Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: a randomized controlled trial. Comparison of two prophylactic single-dose intravenous antibiotic regimes in the treatment of patients undergoing elective colorectal surgery in a district general hospital. Clinical efficacy of continuous infusion of piperacillin compared with intermittent dosing in septic critically ill patients. Randomized, open-label, comparative study of piperacillin-tazobactam administered by continuous infusion versus intermittent infusion for treatment of hospitalized patients with complicated intra-abdominal infection. Continuous vs. intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections: pharmacokinetics/pharmacodynamics, bacterial susceptibility and clinical efficacy. Single-dose v. short-term antibiotic therapy for prevention of wound infection in general surgery. A prospective, randomized double-blind trial. Comparison of one dose versus three doses of prophylactic antibiotics, and the influence of blood transfusion, on infectious complications in acute and elective colorectal surgery. Randomized, controlled study of continuous 5-FU infusion starting immediately after curative surgery for advanced colorectal cancer. Improving appropriateness of antibiotic therapy: randomized trial of an intervention to foster reassessment of prescription after 3 days. Prospective study of replacing administration sets for intravenous therapy at 48- vs 72-hour intervals. 72 hours is safe and cost-effective. Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study. Failure of topically applied antibiotics, added to systemic prophylaxis, to reduce perineal wound infection in abdominoperineal excision of the rectum. Administration of drugs by infusion pumps in palliative medicine. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Continuous versus intermittent administration of ceftazidime in intensive care unit patients with nosocomial pneumonia. Antibiotics in elective colon surgery. A randomized trial of oral, systemic, and oral/systemic antibiotics for prophylaxis. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomized, double-blind, placebo-controlled clinical trial. [Clinical effects of continuous infusion and intermittent infusion of meropenem on bacterial pneumonia in the elderly]. Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Optimal frequency of changing intravenous administration sets: is it safe to prolong use beyond 72 hours? A randomized, prospective study measuring outcomes after antibiotic therapy intervention by a multidisciplinary consult team. Parenteral antibiotic prophylaxis of bacterial infections does not improve cost-efficacy of oral norfloxacin in cirrhotic patients with gastrointestinal bleeding. Empiric therapy for infections in patients with granulocytopenia. Continuous v interrupted infusion of tobramycin plus cefamandole. Prospective randomized trial of systemic antibiotics in patients undergoing liver resection. Selective bowel decontamination for the prevention of infection in acute myelogenous leukemia: a prospective randomized trial. Preoperative cell-mediated immunity and duration of antibiotic prophylaxis in relation to postopertive infectious complications. A controlled trial in biliary, gastroduodenal and colorectal surgery. Oral versus systemic antibiotic prophylaxis in elective colon surgery: a randomized study and meta-analysis send a message from the 1990s.
Patients with pneumonia often remain hospitalized after they are stable clinically, and the duration of intravenous antibiotic therapy is a rate-limiting step for discharge. The purpose of this study was to determine whether implementation of an evidence-based guideline would reduce the duration of intravenous antibiotic therapy and length of stay for patients hospitalized with pneumonia.
                In a seven-site, cluster randomized clinical trial, we enrolled 325 control and 283 intervention patients who were admitted by one of 116 physician groups. Within site, physician groups were assigned randomly to receive a practice guideline alone (control arm) or a practice guideline that was implemented using a multifaceted strategy (intervention arm). The effectiveness of guideline implementation was measured by the duration of intravenous antibiotic therapy and length of stay; differences in the rates of discontinuation and hospital discharge were assessed with proportional hazards models. Medical outcomes were assessed at 30 days.
                Intravenous antibiotic therapy was discontinued somewhat more quickly in the intervention group (hazard ratio [HR] =1.23; 95% confidence interval [CI]: 1.00 to 1.52; P = 0.06) than in the control group. Intervention patients were discharged more quickly, but the difference was not statistically significant (HR = 1.16; 95% CI: 0.97 to 1.38; P = 0.11). Fewer intervention (55% [157/283]) than control (63% [206/325]) patients had medical complications during the index hospitalization (P = 0.04), with no differences in other medical outcomes, including mortality, rehospitalization, and return to usual activities, between treatment arms.
