**7. Acknowledgement**

Our deep gratitude to Hassan Khajehei, PhD, for his valuable copy editing of the chapter.

### **8. References**

276 Special Topics in Cardiac Surgery

antifungal therapy is controversial due to probable increase in side effects and toxicity

Fungal endocarditis may be caused by endogenous or exogenous fungi. The prevention of FE could be through adopting two strategies; one is general and useful for all infections like hand-washing, personal hygiene, and indwelling central venous catheters care, and the other is especially for fungal infections. Practical ways to achieve this goal is use of nondrug or drug prevention (prophylaxis). Avoiding opportunistic endogenous agents like *Candida* spp. which colonize in the human body sites is difficult. The best strategy for the management of *Candida* endocarditis is the evaluation of colonization pre-surgery to determine the susceptibility pattern of the isolated organisms, which may cause infection after surgery and enhance the success of management of systemic or endocarditis candidiasis. Care of central venous catheters is important for reducing candidemia and *Candida* endocarditis; and the removal of all existing central venous catheters for the reduction of morbidity and mortality (106-108) is helpful. However, in patients with obligate

Fungal spores are abundant in the environment, and unfiltered air, dust, and contaminated materials are full of fungal conidia (111, 112). In many cases, fungal infections may occur during the surgery, via contaminated air, surgical site or equipment with conidia. To prevent the contamination, use of high-efficiency particulate air filters for air sterility (113),

Antifungal prophylaxis could be used to avoid the development of fungal infections in high risk patients (114), based on the susceptibility patterns of the etiologic agents in each region. Empiric therapy (antifungal treatment of febrile patients at risk for infections) was first introduced to prevent invasive fungal infections in the 1980s in patients with undiagnosed fevers, particularly invasive candidiasis (115). To prevent the relapse in patients with history of fungal infections who have received complete antifungal therapy, clinicians can turn to

Fungal endocarditis is one of the most serious manifestations of invasive fungal infections. The first line of prevention is decreasing fungal conidia transition during surgery in operating rooms by using high-efficiency particulate air filters and sterile equipment. Early diagnosis and immediate appropriate antifungal therapy are critical for the survival of the respective patients. For high quality care of the patients, echocardiography with noncultural methods such as GM assay and PCR which can detect infection in early stages should be performed. In patients with suspected FE and positive test results, it is recommended that they receive antifungal agents pre-operation and also the clinical management be continued once the documented diagnosis is made based on the sample obtained in the operation room. As high relapses are common, treatment should be followed by careful review of the clinical, mycological (serum GM level and DNA load) and

Our deep gratitude to Hassan Khajehei, PhD, for his valuable copy editing of the chapter.

central venous access, new sites should be obtained (109, 110).

and sterile equipment in the operation room are recommended.

echocardiography sign and symptoms of the infections.

level (104, 105).

**5. Prevention** 

secondary prophylaxis.

**7. Acknowledgement** 

**6. Conclusion** 


Post-Cardiac Surgery Fungal Endocarditis 279

[47] Mylonakis E, Calderwood SB. Infective endocarditis in adults.N Engl J Med

[48] Ferrieri P, Gewitz MH, et al. Unique features of infective endocarditis in childhood.

[49] Kavey RE, Frank DM, et al. Two-dimensional echocardiographic assessment of infective

[50] Morelle W, Bernard M, et al. Galactomannoproteins of *Aspergillus fumigatus*. Eukaryot

[51] Roger TR, Haynes KA, et al. Value of antigen detection in predicting invasive

[52] Stynen D, Sarfati J, et al. Rat monoclonal antibodies against *Aspergillus* galactomannan.

[53] Kappe R, Schulze-Berge A. New cause for false positive results with the Pastorex *Aspergillus* antigen latex agglutination test. J Clin Microbiol 1993;31: 2489–90. [54] Ikuta K, Shibata N, et al. NMR study of the galactomannans of *Trichophyton mentagrophytes* and *Trichophyton rubrum*. Biochem J 1997;323:297-305. [55] Swanink CM, Meis JF, et al. Specificity of a sandwich enzyme-linked immunosorbent assay for detecting *Aspergillus* galactomannan. J Clin Microbiol 1997;35:257–60. [56] Verweij PE, Weemaes CM, et al. Failure to detect circulating *Aspergillus* markers in a

[57] Gangneux JP, Lavarde D, et al. Transient *Aspergillu*s antigenaemia: think of milk.

