##### ADDENDUM to the National PBM Drug Monograph for

####### Micafungin (Mycamine™)

###### VHA Pharmacy Benefits Management Service and Medical Advisory Panel

Since the time of the original monograph (March 2006), 2 randomized,
double-blind non-inferiority trials for the treatment of
candidemia/invasive candidiasis have been published.

-   Kuse ER, Chetchotisakd P, Cunha CA, et al. Micafungin versus
    liposomal amphotericin B for candidemia and invasive candidosis: a
    phase III randomized double-blind trial. Lancet 2007; 369: 1519-27.

-   Pappas PG, Rotstein CMF, Betts RF, et al. Micafungin versus
    caspofungin for treatment of candidemia and other forms of invasive
    candidiasis. Clin Infect Dis 2007; 45: 883-93.

*[Micafungin vs. Liposomal Amphotericin B]{.underline}*

Micafungin 100mg daily was compared to Liposomal AmB 3mg/kg/day. The
primary outcome was overall treatment success in the per-protocol
population defined as a confirmed Candida infection at baseline,
[\>]{.underline} 5 doses of drug, no prohibited medications, and
availability of investigators assessment for overall success at end of
therapy (micafungin n=202; liposomal AmB n=190). The modified
intent-to-treat group (mITT) was defined as [\>]{.underline} 1 dose of
drug and confirmed Candida infection at baseline (n=247 in each group).

Randomization was stratified according to center and baseline
neutropenic status. The minimum duration of therapy was 14 days and the
maximum 4 weeks. Patients with chronic disseminated candidosis, candida
endocarditis or osteomyelitis could receive study drug for up to 8
weeks. If after 5 days of study, mycological persistence or clinical
signs and symptoms in combination with radiographic abnormalities is
demonstrated , the dose of micafungin could be increased to 200mg daily
and liposomal AmB to 5mg/kg/day. The median duration of therapy was 15
days for both groups. Eleven percent of patients in the micafungin group
required a dosage increase compared to 9% in the liposomal AmB group.

At baseline, 13% of the micafungin and 10% of liposomal AmB groups were
neutropenic and 28% and 24% respectively had APACHE II scores \> 20. The
primary site of infection was the blood for approximately 85% of cases.
Non-albican *Candida* spp. was isolated in approximately 61% of all
infections.

The overall success rates are shown in table 1. Micafungin was found to
be non-inferior to liposomal AmB. See appendix for results broken down
by subgroups.

**Table 1:** Overall success rates

  --------------------- ---------------- --------------- -----------------
                        **Micafungin**   **Liposomal     **Diff
                                         AmB**           \[95%CI\]**

  Overall Success       89.6%            89.5%           0.7% \[-5.3 to
  (PP-group)                                             6.7\]

  Overall Success       74.1%            69.6%           4.9% \[-3.0 to
  (mITT)                                                 12.8\]

  Overall Success (ITT) 71.6%            68.2%           3.9% \[-3.9 to
                                                         11.6\]
  --------------------- ---------------- --------------- -----------------

PP= per-protocol group; mITT=modified intent-to-treat group; ITT=
intent-to-treat group

Overall success = both a clinical (complete or partial resolution of
symptoms) and mycological response

Recurrence during the 12-week post-treatment phase was seen in 7
patients in the micafungin group and 6 patients in the liposomal AmB
group. During the treatment phase, 1 patient in the micafungin group and
2 in the liposomal AmB group had a newly emergent Candida infection
(different species than baseline) which resolved for all patients.
During the follow-up period, 3 patients in the micafungin group and 4
patients in the liposomal AmB group had a newly emergent candida
infection. One patient in the micafungin group developed an infection
with *Fusarium* spp. during the treatment phase which did not resolve
during the study.

There was no significant difference in the incidence of serious
treatment-related adverse events. Treatment was discontinued in 4.9% of
micafungin patients and 9% of liposomal AmB patients (p=0.087).