                The multifaceted guideline implementation strategy resulted in a slight reduction in the duration of intravenous antibiotic therapy and a nonsignificant reduction in length of stay, without affecting patient outcomes. Two hundred and twenty-nine patients were entered into a study to compare the effectiveness and safety of two single-shot antibiotic regimes in patients undergoing elective colorectal surgery in two district general hospitals. A single shot of intravenous (IV) latamoxef disodium was as effective as an IV combination of cefuroxime and metronidazole in control of wound infection following elective large bowel surgery when given as a bolus at the time of anaesthetic induction. The incidence of major wound infection was 6% and was evenly distributed in the two treatment groups. Half the major wound infections were associated with faecal fistulae. A single shot of IV antibiotic at the time of anaesthetic induction was safe, simple and an effective prophylaxis against major wound infection. There was a low incidence (1.3%) of serious postoperative bleeding and no serious adverse reactions were noted. The overall mortality was 9%. Death was significantly related to elderly patients, a poor performance status, operative contamination and wound infections. Since the bactericidal effects of beta-lactam antibiotics are time dependent, the optimum strategy for their administration could be continuous infusion. In this prospective, randomised controlled trial to evaluate the clinical efficacy of continuous infusion therapy, we evaluated the outcomes for 40 septic critically ill patients who received piperacillin either continuously (2 g intravenously (i.v.) over 0.5 h as a loading dose followed by 8 g i.v. daily over 24 h (n=20)) or as an intermittent infusion (3 g i.v. every 6h over 0.5 h (n=20)). Results from our study demonstrated that the clinical efficacy of piperacillin as a continuous infusion is superior to intermittent administration in critically ill patients. Change in APACHE II scores from baseline at the end of the second, third and fourth days, respectively, were 4.1, 5.1 and 5.2 for continuous infusion and 2.0, 2.6 and 2.8 for intermittent infusion (P< or =0.04). Considering minimum inhibitory concentrations (MICs) of 16 microg/mL and 32 microg/mL, the percentage of time for which piperacillin plasma concentrations were higher than the MIC (%T>MIC) was calculated for each patient in the two groups. For MICs of 16 microg/mL and 32 microg/mL, %T>MIC in the continuous infusion group was 100% and 65% of the dosing interval, respectively; in the intermittent infusion group, %T>MIC was only 62% and 39% of the dosing interval. There was a significant relationship between clinical results and laboratory data. It was shown that the superiority of the clinical efficacy of continuous infusion could be related to piperacillin pharmacodynamics. Continuous infusion significantly reduced the severity of illness as demonstrated by APACHE II scores during therapy. The purpose of this randomized, multicenter, open-label study was to compare the continuous infusion of piperacillin-tazobactam with the standard intermittent infusion in 262 hospitalized patients with complicated intra-abdominal infections. Within 1 day of surgical intervention, eligible patients were randomized (1:1) to piperacillin-tazobactam 12 g/1.5 g administered continuously over 24 h or 3 g/0.375 g administered over 30 min intermittently every 6 h for 4 to 14 days. The demographics of the patients in the groups were similar, with a median APACHE II score of 7 and a median length of hospitalization of 7 days. Among 167 clinically evaluable patients, 86.4% and 88.4% of the patients treated with the continuous infusion and the intermittent infusion, respectively, were clinically cured or improved at the test-of-cure visit (P = 0.817). Bacteriological success was observed in 83.9% and 87.9% of patients (P = 0.597) in the two groups, respectively, and no differences in bacteriological response by pathogen were noted. Defervesence and white blood cell count normalization occurred in the majority of patients within 3 days and were similar between patients receiving the continuous infusion and those receiving the intermittent infusion. Drug-related adverse events were generally mild and were reported in similar numbers of patients in each arm of the trial. The results of this study support continuous infusion as a safe and reasonable alternate mode of administration of piperacillin-tazobactam for the treatment of complicated intra-abdominal infection. To compare the pharmacokinetics/pharmacodynamics, antibiotic resistance and clinical efficacy of continuous (CA) vs. intermittent administration (IA) of cefotaxime in patients with obstructive pulmonary disease and respiratory infections.
                A randomized controlled prospective nonblinded study was performed in 93 consecutive hospitalized patients requiring antibiotics for acute exacerbations of chronic obstructive pulmonary disease. Forty-seven patients received 2 g of cefotaxime intravenously over 24 h plus a loading dose of 1 g, and 46 patients were given the drug intermittently (1 g three times daily).
                Similar pathogens were identified in both groups, being mostly Haemophilus influenzae (51%), Streptococcus pneumoniae (21%) and Moraxella catharralis (18%). Mean minimal inhibitory concentration (MIC) values were also similar before and after treatment in both groups. Clinical cure was achieved in 37/40 (93%) (CA) vs. 40/43 (93%) (IA) of patients (P = 0.93). In microbiologically evaluable patients, criteria such as 70% of treatment time with antibiotic concentrations > or = MIC (CA 100%vs. IA 60% of patients) and/or > or = 5 x MIC (CA 100%vs. IA 55% of patients) were significantly better following continuous administration (P < 0.01). Samples with suboptimal antibiotic concentrations were found in 0% of CA vs. 65% of IA patients (P < 0.01).
