Infusion-Related Reaction Following Daptomycin Two-Minute Rapid Intravenous Administration

Background:

Erythroderma, or red man’s syndrome, is a common infusion-related reaction following vancomycin administration. Erythroderma following daptomycin rapid infusion has not been documented.

Objective:

To report a case of erythroderma following daptomycin 2-minute intravenous (IV) injection.

Case Report:

A review of published literature suggests that this is the first published case of a flushing (nonallergic) reaction resulting from a 2-minute IV injection of daptomycin that is not present with standard IV infusion. A 69-year-old woman following right knee reconstructive surgery presented with right knee joint swelling, purulent discharge, and fever. Subsequently, she was diagnosed with a presumed postsurgical infection and was initiated on vancomycin therapy. Following removal of the infected hardware, the patient was discharged and continued outpatient vancomycin therapy. The patient’s renal function began to decline and therapy was discontinued. Daptomycin 6 mg/kg every 48 hours was initiated via 2-minute IV push. On the initial dose, approximately 2 hours post IV infusion, the patient began to notice redness and a warm sensation on her face, neck, and upper part of the chest. Diphenhydramine 25 mg provided limited immediate relief, but all symptoms subsided within 3 to 4 hours. The patient received her next dose 48 hours later over a 40-minute IV infusion with no adverse effects. Subsequent infusions continued at the same dose over 30 minutes for 4 weeks with no further adverse effects.

Conclusion:

A 2-minute intravenous injection of daptomycin in this patient yielded a reaction that was not present on rechallenge with standard, extended infusion.Key Words: daptomycin, erythroderma, rapid infusion, red man’s syndrome, Staphylococcus aureusDaptomycin is a bactericidal lipopeptide antibiotic commonly used for drug-resistant gram-positive pathogens.¹ Daptomycin was originally approved by the US Food and Drug Administration (FDA) in September 2003 as a once-daily 30-minute intravenous (IV) infusion. In November 2010, the FDA approved a 2-minute rapid IV injection based on data from 2 consecutive pharmacokinetic and safety evaluation studies.^2,3 Daptomycin pharmacokinetic parameters were comparable with the 2-minute IV administration group when compared to the 30-minute IV infusion at a dose of 6 mg/kg.⁴ Although rapid infusions offer convenience and potential cost-savings opportunities, there is potential increased risk of infusion-related adverse events. Infusion-related events may include local reactions, such as phlebitis, pain, tenderness, or local erythema, and systemic reactions manifesting as either dermatologic and cardiovascular complications or anaphylaxis. These reactions have been documented with several antimicrobial infusions including ciprofloxacin, amphotericin B, vancomycin, and others agents that stimulate histamine release.⁵ Vancomycin has been classically associated with infusion-related erythroderma or red man’s syndrome. Signs and symptoms of a reaction will often initiate within 1 hour from the start of the infusion.^5,6 For this reason, the preferred infusion rate for vancomycin is no more than 10 mg/min.⁷ In reports to date, local infusion site–related reactions following 2-minute rapid infusion of daptomycin were mild and of short duration, with no systemic flushing reported in the peerreviewed literature. We report a case of an infusion-related reaction with significant flushing secondary to daptomycin following 2-minute IV push that was absent on rechallenge with an extended infusion.     

Determination of Non-Recrystallization Temperature for Niobium Microalloyed Steel

In the present investigation, the non-recrystallization temperature (T_NR) of niobium-microalloyed steel is determined to plan rolling schedules for obtaining the desired properties of steel. The value of T_NR is based on both alloying elements and deformation parameters. In the literature, T_NR equations have been developed and utilized. However, each equation has certain limitations which constrain its applicability. This study was completed using laboratory-grade low-carbon Nb-microalloyed steels designed to meet the API X-70 specification. Nb- microalloyed steel is processed by the melting and casting process, and the composition is found by optical emission spectroscopy (OES). Multiple-hit deformation tests were carried out on a Gleeble^® 3500 system in the standard pocket-jaw configuration to determine T_NR. Cuboidal specimens (10 (L) × 20 (W) × 20 (T) mm³) were taken for compression test (multiple-hit deformation tests) in gleeble. Microstructure evolutions were carried out by using OM (optical microscopy) and SEM (scanning electron microscopy). The value of T_NR determined for 0.1 wt.% niobium bearing microalloyed steel is ~ 951 °C. Nb- microalloyed steel rolled at T_NR produce partially recrystallized grain with ferrite nucleation. Hence, to verify the TNR value, a rolling process is applied with the finishing rolling temperature near TNR (~951 °C). The microstructure is also revealed in the pancake shape, which confirms T_NR.     

