Journal of Antimicrobial Chemotherapy (1978) 4 (Suppl. B), 183-187
Surgical considerations in skin and soft-tissue infections and osteomyelitis treated with cefoxitin sodium
R. L. Perkins
Seven patients considered for surgical intervention were among 24 patients treated with cefoxitin sodium. Of the 7,4 had major bacterial abscesses and cellulitis of skin and soft tissue that required surgical drainage and debridement; bacteriologic cures were obtained in all 4. The other 3 patients were diabetic and had polymicrobic osteomyelitis of the feet with overlying or contiguous ulcerations with cellulitis, necessitating debridement in addition to cefoxitin therapy; all were cured clinically and bacteriologically without resort to amputation.
Introduction The management of major bacterial abscesses of skin-soft-tissues and of osteomyelitis, with or without associated cellulitis, often requires combined surgical and medical intervention. Certain newer antibacterial agents, such as cefoxitin sodium, a cephamycin, may offer significant advantages for the treatment of such lesions. The antibacterial spectrum of cefoxitin includes the aerobic Gram-positive coccal organisms commonly encountered, excepting enterococci, many aerobic Gram-negative bacilli, and other strains that may be relatively resistant to cephalothin. In addition, cefoxitin has significant activity in vitro against facultative and obligate anaerobic Gram-negative and Gram-positive organisms (Neu, 1974; Heseltine, Busch, Meyer & Finegold, 1977). Thus, in skin and soft-tissue lesions or in osteomyelitis, when a surgical procedure is required or contemplated, cefoxitin may, as a single agent, provide adequate antibacterial coverage and, along with proper supportive care, minimize the nature and extent of the surgery.
Patients and methods Twenty-four patients admitted to The Ohio State University Hospitals with acute skinsoft-tissue, bone, or respiratory infections caused by organisms known or suspected to be sensitive to cefoxitin were entered into the study. Seven of the patients had serious skinsoft tissue infections or osteomyelitis and are the subject of this report. Informed consent with written permission was obtained in each case. Bacteriologic diagnoses were based on Gram stains and pretreatment cultures from infected tissues, fluid aspirates, exudates, or bone biopsies. O3O5-7453/78/O7OI-B183 $01.00/0
183 © (1978) The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 26, 2015
Division of Infectious Diseases, Department of Medicine, The Ohio State University, Columbus, Ohio, U.S.A.
R . L . Perkins
184
Table I. Cefoxitin-treated patients with abscessesi requiring incision and drainage Infecting organisms
MIC Otg/ml)
Underlying disease
Abscess, labia
Peptococcus spp.
=*01
Diabetes mellitus Decreased IgA
Clinical and bacteriological
8
Abscess, scalp
Bacteroides fragHis Staphylococcus epidermidis Staph. aureus
Diabetes mellitus
13
Abscess, back
Peptococcus spp.
18
Abscess, leg
B. melaninogenicus Staph. aureus
Clinical and bacteriologic cure Clinical failure, bacteriologic cure Clinical and bacteriologic
Patient
no. 7
Lesion
Results
cure
0-2 20 4-0
Diabetes mellitus
not tested 0-2 Old trauma
cure Minimum inhibitory concentrations (MIC) of cefoxitin for aerobic and facultatively anaerobic isolates were determined by a micro-dilution procedure (Conrath, 1972), using 10B to 106 colony-forming units/ml as the final inoculum. The MIC of cefoxitin for each anaerobic isolate was determined by the method of Rotilie, Fass, Prior & Perkins (1975). Cefoxitin concentrations in sera and urine were determined by a disc-diffusion method utilizing Staphylococcus aureus B-2786e as the assay organism (Simon & Yin, 1970). Cefoxitin sodium, 1 to 2 g in 100 to 200 ml of 5 % dextrose solution, was given as a 30-min i.v. infusion every 4 to 6 h. Clinical monitoring and serial laboratory observations, including serial cultures before, during, and after therapy, complete blood counts, direct Coombs test, urinalysis, blood urea nitrogen, serum creatinine, aJkaline phosphatase, SGOT, SGPT, LDH, and serum electrolytes, were employed to determine responses to therapy and to detect any adverse reactions. Results
All 7 patients were initially considered for immediate surgical intervention. Four had major abscesses of skin and soft tissue, each associated with extensive cellulitis; 3 of the 4 had underlying diabetes mellitus, and the fourth had an earlier trauma and old surgical Figure 1. Plantar aspect of foot of Patient no. 24 on admission, showing marked necrosis of skin, vesiculation, and through-and-through suppuration. Figure 2. Initial ventral incision for debridement and decompression of wound. Figure 3. Initial dorsal incision for debridement and decompression of wound. Figure 4. Marked healing after 3 weeks of cefoxitin therapy. Figure 5. Dorsal wound almost closed after 42 days of cefoxitin therapy. Figure 6. Plantar wound almost closed after 42 days of cefoxitin therapy. Figure 7. X-rays of foot of Patient no. 24, (a) before, and (b) after cefoxitin therapy for 42 days, (a) Swelling of foot, gas in tissues, and bone destruction are evident (b) Note resolution of lesions, with small sequestrum still present at base of second raetatarsal.
