Antibiotic prophylaxis in open-heart surgery patients: comparison of cefamandole and cefuroxime

The efficacy of cefamandole and cefuroxime in preventing postoperative wound infections was compared in 3037 patients undergoing open-heart surgery. Antibiotic prophylaxis in 1467 patients having coronary artery bypass and valve replacement surgery was cefamandole 2 g iv preoperatively followed by 2 g q6h for five days postoperatively; 1570 patients received cefuroxime 1.5 g iv preoperatively then 1.5 g iv q 12h for three days postoperatively. Postoperative wound infections (sternal and leg wounds) were studied in each treatment group. In the cefamandole study group, 27 patients (1.8 percent) developed postoperative wound infections (9 sternal and 18 leg wounds). In the cefuroxime treatment group, 19 patients (1.2 percent) developed postoperative wound infections (9 sternal and 10 leg wounds). Overall, no statistical difference was found between the two antibiotics in preventing postoperative wound infections. However, in patients having valve replacement surgery, cefuroxime was found statistically more effective than cefamandole prophylaxis in preventing sternal wound infections (no infections in 284 patients compared with five infections in 205 patients, respectively, p = 0.01). The most common organism isolated from infected wounds with cefamandole was Staphylococcus aureus followed by S. epidermidis compared with cefuroxime which had S. epidermidis followed by S. aureus. Cefuroxime was found to be as effective as cefamandole and considerably less expensive in preventing postoperative wound infections in patients undergoing open-heart surgery.     

Antibiotic prophylaxis in elective cholecystectomy: a randomized, double blinded study comparing ciprofloxacin and cefuroxime

A prospective, randomised and double blind study was undertaken to compare the prophylactic efficacy of ciprofloxacin and cefuroxime in 155 patients undergoing elective cholecystectomy. Patients with past history of jaundice or presence of jaundice, diabetes mellitus, common bile duct stones and previous biliary tract surgery were excluded. Patients were allocated to the following groups: group A-no antibiotic (n = 30); group B-ciprofloxacin (200 mg i/v before surgical incision and a second dose after 12 hrs) (n + 45); group C-ciprofloxacin given only post operatively (200 mg i/v, 12 hourly X 2 days followed by oral 500 mg twice daily X 3 days) (n = 35); group D-cefuroxime (750 mg i/v before surgical incision and a second dose after 12 hrs) (n = 45). Efficacy of the antibiotic was defined as a patient being free of post operative wound infection. Maximum numbers of infection occurred in group A (26.67%) and group C (25.71%). The incidence of wound infection was significantly lower when ciprofloxacin was used as prophylaxis (group B) than when used post operatively (group C) only (P < 0.05). Patients who received ciprofloxacin (group B) and cefuroxime (group D) as prophylaxis had significantly reduced incidence of infection (4.44% and 6/67% respectively); no statistically significant difference was found between these groups. Ciprofloxacin could be used as prophylactic antimicrobial in elective cholecystectomy in developing countries because of its effectiveness, economy and ready availability.     

Long-term oral ciprofloxacin for infection prophylaxis in allogeneic bone marrow transplantation

The efficacy of oral ciprofloxacin to prevent bacterial infections during the first three months after allogeneic bone marrow transplantation (BMT) was assessed prospectively. Twenty-three recipients of lymphocyte depleted marrow grafts received ciprofloxacin orally, 500 mg twice daily for 90 days after BMT. Nine patients had no infections during ciprofloxacin prophylaxis; in the remaining 14 patients 19 febrile episodes occurred. No infections could be attributed to Gram-negative rods nor to fungal micro-organisms on the basis of the micro-organisms isolated. One infection, a pneumonia due toBacteroides melaninogenicus, proved to be fatal. Allergic skin reactions were observed in three patients, but neither hematological nor nephrological side-effects could be substantiated in patients who were treated concomitantly with cyclosporine. Prolonged administration of ciprofloxacin turned out to be safe and effective in preventing serious aerobic bacterial infections during the first three months after BMT.     

