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Chloromycetin-streptomycin therapy in endodontics
Endodontia CHLOROMYCETIN-STREPTOMYCIN
THERAPY
A Preliminary SAMUEL SELTZER, D.D.S.,
AND LB.
IN ENDODONTICS
Report
BENDER, D.D.S.,
T
PHILADELPHIA,
PA.
HE development of an effective antibiotic mixture for root canal therapy has now reached a stage where, in the majority of cases, it is possible to obtain a negative culture after one treatment. Previous reports*’ z dealing with the use of penicillin of low unitage were not too encouraging. When the concentration of penicillin was increased, the treatment. was more effective.3r 4 However, it was found that this antibiotic failed to sterilize many root canals i:nfected with gram-negative organisms. Subsequently, combinations of peniciillin and streptomycin in peanut oil” and in propylene glycol’j were employed. Keports showed that the combination of the two antibiotics was not only a highly effective bactericide, but also a synergistic effect existed against certain bacteria.’ It was found that even with this combination, it was still not possible to sterilize every infected root canal with one treatment. Further studies81 g demonstrated that several groups of organisms, occasionally encountered in infected root canals, were either not susceptible to penicillin and streptomycin or developed rapid resistance to them. Among these resistant organisms were alpha streptococci and streptococci of the enterococci group. Laboratory tests against these resistant strains were conducted with iseveral antibiotics.1° It was found that chloramphenicol (Chloromycetin) ,+ a was highly effective against these resistant crystalline synthetic antibiotic, strains. In addition, it has a wide spectrum against many other pathogenic bacteria. Chloramphenicol (Chloromycetin) is a pure chemical substance, D (-) three-l-p-nitrophenyl-2-dichloroacetamido-1, 3-propanediolll It is a neutral, white crystalline substance with a bitter taste. It is stable in neutral and acid solutions. It is moderately soluble in water and in propylene glycol. Solutions are stable at room temperature and remain stable even upon heating. In comparing the antibacterial spectrum of chloramphenicol and streptomycin, it appeared that these two antibiotics together were capable of killing every type of organism encountered in an infected root canal, with the exception of fungi. In addition, both these antibiotics are soluble and stable in propylene glycol at room temperature. This is an important factor for economic reasons since it is obviously more economical to have an antibiotic mixture with long shelf life. The need for making up fresh solutions for each new endodontic case is obviated. *Supplied by Parke, Davis & Company, Detroit, Mich. 1279
Since penicillin is not stable in aqueous or semiaqueous solutiorq the necessity for using it was apparently no longer present. Therefore7 il mixture of I Gm. of streptomycin (calcium chloride complex ) ant1 I (:m. of’ chloramghenicol in 2 ml. of propylene glycol was prepa&. This report deals with t,he results of a clinical trial of this caornbination of antibiotics.
Procedure
*
Access to the root canal was obtained with sterile burs. After the root canal was entered, a culture was taken by inserting a. sterile paper point into the canal, allowing it to remain for one rninutz and then dropping this paint into a tube of brain-heart infusion broth. The canal was then enlarged with reamers and files. Following this, a mixture of streptomycin and chloramphenicol in propylene glycol was pumped into the canal with a sterile iridioplatinum wire. A short, blunt point moistened with the same mixture was then sealed into the canal and the patient was dismissed. At, the following visit, the old paper point was discarded, the canal was dried with f’rcsh sterile paper points, and another culture was taken. The same treatment was then repeated. Cultures were allowed to incub,atc for one week before results wcrc recorded. Positive cultures were then identified ba.cteriologicnlly. _-- -____
__._____ NO. OF CASES
---_.---
__0
t
Acute
serous
I3
i
a
Acute
suppurative
14
11
3
ulcerative _____~_________~~
Chronic Necrosis Acute
and D.A.
Chronic
D.A.
gangrene
8
3 --
15
abscew abscess
Total
5 ..-....--.
7
_---
-s
18
Ii
28
18
IO
%tl
63
3.5
1
Results Cases were grouped under two general headings, depending upon whether or not the pulps were vital when treatment was begun. The first heading comprised the various pulpitides with the following clinical diagnoses: acute serous pulpitis, acute suppurative pulpitis, and chronic ulcerative pulpitis. The second heading consisted of those cases in which the pulps had died and the This group included those cases with the periapical tissues were involved. clinical diagnosis of necrosis and gangrene of pulp, acute dent,oalveolar abscess, and chronic dentoalveolar abscess. Under the first grouping a total of 37 cases were treated. Of these, 21 were preoperatively positive and 16 were negative when cultured before treatment.
