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Meta-Analysis
. 2017 Jun 3;6(6):CD003914.
doi: 10.1002/14651858.CD003914.pub4.

Empirical antibiotics targeting gram-positive bacteria for the treatment of febrile neutropenic patients with cancer

Ofrat Beyar-Katz  1 , Yaakov Dickstein, Sara Borok, Liat Vidal, Leonard Leibovici, Mical Paul
Affiliations
Meta-Analysis

Empirical antibiotics targeting gram-positive bacteria for the treatment of febrile neutropenic patients with cancer

Ofrat Beyar-Katz et al. Cochrane Database Syst Rev. .

Abstract

Background: The pattern of infections among neutropenic patients with cancer has shifted in the last decades to a predominance of gram-positive infections. Some of these gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment.

Objectives: To assess the effectiveness of empirical anti-gram-positive (antiGP) antibiotic treatment for febrile neutropenic patients with cancer in terms of mortality and treatment failure. To assess the rate of resistance development, further infections and adverse events associated with additional antiGP treatment.

Search methods: For the review update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (May 2012 to 2017), Embase (May 2012 to 2017), LILACS (2012 to 2017), conference proceedings, ClinicalTrials.gov trial registry, and the references of the included studies. We contacted the first authors of all included and potentially relevant trials.

Selection criteria: Randomised controlled trials (RCTs) comparing one antibiotic regimen versus the same regimen with the addition of an antiGP antibiotic for the treatment of febrile neutropenic patients with cancer.

Data collection and analysis: Two review authors independently assessed trial eligibility and risk of bias, and extracted all data. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated. A random-effects model was used for all comparisons showing substantial heterogeneity (I2 > 50%). Outcomes were extracted by intention-to-treat and the analysis was patient-based whenever possible.

Main results: Fourteen trials and 2782 patients or episodes were included. Empirical antiGP antibiotics were tested at the onset of treatment in 12 studies, and for persistent fever in two studies. The antiGP treatment was a glycopeptide in nine trials. Eight studies were assessed in the overall mortality comparison and no significant difference was seen between the comparator arms, RR of 0.90 (95% CI 0.64 to 1.25; 8 studies, 1242 patients; moderate-quality data). Eleven trials assessed failure, including modifications as failures, while seven assessed overall failure disregarding treatment modifications. Failure with modifications was reduced, RR of 0.72 (95% CI 0.65 to 0.79; 11 studies, 2169 patients; very low-quality data), while overall failure was the same, RR of 1.00 (95% CI 0.79 to 1.27; 7 studies, 943 patients; low-quality data). Sensitivity analysis for allocation concealment and incomplete outcome data did not change the results. Failure among patients with gram-positive infections was reduced with antiGP treatment, RR of 0.56 (95% CI 0.38 to 0.84, 5 studies, 175 patients), although, mortality among these patients was not changed.Data regarding other patient subgroups likely to benefit from antiGP treatment were not available. Glycopeptides did not increase fungal superinfection rates and were associated with a reduction in documented gram-positive superinfections. Resistant colonisation was not documented in the studies.

