Antibiotics

J. Worth Estes, M.A.,M.D.
Professor of Pharmacology
Boston University School of Medicine

Questions or comments should be mailed to Carol Walsh

Experimental data for a new antibacterial agent, Drug A, are presented below.

Toxicity studies in uninfected mice indicate that the LD50 of Drug A is about the same as that for penicillin G. Drug A is distributed, in man, in the extracellular fluid compartment, and has a half-life in the plasma of 1.5 hours. Approximately 30% of a rapidly injected intravenous dose of Drug A is found unchanged in the urine within 12 hours of its administration. At pH 2.5, in vitro, Drug A irreversibly loses all of its antibacterial potency.

The in vitro antibacterial effectiveness of Drug A and penicillin G was studied using microorganisms isolated from patients ill with bacterial infections. The minimally effective concentration (MEC) for Drug A and penicillin G are given in Table I. Suppression of growth for 24 hours after inoculation was the criterion of effectiveness.

Table I
Organism MEC (µg/ml)
Drug A Penicillin G
Streptococcus pneumoniae
Streptococcus hemolyticus
(Patient 1)
Streptococcus hemolyticus
(Patient 2)
Streptococcus hemolyticus
(Patient 3)
Streptococcus hemolyticus
(Patient 4)
Staphylococcus aureus
(Patient 5)
Staphylococcus aureus
(Patient 6)
Staphylococcus aureus
(Patient 7)
Staphylococcus aureus
(Patient 8)
0.15
0.28
0.17
0.10
0.35
2.00
4.00
2.50
3.10
0.040
0.025
0.019
0.008
0.037
0.190
0.250
100.000
70.00

The effects of penicillin G, vancomycin, Drug A, and bacitracin on bacterial growth and viability were measured using a bacterial strain (called no. 28) isolated from a patient. The data obtained are given in Table II. The control culture medium contained no antibacterial agent. All the culture media contained p-aminobenzoic acid in excess of the normal requirements for bacterial growth. All cultures contained 10^7 viable colonies per ml of broth at the start of incubation. After 8 hours of incubation each culture contained the number of colonies listed in Table II.

Table II
Antibiotic Added To Broth Number of Viable Bacterial Colonies
per ml of broth after 8 hours of incubation
None
Penicillin G (10mg/ml)
Vancomycin (10mg/ml)
Drug A (10mg/ml)
Bacitracin (10mg/ml)
10^12.0
10^11.5
10^5.0
10^4.5
10^3.5

I. It can be inferred from the data in Table I that drug A is:

II. Vancomycin, bacitracin, Drug A, and penicillin G were administered parenterally to mice experimentally infected with the bacterial strain isolated from Patient No. 7. The available data suggest that, with optimum treatment schedules:

III. From the data available, you can conclude that:

IV. From the data available in the Tables above, and from your knowledge of other bacterial agents, it can be concluded that:

V. You can infer, from the available data, that the plasma half-life of Drug A in a patient with renal insufficiency (after parenteral administration) would be:

VI. Agents which provide effective treatment for tuberculosis include:

VII. The acetylated biotransformation products of sulfonamides:

VIII. Which of the following would you expect to have the smallest therapeutic index in man:

IX. Which of the following is (are) contraindicated in the treatment of infections caused by appropriately sensitive organisms in patients who also have elevated plasma bilirubin concentrations, prolonged prothrombin times, and low serum albumin concentrations:

X. Delayed hypersensitivity following the administration of penicillin is attributable to :