Harbeck, N., Lipatov, O., Frolova, M., Udovitsa, D., Topuzov, E., Ganea-Motan, D.E., . . . Blackwell, K. (2016). Randomized, double-blind study comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Future Oncology, 12, 1359–1367.
The purpose of the PROTECT-1 study was to confirm efficacy and safety of the biosimilar pegfilgrastim (LA-EP2006) with reference pegfilgrastim (Neulasta®) in the reduction of duration of severe neutropenia (DSN) in patients with breast cancer receiving myelosuppressive chemotherapy.
1:1 stratified randomization of adult (aged 18 years or older) women with breast cancer (stratified by Europe, Asia, or European region and receipt of adjuvant or neoadjuvant myelosuppressive TAC regimen chemotherapy [docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclosphosphamide 500 mg/m2]) into a one of two groups to receive either LA-EP2006 or Neulasta. TAC was administered on day 1 of each cycle and then every 3 weeks up to 6 cycles. Patients could remain in the study if they had a 25% reduction in chemotherapy due to a grade 3-4 nonhematologic toxicity, grade 4 thrombocytopenia, or febrile neutropenia. A 6 mg subcutaneous injection of LA-EP2006 or Neulasta was administered on day 2 of each cycle (24 hours or longer following the end of chemotherapy). Patients were followed for 6 months following the last dose of LA-EP2006 or Neulasta.
PHASE OF CARE: Active anti-tumor treatment
Randomized, double-blind study
Outcomes of mean duration of severe neutropenia–number of consecutive days of grade IV neutropenia: ANC 0.5x109/L or less during cycle 1, depth of ANC nadir, time to ANC recover (nadir to ANC 2 x 109/L or greater in cycle 1; incidence of febrile neutropenia (PO temp 38.3oC or greater with ANC 0.5 x 109 or less) or neutropenic sepsis (FN/NS) by cycle and across cycles; number of patients with fever(PO temp 38.3oC or greater) per cycle; number of patients with infections per cycle and across cycles; and infection-related mortality. Safety was also measured through the incidence, occurrence, and severity of treatment-emergent adverse events (TEAEs) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. FNs were reported as AEs. ELISA testing was used to validate immunogenicity of LA-EP2006 or Neulasta.
RESULTS: There were no demographic differences between groups. 159 patients were in the LA-EP2006 group and 157 were in the neulasta group. 19 and 7 discontinued treatment in the LA-EP2006 and neulasta groups, respectively. 2 patients in the neulasta group died from infections; 4 patients in the LA-EP2006 group died (cause of death not disclosed). In cycle 1, the DSN was 0.75 (SD = 0.88) days with LA-EP2006 and 0.83 (SD = 0.9) days with Neulasta. The difference between the groups was 0.07 days (90% CI [-0.09, 0.23]; 95% CI [-0.12, 0.26]).Similar findings in the per protocol analysis No clinically meaningful differences were found between groups for depth of ANC nadir, mean days to ANC recovery, and time course of mean ANC. Frequency of infections (cycle 1: 4.4%, n = 7 versus 2.5%, n = 4; across cycles: 13.8%, n = 22 versus 15.3%, n = 24). No differences between groups were found for safety (TEAE 1 or greater 88.1% LA-EP2006 and 82.8% neulasta) or neutralizing antibodies.
LA-EP2006 was found to be as effective and safe as neulasta. Use of biosimilar pegfilgrastim can potentially increase the availability of patients receiving prophylactic pegfrilgrastim for improved outcomes while undergoing chemotherapy treatment for cancer.
Infections were not defined and the causes of death of the four patients in the LA-EP2006 arm were not disclosed.
Nurses being aware of biosimilars for pegfilgratim can help guide practice for use of prophylactic pegfilgrastim when standard pegfilgrastim (neulasta) is not available. In addition, nurses can assess patients for risks of adverse events related to chemotherapy treatments.
Donkor, K.N., Selim, J.H., Waworuntu, A., & Lewis, K. (2017). Safety and efficacy of pegfilgrastim when given less than 14 days before the next chemotherapy cycle: Review of every 14-day chemotherapy regimen containing 5-FU continuous infusion. Annals of Pharmacotherapy, 51, 840–847.
