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This article has Open Peer Review reports available.

How does Open Peer Review work?

BMC Infectious Diseases 2012 12 :153

https://doi.org/10.1186/1471-2334-12-153

© Thønnings and Østergaard; licensee BioMed Central Ltd.2012

Received: 30December2011

Accepted: 9July2012

Published: 9July2012

Open Peer Review reports

Abstract

Background

Optimal antibiotic treatment strategies of infections are still needed. Therefore, 30-day case fatality rate (CFR) of Haemophilus bacteremia and efficacy of various antibiotic treatment regimes were studied.

Methods

All episodes of Haemophilus bacteremia in the former Copenhagen County during the period 2000-9 were included in the study. Clinical and biochemical findings and outcome were collected retrospectively from medical records.

Results

105 consecutive episodes were identified (median age: 69 years, with only 4 children <16 years), 72% were due to non-typeable -, 16% to typeable , and 11% to other species. Pneumonia was the most common primary focus (in 48%), and 58% of the patients had Charlson comorbidity index > 1. Definitive antibiotic therapy was in 26 cases benzylpenicillin, in 12 cases aminopenicillins, in 50 cases cefuroxime and in 16 cases broadspectrum antibiotics, whereas 1 palliative case died without start of therapy. Whereas the use of broadspectrum antibiotics was related to the severity of the disease (admittance to ICU, need for assisted ventilation or hemodialysis, septic shock), no significant difference in clinical features was demonstrated for therapy with benzylpenicillin, aminopenicillin or cefuroxime, except benzylpenicillin was rarely administered to immunosuppressed patients. The CFR was 22% (23/105). The choice of empiric antibiotic therapy was not significantly associated with mortality (adequate vs. inadequate treatment: 23% (21/93) vs. 17% (2/12), respectively,  0.05). In contrast, definite antibiotic therapy with cefuroxime or aminopenicillins resulted in a significantly lower CFR than treatment with benzylpenicillin (12% (6/50) or 0% (0/12) vs. 39% (10/26), respectively, Log rank test  0.02). When adjustments were made for other identified risk factors in bivariate logistic regression analysis, treatment with cefuroxime was still were found to be associated with a significantly lower CFR than for benzylpenicillin: OR: 0.21 (0.06-0.69),  0.01 (hospital-acquired bacteremia), OR: 0.27 (0.08-0.91),  = 0.04 (polymicrobial episodes), OR: 0.16 (0.04-0.59),  0.006 (admittance at intensive care unit), OR: 0.22 (0.06-0.82),  0.02 (alcohol abuse), OR: 0.15 (0.04-0.60),  0.008 (altered mental state), OR: 0.22 (0.07-0.71),  0.01 (temperature < 38 °C), OR: 0.23 (0.07-0.79),  0.02 (septic shock), OR: 0.21 (0.06-0.69),  0.01 (mechanical ventilation).

Conclusion

Our results suggest that, after susceptibility testing, cefuroxime or aminopenicillins are preferable to benzylpenicillins as definitive therapy for bacteremia.

bacteremia still carries a high mortality, and clinical features such as gender, age, acquisition of the bacteremic episode, and the focus of infection have recently been demonstrated to be associated with an increased risk of a fatal outcome [ 1 ]. 3rd generation cephalosporins have been the recommended therapy for childhood meningitis due to type B, because of a more rapid sterilization of the cerebrospinal fluid than in therapy with aminopenicillins [ 2 ] or cefuroxime, and a better outcome of the disease with 3rd generation cephalosporins compared to cefuroxime [ 3 ]. Less is known, however, about the influence of various antibiotic treatment regimes on the outcome of other infections including bacteremia. In Denmark therapy with benzylpenicillin has been recommended for treatment of ampicillin-susceptible infections and has been considered to be as effective as other recommended treatment regimes (e.g. aminopenicillins and cefuroxime). These recommendations provided in some local Danish guidelines were to our knowledge primarily based on results obtained from time-kill experiments showing benzylpenicillin to be as active as amoxicillin against various species [ 4 ], whereas clinical studies comparing benzylpenicillin to other recommended treatment regimes for therapy of bacteremia still are lacking In addition, the European Committee on Antimicrobial Susceptibility Testing (EUCAST: http://www.eucast.org ) has stated that there still are insufficient data for H. to set clinical breakpoints for benzylpenicillin [ 5 ]. Thus, optimal antibiotic treatment strategies for infections due to species are still needed.

