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Sensitivity of the tubercle bacillus to streptomycin before and during therapy of pulmonary tuberculosis
160
American
Federation
evident: First, a time interval of forty-eight hours was often required for maximum sickling of the infants’ red cells in contrast to the twentyfour-hour period necessary for the mothers’ cells. Secondly, the infants’ red cells showed only 0.5 to 29.5 per cent sickling while the mothers’ cells showed 84 to 100 per cent sickling. Fetal hemoglobin differs chemically from adult hemoglobin in several respects and, as tested by the alkali denaturation method, does not disappear from infants’ blood until the age of four and one-half months. It is interesting that one of our patients with sicklemia followed from birth developed progressively increased sickling from 6 per cent at birth to 90 per cent at four and one-half months. This is also correlated with the estimated four-month life span of the erythrocyte. In view of these data it is suggested that the low percentage of sickling in newborns is due to the presence of fetal hemoglobin, and that this fetal hemoglobin accounts for the absence of death from sickle cell disease in utero where the low oxygen tension would otherwise cause sickling with the usual disastrous pathologic sequelae.
SENSITIVITY OF THE TUBERCLE BACILLUSTO STREPTOMYCINBEFOREANDDURINGTHERAPY OF PULMONARYTUBERCULOSIS. Jose@ F. Sadusk, Jr., M.D. and (6~ invitation) William E. SW@, Connecticut. (From Internal
Medicine,
Jr.,
M.D.,
the
.New Haven,
Department
Yale University
of School
of Medicine.) In vitro sensitivity of tubercle bacilli isolated from sputa or gastric contents was determined in a group of sixteen patients with pulmonary tuberculosis receiving 1.8 Gm. of streptomycin daily for a period of four.months. In vitro tests were performed in Dubos medium. In all sixteen cases the strains of bacilli isolated prior to treatment were highly sensitive to streptomycin. Fourteen of these sixteen strains were inhibited by 0.5 microgram of streptomycin two strains were inper ml.; the remaining hibited by 1.0 microgram per ml. Loss of sensitivity (ten-fold increase in resistance) began to appear by the end of the first month of therapy together with conversion of positive sputum or gastric washings to negative in other cases as determined by culture. By the end of the third and fourth months of therapy cultures were positive in only nine of the sixteen patients.
for Clinical
Research
Tests of organisms from these nine positive cultures indicated that all of them had developed a ten-fold or greater increase in resistance. Five of these nine strains developed a ten to fifty-fold increase in resistance; the remaining four strains developed a 100 to greater than 2,000-fold increase in resistance. It was not possible with this small group of patients to demonstrate conclusively a correlation between resistance to streptomycin and the clinical course under therapy.
TREATMENT OF PNEUMOCOCCIC MENINGITIS BY SYSTEMICPENICILLIN.H. F. Dowling, M.D., L. K. Sweet, M.D. and H. L. Hirsh, M.D.,
Washington, D. C.
When penicillin is employed in addition to sulfonamides, the fatality rate in pneumococcic meningitis is reduced below that obtained with sulfonamides alone. Nevertheless, results obtained up to the present are far from satisfactory. According to accepted methods of treatment, penicillin is given intrathecally in amounts of 10,000 to 20,000 units per day and systemically in doses of about 500,000 units a day with full doses of sulfadiazine or sulfamerazine systemically. Intrathecal administration of penicillin possesses many disadvantages. Among these are: (1) The possibility of radiculitis or convulsions developing when large amounts are given or when concentration of penicillin in the cerebrospinal fluid reaches high levels; (2) irritative action of penicillin upon the meninges, evidenced by development of pleocytosis and the possibility that this may cause adhesions and block; (3) difficulty and danger of repeated lumbar punctures. Intrathecal penicillin is employed because many investigators have failed to find demonstrable amounts of penicillin in the cerebrospinal fluid after systemic administration. Others have shown, however, that when sufficiently large doses of penicillin are given systemically, therapeutic levels are consistently obtained in the cerebrospinal fluid. After preliminary studies had demonstrated that a therapeutic concentration of penicillin was consistently present in the cerebrospinal fluid of subjects receiving l,OOO,OOO units of penicillin intramuscularly every two hours we administered this dose plus sulfadiazine and sulfamerazine to patients with pneumococcic meningitis. Two patients received one intrathecal dose of penicillin; six received none. Five
American
Federation
evident: First, a time interval of forty-eight hours was often required for maximum sickling of the infants’ red cells in contrast to the twentyfour-hour period necessary for the mothers’ cells. Secondly, the infants’ red cells showed only 0.5 to 29.5 per cent sickling while the mothers’ cells showed 84 to 100 per cent sickling. Fetal hemoglobin differs chemically from adult hemoglobin in several respects and, as tested by the alkali denaturation method, does not disappear from infants’ blood until the age of four and one-half months. It is interesting that one of our patients with sicklemia followed from birth developed progressively increased sickling from 6 per cent at birth to 90 per cent at four and one-half months. This is also correlated with the estimated four-month life span of the erythrocyte. In view of these data it is suggested that the low percentage of sickling in newborns is due to the presence of fetal hemoglobin, and that this fetal hemoglobin accounts for the absence of death from sickle cell disease in utero where the low oxygen tension would otherwise cause sickling with the usual disastrous pathologic sequelae.
