Lege Artis Medicinae

[TIGECYCLINE, A NEW ANTIBIOTIC]

SZALKA András

JANUARY 20, 2007

Lege Artis Medicinae - 2007;17(01)

[Glycylcyclines are a new class of antimicrobial agents, of which tigecycline is the first to have reached the final stage of clinical trials. It is the 9-t-butylglycylamido derivative of minocycline. The addition of a side-chain into position 9 overcomes the problem of the development of resistance typical to tetracyclines. Tigecycline inhibits translation of bacterial proteins through its effect on the 30S ribosomal subunit. The efficacy of tigecycline is impressive against multiresistant Gram-positive bacteria, including methicillin- resistant Staphylococcus aureus, penicillin- resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci, against most genera of Enterobacteriaceae, including extended- spectrum β-lactamase-producing strains, and against most strains of Bacteroides fragilis, as well as atypical pathogens. Clinical studies showed good results in parenteral treatment for complicated skin, soft tissue and intraabdominal infections. Tigecycline will be most useful as empirical monotherapy in infections with suspected polymicrobial etiology and/or multidrugresistant agents.]

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[In vitro sensitivity of human anaerobic pathogenic bacteria for tigecycline and comparative antibiotics in Hungary - Prospective multicentre trial]

NAGY Erzsébet, URBÁN Edit, JAKAB Gabriella, SZIKRA Lenke, MISZTI Cecília, SZABÓ Judit

[INTRODUCTION - Tigecycline, the first member of the glycylcycline family of antibiotics, is a semisynthetic derivative of minocycline. The modified tetracycline nucleus is protected against the resistance mechanisms that inactivate tetracyclines, thus tigecycline is expected to be effective against tetracycline- resistant strains. The aim of this multicenter survey, performed in 2007 and 2008 by three Hungarian laboratories, was to examine the efficiency of this drug against antianaerobic bacteria in vitro. MATERIALS AND METHODS - The participating laboratories isolated 540 strains of Gram-positive and Gram-negative anaerobic bacteria from various infectious sites. These sites represent the classes of infections for which tigecycline was recently approved as a treatment option (skin and soft tissue and intra-abdominalinfections), or for which it will be licensed in the near future (lower respiratory tract infections). Evaluation of antibiotic susceptibility was performed by Etest, and the efficiencies of six antibiotics were determined using MIC values. RESULTS - The 540 strains belonged to 33 different species. Of the 104 strains of Gram-positive anaerobic cocci, 100% proved to be susceptible to tigecycline. Similarly, 98% of the examined Clostridium strains showed susceptibility to this antibiotic. Two of the 56 Prevotella strains were resistant against tigecycline. MIC50 and MIC90 values in the 280 Bacteroides strains were 0.5 μg/ml and 1 μg/ml, respectively, whereas only 1.8% of the tested strains showed low resistance. CONCLUSION - Similarly to the findings of international surveys, our results show that tigecycline is effective against the great majority (97.4% susceptibility) of relevant anaerobic bacteria that are isolated from skin and soft tissue, intra-abdominal and lower respiratory tract infections. Thus, empiric use of tigecycline is recommended in any infections where anaerobic bacteria alone or a mixed flora of aerobic and anaerobic bacteria are likely to be present.]

Clinical Neuroscience

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Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Lege Artis Medicinae

[A short chronicle of three decades ]

KAPRONCZAY Katalin

[Hungarian professional periodicals started quite late in European context. Their publish­ing, editing and editorial philosophy were equally influenced by specific historical and political situations. Certain breaking points of history resulted in termina­tion of professional journals (War of In­de­pendence 1848-1849, First and Se­cond World Wars), however there were pe­riods, which instigated the progress of sciences and founding of new scientific journals. Both trends were apparent in years after the fall of former Hungarian regime in 1990. The structure of book and journal publishing has changed substantially, some publishers fell “victim” others started successfully as well. The latters include the then-established publishing house Literatura Medica and its own scientific journal, Lege Artis Me­di­cinae (according to its subtitle: New Hun­garian Medical Herald) issued first in 1990. Its appearance enhanced significantly the medical press market. Its scientific publications compete with articles of the well-established domestic medical journals however its philosophy set brand-new trends on the market. Concerning the medical community, it takes on its problems and provides a forum for them. These problems are emerging questions in health care, economy and prevention, in close interrelation with system of public health institutions, infrastructure and situation of those providing individual health services. In all of them, Lege Artis Medicinae follows consequently the ideas of traditional social medicine.]

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[What has Go to do with making clinical decisions? One of the greatest intellectual challenges of bedside medicine is making decisions under uncertainty. Besides the psychological traps of traditionally intuitive and heuristic medical decision making, lack of information, scarce resources and characteristics of doctor-patient relationship contribute equally to this uncertainty. Formal, mathematical model based analysis of decisions used widely in developing clinical guidelines and in health technology assessment provides a good tool in theoretical terms to avoid pitfalls of intuitive decision making. Nevertheless it can be hardly used in individual situations and most physicians dislike it as well. This method, however, has its own limitations, especially while tailoring individual decisions, under inclusion of potential lack of input data used for calculations, or its large imprecision, and the low capability of the current mathematical models to represent the full complexity and variability of processes in complex systems. Nevertheless, clinical decision support systems can be helpful in the individual decision making of physicians if they are well integrated in the health information systems, and do not break down the physicians’ autonomy of making decisions. Classical decision support systems are knowledge based and rely on system of rules and problem specific algorithms. They are utilized widely from health administration to image processing. The current information revolution created the so-called artificial intelligence by machine learning methods, i.e. machines can learn indeed. This new generation of artificial intelligence is not based on particular system of rules but on neuronal networks teaching themselves by huge databases and general learning algorithms. This type of artificial intelligence outperforms humans already in certain fields like chess, Go, or aerial combat. Its development is full of challenges and threats, while it presents a technological breakthrough, which cannot be stopped and will transform our world. Its development and application has already started also in the healthcare. Health professionals must participate in this development to steer it into the right direction. Lee Sedol, 18-times Go world champion retired three years after his historical defeat from AlphaGo artificial intelligence, be­cause “Even if I become the No. 1, there is an entity that cannot be defeated”. It is our great luck that we do not need to compete or defeat it, we must ensure instead that it would be safe and trustworthy, and in collaboration with humans this entity would make healthcare more effective and efficient. ]