Significantly more patients receiving liposomal AmB had an increase in
serum creatinine (29.9% vs. 10.3%), rigors (6.4% vs. 0.8%), back pain
(4.5% vs. 0.4%), and infusion-related reactions (28.8% vs. 17%).
Compared to micafungin, liposomal AmB resulted in a higher incidence of
treatment-related hypokalemia (12% vs. 6.8% p=0.053) and pyrexia (12.7%
vs. 8% p=0.087); however, this did not reach statistical significance.
There was no significant difference in change in ALT, AST, and bilirubin
between micafungin and liposomal AmB.

*[Micafungin versus caspofungin]{.underline}*

Micafungin 100mg (n=191) and 150mg (n=199) were compared to caspofungin
50mg (n=188) once daily. The primary endpoint was clinical and
mycological success and end of blinded therapy in the modified
intent-to-treat group defined as [\>]{.underline}1 dose of study drug
with documented baseline candidemia or noncandidemic invasive
candidiasis and no *Candida* endocardiditis, osteomyelitis, or
meningitis.

Randomization was stratified according to geographical region and APACHE
II score. Study medications were administered for 14-28 days or for up
to 8 weeks for chronic disseminated candidiasis or Candida
endophthalmitis. Investigators were encouraged to continue treatment
with study drug for 14 days after a negative culture (for those w/
candidemia) or resolution of symptoms for those with invasive
candidiasis. A switch to oral fluconazole 400mg daily was allowed after
at least 10 days of study drug and if specific criteria were met. The
median duration of treatment was 14 days for all 3 groups. Approximately
20% of patients completed treatment with oral fluconazole.

At baseline, 11.5%, 8.5%, and 5.9% of the micafungin 100mg, 150mg and
caspofungin groups respectively were neutropenic. Approximately 19% of
patients had an APACHE II score \> 20. The primary site of infection was
the blood for approximately 85% of cases. Non-albican *Candida* spp. was
isolated in approximately 55% of all infections.

The overall success rates in the modified intent-to-treat group are
shown in table 2. Micafungin 100mg was found to be non-inferior to
caspofungin. See appendix for results broken down by subgroups.

**Table 2: Overall Success Rates**

+----------------------+---------------+---------------+---------------+
|                      | **Micafungin  | **Micafungin  | **            |
|                      | 100mg**       | 150mg**       | Caspofungin** |
+----------------------+---------------+---------------+---------------+
| Overall Success      | 146/191       | 142/199       | 136/188       |
|                      | (76.4%)       | (71.4%)       | (72.3%)       |
+----------------------+---------------+---------------+---------------+
| Tx diff (micafungin  | 4.1% \[-4.4   | -1.0% \[-9.3  |               |
| -- caspofungin)      | to 12.3\]     | to 7.8\]      |               |
|                      |               |               |               |
| \[95% CI\]           |               |               |               |
+----------------------+---------------+---------------+---------------+

Overall success= clinical (complete or partial resolution of symptoms)
and mycological response at end of blinded therapy

There were 3 emergent fungal infections (different species than
baseline) that developed during the treatment or follow-up periods; 1
case in the micafungin 150mg group, 2 cases in the caspofungin group,
and none in the micafungin 100mg group.

The overall relapse rate (those confirmed by culture and those where
empiric antifungal tx was administered) during the post-treatment period
was 19.8% (n=22), 15.2% (n=16), and 20% (n=20) for micafungin 100mg,
150mg and caspofungin respectively. Among these cases 13/58 were
confirmed by culture.

The number of adverse events related to hepatic, renal, injection site
reactions, histamine/allergic-type reactions, infusion-related
reactions, and hemolysis was similar among all groups. Events leading to
discontinuation of therapy included liver function abnormalities (n=6),
rash (n=3), leucopenia (n=1), thrombocytopenia (n=1), thrombocytosis
(n=1), hypokalemia (n=1), seizures (n=1), confusion (n=1), renal failure
(n=1), and malaise (n=1).