ICHLOROMYCETIX-STREPTOMYCIK
THERAPY
IN
EKDODONTICS
1281
In the second grouping 61 cases were treated. Forty-two of these were positive preoperatively and 19 were negative. The total of preoperative positive cultures in both groups was 63. Cases that were preoperatively negative were not used for clinical evaluation. After one treatment with the chloramphenicol-streptomycin mixture, 51 (80.95 per Twelve cent) cases were found to be negative upon examination by culture. cases (19.05 per cent) remained positive. Identification of these organisms revealed that all 12 were fungi of the Candida group.
Discussion By taking a preoperative culture, a better evaluation of the efficacy of the treatment was obtained. Only those cases yielding a positive culture preoperatively were used to evaluate the efficacy of the antibiotics. It was found that approximately 36 per cent of the cases which are referred for root canal therapy are originally sterile. This percentage is in agreement with the percentage of negative cultures obtained in one of our previous studies.12 We also found that approximately another 20 per cent of the cases can be rendered sterile by proper mechanical and chemical cleansing of the root canal prior to medication. Thus it is possible to eliminate immediately about 55 to 60 per cent of the cases from consideration. The other 40 to 45 per cent of the cases must be sterilized by antimicrobial agents. The results show that the combination of chloramphenicol and streptomycin in propylene glycol is capable of sterilizing 80.95 per cent of all infected pulpless teeth. This combination is completely effective against all bacteria encountered in a root canal. The only organisms unaffected by this mixture are fungi (Monilia), which are found in about 20 per cent of the cases. Antibiotics appear to have an enhancing effect on Monilia. HarrisI reported the development of moniliasis in patients treated with chloromycetin. Foley and WinterI observed that penicillin enhanced the development of Candida albicans in chick embryos and in rabbits. A stimulatory effect was also noted in vitro. The combination of chloramphenicol and streptomycin in propylene glycol is a stable mixture and thus economical to use. Ehrlich’” reported that 90 mg./ml. of chloromycetin in propylene glycol is stable for at least six months. Streptomycin in propylene glycol likewise has been found to be stable for at least a year. The incorporation of penicillin in the mixture.is not absolutely necessary. The use of penicillin might be advantageous, however, because of its rapid killing effect on susceptible organisms. This factor is of clinical importance in treating acute infections. However, until a medium for penicillin is developed in which it remains stable at room temperature, it should be left out of the mixture. Chloramphenicol and streptomycin are more effective than penicillin and streptomycin, inasmuch as an additional 6 to 8 per cent of the cases which are unaffected by the latter combination are sterilized. These cases comprise those infected with alpha streptococci and streptococci of the enterococci group,
namely, Rtreptococcus faecalis, S’trcptococcus zy~~~oyenes, and Ntrcptocnmu liycefuciexs. Twent,y per cent oi’ the cases which arc unaffected t)y either caombination are infected with fungi. Summary and Conclusions 7. The combination of 1 Gnl. of chloramphenicol (Chloromycet,in) and 1 Gm. of streptomycin (calcium chloride caomples) in 2 ml. of propylene glycol was clinically tested in root canal therapy. 2. Ninety-eight cases were studied. Of these 63 were preoperatively positive and 35 were negative. The 35 negative cultures were discarded. 3. All bacteria were killed by the combination in one treatment. This represented approximately 80 per cent of the infected cases. 4. The only organisms resistant to the combination were the fungi. These were present in approximately 20 per cent of t,he cases.
References 1. Shaw, 2. 3. 4. 5. 6.
F. E., Sprawson, E., and May, H. B.: The Bacteriological Examination of Infected Dental Pulp Canals and Use of Penicillin in Pulp Canal Therapy, Brit. M. J. 1: 551, 1945. Evaluation of i2ntibiotic+ ALrents for ISoot Canal Treatment. New Grossman, L. I.: AL, York J. Dent, 15: 232, 1943. Stewart, G.: Comparative Methods of Usin u‘ Penicillin in the Treatment of Vincent’s Infection and-other Oral Lesions, J. Amy Dent. A. 33: 725, 1946. Bender, I. B.: Penicillin in Root Canal Therapy: Report of Fifty-t.hree (‘rises. .l. i\m. Dent. 9. 34: 93 1947. Grossman. L.: Prellminarv Reaort on the [ise of a Perricillin-Strentorrlv~inI Susuension L . in Endodontia, J. En&don%a 3: 39, 1948. Seltzer, S., and Bender, I. B.: The Eficacy of Various Drugs Against Monilia Albicans Isolated From the Root Canal of an infected Pulpless I’ooth, ORAT. SITTRG., ORAL MED.,
7. Bender, Its 169: 8. Bender, on AND
AND
ORAL
PATH.
