Appendix G: Diabetic foot problems - full evidence tables – review questions 11 - 16

Title: Treatment and Long-Term Follow-Up of Foot Infections in Patients with Diabetes or Ischemia: A Randomized, Prospective, Double-Blind Comparison of Cefoxitin and Ceftizoxime Level of Patient Population/ Selection/Inclusion criteria Intervention Comparison Follow-up Outcome and Results Evidence Characteristics ID: 4914 Total no. of patients: Inclusion: Ceftizoxime, Every 3 days. Table 1: Clinical responses Baseline = 63 up to 4 gm IV Cefoxitin, up to2 Subsequent Level of Ceftizoxime – 33 (1) a history or clinical evi- every eight gm IV every four follow-up evalu- evidence: (5 unevaluable) dence of peripheral arterial hours. hours. ations were Number with Satisfactory () insufficiency or diabetes made after 3, 6, Clinical Response/ Total Cefoxitin- 30 mellitus; (2) isolation of Dosages of 9, and 12 Number Treated Study (5-unevaluable) bacterial organisms from study months. type: wound, soft tissue, or medication Dosages of Ceftizoxime Cefoxitin study RCT Some patients, after bone; (3) two or more signs were reduced medication were All evaluable 23/28 17/25 completing the study, of infection, including local for patients Authors: heat, drainage, erythema, with renal reduced for patients received oral antibiotics for patients with Hughes variable lengths of time at or temperature greater dysfunction. et al. than 38 °C. renal Osteomyelitis 10/14 8/12 the discretion of their dysfunction. (1987) physician. Soft tissue 13/14 9/13 Placebo Exclusion: infections Baseline characteristics: infusions were

given at appropriate Infections 0/1 1/4 Evaluable patients were Excluded for previous associated similar with regard to age, intervals to penicillin or cephalosporin patients in the with sex, duration of therapy, and allergy, rapidly progressive bacteremia associated conditions. ceftizoxime underlying disease, group to

concomitant infection, or maintain Satisfactory clinical responses were observed in Setting: antibiotic therapy effective double-blind 82% of patients treated with ceftizoxime and 68% 2 Veterans Administration against the bacterial conditions. of patients treated with cefoxitin. medical centers (VAMC) isolates within three days preceding initiation of-the Relative Risk- 23/28 ÷ 17/25 = 1.20 study. Treatment of osteomyelitis with either agent was particularly encouraging, being only slightly less successful than treatment of soft tissue infections. Infections associated with bacteremia frequently were clinically unsatisfactory.

There was no significant difference between responses of patients with peripheral vascular disease alone and responses of diabetics with or without apparent peripheral vascular disease.

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55 Appendix G: Diabetic foot problems - full evidence tables – review questions 11 - 16

The in vitro susceptibilities of selected bacterial isolates are 161 of 185 (87%) isolates tested were susceptible to ceftizoxime and 148 of 183 (81%) were susceptible to cefoxitin.

Long term Follow up

3 months

After three months of follow-up, six patients in each group had relapses of infection at the same site, which required parenteral antibiotics.

12 months

After 12 months, of 23 patients who initially had satisfactory clinical responses to ceftizoxime, eight were free of infection (at the same site), nine had relapsed, two had died of unknown causes, and four had failed to return for follow-up.

Seventeen patients had initially satisfactory clinical responses to cefoxitin. After 12 months, seven remained free of infection, eight had relapsed, and two had not returned for follow-up.

Five of 12 patients with soft tissue infections and two of 11 with osteomyelitis were known to have satisfactory long-term outcomes.

Adverse events

Adverse effects were observed in 16/33 (48%) patients receiving ceftizoxime and in 19/30 (63%) patients receiving cefoxitin. These consisted

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56 Appendix G: Diabetic foot problems - full evidence tables – review questions 11 - 16

mostly of minor laboratory abnormalities, which resolved with discontinuation of therapy.

Relative Risk- 16/33 ÷ 19/30 = 0.76 Additional comments:

Randomisation (Computer-generated Code) was performed. Blinding performed. Power calculation not used. Allocation concealment not mentioned. Confounding not mentioned. Patients lost to follow up and excluded after randomisation was mentioned. All parameters were not analysed as intention to treat.

Reference: Hughes, CE, Johnson, CC, Bamberger, DM, Reinhardt, JF, Peterson, LR, Mulligan, ME, Gerding, DN, George, WL, Finegold, SM Treatment and long-term follow-up of foot infections in patients with diabetes or ischemia: a randomized, prospective, double-blind comparison of cefoxitin and ceftizoxime. Clinical Therapeutics 1987; 10: Suppl-49.

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