**Table 3: Adverse Events**

  ---------------------- ---------------- ---------------- -----------------
                         **Micafungin     **Micafungin     **Caspofungin**
                         100mg**          150mg**          

  Treatment-emergent     22%              22.8%            23.8%
  adverse events                                           

  Study drug-related     5 (2.5%)         6 (3%)           7 (3.6%)
  adverse event leading                                    
  to withdrawal                                            
  ---------------------- ---------------- ---------------- -----------------

**Appendix**: Published Clinical Trials for Treatment of Candidemia

+-----+----------+------------+------------+---------------------------+
| **S | **In     | **Dose**   | **De       | **Results**               |
| tud | clusion/ |            | mographics |                           |
| y** | e        |            | and        |                           |
|     | xclusion |            | baseline   |                           |
|     | cr       |            | values**   |                           |
|     | iteria** |            |            |                           |
+-----+----------+------------+------------+---------------------------+
| K   | [\>]{.un | 1:1        | **Age      | <table>                   |
| use | derline} | ran        | (years):** | <colgroup>                |
| 2   | 16 years | domization | 54.5/ 56   | <col                      |
| 007 | old      | stratified |            | style="width: 43%" />     |
|     |          | by center  | **%        | <col                      |
| R,  | Clinical | and        | neut       | style="width: 28%" />     |
| DB, | signs of | baseline   | ropenic:** | <col                      |
| m   | systemic | n          | 13%/ 10%   | style="width: 28%" />     |
| ult | candida  | eutropenic |            | </colgroup>               |
| ina | i        | status     | **APACHE   | <tbody>                   |
| tio | nfection |            | II         | <tr class="odd">          |
| nal |          | Micafungin | score:**   | <td></td>                 |
|     | [\>]{.un | 100mg      | 15.8/ 15.6 | <td><stron                |
| Non | derline} | daily vs.  |            | g>Micafugin</strong></td> |
| -in | 1 +      |            | **APACHE   | <td><strong>Liposomal     |
| fer | culture  | Liposomal  | score\>    | AmB</strong></td>         |
| ior | for      | AmB        | 20:** 28%/ | </tr>                     |
| ity | candida  | 3mg/kg/day | 24%        | <tr class="even">         |
| st  | from     |            |            | <td>Median daily          |
| udy | blood or | If after 5 | **H        | dose</td>                 |
|     | other    | days of    | ematologic | <td>100mg</td>            |
| P   | sterile  | study,     | d          | <td>3mg/kg</td>           |
| rim | site     | m          | isorder:** | </tr>                     |
| ary | within   | ycological | 19%/ 13%   | <tr class="odd">          |
| an  | the      | p          |            | <td>Median duration of    |
| aly | previous | ersistence | **Acute    | tx</td>                   |
| sis | 4 days   | or         | l          | <td><p>15 days</p>        |
| ba  |          | clinical   | eukemia:** | <p>(max 42                |
| sed | **Exclu  | signs and  | 9%/ 7%     | days)</p></td>            |
| on  | sions:** | symptoms   |            | <td><p>15 days</p>        |
| the | positive | in         | **Solid    | <p>(max 56                |
| per | cultures | c          | organ      | days)</p></td>            |
| -pr | only     | ombination | tumor:**   | </tr>                     |
| oto | from     | with       | 14%/ 20%   | <tr class="even">         |
| col | oropha   | ra         |            | <td>% requiring ↑in       |
| p   | ryngeal, | diographic | **D        | dose</td>                 |
| op. | eso      | abn        | iabetes:** | <td>11%</td>              |
|     | phageal, | ormalities | 12%/ 12%   | <td>9%</td>               |
|     | urine    | is         |            | </tr>                     |
|     | sputum   | de         | **Tra      | <tr class="odd">          |
|     | BAL      | monstrated | nsplant:** | <td>Overall               |
|     | sp       | , the dose | 8%/ 4%     | Success¶</td>             |
|     | ecimens, | of         |            | <td>89.6%</td>            |
|     | in       | micafungin | **Systemic | <td>89.5%</td>            |
|     | dwelling | could be   | anti       | </tr>                     |