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 26, 2015
32
scarring in the area of infection (Table I). Incision and drainage were necessary in each case. The infecting organisms obtained by culture of the drainage material included Sfaph. aureus in 2 patients and, primarily, mixed anaerobic flora in the other 2. The organisms proved susceptible to cefoxitin, and bacteriologic cures were obtained in all 4 cases. The remaining 3 patients had diabetes mellitus as well as osteomyelitis of the metatarsa! and tarsal bones; in each case, the infecting organisms included both aerobic and anaerobic bacteria (Table II). For all 3 patients, consultants considered surgical amputation of the foot a definite possibility. After being treated with cefoxitin 8 g/day, and undergoing minor, but repeated, debridement of overlying skin ulcerations, 2 patients (nos. 15 and 21) showed evidence of clinical and bacteriologic cures. The third patient (no. 24) had, in addition to diabetes and osteomyelitis, more massive soft-tissue involvement, marked necrosis of the skin, vesiculation, and through-and-through suppuration (Figure 1). A general surgical consultant recommended amputation below the knee. On the fifth day of cefoxitin therapy, however, an orthopedic consultant incised the foot on both dorsal and ventral aspects to debride and decompress the wound (Figures 2 and 3). After three weeks of cefoxitin therapy and further debridement the wounds showed marked healing (Figure 4). Cefoxitin therapy was continued for 42 days, and the wounds showed closure soon therafter (Figures 5 and 6). X-rays made before cefoxitin therapy showed marked swelling of the foot, with gas in the tissues and evidence of bone destruction; later X-rays showed resolution of the lesions, except for a small sequestrum at the base of the second metatarsal (Figure 7). The sequestrum was excised because it caused minor discomfort during walking. All tissue and bone samples were sterile on aerobic and anaerobic culture, nor was there any histologic evidence of osteomyelitis. The patient is now completely ambulatory and the wounds have healed. No significant adverse reactions were observed in the 7 patients, although mild transient eosinophilia occurred in 2 patients. Phlebitis did not occur in Patient no. 24, despite 42 days of intermittent i.v. therapy. Discussion Advanced, necrotizing skin-soft tissue infections or osteomyelitis in diabetic patients,
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 26, 2015
24
Osteomyelitis, foot
Infecting organisms
Soft-tissue and bone infections
187
Acknowledgements The author thanks Richard B. Prior, Ph.D., and Ms Beth Ann Bailey for expert technical assistance. This study was supported in part by a grant from Merck Sharp & Dohme Research Laboratories. References Conrath, T. B. Handbook of Microtitcr Procedures. Dynatech Corp., Cambridge, Mass. (1972), pp. 30-36. Heseltine, P. N. R., Busch, D. F., Meyer, R. D. & Finegold, S. M. Cefoxitin: Clinical evaluation in thirty-eight patients. Antimicrobial Agents and Chemotherapy 11: 427-34 (1977). McCloskey, R. V. Results of a clinical trial of cefoxitin, a new cephamycin antibiotic. Antimicrobial Agents and Chemotherapy 12: 636-41 (1977). Neu, H. C. Cefoxitin, a semisynthetic cephamycin antibiotic: antibacterial spectrum and resistance to hydrolysis by Gram-negative beta-lactamases. Antimicrobial Agents and Chemotherapy 6: 170-6(1974). Rotilie, C. A., Fass, R. J., Prior, R. B. & Perkins, R. L. Microdilution technique for antimicrobial susceptibility testing of anaerobic bacteria. Antimicrobial Agents and Chemotherapy 7: 311-5 (1975). Simon, H. J. & Yin, E. J. Microbioassay of antimicrobial agents. Applied Microbiology 19: 573-9 (1970).