Authors' conclusions: Based on very low- or low-quality evidence using the GRADE approach and overall low risk of bias, the current evidence shows that the empirical routine addition of antiGP treatment, namely glycopeptides, does not improve the outcomes of febrile neutropenic patients with cancer.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Failure.
5
5
Mortality.
1.1
1.1. Analysis
Comparison 1 Mortality, Outcome 1 Overall mortality.
1.2
1.2. Analysis
Comparison 1 Mortality, Outcome 2 Overall mortality (adequate allocation concealment).
1.3
1.3. Analysis
Comparison 1 Mortality, Outcome 3 Overall mortality (intention to treat).
1.4
1.4. Analysis
Comparison 1 Mortality, Outcome 4 Mortality in Gram‐positive infections.
1.5
1.5. Analysis
Comparison 1 Mortality, Outcome 5 Overall mortality (antiGP not covering Gram‐negatives).
1.6
1.6. Analysis
Comparison 1 Mortality, Outcome 6 Infection‐related fatality.
2.1
2.1. Analysis
Comparison 2 Treatment failure, Outcome 1 Overall failure (disregarding modifications).
2.2
2.2. Analysis
Comparison 2 Treatment failure, Outcome 2 Failure, modifications included.
2.3
2.3. Analysis
Comparison 2 Treatment failure, Outcome 3 Failure, modifications included (adequate allocation concealment).
2.4
2.4. Analysis
Comparison 2 Treatment failure, Outcome 4 Failure, modifications included (intention to treat).
2.5
2.5. Analysis
Comparison 2 Treatment failure, Outcome 5 Failure, modifications included (antiGP not covering Gram‐negatives).
2.6
2.6. Analysis
Comparison 2 Treatment failure, Outcome 6 Failure in Gram‐positive infections.
2.7
2.7. Analysis
Comparison 2 Treatment failure, Outcome 7 Febrile at 72 hrs. on empirical Tx.
2.8
2.8. Analysis
Comparison 2 Treatment failure, Outcome 8 Addition of amphotericin.
3.1
3.1. Analysis
Comparison 3 Superinfections, Outcome 1 Any superinfections.
3.2
3.2. Analysis
Comparison 3 Superinfections, Outcome 2 Bacterial superinfections.
3.3
3.3. Analysis
Comparison 3 Superinfections, Outcome 3 Gram‐positive superinfections.
3.4
3.4. Analysis
Comparison 3 Superinfections, Outcome 4 Fungal superinfections.
4.1
4.1. Analysis
Comparison 4 Adverse events, Outcome 1 Any adverse events.
4.2
4.2. Analysis
Comparison 4 Adverse events, Outcome 2 Rash/ allergy.
4.3
4.3. Analysis
Comparison 4 Adverse events, Outcome 3 Any nephrotoxicity.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Bucaneve 2014 {published data only}
    1. Bucaneve G, Micozzi A, Picardi M, Ballanti S, Cascavilla N, Salutari P, et al. Results of a multicenter, controlled, randomized clinical trial evaluating the combination of piperacillin/tazobactam and tigecycline in high‐risk hematologic patients with cancer with febrile neutropenia. Journal of Clinical Oncology 2014;32(14):1463‐71. - PubMed
Cometta 2003 {published data only}
    1. Cometta A, Kern WV, Bock R, Paesmans M, Vandenbergh M, Crokaert F, et al. Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin‐tazobactam monotherapy. Clinical Infectious Diseases 2003;37(3):382‐9. - PubMed
    1. Cometta A, Kern WV, Debock R, Paesmans M, Vandenbergh M, Crokaert F, et al. An EORTC‐IATG double‐blind trial of vancomycin (Van) versus placebo (Pla) for persistent fever in neutropenic cancer patients (NCP) given piperacillin/tazobactam (PT) monotherapy. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. 2001:445.
    1. Viscoli C, Cometta A, Kern WV, Bock R, Paesmans M, Crokaert F, et al. Piperacillin‐tazobactam monotherapy in high‐risk febrile and neutropenic cancer patients. Clinical Microbiology and Infection 2006;12:212‐6. - PubMed
    1. Wade JC, Glasmacher A. Vancomycin does not benefit persistently febrile neutropenic people with cancer. Cancer Treatment Reviews 2004;30(1):119‐26. - PubMed
Del Favero 1987 {published data only}
    1. Favero A, Menichetti F, Guerciolini R, Bucaneve G, Baldelli F, Aversa F, et al. Prospective randomized clinical trial of teicoplanin for empiric combined antibiotic therapy in febrile, granulocytopenic acute leukemia patients. Antimicrobial Agents and Chemotherapy 1987;31(7):1126‐9. - PMC - PubMed
de Pauw 1985 {published and unpublished data}
    1. Pauw B, Williams K, Neeff J, Bothof T, Witte T, Holdrinet R, et al. A randomized prospective study of ceftazidime versus ceftazidime plus flucloxacillin in the empiric treatment of febrile episodes in severely neutropenic patients. Antimicrobial Agents and Chemotherapy 1985;28(6):824‐8. - PMC - PubMed
EORTC 1991 {published data only}
    1. EORTC‐1991. Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. European Organization for Research and Treatment of Cancer (EORTC) International Antimicrobial Therapy Cooperative Group and the National Cancer Institute of Canada‐Clinical Trials Group. Journal of Infectious Diseases 1991;163(5):951‐8. - PubMed
