Antibiotic Resistance

Antibiotic Resistance

i Ii 0022-534 7/82/1284-0871$02.00/0 Vol. 128, October Printed in U.S.A. THE JOURNAL OF UROLOGY Copyright© 1982 by The Williams & Wilkins Co. ABS...

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0022-534 7/82/1284-0871$02.00/0 Vol. 128, October Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright© 1982 by The Williams & Wilkins Co.

ABSTRACTS INFECTIONS AND ANTIBIOTICS

in the treatment of serious fungal infections. 6) Preventing inactivation of the effective antibiotic. H.M.S. 59 references

Principles of Antibiotic Therapy G. M. ELIOPOULOS AND R. C. MoELLERING, JR., Harvard Medical School and Infectious Disease Unit, Department of Medicine, Massachusetts General Hospital, and New England Deaconess Hospital, Boston, Massachusetts

Antibiotic Resistance

M. H. GRIECO, Divisions of Infectious Diseases and Epidemiology and Allergy and Clinical Immunology, R. A. Cooke Institute of Allergy, St Luke's-Roosevelt Hospital Center and Columbia University College of Physicians and Surgeons, New York, New York

Med. Clin. N. Amer., 66: 3-15 (Jan.) 1982 The cornerstone of rational management of the patient with an infection remains the isolation and identification of the infecting microbial pathogen and the determination of its susceptibility to antimicrobial agents. The risks of certain infections may be increased by a number of underlying defects in the host's defense mechanisms. The diagnostician also must be aware of unusual exposures or epidemiologic patterns that will influence the choice of the antibiotic. Once the list of possible etiologic agents has been narrowed empiric therapy can be begun, pending isolation and susceptibility testing of the pathogen. In choosing the most appropriate antibiotic it must be decided whether a bacteriostatic agent will suffice or whether bactericidal therapy is needed. Next it must be determined if adequate levels of the chosen antibiotic can be achieved in the infected tissues. The route chosen for the administration and the frequency of the antibiotic depend on a number of host factors as well as the biochemical characteristics of the drug. Better understanding of the pharmacokinetics of antibiotics should provide the basis for rational therapy and this symposium presents the data from which recommendations can be drawn. H.M.S. 130 references

Med. Clin. N. Amer., 66: 25-37 (Jan.) 1982 Bacteria can become resistant to drugs by spontaneous mutation, recombination with a resistant strain of bacteria and acquisition of a plasmid. While the spontaneous mutation rate producing 1 drug-resistant gene is relatively low, occurring once every 105 to 109 cell division, a pool of several resistant genes can accumulate on plasmids in a bacterial population and can be perpetuated by the selective pressures of continuous antibiotic usage. Plasmids can be found in gram-negative and grampositive bacteria. Plasmids can carry drug-resistant genes that produce proteins that 1) alter the attachment of the antibiotic to a ribosome (tetracyclines and aminoglycosides), 2) alter the permeability of the cell membrane to the antibiotic (penicillin, chloramphenicol, tetracycline, aminoglycosides), 3) inactivate the antibiotic (penicillin and cephalosporin) and 4) alter the target enzyme so the antibiotic has no effect (trimethoprim and sulfonamides). The major reservoir ofresistant bacteria is most commonly the colonized patients themselves rather than the inanimate environment and transmission usually is achieved by passive carriage on the hands of medical personnel. 1 figure, 4 tables, 78 references

Antibiotic Combinations

John F. Cicmanec University of Cincinnati Cincinnati, Ohio

J. TENENBAUM AND M. H. KAPLAN, Division of Infectious Diseases and Immunology, North Shore University Hospital and Cornell University Medical College, New York, New York

M.

Principles of Antibiotic Tissue Penetration and Guidelines for Pharmacokinetic Analysis

Med. Clin. N. Amer., 66: 17-24 (Jan.) 1982 Better understanding of the pharmacology of new antibiotics has helped define clinical settings when the use of > 1 drug is advantageous. There are 6 situations when ;;;2 agents have been shown to be useful. 1) To treat mixed bacterial infections in which the organisms are not susceptible to a common agent. An example is intra-abdominal sepsis secondary to intestinal perforation. These mixed infections are best treated with either clindamycin, chloramphenicol, metronidazole or the semisynthetic penicillins (carbenicillin or ticarcillin) for their anaerobic coverage combined with an aminoglycoside for its aerobic gramnegative efficacy. 2) Antibiotic synergism against the causative organism. An example of this is trimethoprim and sulfamethoxazole, which are bacteriostatic only when used alone but bactericidal in combination against a variety of micro-organisms. 3) Overcoming tolerance (the resistance of an organism to the lethal action of an otherwise bactericidal agent). 4) Preventing the development of resistance against the most effective antibiotic. 5) Decreasing the toxicity of the most effective agent. An example is the use of amphotericin B and 5-fluorocytosine

J. J. ScHENTAG AND F. M. GENGO, State University of New York at Buffalo, School of Pharmacy, Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York Med. Clin. N. Amer., 66: 39-49 (Jan.) 1982

In the analysis of antibiotic pharmacokinetics tissue penetration is a most commonly used phrase. However, it is defined imprecisely. Also, there are some other factors that add confusion to the available tissue penetration studies. There are 7 major factors influencing the antibiotic tissue concentration: 1) serum concentration, 2) binding to serum proteins, 3) binding at the tissue site, 4) delays in penetration owing to membranes, 5) transport systems that control tissue penetration, 6) blood flow to the tissue site and 7) effects of disease on penetration barriers and local binding sites. Since there are so many factors the authors recommend evaluating tissue penetration at the steady state by direct measurement of the tissue concentration and dividing this state, tissue concen-

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