scholarly journals Continuous Infusion Vancomycin in Pediatric Patients: A Critical Review of the Evidence

2020 ◽  
Vol 25 (3) ◽  
pp. 198-214
Author(s):  
Heather L. Girand

OBJECTIVE To evaluate the use of continuous infusion vancomycin in pediatric patients. DATA SOURCES AND STUDY SELECTION PubMed, Cochrane Library, International Pharmaceutical Abstracts, and Google Scholar were searched to identify relevant published articles (1977 to November 2019) using the following search terms: vancomycin, neonates, pediatrics, infusion, continuous, administration, children, nephrotoxicity, pharmacokinetics, and pharmacodynamics. All English-language primary references that evaluated continuous infusion vancomycin in pediatric patients were included in this review. DATA SYNTHESIS Vancomycin is typically administered with intermittent infusions, but continuous infusion is an alternative delivery method used to improve achievement of target serum concentrations. Fifteen articles were reviewed that evaluated continuous infusion vancomycin in pediatric patients. Study data were heterogeneous with limited evidence to support improved clinical or microbiologic outcomes as compared with intermittent dosing. Potential benefits and limitations of continuous infusions are discussed. CONCLUSIONS Currently available evidence is lacking to support routine implementation of continuous infusion vancomycin in pediatric patients. However, it is a therapeutic option in certain clinical conditions and could be beneficial for individuals with serious Gram-positive infections where rapid achievement of target serum concentrations is critical. Continuous infusions may also benefit individuals who do not achieve target concentrations or who experience significant red man syndrome with traditional dosing, particularly when high daily doses are required. Optimal dosing and ideal target serum concentrations have not been established and may vary for different populations. Future prospective randomized clinical trials should be performed to identify optimal dosing and monitoring regimens and determine comparative safety and efficacy with traditional intermittent dosing in various pediatric populations.

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S2-S2
Author(s):  
Sindhu Mohandas ◽  
Kanokporn Mongkolrattanothai ◽  
Leslie Stach ◽  
Regina Orbach ◽  
Michael Neely

Abstract Background Isavuconazole (ISZ), dosed as the pre-drug isavuconazonium (ISM), is active against a wide variety of clinically important fungal pathogens. ISM is approved for the treatment of invasive aspergillosis and mucormycosis in adults ≥18 years of age. We present our experience with ISM to treat proven or probable fungal infection in immunocompromised pediatric patients. Methods Retrospective review of patients who received ISM at our institution between April 2016 and April 2019, we abstracted demographic information, primary diagnosis, indication for ISM therapy, ISZ serum concentrations if available, and outcomes. Results Of 14 patients who received ISM, 11 were ≤18 years of age (range 6–18 years). Underlying conditions included leukemia (n = 7), lymphoma (n = 1), post BMT (n = 1), diabetes (n = 1), and cardiac transplant (n = 1). Nine (82%) had proven invasive fungal infection (IFI) with aspergillosis (n = 2), zygomycosis (n = 3), mixed aspergillosis and zygomycosis (n = 2), mixed Rhizopus and Scedosporium (n = 1), and pathology only (n = 1) and 2 had probable IFI. Five of these 11 patients received combination ISM and liposomal amphotericin initially and the other 6 received liposomal amphotericin with or without other azoles prior to changing to ISM monotherapy. This was followed by monotherapy with ISM in 10 patients after a mean of 26 days (range 6–63) and continued dual therapy in the one. ISM dosing was 10 mg/kg q8h on days 1 and 2, followed by q24 thereafter, up to a maximum of 372 mg/dose. There were 19 measured ISZ serum concentrations obtained from 8 patients after >1 week of verified inpatient dosing, ranging from 1.0 to 7.5 mg/L, above the MIC in all cases when known. Three (27%) patients died of underlying non-mycological causes, 1 (9%) died of progressive scedosporiosis, and 7 (64%) improved. ISM was well tolerated with no dose-limiting, drug-related toxicities noted. Conclusions ISM is a well-tolerated therapeutic option in pediatric patients at risk for or with invasive mycosis. Only 1 of our 11 patients died from progressive fungal disease.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S718-S718
Author(s):  
Kanokporn Mongkolrattanothai ◽  
Sindhu Mohandas ◽  
Leslie Stach ◽  
Regina Orbach ◽  
Michael Neely