Results of a prospective,randomized, double blind comparison of the efficacy and the safety of sequential ciprofloxacin (intravenous/oral)+metronidazole (intravenous/oral) with ceftriaxone (intravenous)+metronidazole (intravenous/oral) for the treatment of intra-abdominal infections

The efficacy and the safety of sequential intravenous/oral (i.v./p.o.) ciprofloxacin (CIPX) plus i.v./p.o. metronidazole (MTR) was compared with i.v. ceftriaxone (CTRX) plus i.v./p.o. MTR in the treatment of complicated intra-abdominal infections. One hundred and forty two patients received study medications. Of these, 135 could be studied. Sixty-nine patients were randomized in the CIPX arm of the study and 66 in the CTRX arm. In the CIPX group 58 patients were switched to oral treatment and 11 patients remained in the intravenous arm. In the CTRX group 57 patients switched to oral MTR continuing i.v. CTRX and 9 patients remained in the i.v. branch. Success rates at the end of treatment in patients who switched to oral were 100% in both the CIPX group and the CTRX group. For validated patients continuing on oral, the success rates at the end of treatment were 63.6 and 33.3% in the CIPX and CTRX groups respectively. Overall success rates at the end of treatment and follow-up in all patients were 94.2% in the CIPX group and 89.4% in the CTRX group. Overall success rates at the end of treatment in patients with proven bacterial infection were 92.9% in the CIPX group and 88.3% in the CTRX group. Duration of hospitalization (days) for studied patients was 22.7+/-8.2 in the CIPX and 19.6+/-14.5 in the CTRX group. There was no statistical difference between the CIPX and CTRX groups in both the intent to treat and in the modified intent to treat populations. Conversion to oral therapy with CIPX/MTR was as effective as continued intravenous therapy with CTRX and oral MTR in those patients able to tolerate oral feeding.     

Chlorimipramine: A double-blind comparison of intravenous versus oral administration in depressed patients

A double-blind study was carried out in 30 patients to compare the results of chlorimipramine given orally and intravenously.The speed of onset of action and the overall improvement were excellent for both treatment modalities. No significant differences were found favoring either way of administration. As a consequence, our results do not support previous reports that suggest advantages and rationale for the intravenous usage of chlorimipramine.Also called Anafranil^® abroad and Clomipramine in the U.S.A.This investigation was supported in part by research grant MYP-5106 from the National Institute of Mental Health, U.S. Public Health Service.We thank Ms. Carol Umland, R. N. and Ms. Connie Ball, R. N. for their cooperation and dedication which made possible the successful completion of this study.     

Single-dose pharmacokinetics of oral ciprofloxacin in patients with cystic fibrosis

The single-dose pharmacokinetics of oral ciprofloxacin were studied in ten patients with cystic fibrosis aged 18 to 34 years. Each patient received three different drug doses (500 mg, 750 mg, and 1,000 mg) at successive one-week intervals. Dosing and drug assays were double blinded. Blood and urine were assayed over the 48 hours following each dose. Ciprofloxacin was absorbed from the gastrointestinal tract. Peak serum concentrations averaged 2.8, 4.5, and 4.6 micrograms/mL respectively at the three doses, well above the mean inhibitory concentrations of most isolates of Pseudomonas aeruginosa. Time to peak concentration was approximately two hours. The range of sputum levels in three patients was 1.1-2.1 micrograms/mL at four hours after the three doses. The serum elimination half-life was 3.7 hours and was independent of dose. Urinary recovery was 26%; greater than 90% of urinary excretion occurred within the first 12 hours. The results of this study indicate that ciprofloxacin has potential for use in the treatment of P aeruginosa infections in patients with cystic fibrosis.     

静脉注射/口服莫西沙星和静脉注射头孢曲松/口服头孢呋辛酯治疗院内获得性肺炎的疗效比较

目的:比较莫西沙星和头孢曲松/头孢呋辛酯治疗院内肺炎(HAP)的有效性和安全性.方法:161例HAP病例随机分为2组,莫西沙星组患者静脉注射400mg莫西沙星,每日一次,3～5d后改为口服400mg莫西沙星.头孢曲松组患者静脉注射2g头孢曲松,每日2次,3～5 d后改为口服500 mg头孢呋辛酯,治疗共持续7～14d.主要的疗效指标是在治疗期结束后7～15 d内的临床反应,次要观察指标为治疗后31 d内的临床和细菌学反应.结果:对其中120例进行PP分析(每组60例),莫西沙星和头孢曲松组的临床治愈率分别为87％和83％[95％ CI(-9.77,15.96)].两组次要终点指标相当.两种疗法都有良好的安全性和耐受性.结论:静脉注射/口服莫西沙星是治疗轻-中度HAP的一种替代疗法.     

