and body weight were collected. Results: We measured high (≥10 µg/mL) natalizumab trough concentrations in 94% of patients. Intra-individual concentrations were stable. The spread in concentrations was substantial and did not correlate with disease activity. We found a negative association between natalizumab concentration and body weight (β = −0.30, p = 0.010). Interpretation: The majority of patients showed high natalizumab serum concentrations at time of re-dosing. Alternative treatment regimens could lead to more efficient use of natalizumab, but caution is warranted regarding the possibility of recurrence of disease activity. Prospective clinical trials are needed to establish the safety of extended dose intervals in natalizumab treatment.


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