Trimethoprim-sulfamethoxazole plus amikacin as first-line therapy and imipenem/cilastatin as second empirical therapy in febrile neutropenic patients with hematological disorders.

One hundred and thirty-nine consecutive episodes of fever were evaluated in 55 patients with hematological disorders during persistent neutropenia. In 121 instances, patients were given trimethoprim-sulfamethoxazole + amikacin (TMP/SMZ + AMI) as an initial antibiotic regimen with clinical success in 51% (i.e. antibiotic treatment was not changed within the first 7 days). Imipenem/cilastatin (I/C) therapy was instituted in: (a) 22 episodes with clinical failure and fever of unknown origin during TMP/SMZ + AMI therapy and (b) 18 episodes with a second fever episode during initially successful TMP/SMZ + AMI therapy. The response rate for all 40 I/C treated episodes was 80%. One neutropenic patient in the whole series died from infectious complications within four weeks from institution of therapy. TMP/SMZ+AMI seems to be a safe and inexpensive "standard" antibiotic regimen in neutropenic patients. I/C appears to have good efficacy when used as secondary therapy after failure with TMP/SMZ+AMI.     

Imipenem/Cilastatin Monotherapy as Salvage Treatment in Febrile Neutropenic Patients

Abstract

Imipenem/cilastatin (I/C) monotherapy was used as salvage treatment in 55 neutropenic patients (58 fever episodes) after treatment failure on first-line antibiotic therapy. Successful antibiotic treatment was defined as eradication of all signs, symptoms and microbiologic evidence of infection on I/C monotherapy alone. Twentyfive out of the 58 episodes (43%) were classified as success, 6 episodes (10%) as initial response but the regimen had to be modified (amphotericin B was added) and 27 episodes (47 %) as failures. In episodes with documented infections 9 out of 23 (39%) were classified as success. All patients survived during the first 72 hours after change to I/C therapy. One patient had to discontinue I/C due to a skin rash.

In conclusion, the use of a treatment algorithm with I/C monotherapy as second-line treatment was safe and effective. Other antimicrobial agents, most often vancomycin and/or amphotericin B, had to be added in half of the patients.     

Cefepime as empirical monotherapy in febrile patients with hematological malignancies and neutropenia: a randomized, single-center phase II trial.

The purpose of this phase II trial was to evaluate the efficacy and safety of cefepime monotherapy in patients with neutropenia expected to last more than 7 days. Sixty-nine patients with neutropenia (<0.5 x 10(9)/1) were randomized during 94 episodes of fever to receive either cefepime monotherapy (n=76) or combination therapy with trimethoprim/sulfamethoxazole plus amikacin (TMP/SMZ plus AMI, n=18). A successful response to cefepime was seen in 31/76 (41%) episodes, with 10/36 (28%) in microbiologically documented infections, 3/4 (75%) in clinically documented infections and 18/36 (50%) in fever of unknown origin. No patient in either treatment group died due to the presenting infection. One patient in the cefepime group discontinued treatment due to a rash. Susceptibility testing of blood isolates by E-test strip showed low MIC values to cefepime for most isolates. It is concluded that cefepime monotherapy appeared both safe and effective as empirical therapy in patients with febrile neutropenia.     

An Open Evaluation of Triple Antibiotic Therapy Including Vancomycin for Febrile Bone Marrow Transplant Recipients with Severe Neutropenia

Abstract

Infectious complications still represent a major problem in patients submitted to bone marrow transplant (BMT); approximately 40% of febrile episodes are associated with infection and one-third of these are bacteremias. Opinions about the best appropriate empiric regimens are based on evaluation of cost, potential for adverse side-effects, development of bacterial resistance, prevalent nosocomial infections.

In order to assess the clinical and microbiological effectiveness of an aggressive approach, we performed a prospective open study in 72 neutropenic febrile BMT patients, employing a triple antibiotic association including amikacin 500mg x 8h, ceftazidime 2g x 8h, vancomycin 500mg x 8h as first-line empiric treatment. For the purpose of this study, a lasting return of temperature to normal and complete disappearance of either clinical or bacteriological signs of infection without any modification of therapy was considered as success; the persistence of fever after 72 hours or a protocol change was considered as failure. Eighty episodes were enrolled during the course of the study; bacteriological evidence of infection was obtained in 23 (28.7%) febrile episodes. Median duration of antibiotic administration and of febrile episodes were 5 and 2 days respectively. Overall response rate based on clinical responses was 87% and 91% in microbiological documented infections. Death due to sepsis nor toxicity were observed. This triple antibiotic combination appears to be a very effective regimen for the empiric treatment of febrile episodes in severely neutropenic BMT recipients.     

