Interaction Between Valproate and Meropenem: A Retrospective Study

Background: Valproate and meropenem are frequently used in the intensive care unit to treat seizures and serious infections, respectively. Several case reports have described a remarkable interaction between the drugs when administered concurrently. The interaction leads to a significant drop in plasma concentrations of valproate within 24 hours and relapse of seizures in some patients. Objective: To evaluate a consecutive population of hospitalized patients who were simultaneously treated with meropenem and valproate and assess the effect on epileptic activity. Methods: A retrospective study of an 18 month period was performed to assess the extent and clinical impact of this interaction. To assess the relevance of the interaction, the time-relationship between the drop in plasma concentrations and relapse in seizure activity and/or deterioration of electroencephalogram recordings was determined. We investigated other contributing preconvulsive cofactors and concomitant antiepileptic treatment. Drug interaction probability scale (DIPS) scores were calculated. Results: Thirty-nine patients were treated simultaneously with valproate and meropenem. The pharmacokinetic interaction was observed in all 39 patients, with an average drop in valproate plasma concentrations of 66%, The decrease occurred within 24 hours, as shown in 19 patients who had daily plasma concentration monitoring, The clinical impact of the interaction could not be assessed in 19 (49%) patients due to death (n = 13) or incomplete charts (n = 6). In the remaining 20 (51%) patients, DIPS scores were calculated and clinical relevance was assessed. The interaction was considered to be probable in 16 patients and possible in 4, as calculated by the DIPS. The interaction contributed to electroclinical deterioration in 11 patients. Conclusions: The pharmacokinetic interaction between valproate and meropenem was present in all patients and led to a drop of valproate concentrations with an average of 66% within 24 hours. This interaction was clinically relevant with electroclinical deterioration in 55% of patients. To avoid patients’ possible neurologic deterioration, meropenem and valproate should not be administered together.

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Pharmacokinetics of culture-directed antibiotics for the treatment of peritonitis in automated peritoneal dialysis: A systematic narrative review

Peritoneal Dialysis International ◽

10.1177/0896860821990528 ◽

2021 ◽

Vol 41 (3) ◽

pp. 261-272

Author(s):

Chau Wei Ling ◽

Kamal Sud ◽

Connie Van ◽

Syed Tabish Razi Zaidi ◽

Rahul P. Patel ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Case Reports ◽

Plasma Concentrations ◽

Case Series ◽

Therapeutic Drug ◽

Pharmacokinetic Studies ◽

Pharmacokinetic Data ◽

Automated Peritoneal Dialysis ◽

Final Study ◽

Drug Plasma

The objectives of this study were to provide a summary of the pharmacokinetic data of some intraperitoneal (IP) antibiotics that could be used for both empirical and culture-directed therapy, as per the ISPD recommendations, and examine factors to consider when using IP antibiotics for the management of automated peritoneal dialysis (APD)-associated peritonitis. A literature search of PubMed, EMBASE, Scopus, MEDLINE and Google Scholar for articles published between 1998 and 2020 was conducted. To be eligible, articles had to describe the use of antibiotics via the IP route in adult patients ≥18 years old on APD in the context of pharmacokinetic studies or case reports/series. Articles describing the use of IP antibiotics that had been recently reviewed (cefazolin, vancomycin, gentamicin and ceftazidime) or administered for non-APD-associated peritonitis were excluded. A total of 1119 articles were identified, of which 983 abstracts were screened. Seventy-three full-text articles were assessed for eligibility. Eight records were included in the final study. Three reports had pharmacokinetic data in patients on APD without peritonitis. Each of cefepime 15 mg/kg IP, meropenem 0.5 g IP and fosfomycin 4 g IP given in single doses achieved drug plasma concentrations above the minimum inhibitory concentration for treating the susceptible organisms. The remaining five records were case series or reports in patients on APD with peritonitis. While pharmacokinetic data support intermittent cefepime 15 mg/kg IP daily, only meropenem 0.5 g IP and fosfomycin 4 g IP are likely to be effective if given in APD exchanges with dwell times of 15 h. Higher doses may be required in APD with shorter dwell times. Information on therapeutic efficacy was derived from case reports/series in individual patients and without therapeutic drug monitoring. Until more pharmacokinetic data are available on these antibiotics, it would be prudent to shift patients who develop peritonitis on APD to continuous ambulatory peritoneal dialysis, where pharmacokinetic information is more readily available.

