Microorganisms do not distinguish between religion, ideology, background or color of skin - they simply use our body as a support to grow on or in, sometimes causing disease or even killing us on the occasion. In addition to our natural, biological defenses (for which our immune system is responsible) we, the people, can defend ourselves against this invisible threat in order to form a more perfect world. And our weapon? Antibiotics.There are currently two basic and pressing questions: "Do people have full access to the available information about antibiotics?" and "Do antibiotics work properly?" Twice the answer is "No" and in consequence the next question arises "Are there any improvements or even solutions ahead?"  Scientists are making an effort to answer this with a "Yes" and here I present my contribution to this important field.

Answers and Perspectives
Which information about antibiotics is limited?
Current Situation
The properties of every licensed antibiotic are described in detail in a patient information leaflet that is provided together with the drug. In addition, physicians and pharmacists have access to more detailed information in specialized press releases. For these professionals, antibiotic activity spectra that list the panel of microorganisms against which the drugs are likely to work are summarized in books or are available in the internet, for example the Johns Hopkins ABx guide. However, these publications can only be searched for a limited number of antibiotics, e.g., the ABx guide lists only those antibiotics that are licensed in the United States. Finding general information about drugs is relatively easy; however, information on the effectiveness of different drugs against a specific pathogenic species is difficult. It is therefore time-consuming to get a complete overview of the available data, which conflicts with the pressure to treat a patient as soon as possible.

Antibiotics are prescribed according to local experiences, general guidelines and professional recommendations, e.g., as provided by the European Society of Clinical Microbiology and Infectious Diseases.

However, due to microbial resistances, which vary by location, the recommended antibiotics might fail to work. In such cases, the optimal treatment can be determined in microbiological laboratories through examination of patient samples (blood, urine, sputum etc.) from which the causative microorganism is isolated. By means of extensive testing against a panel of antibiotics (called an antibiogram) the most effective drugs can be identified. In rare occasions (with a disturbing tendency of becoming more common), a suitable antibiotic cannot be identified due to extreme multiple resistance. Some infectious organisms exist that are no longer treatable with antibiotics.

Because information about many, mostly older drugs or drugs available elsewhere in the world is scattered over the literature, fast decisions based on a broad spectrum of information are hampered.
Thoughts

In February this year, I had a thought-provoking talk with an orthopedic surgeon. He told me that, before he would inform an infected patient that unfortunately the infection cannot be cured with drugs, he wanted to be sure to be optimally informed about all available details of possible anti-infective drugs. He complained how difficult it was to reach that required level of information.The physician was right: no directory existed at that time that summarized in detail and extensively the antimicrobial properties of licensed drugs. His comment related to my previous work, which was exactly to produce a collection of the data he was so eagerly seeking. It has always been hard for me to believe statements saying that there is a strong need for new drugs. How do they know, as long as the activities of existing drugs have never been systematically summarized? In the year 2003 I decided to collect relevant data on this topic. 

AmicBase Drugs- the unlimited data schedule
At that time I had already produced a computer database about antimicrobial active plant constituents that can be found in plant extracts and essential oils. This data collection was supplemented with preservatives, cosmetic chemicals, fatty acids for comparison purposes and - very important - animal toxicity data of the respective compounds. These data are essential to select compounds that are both highly toxic towards microorganisms and at the same time safe to use in animals. The work was becoming more and more interesting as the database grew, since never before such data had been collected at this scale. The name of the database was "AmicBase-EssOil" and it could address a most interesting question: "Are plant-derived compounds superior to antibiotic drugs?" Because I had not systematically added drug data at that time I went back to the literature and introduced a classification of antibiotic drugs and others. 
AmicBase Marketing

The data collections were for sale through my company "ReviewScience", which attracted customers from both universities and companies, even very big ones. A change of law, in 2003, restricted advertising by email in Germany, which meant that I could no longer market my database. There also existed an online version of AmicBase. I was convinced that many people were interested in some of the data, even though they would not necessarily want to purchase the entire database on CD-ROM.Given the situation back then, I was pleased to negotiate with an international publisher of scientific literature, who offered to sell and market my product. The agreement was that they would both sell the database as a CD-ROM and provide it online. After some delay, in 2005 the CD-ROM became available under the name AmicBase 2005 for a price of $8,600 per copy. However, the publisher didn't do all they had promised, so that sales soon dried up, and an online version was never made available. I decided to continue my efforts without the publisher, and to make the database available free-of-charge via the internet.