Erjavec 2000 {published data only}
    1. Erjavec Z, Vries‐Hospers HG, Laseur M, Halie RM, Daenen S. A prospective, randomized, double‐blinded, placebo‐controlled trial of empirical teicoplanin in febrile neutropenia with persistent fever after imipenem monotherapy. Journal of Antimicrobial Chemotherapy 2000;45(6):843‐9. - PubMed
Karp 1986 {published and unpublished data}
    1. Karp JE, Dick JD, Angelopulos C, Charache P, Green L, Burke PJ, et al. Empiric use of vancomycin during prolonged treatment‐induced granulocytopenia. Randomized, double‐blind, placebo‐controlled clinical trial in patients with acute leukemia. American Journal of Medicine 1986;81(2):237‐42. - PubMed
Lawson 1979 {published and unpublished data}
    1. Lawson RD, Gentry LO, Bodey GP, Keating MJ, Smith TL. A randomized study of tobramycin plus ticarcillin, tobramycin plus cephalothin and ticarcillin, or tobramycin plus mezlocillin in the treatment of infection in neutropenic patients with malignancies. American Journal of Medical Sciences 1984;287(1):16‐23. - PubMed
Marie 1991 {published data only}
    1. Marie JP, Pico J, Lapierre V, Maulard C, Pappo M, Chiche D, et al. Empirical treatment of febrile episodes in cancer patients with prolonged neutropenia: comparative study of ceftazidime alone, ceftazidime+amikacin, and ceftazidime+vancomycin [Traitement empirique des episodes febriles survenant chez les patients cancereux presentant une neutropenie prolongee: essai comparatif ceftazidime seule, ceftazidime+amikacine et ceftazidime+vancomycine]. Medicine et Maladies Infectieuses (Medicine and Infectious Diseases) 1991;21:386‐8.
    1. Marie JP, Pico JL, Chiche D, Fitoussi F, Delmer A, Baume D, et al. Antibiotic therapy protocol using ceftazidime 3g/day alone or in combination with vancomycin or amikacin. In febrile episodes in neutropenic patients. Presse Medicale (Medical Press) 1988;17(37):1968‐70. - PubMed
    1. Marie JP, Vekhoff A, Pico JL, Guy H, Andremont A, Richet H. Neutropenic infections: a review of the French Febrile Aplasia Study Group trials in 608 febrile neutropenic patients. Journal of Antimicrobial Chemotherapy 1998;41 Suppl D:57‐64. - PubMed
    1. Pico JL, Marie JP, Chiche D, Guiguet M, Andremont A, Lapierre V, et al. Should vancomycin be used empirically in febrile patients with prolonged and profound neutropenia? Results of a randomized trial. European Journal of Medicine 1993;2(5):275‐80. - PubMed
Menichetti 1986 {published data only}
    1. Menichetti F, Favero A, Guerciolini R, Tonato M, Aversa F, Roila F, et al. Empiric antimicrobial therapy in febrile granulocytopenic patients. Randomized prospective comparison of amikacin plus piperacillin with or without parenteral trimethoprim/sulphamethoxazole. Infection 1986;14(6):261‐7. - PubMed
Molina 1993 {published data only}
    1. Molina F, Pedro L, Rosell R, Barnadas A, Font A, Maurel J, et al. Randomized open and prospective study of two antibiotic schedules (with and without teicoplanin) for post‐chemotherapy episodes of neutropenic fever. Oncologia: IV Congresso Nacional de la SEOM. 1993; Vol. 16:247.
Novakova 1991 {published and unpublished data}
    1. Pauw BE, Novakova IR, Donnelly JP. Options and limitations of teicoplanin in febrile granulocytopenic patients. British Journal of Haematology 1990;76(Suppl 2):1‐5. - PubMed
    1. Novakova I, Donnelly JP, Pauw B. Ceftazidime as monotherapy or combined with teicoplanin for initial empiric treatment of presumed bacteremia in febrile granulocytopenic patients. Antimicrobial Agents and Chemotherapy 1991;35(4):672‐8. - PMC - PubMed
    1. Novakova I, Donnelly JP, Muytjens HL, Pauw B. Ceftazidime as monotherapy or combined with teicoplanin for initial empiric treatment of presumed bacteremia in febrile granulocytopenic patients. 28th Interscience Conference Antimicrobials Agents and Chemotherapy. American Society of Microbiology, 1988:16. - PMC - PubMed
Ramphal 1992 {published data only}
    1. Ramphal R, Bolger M, Oblon DJ, Sherertz RJ, Malone JD, Rand KH, et al. Vancomycin is not an essential component of the initial empiric treatment regimen for febrile neutropenic patients receiving ceftazidime: a randomized prospective study. Antimicrobial Agents and Chemotherapy 1992;36(5):1062‐7. - PMC - PubMed
Verhagen 1987 {published and unpublished data}
    1. Verhagen CS, Pauw B, Witte T, Janssen J, Williams K, Mulder P, et al. Randomized prospective study of ceftazidime versus ceftazidime plus cephalothin in empiric treatment of febrile episodes in severely neutropenic patients. Antimicrobial Agents and Chemotherapy 1987;31(2):191‐6. - PMC - PubMed