|     | urinary  | increased  | biotics:** | <tr class="even">         |
|     | c        | to 200mg   | 97%/ 97%   | <td>Overall Success       |
|     | atheter, | daily and  |            | †</td>                    |
|     | [\>]{.un | liposomal  | **IV       | <td>74.1%</td>            |
|     | derline} | AmB to     | c          | <td>69.6%</td>            |
|     | 3 days   | 5mg/kg/day | atheter:** | </tr>                     |
|     | of       |            | 84%/ 80%   | <tr class="odd">          |
|     | systemic | Minimum tx |            | <td>Complete/partial      |
|     | an       | duration   | **ICU:**   | response †</td>           |
|     | tifungal | 14 days    | 55%/ 56%   | <td>64.4%/ 9.7%</td>      |
|     | w/i      | and        |            | <td>60.7%/ 8.9%</td>      |
|     | previous | maximum 4  | **Systemic | </tr>                     |
|     | week     | weeks (8   | steroids/  | <tr class="even">         |
|     | (except  | weeks      | antineop   | <td><p><u>Success by      |
|     | for      | allowed    | lastics/** | dx</u> ¶</p>              |
|     | neu      | for        |            | <p>•Candidemia</p>        |
|     | tropenic | oste       | *          | <p>•Invasive              |
|     | patients | omyelitis, | *immunomod | candidiasis</p></td>      |
|     | r        | end        | ulators:** | <td><p>90.6%              |
|     | eceiving | ocarditis, | 42%/ 42%   | (154/170)</p>             |
|     | an       | or chronic |            | <p>84.4%                  |
|     | tifungal | di         | **TPN:**   | (27/32)</p></td>          |
|     | proph    | sseminated | 25%/ 27%   | <td><p>148/163            |
|     | ylaxis), | c          |            | (90.8%)</p>               |
|     | ALT/AST  | andidosis) | **D        | <p>81.5%                  |
|     | \> 10 x  |            | ialysis:** | (22/27)</p></td>          |
|     | ULN,     |            | 13%/ 9%    | </tr>                     |
|     | b        |            |            | <tr class="odd">          |
|     | ibirubin |            | Values are | <td><p><u>Success by      |
|     | \> 5xULN |            | for        | organism</u> ¶</p>        |
|     |          |            | m          | <p>•C. albicans</p>       |
|     |          |            | icafungin/ | <p>•C. tropicalis</p>     |
|     |          |            | liposomal  | <p>•C. parapsilosis</p>   |
|     |          |            | AmB        | <p>•C. glabrata</p>       |
|     |          |            |            | <p>•C. krusei</p></td>    |
|     |          |            |            | <td><p>76/86              |
|     |          |            |            | (88.4%)</p>               |
|     |          |            |            | <p>48/52 (92.3%)</p>      |
|     |          |            |            | <p>33/37 (89.2%)</p>      |
|     |          |            |            | <p>19/23 (82.6%)</p>      |
|     |          |            |            | <p>5/6 (83.3%)</p></td>   |
|     |          |            |            | <td><p>75/84              |
|     |          |            |            | (89.3%)</p>               |
|     |          |            |            | <p>100/112 (89.3%)</p>    |
|     |          |            |            | <p>41/43 (95.3%)</p>      |
|     |          |            |            | <p>26/30 (86.7%)</p>      |
|     |          |            |            | <p>12/15 (80%)</p></td>   |
|     |          |            |            | </tr>                     |
|     |          |            |            | <tr class="even">         |
|     |          |            |            | <td><p><u>Success by      |
|     |          |            |            | APACHE II</u></p>         |
|     |          |            |            | <p>• <u>&lt;</u> 20</p>   |
|     |          |            |            | <p>• &gt; 20</p></td>     |
|     |          |            |            | <td><p>131/142            |
|     |          |            |            | (92.3%)</p>               |
|     |          |            |            | <p>31/39                  |
|     |          |            |            | (79.5%)</p></td>          |
|     |          |            |            | <td><p>116/131            |
|     |          |            |            | (88.5%)</p>               |
|     |          |            |            | <p>33/37                  |
|     |          |            |            | (89.2%)</p></td>          |
|     |          |            |            | </tr>                     |
|     |          |            |            | <tr class="odd">          |
