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What Is MIC?

 

The MIC is the lowest concentration of antimicrobial agent which inhibits the growth of the microorganism.

A current definition of the Minimum Inhibitory Concentration, MIC, is "the lowest concentration which resulted in maintenance or reduction of inoculum viability".

Antibiotic resistance is the ability of a microorganism to withstand the effects of an antibiotic. Antibiotic resistance develops through mutation or plasmid exchange between bacteria of the same species. If a bacterium carries several resistance genes, it is called multiresistant or, informally, a superbug.

Antibiotic resistance is a consequence of evolution via natural selection. The antibiotic action is an environmental pressure; those bacteria which have a mutation allowing them to survive will live on to reproduce. They will then pass this trait to their offspring, which will be a fully resistant generation.

Several studies have demonstrated that patterns of antibiotic usage greatly affect the number of resistant organisms which develop. Overuse of broad-spectrum antibiotics, such as second and third generation cephalosporins, greatly hastens the development of methicillin resistance, even in organisms that have never been exposed to the selective pressure of methicillin per se. Other factors contributing towards resistance include incorrect diagnosis, unnecessary prescriptions, improper use of antibiotics by patients, and the use of antibiotics as livestock food additives for growth promotion.

The determination of the MIC involves a semi-quantitative test procedure which gives an approximation to the least concentration of an antimicrobial needed to prevent microbial growth. In the recent past, the method used tubes of growth broth containing a test level of preservative, into which an inoculum of microbes was added. The end result of the test was the minimum concentration of antimicrobial which gave a clear solution, i.e., no visual growth.

Currently, the tubes have been replaced by a semi-automated microtitre method. Where the turbidity of the test compound interferes with the test, indicators can be used for the determination of the end-point.

A broad-spectrum antibiotic is so called due to its activity against a wide range of infectious agents. A good example is amoxicillin.

Broad-spectrum antibiotics are used in roughly two medical situations:

Where the infectious agent will not become known in the course of the disease, e.g. in a child moderately ill with bronchitis. In this case no cultures are being taken. When the patient is ill enough to warrant antibiotic treatment, even though culture results are not yet known. This occurs, for example, in meningitis, where the patient is so ill that he/she would die within hours if broad-spectrum antibiotics are not initiated. Generally, the spectrum is "narrowed down" when the causative agent of an infection becomes known, and the broad-spectrum agent is replaced by a narrower-spectrum antibiotic. This is supposed to limit the development of antibiotic resistance, although evidence for this practice is unclear.

The minimum inhibitory concentration is the minimum concentration of the antibacterial agent in a given culture medium below which bacterial growth is not inhibited.

The cephalosporins, are a class of ß-lactam antibiotics. Together with cephamycins they belong to a sub-group called cephems.

Cephalosporin was first isolated from cultures of Cephalosporium acremonium from a sewer in Sardinia in 1948 by an italian scientist Giuseppe Brotzu. He noticed that these cultures produced a substance that was effective against salmonella typhi, the cause of typhoid. In 1960s, Eli Lilly launched the first cephalosporins on the market.

Cephalosporins work the same way as penicillins, they interfere with the peptidoglycan synthesis of the bacterial wall by inhibiting the final transpeptidation needed for the cross-links. This effect is bactericidal.

Staphylococcus aureus (colloquially known as "Staph aureus") is one of the major resistant pathogens. Found on the mucous membranes and the skin of around a third of the population, it is extremely adaptable to antibiotic pressure. It was the first bacterium in which penicillin resistance was found -- in 1947, just four years after the drug started being mass-produced. Methicillin was then the antibiotic of choice. MRSA (methicillin-resistant Staphylococcus aureus) was first detected in Britain in 1961 and is now "quite common" in hospitals. MRSA was responsible for 37% of fatal cases of blood poisoning in the UK in 1999, up from 4% in 1991. Half of all S. aureus infections in the US are resistant to penicillin, methicillin, tetracycline and erythromycin.

This left vancomycin as the only effective agent available at the time. A new class of antibiotics, oxazolidinones, became available in the 1990s, and the first commercially available oxazolidinone, linezolid, is comparable to vancomycin in effectiveness against MRSA. However, VRSA (Vancomycin-resistant Staphylococcus aureus) was first identified in Japan in 1997 and has since been found in hospitals in England, France and the US.

For an antimicrobial agent to be effective, it must reach the site of infection in sufficient concentration and duration to inhibit pathogen growth. Since the introduction of the short-half-life antibiotic aqueous penicillin G 60 years ago, the traditional approach to predicting in vivo efficacy of antimicrobial agents has been to compare the peak antimicrobial serum concentration with the minimum concentration of the antibiotic that inhibits growth of the pathogen. This minimum inhibitory concentration (MIC) usually is measured in a test tube or on an agar plate.

VRSA is also termed GISA (glycopeptide intermediate Staphylococcus aureus) or VISA (vancomycin intermediate Staphylococcus aureus), indicating resistance to all glycopeptide antibiotics.

Enterococcus faecium is another superbug found in hospitals: penicillin resistance was seen in 1983, vancomycin resistance (VRE) in 1987 and linezolid resistance (LRE) in the late 1990s.

The sensitivity of bacterial strains to antibacterial agents is generally defined by the minimum inhibitory concentration (MIC) of a particular agent in vitro. Against the species under investigation. This method is unsuitable, however. for species which develop intracellularly such as mycobacteria.

Penicillin-resistant pneumonia (or pneumococcus, caused by Streptococcus pneumoniae) was first detected in 1967, as was penicillin-resistant gonorrhea. Resistance to penicillin substitutes is also known beyond S. aureus. By 1993 Escherichia coli was resistant to five fluoroquinolone variants. Mycobacterium tuberculosis is commonly resistant to isoniazid and rifampin and sometimes universally resistant to the common treatments. Other pathogens showing some resistance include Salmonella, Campylobacter, and Streptococci.

The MIC of the infecting pathogen and the drug's half-life have been used to determine an antibiotic's dose and interval. If the offending pathogen's MIC was below a predetermined breakpoint, based on the peak serum level for that antibiotic, the organism was considered susceptible and therapy would be initiated. The MIC still provides a good prediction of the potency of an antibiotic against a given pathogen, but it does not provide any information on the time course of the activity or the activity at the site of infection.

Staphylococcus aureus (also known as golden staph) is a bacterium, frequently living on the skin or in the nose of a healthy person, that can cause illnesses ranging from minor skin infections (such as pimples, boils, and cellulitis) and abscesses, to life-threatening diseases such as pneumonia, meningitis, endocarditis and septicemia.

Each year some 500,000 patients in American hospitals contract a staphylococcal infection. By changing its chemical makeup slightly to evade attack, S. aureus has become resistant to many commonly used antibiotics (see discussion about MRSA). In 1997, physicians were alarmed to encounter staph strains that resist even vancomycin, which used to work when all else failed. Problems with S. aureus in hospitals are not a recent occurance, as penicillin resistant forms have existed since the 1950's.

Staphylococcus aureus appears as a gram-positive coccus, in grape-like clusters when viewed through a microscope. More characteristic is its appearance when grown out on agar plates. It appears as large, round golden-yellow (which is where the name aureus comes from) colonies, with beta-haemolysis of blood agar.

Staph infections can be spread through contact with pus from an infected wound, skin to skin contact with an infected person, and contact with objects such as towels, sheets, clothing, or athletic equipment used by an infected person.

In the hospital laboratory, Staphylococcus aureus is differentiated from most other staphylococci by the coagulase test. Staphylococcus aureus is coagulase-positive.

Please note that Golden Staph is known as a 'Superbug' due to its high immunity and resistance against standard antibiotic treaments.

When a bacteria population can be exposed to an antibiotic in-vitro in the same way as it is in vivo, the in-vitro experiments quantify the efficacy of the antibiotic. When the antibiotic has strong side effects, one has to optimize between those effects and the risk of losing control over the bacteria population. In such critical cases an in-vitro model with only one parameter, the Minimum Inhibitory Concentration, may not be able to describe the development of an in-vitro bacteria population accurately enough.

Antibiotics can also be classified by the organisms against which they are effective, and by the type of infection in which they are useful, which depends on the sensitivities of the organisms that most commonly cause the infection and the concentration of antibiotic obtainable in the affected tissue.

Side effects. Side effects range from slight headache to a major allergic reaction. One of the more common side effects is diarrhea, which results from the antibiotic disrupting the balance of intestinal flora, the "good bacteria" that dwell inside the human digestive system. Other side effects can result from interaction between the antibiotic and other drugs, such as elevated risk of tendon damage from administration of a quinolone antibiotic with a systemic corticosteroid.

Antibiotic misuse. Common forms of antibiotic misuse include taking an inappropriate antibiotic, in particular the use of antibacterials for viral infections like the common cold, and failure to take the entire prescribed course of the antibiotic, usually because the patient feels better before the infecting organism is completely eradicated. In addition to treatment failure, these practices can result in antibiotic resistance. In the United States, a vast quantity of antibiotics is routinely included as low doses in the diet of healthy farm animals, as this practice has been proved to make animals grow faster. Opponents of this practice, however, point out the likelihood that it also leads to antibiotic resistance, frequently in bacteria that are known to also infect humans, although there has been little or no evidence as yet of such transfer of antibiotic resistance actually occurring.

Antibiotic resistance. One side effect of misusing antibiotics is the development of antibiotic resistance by the infecting organisms, similar to the development of pesticide resistance in insects. Evolutionary theory of genetic selection requires that as close as possible to 100% of the infecting organisms be killed off to avoid selection of resistance; if a small subset of the population survives the treatment and is allowed to multiply, the average susceptibility of this new population to the compound will be much less than that of the original population, since they have descended from those few organisms which survived the original treatment. This survival often results from an inheritable resistance to the compound, which was infrequent in the original population but is now much more frequent in the descendants thus selected entirely from those originally infrequent resistant organisms.

Antibiotic resistance has become a serious problem in both the developed and underdeveloped nations. By 1984 half the people with active tuberculosis in the United States had a strain that resisted at least one antibiotic. In certain settings, such as hospitals and some child-care locations, the rate of antibiotic resistance is so high that the normal, low cost antibiotics are virtually useless for treatment of frequently seen infections. This leads to more frequent use of newer and more expensive compounds, which in turn leads inexorably to the rise of resistance to those drugs, and a never-ending ever-spiraling race to discover new and different antibiotics ensues, just to keep us from losing ground in the battle against infection. The fear is that we will eventually fail to keep up in this race, and the time when people did not fear life-threatening bacterial infections will be just a memory of a golden era.

Another example of selection is Staphylococcus aureus, which could be treated successfully with penicillin in the 1940s and 1950s. At present, nearly all strains are resistant to penicillin, and many are resistent to nafcillin, leaving only a narrow selection of drugs such as vancomycin useful for treatment. The situation is worsened by the fact that genes coding for antibiotic resistance can be transferred between bacteria, making it possible for bacteria never exposed to an antibiotic to acquire resistance from those which have. The problem of antibiotic resistance is worsened when antibiotics are used to treat disorders in which they have no efficacy, such as the common cold or other viral complaints, and when they are used widely as prophylaxis rather than treatment (as in, for example, animal feeds), because this exposes more bacteria to selection for resistance.

Beyond antibiotics. Unfortunately, the comparative ease of finding compounds which safely cured bacterial infections proved much harder to duplicate with respect to fungal and viral infections. Antibiotic research led to great strides in our knowledge of basic biochemistry and to the current biological revolution; but in the process it was discovered that the susceptibility of bacteria to many compounds which are safe to humans is based upon significant differences between the cellular and molecular physiology of the bacterial cell and that of the mammalian cell. In contrast, despite the seemingly huge differences between fungi and humans, the basic biochemistries of the fungal cell and the mammalian cell are much more similar; so much so that there are few therapeutic opportunities for compounds to attack a fungal cell which will not harm a human cell. Similarly, we know now that viruses represent an incredibly minimal intracellular parasite, being stripped down to a few genes worth of DNA or RNA and the minimal molecular equipment needed to enter a cell and actually take over the machinery of the cell to produce new viruses. Thus, the great bulk of viral metabolic biochemistry is not merely similar to human biochemistry, it actually is human biochemistry, and the possible targets of antiviral compounds are restricted to the relatively very few components of the actual virus itself.

Staphylocccus Aureus (SA) or Golden Staph is developing resistance even to more extreme antibitotics such as Vancomycin.

