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Bacitracin in local treatment of pyogenic infections
C o m m e n t s on Current Literature B A C I T R A C I N IN L O C A L T R E A T M E N T OF P Y O G E N I C I N F E C T I O N S B A C I T R A C I N , a chemotherapeutic substance isolated from a sporulating bacillus of tile Bacillus subtilis group, 1 was identified as a diffusable polypeptide possessing' antibiotic activity against a variety of grmn-positive bacteria and against spirochetes. E a r l y experimental studies in animals showed that bacitracin is absorbed slowly and that it is excreted by glomerular filtration. Its therapeutic potentialities seemed favorable. F u r t h e r investigations, however, revealed that renal lesions were produced in animals where large doses were administered. Since these toxic renal manifestations were not correlated with the antibacterial potency of different sampJes of. bacitracin, it seemed likely that the toxicity might be due to impurities, and f u r t h e r efforts were made to refine the substance. In human subjects cautious clinical trials with baeitracin administered systemically gave reasonably good therapeutic results, but here again transient albuminuria and other signs of. nephrotoxieity dampened enthusiasm for its general use, particularly in view of the fact that penicillin and bacitracin have an antibacterial spectrum which is ahnost identical. However, safe, effective agents for local t h e r a p y in pyogenie infections of the skin constitute a real need, and for this purpose baeitracin is proving particularly suitable. Meleney and Johnson 2 in 1947 reported favorable results with bacitraein in the topical treatment of 100 eases of surgical inf.ection, ineluding a variety of. types. Solutions or ointments containing 10 to 100 units of bacitracin per milliliter were used. Eighty-eight per cent of these infections responded to treatment, even when some of the gram-positive organisms isolated from the area were shown by culture studies to be penicillin-resistant streptococci or staphylococci. More recently Mi]ler, Slatkin, and Johnson a have reported the results of a careful evaluation of. baeitracin in local treatment of pyogenic infections. Various base preparations were used as ointments, containing varying concentrations of bacitracin. In the laboratory and elinieaI appraisal of these preparations three features were considered: the physical properties of the base preparation, the stability of the antibiotic when incorporated in the ointment, and the release of the bacitraein content. Of fourteen ointment bases tried, three were definitely superior : Carbowax 1540 50 Gin. Base No. 2 Carbowax Carbowax
Base No. 8
Base No. 10
200 4000
50 Gin. 25 Gm.
Cetyl aleehol Glycerin Sodium lauryl sulfate Distilled water Lanette wax White petrolatum U.S.P. Liquid petrolatmn U.S.P. Distilled water
10 Gin. 10 Gin. 1 Gm. 74: e.e. 20 Gin. 20 Gin. 30 e.e. 30 e.e.
Bacitracin was added to each ointment base, 500 units per gram being incorporated in some samples and 1,000 units in others. The ointments remained stable and therapeutically effective for at least two weeks without refrigeration. B y laboratory tests oil-in water and greaseless carbowax bases were found best for stability and for release of bacitracin. 790
COMMENTS
ON
CURRENT
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Tilt m a j o r i t y of the patients studied were seen in the Outpatient Clinie. i n all eases bacteriaI cultures of the lesions were taken before t r e a t m e n t in order to identify the causative organism and test its sensitivity to baeitracin. Of sixty-eight patients treated for p r i m a r y superficial skin infections, fifty responded favorably. I n eighteen patients, eleven of whom had follieulitis of the beard, the therapeutic response was unsatisfactory. However, in six of these so-called failures, a]l of whom had follieulitis of the beard, the infection was kept u n d e r control and the area free of lesions so long as the ointment was used daily. ~rhe remaining seven instances of failure included one ease of infectious eezematoid dermatitis, three eases of vesieulopustular eruption of the bands, one folliculitis elsewhere t h a n of the beard, and two eases of perifollieulitis capitis. A n o t h e r group included in this o u t p a t i e n t study comprised patients with dermatoses complicated by seeondary bacterial infection. While the secondary bacterial infection was cured in this group, baeitraein ointments were of no value against the p r i m a r y dermatoses. No better clinical results were obtained in any of the eases with ointments containing 1,000 units of antibiotic p e r g r a m than with those containing 500 units per gram. On the basis of their experience the authors conclude that baeitraein is an effeetive agent f o r local t h e r a p y in pyogenie infections of the skin. I t s effectiveness approximates that of penicillin, the sulfonamide drugs, a n d n i t r o f u r a zone, and its real s u p e r i o r i t y consists in the low rate of sensitization of the patient, one-half of one per cent sensitization being recorded thus far. This situation is in contrast 'to the findings with penicillin where 6 per cent of patients were sensitized, and with sulfonamides and nitrofurazone, where 5 per cent were sensitized to the drugs. No cutaneous reactions to bacitraein have been reported. I n one patient this antibiotic in ointment form was applied daily for 300 days with no evidence of cutaneous sensitization. While baeitracin is toxic when administered parenterally, this is not the case a p p a r e n t l y when it is used as a local therapeutie agent, even where the ointment is applied over widespread areas of the body surface. I f more evidence is added t h a t such is the case and that sensitization ott prolonged use is minimal, the advantages of local bacitraein are obvious. W h e r e patients develop sensitization to other agents such as penieil]in and sulfa drugs, and p a r t i c u l a r l y where the causative organisms become resistant to these medications, bacitraein may be of considerable importance in the local t h e r a p y of skin infections. ~USSELL g. BLATTNER. REFERENCES
1. Johnson, B. A., Anker, tI., and Meleney, ~P. I~.: A New Antibiotic Produced by a Member of the B. subtilix Group~ Science 102: 376, 1945. 2. Meleney, IF. I,., and Johnson, 13. A.: Baeitraein Therapy: rl?'he J~irst Hundred Cases of Surgical Infections Treated Locally With the Antibiotic, J..A.M.A. 133: 675, 1947. 3. Miller~ & L.~ Slatkln, IVI. It, and .Johnson, ]3. A. : Evaluation of t)aeitraeln in Local Treatment of Pyogenie Infeetions~ Arch. Dermato and Syph. 60: 106, 194-9o
