Medical Mycology Case Reports 2 (2013) 4–6
Contents lists available at ScienceDirect
Medical Mycology Case Reports journal homepage: www.elsevier.com/locate/mmcr
Sternal osteomyelitis caused by Aspergillus fumigatus following cardiac surgery: Case and review Kingsley A. Asare a,b,n, Maximillian Jahng a, Jennifer L. Pincus a,c, Larry Massie a,c, Samuel A. Lee a,b a
New Mexico Veterans Affairs Health Care System, Albuquerque, NM, USA Division of Infectious Diseases, The University of New Mexico, Albuquerque, NM, USA c Division of Pathology, The University of New Mexico, Albuquerque, NM, USA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 5 November 2012 Accepted 3 December 2012
Postsurgical sternal wound infection is a serious post-operative complication of cardiac surgery. Aspergillus infection of the sternum is extremely rare. We describe a case of sternal infection due to Aspergillus in an immunocompetent patient following aortic valve replacement. Published by Elsevier B.V on behalf of International Society for Human and Animal Mycology
Keywords: Aspergillus Case report Invasive aspergillosis Sternal osteomyelitis infection
1. Introduction Aspergillus species are ubiquitous molds found in organic matter. Although more than 100 species have been identified, the majority of human disease is caused by Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus [1,2]. The most common method of transmission of fungal spores to the human host is via inhalation of conidia from the environment, resulting in the spores settling in the alveoli. Accordingly, most infections due to Aspergillus involve the respiratory system; overall, invasive infections occur most often in patients who are immunocompromised [1,2]. One of the rare presentations of invasive aspergillosis is infection of the sternum, with a limited number of prior reports in the literature. Aspergillus sternal osteomyelitis is rare in immunocompetent patients [3,5,6]. We report a case of A. fumigatus infection of the sternum and rib in an immunocompetent individual following cardiac surgery.
2. Case The patient is a 69-year-old male with a history of coronary artery disease, who had a 5-vessel coronary artery bypass graft in 1996. He underwent mechanical aortic valve replacement and coronary artery bypass graft surgery in June 2011 (day 0). On day n Corresponding author at: Division of Infectious Diseases, The University of New Mexico, Albuquerque, NM, USA. Tel.: þ 1 505 272 5666; fax: þ 1 505 272 4435. E-mail address: [email protected] (K.A. Asare).
160, he noted a ‘‘pimple’’ on the mid portion of his sternotomy incision for which he was seen in outpatient clinic on day 177. On examination, the incision was closed except for a small pustule mid-sternum. The pustule was unroofed to reveal a small pocket located superiorly to the mid-sternum, which was subsequently packed with iodoform gauze. A positron emission tomographycomputerized tomography (PET-CT) scan showed significant inflammation in the vicinity of the pustule, a small retrosternal abscess with anterior extension to the skin, and a fluid collection behind the sternum. Due to the location and involvement of the inflamed pocket, a decision to remove the involved sternal wire was made. The patient was taken to the operating room on day 192 where an ellipse of skin, around and including the sinus tract, was removed. The specimen was sent for Gram stain and culture immediately after removal. The sternal wire was removed and the small amount of pus that was associated with the wire was sent for culture as well. On day 197, the drainage culture from chest wall was finalized with two different coagulase negative staphylococci, Staphylococcus warneri and Staphylococcus epidermidis. At baseline, the erythrocyte sedimentation rate (ESR) was 40 (Ref.: r20). The patient was started on intravenous vancomycin for a planned duration of 6 weeks. Vancomycin serum troughs were Z14 mcg/mL throughout therapy. Five days prior to completion of vancomycin, on day 232, he developed neutropenia and the vancomycin was discontinued. Examination revealed the wound was 5 mm in diameter and did not probe to bone. The ESR remained elevated 43 (Ref.: r20) and the patient was started on suppressive treatment with oral clindamycin since the two coagulase negative staphylococci were susceptible. On day 269,
