A clinical study of terramycin in dentistry

Oral A CLINICAL JULIUS

STUDY

Medicine

OF TERRAMYCIN

SCHAFFER,

D.D.S.,**

IN DENTISTRY”

NEW YORK, N. Y.

are an established and valuable adjunct to the practice of NTIBIOTICS dentistry. The oral cavity, as approachable as the skin, has, like the skin, been exposed to a veritable barrage of antibiotic agents. Of these, penicillin, aureomycin, and terramycin deserve the greatest consideration at present because they are effective against almost all the pathogens of the mouth. Oral infections still develop which do not respond t.o penicillin, aureomycin, or terramycin. They give emphasis to the need for laboratory study and culture as soon as resistance is encountered. Penicillin, because of its historical precedence and proved efficacy, is at present the antibiotic of choice. The appearance of resistant strains of bacteria, of toxic reactions and sensitization of patients, has accentuated the importance of the newer broad-spectrum antibiotics. The great advantage of aureomycin and terramycin is that they can and should he given by mouth (the intramuscular injection is painful, and phlebitis may follow its intravenous use). They have a wide application in the treatment of infections caused by both gram-positive and gram-negative bacteria, as well as many of the spiroehetal, rickettsial, and protozoan infections. The unfavorable results following the use of the broad-specbrum antibiotics are nausea, vomiting, and diarrhea. The incidences of these side reactions are less after the ingestion of terramycin than aureomycin. The disappearance of the dominant bacterial strains may leave the resistant yeasts, Candida and Micrococci, as the principal contaminants. The use of antibiotics in dental procedures is justified by experience in its empiric use, and an extensive bibliography of case reports. The proper evaluation of antibiotic preparations in the mouth must await an adequately controlled series. This formidable task is yet to be performed. The purpose of the present report is to present the clinical results obtained with terramycin.

A

Methods of Study A clinical study of terramycin, used in a routine manner as the antibiotic of choice whenever and wherever indicated, was made at a municipal hospital.+ Before the study began, whenever an antibiotic was needed, penicillin was administered intramuscularly in adequate therapeutic dosages. During *A study made by the Dental Department of Sydenlmm Hospital: all terramycin hydrochloride used in this experiment wa.? given by Chas. Pfizer & Co., Inc., Brooklyn, N. y. **Associate Visiting Dentist, Sydenham Hospital. TSydenham Hospital. 965

966

JIJIms

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the period of this Andy (approximately six mont,hs) all patients appearing for dental treatment who neetleti antibiotic t,heraI)y were given terrnnlycin as the antibiotic of choice. PaGents received oral preparations of terramycin for a total of 1.5 to 23 grams a day. The average length of oral treatment was 2.66 (lays. The typical dosage was 250 mg. every three hours. A series of 120 I)atirnts was recorded and analyzed. They I)resentetl t,hemselves for treatment, of 17 different clinical conditions. In the opinion of the various clinicians who treated the individual paGents, 99 or X2.5 per cent of the patients responded “e~elleut’~ to the therapy; 18 or 15 l)er cent were considered a “ good ” resl)onse ; and Z or 2.5 per cent of the patients responded Clpoor” to terramycin. The total number of patients analyzed was divided into 61 (50.9 per cent) fernales and 59 (49.1 per cent) males. Of the nine patients with side reactions. six (66.6 per cent) were female.

Findings No sensitivity to terramycin in any form was reported. toward side reactions reported in ninr, or 7.5 per cent of the patients reported more than one side effect. d breakdown of follows : Nausea Diarrhea Dry socket, Dizziness Interference with healing (reported terramycin with interference tion of a normal riot “)

as (‘clumping with the forma-

of

There were un120 cases. Two these symptoms 1 4 1 1 1

The nausea and diarrhea were encountered in those cases where the antibiotic was given orally. When the drug was given with cold milk, the diarrhea and nausea were controlled. Excellent (although empiric) results have been reported with the administration of a. teaspoonful of Coca-Cola syrup. Of the nine cases with side reactions, two patients reported a previous sensitivity to penicillin. One other patient who was given terramycin at the hospital, and had side effects, was given penicillin by a private physician concurrently. In the one case where healing was interfered with, the contents of a 250 mg. capsule had been dusted into the socket. This procedure in itself does not explain the poor healing; rnany clinicians reported doing the same thing with excellent or good results. Definite incompatibility exists between penicillin and terramycin. They should not be given together. Good principles in using antibiotics are to strike fast and hard, giving high therapeutic dosages. If there has been no favorable clinical response after thirty-six to forty-eight hours the type of antibiotic should then be changed. Terramycin is available to the dentist in a variety of forms. For topical use there are dental cones, dental ointment, troches, and soluble tablets. In addition, capsules of crystalline terramycin hydrochloride and coated tablets

TF,RRANYCIN

IN

DENTISTRY

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of terramycin (amphoteric ) were suspension of crystalline t~t~I~illtl~~~itl used effectively wit,h chiltlrcn. TABIS

I I.