References to studies excluded from this review

Berger 2002 {published data only}
    1. Berger C, Kindli K, Niggli D, Nadal D. Meropenem therapy in febrile neutropenic children with cancer seldom affords addition of a glycopeptide. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology, 2002:251.
De Pauw 1997 {published data only}
    1. Pauw BE, Raemaekers JMM, Schattenberg T, Donnelly JP. Empirical and subsequent use of antibacterial agents in the febrile neutropenic patient. Journal of Internal Medicine. Supplement 1997;242(740):69‐77. - PubMed
Dompeling 1996 {published data only}
    1. Dompeling EC, Donnelly JP, Deresinski SC, Feld R, Lane‐Allman EF, Pauw BE. Early identification of neutropenic patients at risk of grampositive bacteraemia and the impact of empirical administration of vancomycin. European Journal of Cancer 1996;32A(8):1332‐9. - PubMed
Elting 1996 {published data only}
    1. Elting LS, Rubenstein EB, Rolston KV, Manzullo E, Bodey GP. Impact of vancomycin (vanc) use on duration of fever and mortality in neutropenic patients with gram positive bacteremia (GPB). Proceedings of the Annual Meeting of the American Society of Clinial Oncology. 1996.
Elting 1997 {published data only}
    1. Elting LS, Rubenstein EB, Rolston KV, Bodey GP. Outcomes of bacteremia in patients with cancer and neutropenia: observations from two decades of epidemiological and clinical trials. Clinical Infectious Diseases 1997;25:247‐59. - PubMed
EORTC 1983 {published data only}
    1. EORTC‐1983. Combination of amikacin and carbenicillin with or without cefazolin as empirical treatment of febrile neutropenic patients. The International Antimicrobial Therapy Project Group of the European Organization for Research and Treatment of Cancer. Journal of Clinical Oncology 1983;1(10):597‐603. - PubMed
Fauser 1991 {published data only}
    1. Fauser AA, Lang E, Dolken G, Bross KJ, Schmid J, Sorgel F. Treatment of severe sepsis in bone marrow transplant recipients with teicoplanin in combination with beta‐lactams and aminoglycosides. Infection 1991;19:195‐200. - PubMed
Granowetter 1988 {published data only}
    1. Granowetter L, Wells H, Lange BJ. Ceftazidime with or without vancomycin vs. cephalothin, carbenicillin and gentamicin as the initial therapy of the febrile neutropenic pediatric cancer patient. Pediatric Infectious Diseases Journal 1988;7:165‐70. - PubMed
Jones 1986 {published data only}
    1. Jones PG, Rolston KV, Fainstein V, Elting L, Walters RS, Bodey GP. Aztreonam therapy in neutropenic patients with cancer. American Journal of Medicine 1986;81:243‐8. - PubMed
Kramer 1986 {published data only}
    1. Kramer BS, Ramphal R, Rand KH. Randomized comparison between two ceftazidime‐containing regimens and cephalothin‐gentamicin‐carbenicillin in febrile granulocytopenic cancer patients. Antimicrobial Agents and Chemotherapy 1986;30(1):64‐8. - PMC - PubMed
Libanore 1991 {published data only}
    1. Libanore M, Bicocchi R, Pantaleoni M, Montanari P, Singhinolfi L, Ghinelli F. Teicoplanin in the therapy of Gram‐positive infections in immunocomprised patients [La Teicoplanina nella Terapia di Infezioni da Gram‐positivi nell'ospite immunocompomesso]. Giornale Italiano di Chemioterapia (Italian Journal of Chemotherapy) 1991;38:167‐9. - PubMed
Lim 1990 {published data only}
    1. Lim S, Smith MP, Goldstone AH, Machin SJ. A randomized prospective study of ceftazidime and ciprofloxacin with or without teicoplanin as an empiric antibiotic regimen for febrile neutropenic patients. British Journal of Haematology 1990;76 Suppl 2:41‐4. - PubMed
Link 1994 {published data only}
    1. Link H, Maschmeyer G, Meyer P, Hiddenmann W, Stille W, Helmerking M, et al. Interventional antimicrobial therapy in febrile neutropenic patients. Annals of Hematology 1994;69:231‐43. - PubMed
    1. Maschmeyer G, Link H, Hiddenmann W, Meyer P, Helmerking M, Adam D. Interventional antimicrobial strategy in febrile neutropenic patients. Results of a multicenter study in 1260 patients with hematological malignancies. The Interventional Antimicrobial Strategy Study Group, Paul Erlich Society for Chemotherapy. Onkologie (Oncology) 1990;13:38‐42. - PubMed
Liu 2000 {published data only}
    1. Liu AJ, Chen SL. Analyze the curative effect of norvancomycin using at 44 patients with agranulocyte after chemotherapy. Contemporary Medicine 2000;6(5):63‐4.
Martino 1992 {published data only}
    1. Martino P, Micozzi A, Gentile G, Raccah R, Girmenia C, Mandelli F. Piperacillin plus amikacin vs. piperacillin plus amikacin plus teicoplanin for empirical treatment of febrile episodes in neutropenic patients receiving quinolone prophylaxis. Clinical Infectious Diseases 1992;15(2):290‐4. - PubMed
    1. Micozzi A, Venditti M, Amadori S, Pulsoni A, Tirindelli C, Martino P. Teicoplanin in the treatment of gram‐positive bacteraemia in neutropenic patients. British Journal of Haematology 1990;76 Suppl 2:19‐23. - PubMed
Moroni 1987 {published data only}
    1. Moroni C, Viscoli C, Boni L, Garaventa A, Dini G, Haupt R, et al. A randomized study of the empirical antibiotic therapy of the infections in neutropenic patients, affected by neoplastic diseases in paediatric age and under a fever attack. Giornale di Malattie Infettive e Parassitarie (Journal of Infectious and Parasitic Dieases) 1987;39:1194‐8.
Novakova 1990 {published data only}
    1. Novakova IR, Donnelly JP, Verhagen CS, Pauw BE. Teicoplanin as modification of initial empirical therapy in febrile granulocytopenic patients. Journal of Antimicrobial Chemotherapy 1990;25(6):985‐93. - PubMed
Pizzo 1982 {published data only}
    1. Pizzo AP, Robichaud KJ, Fred AG, Witebsky FG. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. American Journal of Medicine 1982;72:101‐11. - PubMed
Pizzo 1986 {published data only}
    1. Pizzo P, Hathorn JW, Hiemenz J, Browne M, Commers J, Cotton D, et al. A randomized trial comparing ceftazidime alone with combination antibiotic therapy in cancer patients with fever and neutropenia. New England Journal of Medicine 1986;315:552‐8. - PubMed
Rubin 1988 {published data only}
    1. Rubin M, Hathorn JW, Marshall D, Gress J, Steinberg SM, Pizzo PA. Gram‐positive infections and the use of vancomycin in 550 episodes of fever and neutropenia. Annals of Internal Medicine 1988;108(1):30‐5. - PubMed

