Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party.

The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed. The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations. The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II. Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations. The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements. Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing. Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers. Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data. The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved. This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains. Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use.

Safety and performance of the second generation EnligHTN™ Renal Denervation System in patients with drug-resistant, uncontrolled hypertension.

BACKGROUND AND AIMS: Catheter-based renal denervation for the treatment of drug-resistant hypertension has been intensively investigated in recent years. To date, only limited data have been published using multi-electrode radiofrequency ablation systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and performance of the second generation EnligHTN™ Renal Denervation System. METHODS: This first-in-human, prospective, multi-center, non-randomized study included 39 patients (62% male, mean age 63 years, and mean baseline office blood pressure 174/93 mmHg) with drug-resistant hypertension. The primary safety and performance objectives were to characterize, from baseline to 6 months post procedure, the rate of serious procedural and device related adverse events, as adjudicated by an independent Clinical Events Committee, and the reduction of office systolic blood pressure. RESULTS: Renal artery denervation, using the second generation EnligHTN multi-electrode system significantly reduced office blood pressure from baseline to 1, 3, 6, 12, 18 and 24 months by 19/7, 26/9, 25/7, 23/7, 25/8 and 27/9 mmHg, respectively (p ≤ 0.0005). No serious device or procedure related adverse events affecting the renal arteries or renal function occurred through 24 months of follow-up. CONCLUSIONS: Renal sympathetic denervation using the second generation EnligHTN Renal Denervation System resulted in safe, rapid, and significant mean office blood pressure reduction that was sustained through 24 months. Future studies will need to address the utility of this system against an appropriate sham based comparator.

Rates of stent thrombosis in bare-metal versus drug-eluting stents (from a large Australian multicenter registry).

Recent reports suggest that drug-eluting stents (DESs) may increase the risk of stent thrombosis (ST) relative to bare-metal stents (BMSs). Therefore, the aim of this study was to compare DES and BMS outcomes with a specific focus on ST. We analyzed 30-day and 1-year outcomes of 2,919 patients who underwent percutaneous coronary intervention with stent implantation from the Melbourne Interventional Group registry. Academic Research Consortium definitions of ST were used: (1) definite ST (confirmed using angiography in patients with an acute coronary syndrome), (2) probable ST (unexplained death <30 days or target-vessel myocardial infarction without angiographic confirmation), and (3) possible ST (unexplained death >30 days). Multivariate analysis was performed to identify predictors of ST. The incidence of ST (early or late) was similar between BMSs and DESs (1.6% vs 1.4%; p=0.66), and DES use was not predictive of ST. Independent predictors of ST included the absence of clopidogrel therapy at 30 days (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.29 to 5.29, p<0.01), renal failure (OR 3.30, 95% CI 1.43 to 7.59, p<0.01), index procedure presentation with an acute coronary syndrome (OR 2.59, 95% CI 1.14 to 5.87, p=0.02), diabetes mellitus (OR 2.25, 95% CI 1.19 to 4.23, p=0.01), and total stent length >or=20 mm (OR 1.85, 95% CI 1.00 to 3.42, p=0.04). In conclusion, DESs were not associated with increased risk of ST compared with BMSs at 12 months in this large Australian registry that selectively used DESs for patients at high risk of restenosis.

A rare complication of left ventricular rupture--right ventricular intramyocardial dissection with left-to-right shunting.

Left ventricular (LV) rupture is an uncommon catastrophic complication post myocardial infarction. We describe 2 rare cases of LV rupture complicating inferior ST Elevation Myocardial Infarction (STEMI) causing right ventricular (RV) intramyocardial dissection with left-to-right shunting.

Drug-eluting stent-induced left anterior descending coronary artery aneurysm: repair by pericardial patch--where are we headed?

Deployment of drug-eluting stents has been associated with late thrombosis and restenosis on withdrawal of antiplatelet agents. We report a complication of inflammation and localized coronary artery aneurysms immediately adjacent to the stent after 4 years of implantation. Late chronic inflammatory responses may evolve for up to 4 years after sirolimus-eluting stent implantation and can cause weakening, erosion, and aneurysms of the coronary arteries.

The clinical outcome of restricting drug-eluting stents to patients at highest risk of restenosis.

