scholarly journals 272. Clinical Utility of Sulfamethoxazole Serum Level Monitoring in the Treatment of Brain Abscesses due to Nocardia Species

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S242-S242
Author(s):  
Cristina G Corsini Campioli ◽  
Christina G Rivera ◽  
Kristin Mara ◽  
Omar Abu Saleh
Keyword(s):  
Serum Level ◽  
Drug Toxicity ◽  
Fluid Collection ◽  
Kidney Injury ◽  
Treatment Interruption ◽  
Therapeutic Drug ◽  
Induction Phase ◽  
Length Of Treatment ◽  
Serum Monitoring ◽  
Level Monitoring

Abstract Background Although trimethoprim-sulfamethoxazole (TMP-SMX) has consistently demonstrated significant interindividual variability, therapeutic drug monitoring is used to optimize dosing and avoid adverse reactions that may contribute to treatment interruption. While data exists on the use of SMX level monitoring in pneumocystis, there is a lack of data in SMX serum monitoring utility for invasive Nocardia infections. Methods We retrospectively reviewed adults who received TMP-SMX to treat nocardial brain abscess (BA) and underwent SMX testing level from January 2010 to December 2020. Results Overall, 24 patients had Nocardia spp. BA; Twenty-two (91.7%) were treated with TMP-SMX, and 16/22 (72.7%) had a documented SMX serum level. The median age was 64 (IQR 58-69) years, and the majority were males (77.3%). Compared to those who did not have a documented SMX serum level, patients with SMX levels had a higher prevalence of hemodialysis (HD, 42.9% vs. 33%; P=.99) and malignancy (50% vs. 33.3%; P=.65). The most common BA location was the frontal lobe (43.8% vs. 33.3%; P=.99), with a single (68.8% vs. 50%; P=.62) and smaller (1.3 vs. 1.9 cm; P=.58) brain fluid collection, and with fewer midline shift (6.3% vs. 16.7%; P=.48), respectively. The median TMP-SMX duration was 350 days (P=.31). The most common dosing was 2-double strength, three times a day (31.8%). The SMX median level was 158.5 (IQR 120-218) mcg/mL, collected at two hours (75%) post-administration in the induction phase (81.3%). The most common recommendation was to continue therapy based on the level results. Eleven (46%) patients had a level >150 mcg/mL, and 5 (45.5%) reported drug toxicity, including nausea in 3, acute kidney injury in 2, and thrombocytopenia in 2 patients. Ninety-four percent of the patients with SMX levels had surgical intervention for therapeutic purposes vs. 83% of those without it (P=.65). A total of 11 (50%) patients were cured, 3 (18.8%) relapsed, and 2 (12.5%) died. Conclusion Patients with SMX serum level monitoring are more likely to be on HD, during the induction phase and among those with higher and more frequent dosing. About half of patients with SMX levels >150 mcg/mL experienced drug toxicity; however, SMX levels did not impact patient outcome and length of treatment. Disclosures All Authors: No reported disclosures

scholarly journals 1319. Pharmacokinetics of Ceftolozane/Tazobactam in Patients with Burns

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S670-S671
Author(s):  
Ronald G Hall ◽  
Jotam Pasipanodya ◽  
William C Putnam ◽  
John Griswold ◽  
Sharmila Dissanaike ◽  
...  
Keyword(s):  
Human Plasma ◽  
Kidney Injury ◽  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Population Parameter ◽  
Full Thickness ◽  
Severe Burns

Abstract Background Antimicrobial dosing in moderate/severe burns patients is complicated due to the potential unpredictable hyperdynamic pathophysiologic states including 1) hypoproteinemia, 2) acute kidney injury and 3) onset of septicemia. Therefore, distribution assumptions about the population pharmacokinetic (PopPK) profiles of either endogenous or xenobiotic pharmacophores in this patient population can lead to biased parameter estimates. In order to prevent potential bias an agnostic nonparametric adaptive grid approach to describe ceftolozane/tazobactam (C/T) PopPK profiles in patients with partial- and full-thickness burns was employed. Methods A human clinical PK study in burn patients was conducted using the standard approved dose of C/T (2 grams/1 gram). A single intravenous dose was administered over 60 minutes. Whole blood was obtained pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours following the start of infusion. LC-MS/MS bioanalytical methods were developed, validated and employed to determine C/T concentrations in human plasma. PopPK were modeled using Pmetrics package for R. One-, two- and three-compartment models were examined and compared. The influence of several parameters, including %body surface area burns, creatinine clearance (CrCL), weight, albumin and age were tested. Results The bioanalytical method for determination of C/T in human plasma met all recommended criteria of the LC-MS/MS. Five males and one female (ages 24 to 66 years), contributed 148 plasma PK samples. The female had 35% partial-thickness burns. The males had full-thickness burns ranging from 27 to 66%. The median CrCL was 104 mL/min (range 73-148 mL/min). Two-compartment model with absorption (Ka) from compartment 1 to 2 and elimination from compartment 2 (Ke), with nonlinear interactions between C/T elimination and CrCL best described the data. Figure A show that bias was minimal. Importantly, both drugs exhibited marked variability for both volume and elimination (Table), since volume was bimodally distributed (Figure B). A) Observation-versus-Prediction; B) Estimated Ke, V and Ka population parameter densities Summary of pharmacokinetic parameters Conclusion C/T exhibited high variability surpassing that observed with severe infections, suggesting that dose adjustment and/or may be therapeutic drug monitoring may be needed to balance target attainment from dose-related toxicities. Disclosures Ronald G. Hall, II, PharmD, MSCS, Medical Titan Group (Grant/Research Support)Merck (Research Grant or Support)