Abstract Background Isavuconazole (ISZ), dosed as the pre-drug isavuconazonium (ISM), is active against a wide variety of clinically important fungal pathogens. ISM is approved for the treatment of invasive aspergillosis and mucormycosis in adults ≥18 years of age. We present our experience with ISM to treat proven or to prevent fungal infection in pediatric patients. Methods In a retrospective review of patients who received ISM at our institution between April 2016 and April 2019, we abstracted demographic information, primary diagnosis, indication for ISM therapy, ISZ serum concentrations if available, and outcomes. Results Of 16 patients who received ISM, 12 were < 18 years of age (range 6–17 years). Underlying conditions included leukemia (n = 8), lymphoma (n = 1), post BMT (n = 1), diabetes (n = 1), and cardiac transplant (n = 1). Nine (75%) had proven invasive fungal infection with aspergillosis (n = 2), zygomycosis (n = 3), mixed aspergillosis and zygomycosis (n = 2), mixed Rhizopus and Scedosporium (n = 1), and pathology only (n = 1). Five of these 9 patients received combination ISM and liposomal amphotericin initially, followed by monotherapy with ISM in 4 patients after a mean of 26 days (range 6–63), and continued dual therapy in the fifth. The other 4 received liposomal amphotericin with or without other azoles prior to changing to ISM monotherapy. ISM dosing was 10 mg/kg q8h on days 1 and 2, followed by q24 thereafter, up to a maximum of 372 mg/dose. There were 19 measured ISZ serum concentrations obtained from 8 patients after >1 week of verified inpatient dosing, ranging from 1.0 to 7.5 mg/L, above the MIC in all cases when known. Five (42%) patients died of underlying non-mycological causes, 1 (8%) died of progressive scedosporiosis, and 6 (50%) improved. The two patients receiving ISM prophylaxis did not suffer a breakthrough fungal infection. ISM was well tolerated with no dose-limiting, drug-related toxicities noted. Conclusion ISM is a well-tolerated therapeutic option in pediatric patients at risk for or with invasive mycosis. Only 1 of our 12 patients died from progressive fungal disease. Disclosures All authors: No reported disclosures.


2017 ◽  
Vol 34 (09) ◽  
pp. 833-838 ◽  
Author(s):  
Jennifer Dannelley ◽  
Erin Martin ◽  
Hala Chaaban ◽  
Jamie Miller

AbstractMetronidazole dosing recommendations vary significantly for premature infants in pediatric dosing references and can result in confusion for prescribers. We performed a literature search identifying articles evaluating the pharmacokinetics and dosing of metronidazole in premature infants. The search was limited to English-language articles in MEDLINE (January 1946 to December 2016), EMBASE (January 1974 to December 2016), and International Pharmaceutical Abstracts (January 1970 to December 2016). Reference citations from relevant articles were also reviewed. Six pharmacokinetic studies, representing 152 neonates, were included; however, only three of the well-defined studies were reviewed in depth, and the other three studies were considered foundational. The pharmacokinetic studies included in this review indicate that some published dosing recommendations in pediatric dosing references may result in subtherapeutic metronidazole concentrations. Therefore, postmenstrual age based dosing recommendations were provided by the authors of these pharmacokinetic studies based on a pharmacodynamic target of 6 to 8 mg/L; yet, these dosing recommendations differ from one another. The pharmacokinetic studies included in this review provide some guidance to dosing; however, a major limitation is that outcomes of clinical efficacy and safety were not evaluated. Future studies targeting the optimal dosing and serum concentrations required for clinical efficacy are needed.


2021 ◽  
Vol 12 ◽  
pp. 204062232199343
Author(s):  
Chenxi Feng ◽  
Rongrong Chen ◽  
Keer Wang ◽  
Chengping Wen ◽  
Zhenghao Xu

Background: GuiZhi-ShaoYao-ZhiMu decoction (GSZD), a traditional Chinese herbal medication, has been frequently used as an add-on medication to methotrexate (MTX) for rheumatoid arthritis (RA) treatment in China. This meta-analysis evaluated the efficacy and safety of adding GSZD to MTX for RA treatment. Methods: We performed a systematic search of PubMed, Web of Science, EMBASE, and the Cochrane Library (all databases) for English-language studies and WanFang, VIP, and CNKI for Chinese-language studies up to 28 July 2020. Data from selected studies, mainly the response rates and rate of adverse events (AEs), were extracted independently by two authors, and a random-effects model (Mantel–Haenszel method) was used for the meta-analysis. Results: A total of 14 randomized controlled trials and 1224 patients were included (623 patients in the GSZD + MTX group and 601 patients in the MTX group). For efficacy, the meta-analysis found that combining GSZD with MTX increased the effective rate [relative risk (RR) = 1.24, 95% confidence interval (CI): 1.18–1.30, based on 1069 patients], defined as >30% efficacy, American College of Rheumatology 20, or a decrease of disease activity score 28 >0.6. Adding GSZD reduced the swollen and tender joint counts, the duration of morning stiffness, the levels of C-reactive protein and rheumatoid factor, and erythrocyte sedimentation rate. The adjuvant therapeutic effect of GSZD was independent of the dose of MTX or the combined utilization of other drugs in both groups. For safety, adding GSZD was associated with a lower rate of total AEs (RR = 0.46, 95% CI: 0.26–0.83, based on 615 patients) and gastrointestinal tract AEs (RR = 0.46, 95% CI: 0.24–0.88, based on 537 patients). Conclusion: Combining GSZD with MTX may be a more efficacious and safer strategy for treating RA compared with MTX alone. Further large studies are warranted to investigate the long-term efficacy and safety of adding GSZD to MTX for RA treatment.