The purpose of the study was to determine the efficacy and safety of administering pegfilgrastim less than 14 days from the next chemotherapy cycle in patients receiving a regimen containing 5-FU that infuses over at least 46 hours or more.
Authors reviewed the electronic health record for criteria of patients who received chemotherapy containing 5-FU over at least 46 hours. In addition to demographic data, each unique chemotherapy cycle was evaluated, and patients were put into 1 of 4 groups: (a) Cycles of chemotherapy where pegfilgrastim was given less than 14 days from the next chemotherapy cycle; (b) cycles where pegfilgrastim was given more than 14 days from the next chemotherapy cycle;(c) cycles where filgrastim was given instead of pegfilgrastim after chemotherapy; (d) cycles where no colony stimulating factors were given.
PHASE OF CARE: Active anti-tumor treatment
This was a single-institution retrospective cohort study of patients who received chemotherapy treatment from June 2013 to December 2015.
Counts and percentages were used for data analysis of demographic data as well as generalized linear models to compare mean ANC and WBC counts of the four different groups within the analysis. A generalized linear model with generalized estimating equations was used to compare mean ANC and WBC with 95% CI limits. Poisson regression models were used to estimate relative risk for neutropenia. All analyses were two sided and conducted at a significance level of 0.05.
The primary study outcome was the number of chemotherapy cycles with neutropenia, febrile neutropenia, and/or hospitalization in cycles where pegfilgrastim was given less than 14 days before the next chemotherapy cycle. The secondary outcome was evaluation of the incidences of neutropenia, mean ANC, and mean WBC for each of the four groups that were evaluated as part of this analysis. 536 total chemotherapy cycles were evaluated based on inclusion criteria. The group that received pegfilgrastim less than 14 days from their chemotherapy cycle did not show evidence of neutropenia or hospitalization as a result of febrile neutropenia. This group demonstrated a mean ANC and WBC count that was statistically significantly higher than the other three research groups as noted above.
Based on the data reviewed, it does not appear as though administering pegfilgrastim less than 14 days before the next chemotherapy cycle causes harm to patient nor increased myeloid toxicity. While this study was small and specific to one site, it may be beneficial for continued research with a larger sample.
As nurses are the ones to administer pegfilgrastim, it is important for nurses to understand the implications of administration of the drug and how it impacts patient outcomes.
Bokemeyer, C., Gascon, P., Aapro, M., Ludwig, H., Boccadoro, M., Denhaerynck, K., . . . MacDonald, K. (2017). Over- and under-prophylaxis for chemotherapy-induced (febrile) neutropenia relative to evidence-based guidelines is associated with differences in outcomes: Findings from the MONITOR-GCSF study. Supportive Care in Cancer, 25, 1819–1828.
This study used the amended EORTC algorithm (that classified patients based on prophylaxis intensity levels, for myelotoxic chemotherapy regimen and patient risk factors associated with CIN/FN) to explore the impact of prophylaxis intensity using biosimilar filgrastim comparing these outcomes with dosing for under, correctly, or over prophylaxis guideline-recommended levels.
This was a real-world observational study evaluating patients as they received myelosuppressive chemotherapy and CIN/FN prophylaxis with biosimilar filgrastim. The evaluation of data for the study stratified patients into groups with biosimilar GCSF by prophylaxis intensity levels (under, correctly, or over-prophylaxis). Patient outcomes were compared first on demographics and clinical status at the start of chemotherapy to identify prophylaxis patterns, clinical, and safety outcomes. Data for patient-level evaluations were collected as patients progressed through chemotherapy treatments to isolate outcomes experienced at any time during the whole period of chemotherapy. The study collected ongoing data for a cycle-level analyses to evaluate outcomes during a particular cycle and from one cycle to the next, to evaluate outcomes as patients progressed through their cycles of chemotherapy.
