Chemioterapia : international journal of the Mediterranean Society of Chemotherapy最新文献

Cefotetan is a semi-synthetic cephamycin antibiotic. It has combined activity against aerobes and anaerobes which makes it of particular use in the treatment and prevention of intra-abdominal infections in the surgical patient. In the course of 3 years we have evaluated the therapeutic use of cefotetan in 107 patients. Early in the evaluation of this antibiotic we used cefotetan in combination with aminoglycosides in 35 severely ill patients with intra-abdominal infections. These patients were generally in poor condition. Good results were obtained in this high risk group. A further 72 patients received cefotetan monotherapy, usually at a dose of 2 g twice daily. The majority of these patients presented with intra-abdominal infections. Overall a successful clinical response of 94% was obtained with antibiotic therapy. In conclusion the results obtained support the therapeutic use of cefotetan in the treatment of moderate to severe intra-abdominal infection.

Six volunteers received intravenously a single 1 g dose of cefoxitin or cefotetan. The 2 groups were crossed after a week of washout. Five strains each of Escherichia coli, Klebsiella pneumoniae, Bacteroides fragilis and Bacteroides thetaiotaomicron susceptible to the administered drugs were tested for serum bactericidal activity (SBA). Blood samples were obtained before and 0.5, 3.0 and 12.0 hours after antibiotic injection. SBA was determined using microtitre procedures. Anaerobic bacteria were incubated in an anaerobic chamber. Cefotetan showed a very high SBA both against aerobes and anaerobes over the 12 hour sampling time. Cefoxitin reached satisfactory SBA values only 0.5 hours after administration.

Cefotetan is a broad spectrum cephamycin antibiotic with a long serum half-life (3-4.5 h): this is explained, in part, by serum-protein-binding (SPB) of 88%. The rate of kill of Staphylococcus aureus by cefotetan was assessed in human serum or broth containing reducing concentrations of drug simulating those seen following a 1 g intravenous dose to man. Cefotetan was bactericidal in serum despite the assumed concentration of unbound drug never reaching the minimum inhibitory concentration (MIC) for the test strain. In a separate study, ceftriaxone (SPB 96%) was more active in broth (MIC 4 mg/1) than cefotetan (MIC 16 mg/1). In 100% serum the minimum bactericidal concentration (MBC) of ceftriaxone was 64 mg/1 whilst the MBC for cefotetan was 16 mg/1.

In a randomised clinical trial, 102 women who underwent vaginal hysterectomy were given a single preoperative 2g dose of cefotetan (CTT) (52 pts) or three perioperative 2g doses of cefoxitin (CFX) plus 0.5g metronidazole (50 pts) as antibiotic prophylaxis. No statistically significant differences between the groups were detected in the clinical response (100% for both groups). The incidence of major wound infection (2% CTT and 0% CFX) were also comparable between the two treatment groups; post-operative changes in body temperature, duration of hospitalisation and post-operative urinary tract infections (16% CTT and 20% CFX) were similar. Both drugs were well tolerated. Twenty nine of the 102 patients were further investigated to determine the pharmacokinetics following a single 2g dose of CTT or CFX, in both serum and tissue. Although both antibiotics provided good concentrations during the early phase of surgery, CTT levels persisted for a longer time period. These results confirm that single dose cefotetan is equally as effective and safe as multiple dose cefoxitin plus metronidazole for prophylaxis in patients undergoing vaginal hysterectomy.

Two sequential randomised studies were performed to assess the efficacy of 3 different cephalosporins in the treatment of established intra-abdominal infections. In the first study 102 of 109 (94%) patients given cefotetan 2g iv every 12 hours had a satisfactory clinical response compared to 51 of 56 (91%) patients given latamoxef 2g iv every 8 hours. In the second study cefotetan 2g iv every 12 hours was compared to cefoxitin 2g iv every 6 hours with satisfactory clinical responses in 93 of 95 (98%) cefotetan-treated patients and 41 of 43 (95%) cefoxitin-treated patients. Overall response rates in the two studies were lower in patients with severe peritonitis (82%) or nosocomial infections (70%). Twelve-hourly dosing with cefotetan appears to be as effective and well tolerated in regional peritonitis as treatment with shorter-acting agents.

Single dose cefotetan was compared with either a combination of metronidazole and cefazolin given for 24 hours or 3 doses of cefuroxime as prophylaxis in elective abdominal surgery. Wound infections and infections at remote sites (UTI and RTI) were similar in all groups. In a third group prophylaxis of abdominal surgery using a single 2g dose of cefotetan was compared to 2 doses of the same drug, given 12 hours apart. There was no demonstrable advantage to giving 2 doses. The low incidence of post-operative infections seen in all groups indicates the efficacy of cefotetan in the surgical prophylaxis of elective abdominal surgery.

