Articles |
Management of candidiasis in the intensive care unit
Department of Microbiology, Norfolk and Norwich University Hospital, Norwich NR2 3TX, UK
* Tel: +44-1603-611816; Fax: +44-1603-620190; E-mail: sschelenz{at}doctors.org.uk
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Abstract |
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 Top Abstract IntroductionCandida colonization and the...Management of candidaemia in...Preventative measures and the...ConclusionsTransparency declarationsReferences |
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In the last two decades, Candida has emerged as an important opportunistic pathogen. Patients admitted to the intensive care unit (ICU) are particularly susceptible to this infection because of the severity of their underlying illness and the excess use of medical and surgical interventions. The frequent use of antibiotics, central venous catheters and other intravascular devices as well as poor gut motility or abdominal surgery place these patients at high risk of infection, which contributes to the morbidity and mortality of the already critically ill patient. Early recognition and appropriate management of invasive candidiasis are therefore important. This article addresses important management issues such as the role of screening for Candida colonization, the use of prophylaxis and the choice of antifungal agents for the treatment of presumed and proven invasive candidiasis in the adult ICU setting.
Keywords: ICUs , treatment , prophylaxis
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Introduction |
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TopAbstractIntroductionCandida colonization and the...Management of candidaemia in...Preventative measures and the...ConclusionsTransparency declarationsReferences |
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Nosocomial Candida infections such as candidaemia have emerged as an increasing problem during the last two decades. The hospital-wide incidence of candidaemia in the UK is approximately 3 per 100 000 bed days, and 40% to 52% of all cases occur in the intensive care unit (ICU).1–3
National surveillance studies have shown that the incidence of infection varies greatly between different types of ICUs.4 Among surgical ICUs (SICUs), the candidaemia rate can vary as much as 0.50–1.73 per 1000 patient days.5 In general, ICUs caring for high-risk patients such as abdominal surgical or immunosuppressed patients have a higher incidence of invasive candidiasis than general medical ICUs/SICUs as illustrated by the National Epidemiology of Mycosis Survey study.4 The difference in infection rates is mainly due to the patient case mix and risk factors, but may also be influenced by the specific management of the infection in particular units. There are a number of well-described general risk factors such as old age, very low birth weight in premature neonates, diabetes mellitus and immunosuppression.3,6 In addition, multivariate analyses have identified some specific independent risk factors in SICU patients (Table 1).7,8
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Candidaemia is associated with considerable morbidity in critically ill patients leading to an overall prolonged ICU stay, a longer duration of mechanical ventilation and haemodialysis.9,10 The attributable mortality is
38%,11 although it can vary between 5% and 71%.12–14 The economic burden of a candidaemia case in an ICU has been estimated to be in the region of 
16 000.15 Because of the substantial morbidity, mortality and economic cost of invasive candidiasis, the appropriate management of this infection is important. |
Candida colonization and the role of screening |
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TopAbstractIntroductionCandida colonization and the...Management of candidaemia in...Preventative measures and the...ConclusionsTransparency declarationsReferences |
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Candida species frequently colonize non-sterile sites in the body, particularly the skin, mouth, gut and genitals. In SICU patients, the most frequently colonized sites are the oropharynx (63%), urine (25%) and gut (11%), but Candida can also be found in other areas such as the lumen of medical devices including urinary catheters and wound drains.16 The risk of colonization increases with the duration of the ICU stay, the use of urinary catheter and the use of antibiotics such as vancomycin or imipenem.17,18
Typing of Candida isolates has shown that those patients who develop invasive candidiasis have previously been colonized by the same strain with a median time from colonization to infection of 8 days.19,20 Unfortunately, there are no validated laboratory markers that can reliably predict or detect early invasive candidiasis in ICU patients. In the past, researchers have tried to predict infection by measuring the Candida colonization of distinct body sites (upper respiratory or stomach samples, urine and wound swabs) divided by the number of sites tested, which became known as the colonization index (CI).20 Although the negative predictive value was 100%, the positive predictive value for candidaemia was relatively low (66%) and could only be improved if the CI was corrected by quantitative culture. The cost effectiveness of screening all patients is relatively low, as not every patient is at a high risk of Candida infection. Nevertheless, it is advisable to record and speciate all Candida from clinical samples of ICU patients in order to aid empirical antifungal treatment if it becomes clinically necessary.