Anal cancer treated with radio-chemotherapy: correlation between length of treatment interruption and outcome

2009 ◽  
Vol 24 (12) ◽  
pp. 1421-1428 ◽  
Author(s):  
Stefan Janssen ◽  
Jürgen Meier zu Eissen ◽  
Gerd Kolbert ◽  
Michael Bremer ◽  
Johann Hinrich Karstens ◽  
...  
Keyword(s):  
Anal Cancer ◽  
Treatment Interruption ◽  
Length Of Treatment ◽  
Radio Chemotherapy

Drug level monitoring in palliative patients

2021 ◽  
pp. bmjspcare-2020-002613
Author(s):  
Joanne Bartlett ◽  
Elizabeth Freshwater
Keyword(s):  
Brain Tumour ◽  
Palliative Medicine ◽  
Drug Level ◽  
Therapeutic Drug ◽  
Primary Brain Tumour ◽  
Drug Level Monitoring ◽  
Symptoms And Signs ◽  
Level Monitoring ◽  
Palliative Patients

Palliative medicine is always patient centred and promotes the principle that no unnecessary investigations are performed. The case is reported of a patient with suspected carbamazepine toxicity presenting as progression of symptoms of primary brain tumour. A comparison is made of the symptoms and signs of toxicity versus tumour, and an aid for deciding when to perform therapeutic drug level monitoring for some common drugs.

scholarly journals Thiopurines’ Metabolites and Drug Toxicity: A Meta-Analysis

2020 ◽  
Vol 9 (7) ◽  
pp. 2216
Author(s):  
Paula Sousa ◽  
Maria Manuela Estevinho ◽  
Cláudia Camila Dias ◽  
Paula Ministro ◽  
Uri Kopylov ◽  
...  
Keyword(s):  
Systematic Review ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Alanine Aminotransferase ◽  
Odds Ratio ◽  
Drug Toxicity ◽  
Meta Analysis ◽  
Therapeutic Drug ◽  
Gastrointestinal Intolerance ◽  
The Relationship

Many questions remain unanswered regarding therapeutic drug monitoring (TDM) utility with thiopurines. This study aims to establish a relationship between thiopurines’ metabolites and drug toxicity. We performed a systematic review with inclusion of studies evaluating the relationship between thiopurines’ metabolites and drug toxicity. Meta-analysis of mean difference (MD), correlations and odds ratio (OR) was performed. We identified 21,240 records, 72 of which were eligible for meta-analysis. Levels of 6-thioguanine nucleotides (6-TGN) were higher in patients with leukopenia (MD 127.06 pmol/8 × 108 RBC) and gastrointestinal intolerance (MD 201.46 pmol/8 × 108 RBC), and lower in patients with hepatotoxicity (MD −40.6 pmol × 108 RBC). We established a significant correlation between 6-TGN and leukocytes (r = −0.21), neutrophils (r = −0.24) and alanine aminotransferase levels (r = −0.24). OR for leukopenia in patients with elevated 6-TGN was 4.63 (95% CI 2.24; 9.57). An optimal cut-off of 135 pmol/8 × 108 RBC for leukopenia was calculated (sensitivity 75.4%; specificity 46.4%). 6-methylmercaptopurine ribonucleotides (6-MMPR) were significantly associated with hepatotoxicity (MD 3241.2 pmol/8 × 108 RBC; OR 4.28; 95% CI 3.20; 5.71). Levels of 6-MMPR measured in the first 8 weeks of treatment were associated with leukopenia. We conclude that TDM could be used to prevent thiopurines’ toxicity. As optimal metabolites level may vary according to indication, physicians may adapt posology to decrease toxicity without compromising efficacy.

Methotrexate Blood Level Monitoring

1985 ◽  
Vol 19 (5) ◽  
pp. 372-373 ◽  
Author(s):  
Helen St.C. Remington ◽  
Clifford C. Bailey
Keyword(s):  
Blood Level ◽  
Fluid Balance ◽  
Drug Level ◽  
Therapeutic Drug ◽  
High Dose ◽  
High Dose Therapy ◽  
Methotrexate Toxicity ◽  
Management Procedures ◽  
Drug Level Monitoring ◽  
Level Monitoring

Methotrexate toxicity can be avoided following high-dose therapy if certain management procedures are adhered to. These include careful fluid balance management and therapeutic drug level monitoring. A case is reported of an episode of methotrexate toxicity resulting from a fluid balance problem.