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 26, 2015
especially when there is evidence of significant compromise of the local microcirculation, not infrequently leads abruptly to consideration of amputation. In some instances, questions of practicality and economics may unduly reinforce the temptation to resolve the problem quickly by resort to amputation. There is inadequate appreciation of the potential for salvaging such affected digits or extremities, in light of modern microbiologic techniques for identifying the infecting organisms. The combination of sophisticated culture methods and bacterial susceptibility tests, appropriately designed and adequately prolonged parenteral antimicrobial therapy, and meticulous daily minor debridement of wounds often leads to outstanding therapeutic results. Central to success in such cases is the existence of a potent, well-tolerated, effective antimicrobial agent, like cefoxitin in the present cases. A recent report indicates similar success with cefoxitin in infections caused by polymicrobic aerobic or anaerobic organisms (McCloskey, 1977). In summary, common abscesses of skin and soft tissues treated with cefoxitin sodium required classic drainage procedures to accelerate recovery and to achieve bacteriologic cures. In those cases of osteomyelitis of the small bones of the feet in which the extent of the lesions and the presence of polymicrobic infecting flora and underlying disease, such as diabetes mellitus, may suggest a need for amputation, aggressive treatment with a carefully selected, broad-spectrum agent, such as cefoxitin sodium, combined with meticulous debridement and local care, may salvage the digits or limbs.
Surgical considerations in skin and soft-tissue infections and osteomyelitis treated with cefoxitin sodium
R. L. Perkins
Seven patients considered for surgical intervention were among 24 patients treated with cefoxitin sodium. Of the 7,4 had major bacterial abscesses and cellulitis of skin and soft tissue that required surgical drainage and debridement; bacteriologic cures were obtained in all 4. The other 3 patients were diabetic and had polymicrobic osteomyelitis of the feet with overlying or contiguous ulcerations with cellulitis, necessitating debridement in addition to cefoxitin therapy; all were cured clinically and bacteriologically without resort to amputation.
Introduction The management of major bacterial abscesses of skin-soft-tissues and of osteomyelitis, with or without associated cellulitis, often requires combined surgical and medical intervention. Certain newer antibacterial agents, such as cefoxitin sodium, a cephamycin, may offer significant advantages for the treatment of such lesions. The antibacterial spectrum of cefoxitin includes the aerobic Gram-positive coccal organisms commonly encountered, excepting enterococci, many aerobic Gram-negative bacilli, and other strains that may be relatively resistant to cephalothin. In addition, cefoxitin has significant activity in vitro against facultative and obligate anaerobic Gram-negative and Gram-positive organisms (Neu, 1974; Heseltine, Busch, Meyer & Finegold, 1977). Thus, in skin and soft-tissue lesions or in osteomyelitis, when a surgical procedure is required or contemplated, cefoxitin may, as a single agent, provide adequate antibacterial coverage and, along with proper supportive care, minimize the nature and extent of the surgery.
Patients and methods Twenty-four patients admitted to The Ohio State University Hospitals with acute skinsoft-tissue, bone, or respiratory infections caused by organisms known or suspected to be sensitive to cefoxitin were entered into the study. Seven of the patients had serious skinsoft tissue infections or osteomyelitis and are the subject of this report. Informed consent with written permission was obtained in each case. Bacteriologic diagnoses were based on Gram stains and pretreatment cultures from infected tissues, fluid aspirates, exudates, or bone biopsies. O3O5-7453/78/O7OI-B183 $01.00/0
183 © (1978) The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 26, 2015
Division of Infectious Diseases, Department of Medicine, The Ohio State University, Columbus, Ohio, U.S.A.