SENSITIVITY OF THE TUBERCLE BACILLUSTO STREPTOMYCINBEFOREANDDURINGTHERAPY OF PULMONARYTUBERCULOSIS. Jose@ F. Sadusk, Jr., M.D. and (6~ invitation) William E. SW@, Connecticut. (From Internal
Medicine,
Jr.,
M.D.,
the
.New Haven,
Department
Yale University
of School
of Medicine.) In vitro sensitivity of tubercle bacilli isolated from sputa or gastric contents was determined in a group of sixteen patients with pulmonary tuberculosis receiving 1.8 Gm. of streptomycin daily for a period of four.months. In vitro tests were performed in Dubos medium. In all sixteen cases the strains of bacilli isolated prior to treatment were highly sensitive to streptomycin. Fourteen of these sixteen strains were inhibited by 0.5 microgram of streptomycin two strains were inper ml.; the remaining hibited by 1.0 microgram per ml. Loss of sensitivity (ten-fold increase in resistance) began to appear by the end of the first month of therapy together with conversion of positive sputum or gastric washings to negative in other cases as determined by culture. By the end of the third and fourth months of therapy cultures were positive in only nine of the sixteen patients.
for Clinical
Research
Tests of organisms from these nine positive cultures indicated that all of them had developed a ten-fold or greater increase in resistance. Five of these nine strains developed a ten to fifty-fold increase in resistance; the remaining four strains developed a 100 to greater than 2,000-fold increase in resistance. It was not possible with this small group of patients to demonstrate conclusively a correlation between resistance to streptomycin and the clinical course under therapy.
TREATMENT OF PNEUMOCOCCIC MENINGITIS BY SYSTEMICPENICILLIN.H. F. Dowling, M.D., L. K. Sweet, M.D. and H. L. Hirsh, M.D.,
Washington, D. C.
When penicillin is employed in addition to sulfonamides, the fatality rate in pneumococcic meningitis is reduced below that obtained with sulfonamides alone. Nevertheless, results obtained up to the present are far from satisfactory. According to accepted methods of treatment, penicillin is given intrathecally in amounts of 10,000 to 20,000 units per day and systemically in doses of about 500,000 units a day with full doses of sulfadiazine or sulfamerazine systemically. Intrathecal administration of penicillin possesses many disadvantages. Among these are: (1) The possibility of radiculitis or convulsions developing when large amounts are given or when concentration of penicillin in the cerebrospinal fluid reaches high levels; (2) irritative action of penicillin upon the meninges, evidenced by development of pleocytosis and the possibility that this may cause adhesions and block; (3) difficulty and danger of repeated lumbar punctures. Intrathecal penicillin is employed because many investigators have failed to find demonstrable amounts of penicillin in the cerebrospinal fluid after systemic administration. Others have shown, however, that when sufficiently large doses of penicillin are given systemically, therapeutic levels are consistently obtained in the cerebrospinal fluid. After preliminary studies had demonstrated that a therapeutic concentration of penicillin was consistently present in the cerebrospinal fluid of subjects receiving l,OOO,OOO units of penicillin intramuscularly every two hours we administered this dose plus sulfadiazine and sulfamerazine to patients with pneumococcic meningitis. Two patients received one intrathecal dose of penicillin; six received none. Five