|     |          |            |            | <td><p><u>Success by      |
|     |          |            |            | baseline neutrophil       |
|     |          |            |            | count</u> †</p>           |
|     |          |            |            | <p>• <u>&gt;</u> 500      |
|     |          |            |            | cells</p>                 |
|     |          |            |            | <p>• &lt;500              |
|     |          |            |            | cells</p></td>            |
|     |          |            |            | <td><p>164/215            |
|     |          |            |            | (76.3%)</p>               |
|     |          |            |            | <p>19/32                  |
|     |          |            |            | (59.4%)</p></td>          |
|     |          |            |            | <td><p>158/222            |
|     |          |            |            | (71.2%)</p>               |
|     |          |            |            | <p>14/25 (56%)</p></td>   |
|     |          |            |            | </tr>                     |
|     |          |            |            | <tr class="even">         |
|     |          |            |            | <td><p><u>Success</u></p> |
|     |          |            |            | <p>•Catheter              |
|     |          |            |            | removed/replaced</p>      |
|     |          |            |            | <p>•Catheter not          |
|     |          |            |            | removed</p></td>          |
|     |          |            |            | <td><p>107/116            |
|     |          |            |            | (92.2%)</p>               |
|     |          |            |            | <p>24/29                  |
|     |          |            |            | (82.8%)</p></td>          |
|     |          |            |            | <td><p>98/111             |
|     |          |            |            | (88.3%)</p>               |
|     |          |            |            | <p>20/21                  |
|     |          |            |            | (95.2%)</p></td>          |
|     |          |            |            | </tr>                     |
|     |          |            |            | <tr class="odd">          |
|     |          |            |            | <td>Median time to        |
|     |          |            |            | negative culture</td>     |
|     |          |            |            | <td>3 days</td>           |
|     |          |            |            | <td>4 days</td>           |
|     |          |            |            | </tr>                     |
|     |          |            |            | <tr class="even">         |
|     |          |            |            | <td>Mycological           |
|     |          |            |            | persistence ¶</td>        |
|     |          |            |            | <td>18/194 (9%)</td>      |
|     |          |            |            | <td>16/174 (9%)</td>      |
|     |          |            |            | </tr>                     |
|     |          |            |            | <tr class="odd">          |
|     |          |            |            | <td>Deaths during tx      |
|     |          |            |            | phase (ITT)</td>          |
|     |          |            |            | <td>47 (18%)</td>         |
|     |          |            |            | <td>46 (17%)</td>         |
|     |          |            |            | </tr>                     |
|     |          |            |            | <tr class="even">         |
|     |          |            |            | <td>Deaths during         |
|     |          |            |            | 12-week follow-up         |
|     |          |            |            | (ITT)</td>                |
|     |          |            |            | <td>106 (40%)</td>        |
|     |          |            |            | <td>108 (40%)</td>        |
|     |          |            |            | </tr>                     |
|     |          |            |            | </tbody>                  |
|     |          |            |            | </table>                  |
|     |          |            |            |                           |
|     |          |            |            | ¶ per-protocol group      |
|     |          |            |            |                           |
|     |          |            |            | † modified                |
|     |          |            |            | intent-to-treat group     |
+-----+----------+------------+------------+---------------------------+

