cefepime and Chemotherapy-Induced-Febrile-Neutropenia

Beta lactams are standard empirical therapy for febrile neutropenia (FN). The aim of this study was to evaluate the efficacy and safety of cefepime monotherapy compared with cefoperazone/sulbactam plus amikacin (CS + A) for empirical treatment of high risk FN.. One hundred seventy-five patients with 336 FN episodes were randomized to receive either cefepime (2 g q8h for adults and 50 mg/kg q8h for children) or CS (2 g q8h for adults and 50 mg/kg q8h for children) plus amikacin (15 mg/kg once a day). Positive response was defined as afebrile within 72 h of starting antibiotics, persistent afebrile status more than 48 h and no requirement of second-line antibiotics and antifungal agents.. Three hundred thirty-six episodes were assessable for efficacy (168 cefepime, 168 CS + A). The positive response to antibiotics was identical for cefepime (53%) and CS + A (53%). Positive response was similar in MDI (microbiologically documented infection), 50 vs. 35% (p = 0.248), CDI (clinically documented infection), 50 vs. 35% (p = 0.259), combination CDI + MDI, 25 vs. 15% (p = 0.400), FUO (fever of unknown origin), 68 vs. 72% (p = 0.577) respectively in the two groups. The successful discontinuation of antibiotics at 72 h in FUO was similar in both groups (60 vs. 59%, p = 0.544). Total drug-related adverse events were similar in both groups (8 vs. 6%) except renal dysfunction was high in CS + A (1 vs. 7 events). Mortality was the same between two groups (8 vs 7%).. Cefepime monotherapy and CS + A had similar efficacy as first-line therapy for FN. Discontinuation of empirical antibiotics is safe and feasible approach in selected group of FUO patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Agents; Cefepime; Cefoperazone; Cephalosporins; Chemotherapy-Induced Febrile Neutropenia; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neoplasms; Sulbactam; Survival Analysis; Withholding Treatment; Young Adult

We conducted an open-label, randomized study to evaluate the clinical efficacy of cefozopran, meropenem or imipenem-cilastatin using cefepime as a control in febrile neutropenia (FN) patients. Three hundred and seventy-six patients received cefepime, cefozopran, meropenem or imipenem-cilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in cefozopran, meropenem or imipenem-cilastatin patients compared with cefepime in the per-protocol population (delta = 10%). The response rates for cefozopran, meropenem and imipenem-cilastatin were not significantly different compared with cefepime (cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) (p = 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for cefozopran, meropenem and imipenem-cilastatin compared with cefepime were -5.9% (95% confidence interval (CI): -20.1-8.4), -0.7% (95% CI: -14.6-13.3), and 5.7% (95% CI: -8.1-19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3-5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count ≤ 100 × 10(6)/L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3-5, p = 0.006, and 76% versus 48% at day 7, p = 0.002). Our results suggest that the effects of these four drugs as empiric therapy were virtually the same for adult FN patients, although non-inferiority was shown only in imipenem-cilastatin compared with cefepime (clinical trial number: UMIN000000462).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefepime; Cefozopran; Cephalosporins; Chemotherapy-Induced Febrile Neutropenia; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Humans; Imipenem; Male; Meropenem; Middle Aged; Prospective Studies; Thienamycins; Young Adult

We assessed the efficacy and safety of cefepime monotherapy (1 g intravenously every 8 h) for febrile neutropenia in patients with lung cancer in a multi-institutional phase II study. Patients treated with chemotherapy with or without radiotherapy for lung cancer were eligible for this study. Other eligibility criteria included fever (temperature of ≥38.0 °C) and an absolute neutrophil count of <500/mm(3) or <1000/mm(3) with an expected decline to <500/mm(3) within the next 48 h. Risk assessment was performed using the Multinational Association of Supportive Care in Cancer risk-index score. Cefepime 1 g was given intravenously every 8 h. The primary endpoint was the response rate at the end of cefepime therapy. Co-administration of granulocyte-colony-stimulating factor was permitted. Of 54 patients enrolled, 39 were classified in the low-risk group and 15 in the high-risk group. Overall response rate was 78% (95% CI: 64.4-88.0%). The response rates were 85% (95% CI: 69.5-94.1%) in the low-risk group and 60% (95% CI: 32.3-83.7%) in the high-risk group, respectively. One patient died from septic shock due to Enterobacter cloacae bacteremia. There was no significant adverse event. Cefepime 1 g intravenously every 8 h appears to be effective for febrile neutropenia in patients with lung cancer, especially in those with low-risk febrile neutropenia, and is well tolerated.. UMIN Clinical Trials Registry, UMIN000006157.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antineoplastic Agents; Cefepime; Cephalosporins; Chemoradiotherapy; Chemotherapy-Induced Febrile Neutropenia; Female; Humans; Lung Neoplasms; Male; Middle Aged