[58] Adam O, Aupe´rin A, et al. Treatment with piperacillin-tazobactam and false-positive

[59] Mattei D, Rapezzi D, et al. A false-positive *Aspergillus* galactomannan enzyme-linked

[60] Singh N, Obman A, et al. Reactivity of Platelia *Aspergillus* galactomannan antigen with

[61] Hashiguchi K, Niki Y, et al. Cyclophosphamide induces false positive results in

[62] Pinel C, Fricker-Hidalgo H, et al. Detection of circulating *Aspergillus fumigatus*

[63] Sulahian A, Boutboul F, et al. Value of antigen detection using an enzyme immunoassay

patient with chronic granulomatous disease and invasive aspergillosis. J Clin

*Aspergillus* galactomannan antigen test results for patients with hematological

immunosorbent assay results in vivo during amoxicillin-clavulanic acid treatment.

piperacillin-tazobactam: clinical implications based on achievable concentrations in

galactomannan: value and limits of the Platelia test for diagnosing invasive

in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric hematology units during a 4-year prospective study. Cancer 2001;91: 311-18. [64] Walsh TJ, Hathorn JW, et al. Detection of circulating *Candida* enolase by immunoassayin patients with cancer and invasive candidiasis. N Engl J Med 1991; 324:1026-31. [65] Mohan das V, Ballal M. Proteinase and phospholipase activity as virulence factors in *Candida* species isolated from blood. Rev Iberoam Micol 2008;25:208-10. [66] Sendid B, Poirot JL, et al. Combined detection of mannanaemia and anti-mannan

antibodies as a strategy for the diagnosis of systemic infection caused by

endocarditis in children. Am J Dis Child 1983;137:851-6.

pulmonary aspergillosis. Lancet 1990;336:1210-13.

malignancies. Clin Infect Dis 2004;38:917-20.

aspergillosis. J Clin Microbiol 2003;41:2184-86.

serum. Antimicrob Agents Chemother 2004;48:1989-92.

detection of *Aspergillus* antigen in urine. Chest 1994;105:975-6.

pathogenic *Candida* species. J Med Microbiol 2002;51:433-42.

J Clin Microbiol 2004;42:5362-63.

2001;345:1318-30.

Cell 2005;4: 1308-16.

Circulation 2002;105:2115-26.

Infect Immun 1992;60:2237-45.

Microbiol 2000;38:3900–1.

Lancet 2002;359:1251.


[24] Jain D, Oberoi JK, et al. *Scopulariopsis brevicaulis* infection of prosthetic valve resembling aspergilloma on histopathology. Cardiovasc Pathol. 2010. ( Article in Press) [25] Kumar P, Muranjan MN, et al. *Candida tropicalis* endocarditis: Treatment in a resource-

[26] Dummer JS. *Pneumocystis carinii* infections in transplant recipients. Semin Respir Infect

[27] Mermel LA, Farr BM, et al. Guidelines for the management of intravascular catheter-

[28] Raad I, Hanna H, et al. Intravascular catheter-related infections: advances in diagnosis,

[29] Levy I, Shalit I, et al. *Candida* endocarditis in neonates: report of five cases and review of

[36] Durack DT, Lukes AS, et al. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med 1994; 96:200–09 [37] Melgar GR, Nasser RM, et al. Fungal prosthetic valve endocarditis in 16 patients. An 11 year experience in a tertiary care hospital. Medicine 1997; 76:94-103. [38] Kahn FW, Jones JM, et al. The role of bronchoalveolar lavage in the diagnosis of invasive pulmonary *Aspergillus*. Am J Clin Pathol 1986;86(4):518-23. [39] Thaler M, Pastakia B, et al. Hepatic candidiasis in cancer patients: the evolving picture