MRSA, or methicillin-resistant Staphylococcus aureus, is a bacterium that has developed antibiotic resistance, first to penicillin in 1947, and later to methicillin. Popularly termed a "superbug", it was first discovered in Britain in 1961 and is now widespread. While an MRSA colonisation in an otherwise healthy individual is not usually a serious matter, infection with the organism can be life-threatening to patients with deep wounds, intravenous catheters or other foreign-body instrumentation; or as a secondary infection in patients with compromised immune systems.

Antimicrobial agents that exhibit time-dependent killing demonstrate little difference in rate and extent of killing once the concentration is 2 to 4 times above the MIC; the rate of killing is constant and is not affected by further increases in antimicrobial concentrations. The length of time the antibiotic concentration remains above the MIC affects killing, which is described by the ratio: time greater than MIC (T > MIC). Thus, the goal of therapy with these agents is to maintain the concentration above the MIC for as long as possible during the dosing interval.

Antibiotics that exhibit time-dependent killing include [beta]-lactams, macrolides (with the exception of azithromycin), and clindamycin. (2,8) The dosage adjustments for these agents differ from concentration-dependent agents. Generally, intervals should be maintained to keep the concentration above the MIC for the longest duration of time possible, because little is gained by increasing peak concentrations if T > MIC is inadequate.

Because cystic fibrosis patients are often treated with multiple antibiotics in hospital settings, they are often colonized with MRSA, potentially increasing the rate of life-threatening MRSA pneumonias among them. The risk of cross-colonization has led to increased use of isolation protocols among these patients.

Antibiotic pharmacodynamics is an evolving science that focuses on the relationship between drug concentration and pharmacologic effect, which is an antibiotic-induced bacterial death that also can manifest as an adverse drug reaction. The pharmacologic action of antibiotics usually can be described as concentration dependent or independent, although such classifications are highly reliant on the specific antibiotic and bacterial pathogen being studied. Quantitative pharmacodynamic parameters, such as ratio of the area under the concentration-time curve during a 24-hour dosing period to minimum inhibitory concentration (AUC0-24:MIC), ratio of maximum serum antibiotic concentration to MIC (Cmax:MIC), and duration of time that antibiotic concentrations exceed MIC (T>MIC), have been proposed as likely predictors of clinical and microbiologic success or failure for different pairings of antibiotic and bacteria. Thus far, most pharmacodynamic data reported have focused on fluoroquinolones, but work has been conducted on vancomycin, ß-lactams, macrolides, aminoglycosides, and other antibiotics.

Despite the development of a number of different pharmacodynamic modeling systems, remarkable agreement exists between in vitro, animal, and limited human data. Although still somewhat premature and requiring additional clinical validation, antibiotic pharmacodynamics will likely advance on four fronts: the science should prove to be extremely useful and represent a cost-effective and efficient method to help develop new antibiotics; formulary committees will likely use pharmacodynamic parameters to assist in differentiating antibiotics of the same chemical class in making antibiotic formulary selections; pharmacodynamic principles will likely be used to design optimal antibiotic strategies for patients with severe infections; and limited data to date suggest that the application of pharmacodynamic concepts may limit or prevent the development of antibiotic resistance. The study of antibiotic pharmacodynamics appears to hold great promise and will likely become a routine part of our daily clinical practices.

In the USA there are increasing reports of outbreaks of MRSA colonisation through skin contact in locker rooms and gymnasiums, even among healthy populations, and MRSA causes as many as 20% of Staph aureus infections in populations that use intravenous drugs.

A last-resort antibiotic, Vancomycin, is used to kill MRSA but several new strains of the bacterium (since the first report in 1997) has been found showing resistance to Vancomycin; those new evolutions of the MRSA bateria are dubbed Vancomycin Intermediate-resistant Staphylococcus aureus (VISA).

Tetracycline is an antibiotic produced by the streptomyces bacterium, indicated for use against many bacterial infections. It is sold under the brand names Tetralysal 300®, Panmycin®, Brodspec® and Tetracap®, among others. It is also used to produce several semi-synthetic derivatives, which are known as the Tetracyclines.

History Tetracycline was first discovered by Lloyd Conover in the research departments of Pfizer. The patent for Tetracycline was first issued in 1955 (patent number 2,699,054). Tetracycline sparked the development of many chemically altered antibiotics and in doing so has proved to be one of the most important discoveries made in the field of antiobiotics.

Mechanism and Resistance Tetracycline inhibits cell growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. The binding is reversible in nature.

Waste left by chickens raised in industrial chicken houses contains a wealth of bacteria that have antibiotic multi-resistance genes, a new study has found.

Since the development of antibiotics, bacteria have been able to mutate and become resistant to them. In this new study, researchers show how bacteria are able to become resistant to many antibiotics at one time by pasting together genes that are resistant to many antibiotics.

Cells become resistant to tetracyline by at least two mechanisms: efflux and ribosomal protection. In efflux, a resistance gene encodes a membrane protein that actively pumps tetracycline out of the cell. This is the mechanism of action of the tetracycline resistance gene on the artificial plasmid pBR322. In ribosomal protection, a resistance gene encodes a protein which binds to the ribosome and prevents tetracycline from acting on the ribosome.

Contraindications Tetracycline use should be avoided during pregnancy and in the very young (less than 6 years) because it will result in permanent staining of teeth causing an unsightly cosmetic result.

Streptomyces is a genus of Actinobacteria. They are Gram-positive, have a high GC-content and can be found predominantly in soil. Most Streptomycetes produce spores.

Macrolides are a family of antibiotics used to treat a wide range of bacterial infections. Each drug within the family slows the growth of or kills specific bacteria; therefore, healthcare practitioners prescribe macrolides based on the individual's current needs.

The complete genome of one of the species, Streptomyces coelicolor, was published in 2002. It contains the largest number of genes of any bacterium characterised so far. Another unique characteristic is that its chromosome is linear instead of circular.

Streptomycetes are characterised by a complex secondary metabolism. They produce a large number of antibiotics that are in clinical use; the now rarely used Streptomycin takes its name directly from the Streptomyces. They are not known to cause disease themselves.

The minimum inhibitory concentration (MIC) of an antibacterial is defined as the maximum dilution of the product that will still inhibit the growth of a test microorganism. The minimum lethal concentration (MLC) of an antibacterial is defined as the maximum dilution of the product that will kill a test organism. MIC/MLC values can be determined by a number of standard test procedures. The most commonly employed methods are the tube dilution method and agar dilution methods. Serial dilutions are made of the products in bacterial growth media. The test organisms are then added to the dilutions of the products, incubated, and scored for growth. This procedure is a standard assay for antimicrobials. The procedure incorporates the content and intent of the American Society for Microbiology (ASM) recommended methodology.

Erythromycin is a macrolide antibiotic which has an antimicrobial spectrum similar or slightly wider to that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma. It is also used to treat outbreaks of chlamydia, syphilis, and gonorrhea.

Erythromycin is produced from a strain of the actinomyces Saccaropolyspora erythraea, formerly known as Streptomyces erythraeus.

Abelardo Aguilar, a Filipino scientist, sent some soil samples to his employer Eli Lilly in 1949. Eli Lilly’s research team, led by J. M. McGuire, managed to isolate erythromycin, and it was subsequently launched in 1952 under the brand name Ilosone (after the Philippine region of Iloilo where it was originally collected from). Erythromycin was formerly also called ilotycin.

Available forms Erythromycin is available in enteric-coated tablets, oral suspensions, ointments, gels and injections.

Mechanism of action Erythromycin prevents bacteria from growing, by interfering with their protein synthesis. Erythromycin binds to the subunit 50S of the bacterial ribosome, and thus inhibits the translocation of peptides.

Pharmacokinetics Erythromycin is easily inactivated by gastric acids, therefore all orally administered formulations are given as either enteric coated or as more stable salts or esters. Erythromycin is very rapidly absorbed, and diffused into most tissues and phagocytes. Due to the high concentration in phagocytes, erythromycin is actively transported to the site of infection, where during active phagocytosis, large concentrations of erythromycin are released.

Metabolism Most of erythromycin is metabolised by demethylation in the liver. Its main route elimination route is in the bile, and a small portion in the urine. Erythromycin's half-life is 1.5 hours.

Side-effects Gastrointestinal intestinal disturbances such as diarrhoea, nausea, abdominal pain and vomiting are fairly common so it tends not to be prescribed as a first-line drug. More serious side-effects, such as reversible deafness are rare. Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link between erythromycin, ventricular tachycardia and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like verapamil or diltiazem) by interfering with CYP3A4.

Linezolid is a synthetic systemic antibiotic drug.

It was the first commercially available oxazolidinone antibiotic and is usually reserved for the treatment of serious bacterial infections where older antibiotics have failed due to antibiotic resistance. Conditions such as skin infections or nosocomial pneumonia where methicillin or penicillin resistance is found are indicators for linezolid use. Compared to the older antibiotics it is quite expensive.

The drug works by inhibiting the initiation of bacterial protein synthesis; it is the only antibiotic to work in this manner. That and its synthetic nature raised hopes that bacteria would be unable to develop resistance to it and also remove the chance of cross-resistance. (However, in 1997 Staphylococcus aureus was first identified in Japan as being resistant to linezolid.) Linezolid is effective against gram-positive pathogens, noyably E. faecium, S. aureus, S. agalactiae, S. pneumoniae, and S. pyogenes. It has almost no effect on gram-negative bacteria and is only bacteroistatic against most enterococcus species.

Microbiology is the study of microorganisms A micro-organism or microbe is an organism that is so small that it is invisible to the naked eye. The term is synonymous by usage to single-celled organism, and unicellular organism, even though some unicellular protists are visible to the naked eye, and some colonial species are microscopic. All unicellular organisms are able to reproduce themselves without help of other organisms, as opposed to viruses.

Domain: Eukaryota, Kingdoms, Animalia - Animals Fungi Plantae - Plants Protista

Eukaryotes are organisms with complex cells, in which the genetic material is organized into membrane-bound nuclei. They include the animals, plants, and fungi, which are mostly multicellular, as well as various other groups called protists, many of which are unicellular. In contrast, other organisms such as bacteria lack nuclei and other complex cell structures, and are called prokaryotes. The eukaryotes share a common origin, and are often treated formally as a superkingdom, empire, or domain. The name comes from the Greek eus or true and karyon or nut, referring to the nucleus. ..... Click the link for more information. and prokaryotes Prokaryotes are mostly unicellular organisms without a nucleus, in contrast to eukaryotes, organisms that have cell nuclei and may be variously unicellular or multicellular. The difference between prokaryote and eukaryote cell structure is the most important in the living world. Most prokaryotes are bacteria, and the two terms are often treated as synonyms. However, Woese has proposed dividing them into the Bacteria and Archaea (originally Eubacteria and Archaebacteria) on the supposition that these have separate origins. This controversial arrangement is called the three-domain system. ..... Click the link for more information. , fungi

The Fungi (singular: fungus) are a large group of organisms ranked as a kingdom within the Domain Eukaryota. Included are the conspicuous mushrooms, but also many microscopic

The minimum inhibitory concentration is the minimum concentration of the antibacterial agent in a given culture medium below which bacterial growth is not inhibited.

The therapeutic index is thus given by the plasma or tissue toxic concentration divided by the MIC.

Care should be exercised in interpreting the MIC, since it is a culture definition. In tissues the situation may be altered - for example in abcesses the walls may be resistant to the passage of antibiotic.

A common alternate meaning of virus is computer virus. Other meanings, as well as a discussion of pluralization, are at plural of virus.

A virus is a small particle which can infect other biological organisms. Viruses are obligate intracellular parasites meaning that they can only reproduce by invading and taking over other cells as they lack the cellular machinery for self reproduction. The term virus usually refers to those particles which infect eukaryotes (multi-celled organisms and many single-celled organisms), whilst the term bacteriophage or phage is used to describe those infecting prokaryotes (bacteria and bacteria-like organisms). Today, most of the work in microbiology is done using methods from biochemistry Biochemistry is the chemistry of life. Biochemists study the elements, compounds and chemical reactions that are controlled by enzymes and take place in all living organisms.

Biochemistry is focused on the structure and function of cellular components, such as proteins, carbohydrates, lipids, nucleic acids, and other biomolecules. Recently biochemistry has focused more specifically on the chemistry of enzyme-mediated reactions, and on the properties of proteins. and genetics Genetics is the science of genes, heredity, and the variation of organisms. Humans began applying knowledge of genetics in prehistory with the domestication and breeding of plants and animals. In modern research, genetics provides important tools in the investigation of the function of a particular gene, e.g. analysis of genetic interactions. Within organisms, genetic information generally is carried in chromosomes, where it is represented in the chemical structure of particular DNA molecules. ..... Click the link for more information. . It is also related to pathology Pathology is the study of diseases. It is a form of science and a branch of medicine that involves testing samples and diagnosing physical health problems from their evidence. Pathologists are skilled in interpreting test results and physical evidence.