Failure Mechanism of Hybrid Steel Beams with Trapezoidal Corrugated-Web Non-Welded Inclined Folds

Literature of Steel Beams with a thin-walled trapezoidal Corrugated Web (SBCWs) shows that the capacity of SBCWs is affected by both the fatigue cracks initiated along the inclined folds (IFs) and the maximal additional stress located in the middle of the IFs. An experimental investigation on the behaviour of hybrid SBCWs under flexure is presented in this paper. This study focuses on the effect of the welding IF between the web and flanges (IFs welded or non-welded), the horizontal-fold length (200, 260, and 350 mm), and transversal flange stiffeners on the failure mechanism of the SBCW under three line load. Accordingly, six hybrid specimens were fabricated, instrumented, and tested (five SBCW specimens and one specimen with a flat web). The test setup was designed to generate shear and a moment in the testing zone via three-point bending. The results indicated that non-welded IFs specimens with or without flange stiffeners failed owing to web tearing after web and flange local buckling. The failure mode of the specimen with continuous welding between the web and flanges was local flange buckling. Finally, the paper presents a comparison between the experimental results and the European Code to predict the capacity of the flange towards local buckling. It was concluded that the non-welding the IFs affected the inelastic behaviour and the capacity of the SBCWs. In addition, the bending resistance equations presented by EN 1993-1-5 can safely predict the test results of the non-welded inclined fold and yield a high safe variation.     

The sponge/Matrigel angiogenesis assay

It has become increasingly clear that definitive tests for angiogenesis require in vivo assays. Recently, the Matrigel plug assay has become the method of choice for many studies involving in vivo testing for angiogenesis. In this assay, test angiogenesis-inducing compounds such as bFGF or tumor cells are introduced into cold liquid Matrigel which, after subcutaneous injection, solidifies and permits penetration by host cells and the formation of new blood vessels. Assessment of angiogenesis in the Matrigel plug is achieved either by measuring hemoglobin or by scoring selected regions of histological sections for vascular density. We now describe a modification of the Matrigel plug assay which permits a more precise visualization of the angiogenic reaction, provides directional information, requires no histological analysis, and lends itself to photographic documentation and image analysis protocols. We illustrate the assay by describing dose- and time-dependent responses to tumors of murine and human origin, to angiogenesis-inducing factors such as bFGF (FGF-2) and VEGF and to anti-angiogenic agents such as endostatin. The method has been used as well to demonstrate blood vessel recruitment by embryonic chick aortic arch rudiments. Additionally it has been able to detect strain-dependent differences in susceptibility to angiogenic stimulation.     

Predictors of poor outcome of decompressive craniectomy in pediatric patients with severe traumatic brain injury: a retrospective single center study from Pakistan

Objective

This study aimed to determine the risk factors associated with poor outcome of decompressive craniectomy (DC) for severe traumatic brain injury (TBI) in pediatric patients.

Methods

This retrospective study is conducted on pediatric population (age 1–15 years) presenting with TBI who underwent DC at our institute between January 2000 and 2010. Based on Glasgow outcome score (GOS) at a minimum follow-up of 5 months, patients were divided into two groups, namely poor outcome (GOS 1, 2, and 3) and good outcome (GOS 4 and 5). Records were reviewed and analyzed for preoperative and intraoperative predictors.

