Pefloxacin and vancomycin vs. gentamicin, colistin sulphate and vancomycin for prevention of infections in granulocytopenic patients: a randomised double-blind study. Randomized trial of the addition of gram-positive prophylaxis to standard antimicrobial prophylaxis for patients undergoing autologous bone marrow transplantation. Imipenem versus gentamicin combined with either cefuroxime or cephalothin as initial therapy for febrile neutropenic patients. Prophylactic antibiotics in cirrhotics with upper gastrointestinal hemorrhage: a prospective, controlled trial. Observations using antiendotoxin antibody (E5) as adjuvant therapy in humans with suspected, serious, gram-negative sepsis. Prevention of gram-positive infections after bone marrow transplantation by systemic vancomycin: a prospective, randomized trial. A prospective, randomized, double-blinded, placebo-controlled trial of empirical teicoplanin in febrile neutropenia with persistent fever after imipenem monotherapy. Comparison of imipenem versus cefuroxime plus tobramycin as empirical therapy for febrile granulocytopenic patients and efficacy of vancomycin and aztreonam in case of failure. Empirical antimicrobial monotherapy in patients after high-dose chemotherapy and autologous stem cell transplantation: a randomised, multicentre trial.
To test the value of pefloxacin for the prevention of infections in patients with chemotherapy-induced neutropenia, oral pefloxacin plus vancomycin (PV) (n = 76) or gentamicin, colistin sulphate and vancomycin (GCV) (n = 74) were administered in a randomised double-blind study. Infections were significantly less severe in the PV than in the GCV group. Patients receiving PV had significantly fewer episodes of bacteraemia and central venous line infections than patients treated with GCV. Gram-positive and gram-negative infections were significantly less frequent in patients receiving PV, because of fewer infections with Staphylococcus species and enterobacteriaceae. Stool culture detected significantly more gram-positive organisms in the PV group and more gram-negative organisms in the GCV group. Thus, PV was more efficacious than GCV for the prevention of gram-positive and gram-negative infections in the neutropenic patients, despite lower efficacy in eradicating gram-positive organisms from the lower intestinal tract. The purpose of the study reported here was to investigate the impact of prophylaxis against gram-positive infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation in a randomized trial. Forty-three patients undergoing high-dose chemotherapy with autologous bone marrow transplant were enrolled in a nonblinded randomized trial to receive or not to receive prophylaxis for gram-positive infections with 10(6) U of penicillin intravenously (i.v.) every 6 h (q6h) (if penicillin allergic, 750 mg of vancomycin i.v. q12h) in addition to standard antimicrobial prophylaxis with 400 mg of norfloxacin orally three times a day, 200 mg of fluconazole orally once a day, and 5 mg of acyclovir per kg of body weight i.v. q12h. The patients were being treated for germ cell cancer (n = 15), breast cancer (n = 16), Hodgkin's disease (n = 3), non-Hodgkin's lymphoma (n = 4), acute myeloid leukemia (n = 1), acute lymphoblastic leukemia (n = 1), and ovarian cancer (n = 3). The trial was stopped because of excess morbidity in the form of streptococcal septic shock in the group not receiving gram-positive prophylaxis. There were significantly fewer overall infections (10 versus 3; P = 0.016) and streptococcal infections (9 versus 1; P = 0.0078) in the group receiving gram-positive prophylaxis. There were no significant differences in the numbers of deaths, duration of broad-spectrum antibiotics, or incidence of neutropenic fever between the two groups. Prophylaxis for gram-positive infections with penicillin or vancomycin is effective in reducing the incidence of streptococcal infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplant. However, this approach may carry a risk of fostering resistance among streptococci to penicillin or vancomycin. A prospective randomized study was conducted to determine the efficacy of imipenem-cilastatin (hereafter referred to as imipenem) (500 mg four times daily) versus combination therapy for febrile neutropenic patients receiving either no prophylaxis or ciprofloxacin for prevention of infections. Combination therapy consisted of gentamicin (80 mg every 8 h) plus either cefuroxime (1,500 mg every 8 h) or cephalothin (1,000 mg every 4 h) for suspected catheter-related infections. Ninety-four neutropenic fever episodes in 87 patients were evaluable for efficacy. The overall clinical rate of response to imipenem was significantly higher than that to combination therapy (91 versus 74%; P = 0.05). The difference in efficacy was most pronounced in patients with microbiologically documented infections (89 versus 53%; P = 0.025), which were predominantly caused by gram-positive bacteria. Differences in susceptibility may have caused the better rate of response to imipenem. Two of 29 gram-positive bacteria were imipenem resistant, whereas 10 were resistant to cephalothin and cefuroxime and 12 were resistant to gentamicin. No causative gram-negative bacterium and 24 gram-positive bacteria were isolated in 61 fever episodes with ciprofloxacin prophylaxis (oral). In contrast, nine causative gram-negative and five gram-positive bacteria were isolated in 33 episodes without prophylaxis. The difference in distribution proved to be statistically significant for gram-negative (P = 0.0001) as well as gram-positive (P = 0.025) bacteria, indicating that ciprofloxacin effectively prevented the occurrence of gram-negative bacteria and may have contributed to the relatively large number of gram-positive bacteria isolated. Empirical initial therapy with imipenem may be a valuable alternative to combination therapy for neutropenic fever episodes. Infections are a frequent complication in cirrhotics, and gastrointestinal bleeding may increase the infection rate. Nonabsorbable antibiotics or quinolone have been employed to decrease the incidence of infection. Since most of these studies were performed in western countries, it is still unclear whether this holds true in our Taiwan cirrhotic patients. Thus we conducted this study using a different formula of antibiotics to evaluate the efficacy of reducing infection rates in cirrhotics with upper gastrointestinal bleeding.