2020 ◽  
Vol 11 (5) ◽  
pp. 619-624
Author(s):  
Mark N. Awori ◽  
Jonathan A. Awori ◽  
Nikita P. Mehta ◽  
Obed Makori

Monocusp valves are thought to reduce early operative mortality and morbidity associated with pediatric tetralogy of Fallot repair. As there are no published randomized clinical trials comparing outcomes with and without a monocusp valve, we performed a meta-analysis of observational studies in accordance with established protocols. After systematically searching PubMed, the Cochrane Library, and Google Scholar, 12 studies were included. The operative mortality was compared in 695 patients, and we found no difference between patients with and patients without a monocusp valve. Monocusp valves may not improve operative mortality of tetralogy of Fallot repair in pediatric patients.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Morteza Ghojazadeh ◽  
Seyed Pouya Paknezhad ◽  
Sanam Mohammadzadeh ◽  
Nafiseh Vahed ◽  
Zahra Vand Rajabpour ◽  
...  

Context: Procedural sedation (PS) plays an important role in facilitating emergency procedures. Dexmedetomidine is an alpha-adrenergic agonist which can play a role in this issue. This study aimed to systematically review the literature about the role of dexmedetomidine in PS in the emergency department (ED). Methods: In this study, several databases, namely PubMed, Embase, Ovid, ProQuest, Scopus, Web of Science, and Cochrane Library, were searched since 1999 up to November 30, 2020. The inclusion criteria in this study were randomized clinical trials performed on ED patients using dexmedetomidine for PS and articles only in the English language. The exclusion criteria were the studies that were not clinical trials or were not performed in the ED, low-quality studies or animal studies. Results: A total of 473 articles were identified in this study. Five studies fulfilled the inclusion and exclusion criteria. Three articles studied the adult population. One study used dexmedetomidine in an intranasal way, and one study used an intramuscular route for drug administration. Conclusions: Although the reviewed studies reported dexmedetomidine as a safe and effective agent for PS, there are not sufficient data on this issue. Therefore, it is required to perform further studies to a draw firmer conclusion.


1998 ◽  
Vol 158 (2) ◽  
pp. 277-283 ◽  
Author(s):  
H Sakurai ◽  
TE Adams

The biphasic effect of oestradiol (E2) on gonadotrope responsiveness is clearly evident in orchidectomized sheep (wethers) receiving E2 and hourly pulses of GnRH. We hypothesized that the duration of E2-induced reduction in gonadotrope responsiveness differed between the breeding (November) and anoestrous (May) seasons in sheep. To test this hypothesis wethers (n = 6/group) were infused (i.v.) with E2 (2 micrograms/50 kg per h) and received hourly pulses of GnRH (200 ng/50 kg per pulse) or saline in May or November. The pattern of LH secretion during the 72 h infusion period was determined. Serum concentrations of LH did not differ with season in control wethers receiving vehicle alone. Similarly, continuous infusion of E2 resulted in a 3-fold reduction in serum LH, irrespective of season. This E2-induced suppression of serum LH was reversed by concurrent episodic delivery of GnRH. The interval between initiation of infusion and return of pretreatment concentrations of LH was taken as a measure of the duration of E2-induced suppression of gonadotrope responsiveness. The duration of this E2-dependent response varied with season, with suppression of gonadotrope responsiveness more prolonged (P < 0.05) in May (36.7 +/- 2.9 h) than in November (14.3 +/- 1.1 h). In a companion study we examined the effect of melatonin on the duration of E2-induced suppression of gonadotrope responsiveness. Wethers received blank or melatonin-containing implants in March. Sixty days after implant insertion (mid-May) wethers received E2 (2 micrograms/50 kg per h) and hourly pulses of GnRH (200 ng/50 kg per pulse) or saline for 72 h. Continuous delivery of E2 alone resulted in a 3-fold decrease in serum concentrations of LH in both control and melatonin-treated wethers. The duration of E2-induced suppression of gonadotrope responsiveness in animals receiving E2 and GnRH was extended (P < 0.05) in wethers with blank implants (48.0 +/- 0.7 h), relative to the duration of suppression in melatonin-treated wethers (14.5 +/- 1.0 h). Taken together these data indicate that E2-induced suppression of gonadotrope responsiveness is more extended during the anoestrous season. However, this seasonal effect can be reversed by continuous administration of melatonin.