2211-7539/$ - see front matter Published by Elsevier B.V on behalf of International Society for Human and Animal Mycology http://dx.doi.org/10.1016/j.mmcr.2012.12.003
K.A. Asare et al. / Medical Mycology Case Reports 2 (2013) 4–6
5
Table 1 Reported cases of Aspergillus spp. sternal infections. Citation
Age, sex
This report 69 yo male
Underlying comorbidities
Presentation after sternotomy
Location of infection
Aspergillus species isolated
Treatment
Outcome
None
9 months
A. fumigatus
Surgical intervention, VORI 500 mg IV for 2 doses, VORI 300 mg/d orally for 6 months
Cure at EOT
10 months
Sternum and left third coastal rib Sternum
A. fumigatus
8 days
Sternum
A. fumigatus
Surgical intervention, AMBd IV 3 weeks, ITRA 200 mg/d orally for 2 months Surgical intervention, ITRA 400 mg/d orally for 30 days
6 years
Sternum
A. fumigatus
LAMB IV, ITRA 200 mg twice daily orally for 10 weeks
No infection at 8-year follow-up Unrelated death 1 month during treatment Cure at EOT
10 months
Sternum
A. flavus
5 months
Sternum
A. flavus
Surgical intervention, LAMB IV (3 mg/kg/d) for 4 weeks, ITRA Cure at EOT 200 mg/d orally 2 months Surgical intervention LAMB (3 mg/kg/d) for 18 days, ITRA Unrelated death 200 mg/d for 3 months 4 months after EOT ABLC IV (5 mg/kg/d) for 20 days, ITRA 200 mg twice daily EOT cure orally for 3 months Cure at EOT Surgical intervention, ITRA 200 mg/d, AMBd 150 mg IV/d, CAS 70 mg, then 50 mg/d for 2 weeks, VORI 200 mg/d orally for 6 weeks Surgical intervention, VORI 400 mg twice daily for 2 days, Cure at EOT then 200 mg/d orally for 6 months
Barzaghi et al. [6] Barzaghi et al. [6]
60 yo, None female 70 yo, None male
Allen et al. [5] Florio et al. [8] Florio et al. [8]
67 yo, Hodgkin’s female disease in remission 74 yo, Renal failure male 63 yo, COPD male
Florio et al. [8] Natesan et al. [4]
56 yo, DM, Asthma male 29 yo, DM, HD female
6 months
Sternum
A. flavus
3 months
Sternum
A. terreus
Verghese et al. [3]
70 yo, male
6 months
Left 7th rib
A. flavus
DM
Abbreviations: ABLC, amphotericin B lipid complex; AMBd, amphotericin B deoxycholate; CAS, caspofungin; COPD, chronic obstructive pulmonary disorder; DM, diabetes mellitus; EOT, end of treatment; HD, hemodialysis; ITRA, itraconazole; LAMB, liposomal amphotericin B; VORI, voriconazole.
the patient presented with purulent drainage from the surgical site. A repeat PET-CT scan demonstrated fluorodeoxyglucose activity at the previously infected site and at the left 3rd costal cartilage border, with tracking from the superficial wound. He was started on 8 days of oral linezolid 600 mg twice daily and was taken to the operating room for third left costal cartilage debridement on day 283. Creamy white pus was noted at the site. The sternal bone removed during surgery was sent for culture and histopathologic analysis. Acute and chronic inflammation with fungal elements was noted on Periodic acid-Schiff and Gomori’s methenamine silver stains. The sternal bone culture grew a rare amount of A. fumigatus. The patient was loaded with two doses of intravenous voriconazole 500 mg (6 mg/kg) spaced 12 h apart, and then started on a maintenance dose of oral voriconazole 300 mg twice daily. A voriconazole level assayed on day 3 of voriconazole treatment was 5 mcg/mL. The patient remains clinically well on long-term antifungal therapy with subsequent normalization of the ESR to 13–20 (Ref.: r20).
3. Discussion This case involves a 69-year-old immunocompetent male who presented with sternal osteomyelitis caused by Aspergillus species. Invasive aspergllosis is mostly seen in immunocompromised hosts, including patients with prolonged and/or profound neutropenia, solid organ or stem cell transplant, and HIV/AIDS. Invasive aspergillosis has also been reported in patients with chronic steroid or TNF-alpha antagonist use, and in rare cases, immunocompetent patients, such as intravenous drug users [1,2]. Other less common infectious sources include local tissue invasion, infection of surgical wounds, and contaminated intravenous catheters [1,7]. Aspergillus osteomyelitis is a rare complication after cardiac surgery, with vertebral involvement being the most common [3–6]. Definitive diagnosis requires biopsy showing invasion with hyphae and positive microbiologic cultures [3–6].