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Management of candidaemia in the ICU |
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TopAbstractIntroductionCandida colonization and the...Management of candidaemia in...Preventative measures and the...ConclusionsTransparency declarationsReferences |
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Once Candida has been isolated from the bloodstream or other types of invasive candidiasis have been diagnosed, it should be acted on promptly. The infection should be treated early (within 48 h) with an appropriate antifungal agent to reduce mortality unless all active treatment has been withdrawn.13,21,22 Without treatment, candidaemia has been associated with a high mortality (58%).1 The majority of ICU patients (87% to 98%) acquiring candidaemia have intravascular lines in situ, which should be removed whenever possible as the failure to do so can prolong the candidaemia and also increase the mortality.1,7,13,23
Treatment is also advisable in asymptomatic patients with positive Candida blood cultures obtained from vascular lines, as one cannot predict which patient may develop infectious complications such as endocarditis or endophthalmitis. Fungal endogenous endophthalmitis is one of the most common complications following candidaemia with an incidence of 9% to 15% in ICU patients.24 Fundoscopy is therefore recommended in all candidaemia patients and treatment may have to be adjusted accordingly.21
For the treatment of invasive candidiasis, there are a range of old and new antifungal agents available that vary in their spectrum of activity, pharmacokinetics, drug–drug interactions, side effects and efficacy. The choice of antifungal agent depends mainly on two factors: firstly, the available information on the causative Candida (species and susceptibility) and secondly, on patient-specific factors that include the site of infection, haemodynamic stability, organ failure and concomitant use of other drugs such as immunosuppressants. If the causative Candida species is not yet known or evidence of infection is based only on histology/microscopy, the first-line antifungal treatment is empirical and has to be based on the local resistance profile of Candida species in the ICU. Azole-resistant or non-albicans strains may be more prevalent in patients who have previously been exposed to azoles. Overall, fluconazole-susceptible Candida albicans remains the most common species causing candidaemia in ICU patients.1,25 However, other Candida species are emerging as significant pathogens as shown by the national surveillance studies in the USA that reported an increase in the adult candidaemia due to Candida glabrata.4 This species has a reduced susceptibility to fluconazole and is the second most common species causing candidaemia in adults in many countries.3,5,26,27
For patients who do not have multi-organ failure or severe sepsis, fluconazole may be used for the empirical treatment of candidaemia.21,28 A broad-spectrum antifungal agent such as amphotericin B or an echinocandin (discussed later) may be used if the patient is haemodynamically unstable or if the patient is known to be colonized with a fluconazole-resistant strain such as Candida krusei.21,28,29
The treatment of proven invasive candidiasis/candidaemia is mainly guided by the Candida species and host factors (Figure 1).21,28,29 The treatment response of older and newer antifungal agents varies between 60% and 90% (Table 2).30–34 The relatively new group of echinocandins (caspofungin, micafungin and anidulafungin) has shown a particularly good efficacy of 73% to 90% in the treatment of candidaemia, although some studies have not been fully published.30–32 In addition, the broad-spectrum anti-candidal activity, good safety profile (low renal and liver toxicity) and low interaction with other drugs make this group of drugs an attractive choice for the empirical or first-line treatment of candidaemia in critically ill patients, in particular those with multi-organ failure or immunosuppression. Some caution should be taken in treating Candida parapsilosis infections, as in vitro susceptibility testing of echinocandins has shown high MICs.35 This group of antifungal agents also penetrates the blood–brain and blood–ocular barrier poorly, and more conventional agents such as amphotericin B, 5-flucytosine or azoles may need to be used for the treatment of CNS infections or fungal endophthalmitis.21,36 Once a patient has been started on antifungal treatment with any agent, it is advisable to repeat blood cultures after 5–7 days to monitor breakthrough infections and response. Most uncomplicated candidaemia cases are treated for 
14 days from the last negative blood culture and resolution of symptoms.21
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Preventative measures and the role of antifungal prophylaxis |
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TopAbstractIntroductionCandida colonization and the...Management of candidaemia in...Preventative measures and the...ConclusionsTransparency declarationsReferences |
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Part of the management of candidiasis is the prevention of invasive infection. Interventions to minimize risk factors such as good operative technique, control of diabetes mellitus, prudent antibiotic use and good line care policies may help prevent Candida infections. An Australian study estimated that 86% of the central venous catheter-related candidaemias could be prevented if the lines were changed after 1 week of insertion.37 Many ICUs already implement such measures, and the question is whether the use of antifungal prophylaxis can reduce the incidence of invasive candidiasis further.