[40] Goodrich JM, Reed EC, et al. Clinical features and analysis of risk factors for invasive candidal infection after marrow transplantation. J Infect Dis 1991;164(4): 731-40. [41] Sinha K, Tendolkar U, et al. Comparison of conventional broth blood culture technique

[42] Horvath LL, Duane R, et al. Detection of simulated candidemia by the BACTEC 9240

[43] Bodey GP, Mardani M, et al. The epidemiology of *Candida glabrata* and *Candida albicans*

[44] Badiee P, Alborzi A, et al. Molecular identification and in-vitro susceptibility of *Candida* 

[45] Badiee P, Alborzi A, et al. Susceptibility of *Candida* species isolated from immunocompromised patients to antifungal agents. EMHJ 2011;17(5):425-30. [46] Karabinos IK, Kokladi M, et al. Fungal endocarditis of the superior vena cava: The Role of Transesophageal Echocardiography. Hellenic J Cardiol 2010; 51: 538-39.

and manual lysis centrifugation technique for detection of fungemia. Indian J

System with Plus Aerobic/F and Anaerobic/F blood culture bottles. J Clin Microb

fungemia in immunocompromised patients with cancer. Am J Med 2002;112:380 – 85.

*albicans* and *Candida dubliniensis* isolated from immunocompromised patients.

prevention, and management. Lancet Infect Dis 2007;7: 645-57.

[30] Pierotti LC, Baddour LM. Fungal endocarditis, 1995–2000. Chest 2002;122:302–10. [31] Sohail MR, Uslan DZ, et al. Infective endocarditis complicating permanent pacemaker and implantable cardioverter-defibrillator infection. Mayo Clin Proc. 2008;83(1):46-53. [32] Cacoub P, Leprince P, et al. Pacemaker infective endocarditis. Am J Cardiol 1998;82:480–4. [33] McCormack J, Pollard J. *Aspergillus* endocarditis 2003-2009. Med Mycol. 2011;49(1):S30-4. [34] Pelletier LL, Petersdorf RG. Infective endocarditis: A review of 125 cases from the University of Washington Hospitals, 1963-1972. Medicine 1977;56:287-314. [35] von Reyn, CF, Levy, BS, et al. Infective endocarditis: An analysis based on strict case

poor setting. Ann Pediatr Cardiol 2010;3(2):174-7.

related infections. Clin Infect Dis 2001; 32: 1249-72.

the literature. Mycoses 2006; 49:43-8.

definitions. Ann Intern Med 1981;94:505-18.

Medical Microb 2009;27(1):79-80.

2003;41:4714–17.

of the syndrome. Ann Intern Med 1988;108(1):88-100.

Iranian Red Crescent Medicine Journal 2009;11(4):391-97.

1990;5(1):50-7.


Post-Cardiac Surgery Fungal Endocarditis 281

[85] Jiménez-Expósito MJ, Torres G, Baraldés A, et al. Native valve endocarditis due to

[86] Pappas PG, Kauffman CA, et al. Clinical practice guidelines for the management of

[87] Nguyen MH, Nguyen ML, et al. *Candida* prosthetic valve endocarditis: prospective study of six cases and review of the literature. Clin Infect Dis 1996; 22:262-7. [88] Melamed R, Leibovitz E, et al. Successful non-surgical treatment of *Candida tropicalis* 

[89] Rajendram R, Alp NJ, et al. *Candida* prosthetic valve endocarditis cured by caspofungin

[90] Talarmin JP, Boutoille D, et al. *Candida* endocarditis: role of new antifungal agents.

