Journal of Antimicrobial Chemotherapy (1978) 4 (Suppl. B), 151-153
Cefoxitin in abdominal sepsis
A. M. Geddes and R. M. L. WUcox
A study of 34 patients was undertaken to determine the efficacy of a new antibiotic, cefoxitin sodium, in the treatment of abdominal sepsis. The most common infection was appendicitis associated with peritonitis. Thirty of the 34 patients were cured by cefoxitin therapy accompanied, when indicated, by surgical drainage. None of the patients developed adverse reactions to the antibiotic, but local pain related to i.v. injection was a common complaint.
Introduction Intra-abdominal sepsis is a common cause of prolonged morbidity and, not infrequently, of death. The severity of this infection varies from relatively mild appendicitis to faecal peritonitis, for which the mortality exceeds 50 %. Most of the infections originate in the large bowel and are caused predominantly by aerobic or anaerobic Gram-negative pathogens, of which Escherichia coli and Bacteroides fragilis are the most common (Lari, Kirk & Howden, 1976). Cefoxitin sodium is active against both these organisms and has significant activity against other Gram-negative bacilli and some Gram-positive bacteria (Kosmidis, Hamilton-Miller, Gilchrist, Kerry & Brumfitt, 1973). The present study was undertaken to determine the efficacy of cefoxitin in the treatment of abdominal sepsis.
Methods Thirty-four patients were selected for treatment with cefoxitin. Their ages ranged from 15 months to 81 years. Sixteen of the 34 patients were children. The most common infection was appendicitis associated with peritonitis, but 6 patients had faecal peritonitis (Table I). Many of the patients were seriously ill, and 12 were septicaemic. Pathogenic bacteria were isolated from peritoneal pus, blood, or wounds in 28 of the 34 patients (Table II). Cefoxitin sodium, diluted with 20 ml of sterile water, was given every 8 h by bolus i.v. injection over a period of 3 min. Treatment was continued for 5 to 7 days. The individual dose was 2 g for adults, 1 -5 g for older children, and 1 g for younger children. A 15-month-old baby was given 0-5 g of cefoxitin every 8 h. During treatment, a careful watch was kept for possible adverse reactions to cefoxitin, and renal and hepatic functions were usually monitored while complete blood counts were carried out before, during, and after treatment Blood levels of cefoxitin were measured in several patients. 151 O3O5-7453/68/07O1-B151 Wl.00/0
© (1978) The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of California, San Fransisco on April 9, 2015
East Birmingham Hospital, Birmingham 59 SST, England
152
A. M. Geddes and R. M. L. Wilcox Table I. Infections in patients with abdominal sepsis treated with cefoxitin Infection
No. of patients 12 6 5 2 2 1 1 1 1 1 1 1
Total
34
Table II. Organisms cultured from 28 of 34 patients with abdominal sepsis*
Escherichia coli Bacteroides fragilis Anaerobic streptococci 'Faecal flora' Staphylococcus aureus Haemolytic streptococci Klebsiella spp.
Peritoneal pus
Blood
Wound
9 4 4 5 1 1 —
7 5 1 — — — 1
1 — 1 — — — —
* In some patients, organisms were cultured from more than one site. Table IE. Serum cefoxitin levels after i.v. bolus injection of a 2-g dose over 3 min* Time after dose
Serum level (mg/1)
5 nun 1h 1-5 h 2h 3h 4h
112-5 36-5 25-8 180 10-2 7-5
•One patient.
Results Thirty of the 34 patients were cured by cefoxitin therapy accompanied, when indicated, by surgical drainage. Only one patient, a boy with B. fragilis septicaemia and a subphrenic abscess consequent to perforation of the appendix, failed to respond to cefoxitin; a resistant B. fragilis strain was cultured from pus from the sub-phrenic abscess after cefoxitin therapy had ended.