口服氢氧化铝对静脉给予环丙沙星的体内药动学影响

目的：探讨临床常见的静脉给予环丙沙星同时经口给予含铝抗酸剂是否合理。方法：采用紫外分光光度法测定家兔血清中的环丙沙星浓度,对静脉给予环丙沙星在口服含铝抗酸剂前后的体内药动学的情况进行了比较。结果：各取血时间点的环丙沙星平均血药浓度数值相近,同时口服含铝抗酸剂不影响经静脉给予环丙沙星的AUC。结论：静脉给予环丙沙星与经口给予含铝抗酸剂是合理的。     

Absorption of oral ciprofloxacin in a patient with cardiogenic shock

Congestive heart failure and cardiogenic shock can alter the absorption process of some drugs. The absorption of ciprofloxacin has been studied in several disease states, but the effect of cardiogenic shock on its absorption is unknown. A 63-year-old man had a large myocardial infarction complicated by cardiogenic shock. When he began taking ciprofloxacin for pneumonia, he had renal and cardiac failure. Ciprofloxacin 500 mg was administered every 24 hours by nasogastric tube. Blood samples were collected 5 minutes prior to the second dose (20 hrs after the initial dose) and then regularly until 11 hours after the dose. Samples were analyzed using high-performance liquid chromatography. The trough concentration 20 hours after the initial dose was 3.7 micrograms/ml, and the serum concentrations after the second dose went from 5.6 to 4.94 micrograms/ml over the 11-hour sampling period. The peak concentration of 5.6 micrograms/ml occurred within 30 minutes after ciprofloxacin administration. It can be concluded from this case study that ciprofloxacin was adequately absorbed in this patient with multiple organ failure.     

Lung tissue concentrations of ciprofloxacin following intravenous administration in patients

Serum and corresponding lung tissue concentrations of ciprofloxacin (Ciprobay) were investigated in 25 patients undergoing open lung surgery for pulmonary malignancies. Drug levels were measured at various times (50-240 min) after completion of a single i.v. dose of 200 mg by bioassay and HPLC. Lung tissue concentrations peaked within one hour after dosing (bioassay: 3.2 micrograms/g, HPLC: 4.5 micrograms/g). Tissue levels exceeded corresponding serum level 3- to 4fold throughout the observation period. The results demonstrate excellent penetration properties of this new antimicrobial compound into lung tissue. Ciprofloxacin was concentrated in the lung and thus by far exceeded known minimum inhibitory concentrations for most nosocomial respiratory pathogens.     

Antibiotic prophylaxis in cardiothoracic surgery: results of a second survey

The use of prophylactic antimicrobials in cardiothoracic surgery has become an accepted medical practice. The choice of drug and the duration of therapy varies among institutions. In 1985, we conducted a telephone survey to determine the choice of prophylactic antimicrobials in cardiothoracic surgery programs across the U.S. We recently conducted this survey for a second time. In our 1988 survey, 51 hospitals responded, with 34 (67%) having a standard antimicrobial regimen. Of all hospitals surveyed, first-generation cephalosporins were the most commonly used agents. First-generation cephalosporins were employed in 33 (48.4%) hospitals, cefamandole in 13 (19.1%), cefuroxime in nine (13.2%), vancomycin in three (4.4%), and vancomycin plus gentamicin in two (2.9%). A variety of other agents were employed by one of the remaining hospitals. Fourteen (27%) hospitals had automatic stop orders for antimicrobial prophylaxis in this indication. Ten (19.6%) institutions had changed the antimicrobial agent(s) used for prophylaxis in the last year. The results of this survey indicate that most hospitals continue to use first-generation cephalosporins for antimicrobial prophylaxis in cardiothoracic surgery, but there is considerable variation among institutions.     

Antibiotic prophylaxis in abdominal hysterectomy, with special reference to the duration of the prophylaxis

Two consecutive open studies were performed of the efficacy of a prophylactic cefuroxime/metronidazole combination in abdominal hysterectomy. The first group received a 24-h regimen, the second group a single pre-operative dose. The incidence of post-operative wound infections and urinary tract infections were similar in both groups [wound infections in 1/75 versus 2/84 patients (NS), urinary tract infections 4/75 versus 3/84 patients (NS), respectively, in the 24-h group and single-dose group]. No significant differences in other parameters, such as pyrexia and duration of post-operative hospitalization, could be detected.     

A comparison between intravenous oxytocin and oral prostaglandin E2 for the induction of labour in parous patients

Summary

A prospective survey was carried out on 187 parous patients, in whom labour was induced by amniotomy and either intravenous oxytocin or oral prostaglandin E₂, (PGE₂).

The results show no significant difference in the performance of each group for the induction to delivery interval, the mode of delivery, the Apgar score at 5 minutes or for third stage anomalies.

The use of oral PGE₂offers advantages to the patient who is spared the discomfort, restriction and minor risks associated with an intravenous infusion; and to the midwife who does not have to make frequent checks on the flow rate if an infusion pump is not available. The method also permits the ancillary equipment, which may well be in limited supply, to be reserved for more ‘at risk’ cases.     