[91] Gumbo T, Taege AJ, et al. *Aspergillus* valve endocarditis in patients without prior

[92] Muehrcke DD, Lytle BW, et al. Surgical and long-term antifungal therapy for fungal

[93] Gilbert HM, Peters ED, et al. Successful treatment of fungal prosthetic valve endocarditis: case report and review. Clin Infect Dis 1996; 22:348-54. [94] Fortún, J; Martín-Dávila, P; et al. Prevention of invasive fungal infections in liver

[95] Badiee P, Alborzi A, et al. Distributions and Antifungal Susceptibility of *Candida*  Species from Mucosal Sites in HIV Positive Patients. AIM 2010;13 (4): 282-7. [96] Limper AH, Knox KS, et al. An official american thoracic society statement: treatment of

[97] Nivoix Y, Ubeaud-Sequier G, et al. Drug interactions of triazole antifungal agents in

[98] Willems L, van der Geest R, et al. Itraconazole oral solution and intravenous

[99] Venkataramanan R, Zang S, et al. Voriconazole inhibition of the metabolism of

[100] Safdar N, Slattery WR, et al. Predictors and outcomes of candiduria in renal transplant

[101] Kuhn DM, George T, et al. Antifungal susceptibility of *Candida* biofilms: unique

[102] Mora-Duarte J, Betts R, et al. Comparison of caspofungin and amphotericin B for

transplant recipients: the role of prophylaxis with lipid formulations of amphotericin B in high-risk patients. Antimicrob Agents Chemother 2003;52: 813–9.

fungal infections in adult pulmonary and critical care patients. Am J Respir Crit

multimorbid patients and implications for patient care. Curr Drug Metab

formulations: a review of pharmacokinetics and pharmacodynamics. J Clin Pharm

tacrolimus in a liver transplant recipient and in liver microsomes. Antimicrob

efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob

therapy without valve replacement. Clin Infect Dis 2005; 40:e72.

prosthetic valve endocarditis. Ann Thorac Surg 1995; 60:538-43.

39:e70.

32:86-9.

Dis 2009; 48:503-35.

Mycoses 2009; 52:60-6.

Care Med 2011;183(1):96-128.

Agents Chemother 2002; 46:3091–93.

Agents Chemother 2002;46:1773–80.

recipients. Clin Infect Dis 2005;40:1413-21.

invasive candidiasis. N Engl J Med 2002;347: 2020–9.

2009;10:395–409.

Ther 2001;26:159–169.

cardiac surgery. Medicine 2000;79:261–8.

*Candida glabrata* treated without valvular replacement: a potential role for caspofungin in the induction and maintenance treatment. Clin Infect Dis 2004;

candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect

endocarditis with liposomal amphotericin-B (AmBisome). Scand J Infect Dis 2000;


[67] Bar W, Hecker H. Diagnosis of systemic *Candida* infections in patients of the intensive care unit. Significance of serum antigens and antibodies. Mycoses 2002; 45:22-28. [68] Odabasi Z, Mattiuzzi G, et al. Beta-D-glucan as a diagnostic adjunct for invasive fungal

[69] Ostrosky-Zeichner L, Alexander BD, et al. Multicenter clinical evaluation of the 1,3-β-D-

[70] Smith PB, Benjamin DK, et al. Quantification of 1, 3-β-D-glucan levels in children:

[71] Petraitiene R, Petraitis V, et al. Cerebrospinal fluid and plasma 1, 3-β-D-glucan as

[72] Badiee P, Kordbacheh P, et al. Early detection of systemic candidiasis in the whole blood of patients with hematological malignancies. Jpn Infec Dis 2009,62: 1-5. [73] Badiee P, Alborzi A, et al. Comparative Study of gram stain, potassium hydroxide

[74] Badiee P, Alborzi A, et al. Invasive fungal infection in renal transplant recipients

[75] Badiee P, Alborzi A, et al. Determining the incidence of aspergillosis after liver

[76] Yamakami Y, Hashimoto A, et al. PCR detection of DNA specific for Aspergillus species

[77] Badiee P, Alborzi A. Detection of *Aspergillus* species in bone marrow transplant patients.

