Outbreak of vancomycin-resistant Enterococcus spp. in an Italian general intensive care unit

Following the identification of two clinical isolates of vancomycin-resistant enterococci (VRE) from intensive care unit (ICU) patients, a surveillance programme detected that six of eight ICU patients were colonised by VRE. Standard epidemic control measures were instituted in the ICU. During a 16-month period, 13 (2.5%) of 509 ICU patients had VRE-positive swabs upon admission, and 43 (8.7%) of 496 VRE-negative patients were colonised by VRE in the ICU. Patients who acquired VRE in the ICU had a longer ICU stay (p < 0.0001). No other statistically significant differences were demonstrated. Two patients had documented infection (infection/colonisation index, 3.6%; overall VRE infection frequency, 0.4%), but both recovered and were discharged. VRE colonisation did not increase the mortality rate. Automated ribotyping identified three clusters containing, respectively, the first 52 Enterococcus faecium isolates, two Enterococcus faecalis isolates, and two further isolates of E. faecium. Multilocus sequence typing demonstrated that two E. faecium isolates representative of the two ribotypes belonged to sequence types 78 and 18, and that these two isolates belonged to the epidemic lineage C1, which includes isolates with a wide circulation in northern Italy. The outbreak was controlled by continuous implementation of the infection control programme, and by the opening of a new unit with an improved structural design and hand-washing facilities.     

Acute biliary pancreatitis. Therapeutic trends

BACKGROUND: Treatment of biliary pancreatitis includes suppression of the biliary cause by cholecystectomy and common bile duct clearance. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy for eradication of biliary stones and laparoscopic cholecystectomy (L.C.) for residual gallbladder stones would be ideal but were once considered to be contraindicated by most surgeons. The timing of definitive biliary tract surgery and the role of ERCP have been the focus of discussion in recent years. METHODS: During a two-year study period 51 patients with acute biliary pancreatitis were studied. Seven patients (14%) underwent emergency laparotomy, necrosectomy, cholecystectomy, exploration of the common bile duct and T-tube insertion, because unstable clinical conditions, with evidence of pancreatic and peripancreatic necrosis on CT-scan. Elective open cholecystectomy and CBD exploration were performed in 7 patients after the resolution of acute pancreatitis during the same hospital admission. RESULTS: Early ERCP and L.C. were associated with favourable outcomes. 33 patients underwent ERCP preoperatively: 17 within 72 hours of admission and 16 after signs of clinical improvement. Laparoscopic cholecystectomy performed 3-25 days after admission was successful in 27 of 29 patients. Postsphincterectomy bleeding occurred in one patient and was treated successfully by endoscopic epinephrine injection. For median hospital stay and recurrence there were statistical differences between early and delayed ERCP. CONCLUSIONS: ERCP and sphincterectomy have a certain role in conjunction with laparoscopic cholecystectomy in the management of patients with acute biliary pancreatitis, particularly in institutions where there is easy access to expert interventional endoscopic techniques. This policy should reduce the risk of cholangitis and recurrent pancreatitis.     

Preclinical efficacy evaluations of XK-469: dose schedule,route and cross-resistance behavior in tumor bearing mice