Ceftazidime and amikacin as empiric antibiotic therapy of febrile granulocytopenic patients with hematological malignancies. Report of 171 consecutive episodes

One hundred and seventy-one consecutive febrile episodes occurring in 130 neutropenic adult patients with hematological malignancies (mainly acute leukemia) were empirically treated with a combination antibiotic therapy consisting of ceftazidime (100 mg/kg/day) + amikacin (15 mg/kg/day). Of these, 161 were evaluable. In the majority of episodes (75 per cent) documented infections were identified as a cause of fever. There were 73 bacteremias (34 Gram-negative, 29 Gram-positive, 10 polymicrobial). One third of patients had pneumonia. Cure without change of the initial regimen was achieved in 45/73 (62 per cent) bacteremic episodes and in 12/13 episodes of microbiologically documented infections without bacteremia. There were 35 clinically documented infections and 26 (74 per cent) of these were cured. Of the 40 patients presenting with possible infections 26 (65 per cent) were cured. Overall, cure without modification of the initial antibiotic combination was achieved in 109/161 episodes (68 per cent). In spite of the frequent occurrence of persistent neutropenia (82 per cent), the infectious mortality was low (8.6 per cent), and often due to superinfection. The deaths due to primary infections were 6/161 (3.7 per cent). Side effects were mild and rare. In our experience ceftazidime + amikacin was an effective and safe empirical regimen for this population of hematologic patients with persistent neutropenia and severe documented infections.     

Comparison of Trimethoprim-Sulfamethoxazole,Cephadroxil and Cefprozil as Prophylaxis for Recurrent Urinary Tract Infections in Children

Abstract

The aim of this study was to compare the efficacy of prophylactic trimethoprimsulfamethoxazole (TMP/SMZ), cefprozil and cephadroxil treatments in children who have recurrent urinary tract infection, but no urinary tract pathology. After acute urinary tract infections (UTIs) were treated, the patients were divided into 3 groupsrandomly and TMP/SMZ was given to 21 patients, cephadroxil was given to 25 patients and cefprozil was given to 34 patients for 3 months—one dose at night. All patients were followed for 6 months following prophylaxis. The frequency of symptomatic UTIs among groups during prophylaxis was not statistically different, however the number of symptomatic UTIs in the cephadroxil group was lower than the other groups. Asymptomatic bacteriuria episodes were detected in TMP/SMZ and cefprozil groups, whereas no asymptomatic bacteriuria episodes were seen in the cephadroxil group. The number of patients with symptomatic UTI during the follow-up period was not different between groups, however all the asymptomatic bacteriuria episodes were encountered in the cefprozil group. In conclusion, in this study cephadroxil was found to be slightly superior to TMP/SMZ and cefprozil in preventing asymptomatic bacteriuria episodes and symptomatic UTIs in children with recurrent UTI and normal urinary tract system.     

Randomized trial of oral versus intravenous antibiotics in low-risk febrile neutropenic patients with lung cancer

BACKGROUND: Neutropenic fever is one of the most serious adverse effects of cancer chemotherapy. Neutropenia may cause a life-threatening bacterial infection. Therefore, febrile neutropenic inpatients are empirically treated with intravenous broad-spectrum antibiotics. Recently, several studies have suggested the presence of low-risk groups among febrile neutropenic patients. METHODS: A prospective randomized trial was conducted to compare treatment with oral ciprofloxacin (200 mg) and amoxicillin-clavulanate (375 mg) administered every 8 h against that with intravenous ceftazidime (1 g) administered every 12 h in low-risk febrile neutropenic patients with lung cancer. All patients received chemotherapy and antibiotic therapy while being hospitalized. RESULTS: A total of 177 patients with lung cancer agreed to participate in this study prior to undergoing chemotherapy. Among them, a total of 36 neutropenic patients with 42 febrile episodes were enrolled in the study. Treatment was successful without the need for modification in 91% of the episodes in patients receiving the oral regimen and 79% of the episodes in patients receiving the intravenous regimen. No treatment-related deaths occurred. One patient developed nausea while receiving the oral regimen, so the oral regimen was changed to the intravenous regimen in this patient. CONCLUSIONS: This prospective study suggested that treatment with oral antibiotics ciplofloxacin plus amoxicillin-clavulanate was effective for low-risk febrile neutropenic patients after chemotherapy.     