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Clinical impact of Helicobacter pylori clarithromycin resistance on eradicating therapies in children: A cohort retrospective study

Digestive and Liver Disease ◽

10.1016/j.dld.2008.07.262 ◽

2008 ◽

Vol 40 (10) ◽

pp. A91-A92 ◽

Cited By ~ 1

Author(s):

R. Francavilla ◽

E. Lionetti ◽

A. Magistà ◽

S. Castellaneta ◽

A. De Canio ◽

...

Keyword(s):

Helicobacter Pylori ◽

Retrospective Study ◽

Clinical Impact ◽

Clarithromycin Resistance

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Gene expression–based discovery of atovaquone as a STAT3 inhibitor and anticancer agent

Blood ◽

10.1182/blood-2015-07-660506 ◽

2016 ◽

Vol 128 (14) ◽

pp. 1845-1853 ◽

Cited By ~ 30

Author(s):

Michael Xiang ◽

Haesook Kim ◽

Vincent T. Ho ◽

Sarah R. Walker ◽

Michal Bar-Natan ◽

...

Keyword(s):

Gene Expression ◽

Retrospective Study ◽

Human Plasma ◽

Patient Outcomes ◽

Anticancer Agent ◽

Plasma Concentrations ◽

Anticancer Efficacy ◽

Key Points

Key PointsThe FDA-approved drug atovaquone is a novel, clinically available inhibitor of STAT3 at standard human plasma concentrations. Atovaquone shows anticancer efficacy in vitro, in vivo, and in a retrospective study of AML patient outcomes after atovaquone treatment.

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Clinical impact of underweight status at diagnosis on elderly patients with acute myeloid leukemia: a retrospective study of JALSG GML200

Annals of Hematology ◽

10.1007/s00277-018-3281-1 ◽

2018 ◽

Vol 97 (8) ◽

pp. 1481-1483 ◽

Cited By ~ 1

Author(s):

Kaito Harada ◽

Noriko Doki ◽

Yasushi Miyazaki ◽

Atsushi Wakita ◽

Shigeki Ohtake ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Retrospective Study ◽

Elderly Patients ◽

Myeloid Leukemia ◽

Clinical Impact ◽

Acute Myeloid

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Navigating Clinical Utilization of Direct-from-Specimen Metagenomic Pathogen Detection: Clinical Applications, Limitations, and Testing Recommendations

Clinical Chemistry ◽

10.1093/clinchem/hvaa183 ◽

2020 ◽

Vol 66 (11) ◽

pp. 1381-1395

Author(s):

Laura M Filkins ◽

Alexandra L Bryson ◽

Steve A Miller ◽

Stephanie L Mitchell

Keyword(s):