**Appendix (continued)**

+-----+----------+----------+-----------+------------------------------+
| **S | **In     | **Dose** | **Dem     | **Results**                  |
| tud | clusion/ |          | ographics |                              |
| y** | e        |          | /         |                              |
|     | xclusion |          | baseline  |                              |
|     | cr       |          | values**  |                              |
|     | iteria** |          |           |                              |
+-----+----------+----------+-----------+------------------------------+
| Pap | [\>]{.un | 1:1:1    | **Age     | <table>                      |
| pas | derline} | rando    | (         | <colgroup>                   |
| 2   | 18 y/o   | mization | years):** | <col style="width: 32%" />   |
| 007 |          | (st      | 56.6/     | <col style="width: 22%" />   |
|     | [\>]{.un | ratified | 55.4/     | <col style="width: 22%" />   |
| R,  | derline} | by       | 55.8      | <col style="width: 22%" />   |
| DB, | 1 +      | region   |           | </colgroup>                  |
| MC  | culture  | and      | **APACHE  | <tbody>                      |
|     | for      | APACHE   | II        | <tr class="odd">             |
| n=  | candida  | II       | score:**  | <td></td>                    |
| 593 | from     | score)   | 15/ 14.8/ | <td><strong>Micafungin       |
|     | blood or |          | 13.9      | 100</strong></td>            |
| Non | other    | Mi       |           | <td><strong>Micafungin       |
| -in | sterile  | cafungin | **APACHE  | 150</strong></td>            |
| fer | site     | 100mg QD | score\>   | <td><stro                    |
| ior | within   |          | 20:**     | ng>Caspofungin</strong></td> |
| ity | the      | Mi       | 18.3%/    | </tr>                        |
| st  | previous | cafungin | 20.1%/    | <tr class="even">            |
| udy | 4 days   | 150mg QD | 19.1%     | <td>Median duration of tx    |
|     |          |          |           | (range)*</td>                |
| mo  | [\>]{.un | Cas      | *         | <td>14 (1-61)</td>           |
| dif | derline} | pofungin | *Baseline | <td>14 (1-56)</td>           |
| ied | 1 of the | 50mg QD  | catheter  | <td>14 (1-43)</td>           |
| ITT | fo       | (70mg    | (%):**    | </tr>                        |
| an  | llowing: | LD)      | 87.4/     | <tr class="odd">             |
| aly | T        |          | 93.6/     | <td><p>% switched to         |
| sis | [\>]{.un | Study    | 92.2      | fluconazole</p>              |
|     | derline} | meds     |           | <p>(median duration of       |
|     | 38ºC or  | admi     | **Prior   | oral tx)</p></td>            |
|     | \<36 ºC; | nistered | a         | <td><p>20.9%</p>             |
|     | SBP \<   | for      | ntifungal | <p>(7.5d)</p></td>           |
|     | 90mmHg   | 14-28    | tx(%):**  | <td><p>15.1%</p>             |
|     | or a     | days or  | 65.6/     | <p>(6.5d)</p></td>           |
|     | decrease | for up   | 62.9/     | <td><p>21.2%</p>             |
|     | of \>    | to 8     | 59.6      | <p>(4 d)</p></td>            |
|     | 30mmg Hg | weeks    |           | </tr>                        |
|     | from     | for      | *         | <tr class="even">            |
|     | b        | chronic  | *Baseline | <td>Overall Success</td>     |
|     | aseline; | diss     | ne        | <td>146/191 (76.4%)</td>     |
|     | local    | eminated | utropenic | <td>142/199 (71.4%)</td>     |
|     | signs    | can      | (%):**    | <td>136/188 (72.3%)</td>     |
|     | and      | didiasis | 11.5/     | </tr>                        |
|     | symptoms | or       | 8.5/ 5.9  | <tr class="odd">             |
|     | of       | Candida  |           | <td><p>Clinical              |
|     | infla    | endopht  | **% w/    | success</p>                  |
|     | mmation; | halmitis | mali      | <p>•Complete response</p>    |
|     | radi     |          | gnancy:** | <p>•Partial                  |
|     | ographic | May      | 35.6/     | response</p></td>            |
|     | findings | switch   | 28.2/     | <td><p>87.4%</p>             |
|     | su       | to oral  | 27.7      | <p>74.3%</p>                 |
|     | ggestive | flu      |           | <p>13.1%</p></td>            |
|     | of       | conazole | **% using | <td><p>87.4%</p>             |
|     | invasive | 400mg    | st        | <p>76.9%</p>                 |
|     | can      | daily    | eroids:** | <p>10.5%</p></td>            |