Of note:
Non-experimental prospective longitudinal observational cohort study (real-world observational study)
Chemotherapy associated FN risk was established using an author developed tool, Patient Risk Score (PRS), for a weighted sum of eight patient risk factors associated with CIN/FN specified in EORTC guidelines; prophylaxis patterns collected for GCSF decisions for primary or secondary prophylaxis and duration of prophylaxis; CIN/FN prior cycle; ECOG performance status; history of repeated infections; cancer tumor type, prior treatments chemotherapy/radiation therapy; and chemotoxicity. Data was collected (patient and cycle levels) for number of episodes of CIN and grade (CIN1/4), number of episodes of FN; number of episodes of CIN/FN related to a hospitalization or chemotherapy disturbance (dose reduction, delay in administration of chemotherapy, cancellation of administration of chemotherapy); and a (worst-case) composite index of occurrence for any of the previous outcomes.
Different rates of CIN, grades 1-4, and CIN/FN-related hospitalization (all p ≤ 0.001)
There was no significant difference for proportions of patients with CIN/FN chemotherapy disturbances.
The proportion of cycles of chemotherapy interruptions due to CIN/FN was significantly higher for under prophylaxes (p = 0.32)
Patient level pairwise analysis: No difference between groups for the likelihood of CIN/FN.
Cycle-level pairwise analysis: likelihood of CIN/FN in any one cycle between under and correctly prophylacted no significant difference
Patients CIN/no GCSF safety differences between groups (except for headaches, p = 0.027, correct and over had higher percentage compared to under)
Comparing biosimilar GCSF prophylaxis intensity groups (under, correct, and over-prophylacted), GCSF support at levels above current guideline recommendations may reduce CIN, FN, and CIN/FN-related hospitalization. Patients who are under-prophylacted with biosimilar GCSF are at higher risk for disturbances to their chemotherapy regimens.
Oncology nurses must evaluate patients for CIN/FN risk each cycle and adhere to current guideline recommendations for CIN/FN prophylaxis with GCSF to reduce risk of CIN/FN and chemotherapy interruptions. Large RCTs are necessary to evaluate if changing current recommended GCSF dosing schedule improves patient-related outcomes, to evaluate patient risk stratification and potential side effects of a different dosing schedule.
Hockings, J.K., Owolabi, D.K., Broyles, J.E., & Wheelis, S.C. (2017). Impact of recommended weight-based dosing of granulocyte-colony stimulating factors in acute leukemia and stem cell transplant patients. Supportive Care in Cancer, 25, 1853-1858.
To evaluate the effect of recommended weight-based GCSF dosing (under, recommended and over) on duration of neutropenia, compared to under and overweight-based dosing; secondary endpoints were LOS, FN incidence, and mortality between all three dosing groups
Retrospective chart review of 75 patients during 94 admissions for treatment of AML/ALL with induction/consolidation chemotherapy or admitted for a HSCT, admissions divided into weight-based dosing groups of GCSF under 5 mcg/kg; recommended 5 mcg/kg (plus or minus 10%); or over 5 mcg/kg; data collected from initiation of G-CSF to three weeks post: for number of documented doses, ANC nadir, neutropenia duration, time to first fever, and patient disposition at end of study period
Retrospective chart review: sample collected from database ICD-9-CM codes for acute leukemia or stem cell transplantation for patients admitted from May 2009 through September 2015
Actual body weight, temperature, neutropenia ANC < 500, nadir ANC; length of neutropenia in number of days; length of stay in number of days; FN incidence (%); mortality incidence (%)
Comparing weight-based dosing of GCSF administered (under 5 mcg/kg; recommended 5 mcg/kg (plus or minus 10%); or more than 5 mcg/kg) during patient admissions for chemotherapy induction/consolidation or HSCT, the study found that recommended dosing for at least three doses leads to lower incidence of febrile neutropenia (p = 0.003); there was no significant differences between the groups for duration of neutropenia, LOS, or mortality rate.
Recommended weight-based dosing of GCSF at 5 mcg/kg of at least three doses showed a reduction in FN incidence for this population of patients
This retrospective chart review indicates that recommended GCSF weight-based dosing of at least three doses reduces risk of FN. Larger multi-site randomized controlled trials need to be conducted that will effectively evaluate differences of weight-based dosing on clinical outcomes to determine best practice. Nurses need to remain vigilant and adhere to current recommended GCSF weight-based dosing to reduce incidence of FN and potential infectious risks.