Bacillus anthracis is an appropriate microbe to begin our examination of pathogenesis, because it was the first bacterium shown to cause a disease by Robert Koch in 1877. Koch was able to grow the microbe in pure culture and demonstrate that injection of B. anthracis into a susceptible host caused the disease anthrax. Many of the methodologies developed in demonstrating the causal relationship between growth of B. anthracis on a host and the disease anthrax have been applied to numerous other maladies to discover their causative agents. The terrorist use of anthrax in 2001 has greatly increased public awareness of the causative bacterium and renewed interest in its identification, treatment and prevention.

Antibiotics can be classified as either concentration- or time-dependent bactericidal agents. Concentration-dependent (or time-independent) antibiotics kill at a greater rate and to a greater extent with increasing antibiotic concentrations, whereas time-dependent (or concentration-independent) antibiotics kill bacteria at the same rate and to the same extent once an appropriate antibiotic threshold concentration has been achieved. Increasing the antibiotic concentration beyond this point typically does not augment the antibacterial activity.

In general, aminoglycosides, fluoroquinolones, and metronidazole (against anaerobic bacteria) are considered concentration-dependent killers, whereas vancomycin, clindamycin, macrolides (with the possible exception of azithromycin), and ß-lactams are considered concentration-independent killers. Our understanding is compromised, however, due to limited data involving a relatively small number of bacterial isolates over a confined range of antibiotic concentrations.

Immunology is a broad branch of biomedical science that covers study of all aspects of the immune system in all organisms. It deals with, among other things, the physiological functioning of the immune system in states of both health and disease; malfunctions of the immune system in immunological disorders (autoimmune diseases, hypersensitivities, immune deficiency, allograph rejection); the physical characteristics of organs in the immune system; and in vitro, in vivo and in situ chemical and physiological properties of biological components of the immune system. Immunology has various applications in several disciplines of science, and as such is further categorised accordingly. Epidemiology is the study of the demographics of disease processes, including the study of epidemics and other diseases that are common enough to allow statistical tools to be applied. So, besides contagious diseases, it also focuses on diabetes, coronary heart disease, high blood pressure and the like. Epidemiology is an important auxiliary branch of medicine, helping to find the causes of diseases and ways of prevention (as in the case of AIDS). It can, using statistical methods such as large-scale population studies, support or refute treatment hypotheses. A pathogen is a biological agent that can cause disease to its host. A synonym of pathogen is "infectious agent". The term "pathogen" is most often used for agents that disrupt the normal physiology of a multicellular animal or plant. However, pathogens can infect unicellular organisms from all of the biological kingdoms (see Viruses, below).

OverviewThe human body has many natural defenses against some of the more common pathogens.

Microbiologists have made many fundamental contributions to biology

Biology studies the variety of life (clockwise from top-left) E. coli, tree fern, gazelle, Goliath beetle Biology is the science of life. It is concerned with the characteristics and behaviors of organisms, how species and individuals come into existence, and the interactions they have with each other and with their environment. Biology encompasses a broad spectrum of academic fields that are often viewed as independent disciplines. Together, they study life over a wide range of scales. Cell biology (cellular biology) is an academic discipline which studies the physiological properties of cells, as well as their behaviours, interactions, and environment; this is done both on a microscopic and molecular level. Cell biology researches both single-celled organisms like bacteria and specialized cells in multicellular organisms like humans.

Understanding the composition. Microbes have many traits that make them ideal model organisms A model organism is one that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. This works because evolution reuses fundamental biological principles and conserves metabolic, regulatory, and developmental pathways.

ß-lactams primarily exhibit concentration-independent activity, and the focus has been on T>MIC as a predictive parameter. Results of an experiment published in 1950 found that the major determinant of penicillin activity against pneumococci in an animal model was the amount of time in which drug concentration remained above minimally effective levels.[1] Increased efficacy with larger doses was attributed to an extension in the time the drug remained above the effective concentration, rather than to an increase in absolute concentrations.

There are many model organisms. The first model organism for molecular biology was probably the bacterium Escherichia coli which is common in the human digestive system (and usually beneficial -- the dangerous is a rare strain). This also led to a study of many bacteriophages, particularly phage lambda.

They are small, therefore they do not consume many resources Some have very short generation times (~30 minutes for E. coli Escherichia coli

Escherichia coli. Cells can easily survive in isolation from other cells They can reproduce by mitotic In biology, mitosis is the process of chromosome segregation and nuclear division that follows replication of the genetic material in eukaryotic cells. This process assures that each daughter nucleus receives a complete copy of the organism's genome. In most eukaryotes mitosis is accompanied with cell division or cytokinesis, but there are many exceptions, for instance among the fungi. There is another process called meiosis, in which the daughter nuclei receive half the chromosomes of the parent, which is involved in gamete formation and other similar processes. The term clone is derived from κλων, the Greek word for "twig". k, b. In horticulture, the spelling clon was used until the twentieth century. The final e came into use to indicate the vowel is a "long o" instead of a "short o"; see the references below on this point. Since the term entered the popular lexicon in a more general context, the spelling clone.

They may be frozen for long periods of time. Even if 90% of the cells are killed by the freezing process, there are millions of cells in a milliliter of liquid culture. Demonstrating that adaptive mutations arise from preadaptation rather than directed mutation. For this purpose, they invented replica plating Replica plating is a technique in which multiple dishes, also known as Petri plates, containing solid (agar-based) microbial media, are inoculated with between thirty and three-hundred colonies of microorganisms from a primary plate (or master dish), reproducing the original spatial pattern of colonies. The technique involves pressing a velvet-covered disk to a primary plate, and then imprinting ..... Click the link for more information. , which allowed them to transfer numerous bacterial colonies In biology, a colony (from Latin colonia) means several individual organisms of the same species living closely together, usually for mutual benefit, such as stronger defences, the ability to attack bigger prey etc. Some insects (ants, for example) live only in colonies. Colonies were probably the first step towards multicellular organisms during evolution. The difference between a multicellular organism and a colony is that individual organisms from a colony can, if separated, survive on their own, while cells from a multicellular lifeform (e.g., liver cells) cannot. Volvox is an example for the border between these two states from their specific locations on one agar-filled petri dish to analogous locations on several other petri dishes. After replicating a plate of E. coli, they exposed each of the new plates to phage

A phage (also called bacteriophage) is a small virus that infects only bacteria. Like viruses that infect eukaryotes, phages consist of an outer protein hull and the enclosed genetic material (which consists of double-stranded DNA in 95% of the phages known) of 5 to 650 kbp (kilo base pairs) with a length of 24 to 200 nm. The vast majority of phages (95%) have a tail to let them inject their genetic material into the host. Phages were discovered independently by Frederick Twort in 1915 and by Félix d’Herelle in 1917. d'Herelle continued his research and development in Stalin's Soviet Union.  They observed that phage-resistant colonies were present at analogous locations on each of the plates, allowing them to conclude that the phage resistance trait had existed in the original colony, which had never been exposed to phage, instead of arising after the bacteria had been exposed to the virus.

The oxazolidinone class was discovered by researchers at EI duPont de Nemours and reported in 1987. Pharmacia Corporation developed linezolid and FDA approval was granted in April 2000. It is sold in the US under the tradename Zyvox in either tablet form, oral suspension powder, or in an inactive medium for intravenous injection.

Side effects include rashes, loss of appetite, diarrhea, nausea, constipation and fever. A small number of patients will incur a severe allergic reaction, or tinnitis, or pseudomembranous colitis, or thrombocytopenia. Linezolid is a weak monoamine oxidase inhibitor (MAOI) and cannot be used with tyramine containing foods or pseudoephedrine.

ß-lactams are generally considered concentration-independent killers of bacteria. Both in vitro and animal data support T>MIC as a pharmacodynamic parameter that predicts activity, though other parameters take on increased importance in select settings. A relatively large body of data from human studies supports administering these agents as a continuous infusion or in shorter dosage intervals, especially in neutropenic patients, to maximize the interval during which drug concentration is kept above the MIC. However, no convincing data are available to support choosing continuous infusions over more conventional dosing schemes in the majority of clinical situations. In addition, whereas limited clinical data have speculated on the optimal duration of T>MIC, definitive values have yet to be established. Clearly, more in vitro and much more human data are needed to validate the importance of T>MIC across the spectrum of infectious diseases.

Aminoglycosides are a group of antibiotics that are effective against certain types of bacteria. They include amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, streptomycin, and tobramycin. Those which are derived from Streptomyces species are named with the suffix -mycin, while those which are derived from micromonospora are named with the suffix -micin.

Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth.

Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Streptomycin was the first effective drug in the treatment of tuberculosis, though the role of aminoglycosides such as streptomycin and amikacin have been eclipsed (because of their toxicity and inconvenient route of administration) except for multiple drug resistant strains.

Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis.

Because of their potential for ototoxicity and renal toxicity, aminoglycosides are administered in doses based on body weight. Blood drug levels and creatinine are monitored during the course of therapy.

Another important consideration in pharmaco-dynamics is the presence or absence of a PAE, which refers to the ability to suppress bacterial growth after a scripted exposure to an antibiotic. In general, ß-lactams produce a PAE only against gram-positive organisms, although some authors suggest the class, especially carbapenems, have a sustained PAE (as well as concentration-dependent activity) against gram-negative organisms. Only agents that interrupt protein or nucleic acid synthesis, such as the macrolides, fluoroquinolones, and aminoglycosides, have been consistently shown to produce a sustained PAE against gram-negative bacteria.

Translating the PAE found with in vitro experiments into a treatment for human infections is potentially problematic. Frequently, the PAE is longer in vivo than in vitro, but in some cases it may be nonexistent in vivo, as is the case with streptococci exposed to penicillins and cephalosporins. Although in vitro PAE data are often generated after single antibiotic exposures and therefore do not simulate a clinical course of multiple antibiotic treatments, clinicians are dependent on literature values because this type of laboratory testing is not routinely done. In summary, the PAE is unique to the pathogen and is generally longer in vivo than in vitro. The PAE may wane with multiple dosing and is not a clinically reported value. Therefore, justifying extended dosage intervals based on PAE is difficult.

There is no oral form of these antibiotics: they are generally administered intravenously, though some are used in topical preparations used on wounds.

Aminoglycosides are completely ineffective against anaerobic bacteria, fungi and viruses.

The MIC portion of this test procedure begins with diluting the test product serially with equal volumes of 2X growth media. The resulting suspensions are 1X growth media with decreasing concentrations of the test product. The dilutions increase in such a way that the next dilution is half as concentrated as the dilution before (i.e. 1:2, 1:4, 1:8, 1:16:, 1:32...). Each dilution is then spiked with 0.05 mL of test culture and the dilutions are incubated.

It is important to keep in mind that MIC cannot be determined without following up with an MLC test. After incubation, the MIC dilution tubes will either be turbid with growth or they will be clear. A tube without turbid growth will result from one of two possible events. Either the challenge microorganisms were killed by the test product, or they were inhibited by the test product. Negative tubes that are suspected of having inhibited microorganisms are subcultured in neutralizer broth. The neutralizer broth tubes are then incubated and scored for growth. A subculture tube that becomes turbid after incubation indicates that the test product was inhibitory at that dilution for that particular organism. If the subculture tubes remain negative after incubation, this indicates that the test product is lethal at that concentration for that particular organism.

Test products that are not clear or precipitate the growth media follow the same basic test procedure described above, but in order to detect growth of the test organisms, each dilution must be plated onto agar and incubated.

An antibiotic is a drug This article is about chemical substances. For other meanings of the word "drug", see Drug (disambiguation) A drug is any substance that can be used to treat an illness, relieve a symptom, or modify a chemical process or processes in the body. The word "drug" is ethymologically derived from the Dutch/Low German word "droog", which means "dry", since in the past, most drugs were dried plant parts. ..... Click the link for more information. that kills or slows the growth of bacteria

Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Omnibacteria Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae. Antibiotics are one class of "antimicrobials", a larger group which also includes anti-viral, anti-fungal, and anti-parasitic drugs. f, h, c. They are relatively harmless to the host, and therefore can be used to treat Therapy or treatment is the remediation of a health problem, after the diagnosis. Types of therapy include:

drug therapy, in which drugs are used to treat an issue massage therapy occupational therapy physical therapy (physiotherapy) psychotherapy, where combinations of drugs and communications are used to treat mental health or personality development issues. radiation therapy recreational therapy speech therapy surgery alternative forms such as crystal therapy

"Infection" is also the title of an episode of the television series Babylon 5; see Infection (Babylon 5). An infection is the detrimental colonization of a host organism by a foreign species. The colonizing organism interferes with the normal functioning and perhaps the survival of the host. The infecting organism is referred to as a pathogen, which may be bacterial, a parasite, fungal, or a virus, prion or viroid. The scientific study of diseases in medicine caused by biological agents is infectious diseases. The term originally described only those formulations derived from living organisms, but is now applied also to synthetic antimicrobials, such as the sulfonamides Sulfonamides, also known as sulfa drugs, are synthetic antimicrobial agents derived from sulfonic acid. In bacteria, these drugs are competitive inhibitors of para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. This reaction is necessary in these organisms for the synthesis of folic acid.