Additional references

Akova 2016
    1. Akova M. Epidemiology of antimicrobial resistance in bloodstream infections. Virulence 2016;7(3):252‐66. - PMC - PubMed
Averbuch 2013
    1. Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica 2013;98(12):1826‐35. - PMC - PubMed
Bucaneve 2005
    1. Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, et al. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. New England Journal of Medicine 2005;353:977‐87. - PubMed
Cometta 2007
    1. Cometta A, Marchetti O, Calandra T. Empirical use of anti‐Gram‐positive antibiotics in febrile neutropaenic cancer patients with acute leukaemia. European Journal of Cancer 2007;5 Suppl:23‐31.
Consensus 1990
    1. From the Immunocompromised Host Society. The design, analysis, and reporting of clinical trials on the empirical antibiotic management of the neutropenic patient. Report of a consensus panel. Journal of Infectious Diseases 1990;161(3):397‐401. - PubMed
Consort statement
    1. Consort statement. http://www.consort‐statement.org/.
Del Favero 2001
    1. Favero A, Menichetti F, Martino P, Bucaneve G, Micozzi A, Gentile G, et al. A multicenter, double‐blind, placebo‐controlled trial comparing piperacillin‐tazobactam with and without amikacin as empiric therapy for febrile neutropenia. Clinical Infectious Diseases 2001;33(8):1295‐301. - PubMed
EARS‐NET
    1. Antibiotic resistance and antibiotic consumption. http://ecdc.europa.eu/EN/HEALTHTOPICS/ANTIMICROBIAL‐RESISTANCE‐AND‐CONSU....
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315(7109):629‐34. - PMC - PubMed
EORTC 1978
    1. Schimpff SC, Gaya H, Klastersky J, Tattersall MH, Zinner SH. Three antibiotic regimens in the treatment of infection in febrile granulocytopenic patients with cancer. The EORTC international antimicrobial therapy project group. Journal of Infectious Diseases 1978;137(1):14‐29. - PubMed
EORTC 1986
    1. Klastersky J, Glauser MP, Schimpff SC, Zinner SH, Gaya H. Prospective randomized comparison of three antibiotic regimens for empirical therapy of suspected bacteremic infection in febrile granulocytopenic patients. Antimicrobial Agents and Chemotherapy 1986;29(2):263‐70. - PMC - PubMed
EORTC 1987
    1. The EORTC International Antimicrobial Therapy Cooperative Group. Ceftazidime combined with a short or long course of amikacin for empirical therapy of gram‐negative bacteremia in cancer patients with granulocytopenia. New England Journal of Medicine 1987;317(27):1692‐8. - PubMed
EORTC 1993
    1. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Efficacy and toxicity of single daily doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia. Annals of Internal Medicine 1993;119(7 Pt 1):584‐93. - PubMed
EORTC 1995
    1. Cometta A, Zinner S, Bock R, Calandra T, Gaya H, Klastersky J, et al. Piperacillin‐tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Antimicrobial Agents and Chemotherapy 1995;39(2):445‐52. - PMC - PubMed
EORTC 1996
    1. Cometta A, Calandra T, Gaya H, Zinner SH, Bock R, Favero A, et al. Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Infection Program. Antimicrobial Agents and Chemotherapy 1996;40(5):1108‐15. - PMC - PubMed
Finch 2005
    1. Finch RG, Eliopoulos GM. Safety and efficacy of glycopeptide antibiotics. Journal of Antimicrobial Chemotherapy 2005;55:5‐13. - PubMed
Freifeld 2011
    1. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clinical Infectious Diseases 2011;52(5):e56‐93. - PubMed
Gafter‐Gvili 2005
    1. Gafter‐Gvili A, Fraser A, Paul M, Leibovici L. Meta‐analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Annals of Internal Medicine 2005;142:979‐95. - PubMed
Gardete 2014
    1. Gardete S, Tomasz A. Mechanisms of vancomycin resistance in Staphylococcus aureus. Journal of Clinical Investigation 2014;124(7):2836–40. - PMC - PubMed
Gurwith 1978
    1. Gurwith M, Brunton JL, Lank B, Ronald AR, Harding GK, McCullough DW. Granulocytopenia in hospitalized patients. II. A prospective comparison of two antibiotic regimens in the empiric therapy of febrile patients. American Journal of Medicine 1978;64(1):127‐32. - PubMed
Higgins 2011a
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org. Chichester, UK: John Wiley & Sons, Ltd.
Higgins 2011b
    1. Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.
Hughes 1990
    1. Hughes WT, Armstrong D, Bodey GP, Feld R, Mandell GL, Meyers JD, et al. From the Infectious Diseases Society of America. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Journal of Infectious Diseases 1990;161(3):381‐96. - PubMed
May 2014
    1. May L, Klein EY, Rothman RE, Laxminarayan R. Trends in antibiotic resistance in coagulase‐negative staphylococci in the United States, 1999 to 2012. Antimicrobial Agents and Chemotherapy 2014;58(3):1404‐9. - PMC - PubMed
Montassier 2013
    1. Montassier E, Batard E, Gastinne T, Potel G, Cochetière MF. Recent changes in bacteremia in patients with cancer: a systematic review of epidemiology and antibiotic resistance. European Journal of Clinical Microbiology and Infectious Diseases 2013;32(7):841‐50. - PubMed
Montecalvo 1994
    1. Montecalvo MA, Horowitz H, Gedris C, Carbonaro C, Tenover FC, Issah A, et al. Outbreak of vancomycin‐, ampicillin‐, and aminoglycoside‐resistant Enterococcus faecium bacteremia in an adult oncology unit. Antimicrobial Agents and Chemotherapy 1994;38(6):1363‐7. - PMC - PubMed
Nesher 2014
    1. Nesher L, Rolston KV. The current spectrum of infection in cancer patients with chemotherapy related neutropenia. Infection 2014;42(1):5‐13. - PubMed
Parmar 1998
    1. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta‐analyses of the published literature for survival endpoints. Statistics in Medicine 1998;17(24):2815‐34. - PubMed
Penack 2011
    1. Penack O, Buchheidt D, Christopeit M, Lilienfeld‐Toal M, Massenkeil G, Hentrich M, et al. German Society of Hematology and Oncology. Management of sepsis in neutropenic patients: guidelines from the infectious diseases working party of the German Society of Hematology and Oncology. Annals of Oncology 2011;22(5):1019‐29. - PubMed
Press 1984
    1. Press OW, Ramsey PG, Larson EB, Fefer A, Hickman RO. Hickman catheter infections in patients with malignancies. Medicine (Baltimore) 1984;63(4):189‐200. - PubMed
Rosa 2014
    1. Rosa RG, Dos Santos RP, Goldani LZ. Mortality related to coagulase‐negative staphylococcal bacteremia in febrile neutropenia: A cohort study. Canadian Journl of Infectious Diseases and Medical Microbiology 2014;25(1):e14‐7. - PMC - PubMed
Schulz 1995
    1. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408‐12. - PubMed
Sievert 2002
    1. Sievert DM, Boulton ML, Stoltman G, Jonhnson D, Stobierski MG, Downes FP, et al. Staphylococcus aureus resistant to vancomycin ‐ United States, 2002. Morbidity and Mortality Weekly Report 2002;51(26):565‐7. - PubMed
Tenover 2001
    1. Tenover FC, Biddle JW, Lancaster MV. Increasing resistance to vancomycin and other glycopeptides in Staphylococcus aureus. Emerging Infectious Diseases 2001;7(2):327‐32. - PMC - PubMed
Yan 2016
    1. Yan CH, Xu T, Zheng XY, Sun J, Duan XL, Gu JL, et al. Epidemiology of febrile neutropenia in patients with hematological disease‐a prospective multicentre survey in China. Zhonghua Xue Ye Xue Za Zhi 2016;37(3):177‐82. - PMC - PubMed
Yapici 2016
    1. Yapici O, Gunseren F, Yapici H, Merdin A, Yaylali ÜÜ, Merdin FA. Evaluation of febrile neutropenic episodes in adult patients with solid tumors. Molecular and Clinical Oncology 2016;4(3):379‐82. - PMC - PubMed