Osteomyelitis occurring in the sternum is uncommon and most cases are seen after sternal trauma or surgery. There have been only 8 reported cases of sternal osteomyelitis due to Aspergillus in immunocompetent patients. All patients were successfully treated with combined surgical and medical therapy except in two of the cases (Table 1). Amphotericin B has historically been the mainstay pharmacologic treatment of Aspergillus infections [10]. More recent data has shown the superiority of voriconazole over amphotericin as the antifungal therapy of choice for most forms of invasive aspergillosis [11]. However, clinical experience with Aspergillus infection of the sternum remains limited. As shown in our case, appropriate diagnostic strategies, including acquisition of deep tissue for histopathologic and microbiologic analyses are paramount for patient management. Timely intervention in our patient with a combination of medical and surgical management has lead to a favorable clinical outcome to date; this combined treatment modality has also lead to cure in other cases [3–5,8,9]. The overall duration of treatment necessary is unclear, but at least 6–8 weeks of antifungal therapy has been recommended by the Infectious Diseases Society of America’s Aspergillosis guidelines, and should depend on clinical response [2].
Conflict of interest None to report. References [1] Perfect JR, Cox GM, Lee JY, Kauffman CA, de Repentigny L, Chapman SW, et al. The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis. Clinical Infectious Diseases 2001;1(33):11 1824–33. Epub. October 22, 2001. [2] Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clinical Infectious Diseases 2008;46:327–60. [3] Verghese S, Chellamma T, Cherian KM. Osteomyelitis of the rib caused by A. flavus following cardiac surgery. Mycoses 2008;52:91–3.
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K.A. Asare et al. / Medical Mycology Case Reports 2 (2013) 4–6
[4] Natesan S, Abraham G, Mathew M, Lalitha MK, Srinivasan CN. Secondary sternal aspergillus OM in a diabetic hemodialysis patient with previous allograft rejection. Hemodialysis International 2007;11:403–5. [5] Allen D, Ng S, Taussig D. Sternal OM caused by A. fumigatus in a patient with previously treated Hodgkin’s disease. Journal of Clinical Pathology 2002;55:616–8. [6] Barzaghi N, Emmi V, Marone P, Mencherini S, Minoli L, Minzioni G. Sternal OM due to A. fumigatus after cardiac surgery. Chest 1994;105(4):1275. [7] Pasqualotto AC, Denning DW. Post-operative aspergillosis. Clinical Microbiology and Infection 2006;12:1060–76.
[8] Florio M, Marroni M, Morosi S, Stagni G. Nosocomial Aspergillus flavus wound infections following cardiac surgery. Le Infezioni in Medicina 2004;12(4):270–3. [9] Vandecasteele SJ, Boelaert JR, Verrelst P, Graulus E, Gordts BZ. Diagnosis and treatment of Aspergillus flavus sterna wound infections after cardiac surgery. Clinical Infectious Diseases 2002;35:887–90. [10] Singh N, Paterson DL. Aspergillus infections in transplant patients. Clinical Microbiology Reviews 2005;18:44–69. [11] Hezbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of Invasive aspergillosis. The New England Journal of Medicine 2002;347:408–15.
Contents lists available at ScienceDirect
Medical Mycology Case Reports journal homepage: www.elsevier.com/locate/mmcr
Sternal osteomyelitis caused by Aspergillus fumigatus following cardiac surgery: Case and review Kingsley A. Asare a,b,n, Maximillian Jahng a, Jennifer L. Pincus a,c, Larry Massie a,c, Samuel A. Lee a,b a
New Mexico Veterans Affairs Health Care System, Albuquerque, NM, USA Division of Infectious Diseases, The University of New Mexico, Albuquerque, NM, USA c Division of Pathology, The University of New Mexico, Albuquerque, NM, USA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 5 November 2012 Accepted 3 December 2012
Postsurgical sternal wound infection is a serious post-operative complication of cardiac surgery. Aspergillus infection of the sternum is extremely rare. We describe a case of sternal infection due to Aspergillus in an immunocompetent patient following aortic valve replacement. Published by Elsevier B.V on behalf of International Society for Human and Animal Mycology
Keywords: Aspergillus Case report Invasive aspergillosis Sternal osteomyelitis infection
1. Introduction Aspergillus species are ubiquitous molds found in organic matter. Although more than 100 species have been identified, the majority of human disease is caused by Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus [1,2]. The most common method of transmission of fungal spores to the human host is via inhalation of conidia from the environment, resulting in the spores settling in the alveoli. Accordingly, most infections due to Aspergillus involve the respiratory system; overall, invasive infections occur most often in patients who are immunocompromised [1,2]. One of the rare presentations of invasive aspergillosis is infection of the sternum, with a limited number of prior reports in the literature. Aspergillus sternal osteomyelitis is rare in immunocompetent patients [3,5,6]. We report a case of A. fumigatus infection of the sternum and rib in an immunocompetent individual following cardiac surgery.
