ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Sept. 1978, p. 498-499 0066-4804/78/0014-0498$02.00/0 Copyright i 1978 American Society for Microbiology
Vol. 14, No. 3 Printed in U.S.A.
Penetration of Clindamycin into Decubitus Ulcers STEPHEN A. BERGER,`* MICHAEL BARZA,2 JANE HAHER,' JAMES J. McFARLAND,' SAMUEL LOUIE, AND ANNE KANE2 Departments ofMedicine and Surgery, The New York Medical College, New York, New York 10029,1 and Department of Medicine, Tufts-New England Medical Center, Boston, Massachusetts 021112 Received for publication 25 April 1978
Forty tissue samples, primarily of skin and bone, were obtained from 29 patients undergoing excision of decubitus ulcers after intravenous injection of 600 mg of clindamycin. Antibiotic concentrations exceeded 2.5 ,ug/g in 80% of the samples. In 50% of the instances, tissue levels were greater than those simultaneously present in the serum.
Clindamycin is currently advocated for the prophylaxis and therapy of infections caused by a variety of anaerobic bacteria (2). Recent studies have implicated such organisms in the etiology of infection associated with decubitus ulcers
rable seeded agar plates by using clindamycin standards prepared in normal human serum. Forty samples were obtained from 29 patients. Six patients, all female, had diabetes mellitus, and the remaining subjects had developed decubiti in the setting of severe neurological disease. Of 29 decubiti, 24 were located over the pelvis or perineum, and 5 were on the lower leg. Tissues were obtained from 30 to 90 min after the administration of clindamycin (Table 1). Antibiotic levels ranged from 2.6 to 24.5 ,ug/g of tissue but were undetectable in eight instances (seven specimens of skin, one of muscle). The levels of antibiotic in two samples of muscle and in two offat and fascia exceeded the concomitant concentrations in serum. Tissue levels exceeded those of serum in 16/32 (50%) instances. For samples in which activity was detectable, the mean and standard error of the ratio of clindamycin in tissue/serum x 100 was 106 ± 19 for skin (23 specimens) and 116 ± 30 for bone (5 specimens). Neither tissue level nor the ratio of tissue to serum level correlated with the patient's age or sex, presence of diabetes mellitus, anatomic location of decubitus, or time elapsed after antibiotic administration. The etiology of decubiti is complex, involving such factors as hypesthesia, trauma, inappropriate local autonomic activity, ischemia, and stasis. Although infection may result from or produce local tissue death, antibiotic therapy does not appear to alter the progression of decubiti or decubitus related sepsis unless debridement is performed (1, 3). Perioperative antibiotic prophylaxis is indicated for "contaminated" or "dirty" surgical procedures. The microbial flora of decubitus ulcers includes such species as Bacteroides fragilis and aerobic or anaerobic gram-positive cocci (1). As such, it is significant that therapeutic local levels
(1,3).
Because it has been the practice at the New York Medical College to administer prophylactic clindamycin to patients before excision of decubiti, a study was undertaken to determine local tissue levels of this antibiotic. Informed consent was obtained from 13 female and 16 male patients ranging in age from 18 to 88 years. None of these subjects had a history of clindamycin allergy; all had blood urea nitrogen and serum bilirubin concentrations within the normal range. Before surgery, each patient received a single intravenous infusion of clindamycin phosphate (Upjohn Co., Kalamazoo, Mich.), 600 mg over 10 min. Local anesthesia was not used. Samples of tissue and serum were obtained simultaneously and frozen at -20°C. The time between antibiotic administration and debridement was recorded, as was the nature and location of decubiti. Segments of necrotic tissue were rinsed briefly in physiological saline, dabbed dry, minced, and weighed in sterile vials. Collagenase solution (Sigma Corporation, 1,000 U/ml of Michaelis barbital buffer with 5 mM CaCl2, pH 7.4) was added to each vial to produce a 20% digest suspension. Clindamycin standards (range, 1.6 to 100,ug/ml) were prepared in collagenase solution, and each mixture was incubated overnight at 370C. After vigorous agitation, tissue digests were assayed by a standard agar diffusion bioassay with Trypticase soy agar plates seeded with a 6-h culture of Staphylococcus aureus ATCC 25923. Serum samples were bioassayed on compa498
NOTES
VOL. 14, 1978
499
TABLE 1. Concentration of clindamycin in tissues and simultaneous serum specimen Time between clindamycin adminnistration and debridement (min)
7 8
30 30 30 35 35 45 45 45
9 10 11
45 45 45
1 2 3
4 5 6
12 13 14 15 16 17 18 19 20 21
50 50 50 50 50 55 55 55 55 60
22
60
23
60
24
60
25 26
65 75
27
80
28 29
85 90
Tissue analyzed
Skin Skin Skin Skin Skin Skin Skin Skin Muscle Skin Skin Skin Muscle Bone Skin Skin Skin Skin Skin Skin Skin Skin Skin Skin Fascia and fat Skin Skin Bone Skin Muscle Bone Skin Bone Skin Skin Fascia and fat Skin Bone Skin Skin
of clindamycin were achievable in 80% of the tissue samples after a single intravenous dose. It is possible that some portion of the antibiotic activity observed in these specimens represents clindamycin from viable tissue or exudate surrounding the decubitus itself. Nevertheless, such local antibiotic levels have similar significance in the prophylaxis and treatment of infection associated with decubiti.