Antimicrob Agents Chemother, 1991 Jul, 35(7), 1309 - 14
Interaction of aminoglycosides with the outer membranes and purified lipopolysaccharide and OmpF porin of Escherichia coli; Hancock RE et al.; The mechanism of uptake of aminoglycosides across the outer membrane of Escherichia coli was reevaluated . Porin-deficient mutants showed no alteration in gentamicin or kanamycin susceptibility . Furthermore, the influence of kanamycin on intrinsic tryptophan fluorescence of porin OmpF (Y . Kobayashi, and T . Nakae, Eur . J . Biochem . 151:231-236, 1985) was shown to be strongly influenced by protein concentration and EDTA . This led to the hypothesis that aminoglycoside-mediated increases and decreases in intrinsic tryptophan fluorescence were due to aggregation-disaggregation of OmpF mediated by interaction at a divalent cation binding site on OmpF . Gentamicin, kanamycin, and polymyxin B increased E . coli outer membrane permeability to the hydrophobic fluorescent compound 1-N-phenyl-naphthylamine (NPN) and the peptidoglycan-degrading enzyme lysozyme . Addition of Mg2+ blocked these permeabilizing activities . Furthermore, gentamicin and polymyxin B bound to Mg(2+)-binding sites on E . coli lipopolysaccharide, as determined in dansyl polymyxin displacement experiments . A polymyxin-resistant, lipopolysaccharide-altered pmr mutant of E . coli had a fourfold-lower MIC of gentamicin and kanamycin and was more poorly permeabilized to 1-N-phenylnaphthylamine than was its parent strain . These data were consistent with uptake of aminoglycosides across the E . coli outer membrane by the self-promoted uptake mechanism.

Chromosoma, 1991 Jul, 100(6), 386 - 94
Structure of the macronuclear polyubiquitin gene in Euplotes; Hauser LJ et al.; The hypotrichous ciliate, Euplotes eurystomus, contains both a transcriptionally inactive micronucleus (MIC) and a transcriptionally active macronucleus (MAC) in the same cell . MAC DNA is small (0.5-20 kb), linear and highly amplified . Each DNA fragment consists of two telomeres, a single coding region, and the necessary control elements to regulate gene transcription and replication . The polyubiquitin gene consists of 898 bp, plus 28 bp of double-stranded and 14 bases of single-stranded DNA of the telomeric repeat G4T4 at each end . The coding region exists as three copies of the ubiquitin gene (690 bp) fused in a head-to-tail arrangement as in other organisms . The stop codon is TAA, as in other Euplotes genes, and is not the rare glutamine codon used in most other ciliates . The 3' nontranslated region contains two presumptive poly(A) addition sites; the 5' nontranslated region possesses two putative TATA boxes, several imperfect direct and inverted repeats, and a possible origin of replication . Nucleosome positioning studies reveal four tightly packed nucleosomes and a non-nucleosomal area containing the probable 5' control region as well as part of the coding region . The 5' area does not contain any DNAse I hypersensitive sites . Although the telomeres are protected from exonuclease digestion, they are not as well protected as Oxytricha telomeres against endonucleases and cleavage by methidium propyl Fe2+ EDTA.

Top Hosp Pharm Manage, 1991 Jul, 11(2), 59 - 69
Drug-usage evaluation: a system for the prospective evaluation of antibiotic utilization in minimum inhibitory concentration documented infections; Sharp WT et al.; Large hospitals appear to have advantages in using specialized clinical practitioners to provide prospective reviews on drug therapy . Using the PRMC pharmacy service as a model, a prospective DUE program can be duplicated in small hospitals with four or five fulltime pharmacists . The minimal requirements are a microbiology laboratory, administrative support, and a pharmacy service committed to providing prospective patient oriented care.

J Arthroplasty, 1991 Jun, 6(2), 179 - 83
Treatment of acutely infected arthroplasty with local antibiotics; Davenport K et al.; The authors have identified 22 patients with acutely infected total joint arthroplasties, 9 hips, and 13 knees . Following organism identification and assessment of the patients' general medical condition, the patients were treated with an implantable antibiotic pump . This allowed the delivery of a high concentration of antibiotic solution to a localized area . Systemic levels of antibiotic were kept to a minimum, thereby eliminating potential serious side effects of antibiotic treatment . Local concentrations were extremely high, exceeding the minimal inhibitory concentration (MIC) in all cases by 8-10-fold . Twenty patients have been followed for 30 months, and of these, 17 patients are considered to be infection free . There were three failures . The organisms that have been treated have been gram negatives, gram positives, and some mixed infections . Results are encouraging with this form of treatment, and additional patients are continually being added to the study.

J Med Assoc Thai, 1991 Jun, 74(6), 327 - 30
An in vitro study on mefloquine/quinine in Plasmodium falciparum malaria; Jariya P et al.; An in vitro designed for determining sensitivity of Plasmodium falciparum strains isolated from Kanchanaburi Province, to Mefloquine/Quinine combination, was carried out . The MIC values of Mefloquine/Quinine for the P.falciparum strains were found to be 0.075/3.75 to 0.225/11.15 nM/ml . The changes observed following the drug treatment were an enlargement of the space between the outer and the inner limiting membrane of the parasitophorous vacuole . These changes were followed by cytoplasmic degeneration and vacuolation.

J Hosp Infect, 1991 Jun, 18 Suppl A, 117 - 29
Single daily dose therapy with aminoglycosides; Nordstrom L et al.; Although aminoglycosides are generally infused every 8 or 12 h, recent data suggest that administration of the total daily dose every 24 h may reduce the risk of oto- and nephrotoxicity and improve efficacy . Aminoglycosides kill bacteria in a dose-dependent manner (i.e . the higher the drug level, the more rapid and complete the bactericidal effect), and exert a post-antibiotic effect (delay in regrowth after the drug concentration falls below its minimum inhibitory concentration for the strain) . Moreover, survivors after initial aminoglycoside exposure are temporarily relatively insensitive to the drug, so longer interdose intervals allow recovery of greater sensitivity . Thus, dosing to achieve higher peak drug levels less often would seem desirable . In several animal models of infection, greater efficacy and less oto- and nephrotoxicity have been associated with once daily dosing of aminoglycosides . Several clinical studies have indicated the importance of high peak serum aminoglycoside levels for efficacy . Limited studies of once daily dosing of these drugs in man have suggested that it is at least as favourable as conventional dosing . Nonetheless, despite the obvious advantages of cost and convenience and the theoretical and experimental indication that once daily dosing is advantageous, we need to test this concept in the clinical situation . Large prospective, randomized, double-blind, comparative studies of once daily and conventional dosing regimens in the treatment of various infections in different patient populations are required.

Enferm Infecc Microbiol Clin, 1991 May, 9(5), 277 - 82
{Pneumococcal meningitis . 6-year review}; Aisa ML et al.; We have reviewed 29 episodes of pneumococcal meningitis seen in a 6-year period (1983-1988) in 11 pediatric patients and 16 adults . An underlying disease or condition was present in 81.5% of cases, in 55.5% there was an anatomical defect, either congenital, acquired or traumatic in origin . Gram stain of CSF was positive in 86% of cases, and latex test was positive in the 22 CSF samples analyzed with this technique . MIC for penicillin ranges from 1 to 2 mcg/ml in 51.7% of cases . These isolates were also resistant to tetracycline (100%), trimethoprim-sulfamethoxazole (100%) and chloramphenicol (87%) . All strains isolated were sensitive to vancomycin, rifampin and cefotaxime . Of all 14 episodes due to penicillin-sensitive strains, 10 cases were treated with this drug and in 4 cases, third generation cephalosporins were prescribed . All cases showed good clinical response . Of all 15 episodes due to penicillin-resistant strains, vancomycin was used first in 10 cases, cefotaxime in three, moxalactam in one and ampicillin plus chloramphenicol in another . Treatment failures (one in cefotaxime and one in moxalactam group) were solved with vancomycin . Of all 12 patients treated with vancomycin, clinical and microbiological cure was achieved in 10 cases . Two additional patients died, one with sterile CSF after 45 days of admission and one few hours after admission . Our data give support to vancomycin as a useful therapeutic option in the treatment of pneumococcal meningitis due to penicillin-resistant strains.

Pathol Biol (Paris), 1991 May, 39(5), 391 - 5
{In vitro activity of cefuroxime against Moraxella (Branhamella) catarrhalis}; Laurans G et al.; Minimal inhibitory concentrations of cefuroxime were determined by an agar dilution procedure and compared with erythromycin and four other beta-lactam antibiotics (amoxycillin, amoxycillin + clavulanate, cefadroxil, cefaclor) on 76 strains of Moraxella (Branhamella) catarrhalis . Sixty four of them produced a beta-lactamase . Results show that the beta-lactamase of Moraxella (Branhamella) catarrhalis abrogates the activity of amoxycillin (MIC 90% = 4 mg/l) meanwhile the combination of amoxycillin-clavulanate is inhibitory at low concentration (MIC 90% = 0.25 mg/l) . There are no difference in MICs between strains producing or not producing beta-lactamase with erythromycin (MIC 90% = 0.25 mg/l) . All the strains evaluated in this investigation, producing or not producing beta-lactamase have MIC 90% less than or equal to 2 mg/l for cefuroxime lower than those obtained for the two other cephalosporins.

Int J STD AIDS, 1991 May-Jun, 2(3), 195 - 9
Gonorrhoea and urogenital chlamydial infection in female prostitutes in Tegucigalpa, Honduras; Venegas VS et al.; The prevalence of gonorrhoea and urogenital chlamydial infection was investigated in female prostitutes in Tegucigalpa, Honduras . Epidemiological data were recorded according to a standardized questionnaire . The median age of the prostitutes was 27 years and the median period of prostitution was 2-4 years . Most of the women (91%) had no occupation other than prostitution and 57% of them had not even completed primary school . In 233 cases when both gonococcal culture and chlamydial antigen detection with a commercial EIA kit were performed the prevalence of gonorrhoea was 25% (59) and that of chlamydial infection 31% (72) . Both diseases were recorded in 9% . The women who had been prostitutes for 2 years or longer had gonorrhoea (P less than 0.01) or chlamydial infection (P less than 0.05) less frequently than those who had practised prostitution for a shorter time period . Among 70 different gonococcal isolates from 241 prostitutes, 40 (57%) belonged to serogroup W II/III . Most (83%) of the 30 W I isolates were beta-lactamase producing (PPNG) like 42% of the W II/III isolates . All non-PPNG isolates, except one had decreased susceptibility to benzylpenicillin (MIC greater than or equal to 0.125 mg/l) and all isolates were susceptible to spectinomycin . Four out of five isolates from the throat were PPNG and the fifth had a benzylpenicillin MIC of 0.5-2.0 mg/lPIP: The prevalence of gonorrhea and urogenital chlamydia infection was investigated among female prostitutes in Tegucigalpa, Honduras . Epidemiological data were recorded according to a standardized questionnaire . The median age of the prostitutes was 27 years old and median period of prostitution was 2-4 years . Most of the women (91%) has no other occupation besides prostitution and 57% of them had not even completed primary school . Among 233 cases when both gonococcal culture and chlamydial antigen detection with a commercial EIA kit were performed, the prevalence of gonorrhea was 25% (59) and that of chlamydial infection 31% (72) . Both diseases were recorded in 9% . The women who had been prostitutes for 2 or more years had gonorrhea (p0.01) or chlamydial infection (p0.05) less frequently than those who had practiced prostitution for a shorter time period . Among 70 different gonococcal isolates from 241 prostitutes, 40 (57%) belonged to serogroup W II/III . Most (83%) of the W I isolates were beta-lactamase producing (PPNG) as were 42% of the W II/III isolates . All non-PPNG isolates except 1 had decreased susceptibility to benzylpenicillin (MIC or= o.125 mg/1) and all isolates were susceptible to spectinomycin . 4 of 5 isolates from the throat were PPNG and the 5th had a benzylpenicillin MIC of 0.5-2.0 mg/l . author's modified

Diagn Microbiol Infect Dis, 1991 May-Jun, 14(3), 265 - 71
Comparison of agar versus broth dilution techniques for determining antibiotic susceptibilities of Ureaplasma urealyticum; Waites KB et al.; We determined minimal inhibitory concentrations (MIC) for tetracycline and erythromycin for 72 clinical isolates using broth and agar dilution methods . Erythromycin MIC ranges were less than 0.125-8 micrograms/ml and 1-64 micrograms/ml in broth and agar, respectively . The erythromycin MIC50 and MIC90 as determined by broth were two dilutions (fourfold) lower than those for agar . Tetracycline MIC ranges in broth and agar were less than 0.125-greater than 64 and 0.25-greater than 64 micrograms/ml, respectively . The tetracycline broth MIC50 was one dilution lower than that for agar . The tetracycline broth MIC90 was 64 micrograms/ml and that for agar was greater than 64 micrograms/ml . Of the strains tested, 98.6% using broth were susceptible or moderately susceptible to erythromycin as compared with 75% using agar, representing a significant difference (p less than 0.001) . For tetracycline, 80.6% of strains were susceptible or moderately susceptible using broth and 73.6% using agar . MICs were determined by agar dilution after 72 and 96 hr of incubation in 32 strains . There was an increase in the erythromycin MIC by one dilution in 16 strains and two dilutions in one strain with the longer incubation . The tetracycline MIC increased by one dilution in nine strains between readings . Broth MICs were reproducible with one dilution for both drugs in 10 of 12 strains tested twice . Agar MICs were reproducible within a maximum of two dilutions (fourfold) . Different interpretations of susceptibility versus resistance may be made depending on which assay is utilized, thus influencing conclusions regarding spectrum of activity of investigational drugs as well as treatment options . The technique employed should always be considered whenever apparently differing drug susceptibility patterns are reported.