                Although clinical cure rates were comparable, continuous cefotaxime administration led to significantly greater proportions of concentrations > MIC and > 5 x MIC compared with intermittent dosing. Continuous administration of cefotaxime at a lower dose [2 g (CA) vs. 3 g (CI)] is equally effective pharmacodynamically and microbiologically, may be more cost-effective and offers at least the same clinical efficacy. Based on these observations, we recommend continuous administration of cefotaxime as the preferred mode of administration. To investigate the effectiveness of a single-dose antibiotic regimen for preventing postoperative wound infection, a prospective, randomized double-blind trial was carried out in patients undergoing "clean-contaminated", "contaminated" or "clean" (vascular) surgery. Both elective and emergency operations were included. Single-dose (preoperative) prophylaxis was compared with short-term prophylaxis (1 dose preoperatively and 2 doses postoperatively). The antibiotics were penicillin, tobramycin and metronidazole in various combinations, and comparisons between single-dose and short-term prophylaxis were made with all the regimens. The incidence of wound infection was 5/277 (1.8%) in the short-term group and 9/287 (3.1%) in the single-dose group. The difference was not statistically significant. Nor was statistically significant difference found when the type of operation and the degree of contamination were considered. Single-dose antibiotic prophylaxis thus gave a low incidence of postoperative wound infection, even in "clean-contaminated" or "contaminated" cases. In a randomized prospective controlled trial involving 311 patients undergoing acute or elective colorectal surgery, the efficacy and safety of two different single dose and one triple dose regimen of antibiotic prophylaxis, as well as the influence of blood transfusion on postoperative infectious complications, were studied. Postoperative infectious complications occurred in a total of 59 patients (19.0 per cent). There were no major differences between the three treatment groups. Thirty-four patients (10.9 per cent) developed abdominal wound infection, 17 patients (5.5 per cent) intra-abdominal abscess and 16 patients (5.1 per cent) anastomotic leakage. Of 202 patients (65.0 per cent) requiring blood transfusion during hospitalization 57 (28.2 per cent; 95 per cent confidence limits of 23-36 per cent) developed infectious complications, whereas two non-transfused patients (1.8 per cent; 95 per cent confidence limits of 0.2 to 6 per cent; P less than 0.001) developed infectious complications. It is concluded that one single dose of antibiotic prophylaxis in acute and elective colorectal surgery is as protective as a triple dose regimen. The development of infectious complications despite antibiotic prophylaxis is strongly related to blood transfusion. The usefulness of adjuvant chemotherapy started immediately following surgery was evaluated.
                A randomized clinical trial was performed on 133 patients with advanced colorectal cancer using oral anticancer agents with one-week continuous 5-FU infusion starting immediately after curative surgery. In Group A and Group B, 300 mg/day of HCFU was orally administered for two years starting two weeks after surgery, and in addition, 333 mg/m2/day of 5-FU was drip infused from the central vein for seven days from the day of surgery in Group B.
                For 1919 days after surgery, there were no significant intergroup differences in overall survival (OS) and disease-free survival (DFS), but OS and DFS in Group B rectal cancer patients were significantly better when compared to Group A rectal cancer patients. On the other hand, OS tended to be better in Group A colon cancer patients, but no significant intergroup differences were seen, while intergroup differences tended to be smaller when corrected for disease stage.
                Continuous 5-FU infusion starting immediately after curative surgery for colorectal cancer was safe. While further investigation is necessary to elucidate the degree of improvement in postoperative prognosis, the results of the present study suggest that continuous 5-FU infusion improves prognosis in advanced rectal cancer. Reassessment of ongoing antibiotic therapy is an important step towards appropriate use of antibiotics. This study was conducted to evaluate the impact of a short questionnaire designed to encourage reassessment of intravenous antibiotic therapy after 3 days.
                Patients hospitalized on the surgical and medical wards of a university hospital and treated with an intravenous antibiotic for 3-4 days were randomly allocated to either an intervention or control group. The intervention consisted of mailing to the physician in charge of the patient a three-item questionnaire referring to possible adaptation of the antibiotic therapy. The primary outcome was the time elapsed from randomization until a first modification of the initial intravenous antibiotic therapy. It was compared within both groups using Cox proportional-hazard modelling.
                One hundred and twenty-six eligible patients were randomized in the intervention group and 125 in the control group. Time to modification of intravenous antibiotic therapy was 14% shorter in the intervention group (adjusted hazard ratio for modification 1.28, 95% CI 0.99-1.67, P = 0.06). It was significantly shorter in the intervention group compared with a similar group of 151 patients observed during a 2 month period preceding the study (adjusted hazard ratio 1.17, 95% CI 1.03-1.32, P = 0.02).