2:
799,
1949.
Effect of Peuicillin-StreptoIn~-~iIl and I. B., and Seltzer, S.: The Synergistic Application in the Treatment of Infected Pulplexs Teeth. 5. Am. Dent. A. 40: 1950. I. B., and Seltzer, S.: The Effect of a Quaternary Ammonium Ty11c’ (lontpound ‘ ‘ Candida Albicans ” Isolat,ed From the Root Canal, OE.\T. Sl-Ra.. OKAI. MED., ORAL
PATH.
2:
1599,
1949.
Treatment of Penicillin-Streptomycin S., Bender, I. B., and Christian, (I.: Resistant Organisms in the Root Canals of Tnfected Pulpless Teeth. Oral Surg., Oral Med.. and Oral Path. 3: 802. 1950. Seltzer, R., and Bender, I. B.: The Use of Chloramphenicol (Chloromyeetin) for Killing Penicillin-Streptomycin Resistant Organisms Encountered in Infected Root Canals. (In press.) Gruhzit, 0. M., Fisher, R. A:, Reutner, T. F., and Martino, E.: Chloramphenicol (Chloromycetin), an AntibiotIc. Pharmacological and Pathological Studies in :lnimals, J. Clin. Investigation 28: 943, 1949. Bender. I. B.. and Seltzer. 5.: The Use of Penicillin-StreDtom\-cin in the Treatment of Iniected’ Pulpless Tekth, ORAL SURG., ORAL MED., AND ORAL PATH. 3: 1070, 1950. Harris. H. .J.: Aureomvcin and Chloramphenicol in Brucellosis. J. A. M. A. 142:
9. Seltzer, 10. 11. 12. 13,
181,
3950.
14. Foley,
G. E., and Winter, W. D., Jr.: increased Mortality Following Penicillin of Chick Embryos Infected With (!andida Albicarrs T’ar. Stellatoidea. Dis. 85: 268, 1949. 15. Ehrlich, J.: Stability of (‘hlorom,vcetill. c Prrsonal c~ortlmullic:ltjor1.‘, 2035
SI’RGCE
1551
CHAIVIPLOST
ST. ST.
Therap) ,J. Infect.
THERAPY
A Preliminary SAMUEL SELTZER, D.D.S.,
AND LB.
IN ENDODONTICS
Report
BENDER, D.D.S.,
T
PHILADELPHIA,
PA.
HE development of an effective antibiotic mixture for root canal therapy has now reached a stage where, in the majority of cases, it is possible to obtain a negative culture after one treatment. Previous reports*’ z dealing with the use of penicillin of low unitage were not too encouraging. When the concentration of penicillin was increased, the treatment. was more effective.3r 4 However, it was found that this antibiotic failed to sterilize many root canals i:nfected with gram-negative organisms. Subsequently, combinations of peniciillin and streptomycin in peanut oil” and in propylene glycol’j were employed. Keports showed that the combination of the two antibiotics was not only a highly effective bactericide, but also a synergistic effect existed against certain bacteria.’ It was found that even with this combination, it was still not possible to sterilize every infected root canal with one treatment. Further studies81 g demonstrated that several groups of organisms, occasionally encountered in infected root canals, were either not susceptible to penicillin and streptomycin or developed rapid resistance to them. Among these resistant organisms were alpha streptococci and streptococci of the enterococci group. Laboratory tests against these resistant strains were conducted with iseveral antibiotics.1° It was found that chloramphenicol (Chloromycetin) ,+ a was highly effective against these resistant crystalline synthetic antibiotic, strains. In addition, it has a wide spectrum against many other pathogenic bacteria. Chloramphenicol (Chloromycetin) is a pure chemical substance, D (-) three-l-p-nitrophenyl-2-dichloroacetamido-1, 3-propanediolll It is a neutral, white crystalline substance with a bitter taste. It is stable in neutral and acid solutions. It is moderately soluble in water and in propylene glycol. Solutions are stable at room temperature and remain stable even upon heating. In comparing the antibacterial spectrum of chloramphenicol and streptomycin, it appeared that these two antibiotics together were capable of killing every type of organism encountered in an infected root canal, with the exception of fungi. In addition, both these antibiotics are soluble and stable in propylene glycol at room temperature. This is an important factor for economic reasons since it is obviously more economical to have an antibiotic mixture with long shelf life. The need for making up fresh solutions for each new endodontic case is obviated. *Supplied by Parke, Davis & Company, Detroit, Mich. 1279
Since penicillin is not stable in aqueous or semiaqueous solutiorq the necessity for using it was apparently no longer present. Therefore7 il mixture of I Gm. of streptomycin (calcium chloride complex ) ant1 I (:m. of’ chloramghenicol in 2 ml. of propylene glycol was prepa&. This report deals with t,he results of a clinical trial of this caornbination of antibiotics.