R . L . Perkins
184
Table I. Cefoxitin-treated patients with abscessesi requiring incision and drainage Infecting organisms
MIC Otg/ml)
Underlying disease
Abscess, labia
Peptococcus spp.
=*01
Diabetes mellitus Decreased IgA
Clinical and bacteriological
8
Abscess, scalp
Bacteroides fragHis Staphylococcus epidermidis Staph. aureus
Diabetes mellitus
13
Abscess, back
Peptococcus spp.
18
Abscess, leg
B. melaninogenicus Staph. aureus
Clinical and bacteriologic cure Clinical failure, bacteriologic cure Clinical and bacteriologic
Patient
no. 7
Lesion
Results
cure
0-2 20 4-0
Diabetes mellitus
not tested 0-2 Old trauma
cure Minimum inhibitory concentrations (MIC) of cefoxitin for aerobic and facultatively anaerobic isolates were determined by a micro-dilution procedure (Conrath, 1972), using 10B to 106 colony-forming units/ml as the final inoculum. The MIC of cefoxitin for each anaerobic isolate was determined by the method of Rotilie, Fass, Prior & Perkins (1975). Cefoxitin concentrations in sera and urine were determined by a disc-diffusion method utilizing Staphylococcus aureus B-2786e as the assay organism (Simon & Yin, 1970). Cefoxitin sodium, 1 to 2 g in 100 to 200 ml of 5 % dextrose solution, was given as a 30-min i.v. infusion every 4 to 6 h. Clinical monitoring and serial laboratory observations, including serial cultures before, during, and after therapy, complete blood counts, direct Coombs test, urinalysis, blood urea nitrogen, serum creatinine, aJkaline phosphatase, SGOT, SGPT, LDH, and serum electrolytes, were employed to determine responses to therapy and to detect any adverse reactions. Results
All 7 patients were initially considered for immediate surgical intervention. Four had major abscesses of skin and soft tissue, each associated with extensive cellulitis; 3 of the 4 had underlying diabetes mellitus, and the fourth had an earlier trauma and old surgical Figure 1. Plantar aspect of foot of Patient no. 24 on admission, showing marked necrosis of skin, vesiculation, and through-and-through suppuration. Figure 2. Initial ventral incision for debridement and decompression of wound. Figure 3. Initial dorsal incision for debridement and decompression of wound. Figure 4. Marked healing after 3 weeks of cefoxitin therapy. Figure 5. Dorsal wound almost closed after 42 days of cefoxitin therapy. Figure 6. Plantar wound almost closed after 42 days of cefoxitin therapy. Figure 7. X-rays of foot of Patient no. 24, (a) before, and (b) after cefoxitin therapy for 42 days, (a) Swelling of foot, gas in tissues, and bone destruction are evident (b) Note resolution of lesions, with small sequestrum still present at base of second raetatarsal.