Meropenem Versus Piperacillin-Tazobactam as Empiric Therapy for Febrile Neutropenia in Pediatric Oncology Patients

Background: Infection is a serious cause of mortality in febrile neutropenia of pediatric cancer patients.Recently, monotherapy has replaced the combination therapy in empirical treatment of febrile neutropenia.Since there has been no reported trial comparing the efficacy of meropenem and piperacillin-tazobactam (PIP/TAZ) monotherapies, the present retrospective study was conducted to compare safety and efficacy in febrileneutropenic children with cancer. Materials and Methods: Charts of febrile, neutropenic children hospitalizedat our center between March 2008 and April 2011 for hemato-oncological malignancies were reviewed. Patientsreceived PIP/TAZ 360 mg/kg/day or meropenem 60 mg/kg/day intravenously in three divided doses. Durationof fever and neutropenia, absolute neutrophil count, modification, and success rate were compared between thetwo groups. Resolution of fever without antibiotic change was defined as success and resolution of fever withantibiotic change or death of a patient was defined as failure. Modification was defined as changing the empiricalantimicrobial agent during a febrile episode. Results: Two hundred eighty four febrile neutropenic episodes weredocumented in 136 patients with a median age of 5 years. In 198 episodes meropenem and in 86 episodes PIP/TAZ were used. Duration of fever and neutropenia, neutrophil count, sex, and primary disease were not differentbetween two groups. Success rates and modification rate between two groups showed no significant differences(p>0.05). Overall success rate in the meropenem and PIP/TAZ groups were 92.4% and 91.9% respectively. Noserious adverse effects occurred in either of the groups. Conclusions: Meropenem and PIP/TAZ monotherapyare equally safe and effective in the initial treatment of febrile neutropenia in children with cancer.     

Comparison of trimethoprim-sulfamethoxazole, cephadroxil and cefprozil as prophylaxis for recurrent urinary tract infections in children

The aim of this study was to compare the efficacy of prophylactic trimethoprim-sulfamethoxazole (TMP/SMZ), cefprozil and cephadroxil treatments in children who have recurrent urinary tract infection, but no urinary tract pathology. After acute urinary tract infections (UTIs) were treated, the patients were divided into 3 groups randomly and TMP/SMZ was given to 21 patients, cephadroxil was given to 25 patients and cefprozil was given to 34 patients for 3 months--one dose at night. All patients were followed for 6 months following prophylaxis. The frequency of symptomatic UTIs among groups during prophylaxis was not statistically different, however the number of symptomatic UTIs in the cephadroxil group was lower than the other groups. Asymptomatic bacteriuria episodes were detected in TMP/SMZ and cefprozil groups, whereas no asymptomatic bacteriuria episodes were seen in the cephadroxil group. The number of patients with symptomatic UTI during the follow-up period was not different between groups, however all the asymptomatic bacteriuria episodes were encountered in the cefprozil group. In conclusion, in this study cephadroxil was found to be slightly superior to TMP/SMZ and cefprozil in preventing asymptomatic bacteriuria episodes and symptomatic UTIs in children with recurrent UTI and normal urinary tract system.     