|     | didiasis | after at | 29.5/     | <td><p>87.2%</p>             |
|     |          | least 10 | 28.7/     | <p>73.4%</p>                 |
|     | **[Ex    | days of  | 21.8      | <p>13.8%</p></td>            |
|     | clusions | study    |           | </tr>                        |
|     | :]{.unde | drug and | **%       | <tr class="even">            |
|     | rline}** | if       | Recent    | <td><p><u>Clinical success   |
|     | p        | specific | surgery   | by dx</u></p>                |
|     | regnant, | criteria | :** 26.5/ | <p>•Candidemia</p>           |
|     | nursing, | were     | 29.7/     | <p>•Invasive                 |
|     | Ch       | met.     | 39.4      | candidiasis</p></td>         |
|     | ild-Pugh |          |           | <td><p>143/163 (87.7%)</p>   |
|     | score \> |          | **% Organ | <p>24/28(85.7%)</p></td>     |
|     | 9, life  |          | tran      | <td><p>148/168 (88.1%)</p>   |
|     | ex       |          | splant:** | <p>26/30 (86.7%)</p></td>    |
|     | pectancy |          | 3.5/ 4.5/ | <td><p>144/161 (89.4%)</p>   |
|     | \< 5     |          | 3.6       | <p>20/26 (76.9%)</p></td>    |
|     | days,    |          |           | </tr>                        |
|     | proven   |          | **%       | <tr class="odd">             |
|     | or       |          | HSCT:**   | <td><p><u>Success by         |
|     | s        |          | 5.0/ 2.0/ | organism</u></p>             |
|     | uspected |          | 2.1       | <p>•C. albicans</p>          |
|     | endoc    |          |           | <p>•C. tropicalis</p>        |
|     | arditis, |          | **%       | <p>•C. parapsilos</p>        |
|     | osteom   |          | Di        | <p>•C. glabrata</p>          |
|     | yelitis, |          | abetes:** | <p>•C. krusei</p></td>       |
|     | men      |          | 31.4/     | <td><p>71/92 (77.2%)</p>     |
|     | ingitis, |          | 36.2/     | <p>21/31 (67.7%)</p>         |
|     | using    |          | 25.5      | <p>22/29 (75.9%)</p>         |
|     | cyclo    |          |           | <p>24/28 (85.7%)</p>         |
|     | sporine, |          | **%       | <p>6/8 (75%)</p></td>        |
|     | use of a |          | Di        | <td><p>71/102 (69.6%)</p>    |
|     | candin   |          | alysis:** | <p>20/33 (60.6%)</p>         |
|     | less     |          | 9.0/      | <p>15/21 (71.4%)</p>         |
|     | than 1   |          | 12.4/     | <p>30/34 (88.2%)</p>         |
|     | month    |          | 12.4      | <p>5/8 (62.5%)</p></td>      |
|     | before   |          |           | <td><p>61/83 (73.5%)</p>     |
|     | random   |          | **%       | <p>24/32 (75%)</p>           |
|     | ization, |          | Cand      | <p>27/42 (64.3%)</p>         |
|     | \>48     |          | idemia:** | <p>22/33 (66.7%)</p>         |
|     | hours of |          | 85.3/     | <p>3/4 (75%)</p></td>        |
|     | t        |          | 84.4/     | </tr>                        |
|     | reatment |          | 85.6      | <tr class="even">            |
|     | with     |          |           | <td><p><u>Success by         |
|     | systemic |          | **%       | APACHE II</u></p>            |
|     | an       |          | invasive  | <p>•<u>&lt;</u> 20</p>       |
|     | tifungal |          | candi     | <p>•&gt; 20</p></td>         |
|     | for      |          | diasis:** | <td><p>125/156 (80.1%)</p>   |
|     | current  |          | 14.7/     | <p>21/35 (60%)</p></td>      |
|     | i        |          | 15.1/     | <td><p>120/159 (75.5%)</p>   |
|     | nfection |          | 13.8      | <p>22/40 (55%)</p></td>      |
|     |          |          |           | <td><p>115/152 (75.7%)</p>   |
|     |          |          | **% C.    | <p>21/36 (58.3%)</p></td>    |
|     |          |          | al        | </tr>                        |
|     |          |          | bicans:** | <tr class="odd">             |
|     |          |          | 48.2/     | <td><p><u>Success by         |
|     |          |          | 51.3/     | baseline neutrophil          |
|     |          |          | 44.1      | count</u></p>                |
|     |          |          |           | <p>•<u>&gt;</u> 500          |
|     |          |          | **% C.    | cells</p>                    |
|     |          |          | trop      | <p>•&lt;500 cells</p></td>   |
|     |          |          | icalis:** | <td><p>128/169 (75.7%)</p>   |
|     |          |          | 16.2/     | <p>18/22 (81.8%)</p></td>    |
|     |          |          | 16.6/ 17  | <td><p>133/182 (73.1%)</p>   |