Why do antibiotics not work properly?
Biochemical resistance
Microorganisms naturally defend themselves against toxic compounds, and will do the same when they encounter an antibiotic (whether a natural antibiotic, or a chemically produced compound that doesn't exist in nature) because it is toxic to them. They can inactivate the threat by various means. Sometimes they change the target to which the antibiotic is supposed to bind, which renders the drug useless. Or they block its uptake or increase its excretion, so that the drug never reaches critical concentrations inside their cells. Lastly, they may be able to chemically modify the drug so that the human weapon becomes inactive. Ever since microorganisms were exposed to antibiotics they concurrently adapted new strategies to combat novel challenges (provided by new pharmaceutical developments) and evolved mechanisms to survive. The consequence can sometimes be fatal for infected patients. There now exist multiple resistant Staphylococcus aureus, Vancomycin-resistant Enterococcus, or highly-resistant E. coli bacteria that can cause life-threatening infections, especially in vulnerable patients such as neonates, the elderly, or immune-suppressed individuals. There are many reports in the press about dangerous strains lurking in hospitals, which infect patients who entered the hospital to get better, only to get worse. Observations of newly discovered antimicrobial resistances do not produce sensational reports in the scientific literature; it has become routine.

Physical resistance
Apart from biochemical resistance, there is another explanation why antibiotics do not always clear an infection. As everybody knows, our body mainly consists of fat and water. Compounds are either soluble in water or in fat - hardly ever in both. Antibiotics are usually water soluble or, if needed, are made water soluble by salt formation. Many microorganisms reside in watery parts of the body, where they can be successfully treated by antibiotics. However, some microbial species, e.g. tuberculosis-causing Mycobacteria, hide themselves in fatty tissue; Staphylococcus aureus is able to reside in bone marrow tissue, which contains a lot of fatty material, too. The past strategy - the invention of new antibiotics with stronger activity in order to kill microorganisms even at very small doses - turned out to be unrewarding.

Water-soluble drugs are unable to penetrate lipid tissue and as a consequence fail to eliminate infections that reside in fatty tissue. Small, lipid soluble, tissue penetrating antibiotics, which would fulfill the preconditions for a successful fight of fatty tissue hiding microorganisms, have never been licensed as antibiotic drugs. One attempt was made to apply for drug admission for a compound of this type in the 1980s in Germany. Despite all requirements having been fulfilled by the applicant, final approval had not happened for unknown reasons. The name of the compound is (-)-alpha-bisabolol and it occurs naturally in the flower essential of chamomile. The subject will be revisited further on.
Patents can make things worse
The argument used persistently by the pharmaceutical industry is that at first novel antibiotic leading structures have to be discovered, which can then be optimized to eventually produce new antibiotics with better activity. But development of novel chemical structures is not always necessary.  Over 20 different types of antibiotics have been discovered since the 1970s that each possess a complete different basic chemical structure, and have a stronger activity than vancomycin, the last reserve antibiotic against many resistant infections, including Staphylococcus aureus. Nevertheless, none of these promising candidates is being developed or marketed as antibiotics. The reason is money. Patent laws reserve the commercial use of an invention to the inventor for 30 years, after which anybody can market it. For this reason, nobody cares for old patented drugs because they have lost their commercial protection, and the costs of development and marketing would outweigh the sales profits, since any competitor can compete with the same product. The result is that nobody markets them. The human resource pool is unnecessarily regarded as empty, ignoring all those worthy drug candidates - with possibly fatal consequences for the all the persons concerned.
Improvements and recommendations 
We need antibiotics of a new type
Lipid-soluble compounds with antibiotic activity that can penetrate deep tissue should be developed in order to deal with fat-containing body compartments. The effectiveness of such drugs has been demonstrated. For instance, in 18 observational reports (-)-alpha-bisabolol from chamomile was successfully used among others to treat bacterial infections such as a deep femur infection caused by resistant Staphylococci. The compound was administered as bath additive and, after being taken up through the skin, had successfully entered the bloodstream. In addition to antibiotic activity, this compound has excellent antifungal, anti-inflammatory and wound healing activity. The antifungal properties and suggested mechanism of action and the low toxicity of (-)-alpha-bisabolol from chamomile essential flower oil point to an outstanding status. The compound was redrawn from drug approval, but is allowed to be used in cosmetic due to its safety, which produces a somewhat curious situation. 