Efficacy of oral prophylactic antibiotics in neutropenic afebrile oncology patients: a systematic review of randomised controlled trials

The use of oral prophylactic antibiotics in oncology patients is still a matter of debate. A systematic review was performed to assess the evidence for the effectiveness of oral prophylactic antibiotics to decrease bacteraemia and infection-related mortality in oncology patients during neutropenic episodes. Medline, Embase and the Cochrane register of controlled trials were searched from 1966 until 2002. The main outcome was the number of patients with documented bacteraemia (Gram-negative or Gram-positive bacteraemia) and infection related mortality. Data-extraction and quality assessment were performed independently by two reviewers. A total of 22 trials met the inclusion criteria. Seventeen trials compared prophylaxis (quinolones or Trimethoprim/sulfamethoxazole (TMP/SMZ)) to no prophylaxis. The incidence of Gram-negative bacteraemia decreased significantly (pooled OR 0.39, 95% CI 0.24-0.62) without an increase in Gram-positive bacteraemia. Quinolone-based regimens showed a stronger reduction in Gram-negative bacteraemia while TMP/SMZ based regimens were more effective in Gram-positive bacteraemia. Infection related mortality due to bacterial causes decreased with the use of prophylactic antibiotics (pooled OR 0.49, 95% CI 0.27-0.88). No increase in fungaemia or fungal related mortality was seen with the use of oral prophylaxis. In conclusion, this study has shown that oral prophylactic antibiotics decreased Gram-negative bacteraemia and infection related mortality due to bacterial causes during neutropenic episodes in oncology patients.     

Ceftriaxone plus Amikacin in a Single Daily Dose as Empiric Antibiotic Therapy in Granulocytopenic Patients

Summary

In our study ceftriaxone plus amikacin were employed as empirical antibiotic therapy. This antibiotic treatment allows for a once daily administration and has a broad spectrum of activity. 21 febrile episodes were treated with an antibiotic regimen of ceftriaxone 50 mg/kg/day and amikacin 30-35 mg/kg/day i.v. An earlier pilot study was carried out in which 47 febrile episodes were treated with an antibiotic regimen of ceftriaxone 80-100 mg/kg/day i.v. and amikacin 30-35 mg/kg/day i.v. in a single dose.

The overall response rate was 76% (16/21) and 79% (37/47) for the pilot study.

During the treatment no side effects were observed and aminoglycoside related toxicity did not occur.

In conclusion, this empiric antibiotic therapy gives a high response rate and allows for a single daily administration.     

Outpatient treatment of neutropenic fever with oral antibiotics and granulocyte colony-stimulating factor.

In recent years, several cancer patients who developed neutropenic fever were effectively treated on an outpatient basis with either intravenous or oral antibiotics. This approach is associated with reduced cost and improved patient convenience. However, the appropriate antibiotic regimen and the role of growth factors have not been established yet. In order to address these issues we performed a nonrandomized phase II study to assess the feasibility and efficacy of an oral antibiotic regimen in combination with granulocyte colony-stimulating factor (G-CSF) for the outpatient treatment of cancer patients with low-risk neutropenic fever. In 50 patients with solid tumors or lymphoma, 60 episodes of neutropenic fever were treated with the combination of oral ofloxacin 400 mg twice a day, oral amoxicillin 1 g 3 times a day and G-CSF 5 microgram/kg/day subcutaneously. Patients receiving G-CSF prophylaxis were eligible for our study. Oral antibiotics were administered for at least 5 days and G-CSF was continued until resolution of neutropenia. Our patients were ambulatory, hemodynamically stable, and without significant comorbidity. Our combination was successful in 57 episodes (95%) with a median time for fever resolution of 3 days (range: 1-5 days). There was no significant toxicity associated with the antibiotic regimen with the exception of one case of reversible renal impairment. The role of G-CSF in the success of our antibiotic treatment is highly questionable since one half of our patients developed fever while on G-CSF prophylaxis. The combination of oral ofloxacin and amoxicillin with G-CSF is highly effective for the outpatient treatment of cancer patients who develop uncomplicated febrile neutropenia. The relative contribution of G-CSF needs clarification with a prospective randomized study.     

An open evaluation of triple antibiotic therapy including vancomycin for febrile bone marrow transplant recipients with severe neutropenia.