AIMS: To assess the clinical outcomes of patients where drug eluting stents (DES) were restricted to those at highest risks of restenosis, we compared three different strategies for stent implantation: bare metal stents (BMS) only, DES only and a group where DES use was restricted (RES). METHOD AND RESULTS: Initial comparison was made between BMS only (279 patients, 316 lesions) and DES only (272 patients, 302 lesions). The endpoints of death, non-fatal myocardial infarction and target lesion revascularisation (TLR) [MACE] were assessed at 12 months. The incidence of MACE in the BMS only and DES only groups were 14% and 7% (p=0.002) and TLR was 8% and 1% (p<0.0001). Comparison was then made between these results and a third group where DES was restricted to patients at highest risk of restenosis. The restricted group (RES) comprised 249 patients (271 lesions) of which 53% received DES. RES remained significantly better than BMS, MACE (14% vs. 8%, p=0.02) and TLR (8% vs. 3%, p=0.02). When RES was compared with DES only, there was no significant difference in MACE (8% vs. 7% p=0.42), but there was a significantly lower TLR rate in the DES only group (1% vs. 3% p=0.04). CONCLUSIONS: The overall incidence of events in patients where DES use was restricted to 53% of patients remains low and this may be an acceptable treatment strategy to reduce costs.

What has happened to antimicrobial usage in primary care in the United Kingdom since the SMAC report? - description of trends in antimicrobial usage using the General Practice Research Database.

BACKGROUND: The aim of the study was to assess antibiotic prescribing within the United Kingdom for three of the Standing Medical Advisory Committee recommendations 'four things which could be done'. METHODS: We conducted a retrospective survey of morbidity and antibiotic prescribing data between 1993 and 2001 using the national General Practice Research Database. Antibiotic prescribing was linked to diagnoses of cough/cold and sore throat; length of antibiotic course for uncomplicated cystitis. RESULTS: The rate of antibiotic prescribing for cough/cold declined between 1993 (43.7 per 1000 patient years at risk) and 1999 (23.5 per 1000 patient years at risk) and has since increased slightly (to 30.5 per 1000 patient years at risk in 2001). Antibiotic prescribing for sore throat declined between 1995 (80.6 per 1000 patient years at risk) and 1999 and has since remained static (42.1 per 1000 patient years at risk in 2001). Trimethoprim was the most commonly used antibiotic for episodes of uncomplicated cystitis and the prescription of 3 day (or less) courses has increased from 16.4 per cent in 1998 to 41.5 per cent in 2001. CONCLUSIONS: For the SMAC recommendation to limit prescribing for uncomplicated cystitis to 3 days in otherwise fit women there has been demonstrable impact since the publication of the SMAC report. For two recommendations (no prescribing of antibiotics for simple coughs and colds; no prescribing of antibiotics for viral sore throats) the impact has been less clear against the background of a general reduction in antimicrobial prescribing.

Automated high-throughput mycobacterial interspersed repetitive unit typing of Mycobacterium tuberculosis strains by a combination of PCR and nondenaturing high-performance liquid chromatography.

Mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing of Mycobacterium tuberculosis complex isolates is portable, 100% reproducible, and highly discriminatory. Nondenaturing high-performance liquid chromatography (non-dHPLC) with use of a WAVE microbial analysis system is a promising method of PCR amplicon analysis as it is low cost and requires no preanalysis processing. The aims of this study were to validate the application of WAVE microbial analysis system technology to MIRU-VNTR typing. A collection of 70 strains were cultivated in liquid culture and extracted using the QIAamp DNA minikit. Novel primers were designed to target the 12 MIRU-VNTR loci (P. Supply et al., J. Clin. Microbiol. 39:3563-3571, 2001). After amplification, each PCR product was analyzed on a WAVE microbial analysis system. The fragment size was calculated from the chromatogram, and the number of tandem repeats at each locus was determined. For the collection of 70 strains 100% concordance was achieved when comparing MIRU-VNTR profiles obtained from agarose gel electrophoresis and PCRs analyzed on a WAVE microbial analysis system. The calculated fragment sizes, obtained from the WAVE microbial analysis system, were sufficiently accurate to ensure 100% confidence when assigning the number of tandem repeats to a MIRU-VNTR locus. This study is the first to report the successful use of non-dHPLC for screening for variations in the number of MIRU-VNTRs in mycobacterial DNA. Non-dHPLC analysis was demonstrated to be a rapid, low-labor input method for the detection and analysis of MIRU-VNTR amplicons. The combination with non-dHPLC further enhances the utility of MIRU-VNTR typing.