2. Case The patient is a 69-year-old male with a history of coronary artery disease, who had a 5-vessel coronary artery bypass graft in 1996. He underwent mechanical aortic valve replacement and coronary artery bypass graft surgery in June 2011 (day 0). On day n Corresponding author at: Division of Infectious Diseases, The University of New Mexico, Albuquerque, NM, USA. Tel.: þ 1 505 272 5666; fax: þ 1 505 272 4435. E-mail address: [email protected] (K.A. Asare).
160, he noted a ‘‘pimple’’ on the mid portion of his sternotomy incision for which he was seen in outpatient clinic on day 177. On examination, the incision was closed except for a small pustule mid-sternum. The pustule was unroofed to reveal a small pocket located superiorly to the mid-sternum, which was subsequently packed with iodoform gauze. A positron emission tomographycomputerized tomography (PET-CT) scan showed significant inflammation in the vicinity of the pustule, a small retrosternal abscess with anterior extension to the skin, and a fluid collection behind the sternum. Due to the location and involvement of the inflamed pocket, a decision to remove the involved sternal wire was made. The patient was taken to the operating room on day 192 where an ellipse of skin, around and including the sinus tract, was removed. The specimen was sent for Gram stain and culture immediately after removal. The sternal wire was removed and the small amount of pus that was associated with the wire was sent for culture as well. On day 197, the drainage culture from chest wall was finalized with two different coagulase negative staphylococci, Staphylococcus warneri and Staphylococcus epidermidis. At baseline, the erythrocyte sedimentation rate (ESR) was 40 (Ref.: r20). The patient was started on intravenous vancomycin for a planned duration of 6 weeks. Vancomycin serum troughs were Z14 mcg/mL throughout therapy. Five days prior to completion of vancomycin, on day 232, he developed neutropenia and the vancomycin was discontinued. Examination revealed the wound was 5 mm in diameter and did not probe to bone. The ESR remained elevated 43 (Ref.: r20) and the patient was started on suppressive treatment with oral clindamycin since the two coagulase negative staphylococci were susceptible. On day 269,
2211-7539/$ - see front matter Published by Elsevier B.V on behalf of International Society for Human and Animal Mycology http://dx.doi.org/10.1016/j.mmcr.2012.12.003
K.A. Asare et al. / Medical Mycology Case Reports 2 (2013) 4–6
5
Table 1 Reported cases of Aspergillus spp. sternal infections. Citation
Age, sex
This report 69 yo male
Underlying comorbidities
Presentation after sternotomy
Location of infection
Aspergillus species isolated
Treatment
Outcome
None
9 months
A. fumigatus
Surgical intervention, VORI 500 mg IV for 2 doses, VORI 300 mg/d orally for 6 months
Cure at EOT
10 months
Sternum and left third coastal rib Sternum
A. fumigatus
8 days
Sternum
A. fumigatus
Surgical intervention, AMBd IV 3 weeks, ITRA 200 mg/d orally for 2 months Surgical intervention, ITRA 400 mg/d orally for 30 days
6 years
Sternum
A. fumigatus
LAMB IV, ITRA 200 mg twice daily orally for 10 weeks
No infection at 8-year follow-up Unrelated death 1 month during treatment Cure at EOT
10 months
Sternum
A. flavus
5 months
Sternum
A. flavus
Surgical intervention, LAMB IV (3 mg/kg/d) for 4 weeks, ITRA Cure at EOT 200 mg/d orally 2 months Surgical intervention LAMB (3 mg/kg/d) for 18 days, ITRA Unrelated death 200 mg/d for 3 months 4 months after EOT ABLC IV (5 mg/kg/d) for 20 days, ITRA 200 mg twice daily EOT cure orally for 3 months Cure at EOT Surgical intervention, ITRA 200 mg/d, AMBd 150 mg IV/d, CAS 70 mg, then 50 mg/d for 2 weeks, VORI 200 mg/d orally for 6 weeks Surgical intervention, VORI 400 mg twice daily for 2 days, Cure at EOT then 200 mg/d orally for 6 months
Barzaghi et al. [6] Barzaghi et al. [6]
60 yo, None female 70 yo, None male
Allen et al. [5] Florio et al. [8] Florio et al. [8]
67 yo, Hodgkin’s female disease in remission 74 yo, Renal failure male 63 yo, COPD male
Florio et al. [8] Natesan et al. [4]
56 yo, DM, Asthma male 29 yo, DM, HD female
6 months
Sternum
A. flavus
3 months
Sternum
A. terreus
Verghese et al. [3]
70 yo, male
6 months
Left 7th rib
A. flavus
DM
Abbreviations: ABLC, amphotericin B lipid complex; AMBd, amphotericin B deoxycholate; CAS, caspofungin; COPD, chronic obstructive pulmonary disorder; DM, diabetes mellitus; EOT, end of treatment; HD, hemodialysis; ITRA, itraconazole; LAMB, liposomal amphotericin B; VORI, voriconazole.