Results

We found 25 patients who were eligible as per selection criteria. Mean age at presentation was 6?±?4 years and there was male preponderance (84 %). Fall (60 %) was the most common mechanism of injury followed by gunshots and road traffic accident. On univariate analysis, presenting GCS ≤5 (p value?=?0.009), delay in presentation of more than 150 min (p value?=?0.010), DC performed after more than 4 h of arrival in hospital (p value?=?0.042), and intraoperative blood loss exceeding 300 ml (p value?=?0.001) were significant predictors of poor outcome.

Conclusion

Our study suggests that DC in children is not only a life-saving procedure, but also leads to a good functional outcome after severe injury. However, patient selection still remains an important aspect, and the above-mentioned factors should be considered while deciding for DC to improve survival. Further prospective studies on larger sample size are warranted to validate our results.     

Inferiorly based thigh flap for reconstruction of defects around the knee joint

Background:

Soft-tissue defects around the knees are common in injured limbs and in the same injury the leg is often involved and the thigh is spared. Furthermore due to pliable and relatively lax skin, we have used inferiorly based thigh flap to reconstruct defects around knee joint.

Aims and Objectives:

The aim of this study is to evaluate the use of inferiorly based thigh flap to cover soft-tissue defects over the proximal one-third of the leg, patellar region, knee, and lower thigh.

Materials and Methods:

This study was conducted during the period between October 2011 and February 2013. Inferiorly based anteromedial thigh fasciocutaneous flap was performed on 12 patients and inferiorly based anterolateral thigh fasciocutaneous flap on four patients. The sites of the soft-tissue defects included patellar regions, infrapatellar region, upper one-third of leg, lower thigh, and over the knee joint.

Results:

Patients were evaluated post-operatively in terms of viability of flap, the matching of the flap with the recipient site, and donor site morbidity. All the flaps survived well except one which developed distal marginal flap loss, one in which wound dehiscence was noticed, and two in which mild venous congestion was observed. Venous congestion in two patients subsided on its own within 3 days. One patient with wound dehiscence achieved complete healing by secondary intention. Patient who developed distal flap loss required debridement and skin grafting. No appreciable donor site morbidity was encountered. Skin colour and texture of the flap matched well with the recipient site.

Conclusions:

The inferiorly based thigh flap is a reliable flap to cover the defect over proximal one-third of the leg, patellar region, knee, and lower thigh.KEY WORDS: Defect around the knee joint, inferiorly based thigh flap, perforator based flap     

Distally based posterior tibial artery perforator flap for coverage of defects around the ankle,heel and lower third of leg

Introduction

Reconstruction of distal leg region remained a difficult task. Free flaps had long been considered as a gold standard for these regions. However, due to various limitations of the free flap, a local fasciocutaneous flap could be considered as a good alternative. In this study, the use of a distally based posterior tibial artery perforator flap had been evaluated in the coverage of defects around the ankle, heel, and lower third of a leg. The study also outlined the donor-site morbidity and the technical details of the surgical procedure.

Methods

In this prospective study, a total of 42 patients with distal lower leg defects were included. The defects were located on the lower third of the leg (n?=?23), ankle (n?=?11), and heel (n?=?8). Reconstruction was performed using distally pedicled posterior tibial artery perforator flaps. Patients were evaluated in terms of viability of the flap, functional gain, and donor-site morbidity. The technical details of the operative procedure have also been outlined.

Results

All the flaps survived well, with the exception of one patient, who experienced complete flap loss. Minor complications were, however, noted in four other patients: One patient developed superficial epidermolysis; one developed postoperative venous congestion, which subsided within 3 days by conservative means, and in two patients, partial loss of the skin graft occurred at the donor site but healed completely with dressing and antibiotics. The patients were followed up for an average period of 6 months, ranging from 1 to 13 months. Donor-site morbidity was minimal.

Conclusions

It was concluded that the distally based pedicled posterior tibial artery perforator flap was a reliable, easy, less time-consuming, and versatile procedure for covering the defects around the ankle, heel, and lower third a leg. Level of Evidence: Level IV, therapeutic study