Procedure
*
Access to the root canal was obtained with sterile burs. After the root canal was entered, a culture was taken by inserting a. sterile paper point into the canal, allowing it to remain for one rninutz and then dropping this paint into a tube of brain-heart infusion broth. The canal was then enlarged with reamers and files. Following this, a mixture of streptomycin and chloramphenicol in propylene glycol was pumped into the canal with a sterile iridioplatinum wire. A short, blunt point moistened with the same mixture was then sealed into the canal and the patient was dismissed. At, the following visit, the old paper point was discarded, the canal was dried with f’rcsh sterile paper points, and another culture was taken. The same treatment was then repeated. Cultures were allowed to incub,atc for one week before results wcrc recorded. Positive cultures were then identified ba.cteriologicnlly. _-- -____
__._____ NO. OF CASES
---_.---
__0
t
Acute
serous
I3
i
a
Acute
suppurative
14
11
3
ulcerative _____~_________~~
Chronic Necrosis Acute
and D.A.
Chronic
D.A.
gangrene
8
3 --
15
abscew abscess
Total
5 ..-....--.
7
_---
-s
18
Ii
28
18
IO
%tl
63
3.5
1
Results Cases were grouped under two general headings, depending upon whether or not the pulps were vital when treatment was begun. The first heading comprised the various pulpitides with the following clinical diagnoses: acute serous pulpitis, acute suppurative pulpitis, and chronic ulcerative pulpitis. The second heading consisted of those cases in which the pulps had died and the This group included those cases with the periapical tissues were involved. clinical diagnosis of necrosis and gangrene of pulp, acute dent,oalveolar abscess, and chronic dentoalveolar abscess. Under the first grouping a total of 37 cases were treated. Of these, 21 were preoperatively positive and 16 were negative when cultured before treatment.
ICHLOROMYCETIX-STREPTOMYCIK
THERAPY
IN
EKDODONTICS
1281
In the second grouping 61 cases were treated. Forty-two of these were positive preoperatively and 19 were negative. The total of preoperative positive cultures in both groups was 63. Cases that were preoperatively negative were not used for clinical evaluation. After one treatment with the chloramphenicol-streptomycin mixture, 51 (80.95 per Twelve cent) cases were found to be negative upon examination by culture. cases (19.05 per cent) remained positive. Identification of these organisms revealed that all 12 were fungi of the Candida group.
Discussion By taking a preoperative culture, a better evaluation of the efficacy of the treatment was obtained. Only those cases yielding a positive culture preoperatively were used to evaluate the efficacy of the antibiotics. It was found that approximately 36 per cent of the cases which are referred for root canal therapy are originally sterile. This percentage is in agreement with the percentage of negative cultures obtained in one of our previous studies.12 We also found that approximately another 20 per cent of the cases can be rendered sterile by proper mechanical and chemical cleansing of the root canal prior to medication. Thus it is possible to eliminate immediately about 55 to 60 per cent of the cases from consideration. The other 40 to 45 per cent of the cases must be sterilized by antimicrobial agents. The results show that the combination of chloramphenicol and streptomycin in propylene glycol is capable of sterilizing 80.95 per cent of all infected pulpless teeth. This combination is completely effective against all bacteria encountered in a root canal. The only organisms unaffected by this mixture are fungi (Monilia), which are found in about 20 per cent of the cases. Antibiotics appear to have an enhancing effect on Monilia. HarrisI reported the development of moniliasis in patients treated with chloromycetin. Foley and WinterI observed that penicillin enhanced the development of Candida albicans in chick embryos and in rabbits. A stimulatory effect was also noted in vitro. The combination of chloramphenicol and streptomycin in propylene glycol is a stable mixture and thus economical to use. Ehrlich’” reported that 90 mg./ml. of chloromycetin in propylene glycol is stable for at least six months. Streptomycin in propylene glycol likewise has been found to be stable for at least a year. The incorporation of penicillin in the mixture.is not absolutely necessary. The use of penicillin might be advantageous, however, because of its rapid killing effect on susceptible organisms. This factor is of clinical importance in treating acute infections. However, until a medium for penicillin is developed in which it remains stable at room temperature, it should be left out of the mixture. Chloramphenicol and streptomycin are more effective than penicillin and streptomycin, inasmuch as an additional 6 to 8 per cent of the cases which are unaffected by the latter combination are sterilized. These cases comprise those infected with alpha streptococci and streptococci of the enterococci group,
namely, Rtreptococcus faecalis, S’trcptococcus zy~~~oyenes, and Ntrcptocnmu liycefuciexs. Twent,y per cent oi’ the cases which arc unaffected t)y either caombination are infected with fungi. Summary and Conclusions 7. The combination of 1 Gnl. of chloramphenicol (Chloromycet,in) and 1 Gm. of streptomycin (calcium chloride caomples) in 2 ml. of propylene glycol was clinically tested in root canal therapy. 2. Ninety-eight cases were studied. Of these 63 were preoperatively positive and 35 were negative. The 35 negative cultures were discarded. 3. All bacteria were killed by the combination in one treatment. This represented approximately 80 per cent of the infected cases. 4. The only organisms resistant to the combination were the fungi. These were present in approximately 20 per cent of t,he cases.
