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Liestal, Switzerland

Baldoni D.,University of Basel | Steinhuber A.,University of Basel | Zimmerli W.,University Medical Clinic | Trampuz A.,University of Basel | Trampuz A.,University of Lausanne
Antimicrobial Agents and Chemotherapy

Ga3+ is a semimetal element that competes for the iron-binding sites of transporters and enzymes. We investigated the activity of gallium maltolate (GaM), an organic gallium salt with high solubility, against laboratory and clinical strains of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), and methicillin-resistant S. epidermidis (MRSE) in logarithmic or stationary phase and in biofilms. The MICs of GaM were higher for S. aureus (375 to 2000 μg/ml) than S. epidermidis (94 to 200 μg/ml). Minimal biofilm inhibitory concentrations were 3,000 to ≥6,000 μg/ml (S. aureus) and 94 to 3,000 μg/ml (S. epidermidis). In time-kill studies, GaM exhibited a slow and dose-dependent killing, with maximal action at 24 h against S. aureus of 1.9 log10 CFU/ml (MSSA) and 3.3 log10 CFU/ml (MRSA) at 3x MIC and 2.9 log10 CFU/ml (MSSE) and 4.0 log10 CFU/ml (MRSE) against S. epidermidis at 10x MIC. In calorimetric studies, growth-related heat production was inhibited by GaM at subinhibitory concentrations; and the minimal heat inhibition concentrations were 188 to 4,500 μg/ml (MSSA), 94 to 1,500 μg/ml (MRSA), and 94 to 375 μg/ml (MSSE and MRSE), which correlated well with the MICs. Thus, calorimetry was a fast, accurate, and simple method useful for investigation of antimicrobial activity at subinhibitory concentrations. In conclusion, GaM exhibited activity against staphylococci in different growth phases, including in stationary phase and biofilms, but high concentrations were required. These data support the potential topical use of GaM, including its use for the treatment of wound infections, MRSA decolonization, and coating of implants. Copyright © 2010, American Society for Microbiology. All Rights Reserved. Source

Burri E.,University of Basel | Burri E.,University Medical Clinic | Beglinger C.,University of Basel
Expert Review of Gastroenterology and Hepatology

Abdominal discomfort including pain, bloating and diarrhea is common. It often arises from functional gastrointestinal disorders but may indicate inflammatory bowel disease (IBD). Calprotectin is an abundant neutrophil protein that is released during inflammation. When measured in feces, it can be used to differentiate between non-organic and inflammatory intestinal disorders, especially to identify IBD. Fecal calprotectin might also be useful to monitor patients with IBD under treatment and to predict the risk of recurrence of active disease prior to clinical relapse. The use of fecal calprotectin has been investigated in a number of gastrointestinal disorders other than IBD, for example, as screening test for colorectal cancer but the available data are limited. This article summarizes the current literature on the use of fecal calprotectin in clinical practice. © 2014 Informa Healthcare. Source

Beetz R.,University Medical Clinic
Current Opinion in Pediatrics

PURPOSE OF REVIEW: The prevalence of urinary tract infections (UTIs) among full-term neonates has been reported to be up to 1.1%, increasing up to 7% among those with fever. UTI in neonates may be the first indicator of underlying abnormalities of kidneys and the urinary tract. RECENT FINDINGS: Early recognition and therapy of UTI and detection of risk factors of fer chances for applying strategies to avoid renal damage and recurrences. However, established diagnostic strategies and prophylactic concepts today are under debate. Currently, the main focus has been on renal changes as indicators for underlying risk factors like vesicoureteral reflux, attaching much importance to dimercaptosuccinyl acid scans. Serum and urine markers will probably allow more restrictive diagnostic imaging. Prenatal and postnatal ultrasound screenings provide additional opportunities for prophylactic measures. SUMMARY: Main objectives in the management of neonatal UTIs are the prevention of acute infection-related complications and renal damage. Neonates and very young infants with suspicious pyelonephritis should obligatorily be treated with a combination of parenterally administered antibiotics. As far as possible, diagnostic imaging should be risk-oriented and restricted to noninvasive, nonstressful procedures. The strategies of antibacterial prophylaxis for the prevention of recurrent UTIs are changing. In infants at risk, its benefits have not yet been proven by evident data. © 2012 Lippincott Williams & Wilkins, Inc. Source

Tafin U.F.,University of Lausanne | Corvec S.,University of Lausanne | Corvec S.,Nantes University Hospital Center | Betrisey B.,University of Lausanne | And 2 more authors.
Antimicrobial Agents and Chemotherapy

Propionibacterium acnes is an important cause of orthopedic-implant- associated infections, for which the optimal treatment has not yet been determined.Weinvestigated the activity of rifampin, alone and in combination, against planktonic and biofilm P. acnes in vitro and in a foreign-body infection model. The MIC and the minimal bactericidal concentration (MBC) were 0.007 and 4 μg/ml for rifampin, 1 and 4 μg/ml for daptomycin, 1 and 8 μg/ml for vancomycin, 1 and 2 μg/ml for levofloxacin, 0.03 and 16 μg/ml for penicillin G, 0.125 and 512 μg/ml for clindamycin, and 0.25 and 32 μg/ml for ceftriaxone. The P. acnes minimal biofilm eradication concentration (MBEC) was 16 μg/ml for rifampin; 32 μg/ml for penicillin G; 64 μg/ml for daptomycin and ceftriaxone; and ≥128 μg/ml for levofloxacin, vancomycin, and clindamycin. In the animal model, implants were infected by injection of 10 9 CFU P. acnes in cages. Antimicrobial activity on P. acnes was investigated in the cage fluid (planktonic form) and on explanted cages (biofilm form). The cure rates were4%for daptomycin, 17% for vancomycin,0%for levofloxacin, and 36% for rifampin. Rifampin cured 63% of the infected cages in combination with daptomycin, 46% with vancomycin, and 25% with levofloxacin. While all tested antimicrobials showed good activity against planktonic P. acnes, for eradication of biofilms, rifampin was needed. In combination with rifampin, daptomycin showed higher cure rates than with vancomycin in this foreign-body infection model. Copyright © 2012, American Society for Microbiology. All Rights Reserved. Source

Erlic Z.,Albert Ludwigs University of Freiburg | Hoffmann M.M.,Albert Ludwigs University of Freiburg | Sullivan M.,Albert Ludwigs University of Freiburg | Franke G.,Albert Ludwigs University of Freiburg | And 13 more authors.
Journal of Clinical Endocrinology and Metabolism

Context: Cancer genetics is fundamental for preventive medicine, in particular in pheochromocytoma-associated syndromes. Variants in two susceptibility genes, SDHC and RET, were found in a kind red with head and neck paraganglioma. This observation of coincident DNA variants, both reported as pathogenic, in two known susceptibility genes prompted the question of their pathogenic relevance. Objective: Our objective was to elucidate the pathogenic role of the detected variants and study the prevalence of such variants. Patients: Patients were registrants from the European-American Pheochromocytoma-Paraganglioma and German von Hippel-Lindau Disease Registries. Design: Analysis of germline mutation screening results for all pheochromocytoma-paragangliomasusceptibility genes, including RET [multiple endocrine neoplasia type 2(MEN2)] and VHL [von Hippel-Lindau disease (VHL)]. Cases in which more than one DNA variant was found were clinically reevaluated,andcosegregation of the disease with the variantwasanalyzed within the registrants' families. A total of 1000 controls were screened for the presence of detected variants, and in silico analyses were performed. Results: Three variants were identified, RET p.Tyr791Phe and p.Ser649Leu and VHL p.Pro81Ser. The frequencies of RET p.Ser649Leu (0.07%) and p.Tyr791Phe (0.9%) compared with controls excluded the two variants' role in the etiology of MEN 2 and VHL. None of the carriers of the RET variants who underwent prophylactic thyroidectomy showed medullary thyroid carcinoma. Clinical reinvestigation of 18 variant carriers excluded MEN2. VHL variant p.Pro81 Ser, also previously described as a mutation, did not segregate with the VHL in one family. In silico analyses for these variants predicted unmodified protein function. Conclusions: RET p.Tyr791Phe and p.Ser649Leu and VHL p.Pro81Ser are definitely not pathogenic mutations for VHL and MEN 2. Misinterpretation results in irreversible clinical consequences. Copyright © 2010 by The Endocrine Society. Source

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