**11. Antimicrobial therapy**

In case of sepsis, we commonly combine in first-line therapy, new cephalosporins and quinolones or aminoglycosides. It is important to note that a great part of these recommendations is adapted from the evidence-based medicine recommendations for the management of chemotherapy-induced neutropenia (field of oncology) [3]. Of course ureidopenicillins betalactam/beta-lactamase inhibitor combinations, as carbapenems, or imipenem can be safely used in these antibiotic combinations. The addition of intravenous vancomycin or teicoplanin is considered in patients at high-risk of serious Gram-positive infections or after 48 hours of continued fever despite first-line of antibiotics with at least cephalosporins [2, 3].

(*p* = 0.057) [5]. Thus, for certain hematologist, the usefulness of HGF remains controversy in such patients. To support this view, the only available prospective randomized study (based on 24 patients with antithyroid-related agranulocytosis) did not confirm the benefit of G-CSF [10]. Nevertheless, this negative result may be related to inappropriate G-CSF doses

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To date, no data is available on the use of pegfilgrastim (a long-acting recombinant G-CSF) in

In this setting, it is important to keep in mind that transfusion of granulocyte concentrates should only be used in exceptional circumstances, and only then for the control of life-

In conclusion, it is important to keep in mind that idiosyncratic drug-induced or drug-associated, severe neutropenia and agranulocytosis remains a potentially serious adverse event due to the frequency of severe sepsis, with severe deep tissue infections (e.g., pneumonia), life-threatening infections, septicemia, and septic shock in two-thirds of all hospitalized patients. In this setting, several poor prognostic factors, impacting the hematological recovery, the duration of hospitalization, and the outcome have been documented: old age, poor performance status, septicemia

situation, modern management, with broad-spectrum antibiotics in case of any sepsis sign and

The authors have no conflicts of interest that are directly relevant to the content of this manuscript. E.Andrès is recipient of a grant from CHUGAI, AMGEN, ROCHE, GSK, and NOVARTIS

but these sponsors had no part in the research or writing of the present manuscript.

No sources of funding were used to assist the preparation of this manuscript.

\*Address all correspondence to: emmanuel.andres@chru-strasbourg.fr

Departments of Internal Medicine, University Hospital of Strasbourg, Strasbourg, France

/L. In this

threatening infections with antibiotic resistance such as perineal gangrene [2].

or shock, comorbidities such as renal failure, and a neutrophil count below 0.1 × 109

HGF is likely to improve the prognosis, with a currently mortality rate around 5%.

(100–200 μg/day).

**13. Conclusions**

**Acknowledgements**

**Funding**

**Author details**

Emmanuel Andrès\* and Rachel Mourot-Cottet

idiosyncratic drug-induced neutropenia [2, 3].

In patients with persistent fever despite broad-spectrum antibiotics against Gram-negative bacilli or Gram-positive cocci or systematically after 1 week of persistent fever, the addition of empirical antifungal agents should be considered, as amphotericin B or related derivates (e.g., liposomal preparation of amphotericin), and voriconazol or caspofungin [2, 3].