|     |          |          |           | <p>9/17 (52.9%)</p></td>     |
|     |          |          | **% C.    | <td><p>129/177 (72.9%)</p>   |
|     |          |          | paraps    | <p>7/11 (63.6%)</p></td>     |
|     |          |          | ilosis:** | </tr>                        |
|     |          |          | 15.2/     | <tr class="even">            |
|     |          |          | 10.6 22.3 | <td><p><u>Success</u></p>    |
|     |          |          |           | <p>•Catheter                 |
|     |          |          | **% C.    | removed/replaced</p>         |
|     |          |          | gl        | <p>•Catheter not             |
|     |          |          | abrata:** | removed</p></td>             |
|     |          |          | 14.7/     | <td><p>100/120 (83.3%)</p>   |
|     |          |          | 17.1/     | <p>29/47 (61.7%)</p></td>    |
|     |          |          | 17.6      | <td><p>102/139 (73.4%)</p>   |
|     |          |          |           | <p>32/47 (68.1%)</p></td>    |
|     |          |          | **% C.    | <td><p>97/125 (77.6%)</p>    |
|     |          |          | krusei:** | <p>30/50 (60%)</p></td>      |
|     |          |          | 4.2/ 4.0/ | </tr>                        |
|     |          |          | 2.1       | <tr class="odd">             |
|     |          |          |           | <td>Mycological              |
|     |          |          | Values    | Success</td>                 |
|     |          |          | are for   | <td>169/191 (88.5%)</td>     |
|     |          |          | m         | <td>166/199 (83.4%)</td>     |
|     |          |          | icafungin | <td>158/188 (84%)</td>       |
|     |          |          | 100mg/    | </tr>                        |
|     |          |          | m         | <tr class="even">            |
|     |          |          | icafungin | <td>Median time to           |
|     |          |          | 150mg/ca  | negative culture</td>        |
|     |          |          | spofungin | <td>2 days</td>              |
|     |          |          | 50mg      | <td>3 days</td>              |
|     |          |          |           | <td>2 days</td>              |
|     |          |          |           | </tr>                        |
|     |          |          |           | <tr class="odd">             |
|     |          |          |           | <td>Mycological              |
|     |          |          |           | persistence during IV tx     |
|     |          |          |           | phase</td>                   |
|     |          |          |           | <td>11/191 (5.8%)</td>       |
|     |          |          |           | <td>23/199 (11.6%)</td>      |
|     |          |          |           | <td>18/188 (9.6%)</td>       |
|     |          |          |           | </tr>                        |
|     |          |          |           | <tr class="even">            |
|     |          |          |           | <td>Deaths during IV tx      |
|     |          |          |           | phase</td>                   |
|     |          |          |           | <td>28/191 (14.7%)</td>      |
|     |          |          |           | <td>29/199 (14.6%)</td>      |
|     |          |          |           | <td>27/188 (14.4%)</td>      |
|     |          |          |           | </tr>                        |
|     |          |          |           | <tr class="odd">             |
|     |          |          |           | <td>Deaths during entire     |
|     |          |          |           | study</td>                   |
|     |          |          |           | <td>58/200 (29%)</td>        |
|     |          |          |           | <td>67/202 (33.2%)</td>      |
|     |          |          |           | <td>51/193 (26.4%)</td>      |
|     |          |          |           | </tr>                        |
|     |          |          |           | </tbody>                     |
|     |          |          |           | </table>                     |
|     |          |          |           |                              |
|     |          |          |           | All data are from the        |
|     |          |          |           | modified ITT group           |
|     |          |          |           |                              |
|     |          |          |           | \*Includes study drug + oral |
|     |          |          |           | fluconazole (if given)       |
+-----+----------+----------+-----------+------------------------------+