Clinical Studies ◽

Pathogen Detection ◽

Clinical Laboratory ◽

Fungal Infections ◽

Case Reports ◽

Study Data ◽

Community Acquired Pneumonia ◽

Clinical Impact ◽

Clinical Utilization ◽

Clinical Indications

Abstract Background Metagenomic next generation sequencing (mNGS) is becoming increasingly available for pathogen detection directly from clinical specimens. These tests use target-independent, shotgun sequencing to detect potentially unlimited organisms. The promise of this methodology to aid infection diagnosis is demonstrated through early case reports and clinical studies. However, the optimal role of mNGS in clinical microbiology remains uncertain. Content We reviewed studies reporting clinical use of mNGS for pathogen detection from various specimen types, including cerebrospinal fluid, plasma, lower respiratory specimens, and others. Published clinical study data were critically evaluated and summarized to identify promising clinical indications for mNGS-based testing, to assess the clinical impact of mNGS for each indication, and to recognize test limitations. Based on these clinical studies, early testing recommendations are made to guide clinical utilization of mNGS for pathogen detection. Finally, current barriers to routine clinical laboratory implementation of mNGS tests are highlighted. Summary The promise of direct-from-specimen mNGS to enable challenging infection diagnoses has been demonstrated through early clinical studies of patients with meningitis or encephalitis, invasive fungal infections, community acquired pneumonia, and other clinical indications. However, the proportion of patient cases with positive clinical impact due to mNGS testing is low in published studies and the cost of testing is high, emphasizing the importance of improving our understanding of ‘when to test’ and for which patients mNGS testing is appropriate.

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Increased teniposide clearance with concomitant anticonvulsant therapy.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.2.311 ◽

1992 ◽

Vol 10 (2) ◽

pp. 311-315 ◽

Cited By ~ 55

Author(s):

D K Baker ◽

M V Relling ◽

C H Pui ◽

M L Christensen ◽

W E Evans ◽

...

Keyword(s):

High Performance ◽

Pediatric Patients ◽

Plasma Concentrations ◽

Substantial Reduction ◽

Systemic Exposure ◽

Pharmacokinetic Interaction ◽

Lymphocytic Leukemia ◽

Control Group ◽

Systemic Clearance ◽

The Mean

PURPOSE A possible pharmacokinetic interaction between teniposide and anticonvulsant medications was evaluated in pediatric patients. PATIENTS AND METHODS The systemic clearance of teniposide was determined in six pediatric patients with acute lymphocytic leukemia receiving concomitant therapy with anticonvulsants. Clearance was then compared with a control group of patients treated with the same protocol therapy and matched for age at diagnosis, sex, and race but not receiving anticonvulsants or other agents known to induce hepatic metabolism or alter protein binding of drugs. Eight blood samples were obtained during and after 4-hour infusions of teniposide, and plasma concentrations were measured by a specific high-performance liquid chromatography (HPLC) assay. A two-compartment model was fitted to each subject's data. RESULTS The mean systemic clearance (range) for the six anticonvulsant-treated patients studied during 22 courses of therapy was 32 mL/min/m2 (range, 21 to 54 mL/min/m2), significantly higher (P less than .001) than the mean value of 13 mL/min/m2 (range, 7 to 17 mL/min/m2) for the control patients studied during 26 courses of therapy. Clearance estimates for control patients were similar to previously published values for pediatric patients. CONCLUSION These data indicate that the systemic clearance of teniposide is consistently increased two- to three-fold by concomitant phenobarbital or phenytoin therapy. The consequent substantial reduction in systemic exposure may reduce teniposide's efficacy.

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Evaluation of target attainment of oral posaconazole suspension in immunocompromised children

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz481 ◽

2019 ◽

Vol 75 (3) ◽

pp. 726-729

Author(s):

Tony Lai ◽

Jan-Willem Alffenaar ◽

Alison Kesson ◽

Sushil Bandodkar ◽

Jason A Roberts

Keyword(s):

