ABSTRACT
The problem of invasive candidiasis among ICU patients is an increasing and evolving one. Despite advances in supportive care, increasing numbers of critically ill and vulnerable patients are susceptible to infection, and the clinical consequences for those who do develop invasive candidiasis remain poor. Evolving epidemiological trends, particularly a relative increase in the incidence of fluconazole-resistant Candida spp., have further complicated management. The recent availability of antifungal agents, such as voriconazole, the echinocandins, and lipid-associated amphotericin B preparations, with improved safety profiles, extended spectra, and proven clinical efficacies, offers new therapeutic options. However, optimizing therapy requires the consideration of numerous factors: the differing pharmacological properties of these agents, cost, the clinical status and progress of the patient, estimates of the likelihood of resistance, and microbiological data as they become available. Because early institution of antifungal therapy appears an important determinant of favorable outcome, accurate early microbiological and clinical markers of invasive candidiasis to guide early antifungal interventions are desperately needed and remain an area of active investigation.
KEYWORDS
Invasive candidiasis - candidemia - antifungal therapy
REFERENCES
-
1
Ostrosky-Zeichner L, Pappas P.
Invasive candidiasis in the intensive care unit.
Crit Care Med.
2006;
34
857-863
-
2
Eggimann P, Garbino J, Pittet D.
Epidemiology of Candida species infections in critically ill non-immunosuppressed patients.
Lancet Infect Dis.
2003;
3
685-702
-
3
Wisplinghoff H, Bischoff T, Tallent S M, Seifert H, Wenzel R P, Edmond M B.
Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study.
Clin Infect Dis.
2004;
39
309-317
-
4
Richards M J, Edwards J R, Culver D H, Gaynes R P.
Nosocomial infections in medical intensive care units in the United States.
Crit Care Med.
1999;
27
887-892
-
5
Richards M J, Edwards J R, Culver D H, Gaynes R P.
Nosocomial infections in combined medical-surgical intensive care units in the United States.
Infect Control Hosp Epidemiol.
2000;
21
510-515
-
6
Jarvis W R, Edwards J R, Culver D H et al..
Nosocomial infection rates in adult and pediatric intensive care units in the United States.
Am J Med.
1991;
91
185S-191S
-
7
Marchetti O, Bille J, Fluckiger U et al..
Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991-2000.
Clin Infect Dis.
2004;
38
311-320
-
8
Rangel-Frausto M S, Wiblin T, Blumberg H M et al..
National epidemiology of mycoses survey (NEMIS): variations in rates of bloodstream infections due to Candida species in seven surgical intensive care units and six neonatal intensive care units.
Clin Infect Dis.
1999;
29
253-258
-
9
Leleu G, Aegerter P, Guidet B.
Systemic candidiasis in intensive care units: a multicenter, matched-cohort study.
J Crit Care.
2002;
17
168-175
-
10
Beck-Sague C, Jarvis W R.
Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990.
J Infect Dis.
1993;
167
1247-1251
-
11
Trick W E, Fridkin S K, Edwards J R, Hajjeh R A, Gaynes R P.
Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989-1999.
Clin Infect Dis.
2002;
35
627-630
-
12
Pelz R K, Lipsett P A, Swoboda S M et al..
Candida infections: outcome and attributable ICU costs in critically ill patients.
J Intensive Care Med.
2000;
15
255-261
-
13
Rentz A M, Halpern M T, Bowden R.
The impact of candidemia on length of hospital stay, outcome, and overall cost of illness.
Clin Infect Dis.
1998;
27
781-788
-
14
Pfaller M A, Diekema D J.
Epidemiology of invasive candidiasis: a persistent public health problem.
Clin Microbiol Rev.
2007;
20
133-163
-
15
Montravers P, Dupont H, Gauzit R et al..
Candida as a risk factor for mortality in peritonitis.
Crit Care Med.
2006;
34
646-652
-
16
Pappas P G, Rex J H, Sobel J D et al..
Guidelines for treatment of candidiasis.
Clin Infect Dis.
2004;
38
161-189
-
17
Groll A H, Gea-Banacloche J C, Glasmacher A, Just-Nuebling G, Maschmeyer G, Walsh T J.
Clinical pharmacology of antifungal compounds.
Infect Dis Clin North Am.
2003;
17
159-191
-
18
Eggimann P, Garbino J, Pittet D.
Management of Candida species infections in critically ill patients.
Lancet Infect Dis.
2003;
3
772-785
-
19
Girois S B, Chapuis F, Decullier E, Revol B GP.
Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis.
Eur J Clin Microbiol Infect Dis.
2006;
25
138-149
-
20
Kulemann V, Bauer M, Graninger W, Joukhadar C.
Safety and potential of drug interactions of caspofungin and voriconazole in multimorbid patients.
Pharmacology.
2005;
75
165-178
-
21
Rex J H, Bennett J E, Sugar A M et al..
A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia.
N Engl J Med.
1994;
331
1325-1330
-
22
Phillips P, Shafran S, Garber G et al..
Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients.
Eur J Clin Microbiol Infect Dis.
1997;
16
337-345
-
23
Kullberg B J, Sobel J D, Ruhnke M et al..
Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial.
Lancet.
2005;
366
1435-1442
-
24
Anaissie E J, Darouiche R O, Abi-Said D et al..
Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature.
Clin Infect Dis.
1996;
23
964-972
-
25
Kontoyiannis D P, Bodey G P, Mantzoros C S.
Fluconazole vs. amphotericin B for the management of candidaemia in adults: a meta-analysis.
Mycoses.
2001;
44
125-135
-
26
Mora-Duarte J, Betts R, Rotstein C et al..
Comparison of caspofungin and amphotericin B for invasive candidiasis.
N Engl J Med.
2002;
347
2020-2029
-
27
Kuse E-R, Chetchotisakd P, da Cunha C A et al..
Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial.
Lancet.
2007;
369
1519-1527
-
28
Reboli A C, Rotstein C, Pappas P G et al..
Anidulafungin versus fluconazole for invasive candidiasis.
N Engl J Med.
2007;
356
2472-2482
-
29 Betts R F, Rotstein C, Talwar D et al.. Comparison of micafungin and caspofungin for candidemia or invasive candidiasis (IC). In: Program and Abstracts of the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco; American Society for Microbiology 2006 abstract M-1308a
-
30 Anaissie E J, White M, Uzon O et al.. Amphotericin B lipid complex versus amphotericin B for treatment of invasive candidiasis: a prospective, randomized, multicenter trial. In: 35th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco; American Society for Microbiology 1996 abstract LM21
-
31
Rex J H, Pappas P G, Karchmer A W et al..
A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects.
, [see comment]
Clin Infect Dis.
2003;
36
1221-1228
-
32
Sobel J D, Revankar S G.
Echinocandins: first choice or first-line therapy for invasive candidiasis?.
N Engl J Med.
2007;
356
2525-2526
-
33
Pachl J, Svoboda P, Jacobs F et al..
A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. [see comment].
Clin Infect Dis.
2006;
42
1404-1413
-
34
Herbrecht R, Fohrer C, Nivoix Y.
Mycograb for the treatment of invasive candidiasis.
Clin Infect Dis.
2006;
43
1083-4
-
35
Lipsett P A.
Surgical critical care: fungal infections in surgical patients.
Crit Care Med.
2006;
34
S215-S224
-
36
Shorr A F, Lazarus D R, Sherner J H et al..
Do clinical features allow for accurate prediction of fungal pathogenesis in bloodstream infections? Potential implications of the increasing prevalence of non-albicans candidemia.
Crit Care Med.
2007;
35
1077-1083
-
37
Trotman R L, Williamson J C, Shoemaker D M, Salzer W L.
Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy.
Clin Infect Dis.
2005;
41
1159-1166
-
38
von Mach M A, Burhenne J, Weilemann L S.
Accumulation of the solvent vehicle sulphobutylether beta cyclodextrin sodium in critically ill patients treated with intravenous voriconazole under renal replacement therapy.
BMC Clin Pharmacol.
2006;
6
6
-
39
Muhl E.
Antimycotic drugs under continuous renal replacement therapy.
Mycoses.
2005;
48
56-60
-
40
Mohammedi I, Piens M A, Padoin C, Robert D.
Plasma levels of voriconazole administered via a nasogastric tube to critically ill patients.
Eur J Clin Microbiol Infect Dis.
2005;
24
358-360
-
41
Harbarth S, Pestotnik S L, Lloyd J F, Burke J P, Samore M H.
The epidemiology of nephrotoxicity associated with conventional amphotericin B therapy.
Am J Med.
2001;
111
528-534
-
42
Harbarth S, Burke J P, Lloyd J F, Evans R S, Pestotnik S L, Samore M H.
Clinical and economic outcomes of conventional amphotericin B-associated nephrotoxicity.
Clin Infect Dis.
