cefepime and Leukemia--Myeloid--Acute

A 55-year old man developed a hemorrhagic pneumonia, likely due to infection with Kytococcus sedentarius during neutropenia following induction chemotherapy for acute myeloid leukemia. Severe mucosal barrier injury and the selective pressure of broad-spectrum antibiotics probably made it possible for this normally harmless commensal to penetrate the gut, spread through the blood stream, and invade the lungs.

Topics: Actinomycetales; Actinomycetales Infections; Acyclovir; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bacterial Translocation; Cefepime; Cephalosporins; Clostridium Infections; Colistin; Cytarabine; Daunorubicin; Drug Therapy, Combination; Etoposide; Fatal Outcome; Hemoptysis; Humans; Hydroxyurea; Immunocompromised Host; Intestinal Mucosa; Leukemia, Myeloid, Acute; Male; Metronidazole; Middle Aged; Neutropenia; Pneumonia, Bacterial; Superinfection; Teicoplanin; Trimethoprim, Sulfamethoxazole Drug Combination

Timely administration of appropriate empirical antibiotics in febrile neutropenia is crucial for favourable patient outcomes. There are guidelines in place recommending such antibiotics. However, regional variations and local epidemiological data must be evaluated to tailor the antibiotics for best possible and rational use. In this study, we audited the clinical and microbiological data of febrile neutropenic episodes occurring at a tertiary care haematology institution. Three hundred and ninety-three febrile neutropenic episodes occurring in 123 patients over a 1-year period were analysed for microbial profile, sensitivity and resistance patterns, and finally clinical outcomes. Gram-negative bacilli (GNB) blood stream infections (46.9%) were more prevalent as compared to gram-positive infections (41.9%). Overall mortality due to complicated neutropenic sepsis was 19.5% (24/123 patients). Increased resistance to carbapenems, beta-lactam beta-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones, and cephalosporins were observed. Cefepime and tigecycline resistance were seen in 20% and 15% GNB isolates, respectively. Chest was the most frequent focus of infection, and acute myeloid leukaemia (AML) was the most common underlying disorder which correlated with the likelihood of death (p < 0.01). Multidrug-resistant GNB (esp. Klebsiella sp.) are still most worrisome isolates in neutropenic patients. Single-agent cefepime or piperacillin-tazobactam/tigecycline combination may be considered empirical agents. Chest infections and AML were independent predictors of poor clinical outcome in neutropenic patients. Regular audit of infections and antibiotic susceptibility data is needed to improve clinical outcomes in patients with febrile neutropenia.

Topics: Adolescent; Adult; Cefepime; Drug Resistance, Multiple, Bacterial; Febrile Neutropenia; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; India; Leukemia, Myeloid, Acute; Male; Middle Aged; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Tigecycline

There exists few pediatric data on the safety and efficacy of prophylactic antibiotics during chemotherapy-induced agranulocytosis.. We prospectively studied the incidence of infection-related fever in 38 children, aged 2-16 years, with acute myeloid leukemia (AML) over 121 chemotherapy treatment cycles. A prophylactic group (n = 18) was given either vancomycin/cefepime (400 mg/m(2), q12 h/50 mg/kg, q12 h) or piperacillin/tazobactam (110 mg/kg, q12 h). Control patients (n = 20) received no preventive antibiotics.. The prophylactic group (59 treatment cycles) experienced fever less frequently than the control group (0.4 vs. 0.9 events; p < 0.001), had a longer interval between agranulocytosis and fever (6.4 vs. 3.8 days; p = 0.007), had a shorter duration of hospitalization (21.5 vs. 28.5 days; p < 0.001), and had a lower rate of lung infection (38.8 vs. 80.0%; p < 0.001). One patient taking vancomycin experienced a skin rash and 3 patients taking piperacillin/tazobactam had diarrhea; these side effects subsided after antibiotics were discontinued.. In children with AML, prophylactic antibiotics during the period of chemotherapy-induced agranulocytosis can effectively reduce the incidence of infectious fever and can shorten the average length of hospital stay, improving treatment success and quality of life.

Topics: Adolescent; Agranulocytosis; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Cefepime; Cephalosporins; Child; Child, Preschool; Female; Fever; Humans; Infection Control; Length of Stay; Leukemia, Myeloid, Acute; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Vancomycin

The potential for cefepime prophylaxis to reduce bloodstream infections (BSIs) in pediatric patients with acute myelogenous leukemia (AML) has been incompletely characterized.. A retrospective quasi-experimental study of patients under 21 years of age admitted with AML from 2010 through 2018 at two affiliated pediatric tertiary-care hospitals before and after the adoption of routine cefepime prophylaxis for afebrile AML patients during profound neutropenia.. The rate of BSIs per 1000 neutropenia days was significantly lower in the prophylaxis group than the baseline group (2.6 vs 15.5, incidence rate ratio [IRR] 0.17, 95% CI 0.09-0.32). Interrupted time-series analysis showed that a sharp reduction in BSIs coincided with the implementation of prophylaxis. Bacteremia with viridans group streptococci was frequent in the baseline group but not observed after adopting prophylaxis. Despite the increased use of cefepime, the rate of cefepime-nonsusceptible BSIs per 1000 neutropenia days decreased (1.6 vs 4.1, IRR 0.40, 95% CI 0.16-0.99). The median number of febrile neutropenia episodes per patient also decreased in the prophylaxis group, as did the proportion of patients admitted to the intensive care unit (ICU) (22/51 (43.1%) vs 26/38 (68.4%); risk difference -25.3%, 95% CI -44.4 to -2.8). A trend was observed toward an increased proportion of patients with Clostridioides difficile infection in the prophylaxis group (10/51 (19.6%) vs 3/38 (7.9%); risk difference 11.7%, 95% CI -3.4 to 29.0).. Cefepime prophylaxis was associated with a significant reduction in BSIs, febrile neutropenia, and ICU admission among pediatric AML patients.

