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.
Ferreira, J.N., Correia, L.R.B.R., Oliveira, R.M., Watanabe, S.N., Possari, J.F., & Lima, A.F.C. (2017). Managing febrile neutropenia in adult cancer patients: An integrative review of the literature. Revista Brasileira De Enfermagem, 70, 1301–1308.
STUDY PURPOSE: Analyzing interventions for management of chemotherapy-induced febrile neutropenia in adult patients with cancer.
TYPE OF STUDY: Systematic review
DATABASES USED: LILACS (Latin American and Caribbean Literature in Health Sciences), SciELO (Scientific Electronic Library Online), BVS (Virtual Library of Health), PubMed, CINAHL (The Cumulative Index to Nursing and Allied Health Literature), and Web of Science
YEARS INCLUDED: 2010-2015
INCLUSION CRITERIA: Primary articles published in English, Portugese, or Spanish, articles with methodology demonstrating interventions related to the management of chemotherapy-induced febrile neutropenia in adult patients, published between 2010-2015, full-text article availability in the selected databases
TOTAL REFERENCES RETRIEVED: 2,892 articles
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Duplicate articles were first removed from the original 2,892 articles retrieved, followed by elimination of articles that did not cover the research topic, and then finally articles that did not meet the inclusion criteria were removed from the original sample.
PHASE OF CARE: Active anti-tumor treatment
Prophylactic use of colony stimulating factors in patients was effective in avoiding reduction of chemotherapy doses and cycle delays. One of the studies cited use of piperacillin/tazobactam as effective treatment for febrile neutropenia while another one compared ciprofloxacin and cefepime, noting cefepime to be more effective. Neither study reviewed by authors presented a strong case for one antibiotic treatment over another. There were some studies included citing use of biomarkers to classify febrile neutropenia risk in patients and treat prophylactically for those at high risk in the outpatient setting.
Based on the review of these 12 studies, it is evident that the prophylactic use of growth stimulating factors in patients with cancer limits episodes of febrile neutropenia, particularly in diseases such as breast cancer and lymphoma where febrile neutropenia is well documented. There was not a general consensus that could be made for a specific antimicrobial treatment for these patients as many studies cited different medications that deemed effective for patients. Authors note lack of interdisciplinary literature regarding febrile neutropenia guidelines.
Authors cite the need to have nurses, as well as pharmacists and other members of the interdisciplinary team, involved in development of guidelines and protocols as all members of the team treat these patients and need to be knowledgeable about febrile neutropenia.
Sanna, M., Caocci, G., Orrù, F., Ledda, A., Vacca, A., Piras, E., . . . La Nasa, G. (2017). Safe fluoroquinolones prophylaxis in blood cancer patients with chemotherapy-induced neutropenia and Glucose-6-Phosphate-Dehydrogenase deficiency. Journal of Clinical Pharmacy and Therapeutics, 42, 733–737.
To describe how safe and effective fluoroquinolone prophylaxis is for patients with a deficiency of enzyme G6PD who are undergoing treatment for hematologic malignancies
Study participants received prophylaxis with either levofloxacin (500 mg/qd) or ciprofloxacin (500 mg/bid) beginning with initial chemotherapy administration until absolute neutrophil count recovers to greater than 1,000. Participants also received prophylactic antifungal therapy (fluconazole, posaconazole, or voriconazole).
PHASE OF CARE: Active anti-tumor treatment
Retrospective cohort study
Patients were identified as having G6PD deficiency based on enzyme activity testing using the G6PD/6PGD Automatic Analyzer (KUADRO), Nurex SRL. Study definitions of “infection” included:
Febrile neutropenia was assigned only when it occurred during the patient’s first episode of neutropenia (absolute neutrophil count of 1,000 mm3 or less). However, authors did not include a definition of acute hemolytic anemia.
Overall, patients with G6PD deficiency had fewer cases of febrile neutropenia (p = 0.01; hazard ratio 0.46; 95% confidence interval [0.25, 0.8]). The subset of patients treated for AML with G6PD deficiency had a higher risk of invasive fungal diseases (p < 0.0001; HR 11.4; 95% CI [3.5, 37.05]) and sepsis due to Candida (p = 0.008; HR 37; 95% CI [2.01, 680.9]). However, incidence of bacterial infection between groups was not statistically significant. Incidence of febrile neutropenia was slightly less (p = 0.01) among study participants with G6PD deficiency. Evaluation of 3,904 red blood cell units administered to study participants identified zero cases of acute hemolytic anemia for all patients regardless of G6PD status.
Fluoroquinolone prophylaxis did not appear to increase risk of acute hemolytic anemia-based on G6PD enzyme status. Patients with G6PD deficiency may be at higher risk of fungal infection, but lower risk of febrile neutropenia during intensive chemotherapy to treat hematologic malignancies.