                The results suggest that a short questionnaire, easily adaptable to automatization, has the potential to foster reassessment of antibiotic therapy. We prospectively studied the safety of replacing intravenous delivery systems, including those used in total parenteral nutrition, at 72- compared with 48-hour intervals in 487 patients. Although the prevalence of contamination of intravenous fluid was higher in administration sets replaced at 72-hour intervals (10/664, 1.5%) than in sets replaced every 48 hours (6/710, 0.8%), the difference is not statistically significant. Contamination in both groups was almost exclusively with small numbers of coagulase-negative staphylococci (range, 1 to 27 colony-forming units/mL); no contaminated infusion was associated with clinical signs of sepsis or concordant bacteremia. Contaminants were recovered less frequently from peripheral venous infusions (0.6%) than from infusions used for central venous access or hemodynamic monitoring (1.5%) or total parenteral nutrition (3.6%); infusions in an intensive care unit were more frequently contaminated (2.5%) than infusions on medical and surgical wards (0.9%). These data indicate that extrinsic contamination of intravenous fluid is a rare cause of endemic nosocomial septicemia, and for most infusions it is unnecessary to routinely replace delivery systems more frequently than every 72 hours. A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections. A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%). Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared. Microbiological and clinical outcomes and safety were similar. CIV patients reached the targeted concentrations faster (36 +/- 31 versus 51 +/- 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 +/- 2.2 versus 11.8 +/- 3.9 per treatment, P < 0.0001). The variability between patients in both the area under the serum concentration-time curve (AUC(24h)) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg(2)/liter(2)/h(2) [P = 0.026] and 414 versus 818 g(2) [P = 0.057], respectively). The 10-day treatment cost per patient was $454 +/- 137 in the IIV group and was 23% lower in the CIV group ($321 +/- 81: P < 0.0001). In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV. In a prospective, randomized trial, prophylactic use of topical antibiotics in addition to systemic prophylaxis was studied in patients undergoing abdominoperineal amputation of the rectum. All patients received gentamicin 80 mg and metronidazole 500 mg intravenously at induction of anesthesia, followed by the same dose 8 hourly for 48 hours. In accordance with the randomization, half of the patients were additionally given gentamicin 160 mg + metronidazole 400 mg topically into the perineal wound at closure. Perineal wound infection appeared in 19 of the 41 patients who received both systemic and topical prophylaxis, and in 18 of the 38 with only systemic antibiotics. Cell-mediated immunity was preoperatively assessed with a skin test (Multitest) in all but three patients. Impairment of cell-mediated immunity was associated with significantly heightened rate of wound infection, and these patients did not benefit from topical antibiotics. A retrospective study was carried out in 100 adult patients with advanced malignant disease. They were given subcutaneous continuous infusions of medication for symptom relief. The drugs were administered through a butterfly needle inserted subcutaneously in the anterior chest wall using a battery-operated infusion pump. The indications for using this technique were inability to swallow due to deteriorating general condition, oesophageal obstruction, intestinal obstruction, severe nausea and vomiting, terminal dyspnoea and poor pain control with oral opiates. All patients received morphine; other drugs administered through the syringe driver included hyoscine, metoclopramide, cyclizine, dexamethasone and midazolam. Ninety-four patients continued subcutaneous infusion until death. The mean duration of treatment was 9.1 days. The treatment was well tolerated by the patients and controlled their symptoms satisfactorily in the great majority. The use of continuous subcutaneous infusion via a syringe driver gives good symptom control. In the last days of life when the patients have difficulty tolerating oral medication, continuous subcutaneous infusion is a superior alternative to frequent intermittent parenteral injections. Inappropriate antibiotic use for pulmonary infiltrates is common in the intensive care unit (ICU). We sought to devise an approach that would minimize unnecessary antibiotic use, recognizing that a gold standard for the diagnosis of nosocomial pneumonia does not exist. In a randomized trial, clinical pulmonary infection score (CPIS) (Pugin, J., R. Auckenthaler, N. Mili, J. P. Janssens, R. D. Lew, and P. M. Suter. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am. Rev. Respir. Dis. 1991;143: 1121-1129) was used as operational criteria for decision-making regarding antibiotic therapy. Patients with CPIS </= 6 (implying low likelihood of pneumonia) were randomized to receive either standard therapy (choice and duration of antibiotics at the discretion of physicians) or ciprofloxacin monotherapy with reevaluation at 3 d; ciprofloxacin was discontinued if CPIS remained </= 6 at 3 d. Antibiotics were continued beyond 3 d in 90% (38 of 42) of the patients in the standard as therapy compared with 28% (11 of 39) in the experimental therapy group (p = 0.0001). In patients in whom CPIS remained </= 6 at the 3 d evaluation point, antibiotics were still continued in 96% (24 of 25) in the standard therapy group but in 0% (0 of 25) of the patients in the experimental therapy group (p = 0.0001). Mortality and length of ICU stay did not differ despite a shorter duration (p = 0.0001) and lower cost (p = 0.003) of antimicrobial therapy in the experimental as compared with the standard therapy arm. Antimicrobial resistance, or superinfections, or both, developed in 15% (5 of 37) of the patients in the experimental versus 35% (14 of 37) of the patients in the standard therapy group (p = 0.017). Thus, overtreatment with antibiotics is widely prevalent, but unnecessary in most patients with pulmonary infiltrates in the ICU. The operational criteria used, regardless of the precise definition of pneumonia, accurately identified patients with pulmonary infiltrates for whom monotherapy with a short course of antibiotics was appropriate. Such an approach led to significantly lower antimicrobial therapy costs, antimicrobial resistance, and superinfections without adversely affecting the length of stay or mortality. A prospective, randomized pilot study was undertaken to compare the efficacy of continuous versus intermittent ceftazidime in ICU patients with nosocomial pneumonia. Ceftazidime was administered either as a 3 g/day continuous infusion (CI) or an intermittent infusion (II) of 2 g every 8 h. In addition, all patients received concomitant once-daily tobramycin. The demographics of the evaluable patients (n = 35) were similar between the groups: age (years), CI 46 +/- 16, II 56 +/- 20; Apache score, CI 14 +/- 4, II 16 +/- 6; time (days) from admission to diagnosis, CI 9 +/- 6, II 9 +/- 6. Clinical efficacy, defined as cure/improvement was similar between groups [n (%), CI 16/17 (94), II 15/18 (83)], while microbiological response was also comparable [n (%), CI 10/13 (76), II 12/15 (80)]. Minimal inhibitory concentrations (MICs) for all isolates were measured throughout the treatment course; there was no development of resistance during therapy for either regimen. While limited clinical data exist, our results suggest that the use of ceftazidime by CI administration maintains clinical efficacy, optimizes the pharmacodynamic profile and uses less antibiotic compared with the standard 2 g every 8 h intermittent dosing regimen. A prospective, randomized double-blind study was undertaken to compare the efficacy of three prophylactic regimens (oral neomycin and erythromycin, intravenous cefoxitin, and a combination of both oral and intravenous antibiotics) in patients undergoing elective colorectal surgery. One hundred sixty-nine patients were randomized and 146 patients were evaluable. Septic complications occurred in 11.4 per cent of patients receiving oral antibiotics only, in 11.7 per cent of patients receiving intravenous cefoxitin alone, and in 7.8 per cent of patients receiving both oral and intravenous antibiotics. These differences were not statistically different. The greatest number of septic complications occurred in those patients with anastomotic disruptions. Two patients died (1.3%), both of whom had major anastomotic failures. There was no advantage between any of the groups in the incidence of wound infection (3.9-6.8%). Thus, no advantage could be identified in this study in the combination of oral and intravenous antibiotics in elective colorectal surgery. We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infections, organ dysfunctions, and mortality in a predominantly surgical and trauma intensive care unit (ICU) population. A total of 546 patients were enrolled and stratified according to Acute Physiology and Chronic Health Evaluation (APACHE)-II scores. They were then randomized to receive either 2 x 400 mg of intravenous ciprofloxacin for 4 days, together with a mixture of topical gentamicin and polymyxin applied to the nostrils, mouth, and stomach throughout their ICU stay or to receive intravenous and topical placebo. When receiving prophylaxis, significantly fewer patients acquired infections (p = 0.001, risk ratio [RR], 0.477; 95% confidence interval [CI], 0.367-0.620), especially pneumonias (6 versus 29, p = 0.007), other lower respiratory tract infections (39 versus 70, p = 0.007), bloodstream infections (14 versus 36, p = 0.007), or urinary tract infections (36 versus 60, p = 0.042). Also, significantly fewer patients acquired severe organ dysfunctions (63 versus 96 patients, p = 0.0051; RR, 0.636; 95% CI, 0.463-0.874), especially renal dysfunctions (17 versus 38; p = 0.018). Within 5 days after admission, 24 patients died in each group, whereas 28 patients receiving prophylaxis and 51 receiving placebo died in the ICU thereafter (p = 0.0589; RR, 0.640; 95% CI, 0.402-1.017). The overall ICU mortality was not statistically different (52 versus 75 fatalities), but the mortality was significantly reduced for 237 patients of the midrange stratum with APACHE-II scores of 20-29 on admission (20 versus 38 fatalities, p = 0.0147; RR, 0.508; 95% CI, 0.295-0.875); there was still a favorable trend after 1 year (51 versus 60 fatalities; p = 0.0844; RR, 0.720; 95% CI, 0.496-1.046). Surveillance cultures from tracheobronchial, oropharyngeal, and gastric secretions and from rectal swabs did not show any evidence for the selection of resistant microorganisms in the patients receiving prophylaxis. We compared the clinical effects of continuous infusion and intermittent infusion of meropenem (MEPM) on bacterial pneumonia in the elderly. The subjects were elderly patients (over 65) with moderate community-acquired bacterial pneumonia whose performance status was 3 or 4. They were randomly divided into an intermittent group (0.5 g MEPM was infused morning and evening) and a continuous infusion group (1.0 g/day over 24 hours was infused continuously), and the clinical effects were reviewed prospectively. Clinical efficacy on the third day was 64.0% in the intermittent infusion group and 72.0% in the continuous infusion group, and the overall clinical efficacy was 76.0% in the intermittent infusion group and 80.0% in the continuous infusion group. Administration periods were 13.2 +/- 5.7 days in the intermittent infusion group and 12.1 +/- 4.5 days in the continuous infusion group. These results show no statistically significant difference, and suggest that continuous infusion of MEPM did not have better clinical effect than intermittent administration twice a day in the treatment of elderly patients with moderate community-acquired bacterial pneumonia. Intravenously administered antimicrobial agents have been the standard choice for the empirical management of fever in patients with cancer and granulocytopenia. If orally administered empirical therapy is as effective as intravenous therapy, it would offer advantages such as improved quality of life and lower cost.
                In a prospective, open-label, multicenter trial, we randomly assigned febrile patients with cancer who had granulocytopenia that was expected to resolve within 10 days to receive empirical therapy with either oral ciprofloxacin (750 mg twice daily) plus amoxicillin-clavulanate (625 mg three times daily) or standard daily doses of intravenous ceftriaxone plus amikacin. All patients were hospitalized until their fever resolved. The primary objective of the study was to determine whether there was equivalence between the regimens, defined as an absolute difference in the rates of success of 10 percent or less.
                Equivalence was demonstrated at the second interim analysis, and the trial was terminated after the enrollment of 353 patients. In the analysis of the 312 patients who were treated according to the protocol and who could be evaluated, treatment was successful in 86 percent of the patients in the oral-therapy group (95 percent confidence interval, 80 to 91 percent) and 84 percent of those in the intravenous-therapy group (95 percent confidence interval, 78 to 90 percent; P=0.02). The results were similar in the intention-to-treat analysis (80 percent and 77 percent, respectively; P=0.03), as were the duration of fever, the time to a change in the regimen, the reasons for such a change, the duration of therapy, and survival. The types of adverse events differed slightly between the groups but were similar in frequency.
                In low-risk patients with cancer who have fever and granulocytopenia, oral therapy with ciprofloxacin plus amoxicillin-clavulanate is as effective as intravenous therapy. To determine the safety and cost-effectiveness of replacing the intravenous (IV) tubing sets in hospitalized patients at 4- to 7-day intervals instead of every 72 hours.
                Prospective, randomized study of infusion-related contamination associated with changing IV tubing sets within 3 days versus within 4 to 7 days of placement.
                A tertiary university cancer center.
                Cancer patients requiring IV infusion therapy were randomized to have the IV tubing sets replaced within 3 days (280 patients) or within 4 to 7 days of placement (232 patients). Demographic, microbiological, and infusion-related data were collected for all participants. The main outcome measures were infusion- or catheter-related contamination or colonization of IV tubing, determined by quantitative cultures of the infusate, and infusion- or catheter-related bloodstream infection (BSI), determined by quantitative culture of the infusate in association with blood cultures in febrile patients.
                The two groups were comparable in terms of patient and catheter characteristics and the agents given through the IV tubing. Intent-to-treat analysis demonstrated a higher level of tubing colonization in the 4- to 7-day group versus the 3-day group (median, 145 vs 50 colony-forming units; P=.02). In addition, there were three episodes of possible infusion-related BSIs, all of which occurred in the 4- to 7-day group (P=.09). However, when the 84 patients who received total parenteral nutrition, blood transfusions, or interleukin-2 through the IV tubing were excluded, the two groups had a comparable rate of colonization (0.4% vs 0.5%), with no catheter- or infusion-related BSIs in either group.