Topics: Cefepime; Child; Febrile Neutropenia; Humans; Leukemia, Myeloid, Acute; Retrospective Studies; Sepsis

Febrile neutropenia (FN) occurs in up to 80% of patients with hematologic malignancies. Evidence suggests using extended infusions (EI) of beta-lactams can improve outcomes in some populations, but there is limited clinical literature comparing cefepime standard infusion (SI) versus EI for FN. The FDA-approved regimen for FN was used at a large community teaching hospital for patients with FN until a hospital-wide EI beta-lactam protocol was introduced that allowed for EI cefepime in FN at the physicians' discretion. We sought to compare outcomes between patients with FN who received SI and EI cefepime.. Patients with acute myeloid or lymphocytic leukemia who developed FN between April 2014 and January 2021 were included in this single-center, retrospective study. The primary outcome was to compare mean time to defervescence after the initiation of cefepime SI or EI regimens. SI regimens consisted of IV cefepime 2G q8h/0.5 h, and EI regimens as IV cefepime 1G q8h/4 h. Secondary outcomes included 30-day all-cause mortality, hospital length of stay (LOS), duration of cefepime, and need to escalate therapy.. Overall, 193 patients were included. Baseline characteristics were similar between groups. Time to defervescence was significantly shorter with EI compared with the SI group (median 48 h [48-100.5] vs. 70 h [48-113], p = 0.005). Cefepime duration of therapy was significantly shorter in the EI compared with the SI group (median 6.0 days vs. 8.0 days, p = 0.002). There was no difference between other secondary outcomes including LOS, mortality, and antibiotic escalation.. Despite reduced total daily dose of cefepime, EI cefepime administered as a 1G/0.5 h LD followed 2 h later by 1G q8h/4 h for FN acutely achieves more rapid defervescence than the FDA-approved SI regimen and ultimately attains comparable patient outcomes.

Topics: Anti-Bacterial Agents; beta-Lactams; Cefepime; Cephalosporins; Febrile Neutropenia; Humans; Leukemia, Myeloid, Acute; Retrospective Studies

Topics: Aeromonas veronii; Aged; Anti-Bacterial Agents; Cefepime; Ciprofloxacin; Combined Modality Therapy; Conservative Treatment; Consolidation Chemotherapy; Debridement; Drug Therapy, Combination; Fasciitis, Necrotizing; Gram-Negative Bacterial Infections; Humans; Leukemia, Myeloid, Acute; Male; Treatment Outcome

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

Based on 2 meta-analyses, the Food and Drug Administration issued a communication in 2009 regarding the potential risk of death in patients treated with cefepime. Pediatric patients with acute myelogenous leukemia (AML) have frequent episodes of fever necessitating the use of antibiotics such as cefepime. We evaluated the association of cefepime and other beta-lactam antibiotic exposures with all cause in-hospital mortality in pediatric AML patients.. We performed a retrospective cohort study using the Pediatric Health Information System, an inpatient database. Exposure to cefepime, ceftazidime, antipseudomonal penicillin, and carbapenems was evaluated for each 30-day period within the first year from AML diagnosis. Cox regression analysis was used to compute hazard ratios (HR) for death adjusting for demographics, clinical variables, and clustering by hospital. The final analysis used 2 distinct time periods (0-3 months and >3-12 months) to account for variation in proportional hazards over time.. No differences between the HRs for mortality were observed for the time period of 0 to 3 months (cefepime vs. ceftazadime: HR=1.33, 95% CI: 0.70-2.52; cefepime vs. antipseudmonal penicillin: HR=0.86, 95% CI: 0.34-2.13; and cefepime vs. carbapenems: HR=1.08, 95% CI: 0.50-2.35) or the time period of >3 to 12 months after diagnosis (cefepime vs. ceftazadime: HR=1.29, 95% CI: 0.53-3.15; cefepime vs. antipseudomonal penicillin: HR=1.08, 95% CI: 0.44-2.66; and cefepime vs. carbapenems: HR=1.03, 95% CI: 0.45-2.33).. In this cohort of pediatric AML patients, cefepime exposure in the 30 days preceding death did not result in an increased mortality risk when compared with ceftazidime, antipseudomonal penicillins, or carbapenems.

Topics: Adolescent; Animals; Anti-Bacterial Agents; Cefepime; Cephalosporins; Child; Child, Preschool; Cohort Studies; Female; Humans; Immunocompromised Host; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Male; Opportunistic Infections; Retrospective Studies