Case Report: Subtherapeutic Vancomycin and Meropenem Concentrations due to Augmented Renal Clearance in a Patient With Intracranial Infection Caused by Streptococcus intermedius.

Streptococcus intermedius occasionally causes brain abscesses that can be life-threatening, requiring prompt antibiotic and neurosurgical treatment. The source is often dental, and it may spread to the eye or the brain parenchyma. We report the case of a 34-year-old man with signs of apical periodontitis, endophthalmitis, and multiple brain abscesses caused by Streptococcus intermedius. Initial treatment with meropenem and vancomycin was unsuccessful due to subtherapeutic concentrations, despite recommended dosages. Adequate concentrations could be reached only after increasing the dose of meropenem to 16 g/day and vancomycin to 1.5 g × 4. The patient exhibited high creatinine clearance consistent with augmented renal clearance, although iohexol and cystatin C clearances were normal. Plasma free vancomycin clearance followed that of creatinine. A one-day dose of trimethoprim-sulfamethoxazole led to an increase in serum creatinine and a decrease in both creatinine and urea clearances. These results indicate that increased tubular secretion of the drugs was the cause of suboptimal antibiotic treatment. The patient eventually recovered, but his left eye needed enucleation. Our case illustrates that augmented renal clearance can jeopardize the treatment of serious bacterial infections and that high doses of antibiotics are needed to achieve therapeutic concentrations in such cases. The mechanisms for regulation of kidney tubular transporters of creatinine, urea, vancomycin, and meropenem in critically ill patients are discussed.

Prevalence of and factors influencing vitamin D deficiency in paediatric patients diagnosed with cancer at northern latitudes.

AIM: To investigate the prevalence of vitamin D deficiency among children with non-haematological malignancies and to explore possible causes of low vitamin D levels among these patients. METHODS: We performed a cross-sectional study of 458 children diagnosed with solid tumours, brain tumours, non-Hodgkin lymphoma or Hodgkin disease at the University Children's Hospital, Uppsala, Sweden. Serum 25-hydroxyvitamin D and parathyroid hormone levels were measured in samples taken at the time of cancer diagnosis and related to clinical data. Vitamin D deficiency was defined as a 25-hydroxyvitamin D level below 50 nmol/L. RESULTS: The prevalence rate of vitamin D deficiency among children with non-haematological malignancies was 41%. There was no association between sex or diagnosis and vitamin D status. Vitamin D deficiency was more common among school children than preschool children (51% vs. 24%). Older age, season outside summer, and a more recent calendar year were significant predictors of lower 25-hydroxyvitamin D. There was a significant, albeit weak, negative correlation between 25-hydroxyvitamin D and parathyroid hormone. CONCLUSION: Vitamin D deficiency is common among children diagnosed with cancer, particularly among school-aged children diagnosed outside summer. The prevalence appears to be increasing, underlining the need for adequate replacement of vitamin D in these patients.

Vitamin D status in children with leukemia, its predictors, and association with outcome.

BACKGROUND: Children and adolescents with leukemia are potentially at high risk of vitamin D inadequacy, which may have clinical relevance for skeletal morbidity, infections, and cancer outcome. This study aimed to evaluate vitamin D status at the time of diagnosis to investigate its predictors and association with overall survival in children with leukemia. PROCEDURE: We included all 295 children and adolescents diagnosed with leukemia at our institution between 1990 and 2016 who had available serum sample from the time of diagnosis. We analyzed serum 25-hydroxyvitamin D and parathyroid hormone levels and correlated them with clinical data. RESULTS: The 25-hydroxyvitamin D level was deficient (< 25 nmol/L), insufficient (25-50 nmol/L), sufficient (50-75 nmol/L), and optimal (> 75 nmol/L) in 6.4%, 26.8%, 39.7%, and 27.1% of the children, respectively. Older age and a more recent time of sampling (calendar year) predicted lower 25-hydroxyvitamin D level. In preschool children (age ≤6 years), lower 25-hydroxyvitamin D level was also associated with acute myeloid leukemia, and a 25-hydroxyvitamin D level < 50 nmol/L was associated with inferior overall survival. In school-aged children (age > 6 years), the 25-hydroxyvitamin D level showed significant seasonal variation. CONCLUSION: It remains unclear whether vitamin D supplementation in pediatric leukemia patients will improve outcome.