P0647ACUTE KIDNEY INJURY SECONDARY TO SUCROSE CONTAING INTAVENOUS IMMUNOGLOBULIN

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sadiq Al Lawati ◽  
Issa Al Salmi ◽  
SUAD Hannawi
Keyword(s):  
Acute Kidney Injury ◽  
Serum Level ◽  
Kidney Function ◽  
Viral Infections ◽  
Kidney Transplant Recipient ◽  
Transplant Rejection ◽  
Organ Transplant ◽  
Vital Signs ◽  
Kidney Injury ◽  
Kaposi Sarcoma

Abstract Background and Aims Intravenous immunoglobulins (IVIG) are pooled polyvalent IgG antibodies extracted from the human plasma. While the initial indications were mainly immune deficiency states and some autoimmune diseases, the usage has been widened to include several immune mediated diseases, viral infections, and organ transplant rejection. Stabilizers in IVIG may include sugars, such as sucrose, glucose, or maltose. Sucrose in IVIG preparations may cause acute kidney injury. We report the case of a renal transplant patient who developed acute kidney injury due to sucrose nephropathy following the administration of sucrose containing IVIG. Method Four months after transplantation he was referred to our Hospital for deterioration of kidney function with eGFR (by MDRD formula) of 27ml/min. Cytomegalovirus virus (CMV) PCR turned positive (3300 copies/ml). Cyclosporine levels were high (C2: 2937 ng/ml) and hence, cyclosporine dose was adjusted. Induction therapy with Injection Ganciclovir for 2 weeks, followed by therapeutic dose of oral Valganciclovir was administered for the treatment of CMV infection. Skin examination revealed annular purple patches, suspicious of Kaposi Sarcoma, on the upper limbs. Skin biopsy confirmed the diagnosis. It was planned to give total IVIG of 2 gm/ kg in four daily divided doses. After completion of the second dose, serum creatinine increased to 370 µmol/L. He was clinically asymptomatic, euvolumic, vital signs were stable, and his urine output remained normal and his urinalysis was inactive. Results The ultrasound of the transplant kidney was normal with normal resistivity index. IVIG was stopped. He was well hydrated and underwent ultrasound guided biopsy. The graft biopsy showed acute tubular injury with flattening and vacuolation of tubular epithelial cells. Mitosis indicating tubular regeneration was seen. There was mild focal interstitial inflammation (20%) with mild lymphocytic tubulitis not amounting to graft rejection. Immunohistochemistry for C4d and polyomavirus (BKV) were both negative. The features were most consistent with sucrose induced nephropathy (Figure 1). Subsequent visits showed a decrease in BKV-PCR serum level and eventually undetected serum level of BKV-PCR at follow up about a month later. Conclusion In this paper, we presented a case of a living unrelated kidney transplant recipient who developed BKV nephropathy and developed impaired kidney function. The patient also had new onset diabetes mellitus after kidney transplantation (NODAT) but was otherwise in good general health. Treatment included sucrose containing IVIG. The patient subsequently developed acute kidney injury. The outcome was favorable with recovery of filtration rate to the baseline within 21 days without the need for dialysis. We conclude that the administration of sucrose containing IVIG may lead to acute kidney injury. We recommend the use of sucrose-free IVIG whenever possible. In all cases, caution is required when administrating IVIG.

Acute kidney injury and perinephric fluid collection: Answers

2019 ◽  
Vol 35 (6) ◽  
pp. 983-984
Author(s):  
Tuba Kurt ◽  
Fatma Aydin ◽  
Bilge Karabulut ◽  
Umut Selda Bayrakçı ◽  
Nermin Uncu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Fluid Collection ◽  
Kidney Injury

scholarly journals Tacrolimus Toxicity due to Biliary Obstruction in a Combined Kidney and Liver Transplant Recipient

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Samuel Chan ◽  
Michael T. Burke ◽  
David W. Johnson ◽  
Ross S. Francis ◽  
David W. Mudge
Keyword(s):  
Transplant Recipient ◽  
Biliary Obstruction ◽  
Kidney Transplant Recipient ◽  
Kidney Injury ◽  
Therapeutic Window ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Liver And Kidney ◽  
The Impact ◽  
Very High

The immunosuppressant tacrolimus has a narrow therapeutic window, necessitating therapeutic drug monitoring to maintain efficacy and minimise toxicity. There are very few reports examining the impact of impaired biliary excretion on tacrolimus blood levels or toxicity. We report the case of a 26-year-old combined liver and kidney transplant recipient, who developed acute biliary obstruction leading to tacrolimus toxicity with very high blood tacrolimus levels. Despite a careful evaluation, no alternative cause was found for her acute kidney injury, and her kidney function returned to previous baseline within several days following treatment of the biliary obstruction and temporary withdrawal of tacrolimus.

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