Infective complications are often seen in colorectal surgery. These even occur in cases of elective surgery and in patients where adequate bowel preparation has been performed and is due to the very high numbers of bacteria colonising the bowel. Several controlled clinical studies showed that antimicrobial prophylaxis is effective in preventing infective complications and the lack of prophylaxis is no longer justified. Antimicrobial prophylaxis can be oral (poorly absorbed antibiotics aimed to reduce the number of bacteria in the bowel) or systemic (aimed to reach a high tissue concentration when bacterial contamination occurs, in order to prevent colonisation) or a combination of the two. Which is to be preferred is still controversial. Systemic prophylaxis should have the following features: 1) use of a single agent with a broad spectrum of action, effective both on aerobes and anaerobes; 2) rapid I.V. administration, at the beginning of surgery; 3) good tissue penetration; 4) long half-life, in order to assure that the single dose will cover the whole duration of surgery; 5) good therapeutic ratio. The use of long half-life cephalosporins, particularly cefotetan, was shown to be highly beneficial. Prophylaxis can fail if contamination during surgery is severe, with a particularly high bacterial count. The degree of contamination of the operating field can be evaluated both by surgeon's judgment, and by tissue or peritoneal cavity lavage fluid sampling and culture. In case of severe contamination (bacterial number greater than 10(5) CFU/ml of fluid or mg of tissue) prolonging of antibiotic therapy for some days is justified. Otherwise, no evidence supports its prolongation beyond surgery.

In a prospective randomised study 60 patients with gynaecological or intra-abdominal infections were given either 2g iv every 12 hours of cefotetan or a combination of netilmicin (150mg iv every 12 hours) and clindamycin (600mg iv every 8 hours). The clinical condition of nearly half the patients (26 of 60) was characterized as serious and surgical manipulation and drainage were performed in 57 of the 60 patients. The clinical response was similar in both groups with 21 of 29 patients in the cefotetan group and 29 of 33 patients in the netilmicin plus clindamycin group. Side effects were few and mild in nature with no significant differences between the two groups. This work is continuing but the results to date suggest that cefotetan monotherapy is a safe and effective alternative to a combination of netilmicin and clindamycin in the treatment of gynaecological and intra-abdominal infections.

Antimicrobial prophylaxis is recommended in all clean-contaminated surgery where the critical threshold of number and virulence of the contaminating organisms with respect to host resistance is reached. Obstetric and gynaecological surgery is clean-contaminated and risk of infection due to aerobic and anaerobic bacteria without prophylaxis can be quantified at 30-40% for vaginal hysterectomy, 10-35% for abdominal hysterectomy and 10-34% for caesarean section. To assess the role of two different cephalosporins as short term prophylaxis, we carried out a multicentre randomised study involving a single 2 g i.v. dose of cefotetan in comparison with two doses of cefazolin (2 g i.v. before surgery and after 8 hours). Criteria for exclusion were: exposure to antibiotics within 7 days, preoperative infection, hypersensitivity to beta-lactams. Four hundred and sixty patients entered the study, of which 229 received cefotetan and 231 cefazolin. No significant differences in mean age, obesity, preoperative weight loss, diabetes, type of disease, type of surgery (vaginal or abdominal hysterectomies and caesarean sections) and number of pregnancies and abortions existed between the two groups of patients. The total rate of infected patients undergoing hysterectomy was 8.6% (13/151) in the cefotetan group and 17.4% (29/167) in the cefazolin group (p less than 0.05). This difference was due to cases of symptomatic bacteriuria and antibiotic retreatment, while wound infections were not significantly different (2.6% and 1.8% respectively). Among patients undergoing caesarean section, 9 of 78 (11.5%) and 7 of 64 (10.9%) were infected following cefotetan and cefazolin, respectively (not significant). Cefotetan mean tissue concentrations in gynaecological organs were higher than those of cefazolin (25.5-44.8 vs. 7.4-9.5 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Twelve hospitalised patients, affected by biliary tract infections, were treated with cefotetan at dosages ranging between 4 and 6 g daily i.v. In only 11 patients was the aetiological agent identified. Eleven patients (91.67%) completely recovered from their infections and the pathogens were eradicated; the treatment failed in only 1 patient (8.33%). Furthermore, determinations were made of cefotetan concentrations in serum, gallbladder bile, gallbladder wall and gallstones of 14 patients undergoing cholecystectomy: in 7 patients after only 1 injection i.v. of 2 g and in 7 patients after 7 injections i.v. of 2 g at intervals of 12 h. The levels recorded were several times higher than the minimum inhibitory concentrations against bacteria that are most often responsible for biliary infections. Cefotetan is a promising and effective antimicrobial agent in the therapy of biliary tract infections.