Perfusion ◽  
2020 ◽  
pp. 026765912097432
Author(s):  
Reut Kassif Lerner ◽  
Uri Pollak

Therapeutic plasma exchange in children is increasingly recognized as a life-saving treatment and is challenged by some technical considerations. As extracorporeal membrane oxygenation has been used for nearly half a century for refractory reversible respiratory and/or cardiac failure in both pediatric and adult populations, it may serve as an extracorporeal platform for therapeutic plasma exchange. It is most commonly described in patients with sepsis with multiple organ failure or thrombocytopenia associated multi organ failure. Additional pathophysiological processes of inflammatory and immunological storms might benefit from the combination of extracorporeal membrane oxygenation and plasma exchange. This is a nonmethodological review of English-language reports of therapeutic plasma exchange performed in patients supported by extracorporeal membrane oxygenation, both pediatric and adult, searching six databases, MEDLINE, Clinical Key, GOOGLE SCHOLAR, CINAHL, Cochrane library, and EMBASE.


2020 ◽  
Vol 45 (6) ◽  
pp. 589-597
Author(s):  
BGS Casado ◽  
EP Pellizzer ◽  
JR Souto Maior ◽  
CAA Lemos ◽  
BCE Vasconcelos ◽  
...  

Clinical Relevance The use of laser light during bleaching will not reduce the incidence or severity of sensitivity and will not increase the degree of color change compared with nonlaser light sources. SUMMARY Objective: To evaluate whether the use of laser during in-office bleaching promotes a reduction in dental sensitivity after bleaching compared with other light sources. Methods: The present review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and is registered with PROSPERO (CDR42018096591). Searches were conducted in the PubMed/Medline, Web of Science, and Cochrane Library databases for relevant articles published up to August 2018. Only randomized clinical trials among adults that compared the use of laser during in-office whitening and other light sources were considered eligible. Results: After analysis of the texts retrieved during the database search, six articles met the eligibility criteria and were selected for the present review. For the outcome dental sensitivity, no significant difference was found favoring any type of light either for intensity (mean difference [MD]: −1.60; confidence interval [CI]: −3.42 to 0.22; p=0.09) or incidence (MD: 1.00; CI: 0.755 to 1.33; p=1.00). Regarding change in tooth color, no significant differences were found between the use of the laser and other light sources (MD: −2.22; CI: −6.36 to 1.93; p=0.29). Conclusions: Within the limitations of the present study, laser exerts no influence on tooth sensitivity compared with other light sources when used during in-office bleaching. The included studies demonstrated that laser use during in-office bleaching may have no influence on tooth color change.


2019 ◽  
Vol 25 (15) ◽  
pp. 1783-1790 ◽  
Author(s):  
Rosario Pastor ◽  
Josep A. Tur

Background: Several drugs have been currently approved for the treatment of obesity. The pharmacokinetic of liraglutide, as well as the treatment of type 2 diabetes mellitus, have been widely described. Objective: To analyze the published systematic reviews on the use of liraglutide for the treatment of obesity. Methods: Systematic reviews were found out through MEDLINE searches, through EBSCO host and the Cochrane Library based on the following terms: "liraglutide" as major term and using the following Medical Subject Headings (MesH) terms: "obesity", "overweight", "weight loss". A total of 3 systematic reviews were finally included to be analyzed. Results: From the three systematic reviews selected, only two included the randomized clinical trials, while the third study reviewed both randomized and non-randomized clinical trials. Only one review performed statistical tests of heterogeneity and a meta-analysis, combining the results of individual studies. Another review showed the results of individual studies with odds ratio and confidence interval, but a second one just showed the means and confidence intervals. In all studies, weight loss was registered in persons treated with liraglutide in a dose dependent form, reaching a plateau at 3.0 mg dose, which was reached just in men. Most usual adverse events were gastrointestinal. Conclusion: More powerful and prospective studies are needed to assess all aspects related to liraglutide in the overweight and obesity treatment.


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