Pathol Biol (Paris), 1991 May, 39(5), 534 - 8
{Laboratory's controls of antifungal treatment by the fluconazole of the candidiasis in immunocompromised patients}; Blancard A et al.; The use of antifungal drugs in immunocompromised patients impose to the laboratory the control of the efficacy of these therapy . With fluconazole, one of the most recent antifungal agents these control use a special method (Central Research Pfizer) different of those they are used with others antifungals . We have comparatively tested, using MIC technic four broth mediums (High Resolution medium (Oxoid) YMB (Difco) YNB dextrose (Autobac) and Casitone) and three agar mediums (HR, YMA, Casitone) incubated at 28 degrees C for 24 and 48 h . The strains of yeasts are isolated from oro-pharyngeal prelevements on HIV antibody positive patients observed during six to twelve months and eventually treated by fluconazole . Sixty patients are controlled, 33 give one or more positive cultures with 74 strains of C . albicans and four other yeasts . By determination of the MICs with seven different methods we find any resistant strains with the MICs range from 3.12 to 12.5 or 25 micrograms/ml.

Pathol Biol (Paris), 1991 May, 39(5), 511 - 4
{Diffusion of roxithromycin in gingival tissue}; Jehl F et al.; The gingival penetration of roxithromycin was evaluated at steady-state in twenty nine patients treated by 150 mg orally every 12 h during five days . Tissue specimen were sampled at 2 h (n = 6), 4 h (n = 6), 6 h (n = 5), 8 h (n = 6) and 12 h (n = 6) after the 10th administration . One blood sample was drawn at the same times . Serum and tissue concentrations of roxithromycin were measured by high performance liquid chromatography (HPLC) . Serum peak level, measured at the 4th h, reached 6.60 +/- 1.15 micrograms/ml . The tissue peak concentration was 4.63 +/- 1.84 micrograms/g at the 8th h . Between the 4th and 10th hour after administration, the tissue concentrations are above 2 micrograms/g, i.e . above roxithromycin MIC 90 against most of the encountered pathogens in stomatologic infections.

Pathol Biol (Paris), 1991 May, 39(5), 442 - 5
{Comparative study of minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) values for tetracycline, monocycline, erythromycin and rokitamycin against eleven strains of Chlamydia trachomatis}; Bianchi A et al.; We evaluated the efficacy of tetracycline, minocycline, erythromycin and rokitamycin (rikamycine, TMS-19Q) in controlling in vitro propagation of Chlamydia trachomatis in HeLa 229 cells . Ten recent clinical isolates of Chlamydia trachomatis and one fast-growing strain were tested with inocula of 100-1,000 inclusion forming units per well of a 96-wheel microculture plate . Chlamydia trachomatis inclusions were detected by an immunoperoxidase-antiperoxidase procedure (PAP), including a genus-specific monoclonal antibody . Minimal inhibitory concentration (MIC) geometric means and ranges were respectively 0.128, 0.015-0.25 mg/l tetracycline, 0.001, less than or equal to 0.001-0.004 mg/l minocycline, 0.187, 0.031-0.5 mg/l erythromycin, and 0.005, less than or equal to 0.001-0.062 mg/l rokitamycin; minimal lethal concentration (MLC) geometric means and ranges were 6.79, 0.125-32 mg/l tetracycline, 0.225, 0.062-2 mg/l minocycline, 3.37, 1-32 mg/l erythromycin, and 0.112, 0.031-1 mg/l rokitamycin . Since rokitamycin appears to be the more bactericidal from the four antibiotics tested, clinical studies in sexually transmitted diseases are indicated.

Rev Infect Dis, 1991 May-Jun, 13(3), 376 - 8
Peritonitis due to Prototheca wickerhamii in a patient undergoing chronic ambulatory peritoneal dialysis; Sands M et al.; A 72-year-old man who was undergoing chronic ambulatory peritoneal dialysis developed peritonitis due to Prototheca wickerhamii . Results of in vitro sensitivity testing revealed that the organism was sensitive to amphotericin B (MIC, 0.4 micrograms/mL) but resistant to fluconazole (MIC, greater than 80 micrograms/mL) . The patient was successfully treated medically with a combination of intravenous amphotericin B and oral doxycycline.

Infection, 1991 May-Jun, 19(3), 138 - 9
Combined activity of trospectomycin and colloidal bismuth subcitrate against Helicobacter pylori in vitro; Vogt K et al.; The combined activities of trospectomycin, a spectinomycin analogue, and colloidal bismuth subcitrate against Helicobacter pylori were investigated, the agar dilution method being employed . Forty-seven strains of H . pylori were examined . An additive effect was observed in 89%, and a synergistic interaction in 11% of the isolates . There was no antagonism observed . The MIC50 of trospectomycin against H . pylori was 2 mg/l; the MIC ranged from 0.5 to 4 mg/l.

Antimicrob Agents Chemother, 1991 May, 35(5), 824 - 30
Effect of monodesethyl amodiaquine on human polymorphonuclear neutrophil functions in vitro; Labro MT et al.; We have previously observed that the antimalarial drug amodiaquine impairs the human polymorphonuclear neutrophil (PMN) oxidative burst in vitro . However, the drug acted at a concentration of 100 micrograms/ml, far higher than that which is achievable therapeutically . Since amodiaquine is extensively metabolized into monodesethyl amodiaquine, we investigated whether the metabolite modified PMN functions at lower concentrations than amodiaquine does . Monodesethyl amodiaquine strongly depressed PMN chemotaxis and phagocytosis at concentrations as low as 10 micrograms/ml . This inhibition was reversed by washing out the drug . The PMN oxidative burst was markedly depressed by monodesethyl amodiaquine, whatever the assay technique (luminol-amplified chemiluminescence, lucigenin-amplified chemiluminescence, myeloperoxidase activity) or stimulus used (opsonized zymosan, phorbol myristate acetate, formylmethionyl leucyl phenylalanine) . There were extreme interindividual variations in sensitivity to the depressive effect of monodesethyl amodiaquine when the PMN oxidative burst was assayed in terms of luminol-amplified chemiluminescence or lucigenin-amplified chemiluminescence . PMN samples were divided into two groups on the basis of the MIC of the drug: 60% of the samples were "highly sensitive," being strongly inhibited at concentrations as low as 0.1 micrograms/ml (obtained during therapy), whereas the "moderately sensitive" samples were inhibited at concentrations of 10 micrograms/ml and above . The difference between the two groups was highly significant . This PMN sensitivity to the inhibitory effect of the drug was not related to intrinsic oxidative metabolism . Our data indicate that monodesethyl amodiaquine, the main metabolite of amodiaquine, has a far stronger inhibitory effect on various PMN functions in vitro than the parent drug, warranting relevant in vivo studies.

Can J Surg, 1991 Apr, 34(2), 117 - 22
Efficacy and distribution of single-dose preoperative antibiotic prophylaxis in high-risk gastroduodenal surgery; Lewis RT et al.; Although a single preoperative dose of antibiotic is now the accepted means of preventing postoperative surgical infection, the method has not been investigated adequately . In patients at high risk of infection who underwent gastroduodenal operations, the authors compared single-dose prophylaxis by intravenous cefotaxime (26 patients) with short-course perioperative prophylaxis (27 patients) . No wound infection occurred, but in one patient in each group a subphrenic abscess developed after leakage at the anastomosis . The half-life of cefotaxime (1.23 +/- 0.12 hours) and its apparent volume of distribution (16.7 +/- 2.6 L/1.73 m2 resulted in perioperative levels of the antibiotic in blood (34.76 +/- 4.21 micrograms/mL), gastric mucosa (32.04 +/- 5.22 micrograms/mL) and subcutaneous fat (24.98 +/- 5.89 micrograms/mL) more than twice the usual minimal inhibitory concentration of the drug for organisms grown from the stomach contents and wound fat . These clinical and pharmacologic findings validate the efficacy of a single preoperative intravenous dose of the antibiotic in preventing postoperative infection in high-risk patients who undergo gastroduodenal surgery.

Biochem Int, 1991 Apr, 23(6), 1041 - 7
Interaction of rifampicin with nonprotein thiols in mycobacterium smegmatis; Kumar S et al.; In this study, the interaction of Rifampicin (RIF) with cellular glutathione (GSH) in Mycobacterium smegmatis has been investigated . Minimum inhibitory concentration of RIF for M . smegmatis was demonstrated to be 17 micrograms ml-1 medium . Three subinhibitory concentrations viz . 5, 10 and 15 micrograms RIF ml-1 medium were used to study its interaction with cellular non protein thiols (NPSH) . Maximum depletion (57.8%) in NPSH levels {5, 5'-dithiobis (2-nitrobenzoic acid) assay} was observed on second day when the cells were grown in the presence of 15 micrograms RIF ml-1 medium . When the same samples were assayed for GSH levels (glyoxylase assay) the depletion of GSH levels by RIF was still observed, confirming the earlier findings . GSH depletion paralleled with growth inhibition and reached to normal level on 5th day of growth . Cellular depletion of GSH was also observed when 3 day grown cells of M . smegmatis were exposed to various concentrations of RIF (20, 40 and 60 micrograms ml-1 medium) for different time intervals . Maximum depletion of NPSH levels was observed when 3 day grown cultures were treated with 60 micrograms RIF ml-1 medium for a period of 6 h . The results of this study clearly demonstrate that RIF depletes cellular GSH levels regardless of the fact that the drug is included in the medium before inoculating it or after the cells have been grown for a period of three days . The depletion of cellular GSH levels by RIF in M . smegmatis may contribute towards its antituberculous activity.

Cesk Zdrav, 1991 Apr, 39(2), 76 - 81
{Realistic possibilities of utilization of a personal computer in the office of a general practitioner}; Masopust V; In May 1990 work on the programme "Computer system of the health community doctor Mic DOKI was" completed which resolves more than 70 basic tasks pertaining to the keeping of health documentation by health community doctors; it resolves automatically the entire administrative work in the health community, makes it possible to evaluate the activity of doctors and nurses it will facilitate the work of control organs of future health insurance companies and contribute to investigations of the health status of the population . Despite some problems ensuing from the contemporary economic situation of the country, the validity of contemporary health regulations and minimal training of our health personnel in the use of personal computers computerization of the health community system can be considered an asset to the reform of the health services which is under way.

Eur J Clin Microbiol Infect Dis, 1991 Apr, 10(4), 240 - 8
The mode of action of quinolones: the paradox in activity of low and high concentrations and activity in the anaerobic environment; Lewin CS et al.; All 4-quinolones that have been examined display rapid bactericidal activity which is biphasic . At concentrations above the MIC, the lethality of the drugs increases until a concentration known as the optimum bactericidal concentration (OBC) beyond which the bactericidal activity then declines . The biphasic response appears to be due to the inhibition of RNA synthesis at concentrations above the OBC, as RNA synthesis is required for the full bactericidal activity of the 4-quinolones . However, differences in the biphasic response are observed as some fluoroquinolones are still able to kill bacteria in the absence of bacterial protein or RNA synthesis, thus reducing the inhibition of bactericidal activity at concentrations above the OBC . It has been proposed that this ability to kill bacteria in the absence of protein or RNA synthesis is due to the possession of an additional bactericidal mechanism by these fluoroquinolones . Oxygen also appears to be essential for the lethality of the clinically available 4-quinolones although it is not required for the drugs to inhibit bacterial multiplication . Therefore these drugs are not bactericidal under anaerobic conditions.

J Ethnopharmacol, 1991 Mar, 31(3), 263 - 76
Plants used in Guatemala for the treatment of dermatophytic infections . 1 . Screening for antimycotic activity of 44 plant extracts; Caceres A et al.; Skin infections are common diseases in developing countries, of which dermatophytoses are of particular concern in the tropics, especially in infants . Through ethnobotanical surveys and literature review 100 plants were detected as being used in Guatemala for the treatment of dermatophytoses . Of these, 44 plants were screened for in vitro activity against the most common dermatophytes (Epidermophyton floccosum, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes and Trichophyton rubrum) . Results showed that aqueous extracts from 22 of the plants tested inhibit one or more of the dermatophytes . The most commonly inhibited dermatophytes were E . floccosum (43.2%), T . rubrum (36.0%), and T . mentagrophytes (31.8%); the less inhibited were M . canis (22.7%) and M . gypseum (24.0%) . Plants of American origin which exhibited anti-dermatophyte activity were: Byrsonima crassifolia, Cassia grandis, Cassia occidentalis, Diphysa carthagenensis, Gliricidia sepium, Piscidia piscipula, Sambucus mexicana, Smilax regelii, Solanum americanum and Solanum nigrescens . Fungicidal and fungistatic activities as well as the minimal inhibitory concentration were demonstrated . These results provide a scientific basis for the use of these plants for the treatment of dermatophyte infections in man.

J Vet Pharmacol Ther, 1991 Mar, 14(1), 78 - 89
Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration; Wilson WD et al.; The pharmacokinetics and bioavailability of ticarcillin and clavulanate were determined after intravenous (i.v.) or intramuscular (i.m.) administration of ticarcillin disodium (50 mg/kg) combined with clavulanate potassium (1.67 mg/kg) to groups of healthy foals at 3 days and 28 days of age . After i.v . administration of the combination to five foals, the disposition kinetics of ticarcillin and clavulanate were best described using a two-compartment open model . Mean plasma elimination-rate constant (beta) and clearance (ClB) for ticarcillin were significantly less (P less than 0.01), and volume of distribution at steady state (Vd(ss)) was significantly larger (P less than 0.05), in the foals at 3 days compared with 28 days of age . This indicated that renal excretion mechanisms were immature and ticarcillin was more widely distributed in 3-day-old foals . The mean elimination rate constant for clavulanate was significantly less (P less than 0.01) at 3 days than at 28 days of age . Values of the major kinetic terms describing the disposition of ticarcillin after i.m . administration to five 3-day-old foals were not significantly different from values of these parameters in the same foals at 28 days of age . After i.m . administration of the drug combination, plasma clavulanate concentrations peaked significantly later (P less than 0.01), and the elimination-rate constant (kd) for clavulanate was significantly less (P less than 0.01), in 3-day-old foals than in 28-day-old foals . The bioavailabilities of ticarcillin and clavulanate after i.m . administration in 3-day-old foals were 100% and 88.3%, respectively, and in 28-day-old foals were 100% and 27.4%, respectively . Mean plasma ticarcillin concentrations exceeded 16 micrograms/ml for a longer period after i.m . administration of the drug combination than after i.v . administration to foals of both age groups . By virtue of the frequency of administration required and the painful response elicited by i.m . injection, it is recommended that when the combination of ticarcillin disodium (50 mg/kg) and clavulanate potassium (1.67 mg/kg) is used in foals to treat infections caused by susceptible organisms (MIC less than or equal to 16 micrograms/ml), it should be administered i.v . four times daily.

J Antimicrob Chemother, 1991 Mar, 27(3), 335 - 41
Bronchial penetration of ofloxacin after single and multiple oral dosage; Davey PG et al.; Simultaneous bronchial biopsy and serum samples were obtained from 14 patients after a single oral dose of 200 mg ofloxacin and from ten patients during the course of multiple dose oral treatment, (200 mg ofloxacin bd) for acute exacerbations of chronic bronchitis . Duplicate bronchial samples from different parts of the lung were obtained from five patients . Concentrations in bronchial mucosa were equal to or higher than serum concentrations . There were no statistically significant differences in concentrations after single or multiple doses but there appeared to be a trend towards higher concentrations after multiple doses . After a single dose bronchial and serum concentrations ranged from 1.3 to 15.5 mg/kg and from 0.1 to 5.0 mg/l, respectively, between 1 and 6 h after dosing . After multiple dosing of patients with acute exacerbations of chronic bronchitis bronchial and serum concentrations ranged from 1.7 to 21.0 mg/kg and 1.0 to 6.1 mg/l, respectively between 1 and 12 h . g, g, j, c, f. The percentage difference in ofloxacin concentrations in five duplicate bronchial samples from different parts of the lung was -4%, (95% confidence intervals +22% to -30%) . Thus, the model of bronchial sampling after single dosing of patients before diagnostic bronchoscopy gave results that were similar to those obtained after multiple dosing of patients with acute exacerbations of chronic bronchitis . After multiple dosing ofloxacin concentrations were greater than 1 mg/l or greater than 1 mg/kg in serum and bronchial mucosa throughout the dosing interval, which is above the MIC for most respiratory pathogens.

J Antimicrob Chemother, 1991 Mar, 27(3), 319 - 27
Biphasic kinetics of bacterial killing by quinolones; Carret G et al.; The early phases of the bactericidal dynamics of three quinolones against two Escherichia coli strains were studied . Four concentrations of nalidixic acid, pefloxacin and ofloxacin were tested against each strain . In each case biphasic killing of bacteria was observed after a lag phase, and a biexponential model of microbial death could be fitted to the data . A direct relationship existed between the length of the lag phase and the drug concentration . The other parameters of the model appeared to be either strain-dependent, drug-dependent or both, and were characterised by narrow fluctuations . The degree of killing was always higher for ofloxacin . A paradoxical effect seemed to exist for nalidixic acid and pefloxacin in that survival was greater in the presence of 5 x MIC than in the presence of 3 x MIC . It was clear that ofloxacin did not act in the same way as nalidixic acid and pefloxacin . The study illustrated the relevance of mathematical modelling to investigations of the bactericidal effects of antibiotics.

DICP, 1991 Mar, 25(3), 284 - 8
Ceftazidime in the elderly: appropriateness of twice-daily dosing; Sirgo MA et al.; The disposition of drugs in the elderly is particularly relevant with antiinfectives, because this population has an increased risk of infections . Renal function deteriorates with age, yet dosage guidelines for antibiotics that allow for this reduction remain to be established . Ceftazidime, a cephalosporin with enhanced antipseudomonal activity that is eliminated primarily by glomerular filtration, has been evaluated in the elderly . Herein, we review ceftazidime's pharmacokinetic profile and dosing considerations in this population . Several aspects of renal function deteriorate with the normal aging process, including a decreased glomerular filtration rate (GFR) . Using serum creatinine concentrations as an estimate of the GFR in the elderly is unreliable; a more reliable way of estimating GFR is the use of inulin or 51Cr-editic acid clearance or calculation from formulas or nomograms based on age, weight, sex, and serum creatinine . From pharmacokinetic studies it was found that the elderly individual without renal disease generally has an increased elimination half-life and decreased clearance of ceftazidime compared with a young person . A positive correlation (r = 0.7-0.95) was shown between ceftazidime clearance and GFR, suggesting that estimates of GFR may be used to determine the ceftazidime dose . In several studies, the trough (after 12 hours) ceftazidime serum concentration exceeded by several fold its minimum inhibitory concentration required to inhibit 90% of organisms for most commonly encountered organisms; efficacy and safety were also confirmed with an every-12-hour regimen . A twice-daily dosage regimen for ceftazidime in elderly patients with normal renal function should be considered based on age-related decreases in renal function and drug elimination.

J Infect, 1991 Mar, 22(2), 143 - 52
Dapsone in low doses prevents Pneumocystis carinii pneumonia in the rat model; Gonzalez-Ruiz A et al.; Less toxic drugs are needed for the prophylaxis and treatment of Pneumocystis carinii pneumonia (PCP) in patients with AIDS . Rats immunosuppressed with cortisone were given dapsone, chlorproguanil (CPG) and chlorcycloguanil (CCG), alone or in combination, in the diet and the P . carinii attack rate was compared with that of untreated controls . Dapsone alone at doses of 25 and 5 mg/kg/day was 100% effective in preventing PCP . The efficacy of CPG and CCG, however, could not be properly assessed because of the lack of acceptance of the diet by the animals . Even so, as a result of the findings with dapsone in this study, and because of its pharmacokinetics and minimum inhibitory concentration for P . carinii in vitro, a clinical trial of reduced dosage of dapsone given prophylactically to human beings is suggested . Such a trial may show a decrease in the toxicity of the drug that usually accompanies its long-term administration but retention of its efficacy.

J Bone Joint Surg Br, 1991 Mar, 73(2), 246 - 52
A bioabsorbable delivery system for antibiotic treatment of osteomyelitis . The use of lactic acid oligomer as a carrier; Wei G et al.; We prepared a composite of D,L-lactic acid oligomer and dideoxykanamycin B for use as a biodegradable antibiotic delivery system with sustained effect . The composite was implanted in the distal portion of the rabbit femur, and the effective concentration of the antibiotic was measured in the cortex, the cancellous bone, and the bone marrow . In all bone tissues around the implant, the concentration of antibiotic exceeded the minimum inhibitory concentration for the common causative organisms of osteomyelitis for six weeks . Most of the implant material had been absorbed and the bone marrow had been repaired to a nearly normal state within nine weeks of implantation . The implant caused no systemic side effects, and it is likely to prove clinically useful as a drug delivery system for treating chronic osteomyelitis.

Southeast Asian J Trop Med Public Health, 1991 Mar, 22(1), 72 - 6
Plasma quinine levels in patients with falciparum malaria when given alone or in combination with tetracycline with or without primaquine; Karbwang J et al.; Quinine has been an effective drug for severe chloroquine-resistant falciparum malaria . However, there has been a decline in the sensitivity of Plasmodium falciparum to quinine . In 1978-1979 the cure rate was 94% compared to 86% in 1979-1980 and 76% in 1980-1981 . The combination of quinine and tetracycline has improved the cure rate to 95-100% . However, the mechanism responsible for this has not been identified . We have compared plasma quinine levels on day 2, day 5 and day 7 (before and at 2 hours after dosing) in twenty-one patients with acute falciparum malaria who were treated with quinine alone (8 patients) or quinine in combination with tetracycline (8 patients) or quinine with tetracycline and primaquine (5 patients) . All patients who received combination of quinine and tetracycline with or without primaquine responded well to the treatment with no recrudescence . Two patients who were treated with quinine alone had RI responses . Plasma quinine concentrations from the quinine alone group were significantly lower than those obtained from combination groups on days 2, 5 and 7 . The minimal plasma quinine levels from quinine alone group were all lower than MIC, ie below 10 micrograms/ml while those obtained from the combination group were higher than MIC for 7 days . The results from the present study suggest that tetracycline has influence on the maintenance of plasma quinine levels above MIC throughout the treatment period . Therefore, this must be one possible explanation for the better cure rate.

Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi, 1991 Mar, 7(1), 56 - 7, 78
{Preliminary investigation of effect of pyocyanin on common bacteria in burn wound}; Bai G; Pyocyanin was extracted from culture medium of Ps . aeruginosa by Frank's method . Minimum inhibitory concentration (MIC) & minimum bactericidal concentration (MBC) of pyocyanin for 6 species of bacteria isolated from burn wounds were determined . The results of MIC & MBC: S . aureus 12.5 micrograms/ml, 50 micrograms/ml; E . coli 25 micrograms/ml, 100 micrograms/ml; P . vulgaris 50 micrograms/ml, 200 micrograms/ml; C . freundii 100 micrograms/ml, 400 micrograms/ml; S . epidermidis 12.5 micrograms/ml, 50 micrograms/ml; no inhibitory effect on Ps . aeruginosa . According to the laboratory results and clinical findings, the authors believe that when there is a dominant growth of Ps . aeruginosa in burn wounds there may be pyocyanin production to inhibit or kill other species of bacteria.