Liu, J.Y., Sheng, Y.J., Ding, X.C., Tang, H., Tong, S.W., Zhang, D.Z., . . . Hu, H.D. (2015). The efficacy of lamivudine prophylaxis against hepatitis B reactivation in breast cancer patients undergoing chemotherapy: A meta-analysis. Journal of the Formosan Medical Association, 114, 164-173.
STUDY PURPOSE: Evaluate the efficacy of lamivudine prophylaxis (100 mg daily) on HBsAg seropositive patients with breast cancer undergoing chemotherapy.
TYPE OF STUDY: Meta analysis and systematic review
DATABASES USED: Medline, Embase, and the Cochrane databases
INCLUSION CRITERIA: (a) Types of studies: randomized controlled cohort, retrospective comparative case series, and prospective, controlled, non-randomized studies; (b) studies that included a lamivudine prophylaxis group and a group that did not receive lamivudine prophylaxis; and (c) all patients received chemotherapy and were HBsAg sero-positive.
EXCLUSION CRITERIA: Patient populations were excluded if: (a) the study did not measure HBV reactivation/flare as a specific outcome; (b) the patients did not receive chemotherapy; (c) patients had HIV co-infection; (d) patients had hepatitis D virus, hepatitis C virus, or other liver diseases; (e) there was no lamivudine prophylaxis and non-prophylaxis group; and (f) there was insufficient analytic information available.
TOTAL REFERENCES RETRIEVED: 16
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two independent reviewers retrieved and evaluated studies using a validated tool for scoring the quality of the study. Meta-analysis was performed using Review Manager Software 5.0.
PHASE OF CARE: Active anti-tumor treatment
Lamivudine prophylaxis significantly reduced the risk of HBV reactivation in HBsAg seropositive patients (RR = 0.23, 95% CI [0.13, 0.39], p < 0.00001); the risk of hepatitis (RR = 0.2, 95% CI [0.08, 0.47], p =0.002); the rate of overall chemotherapy disruptions (RR = 0.36, 95% CI [0.21, 0.64], p = 0.0004); and the rate of delay of eight days or greater between cycles in those patients who completed chemotherapy (RR = 0.42, 95% CI [0.21, 0.82], p = 0.01).
Lamivudine 100 mg daily used as prophylaxis for HBsAg-seropositive patients undergoing chemotherapy significantly reduces the risk of hepatitis B reactivation and prevents chemotherapy delays.
Lamivudine 100 mg daily is recommend to prevent hepatitis B reactivation in patients who are HbsAg seropositive. There is no consensus on timing and duration of lamivudine prophylaxis. Some experts recommend lamivudine should be started at least one week before initiation and be continued until at least six weeks after the chemotherapy.
Wang, C.H., Kan, L.P., Lin, H.A., Chang, F.Y., Wang, N.C., Lin, T.Y., . . . Lin, J.C. (2016). Clinical efficacy and safety of primary antifungal prophylaxis with posaconazole versus fluconazole in allogeneic blood hematopoietic stem cell transplantation recipients: A retrospective analysis of a single medical center in Taiwan. Journal of Microbiology, Immunology, and Infection, 49, 531–538.
To determine the safety and efficacy of posaconazole versus fluconazole as antifungal prophylaxis in patients receiving allo-HSCT during early neutropenic phase without GVHD
Medical records were retrospectively reviewed for allo-HSCT recipients from a single institution, who received oral fluconazole (January 2005 to June 2011) or oral posaconazole (June 2011 to December 2013) during the early neutropenic stage.
PHASE OF CARE: Transition phase after active treatment
All patients who received allo-HSCT in the HSCT-dedicated room and were given prophylactic oral posaconazole (June 2011 to December 2013) or fluconazole (January 2005 to June 2011) were included. Exclusions were active infections, secondary fungal infections, or given an agent other than the two stated. Observation began seven days prior to transplantation and continued 90 days after transplantation.
Suspected invasive fungal infection was characterized as unexplained persistent fever that lasted 72-96 hours despite empiric broad spectrum antibiotics. Clinical and laboratory values were collected at baseline and throughout the study. ALT, AST, and total bilirubin were collected for hepatic toxicity. Incidence of neutropenic fever and overall mortality at 90 days post-transplantation was assessed.