XK-469 is advancing to Phase I clinicaltrials. Preclinical studies were carriedout to assist in clinical applications.Dose-schedule route testing: Singledose IV treatment with XK-469 producedlethality (LD20 to LD 100) above 142 mg/kg.Optimum treatment required total dosages of350 to 600 mg/kg. Furthermore, highindividual IV dosages (100 to 142 mg/kg)were poorly tolerated, producingsubstantial weight loss (8 to 18% of bodyweight), poor appearance, and slow recovery(8 to 12 days). A 1-hour infusion ofdosages more than 140 mg/kg, or BIDinjections 6 hrs apart, did not reducelethality. However, lower individualdosages of 40 to 50 mg/kg/injection IV werewell tolerated and could be given daily toreach an optimum total dose with minimaltoxicities. Likewise, 75 mg/kg/injection IVcould be used every other day to reachoptimal treatment. The necropsy profiles ofdeaths from toxic dosages were essentiallyidentical regardless of schedule (deaths 4to 7 days post treatment). The profileswere: paralytic ileus or gastroparesis; GIepithelial damage; and marrow toxicity.Interestingly, the key lethal events wererapidly reversible and simple to overcomewith lower dosages given daily or everyother day. Based on these results, the highdose, Q21day schedule should be avoided inclinical applications. Instead, a splitdose regimen is recommended (e.g., daily,every other day, or twice weekly). XK-469was also well tolerated by the oral route,requiring 35% higher dosages PO to reachthe same efficacy and toxicity as producedIV. Cross-resistance studies: XK-469resistance was produced by optimumtreatments of IV implanted L1210 leukemiaover seven passage generations. Thisleukemia subline (L1210/XK469) had reducedsensitivity to VP-16 (with a 4.0 log killin IV implanted L1210/XK469 compared to an8.0 log kill against IV implanted L1210/0). It also had a reduction in the sensitivityto 5-FU (with a 2.0 log kill in theimplanted L1210/XK469 compared to a 4.0 logkill against IV implanted L1210/0). Otheragents were approximately as active againstthe resistant tumor, including: Ara-C,Gemzar, Cytoxan, BCNU, DTIC, and CisDDPT. No case of collateral sensitivity wasobserved; i.e., no agent was markedly moreactive against the resistant sublineL1210/XK-469 than against the parent tumorin mice.     

Actions of Androctonus australis and Leiurus quinquestriatus venoms in the rat isolated atria and anesthetized rats; effect of magnesium and lidocaine

In rat isolated atria, Androctonus australis (Aa), Leiurus quinquestriatus quinquestriatus (Lqq), and L. q. hebraceus (Lqh) venoms produced intense contracture, alterations in the force and frequency of the spontaneous atrial contractions, and delayed afterdepolarizations (DAD). It was shown by means of tetrodotoxin-induced blockade of neurotransmitter release that the contracture and DAD were produced by the action of the venoms on the atrial cell membrane (direct action) while alterations in the force and frequency of the spontaneous atrial contractions were caused by acetylcholine and norepinephrine released by the venoms (indirect action). The irregularities in the spontaneous contractions and DAD were suppressed by magnesium and lidocaine which, however, caused only a small reduction in the intensity of the atrial contracture. The venom-induced DAD was also abolished by ryanodine and intensified by an increase in [Ca2+]0. In anesthetized rats, Aa, Lqq, and Lqh venoms induced hypertension, arrhythmias, and T wave inversion. The arrhythmias included bradycardia, ventricular and supraventricular extrasystoles, unsustained and sustained ventricular tachycardia with torsade de pointes episodes. Magnesium and lidocaine abolished them, and magnesium also counteracted the hypertension. These results suggest that magnesium and lidocaine, particularly magnesium, may be useful in the treatment of the arrhythmias, hypertension, and other disorders associated with Buthinae scorpion envenomation.     

Early detection of secondary caries using quantitative,light-induced fluorescence

The authors hypothesize that the arrestment and remineralization of these lesions could be improved if secondary caries could be detected and monitored at earlier stages. Traditional diagnostic techniques detect secondary caries when it is relatively advanced and when significant tissue has been lost. This in vitro study evaluated the Quantitative Light-induced Fluorescence (QLF) system for detecting and monitoring demineralization surrounding tooth-colored restorations. This investigation was divided into three studies. The first study evaluated QLF for the detection and measurement of chemically induced lesions surrounding resin composite restorations. The second study evaluated QLF for the detection of demineralization around different tooth-colored restorations (glass ionomer, resin composite, compomer and smart material) created in a microbial caries model. Finally, the third study tested whether QLF was effective at detecting early wall lesions adjacent to resin composite restorations. Data from Study 1 demonstrated the potential for QLF to detect very early secondary caries and to distinguish between the different stages of early demineralization. Study 2 confirmed the potential for QLF to detect early secondary caries created by cariogenic bacteria and concluded that the four types of materials differed in their ability to prevent secondary caries in this model, with the glass ionomer being the most effective and the non-fluoride releasing composite performing the worst, which allowed for the development of larger lesions. The results of Study 3 suggest a potential application of the QLF system to detect early wall lesions. Data from this investigation strongly suggest that QLF is a potentially viable technology to detect and monitor early secondary caries.