Minerva Stomatol, 1991 Mar, 40(3), 151 - 6
{The interference of miocamycin on the adhesiveness and coaggregation of the bacteria responsible for periodontopathies}; Chisari G et al.; The authors studied the effect miocamycin has on the adherence and coaggregation of pathogenic bacteria in periodontopathy . The data obtained by optic microscopy, after treatment of the strains with doses of miocamycin equal to 1/4 and 1/8 of the MIC after 3 and 6 hours, shows the interference effect on the coaggregation and adhesivity of the antibiotic . These results have been confirmed by the observations obtained by scanning electron microscope (SEM).

Mycopathologia, 1991 Mar, 113(3), 159 - 64
Onychomycosis caused by Scopulariopsis brumptii . A case report and sensitivity studies; Naidu J et al.; Scopulariopsis brumptii was isolated from nail lesions in left hand of a 42 year-old-farmer . The direct microscopic examination of the nail samples revealed light brown, septate, branched fungal hyphae along with thick-walled spherical cells . The histopathological examination showed involvement of internal phase of the nail plate . Amongst the antimycotics tested against S . brumptii 'In vitro' oxiconazole was found to be the most active with MIC value of 10 micrograms/ml-1 . This report documents the first instance of onychomycosis caused by S . brumptii.

Ann Hematol, 1991 Feb, 62(1), 16 - 21
A classification of acute leukaemia for the 1990s; Catovsky D et al.; The need for reproducibility in the classification of acute leukaemia has made it necessary to incorporate information derived from new techniques which have become essential for the study of these disorders . In addition to classic morphology and cytochemistry (FAB proposals), it is necessary to add immunology and cytogenetics (MIC proposals), as well as to investigate further the biological and diagnostic significance of molecular events . As a result of these investigations a new group of leukaemias merit recognition as distinct entities . These include three types of ALL with specific chromosome abnormalities, namely, i) t (9;22), ii) t (4;11) and iii) t (1;19) and four subtypes of AML, i) with minimal differentiation or AML-M0, ii) with basophilic precursors or M2Baso, iii) AML (M4/M5) with t (8;16) and iv) AML with trilineage myelodysplasia . Biphenotypic acute leukaemia constitutes also a distinct entity with features of ALL and AML and represents a malignancy probably affecting multipotent stem cells . We propose an objective evaluation system for biphenotypic leukaemias based on a score in which the various lineage markers are graded according to their known specificity.

Eur J Vasc Surg, 1991 Feb, 5(1), 87 - 91
Clinical and pharmacokinetic evaluation of gentamycin containing collagen in groin wound infections after vascular reconstruction; Jorgensen LG et al.; Fourteen patients with localised groin wound graft infection after vascular reconstruction were included in this study to evaluate the clinical effect and the pharmacokinetic profile of gentamycin containing collagen for local antibiotic treatment . All patients were treated by surgical revision and the implantation of one collagen sponge containing 130 mg gentamycin in addition to systemic antibiotics . At follow-up (median 10 months, range 6-15 months), 13 of the 14 patients were cured with a patent reconstruction, giving a success rate in this series of 93% . The pharmacokinetic study showed a very high initial gentamycin concentration in wound fluid, which neatly exceeded the MIC values for most bacteria normally considered resistant to gentamycin . These high MIC values were sustained for 2 to 3 days . In conclusion, this study demonstrated a good clinical effect of gentamycin containing collagen with a high cure rate . In the wound fluid an initial high concentration of gentamycin was achieved which lasted for 2-3 days.

J Infect Dis, 1991 Feb, 163(2), 311 - 8
Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis; Pfister HW et al.; In this prospective, randomized, open trial, 33 patients with Lyme neuroborreliosis were assigned to a 10-day treatment with either ceftriaxone, 2 g intravenously (iv) every 24 h (n = 17), or cefotaxime, 2 g iv every 8 h (n = 16) . Of the 33 patients, 30 were eligible for analysis of therapeutic efficacy . Neurologic symptoms improved or even subsided in 14 patients of the cefotaxime group and in 12 patients of the ceftriaxone group during the treatment period . At follow-up examinations after a mean of 8.1 months, 17 of 27 patients examined were clinically asymptomatic . In one patient Borrelia burgdorferi was isolated from the cerebrospinal fluid (CSF) 7.5 months after ceftriaxone therapy . CSF antibiotic concentrations were above the MIC 90 level for B . burgdorferi in nearly all patients examined . Patients with Lyme neuroborreliosis may benefit from a 10-day treatment with ceftriaxone or cefotaxime . However, as 10 patients were symptomatic at follow-up and borreliae persisted in the CSF of one patient, a prolongation of therapy may be necessary.

Am Rev Respir Dis, 1991 Feb, 143(2), 268 - 70
Comparison of bacteriostatic and bactericidal activity of isoniazid and ethionamide against Mycobacterium avium and Mycobacterium tuberculosis; Heifets LB et al.; Minimal inhibitory and bactericidal concentrations (MIC and MBC) of isoniazid and ethionamide were determined in 7H12 broth in experiments with 68 Mycobacterium avium strains and 14 wild drug-susceptible M . tuberculosis strains . MICs of isoniazid for M . tuberculosis were from 0.025 to 0.05 microgram/ml, and for M . avium from 0.6 to greater than 10.0 micrograms/ml . MICs of ethionamide for M . tuberculosis were from 0.3 to 1.25 micrograms/ml, and 42.7% of M . avium strains were within the same range . Isoniazid and ethionamide were highly bactericidal against M . tuberculosis, but they had very low bactericidal activity against M . avium.

J Gen Virol, 1991 Feb, 72 ( Pt 2), 431 - 3
Stabilization of human rhinovirus serotype 2 against pH-induced conformational change by antiviral compounds; Gruenberger M et al.; Four WIN compounds with anti-picornavirus activities were tested for their ability to stabilize human rhinovirus serotype 2 (HRV-2) against low pH-induced conformational changes in vitro, as determined by specific immunoprecipitation . These results were compared to the minimal inhibitory concentration (MIC) as measured in a plaque reduction assay . A direct relationship was observed between the concentration of the compound that prevented the low pH-induced conformational changes and the MIC, indicating that stabilization is an important element in the mode of action of these drugs against HRV-2.

J Antimicrob Chemother, 1991 Feb, 27 Suppl A, 43 - 5
The in-vitro activity of clarithromycin and other macrolides against the type strain of Chlamydia pneumoniae (TWAR); Ridgway GL et al.; The activity of oxytetracycline and seven macrolide antibiotics was investigated against a prototype strain of Chlamydia pneumoniae in cell culture . Following incubation, inoculated cell monolayers were fixed in methanol and stained with a genus specific immunofluorescent monoclonal antibody before examination for inhibition of inclusion formation . The most active agent was clarithromycin (MIC 0.007 mg/l), followed by erythromycin (0.06 mg/l) . Other macrolides were less active; josamycin and roxithromycin (0.25 mg/l), midecamycin acetate and azithromycin (0.5 mg/l) and spiramycin (4.0 mg/l) . The MIC of oxytetracycline was 0.25 mg/l . Clinical evaluation of clarithromycin for C . pneumoniae lower respiratory infection is indicated.

Zhonghua Yi Xue Za Zhi (Taipei), 1991 Feb, 47(2), 86 - 90
Change of circulating thyroid autoantibody titers in Graves' hyperthyroidism after antithyroid drugs therapy; Lin HD et al.; Parallel measurements of circulating thyroglobulin (Tg), microsomal {TPO(mic)} and TSH-receptor antibodies {TSH-R(rr)} were performed in 30 cases of Graves' hyperthyroid patients who received antithyroid drug (ATD) therapy for 2.8 +/- 1.7 years (range: 0.5-5.0 years) . Before ATD therapy, positive Tg, TPO(mic) and TSH-R(rr) antibodies were found in 33.3%, 83.3% and 86.7% of our patients with Graves' disease, respectively . The titers of Tg and TPO(mic) antibodies remained unchanged in most patients after ATD treatment . However, the TSH-R(rr) antibody titers decreased in 46.7%, elevated in 26.7% and unchanged in 26.7% after ATD therapy . Six cases got long-term remission . Measurements of Tg and TPO antibodies have no value in forecasting the outcome of the disease . The change of circulating TSH-R(rr) antibody from positive to negative is more predictive of remission after ATD therapy than the decrease of thyrotropin-binding inhibiting immunoglobulin index only . However, the former change indicating a persistent remission is not certain.

Toxicol Appl Pharmacol, 1991 Feb, 107(2), 253 - 68
Long term pulmonary impairment following a single exposure to methyl isocyanate; Ferguson JS et al.; Groups of guinea pigs were exposed for 3 hr to 6, 13, 19, 27, or 37 ppm of methyl isocyanate (MIC) . Pulmonary performance was evaluated immediately postexposure and for a period of 1 year in the animals surviving 19 or 37 ppm of MIC . At 6 and 13 ppm deterioration of pulmonary performance was observed but complete recovery occurred within a few weeks . In those animals surviving 19 or 37 ppm some recovery occurred but a long lasting impairment of pulmonary performance was observed . One year after a single exposure to MIC these animals presented a condition best described as chronic obstructive lung disease . Using flow-volume measurements during air breathing and during CO2 challenge, animals surviving at 19 or 37 ppm presented typical abnormalities associated with airflow limitation along the conducting airways . One year after exposure lung hyperinflation was also present . At this time the poor ventilatory response to CO2 was due to mechanical limitation of lung expansion during inspiration and airflow limitation during expiration . The findings were similar to humans with severe obstructive lung disease . Microscopic examination substantiated the flow-volume measurements in that the main bronchi, small bronchi, and bronchioles were found to have an increase in dense fibrous tissue, while the alveolar level was characterized by destruction of alveolar walls and an increase in septal thickness . Thus a single exposure to MIC, if the concentration is high enough, is sufficient to induce permanent pulmonary toxicity.

J Med Vet Mycol, 1991, 29(1), 45 - 52
Studies on the mode of action of tolnaftate in Microsporum gypseum; Gupta MP et al.; Studies were performed on the mode of action of tolnaftate and resistance to this drug in Microsporum gypseum . Cells grown in the presence of tolnaftate (at the IC 50) showed a reduced content of total phospholipids and sterols whereas there was an increase in total RNA content . Incubation of cells with tolnaftate (at 10 x MIC), followed by addition of different macromolecule precursors revealed inhibition of the biosynthesis of all macromolecules except for RNA . The activity of membrane-bound enzymes did not change on treatment with tolnaftate (10 x MIC) whereas an increase in the leakage of intracellular 32P was observed . The content of total phospholipids was higher in tolnaftate-resistant cells, whereas the content of total sterols, DNA, RNA and protein was comparable to that of susceptible cultures . Activity of phosphodiesterase decreased and 5'-nucleotidase increased in tolnaftate-resistant cells . Our results suggest that the antifungal activity of tolnaftate is due to differential action on various targets site(s) which are modified in strains resistant to the drug.

J Vet Diagn Invest, 1991 Jan, 3(1), 66 - 71
Comparison of a veterinary breakpoint minimal inhibitory concentration system and a standardized disk agar diffusion procedure for antimicrobic susceptibility testing; Watson CK et al.; The correlation between the antimicrobic standard disk agar diffusion procedure and a veterinary antimicrobic breakpoint minimal inhibitory concentration system was evaluated . Bacterial isolates representing 5 different genera were tested against 15 antimicrobics . There were 3,795 tests performed; 77.3% of the test results were in agreement, 22.6% were in disagreement . Thirty-one percent of the conflicting results were due to the organism being intermediate on the standard disk agar diffusion procedure . Results suggest that the breakpoint system needs more than 1 antimicrobic dilution per antimicrobic, or a change in some of the single dilutions in the breakpoint system would eliminate some of these discrepancies . Another possibility would be to utilize more than 1 panel design, i.e., 1 for gram-positive organisms, 1 for gram-negative organisms, and 1 for fastidious organisms.

Antimicrob Agents Chemother, 1991 Jan, 35(1), 188 - 91
Comparative in vitro effects of liposomal amphotericin B, amphotericin B-deoxycholate, and free amphotericin B against fungal strains determined by using MIC and minimal lethal concentration susceptibility studies and time-kill curves; Ralph ED et al.; Multilamellar liposomal amphotericin B (L-AmB) was generally less active in vitro against yeast strains than was amphotericin B-deoxycholate or free amphotericin B, although continual agitation of the broth disproportionately increased the activity of L-AmB . Time-kill studies also demonstrated a slower onset of action of L-AmB and supported the hypothesis that liposomes may act as reservoirs for free amphotericin B, which is the active moiety.