Acute effects of coffee on skin blood flow and microvascular function.

OBJECTIVE: Studies on the acute effects of coffee on the microcirculation have shown contradicting results. This study aimed to investigate if intake of caffeine-containing coffee changes blood flow and microvascular reactivity in the skin. METHODS: We measured acute changes in cutaneous vascular conductance (CVC) in the forearm and the tip of the finger, the microvascular response to transdermal iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) and post-occlusive reactive hyperemia (PORH) in the skin, after intake of caffeinated or decaffeinated coffee. RESULTS: Vasodilatation during iontophoresis of ACh was significantly stronger after intake of caffeinated coffee compared to after intake of decaffeinated coffee (1.26±0.20PU/mmHg vs. 1.13±0.38PU/mmHg, P<0.001). Forearm CVC before and after PORH were not affected by caffeinated and decaffeinated coffee. After intake of caffeinated coffee, a more pronounced decrease in CVC in the fingertip was observed compared to after intake of decaffeinated coffee (-1.36PU/mmHg vs. -0.52PU/mmHg, P=0.002). CONCLUSIONS: Caffeine, as ingested by drinking caffeinated coffee acutely improves endothelium-dependent microvascular responses in the forearm skin, while endothelium-independent responses to PORH and SNP iontophoresis are not affected. Blood flow in the fingertip decreases markedly during the first hour after drinking caffeinated coffee compared to decaffeinated coffee.

Pheomelanin-related benzothiazole isomers in the urine of patients with diffuse melanosis of melanoma.

BACKGROUND: Currently used as structural markers for pheomelanin identification and quantitation, benzothiazole compounds derived from isomers of cysteinyldopa have been indicated by recent in vitro studies as new potential pheomelanogenesis intermediates. The presence of benzothiazole compounds in the urine of patients with melanoma with or without diffuse melanosis was investigated. METHODS: Hydrophilic interaction liquid chromatography with zwitterionic stationary phase (ZIC-HILIC) and photo-diode array (PDA) detection was used for analysis of 6-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole-2-carboxylic acid (BTCA-5), and 7-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole-2-carboxylic acid (BTCA-2), derived from 5-S-cysteinyldopa (5-S-CD) and 2-S-cysteinyldopa (2-S-CD) isomers, respectively. After minimal sample preparation, isocratic chromatography allowed efficient separation of the compounds, which were safely identified by their typical absorption features. RESULTS: Three patients with diffuse melanosis, 16 patients with melanoma (stages III and IV) and three healthy subjects were investigated. The urinary BTCAs were found to be highly associated with melanosis but more loosely to excreted 5-S-CD. Analysis of the pigmented fraction of urine following alkaline hydrogen peroxide degradation and quantitation of BTCAs provided evidence for the presence of pheomelanins at high levels in patients with melanosis. CONCLUSION: Identification of free BTCA isomers in urine provides a significant contribution in the field of urinary melanogens, and has important implications for biosynthetic activity of normal and pathologic melanocytes.

Gas chromatography-mass spectrometry analysis of pheomelanin degradation products.

Melanoma is most rapidly increasing in the white population and people with pheomelanin skin type are at high risk to develop melanoma. However, little is known about the pheomelanin structure and function, and further elucidation of this melanin is therefore an important task. A GC/MS method was developed based on hydriodic acid hydrolysis of pheomelanin in the urine. Derivatization was performed with ethyl chloroformate and ethanol:pyridine (4:1, v/v). N,O-Ethoxycarbonyl-ethyl esters were extracted with chloroform and analyzed by GC/MS. 4-Amino-3-hydroxyphenylalanine and 3-amino-4-hydroxyphenylalanine together with one benzothiazinone and two benzothiazole compounds were detected and identified in hydrolyzed samples of synthetic pheomelanin and melanin from the urine of a patient with melanoma. These findings strongly suggest that heterocyclic pheomelanin-type units are incorporated in the pigment structures.