We investigated the treatment outcomes before and after the addition of amikacin to cefepime monotherapy as an initial empirical antibiotic treatment in pediatric cancer patients with febrile neutropenia.. This was a retrospective historical cohort study. The subjects were pediatric cancer patients who visited the emergency room at the Samsung Medical Center, Seoul, Korea, due to chemotherapy-induced febrile neutropenia, between January 2011 and December 2016. Since September 2014, the empirical antimicrobial treatment regimen for febrile neutropenia was changed from high-dose cefepime monotherapy to combination therapy of adding a single dose of amikacin.. Two hundred twenty-five bacteremia episodes in 164 patients were reported during the study period. Bacteremia caused by cefepime-resistant Gram-negative bacteria was observed in 16% of patients before September 2014 and in 21% of the patients after September 2014 (P = 0.331). Use of appropriate empirical antibiotic treatments increased from 62% to 83% following addition of amikacin to cefepime treatment (P = 0.003). The duration of fever was shorter in the cefepime plus amikacin group than in the cefepime group (22 vs. 34 hours, P = 0.014); however, rates of septic shock and pediatric intensive care unit hospitalizations were not significantly different between the 2 groups (septic shock, both 7%, P = 0.436; pediatric intensive care unit 3% vs. 1%, P = 0.647).. We observed no additional benefit of amikacin addition to high-dose cefepime monotherapy. Therefore, adding amikacin to cefepime monotherapy in conditions where cefepime-resistant Gram-negative bacteremia amounts to 20% or less may not be justified.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Bacteremia; Cefepime; Chemotherapy-Induced Febrile Neutropenia; Child; Child, Preschool; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Infant; Male; Neoplasms; Retrospective Studies; Treatment Outcome

Patients with acute leukemia are susceptible to chemotherapy-induced severe myelosuppression, and therefore are at a high risk for febrile neutropenia (FN). In such cases, the use of broad-spectrum antibiotics such as fourth-generation cephalosporins and carbapenems is recommended as first-line antimicrobial treatment; however, the effectiveness of these agents in patients with acute myeloid leukemia (AML) has not been investigated in detail. We retrospectively examined and evaluated the effectiveness of first-line antibiotic treatment regimens for chemotherapy-induced FN in patients with AML in Japanese Red Cross Nagoya Daiichi Hospital. The evaluated first-line treatment regimens were as follows: cefozopran (CZOP) + amikacin (AMK) in 38 cases, cefepime (CFPM) alone in 2 cases, CFPM + AMK in 2 cases, piperacillin (PIPC) + AMK in 2 cases, and CZOP alone in 1 case. Additionally, prophylactic antifungal agents were administered in all cases. Markedly effective, effective, moderately effective, and ineffective responses occurred in 31.1%, 8.9%, 8.9%, and 51.1%, respectively, of the treated cases. The response rate, defined as the combination of markedly effective and effective outcomes, was 40.0%. In 11 cases, impairment of renal functions were observed, and they were associated with combination treatments including AMK; nine of these were associated with a glycopeptide. The combination of CZOP with AMK (84.4%) was the most commonly used first-line treatment for FN in patients with AML; carbapenem or tazobactam/PIPC has never been used for treatment of such cases. Our findings demonstrate that fourth-generation cephems will be an effective first-line treatment for FN in patients with AML in our hospital.

Topics: Adult; Aged; Amikacin; Anti-Bacterial Agents; Antifungal Agents; Cefepime; Cefozopran; Cephalosporins; Chemotherapy-Induced Febrile Neutropenia; Female; Humans; Male; Middle Aged; Piperacillin; Retrospective Studies

Intensive chemotherapy for pediatric acute myeloid leukemia incurs the risk of infectious complications, but the benefits of antibiotic prophylaxis remain unclear.. In the current study, among 103 children treated on the AML02 protocol between October 2002 and October 2008 at St. Jude Children's Research Hospital, the authors retrospectively assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia, clinically or microbiologically confirmed infections (including bacteremia), and antibiotic resistance, as well as on the results of nasal and rectal surveillance cultures. Initially, patients received no prophylaxis or oral cephalosporin (group A). The protocol was then amended to administer intravenous cefepime alone or intravenous vancomycin plus either oral cephalosporin, oral ciprofloxacin, or intravenous cefepime (group B).. There were 334 infectious episodes. Patients in group A had a significantly greater frequency of documented infections and bacteremia (both P < .0001) (including gram-positive and gram-negative bacteremia; P = .0003 and .001, respectively) compared with patients in group B, especially viridans streptococcal bacteremia (P = .001). The incidence of febrile neutropenia without documented infection was not found to be different between the 2 groups. Five cases of bacteremia with vancomycin-resistant enterococci (VRE) occurred in group B (vs none in group A), without related mortality. Two of these cases were preceded by positive VRE rectal surveillance cultures.. Outpatient intravenous antibiotic prophylaxis is feasible in children with acute myeloid leukemia and reduces the frequency of documented infection but not of febrile neutropenia. Despite the emergence of VRE bacteremia, the benefits favor antibiotic prophylaxis. Creative approaches to shorten the duration of prophylaxis and thereby minimize resistance should be explored.

Topics: Administration, Oral; Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Bacterial Infections; Candidiasis; Cefepime; Cephalosporins; Chemotherapy-Induced Febrile Neutropenia; Child; Child, Preschool; Ciprofloxacin; Consolidation Chemotherapy; Drug Therapy, Combination; Feasibility Studies; Female; Humans; Incidence; Induction Chemotherapy; Infant; Infusions, Intravenous; Leukemia, Myeloid, Acute; Male; Neoplasm Staging; Nose; Outpatients; Rectum; Retrospective Studies; Treatment Outcome; Vancomycin; Young Adult