the patient presented with purulent drainage from the surgical site. A repeat PET-CT scan demonstrated fluorodeoxyglucose activity at the previously infected site and at the left 3rd costal cartilage border, with tracking from the superficial wound. He was started on 8 days of oral linezolid 600 mg twice daily and was taken to the operating room for third left costal cartilage debridement on day 283. Creamy white pus was noted at the site. The sternal bone removed during surgery was sent for culture and histopathologic analysis. Acute and chronic inflammation with fungal elements was noted on Periodic acid-Schiff and Gomori’s methenamine silver stains. The sternal bone culture grew a rare amount of A. fumigatus. The patient was loaded with two doses of intravenous voriconazole 500 mg (6 mg/kg) spaced 12 h apart, and then started on a maintenance dose of oral voriconazole 300 mg twice daily. A voriconazole level assayed on day 3 of voriconazole treatment was 5 mcg/mL. The patient remains clinically well on long-term antifungal therapy with subsequent normalization of the ESR to 13–20 (Ref.: r20).
3. Discussion This case involves a 69-year-old immunocompetent male who presented with sternal osteomyelitis caused by Aspergillus species. Invasive aspergllosis is mostly seen in immunocompromised hosts, including patients with prolonged and/or profound neutropenia, solid organ or stem cell transplant, and HIV/AIDS. Invasive aspergillosis has also been reported in patients with chronic steroid or TNF-alpha antagonist use, and in rare cases, immunocompetent patients, such as intravenous drug users [1,2]. Other less common infectious sources include local tissue invasion, infection of surgical wounds, and contaminated intravenous catheters [1,7]. Aspergillus osteomyelitis is a rare complication after cardiac surgery, with vertebral involvement being the most common [3–6]. Definitive diagnosis requires biopsy showing invasion with hyphae and positive microbiologic cultures [3–6].
Osteomyelitis occurring in the sternum is uncommon and most cases are seen after sternal trauma or surgery. There have been only 8 reported cases of sternal osteomyelitis due to Aspergillus in immunocompetent patients. All patients were successfully treated with combined surgical and medical therapy except in two of the cases (Table 1). Amphotericin B has historically been the mainstay pharmacologic treatment of Aspergillus infections [10]. More recent data has shown the superiority of voriconazole over amphotericin as the antifungal therapy of choice for most forms of invasive aspergillosis [11]. However, clinical experience with Aspergillus infection of the sternum remains limited. As shown in our case, appropriate diagnostic strategies, including acquisition of deep tissue for histopathologic and microbiologic analyses are paramount for patient management. Timely intervention in our patient with a combination of medical and surgical management has lead to a favorable clinical outcome to date; this combined treatment modality has also lead to cure in other cases [3–5,8,9]. The overall duration of treatment necessary is unclear, but at least 6–8 weeks of antifungal therapy has been recommended by the Infectious Diseases Society of America’s Aspergillosis guidelines, and should depend on clinical response [2].
Conflict of interest None to report. References [1] Perfect JR, Cox GM, Lee JY, Kauffman CA, de Repentigny L, Chapman SW, et al. The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis. Clinical Infectious Diseases 2001;1(33):11 1824–33. Epub. October 22, 2001. [2] Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clinical Infectious Diseases 2008;46:327–60. [3] Verghese S, Chellamma T, Cherian KM. Osteomyelitis of the rib caused by A. flavus following cardiac surgery. Mycoses 2008;52:91–3.
6
K.A. Asare et al. / Medical Mycology Case Reports 2 (2013) 4–6
[4] Natesan S, