Cyclosporine Interacts with Mycophenolic Acid by Inhibiting the Multidrug Resistance-Associated Protein 2

In mycophenolate mofetil (MMF)-treated organ transplant recipients, lower mycophenolic acid (MPA) plasma concentrations have been found in cyclosporine (CsA) compared with tacrolimus (Tac)-based immunosuppressive regimens. We previously demonstrated that CsA decreases exposure to MPA and increases exposure to its metabolite MPA-glucuronide (MPAG), possibly by interfering with the biliary excretion of MPAG. To elucidate the role of the multidrug resistance-associated protein (Mrp)-2 in the interaction between MMF and CsA, we treated three groups of 10 Mrp2-deficient rats (TR- rat) for 6 days with either vehicle, CsA (8 mg/kg) or Tac (4 mg/kg) by oral gavage. Hereafter, co-administration with MMF (20 mg/kg) was started in all groups and continued through day 14. The 24-h MPA/MPAG area under the concentration-time curve (AUC) was determined after single (day 7) and multiple MMF doses (day 14). On both study days, there were no significant differences in the mean MPA and MPAG AUC between CsA and Tac-treated animals. We conclude that the pharmacokinetics of MMF are comparable in Mrp2-deficient rats receiving either CsA or Tac as co-medication. This finding suggests that CsA-mediated inhibition of the biliary excretion of MPAG by the Mrp2 transporter is the mechanism responsible for the interaction between CsA and MMF.     

Immunohistochemical localization of pepsinogen A and C containing cells in Barrett's oesophagus

Summary No data are available on the localization of Pepsinogen A (PGA=PG I) and Pepsinogen C (PGC=PG II) positive cells in Barrett's epithelium. Endoscopic biopsy specimens were taken from the columnar epithelium from 23 patients (n=93), and in addition from the cardia from eight healthy control subjects (n=38). The tissue was stained by the immunoperoxidase technique with specific anti-pepsinogen antisera, and double immunostained for PGA and PGC. In the Barrett's epithelium PGA was found in 28 out of 93 biopsy specimens (30.1%) and PGC in 55 out of 93 (59.1%). Chief cells always stained both for PGA and PGC, while clear mucous cells were often PGA– and PGC+. PGA+ and PGC+ cells were found each in 100% of the biopsy specimens with fundic type epithelium, in 21.7% and 70.7% of biopsy specimens with junctional type, in 0% and 26.1% of biopsy specimens with specialized epithelium and in 12.5% and 43.5% of biopsy specimens with mixed junctional/specialized features respectively. Dysplastic epithelium stained always negatively with both anti-pepsinogen antisera. In most control cardia biopsy specimens PGA as well as PGC were demonstrable; occasionally clear mucous glands were PGA– and PGC+.It is concluded that pepsinogen-containing cells can be accurately identified in the Barrett's epithelium; their presence seems related to the histological cell type. Identification of pepsinogen positive cells may contribute to a more accurate morphological classification of the Barrett's epithelium.Presented in part at the Annual Meeting of the American Gastroenterological Association, San Francisco, May 1986     

Rapid identification of Haemophilus influenzae serovar b by gas liquid chromatography using carbohydrate fingerprints

Carbohydrates from whole-cell hydrolysates of 18 strains of the species Haemophilus influenzae (5 strains belonging to serovar b) were analysed by gas-liquid chromatography. The identity of the carbohydrate components was confirmed by comparison with the retention times of reference sugars and by gas chromatography mass spectrometry. Evidence was obtained that Haemophilus influenzae serovar b can easily be identified by the presence of one large peak representing ribitol. The method described can be routinely applied in bacteriological laboratories equipped with a gas chromatograph. It gives results within approximately 4 h, it is reproducible and easy to perform. Even single colonies isolated directly from agar plates can be used for analysis without further subculturing.     

Prognostic performance of clinical assessment tools following hip fracture in patients with chronic kidney disease

International Urology and Nephrology - People living with chronic kidney disease (CKD) are at a higher risk of hip fracture with an associated increased mortality risk compared to individuals...     

Complications After Surgical Treatment of Geriatric Ankle Fractures

The incidence of geriatric ankle fractures is rising and the potential for complications is high in this population. Little is known about factors associated with increased postoperative complications after surgical fixation of ankle fractures in older-age patients. The purpose of this retrospective cohort study was to assess the epidemiology and risk factors for complications after surgically treated ankle fractures in geriatric patients. All patients who were 65 years or older and had a surgically treated ankle fracture were included. Pilon fractures, patients who were initially treated conservatively or who had less than 1 month of follow-up were excluded. Postoperative complications, demographic-, fracture- and surgical data of 282 patients were recorded from two level 2 trauma centers between 2012 and 2017. A total of 87 (30.9%) patients developed a complication, of which wound related complications were most frequently reported. Superficial and deep wound infections were observed in 27 (9.6%) and 18 (6.4%) patients, respectively. Multivariate regression analysis demonstrated increased age to be an independent predictive variable for the occurrence of postoperative complications (odds ratio 1.04; 95% confidence interval 1.00-1.09), while cast immobilization for more than 2 weeks was a protective factor for the development of wound related complications (odds ratio 0.34; 95% confidence interval 0.17-0.66). In conclusion, the incidence of postoperative complications among geriatric patients after surgical treatment of ankle fractures is high and patients should be informed accordingly.     

Bed occupancy rates and hospital-acquired infections—should beds be kept empty?

There is growing evidence that bed occupancy (BO) rates, overcrowding and understaffing influence the spread of hospital-acquired infections (HAIs). In this article, a systematic review of the literature is presented, summarizing the evidence on the adverse effects of high BO rates and overcrowding in hospitals on the incidence of HAIs. A Pubmed database search identified 179 references, of which 44 were considered to be potentially relevant for full-text review. The majority (62.9%) focused on methicillin-resistant Staphylococcus aureus-associated infection or colonization. Only 12 studies were found that provided a statistical analysis of the impact of BO on HAI rates. The median BO rate of the analysed studies was 81.2%. The majority of studies (75%) indicated that BO rates and understaffing directly influence the incidence of HAIs. Only three studies showed no significant association between BO rates and the incidence of HAIs. Interestingly, only one of the included studies detected a seasonal trend in the BO rate. The present review shows an association between BO rates and the spread of HAIs in various settings. Because the evidence on this topic is limited, we conclude that further research is needed in order to analyse the rationale of a threshold BO rate, because keeping beds empty is comparatively costly.     

Neue β‑Laktam-Antibiotika und β‑Laktamase-Inhibitoren gegen multiresistente Gram-negative Erreger

Background

The worldwide spread of multidrug-resistant Gram-negative bacteria (MDR-GN) continues. Treatment options for infections caused by MDR-GN remain scarce and only few new substances are currently in clinical phase II/III studies or have already been granted market approval.

Objectives

To provide an overview about current data on new β?lactam antibiotics and β?lactamase inhibitor combinations, respectively. New macrolides, ketolides and aminoglycosides are not addressed.

Materials and methods

Selective literature research regarding published data on ceftazidim/avibactam, ceftolozan/tazobactam, imipenem/cilastatin?+?relebactam, meropenem/vaborbactam, aztreonam/avibactam and cefiderocol, as well as registered trials.

Results

The development of new antimicrobials for the treatment of MDR-GN infections offers new options for attending physicians. β?Lactamase producers are inhibited by these new substances, though with varying efficacy; however, there are still no adequate treatment options for metallo-β-lactamase (MBL) producers.

Conclusions

Clinical data are still indifferent and come from heterogeneous patient collectives. Direct comparisons with established treatment strategies, such as the “last-resort use” of polymyxins are hardly possible. Cases of early development of resistance have already been described. Finally, the importance of toxicity and optimal dosing—in organ failure or organ replacement procedures such as dialysis—remain unclear.