CLINICAL PHARMACOLOGY
Free carbenicillin is the predominant pharmacologically active fraction of Geocillin. Carbenicillin exerts its antibacterial activity by interference with final cell wall synthesis of susceptible bacteria.
Geocillin is acid stable, and rapidly absorbed from the small intestine following oral administration. It provides relatively low plasma concentrations of antibiotic and is primarily excreted in the urine. After absorption, Geocillin is rapidly converted to carbenicillin by hydrolysis of the ester linkage. Following ingestion of a single 500 mg tablet of Geocillin, a peak carbenicillin plasma concentration of approximately 6.5 mcg/ml is reached in 1 hour. About 30% of this dose is excreted in the urine unchanged within 12 hours, with another 6% excreted over the next 12 hours.
In a multiple dose study utilizing volunteers with normal renal function, the following mean urine and serum levels of carbenicillin were achieved:
| | Mean Urine Concentration of Carbenicillin mcg/ml Hours After Initial Dose |
| DRUG | DOSE | 0–3 | | | | 3–6 | | | 6–24 | |
| Geocillin | 1 tablet
q.6 hr | 1130 | | | | 352 | | | 292 | |
| Geocillin | 2 tablets
q.6 hr | 1428 | | | | 789 | | | 809 | |
| Mean serum concentrations of carbenicillin in this study for these dosages are: |
| | Mean Serum Concentration mcg/ml Hours After Initial Dose |
| DRUG | DOSE | 1/2 | 1 | 2 | 4 | 6 | 24 | 25 | 26 | 28 |
| Geocillin | 1 tablet
q.6 hr | 5.1 | 6.5 | 3.2 | 1.9 | 0.0 | 0.4 | 8.8 | 5.4 | 0.4 |
| Geocillin | 2 tablets
q.6 hr | 6.1 | 9.6 | 7.9 | 2.6 | 0.4 | 0.8 | 13.2 | 12.8 | 3.8 |
Microbiology
The antibacterial activity of Geocillin is due to its rapid conversion to carbenicillin by hydrolysis after absorption. Though Geocillin provides substantial in vitro activity against a variety of both gram-positive and gram-negative microorganisms, the most important aspect of its profile is in its antipseudomonal and antiproteal activity. Because of the high urine levels obtained following administration, Geocillin has demonstrated clinical efficacy in urinary infections due to susceptible strains of:
Escherichia coli
Proteus mirabilis
Proteus vulgaris
Morganella morganii (formerly Proteus morganii)
Pseudomonas species
Providencia rettgeri (formerly Proteus rettgeri)
Enterobacter species
Enterococci (S. faecalis)
In addition, in vitro data, not substantiated by clinical studies, indicate the following pathogens to be usually susceptible to Geocillin:
Staphylococcus species (nonpenicillinase producing)
Streptococcus species
Resistance
Most Klebsiella species are usually resistant to the action of Geocillin. Some strains of Pseudomonas species have developed resistance to carbenicillin.
Susceptibility Testing
Geopen (carbenicillin disodium) Susceptibility Powder or 100 µg Geopen Susceptibility Discs may be used to determine microbial susceptibility to Geocillin using one of the following standard methods recommended by the National Committee for Clinical 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:
| | Disk Diffusion | | |
| | Zone diameter (mm) | | |
| Organisms | | Suscept. | | Intermed. | | Resist. |
| Enterobacter | | ≥23 | | 18–22 | | ≤17 |
| Pseudomonas sp. | | ≥17 | | 14–16 | | ≤13 |
| | Dilution | | |
| | MIC (µg/ml) | | |
| Organisms | | Suscept. | | Moderately Suscept. | | Resist. |
| Enterobacter | | ≤16 | | 32 | | ≥64 |
| Pseudomonas sp. | | ≤128 | | — | | ≥156 |
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 carbenicillin. 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 carbenicillin is used, or if the infection is such that high levels of carbenicillin 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.
|