This retrospective study aims to investigate the efficacy of benzylpenicillin therapy in comparison with cefuroxime/aminopenicillins treatment in 105 consecutive episodes of bacteremia due to in the former Copenhagen County during the time period 2000–2009.

108 episodes of Haemophilus bacteremia were identified from 1 January 2000 to 31 December 2009. Three bacteremic episodes caused by H. haemolyticus , H. parainfluenzae and H. influenzae were considered contaminations, because the patients had no clinical evidence of bacteremia, and they survived without receiving any antibiotic therapy. Two patients had two episodes of Haemophilus bacteremia with different primary infection foci two and five years apart, respectively. These patients were included with both episodes. Thus the study compromised 105 episodes of Haemophilus bacteremia in 103 patients.

In LPS biosynthesis pathway, lpxA, lpxC, KdsA, KdsB and gmhA were considered as valid targets for drug development. Enzymes lpxA and lpxC (catalyzes committed step) contribute to the formation of lipid A which is a conserved core oligosaccharide region of LPS molecules. Lipid A is responsible for toxic effects of gram-negative bacterial infection. The target protein KdsB (CMP-Kdo synthetase) is unique in its direct coupling of KDO (sugar) to cytosine monophosphate (CMP) in KDO biosynthesis which is a part of LPS inner core. Another druggable protein obtained in this pathway is gmhA (lpcA) that catalyzes the first step in biosynthesis of ADP-L-glycero-D-manno heptose [ 48 ]. Inhibiting gmhA would create heptose less core LPS leading to enhanced sensitivity of F. nucleatum to even low concentration of novobiocin, detergents and bile salts [ 49 ].

Prediction of subcellular localization of druggable targets using various online servers delineated that 29 out of 35 target proteins were located in cytoplasm while the rest were in membrane (Additional file 2 : Table S7). Cytoplasmic proteins can be considered for small molecule drug development while membrane or secreted proteins for vaccine development.

Fig. 2

Biological network of host-pathogen protein-protein interactions are shown using Cytoscape. and host interacting proteins are represented in pink and blue color respectively

If a set of proteins are significantly enriched in certain biological processes or pathways, they are likely to play similar role in vivo [ 50 ]. Hence, pathway, functional, disease enrichment analysis and functional annotation clustering were carried out to assess predicted HP-PPIs using Database for Annotation, Visualization and Integrated Discovery (DAVID) [ 51 ]. This analysis resulted in significantly enriched 45 pathways, 306 gene ontology (GO) terms and 21 diseases with minimum count of three gene set and p-value lower than 0.05 in addition to 47 annotation clusters with cut-off enrichment score of > 1 and minimum of three terms.

This analysis was performed based on the assessment that host proteins involved in HPIs possess functional correlation to the pathways that are relevant to pathogen’s infection. Among the obtained pathways from DAVID Functional Annotation Chart analysis, Wnt signaling pathway, ECM-receptor interactions, focal adhesion, toll-like receptor (TLR) signaling and CRC probably suggest the role of F. nucleatum in adhesion, invasion into epithelial cells and triggering of signal transduction pathways that promote CRC [ 1 , 11 , The Grind Standard Continental Wallet in Light Slate Cow Leather Marc Jacobs 2018 New For Sale ZxhbDMVk
, 52 ]. Other attained pathways such as T-cell, B-cell receptor signaling, T-cell, B-cell activation, antigen processing and presentation, Lck and Fyn tyrosine kinases in initiation of TCR activation, viral myocarditis indicate the relevance of F. nucleatum infection to host immune responses [ 11 , Cupro Skirt Complex Soul by VIDA VIDA Free Shipping Manchester 100% Authentic For Sale RWKY0Hyg
, 54 , 55 ]. F. nucleatum infection inhibits T-cell activation by preventing cells to exit G0/G1 phase of cell cycle which may result in local and/or systemic immunosuppression [ 53 ]. Chronic inflammation in periodontal diseases due to F. nucleatum has been reported as potential risk factor for Alzheimer’s disease [ 56 ]. Most of the obtained pathways were in accordance to literature reports while the rest of them could be either false positive or may have an indirect effect which seeks further experimental support. This include renal cell, basal cell, small cell lung, non-small cell lung, endometrial, thyroid, pancreatic, acute myeloid leukemia, glioma, leukocyte transendothelial migration and melanoma.