There is no indication that fluoroquinolone prophylaxis is unsafe or ineffective at reducing the risk of febrile neutropenia, regardless of G6PD enzyme status. If G6PD testing results are available, nurses may need to consider their patients with G6PD deficiency at higher risk for invasive fungal infections while on fluoroquinolone prophylaxis.
Mikulska, M., Averbuch, D., Tissot, F., Cordonnier, C., Akova, M., Calandra, T., . . . European Conference on Infections in Leukemia. (2018). Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines. Journal of Infection, 76, 20–37.
STUDY PURPOSE: To assess whether the recommendation by the European Conference on Infections in Leukemia to use fluoroquinolone prophylaxis for patients with high-risk neutropenia has resulted in a reduction in infection and mortality. A secondary objective was to assess the effect of fluoroquinolone prophylaxis on antibiotic resistance.
TYPE OF STUDY: Meta analysis and systematic review
DATABASES USED: PubMed
YEARS INCLUDED: 2006-2014
INCLUSION CRITERIA: Article assessed fluoroquinolone prophylaxis among patients with high-risk neutropenia undergoing treatment for blood cancer or patients post-hematopoietic cell transplantation (HCT)
EXCLUSION CRITERIA: (a) No assessment of antibiotic prophylaxis; (b) unable to discern whether the research question was relevant; (c) antibiotic prophylaxis included a non-fluoroquinolone
TOTAL REFERENCES RETRIEVED: N = 68
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Multiple statistical methods were applied to evaluate the studies included in the review. In addition, community prevalence of fluoroquinolone resistance was evaluated based on study data included in the review and previous studies.
FINAL NUMBER STUDIES INCLUDED: 14
TOTAL PATIENTS INCLUDED IN REVIEW: 5,930
SAMPLE RANGE ACROSS STUDIES: 45–1,981
KEY SAMPLE CHARACTERISTICS: Study populations included patients with acute leukemias, hematologic malignancies, or post-autologous or allogeneic HCT. Studies included years of observation from 1998–2012.
PHASE OF CARE: Active anti-tumor treatment
Of the 14 studies analyzed, 12 were observational and two were randomized controlled trials. Overall, the odds ratio with fluoroquinolone prophylaxis were:
However, in the analysis of three meta-analyses, published since 2006, Gafter-Gvili et al. (2012) found a statistically significant decrease in overall mortality (2.8% versus 5.3%, p = 0.00012). The rate of infection caused by fluoroquinolone resistant bacteria was 4% for patients who received prophylaxis and for patients who did not receive prophylaxis. There is insufficient data to determine the role of fluoroquinolone prophylaxis on the appearance of new, resistant bacteria.
Fluoroquinolone prophylaxis did not reduce overall mortality for patients with high risk neutropenia. However, there is some evidence that it may reduce the rate of bloodstream infections and febrile neutropenia. Clinically, the impact of prophylaxis may be low since many patients still develop febrile neutropenia and other risks, including Clostridium difficile infection and fluoroquinolone toxicity, were not analyzed. However, since most international guidelines with the exception of Australia, recommend fluoroquinolone prophylaxis, and there is insufficient conclusive evidence to recommend otherwise, the overall recommendation is to follow institutional policies but seriously consider the risks and benefits of prophylaxis for each patient.
Most of the 14 studies included in the analysis (12) were observational.
In the absence of contraindication or risk of complication with prophylaxis, there is insufficient evidence to routinely omit fluoroquinolone prophylaxis. Consider the risks and benefits of fluoroquinolone prophylaxis for each patient individually. Recognize the clinical benefit for an individual may be minimal. Consider review and update to institutional policies accordingly.
Lee, S.S.F., Fulford, A.E., Quinn, M.A., Seabrook, J., & Rajakumar, I. (2018). Levofloxacin for febrile neutropenia prophylaxis in acute myeloid leukemia patients associated with reduction in hospital admissions. Supportive Care in Cancer, 26, 1499–1504.
To evaluate the safety and efficacy of oral levofloxacin in preventing febrile neutropenia (FN) in patients who have received consolidation chemotherapy for acute myeloid leukemia (AML)
Following consolidation chemotherapy with: (1) cytarabine 3 g/m2 IV q 12 hours on days 1, 3, and 5; (2) fludarabine 30 mg/m2 IV on days 1-5, and cytarabine 2 g/m2 IV on days 1-5, with or without filgrastim 300-480 mcg SQ daily beginning on day 6 until neutrophil recovery; or (3) mitoxantrone 6 mg/m2 IV on days 1-3 and cytarabine 2 g/m2 IV q 12 hours on days 1-3 for cycle 1 and 1 g/m2 for cycle 2; hematologists chose whether to prescribe levofloxacin or not. This retrospective chart review compared the levofloxacin group to the no levofloxacin group. The primary efficacy outcome compared rehospitalization rates between those who received levofloxacin and those who did not. Secondary outcomes assessed duration of antibiotic treatment needed for FN and compared rates of Clostridium difficile-associated diarrhea (CDAD) between the two groups.