                From July 1999 to August 2000, all cirrhotic in-patients presenting with upper gastrointestinal bleeding but without infection were enrolled. The patients should not have received antibiotics within 2 weeks before admission and should have expected life expectance more than 7 days. Eligible patients who had received endoscopy within 12 hours of hospitalization were randomly allocated into 2 groups. Group A received intravenous cefazolin 1 gm every 8 hours started before endoscopy. After 3 days of prophylactic parenteral antibiotics, antibiotics were shifted to oral cephalexin of 500 mg every 6 hours for 4 days. Group B served as control subjects. All patients received chest X-ray, blood and urine cultures, and ascites culture and sputum culture if ascites and sputum were found. Patients were excluded when initial blood, urine or ascites culture was positive for bacterial growth.
                Ninety-seven patients were included. Group A was comprised of 47 patients and Group B comprised of 50 patients. There was no significant difference in age, sex, Child-Pugh's score or initial hemoglobin between the 2 groups. Proved infection developed in 6 patients of Group B. By contrast, no proved infection was found in Group A. Three organisms belonged to gram-negative bacilli and 3 organisms were gram-positive cocci. The incidence of proved infection during hospitalization was 0% in Group A and 12.0% in Group B (p = 0.027). If possible infection cases (patient's body temperature more than 38 degrees C for more than 2 days) were included, the infection rate was 6.4% in Group A and 26% in Group B (p = 0.013). Infection-related mortality occurred in 2 patients in Group B, but none in Group A.
                Our prophylactic antibiotic treatment proved safe and effective in reducing the infection rate in cirrhotics with upper gastrointestinal bleeding. To evaluate the safety and efficacy of E5 (Xomen-E5), a murine monoclonal immunoglobulin M antibody, in reducing mortality in patients with serious Gram-negative infections. Phase II, single-site study.
                Randomized, double-blind, placebo-controlled study.
                Surgical, neurosurgical and medical ICUs, comprising approximately 30 beds in a multidisciplinary university hospital.
                Patients with clinical evidence of serious infection admitted to the ICU for monitoring of vital signs and for intensive care nursing. Of the 39 patients enrolled in the study, 23 had documented Gram-negative infection.
                Patients suspected of having life-threatening Gram-negative infections received one of two doses of E5 or placebo. Safety and efficacy were assessed by survival on days 3, 7, and 21, appearance of adverse reactions, development of antimurine antibodies, and effects on BP, urine output, WBC count, and temperature.
                Mortality rate from Gram-negative infection 3 days after the last drug (or placebo) infusion was two (22%) of nine deaths in the placebo group compared with 0 of nine for E5 2.5 mg/kg and 0 of five for E5 7.5 mg/kg. At 21 days after therapy, three patients treated with E5 had died. Only one of these three deaths resulted from infection. Eight of 15 E5 patients tested had immunoglobulin G antimurine antibodies by 3 wks after therapy began, but all were asymptomatic.