Fluconazole had a greater risk for development of invasive fungal infections during the 90 days (42.5% versus 8.3%, p = 0.039) even at higher doses of fluconazole. Both groups had similar rates of neutropenic fevers (83.3% versus 87.5%, p = 0.656) and mortality (8.3% versus 22.5%, p = 0.04). Early discontinuation due to intolerance was lower in posaconazole than fluconazole (8.3% versus 50.0%, p = 0.017). Both had similar rates of GI upset, but fluconazole patients were more likely to have diarrhea. No patient discontinued either drug due to liver impairment, although both groups saw equally elevated laboratory values that normalized after discontinuation except for four patients (n = 1 posaconazole and n = 3 fluconazole).
Results concluded that implementing a prophylaxis regimen with posaconazole for preventing invasive fungal infections in allo-HSCT patients during the early neutropenic phase through 90 days post-transplantation was better tolerated with better efficacy and similar safety concerns when compared to fluconazole.
Small sample (< 100)
Nurses could incorporate evidence-based practices of hand hygiene, isolation, low microbial diets, teaching, and reinforcement plans for these fragile patients to work synonymously with the prophylaxis antifungal.
Mellinghoff, S.C., Panse, J., Alakel, N., Behre, G., Buchheidt, D., Christopeit, M., . . . Cornely, O.A. (2018). Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO). Annals of Hematology, 97, 197–207.
PURPOSE: To provide evidence-based guidelines for the prevention of fungal infections
TYPES OF PATIENTS ADDRESSED: Adults with hematologic malignancies, particularly acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) receiving chemotherapy
RESOURCE TYPE: Evidence-based guideline
PROCESS OF DEVELOPMENT: Guideline was prepared by German clinical experts in hematology, oncology, stem cell transplantation, and infectious diseases. This was done by a stepwise consensus process. Data was extracted and tabulated; the preliminary recommendations were discussed and sent to a committee of authors. Once revised by the authors, there was a discussion by email and telephone conference. If the vote was not unanimous, the majority vote was adopted. The final version was approved by the AGIHO plenary session.
DATABASES USED: Not specifically described
INCLUSION CRITERIA: Clinical trials regarding antifungal prophylaxis in patients with hematologic malignancies
PHASE OF CARE: Active anti-tumor treatment
There were seven clinical trials since the 2014 edition of the recommendations that were included in the 2017 update. These trials included a total of 1,227 patients.
Allogeneic stem cell transplantation recommendations were removed from this guideline and placed in a separate guideline.
Recommended antifungal prophylaxis in patients with neutropenia (neutrophils less than 500 cells/mcl for more than seven days (summary of table 2):
Recommendations for dosages (from table 3):
Recommendation for therapeutic drug monitoring (table 4):
The guidelines are limited to a very specific group of patients–those with hematologic malignancies that will have a low neutrophil count (less than 500 cells/mcl for more than 7 days)
There is strong support for the use of antifungal prophylaxis, but the cost and effectiveness of the antifungal agent must be taken into account. Know the common fungal infectious causes in the geographical area and choose the right drug according to the specific fungus that is thought to be most prominent. Education about fungal infections as well as prevalence in this population is critical.
Lee, C.H., Lin, J.C., Ho, C.L., Sun, M., Yen, W.T., & Lin, C. (2017). Efficacy and safety of micafungin versus extensive azoles in the prevention and treatment of invasive fungal infections for neutropenia patients with hematological malignancies: A meta-analysis of randomized controlled trials. PLOS One, 12, e0180050.