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Jennifer Smith doesn’t like the term “accident.” It implies too much chance and too little culpability.

A “crash” killed her mother in 2008, she insists, when her car was broadsided by another vehicle while on her way to pick up cat food. The other driver, a 20-year-old college student, ran a red light while talking on his mobile phone, a distraction that he immediately admitted and cited as the catalyst of the fatal event.

“He was remorseful,” Smith, now 43, said. “He never changed his story.”

Yetin federal records, the death isn’t attributed to distraction or mobile-phone use. It’s just another line item on the grim annual toll taken by the National Highway Transportation Safety Administration [NHTSA]—one of 37,262 that year. Three months later, Smith quit her job as a realtor and formed Stopdistractions.org, a nonprofit lobbying and support group. Her intent was to make the tragic loss of her mother an anomaly.

To that end, she has been wildly unsuccessful. Nine years later, the problem of death-by-distraction has gotten much worse.

Here is a terrific article which covers gyro stabilization and IMU technology in drones.

Drone Motor Direction And Propeller Design

The motors and propellers are the drone technology which get the UAV into the air and to fly in any direction or hover. On a quadcopter, the motors and propellers work in pairs with 2 motors / propellers rotating clockwise (CW Propellers) and 2 motors rotating Counter Clockwise (CCW Propellers).

They receive data from the flight controller and the electronic speed controllers (ESC) on the drone motor direction to either hover or fly.

Onscreen Real-Time Flight Parameters

Keep track of current flight telemetry and see what your drone sees on your mobile device.

No Fly Zone Drone Technology

In order to increase flight safety and prevent accidental flights in restricted areas, the latest drones from DJI and other manufacturers include a “No Fly Zone” feature.

These no fly zones have been divided into two categories: A and B. Manufacturers can update and change this no fly zone drone technology using firmware updates.

GPS Ready To Fly Mode Drone Technology

When the compass s is calibrated, the drone then seeks the location of GPS satellites. When more than 6 are found, it allows the drone to fly in “Ready To Fly” Mode.

Internal Compass Failsafe Function

Allows the UAV and remote control system to know exactly its flight location. Calibration of the Compass is required to set a home point. The home point is the location where the drone will return to in case of loss of signal between the drone and the remote control system. This is also know as “fail-safe function”.

FPV Live Video Transmission Drone Technology

FPV means “ First Person View ” and it is where a video camera is mounted on the unmanned aerial vehicle and broadcasts the live video to the pilot on the ground. The pilot is flying the aircraft as if they were on-board the aircraft instead of looking at the aircraft from the pilot’s actual ground position.

FPV allows the unmanned aircraft to fly much higher and further than you can from looking at the aircraft from the ground. First Person View allows for more precise flying especially around obstacles.

It also allows for unmanned aerial vehicles to fly very easily indoors, through forests and around buildings where it would not be possible to fly from a fixed position on the ground looking up at the drone in the distance.

The exceptionally fast growth and development of the drone racing league would not be possible without FPV live video transmission technology.

This FPV technology uses radio signal to transmit and receive the live video.

The drone has a multi-band wireless FPV transmitter built in along with an antennae. Depending on the drone, the receiver of the live video signals can be either the remote control unit, a computer, tablet or smartphone device.

last updated 06/26/2018