Management of febrile neutropenia in the perspective of antimicrobial de-escalation and discontinuation

Schmidt‐Hieber, Martin; Teschner, Daniel; Maschmeyer, Georg; Schalk, Enrico

doi:10.1080/14787210.2019.1573670

Cited by 37 publications

(35 citation statements)

References 104 publications

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“…Most cases from the present studies were included before the availability of these guidelines [5, 8] when ceftazidime plus amikacin were recommended as the initial empirical treatment [3, 43, 44]. Nevertheless, since evidence is not conclusive in this regard [45], these therapeutic schedules continue to be adequate for the management of FNEs, with other recent guidelines still including ceftazidime as first-line therapy [36, 46, 47]. In our hands, although initial treatment with ceftazidime plus amikacin was associated with lower mortality -probably because such treatment was not of first choice for severe patients-, further multivariate analysis revealed no differences in mortality depending on the initial antimicrobial therapy.…”

Section: Discussionmentioning

confidence: 99%

A multicenter prospective study of 515 febrile neutropenia episodes in Argentina during a 5-year period

et al. 2019

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For better management of patients with febrile neutropenia, our study investigated the epidemiologic, microbiologic, and clinical characteristics of adult inpatients with febrile neutropenia and their mortality-associated factors. To this end, we carried out a prospective, observational, multicenter study in 28 Argentinian hospitals between 2007 and 2012. We included 515 episodes of febrile neutropenia from 346 patients, median age 49 years. Neutropenia followed chemotherapy in 77% of cases, half of the cases due to hematological malignancies. Most episodes were classified as high-risk according to MASCC criteria, and 53.6% of patients were already hospitalized at the onset of febrile neutropenia. Bloodstream infections were detected in 14% episodes; whereas an infectious source of fever was identified in 80% of cases. Mortality rate achieved to 14.95%. The binary regression analysis showed that persistence of fever at day 7, or neutropenia at day 14, dehydration and tachycardia at the onset of febrile neutropenia as well as prior infections were significantly associated with mortality. In addition to expanding our current knowledge on the features of adult patients with febrile neutropenia, present findings provide useful information for better management of them in Argentina, given the appropriate representativeness of centers participating in the study.

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Section: Discussionmentioning

confidence: 99%

A multicenter prospective study of 515 febrile neutropenia episodes in Argentina during a 5-year period

et al. 2019

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“…Current guidelines recommend an antipseudomonal beta-lactam, such as piperacillin/tazobactam, cefepime or ceftazidime, as first-line choice for empirical treatment of FN patients with hematologic malignancies. Escalation to meropenem is suggested in the absence of a clinical response within 48–72 h [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and P. aeruginosa

et al. 2020

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A population pharmacokinetic analysis of continuous infusion (CI) meropenem was conducted in a prospective cohort of febrile neutropenic (FN) patients with hematologic malignancies. A non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations were performed for identifying the most appropriate dosages for empirical treatment against common Enterobacterales and P. aeruginosa. The probability of target attainment (PTA) of steady-state meropenem concentration (Css)-to-minimum inhibitory concentration (MIC) ratio (Css/MIC) ≥1 and ≥4 at the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoint of 2 mg/L were calculated. Cumulative fraction of response (CFR) against Enterobacterales and P. aeruginosa were assessed as well. PTAs and CFRs ≥ 90% were considered optimal. A total of 61 patients with 178 meropenem Css were included. Creatinine clearance (CLCR) was the only covariate associated with meropenem clearance. Monte Carlo simulations showed that dosages of meropenem ranging between 1 g q8h and 1.25 g q6h by CI may grant optimal PTAs of Css/MIC ≥4 at the EUCAST clinical breakpoint. Optimal CFRs may be granted with these dosages against the Enterobacterales at Css/MIC ≥ 4 and against P. aeruginosa at Css/MIC ≥ 1. When dealing against P. aeruginosa at Css/MIC ≥ 4, only a dosage of 1.5 g q6h by CI may grant quasi-optimal CFR (around 80–87%). In conclusion, our findings suggest that dosages of meropenem ranging between 1 g q8h and 1.25 g q6h by CI may maximize empirical treatment against Enterobacterales and P. aeruginosa among FN patients with hematologic malignancies having different degree of renal function.

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“…Unfortunately, the condition of the patient, as well as the prognosis and treatment, will worsen in relation to the antimicrobial resistance profile of the bacteria associated with the infection [24,25].…”

Section: Multidrug-resistant Post-therapeutic Infectionsmentioning

confidence: 99%

Antibiotic-Resistant Septicemia in Pediatric Oncology Patients Associated with Post-Therapeutic Neutropenic Fever

et al. 2019

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Death in cancer patients can be caused by the progression of tumors, their malignity, or other associated conditions such as sepsis, which is a multiphasic host response to a pathogen that can be significantly amplified by endogenous factors. Its incidence is continuously rising, which reflects the increasing number of sick patients at a higher risk of infection, especially those that are elderly, pediatric, or immunosuppressed. Sepsis appears to be directly associated with oncological treatment and fatal septic shock. Patients with a cancer diagnosis face a much higher risk of infections after being immunosuppressed by chemotherapy, radiotherapy, or anti-inflammatory therapy, especially caused by non-pathogenic, Gram-negative, and multidrug-resistant pathogens. There is a notorious difference between the incidence and mortality rates related to sepsis in pediatric oncologic patients between developed and developing countries: they are much higher in developing countries, where investment for diagnosis and treatment resources, infrastructure, medical specialists, cancer-related control programs, and post-therapeutic care is insufficient. This situation not only limits but also reduces the life expectancy of treated pediatric oncologic patients, and demands higher costs from the healthcare systems. Therefore, efforts must aim to limit the progression of sepsis conditions, applying the most recommended therapeutic regimens as soon as the initial risk factors are clinically evident—or even before they are, as when taking advantage of machine learning prediction systems to analyze data.

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Management of febrile neutropenia in the perspective of antimicrobial de-escalation and discontinuation

Cited by 37 publications

References 104 publications

A multicenter prospective study of 515 febrile neutropenia episodes in Argentina during a 5-year period

A multicenter prospective study of 515 febrile neutropenia episodes in Argentina during a 5-year period

Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and P. aeruginosa

Antibiotic-Resistant Septicemia in Pediatric Oncology Patients Associated with Post-Therapeutic Neutropenic Fever

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