Downloaded from http://jac.oxfordjournals.org/ at University of California, San Fransisco on April 9, 2015
Appendicitis and peritonitis Faecal peritonitis Peritonitis Appendicitis and abscess Diverticulitis Liver abscess Cholangitis Ulcerative colitis Pancreatic abscess Perforation of bile duct Perinephric abscess Psoas abscess
Cefoxitin in abdominal sepsis
153
Discussion The present study confirms the efficacy of cefoxitin sodium in the management of abdominal sepsis. Standard chemotherapy for this condition normally involves the use of more than one antibiotic, e.g., gentamicin to cover aerobic organisms and clindamycin or metronidazole to control anaerobic bacteria. All three of these antibiotics have unwanted side effects, whereas cefoxitin, like the related penicillins and cephalosporins, is relatively free from adverse reactions. The present study supports our previous observations (Geddes et al., 1977) that blood levels of cefoxitin are very high after i.v. administration, even though the antibiotic is excreted rapidly by children. After i.v. injection of a 2-g dose of cefoxitin, bile levels of this drug exceeded 200 mg/1 (Geddes et al., 1977). This finding suggests that therapeutic concentrations of cefoxitin will be found in the bowel lumen as well as in the biliary tract. This study confirms that the pathogens most commonly cultured from patients with peritonitis and other intra-abdominal infections are E. coli and B. fragilis. Both organisms, including strains that produce /3-lactamases, are usually sensitive to cefoxitin. There has been considerable -interest recently in antibiotic prophylaxis before gastrointestinal, biliary tract, or gynaecologic surgery. Cefoxitin might be an appropriate antibiotic for this purpose, and studies of its prophylactic use are indicated. Because i.m. injection of cefoxitin is painful and the antibiotic is not absorbed from the intestinal tract, it is necessary to administer the drug i.v. This procedure is satisfactory and, indeed, desirable for ill patients. In certain conditions, however, e.g., liver abscess or extensive sepsis, treatment may have to be continued for prolonged periods; under such circumstances, for technical reasons the i.v. route becomes less practical. References Geddes, A. M., Schnurr, L. P., Ball, A. P., McGhie, D., Brookes, G. R., Wise, R. & Andrews, J. Cefoxitin—a hospital study. British Medical Journai i: 1126-8 (1977). Kosmidis, J., Hamilton-Miller, J. M. T., Gilchrist, J. N. G., Kerry, D. W. & Brumfitt, W. Cefoxitin, a new semi-synthetic cephamycin: an in vitro and in vivo comparison with cephalothin. British Medical Journal iv: 653-5 (1973). Lari, J., Kirk, D. & Howden, R. Bacteriological survey of acute appendicitis in children. British Journal of Surgery 63: 643-6 (1976).
Downloaded from http://jac.oxfordjournals.org/ at University of California, San Fransisco on April 9, 2015
Three patients died during or after cefoxitin therapy. Thefirstwas a frail and debilitated 87-year-old patient with profound toxaemia who died 24 h after the first injection of cefoxitin. The second death occurred from pulmonary embolism, and the third from rupture of a colonic anastomosis after surgery for diverticulitis. None of the patients developed adverse reactions to the antibiotic, but local pain during i.v. injection was experienced by a number of patients. Some patients developed thrombophlebitis along the vein used for administration of the antibiotic. Table m shows serum cefoxitin levels in 1 patient at various times after bolus i.v. injection of a 2-g dose.
Cefoxitin in abdominal sepsis
A. M. Geddes and R. M. L. WUcox
A study of 34 patients was undertaken to determine the efficacy of a new antibiotic, cefoxitin sodium, in the treatment of abdominal sepsis. The most common infection was appendicitis associated with peritonitis. Thirty of the 34 patients were cured by cefoxitin therapy accompanied, when indicated, by surgical drainage. None of the patients developed adverse reactions to the antibiotic, but local pain related to i.v. injection was a common complaint.
Introduction Intra-abdominal sepsis is a common cause of prolonged morbidity and, not infrequently, of death. The severity of this infection varies from relatively mild appendicitis to faecal peritonitis, for which the mortality exceeds 50 %. Most of the infections originate in the large bowel and are caused predominantly by aerobic or anaerobic Gram-negative pathogens, of which Escherichia coli and Bacteroides fragilis are the most common (Lari, Kirk & Howden, 1976). Cefoxitin sodium is active against both these organisms and has significant activity against other Gram-negative bacilli and some Gram-positive bacteria (Kosmidis, Hamilton-Miller, Gilchrist, Kerry & Brumfitt, 1973). The present study was undertaken to determine the efficacy of cefoxitin in the treatment of abdominal sepsis.
Methods Thirty-four patients were selected for treatment with cefoxitin. Their ages ranged from 15 months to 81 years. Sixteen of the 34 patients were children. The most common infection was appendicitis associated with peritonitis, but 6 patients had faecal peritonitis (Table I). Many of the patients were seriously ill, and 12 were septicaemic. Pathogenic bacteria were isolated from peritoneal pus, blood, or wounds in 28 of the 34 patients (Table II). Cefoxitin sodium, diluted with 20 ml of sterile water, was given every 8 h by bolus i.v. injection over a period of 3 min. Treatment was continued for 5 to 7 days. The individual dose was 2 g for adults, 1 -5 g for older children, and 1 g for younger children. A 15-month-old baby was given 0-5 g of cefoxitin every 8 h. During treatment, a careful watch was kept for possible adverse reactions to cefoxitin, and renal and hepatic functions were usually monitored while complete blood counts were carried out before, during, and after treatment Blood levels of cefoxitin were measured in several patients. 151 O3O5-7453/68/07O1-B151 Wl.00/0
© (1978) The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at University of California, San Fransisco on April 9, 2015
East Birmingham Hospital, Birmingham 59 SST, England
152
A. M. Geddes and R. M. L. Wilcox Table I. Infections in patients with abdominal sepsis treated with cefoxitin Infection
No. of patients 12 6 5 2 2 1 1 1 1 1 1 1
Total
34
Table II. Organisms cultured from 28 of 34 patients with abdominal sepsis*
Escherichia coli Bacteroides fragilis Anaerobic streptococci 'Faecal flora' Staphylococcus aureus Haemolytic streptococci Klebsiella spp.