PHASE OF CARE: Transition phase after active treatment
Retrospective chart review of AML patients, 50 of whom had received levofloxacin following consolidation chemotherapy and 50 of whom had not.
To evaluate the primary outcome, researchers tracked the rate of hospital readmission because of FN. Secondary outcomes considered the total number of days of antibiotic therapy required to recover from FN and counted the number of days between hospital discharge after consolidation chemotherapy and readmission for FN. Safety outcomes compared the rate of CDAD between the levofloxacin and no levofloxacin groups within 30 days following hospital discharge following consolidation chemotherapy, the relative rates of positive blood cultures in FN patients, the relative rates of resistance to levofloxacin from positive bacterial cultures, and the impact of levofloxacin on the spectrum of bacteria identified from positive cultures.
Following the first cycle of consolidation chemotherapy, 42% of patients who received levofloxacin were readmitted for FN. The no levofloxacin group had a readmission rate of 72% (p = 0.002). Results following all cycles of consolidation chemotherapy were less dramatic but still demonstrated the benefit of levofloxacin therapy (51.4% readmission for FN in the levofloxacin group, compared to 67% in the no levofloxacin” group (p = 0.023). There were no significant differences between the two groups in terms of total number of antibiotic treatment days (median 11 versus 10, p = 0.639), mean day of readmission after discharge from receiving consolidation chemotherapy (11.58 versus 10.37, p = 0.205), and rate of positive bacterial culture in readmitted FN patients (28.9 versus 42.9, p = 0.148).
This study supports the previously-established Infectious Diseases Society of America and National Comprehensive Cancer Network guidelines for antibiotic prophylaxis for cancer patients at high risk of developing FN. Levofloxacin use had no significant impact on any of the secondary outcome measures.
This retrospective chart review did not separate the various consolidation chemotherapy regimens into separate arms. The authors searched until they found the intended sample size of patients who had received levofloxacin and those who had not. Of note, the levofloxacin dose and duration of fluoroquinolone therapy was not standardized.
Horita, N., Shibata, Y., Watanabe, H., Namkoong, H., & Kaneko, T. (2017). Comparison of antipseudomonal beta-lactams for febrile neutropenia empiric therapy: Systematic review and network meta-analysis. Clinical Microbiology and Infection, 23, 723–729.
STUDY PURPOSE: To compare the effectiveness and safety of antipseudomonal b-lactam empiric monotherapy for febrile neutropenia by network meta-analysis
TYPE OF STUDY: Meta analysis and systematic review
DATABASES USED: PubMed, Cochrane CENTRAL, EMBASE, and Web of Science Core Collection
YEARS INCLUDED: No year limitation
INCLUSION CRITERIA: Definition of febrile neutropenia was ANC less 500 mcl or less than 1,000 mcl and temperature greater than 38 C for more than one hour or temperature greater than 38.3 C. Patients in both arms had to be treated with IV antipseudomonal beta-lactam antibiotic for initial empiric therapy of febrile neutropenia. GCSF use was allowed.
EXCLUSION CRITERIA: Granulocyte transfusion was excluded. Antibiotics not evaluated in a RCT in the past 10 years (since 2006) were excluded.
TOTAL REFERENCES RETRIEVED: 1,275
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Evaluated quality of each study using 6 domains of the Cochrane risk of bias tool
FINAL NUMBER STUDIES INCLUDED: 50 studies
TOTAL PATIENTS INCLUDED IN REVIEW: 10,872 patients
KEY SAMPLE CHARACTERISTICS: Adult and pediatric febrile neutropenia patients undergoing chemotherapy for either solid tumors or hematologic malignancies.
PHASE OF CARE: Active anti-tumor treatment
APPLICATIONS: Elder care
Treatment success without antibiotic modification was most likely with Cefoperazone/sulbactam followed by imipenem/cilastatin, piperacillin/tazobactam, meropenem, cefepime, cefozopran, ceftazidime and panipenem/betamipron. The risk for all-cause death was lowest in all-cause death were lowest in the imipenem/cilastatin arm and highest in the cefepime arm.
Imipenem/cilastatin followed by piperacillin/tazobactam and meropenem had the best performance in the treatment success without modification and all-cause death.
Antipseudomonal antibiotics are effective for empiric treatment of febrile neutropenia and imipenem/cilastatin, piperacillin/tazobactam, and meropenem had the best performance in the treatment success without modification and all-cause death. This may be due to increasing incidence of extended spectrum beta lactamase-producing bacteria that are resistant to cefepime. However, cefepime is still recommended by major guidelines for initial use and remains a reasonable choice, particularly given the concern of antibiotic resistance using carbapenems as initial empiric therapy for febrile neutropenia.