Biotransformation of 6-thioguanine in inflammatory bowel disease patients: a comparison of oral and intravenous administration of 6-thioguanine

BACKGROUND AND PURPOSE

Although 6-mercaptopurine and azathioprine are effective treatments in inflammatory bowel disease (IBD), many patients discontinue treatment because of side effects. 6-Thioguanine (6-TG) may be an alternative rescue therapy in these intolerant patients but the pharmacokinetics of 6-TG are not fully described. Here we have measured the pharmacokinetics of the biotransformation of 6-TG into the pharmacologically active metabolites, 6-thioguanine nucleotides (6-TGN), in IBD patients.

EXPERIMENTAL APPROACH

In 12 patients with IBD, levels of 6-TGN and activities of thiopurine S-methyltransferase, xanthine oxidase and hypoxanthine guanine-phosphoribosyl-transferase were measured in a two-stage (i.v. and p.o. administration of 0.3 mg·kg⁻¹ 6-TG), prospective study. Median exposure of 6-TGN in red blood cells (RBC) was expressed as the ratio of the area under the curve (AUC) per mg 6-TG after i.v. dosing and that after p.o. dosing.

KEY RESULTS

The median AUC per mg 6-TG was 1068 (p.o.) and 7184 (i.v.) pmol·h (8 × 10⁸ RBC)⁻¹. Median exposure of 6-TGN in RBC was 15% (9–28). Hypoxanthine guanine-phosphoribosyl-transferase activity correlated with peak 6-TGN and with AUC per mg (r = 0.7, P = 0.02 and r = 0.6, P = 0.03 respectively). Thiopurine S-methyltransferase activity was inversely related to AUC per mg (r=−0.8, P = 0.001), whereas that of xanthine oxidase was correlated with a lower peak 6-TGN (r=−0.7, P = 0.02).

CONCLUSIONS AND IMPLICATIONS

The great variability of the AUC per mg for 6-TG observed after p.o. and i.v. administration of 6-TG, was partly explained by variability in activities of metabolizing enzymes. Exposure of 6-TGN was low in all patients.     

Antibiotic prophylaxis in cesarean section: use of cost per case comparison to influence prescribing practices

Results of a previously conducted DUE revealed that 91% of obstetric patients received antibiotic prophylaxis with cefoxitin despite the existence of obstetric department guidelines recommending the use of cefazolin. In the present DUE, antibiotic selection in C-section prophylaxis was reviewed and individual prescribers, both compliant and noncompliant with guidelines, were identified. Over a 2-month period, physicians who prescribed other than cefazolin for C-section prophylaxis were issued "Dear Doctor" letters, reminding them of existing guidelines. A significant change in prescribing patterns following this intervention was not demonstrated. A multidisciplinary approach was then undertaken. Prescribers were stratified by number of procedures, antibiotic requested, and antibiotic cost per case (average and median). Results were reviewed with Co-chiefs of Ob/Gyn. Letters to both compliant and noncompliant prescribers were issued. A grand rounds presentation describing the results of the DUE was also given. A follow-up review showed that the conversion to cefazolin prophylaxis reached 80%, with accompanied extrapolated yearly cost avoidance of nearly $5,500.     

Antibiotic prophylaxis in cardiothoracic surgery 1990: results of a third survey

The use of prophylactic antibiotics for cardiothoracic surgery has become an accepted medical practice. The choice of drug and duration of therapy is controversial, however. In 1985 and 1988 the authors conducted telephone surveys of cardiothoracic surgery programs to determine the most frequently used agents. The survey was repeated in in 1990. In the 1990 telephone survey, all 51 hospitals contacted in 1988 responded. Of the hospitals responding, 31 (61%) had standard regimens used for all patients and 19 (37%) used automatic stop orders for these regimens. In institutions with standard regimens, 18 (58%) used first-generation cephalosporins, 8 (26%) cefuroxime and 4 (13%) cefamandole. First-generation cephalosporins were included in 33 (48%) of the 69 regimens reported to be used in all hospitals surveyed. Cefuroxime, cefamandole, ceftriaxone, and vancomycin were all used in multiple hospitals. Eight (16%) hospitals changed regimen in the last 12 months, with three of these changing to cefuroxime. The data obtained in this most recent survey are similar to the data obtained in the 1985 and 1988 reports. The results of this survey indicated that most hospitals continue to use first-generation cephalosporins for antibiotic prophylaxis in cardiothoracic surgery, but there is considerable variation among institutions.