                In patients at low risk for infection from infusion- or catheter-related infection who are not receiving total parenteral nutrition, blood transfusions, or interleukin-2, delaying the replacement of IV tubing up to 7 days may be safe, as well as cost-effective Our aim was to identify financial and outcome benefits of therapeutic intervention by a multidisciplinary antimicrobial treatment team composed of pharmacists, a clinical microbiologist, and an infectious disease specialist. Of 252 consecutive inpatients receiving suboptimal intravenous antibiotics identified by the clinical pharmacist, 127 were prospectively randomized to intervention and 125 to a control group. The groups were similar with regard to severity of illness, infection type, and time from admission to randomization. Physicians received timely, detailed reviews of relevant microbiologic and clinical data with recommendations of possible optimal antibiotic choices, dosages, and rationales. Median length of stay after randomization for control and intervention groups was 9.0 days and 5.7 days, respectively (3.3-day difference, p=0.0001). Fifteen (12.0%) and eight patients (6.3%), respectively, died, although the time-specific mortality risk was not significantly different when length of postrandomization follow-up and time to death were taken into account. Physician acceptance of suggestions was 89%. Median patient charges for radiology, laboratory, pharmacy, and room were reduced by $4404/intervention, and median hospital costs were reduced by $2642/intervention. A multidisciplinary antimicrobial therapy team can be a useful information source for physicians, improve outcomes in hospitalized patients receiving intravenous antimicrobials, and result in substantial cost savings. Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients.
                Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (n = 28) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (n = 28) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission.
                Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (p = NS). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (p = NS). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2.
                These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection. A combination of tobramycin sulfate and cefamandole nafate was used as initial empiric therapy for the treatment of 71 evaluable febrile (temperature greater than 38.5 degrees C) episodes in 64 (neutrophils, less than 1,000/microL) adult patients with cancer and granulocytopenia. Carbenicillin sodium or ticarcillin disodium was substituted for cefamandole in patients with Pseudomonas infections and in patients in whom the initial regimen was unsuccessful. Twenty-nine episodes were randomized to receive tobramycin by continuous infusion, while 42 were randomized to receive tobramycin by interrupted infusion. Twenty-seven (79%) of the 34 documented infections responded to the initial empiric antibiotic combination, ten (83%) of 12 being given continuous infusion and 17 (77%) of 22 being given interrupted infusion of tobramycin. Nephrotoxic reaction occurred in 7% of patients treated with continuous infusion and 15% treated with interrupted infusion, mostly patients older than 60 years. Tobramycin, by either continuous or interrupted infusion, plus cefamandole is safe and efficacious empiric therapy for infections in patients with cancer and granulocytopenia. Systemic antibiotics are administered frequently after hepatectomy to prevent infective complications, but their effectiveness is uncertain.
                A total of 127 patients with liver tumours were prospectively randomized into two groups after hepatectomy: in group 1 (62 patients) no antibiotics were given until the appearance of infective complications; in group 2 (65 patients) intravenous cephazolin 1 g every 6 h and gentamicin 80 mg every 8 h were given for 7 days. On the day before surgery all patients received bowel preparation by clear liquid diet and oral antibiotics (neomycin 1 g and erythromycin 1 g, given together in three doses).
                The infective complication rate was 23 per cent in both groups (P = 0.95). The hospital costs were higher in group 2 (P < 0.001). Of the group 1 patients, 51 (82 per cent) did not require antibiotic treatment. No patient in either group died after hepatectomy.
                Postoperative systemic antibiotics cannot prevent infective complications, and their routine use after hepatectomy is unnecessary and costly. The use of antibiotics should be delayed until infective complications and persistent septic symptoms occur. Infection is still a frequent cause of morbidity and mortality in acute myelogenous leukemia (AML) patients receiving chemotherapy. Recently the main cause of infection has changed from gram-negative to gram-positive bacteria and the resistance to antibiotics has increased. This study aimed to access the effectiveness of antimicrobial prophylaxis (AP) with orally absorbable antibiotics.
                Ninety-five AML patients receiving chemotherapy at Catholic Hemopoietic Stem Cell Transplantation Center from March 1999 to July 1999 were randomly divided into the AP group (250 mg ciprofloxacin twice a day, 150 mg roxithromycin twice a day, 50 mg fluconazole once a day) and the control group for a prospective analysis.
                The incidence of fever was 82.6% in the AP group and 91.6% in the control group (p = 0.15). Though classification and sites of infections showed no difference between the two groups, the catheter associated infection occurred more frequently in the AP group in significance. The time interval between initiation of chemotherapy and onset of fever, white blood cell (WBC) count at the onset of fever, duration of leukopenia (WBC < 1,000/mm3), duration of systemic antibiotic therapy, mortality due to infection and hospitalization period from the data starting chemotherapy showed no differences between the two groups. Infections due to gram negative bacteria decreased to 33.3% in the AP group (vs. 92% in the control group), but infections due to gram positive bacteria increased to 66.7% (vs. 8% in the control group). Gram negative bacteria showed 100% resistance to ciprofloxacin in the AP group and gram-positive bacteria showed 90-100% resistance to erythromycin, regardless of the presence of AP.
