944 Table 2 shows the criteria used for changing the initial empirical regimen. Most of sites considered persistent fever for 2-4 days or aggravated clinical symptoms for 1-2 days as failure of the first-line antibiotics. Table 3 shows the antibac- terial agents that were prescribed as second-line regimens. The most common approach was to add a glycopeptide regard- less of signs of gram positive infection and change to the second-line regimens. The second-line regimens were as fol- lows: carbapenem with or without aminoglycoside was con- sidered for cases in which cephalosporin or piperacillin/ tazobactam was used as the first-line regimen, and cefepime, ceftazidime, or piperacillin/tazobactam with or without aminoglycoside was used for cases in which piperacillin was used as the first-line regimen. Empirical antifungal and antiviral therapy Table 4 presents the conditions under which antifungal therapy was started. Twenty-seven sites (84.4%) considered adding an antifungal agent after 5-7 days of persistent fever despite antibacterial therapy. And 14 sites initially prescribed antifungal agents to the patients who had a history of inva- sive fungal infection during a previous chemotherapy. Table 5 shows the first-line antifungal agents used for treatment of persistent neutropenic fever. In cases receiving antifungal prophylaxis, amphotericin B deoxycholate or IV itracona- Table 3. Second-line antibiotics prescribed to patients who did not respond to the initial empirical regimen Antibiotic regimen (total number of sites responded=33) Add of or change to cephalosporin, AG or carbapenem (no glycopeptide) Continue with 1st-line antibiotics+glycopeptide Change to 2nd-line antibiotics + glycopeptide Change to 2nd-line antibiotics or add glycopeptide Change to 2nd-line antibiotics+glycopeptide in case of GPC infection Second-line antibiotics other than glycopeptide (total number of sites responded=32) Carbapenem±AG Carbapenem or cefepime/ceftazidime/tazocin±AG AG, aminoglycoside; GPC, gram-positive cocci. N (%) 5 (15.2) 4 (12.1) 9 (27.3) 4 (12.1) 11 (33.3) 26 (81.3) 6 (18.7) Table 5. First-line antifungal agents in persistent neutropenic fever Antifungal agents cAMB Itraconazole (IV) cAMB or itraconazole (IV) Fluconazole (IV) LAMB Total In patients with prophylaxis N (%) 12 (46.1) 6 (24.8) 7 (26.9) 0 (0) 1 (3.8) 26 (100) In patients with- out prophylaxis N (%) 12 (66.7) 4 (22.2) 1 (5.5) 1 (5.5) 0 (0) 18 (100) cAMB, conventional amphotericin B; LAMB, liposomal amphotericin B. S.-M. Choi, S.H. Park, D.-G. Lee, et al. zole were used as the antifungal agents of choice in 25 of 26 sites that responded. Whereas, in cases without antifungal prophylaxis, they were the agents of choice in 17 of 18 sites that responded. Out of 18 sites that responded the rank of preference, 12 sites used amphotericin B as the first-line anti- fungals and 6 sites used IV itraconazole as the first-line anti- fungals. Twenty-two sites responded that they switched to the second-line antifungal agents if persistent fever or deter- ioration of radiological findings occurred after administra- tion of the first-line antifungal agents for 7-10 days. They responded a great variety of second-line antifungal angents such as caspofungin, voriconazole, itraconazole IV, Ampho- tericin B deoxycholate, liposomal amphotericin B, and flu- conazole (only in cases of candidemia). Empirical antiviral therapy was conducted at 20 sites (60.6 %), 17 of which responded that they administered acyclovir in cases of vesicular skin eruption suspicious herpesvirus infection or intractable oral ulcer. Three sites responded that Table 4. Time and situation to start antifungal agents Total number of sites responded=32 N (%) Initial use of antifungals with first line antibacterial agents 15 (46.8) Past history of invasive fungal infection±high dose 14 of steroid Past history of invasive fungal infection±suspicious lesion 1 Not initially but clinical symptom and sign such as Pulmonary infiltrate during broad spectrum 28 (87.5) antibacterial therapy Halo sign on chest CT scan 29 (90.6) Facial swelling and tenderness 17 (53.1) Necrotic escar on perinasal area 19 (59.4) Positive result of culture or non-culture method* 22 (68.7) for fungus Fever during recovery phase of neutropenia 10 (31.2) Isolation of fungus from sputum 12 (37.5) Persistent fever despite antibacterial treatment without any of the above sign for 1-2 days 1 (3.1) 3-5 days 3 (9.4) 5-7 days 27 (84.4) 7-14 days 1 (3.1) *, Galactomannan assay was used at 3 centers. Table 6. Duration of antimicrobial therapy Total number of sites responded=33 Recovery of neutropenia±no infection sign/symptom Regardless of ANC+no infection sign/symptom Afebrile for 2 days Afebrile for 3-5 days Afebrile for 7 days Afebrile for 14 days No specific duration *, Data were not mutually exclusive. ANC, absolute neutrophil count. N* (%) 31 (93.9) 6 (18.1) 6 18 6 2 5