Retrospective Study ◽

Plasma Concentration ◽

Plasma Concentrations ◽

Invasive Fungal Disease ◽

Target Attainment ◽

Breakthrough Infection ◽

H2 Antagonist ◽

Starting Dose ◽

Histamine H2 Antagonist ◽

The Mean

Abstract Background Posaconazole is a broad-spectrum antifungal that is not licensed for use in children <13 years of age. Despite this and by necessity, it is used extensively in paediatric hospitals for prophylaxis of invasive fungal disease. Objectives To determine whether initial prophylactic dosing recommendations attain a posaconazole plasma concentration of ≥700 ng/mL in immunocompromised children <13 years of age. Patients and methods We performed a retrospective study of immunocompromised children <13 years of age receiving posaconazole suspension prophylaxis at a starting dose of 5 mg/kg every 8 h for ≥7 days and who had a posaconazole concentration measured after ≥7 days. Posaconazole plasma concentrations and rate of breakthrough infection were recorded. Results A total of 70 patients were included with a median age of 5 years (range 3 months to 12 years). The mean posaconazole plasma concentration was 783.4 ng/mL (IQR 428.3–980 ng/mL) and the percentage of patients with a posaconazole plasma concentration ≥700ng/mL was 47.9%. Patients who were on a proton pump inhibitor, a histamine H2 antagonist or metoclopramide, had mucositis or were enterally fed had a lower posaconazole plasma concentration compared with patients without these co-administered drugs/mucositis/enteral feeding (542.3 versus 1069.8 ng/mL; P<0.001). The breakthrough invasive fungal infection rate was 4.3% (3/70). Conclusions The studied 5 mg/kg posaconazole suspension every 8 h resulted in target concentrations in only 47.9% of patients and further studies looking at newer posaconazole formulations are needed.

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Clinical impact of leakage in patients with handsewn vs stapled anastomosis after right hemicolectomy: a retrospective study

Colorectal Disease ◽

10.1111/codi.15098 ◽

2020 ◽

Vol 22 (10) ◽

pp. 1286-1292 ◽

Cited By ~ 1

Author(s):

E. Espin ◽

F. Vallribera ◽

E. Kreisler ◽

S. Biondo

Keyword(s):

Retrospective Study ◽

Right Hemicolectomy ◽

Clinical Impact ◽

Stapled Anastomosis

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Impact of infertility treatment in patients with previous history of borderline ovarian tumors: Results of a multicenter study

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.5055 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 5055-5055

Author(s):

A. Fortin ◽

P. Morice ◽

A. Thoury ◽

C. Yazbeck ◽

S. Camatte ◽

...

Keyword(s):

Retrospective Study ◽

Early Stage ◽

Case Reports ◽

Previous History ◽

Infertility Treatment ◽

Ovarian Tumors ◽

Borderline Ovarian Tumors ◽

History Of

5055 Background: The use of infertility drugs (ID) in infertile patients treated conservatively for ovarian malignancies remains theoretically contraindicated. Few recent case reports seem to suggest that ID could be used in patients treated for a borderline ovarian tumors (BOT). The aim of this multicenter retrospective study was to report the outcomes of the largest series of patients with a previous history of a BOT who underwent the use of ID. Methods: A multicenter retrospective study was conducted among centers which participate in the French National Register on In Vitro Fertilization registry to evaluate the outcomes of patients with a previous history of a BOT treated with ID. Four criteria were defined to select cases: 1. Histologic confirmation of BOT, 2. The use of a conservative surgery, 3. The use of ID and 4. A follow-up ≥ 12 months after the end of infertility treatment. Results: Thirty cases fulfilled inclusion criteria. Infertility therapy began in November 1989. Disease stages were: I (n = 20), II /III with noninvasive implants (n = 8) and unknown in 2 cases. The mean number of cycles of ovarian induction per patient was 2.6 (range,1–10). After a median follow-up of 42 months after infertility treatment, 4 recurrences were observed (all of them were borderline tumors on a remaining ovary treated by surgery alone). All patients are currently disease-free. Thirteen patients have since become pregnant. The median interval between treatment of the BOT and the use of ID is shorter in patients who relapsed compared to patients who did not (5 versus 29 months; p=.07). Conclusions: These results suggest that infertility drugs could be safely used in patients who experience infertility after conservative management of an early-stage BOT. A minimal interval should be respected between treatment of the ovarian tumor and the use of infertility drugs in order to decrease the risk of recurrence. No significant financial relationships to disclose.

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