References to other published versions of this review

Paul 2002
    1. Paul M, Vidal L, Cohen M, Clark O, Soares‐Weiser K, Leibovici L. Additional anti‐Gram‐positive antibiotic treatment for febrile neutropaenic cancer patients. Cochrane Database of Systematic Reviews 2002, Issue 4. [DOI: 10.1002/14651858.CD003914] - DOI - PubMed
Paul 2005a
    1. Paul M, Borok S, Fraser A, Vidal L, Cohen M, Leibovici L. Additional anti‐Gram‐positive antibiotic treatment for febrile neutropenic cancer patients. Cochrane Database of Systematic Reviews 2005, Issue 3. [DOI: 10.1002/14651858.CD003914.pub2] - DOI - PubMed
Paul 2005b
    1. Paul M, Borok S, Fraser A, Vidal L, Leibovici L. Empirical antibiotics against Gram‐positive infections for febrile neutropenia: systematic review and meta‐analysis of randomized controlled trials. Journal of Antimicrobial Chemotherapy 2005;55(4):436‐44. - PubMed
Paul 2014
    1. Paul M, Dickstein Y, Borok S, Vidal L, Leibovici L. Empirical antibiotics targeting Gram‐positive bacteria for the treatment of febrile neutropenic patients with cancer. Cochrane Database of Systematic Reviews 2014, Issue 1. [DOI: 10.1002/14651858.CD003914.pub3] - DOI - PubMed

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