References 1. Shaw, 2. 3. 4. 5. 6.
F. E., Sprawson, E., and May, H. B.: The Bacteriological Examination of Infected Dental Pulp Canals and Use of Penicillin in Pulp Canal Therapy, Brit. M. J. 1: 551, 1945. Evaluation of i2ntibiotic+ ALrents for ISoot Canal Treatment. New Grossman, L. I.: AL, York J. Dent, 15: 232, 1943. Stewart, G.: Comparative Methods of Usin u‘ Penicillin in the Treatment of Vincent’s Infection and-other Oral Lesions, J. Amy Dent. A. 33: 725, 1946. Bender, I. B.: Penicillin in Root Canal Therapy: Report of Fifty-t.hree (‘rises. .l. i\m. Dent. 9. 34: 93 1947. Grossman. L.: Prellminarv Reaort on the [ise of a Perricillin-Strentorrlv~inI Susuension L . in Endodontia, J. En&don%a 3: 39, 1948. Seltzer, S., and Bender, I. B.: The Eficacy of Various Drugs Against Monilia Albicans Isolated From the Root Canal of an infected Pulpless I’ooth, ORAT. SITTRG., ORAL MED.,
7. Bender, Its 169: 8. Bender, on AND
AND
ORAL
PATH.
2:
799,
1949.
Effect of Peuicillin-StreptoIn~-~iIl and I. B., and Seltzer, S.: The Synergistic Application in the Treatment of Infected Pulplexs Teeth. 5. Am. Dent. A. 40: 1950. I. B., and Seltzer, S.: The Effect of a Quaternary Ammonium Ty11c’ (lontpound ‘ ‘ Candida Albicans ” Isolat,ed From the Root Canal, OE.\T. Sl-Ra.. OKAI. MED., ORAL
PATH.
2:
1599,
1949.
Treatment of Penicillin-Streptomycin S., Bender, I. B., and Christian, (I.: Resistant Organisms in the Root Canals of Tnfected Pulpless Teeth. Oral Surg., Oral Med.. and Oral Path. 3: 802. 1950. Seltzer, R., and Bender, I. B.: The Use of Chloramphenicol (Chloromyeetin) for Killing Penicillin-Streptomycin Resistant Organisms Encountered in Infected Root Canals. (In press.) Gruhzit, 0. M., Fisher, R. A:, Reutner, T. F., and Martino, E.: Chloramphenicol (Chloromycetin), an AntibiotIc. Pharmacological and Pathological Studies in :lnimals, J. Clin. Investigation 28: 943, 1949. Bender. I. B.. and Seltzer. 5.: The Use of Penicillin-StreDtom\-cin in the Treatment of Iniected’ Pulpless Tekth, ORAL SURG., ORAL MED., AND ORAL PATH. 3: 1070, 1950. Harris. H. .J.: Aureomvcin and Chloramphenicol in Brucellosis. J. A. M. A. 142:
9. Seltzer, 10. 11. 12. 13,
181,
3950.
14. Foley,
G. E., and Winter, W. D., Jr.: increased Mortality Following Penicillin of Chick Embryos Infected With (!andida Albicarrs T’ar. Stellatoidea. Dis. 85: 268, 1949. 15. Ehrlich, J.: Stability of (‘hlorom,vcetill. c Prrsonal c~ortlmullic:ltjor1.‘, 2035
SI’RGCE
1551
CHAIVIPLOST
ST. ST.
Therap) ,J. Infect.