T~:KR.\MY(‘IK

I~IAONOS18 Gingivectomy Vincent ‘5 infection Extractions, surgical Impactions Periodontitis Herpes simplex Pericoronitis Traumatic injury Periostitis It-ith atwess formation Pulpotomy Frenotomy Cysts: radicular and follicular Alveoleetomy Apicoectomy Fracture: maxillary and mandibular Oral-antral fistula Ranula -_____Total

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INB~E(-~IOI\.S. A IielwKT ON 120 (‘“LSES IL --~~--~~-~ Tl VI’AI 1 1 rmClcr.r,EST 1 WOT) 1 1 1 2 1 1 2.5 21 4 11 0 I R :i 12 1 I 4 1 $1 2 z 2.3 5 “H 16 16 1 I 2 4 1 2 2 t’ a 3 3 2 2 I I ~~~ 99 18 139 -____.

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Terramycin cones were used in over sis huntlrrd sockets after the extraction of teeth. Because these patients normally (10not, and (lid not, return for observation, they were not included as part of this report. The failure to ret,urn may be considered an indication of the low toxicity and generally good tolerance to the local application of this antibiotic. How much good was done by placing one or inore 5 mg. cones of an antibiotic in a postextraction wount1 is not known. We do know that the pIacement of the terramycin cones did not cause untoward sequelae. The impression of the dental staff was t,hat the incidence of osteit,is was materially lessened. Terramycin ointment and powder were used on dressings in postoperative wounds of the mouth. The lanolin and petrolatum base of the ointm’ent seemed to prevent the rapid loss of the antibiotic in the Auicl of the mouth. The antibiotic dressing was clinically observetl to be cleaner and with less fetid odor after the usual intervals of use. The sugar-coated terramycin pills were considered more palatable than the cupsuJes, by those patients given the opportunity to judge. In pulpotomy there are certain reyuisite procedures that are assumed: the use of rubber dam, iI sterile field, sterile instt~unlentatioll, calcium hydroxide covering the pulp stumps, ant1 a rigid, ~~oncompressil~lrcement covering the calcium hydroxide. This technique is rather standard, and in the hands of most operators results in a high percentage of functiona,lly healthy teeth. Tt was postulatctl that the addition of terramycin to the calcium hydroxide could be useful in controlling ilny lmlpal l)acteremias caused by contamination or caries. In practice, terramycin hydrochloride (intravenous), which has no starch filler, is crystalline, and sterile, is mixed half and half with sterile calcium hydroxide powder. The resultant bright yellow powder is mised with sterile

TERRAMYCIN

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969

DENTISTRY

distilled water to make a paste which is used as the pulp covering material. Over this paste, which is dehydrated with sterile cotton pellets, an oxyphosphate cement filling is flowed and allowed to harden. The final filling can be inserted over the hardened cement at once. TABLE

III.

TEKRAMYCIN

IN

ORAL

IKFECTIOKS. NIJMBER

DIAGNOSIS

Gingivectomy Vincent’s infection Extractions, surgical Impactions Periodontitis Herpes simplex Pericoronitis Traumatic injury Periostitis with abscess formation Frenotomy cysts : radicular and f ollicular Alveolectomy Apicoectomy Fractures : mandibular and maxillary Oral-antral fistula Ranula Percentage Total

1

1

2

1

3

A REPORT OF

/

4

ON 120

TREATMEKT (

5

CASES

DAYS 1

6

1

7

~ RETURN

1 16 6 5

3 1

1 2

1 4 3 3 1 3

1 2 2 2

1 1 2

6

11

8 1

1

2

1

1

1

1

1

2

2 2 1 38.5 40

1 3.9 4

1 28.8 30

13.4 14

5.8 6

0 0

5.8 6

3.8 4

In the sixteen cases of pulpotomy recorded in our study, the results to date have been uniformly good. It was noted that the post,operative soreness and sensitivity that occasionally occurred were absent. Without histologic evidence it can only be assumed that there was a marked lessening of inflammation, edema, and resultant pericementitis.