In general, plants offer a great number and variability of compounds of this type. Especially so-called sesqui- and diterpenes are an interesting group of pharmacologically active compounds, however, financed research on these often easily available and cheap compounds is rare. The entire AmicBase contains microbiological test results, toxicological data plus calculations of so-called "Therapeutic indices", which allows a selection of safe antimicrobials on the basis of literature data. It may serve in future for creation of new solutions, but at present time the communication of properties of available drugs has priority.

Communication of existing knowledge - Drug data for free in the internet
The decision to publish the drug data of AmicBase free-of-charge in the internet was strongly influenced by the need of such data by physicians, who can use them beneficially to save human lives. Storing the data at home without making them available for public is unreasonable and contrary to the aim of my work. Fortunately, the database technique has developed and allows publishing of databases without much IT knowledge today. In addition, all rights on AmicBase have been returned to me by the former publisher. Thus, inhibitory data of globally licensed drugs plus their trade names (70,000 data records, 30 database fields per record) are now accessible for free and can be reached in the internet at www.reviewscience.com . AmicBase Drugs-Online was chosen as the name for this part of AmicBase. Advantages offered by AmicBase Drugs-Online

AmicBase Drugs-Online can be used for controlling antibiograms. Specific recommendations can be expressed by physicians, which becomes important in case of multi-resistant microbial strains. There may possibly be older drugs that work, but are not typically tested for. Their existence is included in the database, which increases the array of potential active drugs available.
The database helps to find drugs for treatment of infections caused by rare pathogenic microorganisms, where often recommendations on the first and second choice of antibiotics are absent.In cases where the supply of antibiotics is limited, one can identify which antibiotic has the best chances, based on the data collected from the literature. This is of importance in countries with a low medical budget.

The database offers a positive list of drug activities, which is useful in protocols stating the activity of drugs having been used for treatments. This offers legal security for pharmacists and physicians especially in the United States, where treatments have to be documented.
Responses to AmicBase Drugs-Online publishing
Since its date of publication (7th July, 2011), I received many responses to AmicBase Drugs-Online that illustrated the interest for this drug data collection. The National Center for Biotechnology Information (NCBI), which is a division of the National Institutes for Health (NIH, USA), permitted linking to their resources. PubChem and Taxonomy Browser, both maintained by NCBI, interlinked to AmicBase Drugs-Online as referrer database. In PubChem Announcements AmicBase appeared as top message. The department for external communication of the European Centre for Disease Prevention and Control (ECDC) informed: We have forwarded the links to our experts in the ECDC programme on antimicrobial resistance and healthcare-associated infections. The manager of public outreach of the American Microbiological Society (ASM) wrote: Personally I think your database is great.  He will place a report on AmicBase in MicrobeWorld - the ASM news platform. The director of Communicable Disease Control Department, Ministry of Health of Cambodia wrote: We wish to thank you for your communication on this very important subject. Also the deputy head of the Division of EU Affairs and International Relations of the Ministry of Health of the Republic of Lithuania commented: We will share it with our colleagues. The director of Molecular Microbiology and Genomics Consultants in Germany wrote: This is a great site - I'm impressed. Also the deputy director of Central Drug Research Institute (India) commented: It will be very useful to both doctors and researchers in the field. From the Central Tuberculosis institute of the Russian Academy for Medical Science in Moscow (Russia) I received the message: It will be definitely useful for everyone working with infection.The comments and actions of officials encourage in continuing with AmicBase Drugs-Online. 
Written by Dr. Alexander Pauli, reviewed and edited by Dr. Trudy Wassenaar (www.bacteriamuseum.org), 24.8.2011

Written by Dr. Alexander Pauli, reviewed and edited by Dr. Trudy Wassenaar (www.bacteriamuseum.org), 24.8.2011