Antibiogram and plasmid profiling of carbapenemase and extended spectrum Beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae in Abeokuta,South western,Nigeria

Background

The increased reports of ESBL dissemination from various centres in south western, Nigeria and the recent emergence of carbapenem resistant bacteria prompted the conception of this study.

Objectives

To demonstrate the relationship between high molecular weight plasmids and the expression of antibiotic multi-resistance including ESBL and carbapenemase.

Methods

We investigated 97 isolates of selected organisms consisting of 67 E. coli and 30 Klebseilla spp for the presence of plasmids expressing ESBL including carbapenem-hydrolysing enzymes. Beta-lactamase was determined using acidometric method, while ESBL and carbapenemase activity was determined using the double-disk diffusion test as well as the Modified Hodge test (MHT). Plasmid profiles of ESBL and carbapenemase positive isolates were determined according to standard protocols.

Results

An ESBL prevalence rate of 21.6% and carbapenem- resistance rate of 9.3% was recorded. Antibiotic susceptibility profile of ESBL isolates showed 100.0% resistance against Amoxicillin, Cotrimoxazole and Erythromycin. Moderate susceptibility was recorded against the Quinolone class of antibiotics; Meropenem remained the most active antibiotic against ESBL isolates with 62.5% against E. coli and 60% against K. pneumoniae. The plasmid profiles of our study isolates ranged from 11.8kbp to 35.5kbp.

Conclusion

Due to the relationship between high molecular weight plasmids and multi-drug resistance, we hereby recommend regular molecular surveillance of this form in our study setting.     

《英国非酒精性脂肪性肝炎肝移植指南》导读

非酒精性脂肪性肝炎（non—alcoholicsteatohepatitis,NASH）现已成为肝移植愈来愈重要的基础肝病。鉴于晚期NASH患者常并存多种影响肝移植转归的临床问题,而至今尚无针对NASH患者进行肝移植的评估和治疗指南,为此英国移植学会（British Transplant Society,BTS）邀请相关专家制定了指南,以指导肝移植前后NASH患者的处理。     

Extensive Cytoreductive Surgery for Appendiceal Carcinomatosis: Morbidity, Mortality, and Survival

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) are frequently used to treat appendiceal carcinomatosis. Some patients require multivisceral resection because of the volume of disease. It is unclear whether extent of CRS impacts survival in appendiceal carcinomatosis.

Methods

We analyzed 282 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis. Patients were defined as having undergone Extensive CRS (n = 60) if they had >3 organ resections or >2 anastomoses; a subgroup of Extreme CRS patients (n = 10) had ≥5 organ resections and ≥3 anastomoses. Kaplan–Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting outcomes.

Results

Relative to the comparison group, patients undergoing Extensive CRS had a higher median peritoneal carcinomatosis index, operative duration, blood loss, and length of stay. No difference in completeness of cytoreduction, severe morbidity, or 60-day mortality was evident. Subgroup analysis of 10 patients undergoing extreme CRS likewise revealed no increase in severe morbidity or mortality. Median progression-free (PFS) and overall survival (OS) were 23.5 and 74 months in the comparison group; 18.5 (p = 0.086) and 51 (p = 0.85) months in the Extensive CRS group; and 40 months and not reached in the Extreme CRS subgroup. In a multivariable analysis, extent of CRS was not independently associated with PFS or OS.

Conclusions

Extensive CRS is associated with greater OR time, blood loss, and length of stay, but is not associated with higher morbidity, mortality, or inferior oncologic outcomes in patients with appendiceal carcinomatosis.     

Effect of Intrathecal Baclofen Concentration on Spasticity Control: Case Series

Background/Objective: Intrathecal baclofen (ITB) has been shown to be an effective treatment for severe spasticity of spinal or cerebral origin. Although most patients respond well to an ITB trial, there are often difficulties in achieving and/or maintaining such effectiveness with ITB pump treatment. There are few published guidelines for dosing efficacy and no studies looking at the effect of concentration of ITB on spasticity management.

Methods: Case series of 3 adults with severe spasticity treated with ITB pump: a 44-year-old man with C7 tetraplegia using a 40-mL Medtronic SynchroMed II pump with 500-μg/mL concentration; a 35-year-old woman with traumatic brain injury with right spastic hemiplegia using a 18-mL Medtronic SynchroMed EL pump with 2,000-μg/mL concentration; and a 43-year-old woman with spastic diplegic cerebral palsy using a 40-mL Medtronic SynchroMed II pump with 2,000-μg/mL concentration.