                E5 was well tolerated and may have the potential to reduce early morbidity and the mortality rate in seriously ill patients with Gram-negative infections. Results from larger phase III studies are needed to confirm these findings. Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation (BMT) and severe streptococcus septicemia has been reported. In order to evaluate the benefit of a gram-positive prophylaxis after BMT, we conducted a prospective, randomized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies. Patients were randomized to receive (n = 30) or not receive (n = 30) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever. All patients were treated in laminar air-flow rooms, received sterile diet, total gut decontamination, and had central venous catheters placed surgically. Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group (P less than .002). All gram-positive infections occurring in the control group were symptomatic (nine septicemia and two local infections), and one patient with Streptococcus septicemia died with pneumonia. Thus, gram-positive prophylaxis was found to decrease infection morbidity after BMT. Moreover, the number of days with fever (P less than .001), and empiric antibiotic therapy (P less than .01) was reduced without added toxicity or cost. This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis. Glycopeptide antibiotics are used extensively in the empirical treatment of febrile patients with neutropenia. To come to a more rational and restricted application of these expensive drugs and to reduce the risk of emergence of resistance, we carried out a prospective, double-blinded, placebo-controlled single-centre study to investigate whether the addition of teicoplanin improved the outcome of neutropenic patients who remained febrile after 72-96 h of imipenem monotherapy. Patients with known infections caused by imipenem-resistant microorganisms were excluded. From the 114 evaluable episodes (out of a total of 125) in 105 patients who met the eligibility criteria, 56 episodes were randomized to receive teicoplanin and 58 to placebo. At 72 h after the start of the assigned intervention, 52 (45.6%) of the patients were afebrile; at the end of the aplastic phase, 10 (8.8%) had succumbed. There was no difference between the two study arms. When febrile episodes were subdivided between microbiologically documented infections, clinically documented infections and fevers of unknown origin, again no significant differences were observed. With the exception of methicillin-resistant bacteria, Gram-positive infections seemed to respond well to imipenem monotherapy. It is concluded that the addition of teicoplanin on empirical grounds, i.e. for persistent fever only, is not necessary and that the use of glycopeptides should be restricted to well-defined clinical situations where methicillin-resistant bacteria are involved. Furthermore, it seems that many neutropenic patients respond slowly over more than 72-96 h even when they are treated with antibacterial drugs such as imipenem that are effective against the causative microorganism. 143 aplastic episodes with fever in 91 haematological patients with granulocytopenia were treated empirically in a randomized prospective study using either imipenem (Imi) or a combination of tobramycin and cefuroxime (T/C). Response after 72 h was significantly better in patients receiving Imi (44/75 vs 27/68, p < 0.05). This was seen especially in patients with bacteriologically proven infections where the isolated staphylococci and streptococci were more susceptible to Imi. In both groups, patients who failed to respond to the initial antibiotic therapy were given vancomycin and aztreonam (V/A). The response rate after another 72 h, measured using the same criteria as after the first 72 h, did not differ statistically between the groups. One patient in each study group died from the bacterial infection, both from Gram-positive bacteraemia. Duration of fever was significantly shorter in the Imi group (4 days vs 7 days, p < 0.04). Serum peak and trough concentrations of the antibiotics were comparable. Both regimens were well tolerated. Our results show that monotherapy with imipenem is superior to the combination of tobramycin and cefuroxime during the first 72 h of therapy and can be safely administered to neutropenic patients with predominantly Gram-positive infections. A combination of vancomycin and aztreonam, given when initial imipenem treatment has failed, was effective in only a few patients. Adjuvant glycopeptide therapy from the outset in the treatment of febrile granulocytopenic patients did not seem worthwhile. We report on 232 patients undergoing autologous haematopoietic stem cell transplantation (ASCT) entered into a multicentre, randomised trial comparing the efficacy and tolerability of meropenem (MPM) with that of piperacillin/tazobactam (P/T) as empirical antimicrobial first-line therapy for febrile neutropenia. In 27.6% of patients in the MPM group and 22.4% in the P/T group, therapy was initially supplemented with a glycopeptide for venous catheter infection or bacteraemia because of coagulase-negative staphylococci. Complete response rate after 72 h was 63.8% in the MPM group and 49.6% in the P/T group (P = 0.034). Overall complete response rate after treatment modification was 94.0% in the MPM group and 93.1% in the P/T group. Median time to defervescence was 2 d in the MPM group and 3 d in the P/T group. The most frequently isolated pathogens were Gram-positive cocci. Treatment was well tolerated in both groups. One patient (0.4%) died from infection. Empirical first-line therapy with MPM as well as with P/T is safe and effective in febrile episodes emerging after ASCT. Higher response rates to primary treatment can be achieved with MPM.
Current evidence shows that the addition of antiGP treatment, namely glycopeptides, prior to documentation of a Gram-positive infection does not improve outcomes.