Fluconazole prophylaxis has been shown to significantly reduce the risk of invasive candidiasis in neutropenic patients, and its use is well established in many haematology units.38 However, the effectiveness and role of antifungal prophylaxis for non-neutropenic ICU patients are less clear. There have been a number of studies addressing the efficacy of fluconazole prophylaxis in SICU patients.39–42 A recent meta-analysis of four randomized placebo-controlled trials was able to demonstrate that fluconazole reduced the overall Candida colonization rate of patients.43 However, no reduction in the infection rate or survival advantage could be demonstrated, although the incidence of candidaemia may have been too low in these studies to make firm assumptions. It remains unclear whether the use of prophylaxis can reduce the morbidity such as the length of ventilator or ICU bed days. Little is known about the longer-term risks of broadly applied antifungal prophylaxis in terms of resistance development or shift to non-C. albicans strains.
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Conclusions |
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TopAbstractIntroductionCandida colonization and the...Management of candidaemia in...Preventative measures and the...ConclusionsTransparency declarationsReferences |
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Invasive candidiasis is a serious condition in ICU patients that requires early and appropriate management in order to reduce morbidity and mortality. A number of older and newer antifungal agents are available, and the choice should be guided by the Candida species and patient-specific factors. The wide use of antifungal prophylaxis or screening is generally not recommended, although it may be of benefit for a highly selective small group of high-risk patients.
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Transparency declarations |
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TopAbstractIntroductionCandida colonization and the...Management of candidaemia in...Preventative measures and the...ConclusionsTransparency declarationsReferences |
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None to declare.
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References |
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TopAbstractIntroductionCandida colonization and the...Management of candidaemia in...Preventative measures and the...ConclusionsTransparency declarationsReferences |
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1 Kibbler CC, Seaton S, Barnes RA, et al. Management and outcome of bloodstream infections due to Candida species in England and Wales. J Hosp Infect (2003) 54:18–24.[CrossRef][ISI][Medline]
2
Diekema DJ, Messer SA, Brueggemann AB, et al. Epidemiology of candidemia: 3-year results from the emerging infections and the epidemiology of Iowa organism study. J Clin Microbiol (2002) 40:1298–302.
3 Schelenz S, Gransden WR. Candidaemia in a London teaching hospital: analysis of 128 cases over a 7-year period. Mycoses (2003) 46:390–6.[CrossRef][ISI][Medline]
4 Trick WE, Fridkin SK, Edwards JR, et al. Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989–1999. Clin Infect Dis (2002) 35:627–30.[CrossRef][ISI][Medline]
5 Rangel-Frausto MS, Wiblin T, Blumberg HM, 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) 29:253–8.[ISI][Medline]
6 Kao AS, Brandt ME, Pruitt WR, et al. The epidemiology of candidemia in two United States cities: results of a population-based active surveillance. Clin Infect Dis (1999) 29:1164–70.[CrossRef][ISI][Medline]
7 Blumberg HM, Jarvis WR, Soucie JM, et al. Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. Clin Infect Dis (2001) 33:177–86.[CrossRef][ISI][Medline]
8 Wey SB, Mori M, Pfaller MA, et al. Risk factors for hospital-acquired candidaemia. A matched case–control study. Arch Intern Med (1989) 149:2349–53.[Abstract]
9 Peres-Bota D, Rodriguez-Villalobos H, Dimopoulos G, et al. Potential risk factors for infection with Candida spp. in critically ill patients. Clin Microbiol Infect (2004) 10:550–5.[CrossRef][ISI][Medline]
10 Blot SI, Vandewoude KH, Hoste EA, et al. Effects of nosocomial candidemia on outcome of critically ill patients. Am J Med (2002) 113:480–5.[CrossRef][ISI][Medline]
11 Wey SB, Mori M, Pfaller MA, et al. Hospital-acquired candidemia. The attributable mortality and excess length of stay. Arch Intern Med (1988) 148:2642–5.[Abstract]
12 Falagas ME, Apostolou KE, Pappas VD. Attributable mortality of candidaemia: a systematic review of matched cohort and case–control studies. Eur J Clin Microbiol Infect Dis (2006) 25:419–25.[CrossRef][ISI][Medline]
13 Nolla-Salas J, Sitges-Serra A, Leon-Gil C, et al. Candidemia in non-neutropenic critically ill patients: analysis of prognostic factors and assessment of systemic antifungal therapy. Intensive Care Med (1997) 23:23–30.[CrossRef][ISI][Medline]
14 Gudlaugsson O, Gillespie S, Lee K, et al. Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis (2003) 37:1172–7.[CrossRef][ISI][Medline]
15 Olaechea PM, Palomar M, Leon-Gil C, et al. Economic impact of Candida colonization and Candida infection in the critically ill patient. Eur J Clin Microbiol Dis (2004) 23:323–30.[CrossRef]
16 Petri MG, König J, Moecke HP, et al. Epidemiology of invasive mycosis in ICU patients: a prospective multicenter study in 435 non-neutropenic patients. Intensive Care Med (1997) 23:317–25.[CrossRef][ISI][Medline]
17 Charles PE, Dalle F, Aube H, et al. Candida spp. colonization significance in critically ill medical patients: a prospective study. Intensive Care Med (2005) 31:393–400.[CrossRef][ISI][Medline]
18 Richet HM, Andremont A, Tancrede C, et al. Risk factors for candidaemia in patients with acute lymphocytic leukemia. Rev Infect Dis (1991) 13:211–5.[ISI][Medline]
19
Reagan DR, Pfaller MA, Hollis RJ, et al. Characterization of the sequence of colonization and nosocomial candidemia using DNA fingerprinting and a DNA probe. J Clin Microbiol (1990) 28:2733–8.
20 Pittet D, Monod M, Suter PM, et al. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg (1994) 220:751–8.[ISI][Medline]
21 Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis (2004) 38:161–89.[CrossRef][ISI][Medline]
22 Denning DW, Kibbler CC, Barnes RA. British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections. Lancet Infect Dis (2003) 3:230–40.[CrossRef][ISI][Medline]
23 Rex JH, Bennett JE, Sugar AM, et al. Intravascular catheter exchanges and the duration of candidaemia. Clin Infect Dis (1995) 21:994–6.[ISI][Medline]
24 Donahue SP, Greven CM, Zuravleff JJ, et al. Intraocular candidiasis in patients with candidemia. Clinical implications derived from a prospective multicenter study. Ophthalmology (1994) 101:1302–9.[ISI][Medline]
25
Pfaller MA, Diekema DJ, Jones RN, et al. International surveillance of bloodstream infections due to Candida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program. J Clin Microbiol (2001) 39:3254–9.
26 Marchetti O, Bille J, Fluckiger, et al. Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991–2000. Clin Infect Dis (2004) 38:311–20.[CrossRef][ISI][Medline]
27 Poikonen E, Lyytikäinen O, Anttila V-J, et al. Candidemia in Finland, 1995–1999. Emerg Infect Dis (2003) 9:985–90.[ISI][Medline]
28 Slavin MA, Szer J, Grigg AP, et al. Guidelines for the use of antifungal agents in the treatment of invasive Candida and mould infections. Intern Med J (2004) 34:192–200.[CrossRef][ISI][Medline]
29 Flückiger U, Marchetti O, Bille J, et al. Treatment options of invasive fungal infections in adults. Swiss Med Wkly (2006) 136:447–63.[Medline]
30
Mora-Duarte J, Betts R, Rotstein C, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med (2002) 347:2020–9.
31 Ruhnke M, Kuse E, Chetchotisakd P, et al. Comparison of micafungin and liposomal amphotericin B for invasive candidiasis. Abstracts of the Forty-fifth Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2005: Washington, DC, USA. Abstract M-722. American Society for Microbiology.
32 Reboli A, Rotstein C, Pappas P, et al. Anidulafungin vs. fluconazole for treatment of candidemia and invasive candidiasis. Abstracts of the Forty-fifth Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2005: Washington, DC, USA. Abstract M-718. American Society for Microbiology.
33 Kullberg BJ, Sobel JD, 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) 366:1435–42.[CrossRef][ISI][Medline]
34
Rex JH, Bennett JE, Sugar AM, et al. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. N Engl J Med (1994) 331:1325–30.
35
Park S, Kelly R, Nielsen Kahn J, et al. Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates. Antimicrob Agents Chemother (2005) 49:3264–73.
36 Gauthier GM, Nork TM, Prince R, et al. Subtherapeutic ocular penetration of caspofungin and associated treatment failure in Candida albicans endophthalmitis. Clin Infect Dis (2005) 41:e27–8.[CrossRef][ISI][Medline]
37 Stratov I, Gottlieb T, Bradbury R, et al. Candidaemia in an Australian teaching hospital: relationship to central line and TPN use. J Infect (1998) 36:203–7.[CrossRef][ISI][Medline]
38 Slavin MA, Osborne B, Adams R, et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after bone marrow transplantation—a prospective, randomized, double-blind study. J Infect Dis (1995) 171:1545–52.[ISI][Medline]
39 Ables ZA, Blummer NA, Valainis GT, et al. Fluconazole prophylaxis of severe Candida infection in trauma and post surgical patients: a prospective, double-blind, randomized, placebo-controlled trial. Infect Dis Clin Pract (2000) 9:169–75.
40 Eggimann P, Francioli P, Bille J, et al. Fluconazole prophylaxis prevents intra-abdominal candidiasis in high-risk surgical patients. Crit Care Med (1999) 27:1066–72.[CrossRef][ISI][Medline]
41 Pelz RK, Hendrix CW, Swoboda SM, et al. Double-blind placebo-controlled trial of fluconazole to prevent candidal infections in critically ill surgical patients. Ann Surg (2001) 233:542–8.[CrossRef][ISI][Medline]
42 Garbino J, Lew DP, Romand JA, et al. Prevention of severe Candida infections in non-neutropenic, high-risk, critically ill patients: a randomized, double-blind, placebo-controlled trial in patients treated by selective digestive decontamination. Intensive Care Med (2002) 28:1708–17.[CrossRef][ISI][Medline]
43 Shorr AF, Chung K, Jackson WL, et al. Fluconazole prophylaxis in critically ill surgical patients: a meta-analysis. Crit Care Med (2005) 33:1928–35.[CrossRef][ISI][Medline]
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