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Aqueous penicillin G is rapidly absorbed following both intramuscular and subcutaneous injection. Initial blood levels following parenteral administration are high but transient. Penicillins bind to serum proteins, mainly albumin. Therapeutic levels of the penicillins are easily achieved under normal circumstances in extracellular fluid and most other body tissues. Penicillins are distributed in varying degrees into pleural, pericardial, peritoneal, ascitic, synovial, and interstitial fluids. Penicillins are excreted in breast milk. Penetration into the cerebrospinal fluid, eyes, and prostate is poor. Penicillins are rapidly excreted in the urine by glomerular filtration and active tubular secretion, primarily as unchanged drug. Approximately 60 percent of the total dose of 300,000 units is excreted in the urine within this 5-hour period. For this reason, high and frequent doses are required to maintain the elevated serum levels desirable in treating certain severe infections in individuals with normal kidney function. In neonates and young infants, and in individuals with impaired kidney function, excretion is considerably delayed.
Penicillin G exerts a bactericidal action against penicillin-susceptible microorganisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell wall mucopeptide rendering the cell wall osmotically unstable. It is not active against the penicillinase-producing bacteria, which include many strains of staphylococci. While in vitro studies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in the INDICATIONS AND USAGE section has not been documented. Penicillin G exerts high in vitro activity against staphylococci (except penicillinase-producing strains), streptococci (groups A, C, G, H, L, and M), and pneumococci. Other organisms susceptible to penicillin G are N. gonorrhoeae, Corynebacterium diphtheriae, Bacillus anthracis, Clostridia, Actinomyces bovis, Streptobacillus moniliformis, Listeria monocytogenes and Leptospira. Treponema pallidum is extremely sensitive to the bactericidal action of penicillin G. Some species of gram-negative bacilli are sensitive to moderate to high concentrations of the drug obtained with intravenous administration. These include most strains of Escherichia coli; all strains of Proteus mirabilis, Salmonella and Shigella; and some strains of Aerobacter aerogenes and Alcaligenes faecalis.
Penicillin acts synergistically with gentamicin or tobramycin against many strains of enterococci.
Susceptibility Testing: Penicillin G Susceptibility Powder or 10 units Penicillin G Susceptibility Discs may be used to determine microbial susceptibility to penicillin G using one of the following standard methods recommended by the National Committee for Laboratory Standards:
M2-A3, “Performance Standards for Antimicrobial Disk Susceptibility Tests”
M7-A, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically”
M11-A, “Reference Agar Dilution Procedure for Antimicrobial Susceptibility Testing of Anaerobic Bacteria”
M17-P, “Alternative Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria”
Tests should be interpreted by the following criteria:
|Zone Diameter, nearest whole mm|
|Staphylococci||≥ 29||-||≤ 28|
|N. gonorrhoeae||≥ 20||-||≤ 19|
|Enterococci||-||≥ 15||≤ 14|
|Non-enterococcal streptococci and L. monocytogenes||≥ 28||20-27||≤ 19|
|Approximate MIC Correlates|
|Staphylococci||≤ 0.1 μg/mL||β-lactamase|
|N. gonorrhoeae||≤ 0.1 μg/mL||β-lactamase|
|Enterococci||-||≥ 16 μg/mL|
|Non-enterococcal streptococci and L. monocytogenes||≤ 0.12 μg/mL||≥ 4 μg/mL|
Interpretations of susceptible, intermediate, and resistant correlate zone size diameters with MIC values. A laboratory report of “susceptible” indicates that the suspected causative microorganism most likely will respond to therapy with penicillin G. A laboratory report of “resistant” indicates that the infecting microorganism most likely will not respond to therapy. A laboratory report of “moderately susceptible” indicates that the microorganism is most likely susceptible if a high dosage of penicillin G is used, or if the infection is such that high levels of penicillin G may be attained, as in urine. A report of “intermediate” using the disk diffusion method may be considered an equivocal result, and dilution tests may be indicated.
Control organisms are recommended for susceptibility testing. Each time the test is performed the following organisms should be included. The range for zones of inhibition is shown below:
|Control Organism||Zone of Inhibition Range|
|Staphylococcus aureus (ATCC 25923)||27-35|
Last reviewed on RxList: 6/27/2008
This monograph has been modified to include the generic and brand name in many instances.
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