                The AP could not reduce the occurrence of infection or infection associated death in AML patients receiving chemotherapy. On considering increased gram-positive infection and resistance to fluoroquinolone and macrolide, routine prescription of AP should be reconsidered. Further studies that assess the effectiveness of AP in other malignancies, aplastic anemia and bone marrow transplantation are required. In a prospective controlled trial, 750 patients undergoing elective biliary, gastric or colorectal surgery were randomized to receive short-term or long-term antibiotic prophylaxis--cefotaxime for biliary or gastric, and gentamicin/metronidazole for colorectal operations. In all patients, delayed cutaneous hypersensitivity was preoperatively assessed by simultaneous application of seven standardized recall antigens. Positive reaction was defined as mean diameter greater than or equal to 2 mm, anergy as no positive reaction to any antigen, and a 'score' as the sum (in mm) of all the mean diameters of positive reactions. There was no significant difference in septic complication or mortality rates following short-term vs. long-term prophylaxis. Anergy was found in 21 patients (2.8%), while 63 (8.4%) scored 2-4 and 666 (88.8%) greater than or equal to 5. The incidence of postoperative infectious complications was 25% in the patients with score less than 5 and 10% in those scoring greater than or equal to 5, and the corresponding mortality was 14.3 and 2.1% (both p less than 0.001). In the group with preoperative scores less than 5, the duration of antibiotic prophylaxis influenced neither postopertive infectious complications nor mortality. To compare the efficacy of combined oral and systemic antibiotics (combined) versus systemic antibiotics (systemic) alone in preventing surgical site infection in elective surgery of the colon, and to perform a meta-analysis of randomized studies comparing combined versus systemic antibiotics in elective colon surgery.
                A double-blind, placebo-controlled, randomized clinical trial.
                The Queen Elizabeth Hospital, Montreal, a university-affiliated community hospital.
                Two hundred and fifteen patients scheduled to undergo elective surgery of the colon.
                Patients were randomized to receive neomycin and metronidazole orally (109 patients) or identical placebos (106 patients) on the final preoperative day. All were given amikacin and metronidazole intravenously just before operation. Thirteen randomized series comparing combined and systemic antibiotic prophylaxis in elective colon surgery were identified for meta-analysis.
                Rates of postoperative surgical site infections: risk differences, risk ratios (RRs) and 95% confidence intervals (CIs); organisms found in the colon and wound fat at surgery, and in infected wounds.
                Three patients in the systemic group, and 5 in the combined group were excluded. Wound infections occurred in 5 patients in the combined group but in 17 in the systemic group (p < 0.01, RR = 0.29, 95% CI 0.11-0.75). Bacteria isolated from wound infections and wound fat were similar to those found in the colon. They were more frequent in the colon in the systemic group (p < 0.001) and occurred in wound fat in the systemic group twice as often as in the combined group (p < 0.001). By stepwise logistic regression, the presence of bacteria in wound fat at surgery was the strongest predictor of postoperative wound infection (p < 0.002). In the meta-analysis, the summary weighted risk difference in surgical site infections between groups (d(w)) and the summary RR both favoured combined prophylaxis (d(w) = 0.56, 95% CI 0.26-0.86; RR = 0.51, 95% CI 0.24-0.78; p < 0.001).
                In elective surgery of the colon combined oral and systemic antibiotics are superior to systemic antibiotics in preventing surgical site infections. Orally administered antibiotics add value by reducing bacterial loading of the colon and wound fat contamination, both associated with postoperative wound infection. Meta-analysis of randomized clinical trials reported from 1975 to 1995 supports these conclusions.
No differences in mortality, infection recurrence, clinical cure, super-infection post–therapy, and safety outcomes were reported when continuous infusions of intravenous antibiotics were compared with traditional intermittent infusions of antibiotics. However, the wide confidence intervals suggest that beneficial or harmful effects cannot be ruled out for all outcomes. Therefore, the current evidence is insufficient to recommend the widespread adoption of continuous infusion antibiotics in the place of intermittent infusions of antibiotics. Additinal large prospective randomised trials, with consistent and complete reporting of clinical outcome measures, conducted with concurrent pharmacokinetic and pharmacodynamic studies in special populations, are required to determine whether adoption of continuous antibiotic infusions is warranted in specific circumstances.