STUDY PURPOSE: To compare the efficacy and safety of micafungin (MCFG) with triazoles for the prophylaxis and treatment of invasive fungal infections (IFIs) among patients with hematologic malignancies with neutropenia
TYPE OF STUDY: Meta analysis and systematic review
DATABASES USED: PubMed, Embase, Cochrane Central Register of Controlled Trials, and relevant database articles for RCTs
YEARS INCLUDED: (Overall for all databases) through November 2016
INCLUSION CRITERIA: Randomized controlled studies comparing MCFG to the use of triazoles in neutropenic fever. Inclusion criteria consisted of studies that compared efficacy or incidence of AEs in two comparable populations: received IV MCFG for antifungal prevention or treatment and FN defined as absolute neutrophil count less than 1,500/mcl. Search terms included micafungin, micafungin sodium, micamine, FK 463, Echinocandin, Lipopep- tides, antifungal agents, FN, and neutropenic fever
EXCLUSION CRITERIA: Studies that had incomplete data, included duplicate data, did not contain any predetermined clinical outcomes, or could not be pooled with other included studies
TOTAL REFERENCES RETRIEVED: 181
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: PRISMA checklist and a quality assessment of two reviewers following the Cochrane Collaboration Reviewers’ Handbook for Systematic Reviews of Interventions. Articles were scored form 0 (lowest quality level) to 7 (highest quality level) with 1 point given to each area addressed for randomization, concealment of allocation, blinding, reporting of withdrawals, selective reporting, and other bias. Disagreements of assessments were resolved through reviewer discussions.
PHASE OF CARE: Active anti-tumor treatment
APPLICATIONS: Pediatrics
MCFG was found to have a better treatment success rate compared to triazoles (RR = 1.13; 95% CI [1.02, 1.25]; I2 = 87%) in the pooled data for the absence of IFIs during and following treatment. The prophylactic model studies showed better success rates compared to triazoles (RR = 1.15; 95% CI [1.05, 1.25], I2 = 69.1%), but no differences were found with the empiric model studies (RR = 1.04; 95% CI [0.67, 21.61], I2 = 91%). A 20% RR was found for use of MCFG. MCFG also showed a lower incidence of infections compared to triazoles for rotation of anti-fungal agents in eight pooled trials (n = 1,901; RR = 0.66; 95% CI [0.47, 0.94]; I2 = 71.5%). No difference was found between agents for overall mortality. MCFG had a significantly lower rate of premature discontinuation (p < 0.05) and a lower incidence of AEs for hepatic impairment (RR = 0.67; 95% CI [0.22–2.09]; I2 = 67%), neurological complications (RR = 0.7; 95% CI [0.5–0.98]; I 2 = 3.3%), and GI upset (RR = 0.62; 95% CI [20.42, 0.92]; I2 = 0%). There was no publication bias. Heterogeneity was found with age group differences with analyses showing a stronger effect from MCFG in patients younger than age 45 years. Stratified analyses also showed better outcomes with MCFG.
MCFG was better than triazoles for efficacy and fewer AEs when used prophylactically and as effective as triazoles for the treatment of IFIs. MCFGs were also found to be more effective among patients younger than age 45 years. However, mortality was not lower in one group compared to the other.
High heterogeneity
Recommending the use of MCFG prophylactically can decrease the risk of IFIs and related adverse events among patients undergoing treatment for hematologic malignancies.
Keighley, C.L., Manii, P., Larsen, S.R., & van Hal, S. (2017). Clinical effectiveness of itraconazole as antifungal prophylaxis in AML patients undergoing intensive chemotherapy in the modern era. European Journal of Clinical Microbiology and Infectious Diseases, 36, 213–217.
To examine the rate of probable and proven breakthrough invasive fungal infections (bIFI) with the use of itraconazole prophylaxis as well as the effectiveness and tolerability of itraconazole in patients with acute myeloid leukemia (AML)
All patients admitted to the Royal Prince Albert Hospital who had AML and were undergoing chemotherapy and who were receiving itraconazole for antifungal prophylaxis were given itraconazole 200 mg oral solution twice daily starting 1-2 days prior to the chemotherapy and continuing until the neutrophil count was greater than 500.
PHASE OF CARE: Active anti-tumor treatment
Retrospective study
Onset of invasive fungal infection; this was determined three different ways:
bIFI were classified as possible, probable, or proven; a bIFI was one that was diagnosed at least five days after starting antifungal prophylaxis.
