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BMJ No 7103 Volume 315 Editorial Saturday 2 August 1997 Fungal infections in critically ill patients Rates are rising but diagnosis and treatment remain difficult The microbial threat posed by nosocomial fungal infections in critically ill patients has become increasingly apparent in the past 30-40 years.(1) Fungi (predominantly candida species) are now among the most frequently isolated organisms in intensive care units. Two years ago, Pittet and Wenzel reported a 12-fold rise in the reported rate of candida infections in a 12 year study of over 250 000 patients.(2) This trend has been confirmed in other studies in the United States(3) as well as in Europe.(4) The species identified most often has been Candida albicans, but other species (notably Torulopsis glabrata and Candida tropicalis) are being isolated ever more often and are associated with more complications and a higher mortality.(5) Making a diagnosis of candidiasis may often be difficult, but the risk factors are well known and most are commonly found in intensive care units. The presence of one or more risk factors should heighten clinical suspicion. Treatment with broad spectrum antibiotics (and so suppressing the normal intestinal flora(6)) is the single most important factor in promoting overgrowth of candida. Prophylactic antifungal treatment may sometimes be responsible for fungal infections by species other than Candida albicans.(5) Among the other risk factors are a high score on the APACHE (acute physiological and chronic health evaluation) II scale; prolonged ventilation; the presence of intravascular or urinary catheters; total parenteral nutrition; and immunosuppression, which may be induced by major surgery, trauma, burns, cancer, bacterial sepsis, diabetes, steroids, chemotherapy, and immunosuppressive treatment after transplantation.(7) The fungi that cause the infections normally live as commensals in the gut lumen and on mucocutaneous surfaces (skin, oropharynx, and vagina). The susceptible host may be infected either endogenously by organisms from his own gastrointestinal tract or exogenously through hand contact as a result of a breach in hospital policies for infection control.(8,9) Just how intestinal candida get into the bloodstream is not yet certain.(10) Translocation across the gut mucosal barrier has been shown to occur in animal experiments, but some form of mucosal disruption may also be required. Percutaneous intravascular catheters are an important portal of entry for candida, but, fortunately, removal of the catheter usually leads to recovery.(11) The main problem in dealing with candida infection in an intensive care unit is distinguishing between simple colonisation and invasive or disseminated infection. A diagnosis of invasive disease requires the presence of the fungus in normally sterile tissues, while dissemination is defined as invasion of non-contiguous organs secondary to haematogenous spread.(7) The problem is worsened by the many patients with severe infections who have negative blood cultures, while a positive blood culture does not necessarily indicate dissemination.(7)(10) Fever and organ dysfunction are common in critically ill patients, but failure to identify and treat those with disseminated fungal infection will result in a high mortality.(12) Yet candida is a normal component of human commensal flora, and by no means every patient with a positive fungal culture needs treatment. This problem is made more complex by the accumulating evidence that colonisation may precede and lead to infection. If multiple sites are colonised there will be an increased risk of severe infections in patients recovering from abdominal surgery.(13) In practice the chances of invasion or dissemination can be predicted by the extent of pre-existing colonisation - an observation made in several intensive care units, including our own.(12)(14,15) With so many variables, the diagnosis of candida infection in practice remains a clinical decision based on inference. Disseminated fungal infection may be diagnosed with certainty if a patient develops endophthalmitis or a positive fungal culture is made from an organ such as the kidney or lung.(1)(7)(10) However, the number of positive blood cultures or number of colonised sites required for such a diagnosis remains uncertain.(7) If diagnosis is difficult, so is treatment. Prophylactic treatment is generally considered to be unwarranted, even for high risk patients.