Proper Administration

Is Vital

Other things being equal, the clinician who has the better knowledge of the various methods of drug administration will be more successful in the use of antibiotics. For, not only what antibiotic is given, but also how it is given, may determine the difference between success and failure. Simply, it might be said that we have the choice of utilizing drugs of local action (action at the site of application), systemic action (internal or general action which occurs after absorption), and the combination of these two. When a topical antibiotic such as a troche is prescribed, the absorptive ability of the mucous membranes of the mouth and tongue (especially the sublingual area) should be appreciated. Pantus quotes Paulson that the “sublingual space offers a more direct entry into the general circulation than It is erroneous to expect an antibiotic to act locally withdoes the stomach.” Conversely, it out some absorption and subsequent blood stream circulation. is to be expected that the systemically administered antibiotics will act locally t.hrough the salivary secretions.

970

JCLIUS

SCHAFFER

otolaryngologists and dentists iver(I font1 of prescribing Ix~nicillin trochrs ant1 lozenges. This ernpiricaal ant1 fr~ly used form of penicillin proved to have serious limitat,ions : local allergic reactions. tlc\~elopmcnt of resistant strains. ant1 possible sensitization of the intlivitlual to future parentera atlminist~ration of penicillin. ‘I’hlll,tc

Gingivectomy Vincent’s infection Extractions, surgical Impactions Prriodontitis Herpes simplex Pericorouitis Traumatic iu,jury Periostitis Pulpotomy E’renotomy C#S Alvrolrt~tomy Apicoectomy Fractures Oral-xntral fistulx Hanula Total

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41

2.5

8

2

3

37

3

16

1

11

(‘ross-resistance refers to the increased acquired microbial resistance to an antibiotic which is accompanied by a decreased sensitivity to another related agent.l, ’ For example, organisms developing resistance to aureomycin. chloramphenicol, or terramycin in general show a simult,aneous increased resistance to the other two antibiotics. The investigative work on cross-resist,ance has been in vitro. “Should the effects also apply in viva, the possibility of developing cross resistance with a subsequent lessening of the efficiency of a.ntibiotic therapy should be a deterrent to the indiscriminat,e use of antibiotics, particularly those that readily give rise to resista.nce. “* There is no indication of cross-resistance between the I~t~oatl-spect,~unl In fact, organisms resistant antibiotics and dihydrostreptornycin or penicillin. to penicillin or streptomycin seem to show a simultaneous increased sensitivity to terramycin, chloramphenicol. and aureomycin.

Complications

That May Arise

The lesions that may occur on one or more of the mucous surfaces of the body can be produced by, or may become infected with, yeastlike organisms,

TERRAMPCIN

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of which Monilia are the commonest,. Lesions of the mucous membranes may sometimes be due to vitamin B complex deficiencies when the newer antibiotics are being administered. There is no evidence that the administration of the broad-spectrum antibiotics either retards or inhibits the absorption of vitamins from ingested foods, or from capsules and tablets of such vitamins administered by the oral route. The suppression of growth, or death of the susceptible normally growing bacteria in the colon, mouth, and pharynx, results from the administration of the broad-spectrum antibiotics.‘2 When this occurs, organisms which are resistant to the bacteriostatic, or bactericidal, actions of these antibiotics replace the normal flora, causing pronounced changes in the bacterial metabolism. This accounts for the disturbances so frequently noticed in the stools and the elimination habits of pat)ients who are receiving the newer antibiotics in appreciable dosages. There is evidence accumulating to support the administration by mouth of the supplementary vitamins (especially the B complex) to all patients who are receiving two grams or more of the broad-spectrum antibiotics for a period of five or more days. Patients receiving such doses of t,hese antibiotics frequently do not have a normal vitamin intake because of anorexia due to nausea. There have been conflicting reports in the literature as to the effect of terramycin on blood clotting. The belief that antibiotic therapy encourages thromboembolism is rather widespread. Miller and Bass,” on the other hand, in a clinical and laboratory study of the effect of antibiotic drugs on the clotting mechanism, failed to show any coagulative effect produced by the antibiotic drugs. The production of vitamin K, however, is largely dependent on the action of the bacterial flora of the intestinal tract. Vitamin K is necessary for the coagulation of blood and is a buffer against the coumarin compounds used in anticoagulant therapy. “Pending confirmation or clarification of the observations regarding these gut sterilizing antibiotics, they should be administered with caution when the patient is receiving anti-coagulant therapy which interfcrcs with prothrombin production. “U In April, 1951, the Council on Pharmacy and Chemistry of the American Medical Association’ requested that a warning statement be added to the labeling of aureomycin hydrochloride, chlorarnphenicol, and terramycin hydrochloride. The warning was to the effect that, while these antibiotics are highly bacteriostatic for many bacteria, they may cause suppression of suscrpt,ible bacteria and thus encourage the replacement by Monilia and other yeastlike organisms of the normal and abnormal flora. Kligman” states that the side reactions of the broad-spectrum antibiotics may be associated with moniliasis; however, they may also be expressions of various diseases, such as vitamin deficiencies, allergic reactions, bacterial and viral infections, and primary irritation. He insists that isolation of the organism is not always diagnostically decisive. In his experience, lesions that heal rapidly fail to become invaded by Candida albicans.7