Itraconazole was shown to be tolerable with few side effects. CT scans were performed in 55 patients and a bronchoalveolar lavage (BAL) was performed in 20 episodes that were shown to be abnormal on CT scan. Four of those undergoing BAL had positive results constituting probable bIFI. Empiric antifungal therapy was started in 33 patients; there was no evidence of bIFI in 16 of those patients. These possible IFI infections were treated for a median of 19 days with no progression to definitive IFI. Overall bIFI rate was 3.4%. Patients with bIFI have significantly longer length of stays and higher 30-day mortality (11%).
The use of itraconazole is reasonable with low side effects and low rates of bIFI noted in this group. Account of local epidemiology must be considered when choosing an antifungal agent overall.
Cost of the intervention in some areas may be problematic. Nurses should work with their pharmacy colleagues to identify the most common fungal epidemiology before the choice of antifungal therapy is chosen. Education with patients is needed about the importance of taking the medications for prophylaxis to prevent bIFI.
Yemm, K.E., Barreto, J.N., Mara, K.C., Dierkhising, R.A., Gangat, N., & Tosh, P.K. (2018). A comparison of levofloxacin and oral third-generation cephalosporins as antibacterial prophylaxis in acute leukaemia patients during chemotherapy-induced neutropenia. Journal of Antimicrobial Chemotherapy, 73, 204–211.
To compare the efficacy (measured via incidence of febrile neutropenia [FN]) of levofloxacin versus oral third-generation cephalosporins (OTGCs) given as antibacterial prophylaxis during chemotherapy-induced neutropenia in high-risk patients with hematological malignancies. The goal was to demonstrate non-inferiority of OTGCs as an alternate therapy if fluoroquinolones were contraindicated. Secondary outcomes measured the incidence of bacterial infection between prophylactic drugs and compared the specific microorganisms identified in positive cultures.
Following induction chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), high-risk patients were prescribed levofloxacin 500 mg daily as antibiotic prophylaxis if appropriate. Similar patients who could not take levofloxacin because of intolerance, allergy, drug interaction, or previous adverse drug reactions were prescribed OTGCs (either cefdinir 300 mg twice daily or cefpodoxime 200 mg twice daily). The duration of antibiotic therapy was not specified. Chart reviews began with the start of antibiotic prophylaxis and continued until the earliest of 30 days following the last dose of antibiotic prophylaxis, the beginning of consolidation chemotherapy administration, or death. The two groups were compared for incidence of FN and for the secondary outcomes.
PHASE OF CARE: Active anti-tumor treatment
Retrospective chart review, matching patients by OTGCs versus levofloxacin in a 1:2 ratio. Matching factors were age (plus or minus 5 years) and the Charlson comorbidity index (plus or minus 3).
Using retrospective chart review, researchers compared the incidence of FN, time to onset of FN, duration of neutropenia, site of infection, morphology of recovered organisms, and resistance to prophylactic agent.
The incidence of FN within 30 days of initiation of antibiotic prophylaxis was 83.4% (95% CI [65.8, 91.9]) in the OTGC group and 92.5% (95% CI [83.8, 96.5]) in the levofloxacin group, and was similar between the two groups (HR = 0.9, 95% CI [0.54, 1.52], p = 0.7). The median duration of neutropenia was also similar between the two groups, with 46 days (IQR = 26-67 days) for OTGCs and 39 days (IQR = 27-49 days) for levofloxacin. Similarly, the duration of prophylaxis prior to the onset of FN was comparable between the two groups (8 days for OTGCs, IQR = 6-12 days; and 8.5 days for levofloxacin, IQR = 5-13.5 days). Patients receiving OTGCs were significantly more likely to require ICU admission than those receiving levofloxacin (p = 0.04). The two groups had no significant differences in site of infection (p = 0.91) and morphology of recovered microorganism (p = 0.74). The OTGC group experienced significantly more cultures positive for Enterobacter (p = 0.043) than the levofloxacin group.
Although antibiotic prophylaxis with levofloxacin demonstrated advantages over OTGCs in the areas of avoidance of ICU admission and avoidance of cultures positive for the Enterobacter microorganism, OTGCs offer an acceptable alternative for those patients in whom fluoroquinolones are contraindicated.
The positive culture site was an implanted central venous catheter in the majority of patients (61.5%). This reinforces the need for nurses to maintain meticulous hand hygiene and infection control practices when working with central venous catheters.