2002;
35
e120-e127
-
43
Bates D W, Su L, Yu D T.
Mortality and costs associated with amphotericin B therapy.
Clin Infect Dis.
2001;
32
686-693
-
44
Anderson C M.
Sodium chloride treatment of amphotericin B nephrotoxicity: standard of care?.
West J Med.
1995;
162
313-317
-
45
Eriksson U, Seifert B, Schaffner A.
Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial.
BMJ.
2001;
322
579-582
-
46
Kleinberg M.
What is the current and future status of conventional amphotericin B?.
Int J Antimicrob Agents.
2006;
27(Suppl 1)
12-16
-
47
Wingard J R, White M H, Anaissie E et al..
A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia.
Clin Infect Dis.
2000;
31
1155-1163
-
48
Fleming R V, Kantarjian H M, Husni R et al..
Comparison of amphotericin B lipid complex (ABLC) vs. ambisome in the treatment of suspected or documented fungal infections in patients with leukemia.
Leuk Lymphoma.
2001;
40
511-520
-
49
Brooks R G.
Prospective study of Candida endophthalmitis in hospitalized patients with candidemia.
Arch Intern Med.
1989;
149
2226-2228
-
50
Pappas P G.
Invasive candidiasis.
Infect Dis Clin North Am.
2006;
20
485-506
-
51
Rodriguez-Adrian L J, King R T, Tamayo-Derat L G, Miller J W, Garcia C A, Rex J H.
Retinal lesions as clues to disseminated bacterial and candidal infections: frequency, natural history, and etiology.
Medicine.
2003;
82
187-202
-
52
Ostrosky-Zeichner L, Rex J H, Pappas P G et al..
Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States.
Antimicrob Agents Chemother.
2003;
47
3149-3154
-
53
Rex J H, Pfaller M A, Barry A L, Nelson P W, Webb C D.
Antifungal susceptibility testing of isolates from a randomized, multicenter trial of fluconazole versus amphotericin B as treatment of nonneutropenic patients with candidemia.
Antimicrob Agents Chemother.
1995;
39
40-44
-
54
Malani A, Hmoud J, Chiu L, Carver P L, Bielaczyc A, Kauffman C A.
Candida glabrata fungemia: experience in a tertiary care center.
Clin Infect Dis.
2005;
41
975-981
-
55
Nucci M, Anaissie E.
Revisiting the source of candidemia: skin or gut?.
Clin Infect Dis.
2001;
33
1959-1967
-
56
Bross J, Talbot G H, Maislin G, Hurwitz S, Strom B L.
Risk factors for nosocomial candidemia: a case-control study in adults without leukemia.
Am J Med.
1989;
87
614-620
-
57
Blumberg H M, Jarvis W R, Soucie J M et al..
Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study.
Clin Infect Dis.
2001;
33
177-186
-
58
McKinnon P S, Goff D A, Kern J W et al..
Temporal assessment of Candida risk factors in the surgical intensive care unit.
Arch Surg.
2001;
136
1401-1408
-
59
Anaissie E J, Rex J H, Uzun O, Vartivarian S.
Predictors of adverse outcome in cancer patients with candidemia.
Am J Med.
1998;
104
238-245
-
60
Nucci M, Anaissie E.
Should vascular catheters be removed from all patients with candidemia? An evidence-based review.
Clin Infect Dis.
2002;
34
591-599
-
61
Rex J H, Bennett J E, Sugar A M et al..
Intravascular catheter exchange and duration of candidemia.
Clin Infect Dis.
1995;
21
994-996
-
62
Walsh T J, Rex J H.
All catheter-related candidemia is not the same: assessment of the balance between the risks and benefits of removal of vascular catheters.
Clin Infect Dis.
2002;
34
600-602
-
63
Mermel L A, Farr B M, Sherertz R J et al..
Guidelines for the management of intravascular catheter-related infections.
Clin Infect Dis.
2001;
32
1249-1272
-
64
Bennett J E.
Echinocandins for candidemia in adults without neutropenia.
N Engl J Med.
2006;
355
1154-1159
-
65
Oude Lashof A M, Donnelly J P, Meis J F, van der Meer J W, Kullberg B J.
Duration of antifungal treatment and development of delayed complications in patients with candidaemia.
Eur J Clin Microbiol Infect Dis.
2003;
22
43-48
-
66
Garey K W, Rege M, Pai M P et al..
Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study.
Clin Infect Dis.
2006;
43
25-31
-
67
Morrell M, Fraser V J, Kollef M H.
Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality.
Antimicrob Agents Chemother.
2005;
49
3640-3645
-
68
Chen S C, Halliday C L, Meyer W.
A review of nucleic acid-based diagnosis tests for systemic mycoses with an emphasis on polymerase chain reaction-based assays.
Med Mycol.
2002;
40
333-357
-
69
Yeo S F, Wong B.
Current status of nonculture methods for diagnosis of invasive fungal infections.
Clin Microbiol Rev.
2002;
15
465-484
-
70
Obayashi T, Toshida M, Mori T et al..
Plasma (1-> 3)-β-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes.
Lancet.
1995;
345
17-20
-
71
Odabasi Z, Mattiuzzi G, Estey E et al..
Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome.
Clin Infect Dis.
2004;
39
199-205
-
72
Takesue Y, Kakehashi M, Ohge H et al..
Combined assessment of beta-D-glucan and degree of candida colonization before starting empiric therapy for candidiasis in surgical patients.
World J Surg.
2004;
28
625-630
-
73
Digby J, Kalbfleisch J, Glenn A, Larsen A, Browder W, Williams D.
Serum glucan levels are not specific for presence of fungal infections in intensive care unit patients.
Clin Diagn Lab Immunol.
2003;
10
882-885
-
74
Pickering J W, Sant H W, Bowles C AP, Roberts W L, Woods G L.
Evaluation of a (1-> 3)-beta-D-glucan assay for diagnosis of invasive fungal infections.
J Clin Microbiol.
2005;
43
5957-5962
-
75
Ostrosky-Zeichner L.
New approaches to the risk of Candida in the intensive care unit.
Curr Opin Infect Dis.
2003;
16
533-537
-
76
Pittet D, Monod M, Suter P M, Frenk E, Auckenthaler R.
Candida colonization and subsequent infections in critically ill surgical patients.
Ann Surg.
1994;
220
751-758
-
77
Magill S S, Swoboda S M, Johnson E A et al..
The association between anatomic site of Candida colonization, invasive candidiasis, and mortality in critically ill surgical patients.
Diagn Microbiol Infect Dis.
2006;
55
293-301
-
78
Paphitou N I, Ostrosky-Zeichner L, Rex J.
Rules for identifiying patients at increased risk for candidal infections in the surgical intensive care unit: approach to developing practical criteria for systemic use in antifungal prophylaxis trials.
Med Mycol.
2005;
43
235-243
-
79
Leon C, Ruiz-Santana S, Saavedra S et al..
A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization.
Crit Care Med.
2006;
34
730-737
-
80
Piarroux R, Grenouillet F, Balvay P et al..
Assessment of preemptive treatment to prevent severe candidiasis in critically ill surgical patients.
Crit Care Med.
2004;
32
2443-2449
-
81
Dupont H, Bourichon A, Paugam-Burtz C, Mantz J, Desmonts J-M.
Can yeast isolation in peritoneal fluid be predicted in intensive care unit patients with peritonitis.
Crit Care Med.
2003;
31
752-757
-
82
Michalopoulos A S, Geroulanos S, Mentzelopoulos S D.
Determinants of candidemia and candidemia-related death in cardiothoracic ICU patients.
Chest.
2003;
124
2244-2255
-
83
Ostrosky-Zeichner L, Sable C, Sobel J et al..
Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting.
Eur J Clin Microbiol Infect Dis.
2007;
26
271-276
-
84
Playford E G, Webster A C, Sorrell T C, Craig J C.
Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: systematic review and meta-analysis of randomized clinical trials.
J Antimicrob Chemother.
2006;
57
628-638
-
85
Golan Y, Wolf M P, Pauker S G, Wong J B, Hadley S.
Empirical anti-Candida therapy among selected patients in the intensive care unit: a cost-effectiveness analysis.
Ann Intern Med.
2005;
143
857-869
-
86
Eggimann P, Calandra T, Fluckiger U et al..
Invasive candidiasis: comparison of management choices by infectious diseases and critical care specialists.
Intensive Care Med.
2005;
31
1514-1517
-
87
Garey K W, Neuhauser M M, Bearden D T et al..
Evaluation of antifungals in the surgical intensive care unit: a multi-institutional study.
Mycoses.
2006;
49
226-231
Elliott Geoffrey PlayfordM.B. B.S. M.Med.
Infection Management Services, Princess Alexandra Hospital
Ipswich Rd., Woolloongabba, Qld 4102, Australia
Email: geoffrey_playford@health.qld.gov.au