CHARLES ANDERSON A1.DRICH 1888--1949
Base No. 8
Base No. 10
200 4000
50 Gin. 25 Gm.
Cetyl aleehol Glycerin Sodium lauryl sulfate Distilled water Lanette wax White petrolatum U.S.P. Liquid petrolatmn U.S.P. Distilled water
10 Gin. 10 Gin. 1 Gm. 74: e.e. 20 Gin. 20 Gin. 30 e.e. 30 e.e.
Bacitracin was added to each ointment base, 500 units per gram being incorporated in some samples and 1,000 units in others. The ointments remained stable and therapeutically effective for at least two weeks without refrigeration. B y laboratory tests oil-in water and greaseless carbowax bases were found best for stability and for release of bacitracin. 790
COMMENTS
ON
CURRENT
LITEI~ATUIgE
~91
Tilt m a j o r i t y of the patients studied were seen in the Outpatient Clinie. i n all eases bacteriaI cultures of the lesions were taken before t r e a t m e n t in order to identify the causative organism and test its sensitivity to baeitracin. Of sixty-eight patients treated for p r i m a r y superficial skin infections, fifty responded favorably. I n eighteen patients, eleven of whom had follieulitis of the beard, the therapeutic response was unsatisfactory. However, in six of these so-called failures, a]l of whom had follieulitis of the beard, the infection was kept u n d e r control and the area free of lesions so long as the ointment was used daily. ~rhe remaining seven instances of failure included one ease of infectious eezematoid dermatitis, three eases of vesieulopustular eruption of the bands, one folliculitis elsewhere t h a n of the beard, and two eases of perifollieulitis capitis. A n o t h e r group included in this o u t p a t i e n t study comprised patients with dermatoses complicated by seeondary bacterial infection. While the secondary bacterial infection was cured in this group, baeitraein ointments were of no value against the p r i m a r y dermatoses. No better clinical results were obtained in any of the eases with ointments containing 1,000 units of antibiotic p e r g r a m than with those containing 500 units per gram. On the basis of their experience the authors conclude that baeitraein is an effeetive agent f o r local t h e r a p y in pyogenie infections of the skin. I t s effectiveness approximates that of penicillin, the sulfonamide drugs, a n d n i t r o f u r a zone, and its real s u p e r i o r i t y consists in the low rate of sensitization of the patient, one-half of one per cent sensitization being recorded thus far. This situation is in contrast 'to the findings with penicillin where 6 per cent of patients were sensitized, and with sulfonamides and nitrofurazone, where 5 per cent were sensitized to the drugs. No cutaneous reactions to bacitraein have been reported. I n one patient this antibiotic in ointment form was applied daily for 300 days with no evidence of cutaneous sensitization. While baeitracin is toxic when administered parenterally, this is not the case a p p a r e n t l y when it is used as a local therapeutie agent, even where the ointment is applied over widespread areas of the body surface. I f more evidence is added t h a t such is the case and that sensitization ott prolonged use is minimal, the advantages of local bacitraein are obvious. W h e r e patients develop sensitization to other agents such as penieil]in and sulfa drugs, and p a r t i c u l a r l y where the causative organisms become resistant to these medications, bacitraein may be of considerable importance in the local t h e r a p y of skin infections. ~USSELL g. BLATTNER. REFERENCES
1. Johnson, B. A., Anker, tI., and Meleney, ~P. I~.: A New Antibiotic Produced by a Member of the B. subtilix Group~ Science 102: 376, 1945. 2. Meleney, IF. I,., and Johnson, 13. A.: Baeitraein Therapy: rl?'he J~irst Hundred Cases of Surgical Infections Treated Locally With the Antibiotic, J..A.M.A. 133: 675, 1947. 3. Miller~ & L.~ Slatkln, IVI. It, and .Johnson, ]3. A. : Evaluation of t)aeitraeln in Local Treatment of Pyogenie Infeetions~ Arch. Dermato and Syph. 60: 106, 194-9o
CHARLES ANDERSON A1.DRICH 1888--1949