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 26, 2015
32
scarring in the area of infection (Table I). Incision and drainage were necessary in each case. The infecting organisms obtained by culture of the drainage material included Sfaph. aureus in 2 patients and, primarily, mixed anaerobic flora in the other 2. The organisms proved susceptible to cefoxitin, and bacteriologic cures were obtained in all 4 cases. The remaining 3 patients had diabetes mellitus as well as osteomyelitis of the metatarsa! and tarsal bones; in each case, the infecting organisms included both aerobic and anaerobic bacteria (Table II). For all 3 patients, consultants considered surgical amputation of the foot a definite possibility. After being treated with cefoxitin 8 g/day, and undergoing minor, but repeated, debridement of overlying skin ulcerations, 2 patients (nos. 15 and 21) showed evidence of clinical and bacteriologic cures. The third patient (no. 24) had, in addition to diabetes and osteomyelitis, more massive soft-tissue involvement, marked necrosis of the skin, vesiculation, and through-and-through suppuration (Figure 1). A general surgical consultant recommended amputation below the knee. On the fifth day of cefoxitin therapy, however, an orthopedic consultant incised the foot on both dorsal and ventral aspects to debride and decompress the wound (Figures 2 and 3). After three weeks of cefoxitin therapy and further debridement the wounds showed marked healing (Figure 4). Cefoxitin therapy was continued for 42 days, and the wounds showed closure soon therafter (Figures 5 and 6). X-rays made before cefoxitin therapy showed marked swelling of the foot, with gas in the tissues and evidence of bone destruction; later X-rays showed resolution of the lesions, except for a small sequestrum at the base of the second metatarsal (Figure 7). The sequestrum was excised because it caused minor discomfort during walking. All tissue and bone samples were sterile on aerobic and anaerobic culture, nor was there any histologic evidence of osteomyelitis. The patient is now completely ambulatory and the wounds have healed. No significant adverse reactions were observed in the 7 patients, although mild transient eosinophilia occurred in 2 patients. Phlebitis did not occur in Patient no. 24, despite 42 days of intermittent i.v. therapy. Discussion Advanced, necrotizing skin-soft tissue infections or osteomyelitis in diabetic patients,
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 26, 2015
24
Osteomyelitis, foot
Infecting organisms
Soft-tissue and bone infections
187
Acknowledgements The author thanks Richard B. Prior, Ph.D., and Ms Beth Ann Bailey for expert technical assistance. This study was supported in part by a grant from Merck Sharp & Dohme Research Laboratories. References Conrath, T. B. Handbook of Microtitcr Procedures. Dynatech Corp., Cambridge, Mass. (1972), pp. 30-36. Heseltine, P. N. R., Busch, D. F., Meyer, R. D. & Finegold, S. M. Cefoxitin: Clinical evaluation in thirty-eight patients. Antimicrobial Agents and Chemotherapy 11: 427-34 (1977). McCloskey, R. V. Results of a clinical trial of cefoxitin, a new cephamycin antibiotic. Antimicrobial Agents and Chemotherapy 12: 636-41 (1977). Neu, H. C. Cefoxitin, a semisynthetic cephamycin antibiotic: antibacterial spectrum and resistance to hydrolysis by Gram-negative beta-lactamases. Antimicrobial Agents and Chemotherapy 6: 170-6(1974). Rotilie, C. A., Fass, R. J., Prior, R. B. & Perkins, R. L. Microdilution technique for antimicrobial susceptibility testing of anaerobic bacteria. Antimicrobial Agents and Chemotherapy 7: 311-5 (1975). Simon, H. J. & Yin, E. J. Microbioassay of antimicrobial agents. Applied Microbiology 19: 573-9 (1970).
Downloaded from http://jac.oxfordjournals.org/ at University of Birmingham on August 26, 2015
especially when there is evidence of significant compromise of the local microcirculation, not infrequently leads abruptly to consideration of amputation. In some instances, questions of practicality and economics may unduly reinforce the temptation to resolve the problem quickly by resort to amputation. There is inadequate appreciation of the potential for salvaging such affected digits or extremities, in light of modern microbiologic techniques for identifying the infecting organisms. The combination of sophisticated culture methods and bacterial susceptibility tests, appropriately designed and adequately prolonged parenteral antimicrobial therapy, and meticulous daily minor debridement of wounds often leads to outstanding therapeutic results. Central to success in such cases is the existence of a potent, well-tolerated, effective antimicrobial agent, like cefoxitin in the present cases. A recent report indicates similar success with cefoxitin in infections caused by polymicrobic aerobic or anaerobic organisms (McCloskey, 1977). In summary, common abscesses of skin and soft tissues treated with cefoxitin sodium required classic drainage procedures to accelerate recovery and to achieve bacteriologic cures. In those cases of osteomyelitis of the small bones of the feet in which the extent of the lesions and the presence of polymicrobic infecting flora and underlying disease, such as diabetes mellitus, may suggest a need for amputation, aggressive treatment with a carefully selected, broad-spectrum agent, such as cefoxitin sodium, combined with meticulous debridement and local care, may salvage the digits or limbs.