(7)(16) Whether to give early treatment to high risk patients with evidence of substantial colonisation is controversial. Some authorities have suggested starting antifungal treatment if candida is recovered from multiple sites (urine, sputum, or a surgical drain).(10) The British Society for Antimicrobial Chemotherapy (BSAC) has proposed that empirical treatment should be given to patients with candiduria or heavy colonisation at other sites if their clinical condition is deteriorating.(16) This issue remains to be tested in well designed trials. The society recommends treatment in four sets of circumstances in which infection is unequivocal: firstly, a single positive blood culture in a patient who is at risk; secondly, isolation of candida from any sterile site (except urine); thirdly, positive identification of yeast on microscopic examination of a sterile specimen before the results of culture are available; and, fourthly, positive histological features in tissue from patients at risk. Two drugs are in use as standard treatments for candida infections: amphotericin and fluconazole. A third drug, flucytosine, is used as an adjunct. The general lack of toxicity of fluconazole makes it an attractive alternative to amphotericin now that encouraging reports of its efficacy have appeared.(11) Patients who fail to respond to fluconazole may respond to itraconazole, although cross resistance between the various azoles is common and there is little evidence about its efficacy. Jeffrey Lipman Head Intensive Care Unit, Baragwanath Hospital, PO Bertsham, 2013 Johannesburg, South Africa Roger Saadia Professor of surgery Medical School, 7 York Road, Parktown, 2193 Johannesburg, South Africa References 1 Henderson V J, Hirvela E R. Emerging and reemerging microbial threats. Nosocomial fungal infections. Arch Surg 1996;131:330-7. 2 Pittet D, Wenzel R P. Nosocomial bloodstream infections. Secular trends in rates, mortality and contribution to total hospital deaths. Arch Intern Med 1995;155:1177-84. 3 Beck-Sague C M, Jarvis W R, National Nosocomial Infections Surveillance System. Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990. J Infect Dis 1993;167:1247-51. 4 Vincent J L, Bihari D J, Suter P M, Bruining H A, White J, Nicolas-Chanoin M H, et al. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European prevalence of infection in intensive care (EPIC) study. JAMA 1995;274;639-44. 5 Nguyen M H, Peacock J E, Morris A J, Tanner D C, Nguyen M L, Snydman D R, et al. The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance. Am J Med 1996;100:617-23. 6 Samonis G, Anastassiadou H, Dassiou M, Tselentis Y, Bodey G P. Effects of broad-spectrum antibiotics on colonisation of gastrointestinal tracts of mice by Candida albicans. Antimicrob Agents Chemother 1994;38:602-3. 7 Dean D A, Burchard K W. Fungal infection in surgical patients. Am J Surg 1996;171:374-82. 8 Pfaller M A. Nosocomial candidiasis: emerging species, reservoirs and modes of transmission. Clin Infect Dis 1996;22(suppl):S89-94. 9 Strausbaugh L J, Sewell D L, Ward T T, Pfaller M A, Heitzman T, Tjoelker R. High frequency of yeast carriage on hands of hospital personnel. J Clin Microbiol 1994;32:2299-300. 10 Solomkin J S. Pathogenesis and management of candida infection syndromes in non-neutropenic patients. New Horizons 1993;1:202-13. 11 Nguyen M H, Peacock J E, Tanner D C, Morris A J, Nguyen M L, Snydman D R, et al. Therapeutic approaches in patients with candidemia. Evaluation in a multicenter prospective observational study. Arch Intern Med 1995;155:2429-35. 12 Wey S B, Mori M, Pfaller M A, Woolson R F, Wenzel R P. Risk factors for hospital-acquired candidemia. A matched case-control study. Arch Intern Med 1989;149:2349-53. 13 Solomkin J S, Flohr A B, Quie P G, Simmons R L. The role of Candida in intraperitoneal infections. Surgery 1980;88:524-30. 14 Pittet D, Monod M, Suter P M, Frenk A, Auckenthaler R. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg 1994;220:751-8. 15 Marik P E, Scribante J, Lipman J. Candidiasis in an intensive care unit. S Afr J Surg 1993;31:24-7. 16 British Society for Antimicrobial Chemotherapy Working Party. Management of deep Candida infection in surgical and intensive care unit patients. Intensive Care Med 1994;20:522-8. Home | Current issue | Past issues | Classified ads | Career Focus | Feedback Collections | About this site | About the BMJ | BMA | Medline