Tissue antibiotic level (pg/g)
Serum antibiotic level
20.2 4.2 7.0 13.8 11.7 24.0
Vol. 14, No. 3 Printed in U.S.A.
Penetration of Clindamycin into Decubitus Ulcers STEPHEN A. BERGER,`* MICHAEL BARZA,2 JANE HAHER,' JAMES J. McFARLAND,' SAMUEL LOUIE, AND ANNE KANE2 Departments ofMedicine and Surgery, The New York Medical College, New York, New York 10029,1 and Department of Medicine, Tufts-New England Medical Center, Boston, Massachusetts 021112 Received for publication 25 April 1978
Forty tissue samples, primarily of skin and bone, were obtained from 29 patients undergoing excision of decubitus ulcers after intravenous injection of 600 mg of clindamycin. Antibiotic concentrations exceeded 2.5 ,ug/g in 80% of the samples. In 50% of the instances, tissue levels were greater than those simultaneously present in the serum.
Clindamycin is currently advocated for the prophylaxis and therapy of infections caused by a variety of anaerobic bacteria (2). Recent studies have implicated such organisms in the etiology of infection associated with decubitus ulcers
rable seeded agar plates by using clindamycin standards prepared in normal human serum. Forty samples were obtained from 29 patients. Six patients, all female, had diabetes mellitus, and the remaining subjects had developed decubiti in the setting of severe neurological disease. Of 29 decubiti, 24 were located over the pelvis or perineum, and 5 were on the lower leg. Tissues were obtained from 30 to 90 min after the administration of clindamycin (Table 1). Antibiotic levels ranged from 2.6 to 24.5 ,ug/g of tissue but were undetectable in eight instances (seven specimens of skin, one of muscle). The levels of antibiotic in two samples of muscle and in two offat and fascia exceeded the concomitant concentrations in serum. Tissue levels exceeded those of serum in 16/32 (50%) instances. For samples in which activity was detectable, the mean and standard error of the ratio of clindamycin in tissue/serum x 100 was 106 ± 19 for skin (23 specimens) and 116 ± 30 for bone (5 specimens). Neither tissue level nor the ratio of tissue to serum level correlated with the patient's age or sex, presence of diabetes mellitus, anatomic location of decubitus, or time elapsed after antibiotic administration. The etiology of decubiti is complex, involving such factors as hypesthesia, trauma, inappropriate local autonomic activity, ischemia, and stasis. Although infection may result from or produce local tissue death, antibiotic therapy does not appear to alter the progression of decubiti or decubitus related sepsis unless debridement is performed (1, 3). Perioperative antibiotic prophylaxis is indicated for "contaminated" or "dirty" surgical procedures. The microbial flora of decubitus ulcers includes such species as Bacteroides fragilis and aerobic or anaerobic gram-positive cocci (1). As such, it is significant that therapeutic local levels
(1,3).
Because it has been the practice at the New York Medical College to administer prophylactic clindamycin to patients before excision of decubiti, a study was undertaken to determine local tissue levels of this antibiotic. Informed consent was obtained from 13 female and 16 male patients ranging in age from 18 to 88 years. None of these subjects had a history of clindamycin allergy; all had blood urea nitrogen and serum bilirubin concentrations within the normal range. Before surgery, each patient received a single intravenous infusion of clindamycin phosphate (Upjohn Co., Kalamazoo, Mich.), 600 mg over 10 min. Local anesthesia was not used. Samples of tissue and serum were obtained simultaneously and frozen at -20°C. The time between antibiotic administration and debridement was recorded, as was the nature and location of decubiti. Segments of necrotic tissue were rinsed briefly in physiological saline, dabbed dry, minced, and weighed in sterile vials. Collagenase solution (Sigma Corporation, 1,000 U/ml of Michaelis barbital buffer with 5 mM CaCl2, pH 7.4) was added to each vial to produce a 20% digest suspension. Clindamycin standards (range, 1.6 to 100,ug/ml) were prepared in collagenase solution, and each mixture was incubated overnight at 370C. After vigorous agitation, tissue digests were assayed by a standard agar diffusion bioassay with Trypticase soy agar plates seeded with a 6-h culture of Staphylococcus aureus ATCC 25923. Serum samples were bioassayed on compa498
NOTES
VOL. 14, 1978
499
TABLE 1. Concentration of clindamycin in tissues and simultaneous serum specimen Time between clindamycin adminnistration and debridement (min)
7 8
30 30 30 35 35 45 45 45
9 10 11
45 45 45
1 2 3
4 5 6
12 13 14 15 16 17 18 19 20 21
50 50 50 50 50 55 55 55 55 60
22
60
23
60
24
60
25 26
65 75
27
80
28 29
85 90
Tissue analyzed
Skin Skin Skin Skin Skin Skin Skin Skin Muscle Skin Skin Skin Muscle Bone Skin Skin Skin Skin Skin Skin Skin Skin Skin Skin Fascia and fat Skin Skin Bone Skin Muscle Bone Skin Bone Skin Skin Fascia and fat Skin Bone Skin Skin
of clindamycin were achievable in 80% of the tissue samples after a single intravenous dose. It is possible that some portion of the antibiotic activity observed in these specimens represents clindamycin from viable tissue or exudate surrounding the decubitus itself. Nevertheless, such local antibiotic levels have similar significance in the prophylaxis and treatment of infection associated with decubiti.
Tissue antibiotic level (pg/g)
Serum antibiotic level
20.2 4.2 7.0 13.8 11.7 24.0
