Fungal Infection in the ICU Adel Mohamad Alansary, MD

Outline Magnitude of the problem Who are at risk? Diagnosis, another problem. Options for management.

Approximately 10.4% of infections in an ICU are related to Candida species, with the majority being nosocomial. Alberti C, Brun-Buisson C, Burchardi H et al. Intensive Care Med 2002;28:108–21

Most is acquired in ICU

EPIC II Point prevalence study across Europe and other continents. JAMA, December 2, 2009—Vol 302, No. 21

EPIC II

EPIC II JAMA, December 2, 2009—Vol 302, No. 21

It is important to note that Candida occupies 70-90% of fungal infections in the ICU but there are different species of Candida with differential susciptibilty

Alexandria 2008 Nosocomial infections in a medical-surgical intensive care unit. Aly NY, Al-Mousa HH, Al Asar el SM. Of all nosocomial infections, 119 (85%) were culture-confirmed and 21 (15%) were clinically defined culture-negative infections. Of the culture-confirmed nosocomial infections, 81 (68%) were Gram-negative, 32 (27%) Gram-positive and 6 (5%) fungal. Kuwaiti medical journal Med Princ Pract. 2008;17(5):373-7

Infect Control Hosp Epidemiol 2004;25:628–33. Underestimation Difficulty of diagnosis. ICU admission is an independent risk factor for fungal infection. We do not do postmortem examination. 4% of critically ill patients who die in an ICU present an unexpected fungal infection during postmortem examination. Infect Control Hosp Epidemiol 2004;25:628–33.

Mortality rate of fungal infection in ICU Crit Care Med 2006 Vol. 34, No. 3

Conclusion Fungal infection in ICU is 5-18% of all infections. 90 % is Candida with different susceptibility according to species. Attributable mortality reaches 50%.

Risk factors

Risk factors Prolonged length of stay High acuity Diabetes Renal failure Hemodialysis Broad-spectrum antimicrobials Central venous catheter

Risk factors Parenteral nutrition Immunosuppressive drugs Cancer and chemotherapy Severe acute pancreatitis Candida colonization at multiple sites Surgery Transplantation

For Aspergillus Hospital construction works. HIV. Prolonged use of IV steroids. Malnutrition. Liver cirrhosis. COPD.

Factors associated with increased mortality Age. Mechanical ventilation. failure to receive anti-fungal therapy. ICU admission diagnosis. Aspergillous is mainly found in hematoncological patients, not in the ICU setting.

diagnosis

Diagnosis Traditional methods: Microscopic examination. Cultures: Blood cultures yield 50% sensitivity, takes days for candidiasis, weeks for molds.

Radiology Clin Infect Dis 2008;46(12):1813e21.

Candida albicans infection Candida albicans infection in a 28-year-old man with acute myeloid leukemia and hematopoietic stem cell transplant. (a) Transverse thin-section (1-mm collimation, lung window) CT scan of upper lobes shows bilateral multifocal patchy areas of ground-glass opacity and a nodule greater than 1 cm (arrow) with a surrounding halo of ground-glass opacity in the superior segment of the right lower lobe.(b) Low-power photomicrograph shows that ill-defined nodules seen at CT represent intravascular candidiasis and diffuse chronic inflammatory granulation tissue response centered on pulmonary artery. (Hematoxylin-eosin stain; original magnification, ×40.)‏ Franquet T et al. Radiology 2005;236:332-337 ©2005 by Radiological Society of North America

Figure 11c. Cryptococcal meningoencephalitis Figure 11c.  Cryptococcal meningoencephalitis in a 42-year-old man with AIDS who became progressively obtunded. (a) Photograph of a gross specimen of the basal ganglia demonstrates lesions that have a soap bubble appearance (arrows). (b) Photomicrograph (original magnification, ×200; H-E stain) depicts faintly staining yeast (arrow). (c) Axial T2-weighted image shows multiple foci of high signal intensity within the bilateral basal ganglia, findings consistent with gelatinous pseudocysts in dilated perivascular spaces (arrows). Enlargement of the ventricles, consistent with hydrocephalus, is also present. Smith A B et al. Radiographics 2008;28:2033-2058 ©2008 by Radiological Society of North America

Newer Methods Serology: Galactomanann test: specific for Aspergillus. False positive results with Tazobactam/pipracillin. Β D-Glucan (BDG): non specific, requires serial testing. False positive with HD, Bacteremia, Drugs. Negative test rules out fungal infection. (NPV).

PCR: false positive due to environmental contamination, clinical colonization. False negative due to rigid cell wall of Fungi. Combinations: PCR and GM. Use clinical judgment.

So Setting: risk factors. Send cultures. Use GM or BDG. Determine type using: Chrome Agar culture, or chemical reactive testing (API). Always remember radiological signs. It is important to note that we have different types of Candida species with different susceptibility patterns API: analytical profile Index, This system is developed for quick identification of clinically relevant bacteria

So Frontiers: Antifungal susceptibility. PCR. Proteomic methods: mass spectrometry. It is important to note that we have different types of Candida species with different susceptibility patterns

management

Polyenes: Amphotericin B Activity Candida except Candida lusitaniae Aspergillus Except Aspergillus terreus Zygomycosis (Mucor). Dimorphic fungi (Blastomyces, Parracoccidioides, Histoplasma and Coccidioides Toxicity Nephrotoxicity. Hypokalemia. N&V BM suppression Liposomal forms are less toxic

Azoles Fluconazole, Itraconazole, Posaconazole and voriconazole. Activity: Candida species. C. glabrata and C. kruzei are resistant to Fluconazole. Molds and Cryptococcus neoformans are sensitive to Posa and Vori. Glabrata still shows resistance to Voriconazole. Itra: sporanox

Resistance Develops if duration >14 days, with possible cross resistance.

Echinocandins Inhibit glucan synthetase. Active against all Candida including Candida parapspilosis with raised MIC. Active also against Aspergillus. All are well tolerated and given by IV infusion. Caspofungin: cancidas Mycamine: Micafungin

Crit Care Med 2006 Vol. 34, No. 3

Crit Care Med 2006 Vol. 34, No. 3

What about combination therapy? Echinocandin with Voriconazole or AmB. Aspergillosis only. No clear evidence to support.

All in All Awareness about fungal infection in non-neutropenic critically ill patients is increasing. Diagnosis is difficult, but tests are improving. Clinical risk factors, radiology are mainstay of suspicion. GM, BDG, PCR and culture lead to definitive diagnosis.

All in All Array of therapy is increasing allowing tailored treatment. Antifungal susceptibility, TDM allow delivering the right drug with a therapeutic level.

   

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