Infectious complications still represent a major problem in patients submitted to bone marrow transplant (BMT); approximately 40% of febrile episodes are associated with infection and one-third of these are bacteremias. Opinions about the best appropriate empiric regimens are based on evaluation of cost, potential for adverse side-effects, development of bacterial resistance, prevalent nosocomial infections. In order to assess the clinical and microbiological effectiveness of an aggressive approach, we performed a prospective open study in 72 neutropenic febrile BMT patients, employing a triple antibiotic association including amikacin 500 mg x 8h, ceftazidime 2 g x 8 h, vancomycin 500 mg x 8 h as first-line empiric treatment. For the purpose of this study, a lasting return of temperature to normal and complete disappearance of either clinical or bacteriological signs of infection without any modification of therapy was considered as success; the persistence of fever after 72 hours or a protocol change was considered as failure. Eighty episodes were enrolled during the course of the study; bacteriological evidence of infection was obtained in 23 (28.7%) febrile episodes. Median duration of antibiotic administration and of febrile episodes were 5 and 2 days respectively. Overall response rate based on clinical responses was 87% and 91% in microbiological documented infections. Death due to sepsis nor toxicity were observed. This triple antibiotic combination appears to be a very effective regimen for the empiric treatment of febrile episodes in severely neutropenic BMT recipients.     

Once-Daily Dosing Regimen for Aminoglycoside plus Betalactam Combination Therapy of Serious Lower Respiratory Tract Infections

Abstract

Aminoglycosides are important antibacterial agents for treatment of serious gram-negative bacillary infections including lower respiratory tract infection. Once-daily aminoglycosides result in higher peak and lower trough plasma concentrations than conventional multiple daily dosing regimens; once-daily aminoglycoside therapy is equally effective, generally less toxic and much less expensive and therefore this regimen is more and more frequently used for treatment of suspected or confirmed gram-negative bacillary infections and of febrile episodes in neutropenic patients, in particular in combination with an appropriate betalactam antibiotic. Despite the lack of studies on this topic, once-daily aminoglycosides in combination with a betalactam agent can be used in subjects with lower respiratory tract infection, including patients with cystic fibrosis, in which tobramycin appears to be the aminoglycoside antibiotic of choice.     

Outpatient treatment of low-risk neutropenic fever in cancer patients using oral moxifloxacin

BACKGROUND: Oral-based antibiotic therapy is the standard of care in the management of cancer patients with low-risk neutropenic fever. Nevertheless, to the authors' knowledge, the best antibiotic regimen and the feasibility of ambulatory treatment have not been clearly defined. METHODS: The authors evaluated the efficacy and safety of moxifloxacin as outpatient treatment in cancer patients with febrile neutropenia who were selected according to the recently proposed Multinational Association for Supportive Care in Cancer (MASCC) risk assessment model. Moxifloxacin was given at a dose of 400 mg orally once daily. RESULTS: Fifty-four patients with solid and hematologic malignancies, the majority of whom (84%) had advanced disease, were included in the current study. The median neutrophil count at the time of study entry was 340/mm3 (range, 20-950/mm3) and the median duration of neutropenia was 4 days (range, 3-14 days). Of 55 neutropenic episodes, 50 (91%) had a successful outcome with a median time to defervescence of 2 days (range, 1-5 days). A multivariate analysis indicated that severe neutropenia (an absolute neutrophil count of < 100 mm3) was the only independent factor associated with treatment failure (P < 0.04). Moxifloxacin was found to be well tolerated and there were no infectious deaths reported. CONCLUSIONS: The results of the current study demonstrated that moxifloxacin was a highly effective and safe regimen in the outpatient treatment of cancer patients with febrile neutropenia.     

Meropenem versus ceftazidime in the treatment of cancer patients with febrile neutropenia: a randomized, double-blind trial.

PURPOSE: To compare meropenem, a carbapenem antibiotic, with ceftazidime for the empirical treatment of patients with febrile neutropenia. PATIENTS AND METHODS: A prospective, double-blind, randomized clinical trial was conducted at medical centers in North America and the Netherlands. A total of 411 cancer patients (196 treated with meropenem and 215 treated with ceftazidime), who had 471 episodes of fever, participated in the trial. For each neutropenic episode, patients were allocated at random to receive intravenous administration of meropenem (1 g every 8 hours) or ceftazidime (2 g every 8 hours). Treatment could be modified at any time. Key end points were clinical and bacteriologic outcomes, eradication of infecting organism, and adverse events. RESULTS: The rate of successful clinical response at the end of therapy was significantly higher for patients treated with meropenem than for those on ceftazidime for all episodes (54% v 44%, respectively) and for episodes of fever of unknown origin (62% v 46%, respectively), but differences between groups were not statistically significant for clinically defined or microbiologically defined infections. Meropenem was significantly more effective than ceftazidime in severely neutropenic (相似文献   

Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: a prospective randomised controlled single centre study

Neutropenic sepsis remains a potentially life-threatening complication of anticancer chemotherapy. However, it is possible to identify patients who are at low risk for serious complications and for whom less-intensive, more-convenient treatment may be appropriate. The aim of this study was to assess the efficacy and safety of oral antibiotics in conjunction with early hospital discharge in comparison with standard in-patient intravenous antibiotics in patients with low-risk neutropenic fever. In all, 126 episodes of low-risk neutropenic fever occurred in 102 patients. Patients were randomised to receive either: an oral regimen of ciprofloxacin (750 mg 12 hourly) plus amoxicillin-clavulanate (675 mg 8 hourly) for a total of 5 days, or a standard intravenous regimen of gentamicin and tazocin (piperacillin/tazobactam) until hospital discharge. Patients randomised to oral antibiotics were eligible for discharge following 24 h of hospitalisation, if clinically stable and symptomatically improved. The efficacy of the two arms was similar: initial treatment was successful without antibiotic modification in 90% of episodes in the intravenous arm and 84.8% of episodes in the oral arm, P=0.55, absolute difference between the groups 5.2%; 95% confidence interval (CI) for the difference -7 to 17.3%. Only one episode in the oral arm was associated with significant clinical deterioration: this occurred within the initial in-patient assessment period. The median in-patient stay was 4 days in the intravenous arm (range 2-8) and 2 days in the oral arm (range 1-16 days), P&<0.0005. The reduction in hospital stay led to significant cost-savings in the oral arm. In conclusion, this study suggests that oral antibiotics in conjunction with early hospital discharge for patients who remain stable after a 24 h period of in-patient monitoring offers a feasible and cost-effective alternative to conventional management of low-risk neutropenic fever.     

Cefoperazone versus cefotaxime, plus amikacin or sisomicin, in fever and infection in hematologic granulocytopenic patients

Forty patients with leukemia or aplastic anemia were randomized to receive one of the following antibiotic regimens at the onset of fever during granulocytopenia: cefoperazone + amikacin (regimen A), cefoperazone + sisomicin (regimen B), cefotaxime + amikacin (regimen C), cefotaxime + sisomicin (regimen D). All patients were receiving gut decontamination at the time of randomization. Patients were monitored twice weekly with swabs and cultures for bacteria and fungi. Overall, there were 56 febrile episodes: 31 were proven bacterial, 3 were probable, and 16 were of unknown origin. Response rates were comparable in all 4 treatment regimens: 90%, 91%, 92% and 92%, respectively. Three patients died of bacterial infections (2 Gram+, 1 Gram-), one patient died with probable infection, 6 febrile episodes were related to fungal infection (Candida), and 2 patients died. The mortality rate was comparable in all groups. Two patients died of renal failure. Abnormalities in liver function tests were observed, but were without consequences. There were no statistical differences in renal-hepatic toxicity in the 4 arms.     

Ceftriaxone as a Single Agent in Empirical Therapy of Unexplained Fever in Granulocytopenic Children with Solid Tumors

Abstract

The optimal management of fever in granulocytopenic cancer patients remains controversial. Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile granulocytopenic patients with solid tumors. Available data show that response to empiric therapy is often more related to disease classification (solid tumors vs. acute leukemia) than to the regimen used. In this study we based empiric monotherapy on the underlying disease (solid tumors) in treating 33 episodes of fever in 26 granulocytopenic children with cancer. We investigated the potential effectiveness of single daily doses of ceftriaxone administered empirically in febrile granulocytopenic children with solid tumors. Fever was treated successfully with ceftriaxone monotherapy in 91% (30/33) of febrile episodes. None of the patients died as a result of primary infection. These results suggest that empirical monotherapy with once-daily ceftriaxone is safe and effective. In addition, when compared with other extended-spectrum cephalosporins such as ceftazidime, once-daily administration of ceftriaxone reduces cost and patient inconvenience, allowing convenient parenteral therapy even on an outpatient basis.