Urology, 1991, 37(3 Suppl), 4 - 8
Bacterial prostatitis: new methods of treatment; Aagaard J et al.; Four different clinical categories of prostatitis are recognized at present: acute bacterial prostatitis, chronic bacterial prostatitis, nonbacterial prostatitis, and prostatodynia . Treatment results of chronic bacterial prostatitis have, in the past, been rather poor . In addition to local factors (e.g., prostatic calculi), the poor results may well be due, in part, to lack of penetration of the various drugs used into the prostatic tissue and fluid, mostly because of unfavorable lipid solubility, degree of ionization, protein binding, and unfavorable pH gradients from the plasma to prostatic fluid . All of these factors determine the diffusion of a drug into prostatic tissue and fluid . The minimum inhibitory concentrations (MIC) of the various drugs used and the concentration of the drugs actually obtained in the prostate, combined with the influence of pH, inoculum size, and effect of prostatic fluid and prostatic extract on MIC, are important factors in determining at least the theoretical efficacy of various drugs in the treatment of chronic bacterial prostatitis . The new fluoroquinolones have excellent penetration into both animal and human prostates and very low MIC for the infecting organisms and should, from a theoretical standpoint, be ideal in the treatment of chronic bacterial prostatitis . Few clinical studies have been done, and only prospective, randomized clinical trials will determine the relative efficacy of the various quinolones in the treatment of chronic bacterial prostatitis.

Clin Pharmacol Ther, 1991 Jan, 49(1), 6 - 12
Effect of steroids on cerebrospinal fluid penetration of antituberculous drugs in tuberculous meningitis; Kaojarern S et al.; Sixteen patients with oral isoniazid, pyrazinamide, rifampin, and intramuscular streptomycin for tuberculous meningitis were studied . The concentrations of isoniazid, pyrazinamide, rifampin, and streptomycin in cerebrospinal fluid (CSF) obtained 3 hours after administration were 2.40, 34.78, 0.29, and 3.78 micrograms/ml, respectively . The CSF concentrations of isoniazid and pyrazinamide were well above the minimum inhibitory concentration for Mycobacterium tuberculosis . Concentrations of rifampin and streptomycin were above the minimal inhibitory concentration initially but declined below the minimal inhibitory concentration at later times . The CSF penetration of isoniazid, pyrazinamide, rifampin, and streptomycin was about 89%, 91%, 5%, and 20%, respectively . In eight patients who received antituberculous drugs in combination with steroids, the mean CSF and serum concentrations, as well as CSF/serum ratios at various intervals of treatment, were not statistically different (p greater than 0.05) from those of the eight patients who did not receive steroids.

Microbiol Immunol, 1991, 35(4), 289 - 301
Genetic and molecular analysis of spontaneous respiratory deficient (res-) mutants of Escherichia coli K-12; Lewis LA et al.; Respiratory deficient (res-) mutants of E . coli are slow growing microcolonial, anaerobic, catalase and benzidine negative strains whose broad phenotypic alteration may result from pleiotropic mutations in genes of the hemin biosynthetic pathway . They are easily recovered from platings of sensitive cells on concentrations of gentamicin higher than the minimal inhibitory concentration . These mutants show a dramatic change in their biochemical diagnostic profile resulting primarily from deficiencies in the active transport mechanisms of the cell . Using well-marked F- and Hfr strains, 157 mutants were analyzed from 3 different parent strains; all but 2 resulted from mutations in 3 loci of the hemin biosynthetic pathway . Of these a marked skew to hemB- mutations was seen, with more than 80% mapping there . The possibility that this hot spot resulted from transpositional activity was tested by Southern hybridization of EcoRI digests of the chromosomal DNA, using as a probe, a 2.8-kb fragment containing the hemB gene . The WT and other hemB+ control strains contained a 14.6-kb fragment . Of 18 hemB strains tested, 14 showed deletion and insertion mutations which fell into four classes based on the variation in the size of the fragment or on the absence of hybridization . The latter resulted from complete deletion of the hemB gene . An increase in fragment size from 1.5-kb to 3.4-kb was observed in some of the strains.

Immunopharmacol Immunotoxicol, 1991, 13(3), 413 - 24
A study on the B cell activity in protein deficient rats exposed to methyl isocyanate vapour; Saxena AK et al.; The effect of MIC on the humoral immunity of the malnourished (protein deficient) subjects has been investigated . A single exposure of MIC (1.60 mg/l) on protein deficient rats showed no significant change in the body weight and mortality rate compared with the normal but the serum protein levels were found significantly low (P less than 0.01) in the protein deficient diet fed control (PDC) ones . Both PDC and protein deficient MIC exposed (PDMIC) rat showed diminished B-cell proliferation with the optimal dose of LPS, compared to the NDC and normal diet fed MIC exposed (NDMIC) group . Furthermore significant suppression (P less than 0.01) in the B-cell activation by LPS was observed in the PDMIC compared to PDC . The total IgM level in PDMIC was 43% less while 26% higher in NDMIC compared to NDC . The total IgG level in PDMIC and NDMIC was higher (20%) compared to NDC, while 25% less in PDC . The antigen specific B-cell immunity was affected in PDMIC, PDC and NDMIC . As the terminal differentiation process of B-cells were found equally affected in both PDC and NDMIC, it appears that MIC has no synergistic effect on the humoral immunity of the protein malnourished host.

Bull World Health Organ, 1991, 69(4), 459 - 65
Susceptibility of Plasmodium falciparum to different doses of quinine in vivo and to quinine and quinidine in vitro in relation to chloroquine in Liberia; Bjorkman A et al.; Chloroquine-resistant Plasmodium falciparum has been spreading rapidly after its emergence in 1988 in Yekepa . The in vivo and in vitro susceptibilities to quinine and quinidine, compared to chloroquine, were studied by investigating the number of treatment days required for radical cure and estimating the quinine concentrations concomitantly . The minimal inhibitory concentrations (MIC) for schizont maturation in all successful in vitro tests were 5.12 x 10(-6) mol/l for quinine and 1.28 x 10(-6) mol/l for quinidine, indicating that all 50 isolates were sensitive to the two drugs . The IC50 and IC90 values were 0.22 and 0.78 x 10(-6) mol/l for quinine and 0.07 and 0.26 x 10(-6) mol/l for quinidine, respectively . In vitro inhibition of parasites by 1.6 x 10(-6) mol/l of chloroquine was obtained in 31 out of 47 isolates, 16 (34%) being resistant . The IC50, IC90 and geometrical mean MIC for quinine were all about two times higher for the chloroquine-resistant than for the chloroquine-sensitive isolates (P = 0.006) . P . falciparum infected children (n = 64) were randomly allocated to four groups and treated with quinine (10 mg/kg body weight twice daily) for 1 day (3 doses), 2, 4 and 7 days, respectively . All cleared their parasitaemias by day 4 but 5 out of 15 of those treated with only three doses showed a recurrence of parasitaemia between days 7 and 14; these were considered to be recrudescences . In the other groups, recurrent parasitaemias only occurred between days 17 and 28 and were considered to be reinfections.(ABSTRACT TRUNCATED AT 250 WORDS)

Hosp Pract (Off Ed), 1991, 26 Suppl 4, 22 - 8; discussion 50-1
Use of third-generation cephalosporins . Hemophilus influenzae; Yogev R; Meningitis constitutes the major infection associated with H . influenzae . Caution must be used when selecting antibiotic treatment based on MIC data, alone, because bacterial levels in the cerebrospinal fluid are higher than those in the blood, on which MICs are calculated . Certain third-generation cephalosporins are effective in producing maximum killing of H . influenzae in the CSF . This strong bactericidal activity may actually prove to be detrimental, however, by augmenting the inflammatory response, and thus contributing to the complications and the sequelae of meningitis . The addition of an agent to block the exaggerated response may be possible.

Wien Klin Wochenschr, 1991, 103(9), 271 - 3
{Aztreonam, a new approach in the therapy of gonorrhea}; Stoberl C et al.; The isolated gonococcal strains cultured from 99 patients (64 men and 35 women) with uncomplicated genital gonorrhoea were tested with regard to their susceptibility to aztreonam . No resistant strain was found . The bacteriological evaluation of 50 of these strains showed a minimum inhibitory concentration (MIC) of 0.0075 to 3.906 mcg/ml . Four of the tested strains were penicillinase-producing strains of N . gonorrhoeae . 95 patients (95.9%) were cured after administration of a single dose of 1 g aztreonam by intramuscular injection . It was not possible to exclude reinfection of the 4 remaining patients . No side effects were reported.

Chemotherapy, 1991, 37(1), 1 - 5
Antibiotic concentrations in liquor compared to the minimal inhibitory concentrations of isolates in paediatric bacterial meningitis . The Finnish Study Group; Ellmen JK et al.; The susceptibilities of 171 bacteria which caused meningitis in 200 children were tested for their susceptibility as minimal inhibitory concentrations (MICs) for the antibiotics used in therapy . These antibiotics were chloramphenicol, ampicillin, cefotaxime and ceftriaxone . The MICs were compared to the minimal concentrations of the drugs seen in the cerebrospinal fluid (CSF) samples . The minimal bacteriostatic capacity (lowest concentration in CSF/MIC) of both cephalosporins was superior to that of chloramphenicol and ampicillin . The correlation of the finding with the speed of liquor sterilization in the treatment groups is discussed.

Scand J Infect Dis, 1991, 23(3), 377 - 82
Cure of zygomycosis caused by a lipase-producing Rhizopus rhizopodiformis strain in a renal transplant patient; Norden G et al.; A 40-year-old man with renal failure due to membranous glomerulonephritis received a cadaveric renal transplant and immunosuppressive therapy with cyclosporine, azathioprine and steroids . Initially the transplantation was successful . 12 days after the transplantation, however, serous secretion appeared in the wound . Later, black necrosis was seen . Fungal culture showed growth of a zygomycete species . Rhizopus rhizopodiformis, with high in-vitro resistance to amphotericin B, flucytosine, fluconazole, ketoconazole and itraconazole . The MIC value for the allylamine derivative SF86-327 (Exoderil) was 1.6 micrograms/ml . Microscopic examination of sections from a surgical revision showed necrosis of the fat tissue and massive hyphal invasion of the perirenal fat, which contained semi-crystalline material anisotropic as seen in polarized light and characteristically staining with rubeanic acid . These histological data indicate a lipase-induced in-vivo splitting of lipids into fatty acids . In-vitro R . rhizopodiformis showed very high extracellular lipase production . 11 days after initiation of amphotericin B therapy cultures and sections remained positive for rhizopus . Amphotericin B was therefore supplemented with Exoderil orally, cyclosporine and steroids were maintained, and azathioprine was discontinued . The wound granulated, shrank, and healed completely in 10 weeks.

Circ Res, 1991 Jan, 68(1), 245 - 54
Restoration by insulin of impaired prostaglandin E1/I2 receptor activity of platelets in acute ischemic heart disease; Kahn NN et al.; Treatment of normal platelet-rich plasma with a physiological amount of insulin (100 microunits/ml, optimum concentration) for 3 hours at 23 degrees C stimulated the binding of prostaglandin E1 by more than twofold (3,940 +/- 250 sites/10(8) platelets) compared with the nontreated, control platelet-rich plasma (1,590 +/- 265 sites/10(8) platelets) . After platelet-rich plasma from patients with acute ischemic heart disease (n = 43), whose platelets showed impaired prostaglandin E1/I2 receptor activity (850 +/- 100 sites/10(8) platelets), was incubated with insulin (optimum amounts varied from 100 to 200 microunits/ml), the binding of the prostanoid was restored to normal levels (1,790 +/- 140 sites/10(8) platelets) in 75% of the cases . Twenty-five percent of the patients did not respond to the stimulatory effect of insulin . The increased binding of the prostanoid to the insulin-treated platelets also resulted in increased cyclic AMP levels both in normal subjects (44.14 +/- 3.1 pmol/10(8) {insulin-treated} platelets versus 16.35 +/- 2.91 pmol/10(8) {control} platelets) and in patients with acute ischemic heart disease (23.87 +/- 4.1 pmol/10(8) {insulin-treated} platelets versus 7.70 +/- 2.0 pmol/10(8) {control} platelets) by the prostanoid (1.0 microM) . The treatment of platelet-rich plasma with the hormone decreased the minimum inhibitory concentration of the prostanoid from 34 +/- 14 to 15 +/- 9 nM (p less than 0.001) in the case of normal volunteers and from 49 +/- 15 to 32 +/- 11 nM (p = 0.