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It. is interesting (ant1 ~)roves Ilothing) that of t.he cases stutliecl riot one case of moniliasis was reported. l\lith the atlIl~illixt~ation of the l)road-spect.rum antibiotics, the possibility of tllotiilial c~onll)li~;~tio~rs must IF thought of. If encounteretl, interrupt antihiotica treatnletlt. anal prescril)e an alkaline 111 the oral carity. lllotliliasis is not iI I)articulat~ly serious c.011. mouthwash. dition. TREATING

RESULTS EXTRACTIONS

OBTAINED

ISURGICAL)

IMPACTIONS

WITH

IN (25

(11 cases)

TERRAMYClN

TREATING

cases)

WITH

TERRAMYQN

PERIODONTITIS

(12

cases]

I

Conclusions On the basis of clinical experience in 120 patients, there is a definite place for terramycin in the dental materia me-dica. The oral route of administration is much preferred to the intramuscular route by the dentist as well as by the patient.

TERRAMYCIN

IN

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DENTISTRY

Penicillin should be given by intramuscular injection. Since it is not easily absorbed from the gastrointestinal tract, about five times the intramuscular dose has to be given when the oral route is used. The ease of administrat,ion, t,he lack of allergic reactions, the broader spectrum of activity, the relatively short time of therapeusis, and the proved effectiveness ma,ke the broad-spectrum antibiotic (terramycin) a most valuable adjunct to the dentist in private practice. References I. Council on Pharmacy and Chemistry: mvcin Chloramphenicol, J.-A. M. Hvtlrochloride, A. 145: 1267, 1951. -

Warning and

Statement

Terramycin

to Be Included Hydrochloride

in AureoLabeling, -.

2. Editorial, J. A. M. A. 148: 470-471, 1952. General Technic of Medication, Chicago, 1930, American Medical As3. Fantus. B.: so’ciation, p. 137. The Simultaneous Increase in Resistance of 4. Fusillo. M. H.. and Romanskr. M. J.: Bacteria to Aureomycin “and Terramycin Upon Exposure to Either Antibiotic, Antibiotics & Chemother. 1: 107, 1951. 5. Herrell, W. E., Heilman, F. R., and Wellman, W. E.: Some Bacteriologic, Pharmacologic, and Clinical Observations on Terramycin, Ann. New York Acad. SC. 53: 448, 1950. 6. Kligman, A. M.: Are Fungus Infections Increasing as a Result of Antibiotic Therapy9 J. A. M. A. 149: 979-983, 1952. 7. Lipnik, M. K.,, Kligman, A. M., and Strauss, R.: Antibiotics and Fungous Infections, J. Investigation Dermat. 18: 247-260, 1952. The Effect of Antibiotic Drugs on Blood Clotting: 8. Miller, M. A., and Bass, H. E.: Clinical Observations and Resume of Recent Literature. New York State J. Med. 52: 1423, 1952. Terramycin and Aureomycin in Surgical Infections, 9. Pulaski, E. J., and Reiss, E.: J. A. M. A. 149: 35-40, 1952. Serum Sickness From Penicillin, Arch, Dermat. & Syph. 65: 727-730, 10. Riley, K. A.: 1952.

11. Tzanck,

A., Sidi, E., and Gautard, J.: Risks of External Application of Penicillin, Presse med. 50: 713, 1951. 12. Willcox, R. R.: Anorectal Syndrome and Other Mild Side-Effects of Terramycin, Lancet 2: 154, 1951. 13. Wright, I. S.: The Pathogenesis and Treatment of Thrombosis, Circulation, February, 1952.