Results: After reducing ITB concentrations in the pump, either as part of a standard protocol for dye study to assess the integrity of pump and catheter system or secondary to plateau in therapeutic efficacy, patients experienced temporary, significant reduction in spasticity based on range of motion, Modified Ashworth scores, and verbal feedback.

Conclusions: Decreasing the concentration of ITB seems to affect spasticity control. Further research in this area is needed for those patients with refractory spasticity to optimize efficacy of ITB therapy.     

Interferon Gamma and Contact‐dependent Cytotoxicity Are Each Rate Limiting for Natural Killer Cell–Mediated Antibody‐dependent Chronic Rejection

Natural killer (NK) cells are key components of the innate immune system. In murine cardiac transplant models, donor‐specific antibodies (DSA), in concert with NK cells, are sufficient to inflict chronic allograft vasculopathy independently of T and B cells. In this study, we aimed to determine the effector mechanism(s) required by NK cells to trigger chronic allograft vasculopathy during antibody‐mediated rejection. Specifically, we tested the relative contribution of the proinflammatory cytokine interferon gamma (IFN‐γ) versus the contact‐dependent cytotoxic mediators of perforin and the CD95/CD95L (Fas/Fas ligand [FasL]) pathway for triggering these lesions. C3H/HeJ cardiac allografts were transplanted into immune‐deficient C57BL/6 rag^?/?γc^?/? recipients, who also received monoclonal anti–major histocompatibility complex (MHC) class I DSA. The combination of DSA and wild‐type NK cell transfer triggered aggressive chronic allograft vasculopathy. However, transfer of IFN‐γ–deficient NK cells or host IFN‐γ neutralization led to amelioration of these lesions. Use of either perforin‐deficient NK cells or CD95 (Fas)–deficient donors alone did not alter development of vasculopathy, but simultaneous disruption of NK cell–derived perforin and allograft Fas expression resulted in prevention of these abnormalities. Therefore, both NK cell IFN‐γ production and contact‐dependent cytotoxic activity are rate‐limiting effector pathways that contribute to this form of antibody‐induced chronic allograft vasculopathy.     

Nonlinear (amplified) relationship between nuclear occupancy by triiodothyronine and the appearance rate of hepatic alpha-glycerophosphate dehydrogenase and malic enzyme in the rat.

Three separate approaches were applied to examine the general relationship between R, the rate of induction of specific enzymes (mitochondrial alpha-glycero-phosphate dehydrogenase and cytosolic malic enzyme) and q, the fractional nuclear occupancy by triiodothyronine in male Sprague-Dawley rats. Daily 200-microgram injections of triiodothyronine per 10u g body wt for 7 days resulted in saturation of the hepatic nuclear sites and the achievement of an apparent new steady state of enzyme levels. The increase achieved over base-line hypothyroid levels was then compared with the increment over hypothyroid base line characteristic of intact euthyroid animals with 47% of nuclear sites occupied. The maximal theoretical reate of steady-state enzyme induction could be protected on the basis of the observed maximal increase in enzyme activity observed 1 day after the injection of graded doses of hormone and lambda, the known fractional rate of enzyme dissipation. The 24-h dose-response studies were used to generate R as a continuous function of q, both in hypothyroid as well as in euthyroid animals. This approach involved the numerical solution of an ordinary differential equation describing the rate of change of enzyme as a function of R, which was assumed to be uniquely related to q. Results of these analyses indicated that the ratio of the maximal rate of induction of enzyme at full occupancy to the rate of induction under euthyroid conditions assumes a value between 9.0 and 19.5, depending on the precise analytic and experimental approach applied. This value is far in excess of the theoretical ratio 2.13 which on would anticipate if R were linearly related to q and 47% of the nuclear sites occupied under physiological conditions. Thus, the signal for enzyme induction appears to undergo progressjive amplification with increasing nuclear occupancy. Moreover, the curve describing the relationship between R and q appears highly nonlinear throughout (concave upwards). Although the molecular mechanism responsible for amplification is unknown, recognition of this phenomenon may be helpful in understanding tissue effects of thyroid hormone excess. Moreover, the analytic technique for determining R as a function of q may be of general applicability in studying hormonal response systems under nonsteady-state conditions.