Import of antimicrobials

The importance of tissue penetration varies with the site of infection. The CNS is one body site where the importance of antimicrobial penetration is relatively well defined and correlations with clinical outcomes are established. Drugs that do not reach significant concentrations in cerebrospinal fluid should either be avoided or instilled directly when treating meningitis. 

It has always amazed me that the importance of chemical compounds in ecological interactions between plant versus herbivore, insect versus insect, and plant versus plant has been universally accepted, but the importance of antimicrobials in microbial interactions has been ahnost universally denied. 

Several model plants, including 0. sativa, A. thaliana, Z. mays, G. max, and Medicago truncatula, for which genome information is currently available,219 are a rich source of antimicrobial metabolites. Genetic and reverse genetic approaches are providing evidence for the biological importance of antimicrobial compounds in host defense mechanisms. 

The importance of tissue penetration varies with the site of infection. The CNS is one body site where the importance of antimicrobial penetration is relatively well defined and correlations with clinical outcomes are established. Drugs that do not reach significant concentrations in cerebrospinal fluid should either be avoided or instilled directly when treating meningitis. Apart from the bloodstream, other body fluids where drug concentration data are clinically relevant include urine, synovial fluid, and peritoneal fluid. Pharmacokinetic parameters such as area under the concentration-time curve (AUC) and maximal plasma concentration can be predictive of treatment outcome when specific ratios of AUC or maximal plasma concentration to the minimum inhibitory concentration (MIC) are achieved. For... 

Simoncic, B. (2003). Importance of antimicrobial agents for textile finishing. Tekstilec, 46, 64-72. 

Chemical suppHers include basic manufacturers of active ingredients, formulators, and distribution or service industries. The relative importance of each depends greatly upon the industry being suppHed. In many instances, the vendor may supply a number of performance chemicals (eg, corrosion control agents or stabilizers) in addition to the antimicrobial agent. 

The sulfa dmgs are stiH important as antimicrobials, although they have been replaced in many systemic infections by the natural and semisynthetic antibiotics. They are of great value in third world countries where problems of storage and lack of medical personnel make appropriate use of antibiotics difficult. They are especially useful in urinary tract infections, particularly the combination of sulfamethoxazole with trimethoprim. Their effectiveness has been enhanced by co-adniinistration with dihydrofolate reductase inhibitors, and the combination of sulfamethoxazole with trimethoprim is of value in treatment of a number of specific microbial infections. The introduction of this combination (cotrimoxazole) in the late 1960s (1973 in the United States) resulted in increased use of sulfonamides. 

In 1939 the isolation of a mixture of microbial products named tyrotbricin from a soil bacillus was described. Further investigation showed this material to be a mixture of gramicidin and tyrocidine. In rapid succession the isolation of actinomycin (1940), streptothricin (1942), streptomycin (1943), and neomycin (1949), produced by Streptomjces were reported and in 1942 the word antibiotic was introduced. Chloramphenicol, the first of the so-called broad spectmm antibiotics having a wide range of antimicrobial activity, was discovered in 1947. Aureomycin, the first member of the commercially important tetracycline antibiotics, was discovered in 1948. 

Metal compounds, particularly compounds of the heavy metals, have a history of importance as antimicrobial agents. Because of regulations regarding economic poisons in the environment they are no longer widely used in this appHcation. Mercury, lead, cadmium, uranium, and other metals have been imphcated in cases of poisoning that resulted in government response. The metals whose compounds have been of primary interest as antimicrobials are mercury, silver, and copper. 

By far the greatest emphasis in the research and application of microbial antibiotics has been concerned with animal and human health. Despite the extent of the problems relating to plant disease, the practical use of antimicrobial antibiotics in plant agriculture has been limited to a few crops and compounds Only streptomycin and actidione (XI) at present enjoy commercial importance. This may be due in part to the wider applicability of the less expensive synthetic fungicides and in part to the difficulty of arousing much public sympathy for a sick plant. 

Bacterial spores are the most resistant of all microbial forms to chemical treatment. The majority of antimicrobial agents have no useful sporicidal action, with the exception of the aldehydes, halogens and peroxygen compounds. Such chemicals are sometimes used as an alternative to physical methods for sterilization ofheat sensitive equipment. In these circumstances, correct usage of the agent is of paramount importance since safety margins are lower in comparison with physical methods of sterilization (Chapter 20). 

While selection of antimicrobial therapy may be a major consideration in treating infectious diseases, it may not be the only therapeutic intervention. Other important therapies may include adequate hydration, ventilatory support, and other supportive medications. In addition, antimicrobials are unlikely to be effective if the process or source that leads to the infection is not controlled. Source control refers to this process and may involve removal of prosthetic materials such as catheters and infected tissue or drainage of an abscess. Source-control considerations should be a fundamental component of any infectious diseases treatment. It is also important to recognize that there may be many different antimicrobial regimens that may cure the patient. While the following therapy sections... 

After selection and initiation of antimicrobial regimen, there are a number of additional patient care and monitoring considerations that should be addressed to improve the likelihood of a successful outcome. Patient education, deescalation of antimicrobial therapy based on culture results, monitoring for clinical response and adverse effects, and appropriate duration of therapy are important. 

The treatment of intraabdominal infection most often requires the coordinated use of three major modalities (1) prompt drainage, (2) support of vital functions, and (3) appropriate antimicrobial therapy to treat infection not eradicated by surgery. Antimicrobials are an important adjunct to drainage procedures in the treatment of secondary intraabdominal infections however, the use of antimicrobial agents without surgical intervention usually is inadequate. For most cases of primary peritonitis, drainage procedures may not be required, and antimicrobial agents become the mainstay of therapy. 

Important findings from the last 20 years of clinical trials regarding selection of antimicrobials for intraabdominal infections are... 

Stress the importance of complying with the prescribed antimicrobial regimen, and to follow-up with the health care provider if signs and symptoms recur. 

Discuss the importance of timing, duration, and redosing in relation to antimicrobial prophylaxis in surgery. 

Dykhuizen R., Frazer R., Benjamin N., Duncan C., Smith C.C., Golden M. and Leifert C. (1996). Antimicrobial effect of acidified nitrite on gut pathogens the importance of dietary nitrate in host defence . J Antimicrob Agents Chemothe, 40, 1422-1425. 

The most important approach to treatment of IE includes isolation of the infecting pathogen and determination of antimicrobial susceptibilities, followed by high-dose, bactericidal antibiotics for an extended period. 

Antimicrobials are an important adjunct to drainage procedures in the treatment of intraabdominal infections however, the use of antimicrobial agents without surgical intervention is usually inadequate. For some specific situations (e.g., most cases of primary peritonitis), drainage procedures... 

The use of antimicrobials has been controversial, although antibiotics are an important component of treatment. Agents should be selected that are effective against likely pathogens, have the lowest risk of drug interactions, and can be administered in a manner that promotes compliance (see Table 43-1). 

---