Peritoneal pus
Blood
Wound
9 4 4 5 1 1 —
7 5 1 — — — 1
1 — 1 — — — —
* In some patients, organisms were cultured from more than one site. Table IE. Serum cefoxitin levels after i.v. bolus injection of a 2-g dose over 3 min* Time after dose
Serum level (mg/1)
5 nun 1h 1-5 h 2h 3h 4h
112-5 36-5 25-8 180 10-2 7-5
•One patient.
Results Thirty of the 34 patients were cured by cefoxitin therapy accompanied, when indicated, by surgical drainage. Only one patient, a boy with B. fragilis septicaemia and a subphrenic abscess consequent to perforation of the appendix, failed to respond to cefoxitin; a resistant B. fragilis strain was cultured from pus from the sub-phrenic abscess after cefoxitin therapy had ended.
Downloaded from http://jac.oxfordjournals.org/ at University of California, San Fransisco on April 9, 2015
Appendicitis and peritonitis Faecal peritonitis Peritonitis Appendicitis and abscess Diverticulitis Liver abscess Cholangitis Ulcerative colitis Pancreatic abscess Perforation of bile duct Perinephric abscess Psoas abscess
Cefoxitin in abdominal sepsis
153
Discussion The present study confirms the efficacy of cefoxitin sodium in the management of abdominal sepsis. Standard chemotherapy for this condition normally involves the use of more than one antibiotic, e.g., gentamicin to cover aerobic organisms and clindamycin or metronidazole to control anaerobic bacteria. All three of these antibiotics have unwanted side effects, whereas cefoxitin, like the related penicillins and cephalosporins, is relatively free from adverse reactions. The present study supports our previous observations (Geddes et al., 1977) that blood levels of cefoxitin are very high after i.v. administration, even though the antibiotic is excreted rapidly by children. After i.v. injection of a 2-g dose of cefoxitin, bile levels of this drug exceeded 200 mg/1 (Geddes et al., 1977). This finding suggests that therapeutic concentrations of cefoxitin will be found in the bowel lumen as well as in the biliary tract. This study confirms that the pathogens most commonly cultured from patients with peritonitis and other intra-abdominal infections are E. coli and B. fragilis. Both organisms, including strains that produce /3-lactamases, are usually sensitive to cefoxitin. There has been considerable -interest recently in antibiotic prophylaxis before gastrointestinal, biliary tract, or gynaecologic surgery. Cefoxitin might be an appropriate antibiotic for this purpose, and studies of its prophylactic use are indicated. Because i.m. injection of cefoxitin is painful and the antibiotic is not absorbed from the intestinal tract, it is necessary to administer the drug i.v. This procedure is satisfactory and, indeed, desirable for ill patients. In certain conditions, however, e.g., liver abscess or extensive sepsis, treatment may have to be continued for prolonged periods; under such circumstances, for technical reasons the i.v. route becomes less practical. References Geddes, A. M., Schnurr, L. P., Ball, A. P., McGhie, D., Brookes, G. R., Wise, R. & Andrews, J. Cefoxitin—a hospital study. British Medical Journai i: 1126-8 (1977). Kosmidis, J., Hamilton-Miller, J. M. T., Gilchrist, J. N. G., Kerry, D. W. & Brumfitt, W. Cefoxitin, a new semi-synthetic cephamycin: an in vitro and in vivo comparison with cephalothin. British Medical Journal iv: 653-5 (1973). Lari, J., Kirk, D. & Howden, R. Bacteriological survey of acute appendicitis in children. British Journal of Surgery 63: 643-6 (1976).
Downloaded from http://jac.oxfordjournals.org/ at University of California, San Fransisco on April 9, 2015
Three patients died during or after cefoxitin therapy. Thefirstwas a frail and debilitated 87-year-old patient with profound toxaemia who died 24 h after the first injection of cefoxitin. The second death occurred from pulmonary embolism, and the third from rupture of a colonic anastomosis after surgery for diverticulitis. None of the patients developed adverse reactions to the antibiotic, but local pain during i.v. injection was experienced by a number of patients. Some patients developed thrombophlebitis along the vein used for administration of the antibiotic. Table m shows serum cefoxitin levels in 1 patient at various times after bolus i.v. injection of a 2-g dose.