[78] Badiee P, Alborzi A, et al. Early diagnosis of systemic candidiasis in bone marrow

[79] Van Burik JA, Myerson D, et al. Panfungal PCR assay for detection of fungal infection

[80] Badiee P, Alborzi A, et al. Molecular diagnosis of *Aspergillus* endocarditis after cardiac

[81] Loeffler J, Henke N, et al. Quantification of fungal DNA by using fluorescence

[82] Hebart H, Loeffler J, et al. Early detection of *Aspergillus* infection after allogeneic stem

[83] Badiee P, Kordbacheh P, et al. Study on invasive fungal infections in immune-

[84] Utley JR, Mills J, et al. The role of valve replacement in the treatment of fungal

resonance energy transfer and the light cycler system. J Clin Microbiol 2000;38:

cell transplantation by polymerase chain reaction screening. J Infect Dis

compromised patients to present a suitable early diagnostic procedure. Intern J

setting. Clin Vaccine Immunol 2007;14:924–5.

transplant. Exp Clinl Transplant 2010; 3:220-3.

surgery. J Med Microbiol 2009;58( 2):192-5.

transplant recipients. Exp Clin Transplant 2010;2:98-103.

endocarditis. J Thorac Cardiovasc Surg 1975; 69:255–8.

in human blood specimens. J Clin Microbiol 1998:36:1169–75.

J Infect Dev Ctries, 2010;4(8),511-6.

Chemo 2008;52 (11);4121–29.

2004;39:199–205.

2005;41:654–59.

2010; 44:251–6.

5(1):624-9.

586–90.

2000;181:1713–19.

Infect Dis 2009;13:97—102.

infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis

glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis

preliminary data for diagnostic use of the 1, 3-β-D-glucan assays in a pediatric

surrogate markers for detection and monitoring of therapeutic response in experimental hematogenous *Candida* meningoencephalitis. Antimicrob Agents

smear, culture and Nested PCR in the diagnosis of fungal keratitis. Ophthalmic Res

demonstrated by panfungal polymerase chain reaction. Exp Clin Transplant 2007;

in serum of patients with invasive aspergillosis. J Clin Microbiol.1996; 34(10):2464-68.


**13** 

*USA* 

**Sternal Wound Complications** 

Median sternotomy is a commonly performed incision with distinct advantages for exposure of mediastinal and pulmonary hilar structures [1]. However, a well-defined incidence of wound complications is associated with sternotomy, which are costly and potentially lethal in cases of deep sternal wound infection (DSWI) or mediastinitis [2-13]. Not only is DSWI associated with significant perioperative mortality, but historically even successfully treated DSWI is associated with reduced mid- and long-term survival compared with matched cardiac surgical patients without this dreaded postoperative

In the past 10 years, we have accumulated extensive experience with managing DSWI as a referral center for these difficult problems. We and others have formalized a protocol for managing mediastinal infection utilizing negative pressure wound therapy which allows sternal salvage and improved outcomes in the majority of cases of DSWI [14-16]. This report describes our protocol for managing mediastinitis and presents our results for the past 18

Median sternotomy was originally introduced by Milton in 1897 and was performed infrequently for various conditions of the mediastinum until cardiac surgery as a field blossomed in the 1950s [17]. Shumacker first suggested median sternotomy as the procedure of choice for approaches to the heart and great vessels [18] since it avoided the significant pain and other complications, primarily pulmonary- or pleural-based, of the bilateral anterior thoracotomy ("clamshell") incision, which was most frequently used up to that point. However, not until Julian and colleagues demonstrated discrete advantages of the median sternotomy incision for cardiac surgery, particularly improved surgical efficiency, excellent exposure the heart, great vessels, and pulmonary hila, and reduced pulmonary trauma, was a convincing argument for median sternotomy as the incision of choice for cardiac surgical procedures put forth [19 Table 1]. The utility of this incision, the ease and speed of performance, and the common nature of surgically-treated cardiovascular and

**1. Introduction** 

complication [7-12].

**2. Background** 

years.

**Following Cardiac Surgery** 

Zane B. Atkins1 and Walter G. Wolfe2 *1Department of Surgery Durham Veterans Affairs Medical Center Durham, NC 2Department of Surgery Duke University* 

*Medical Center Durham, NC* 

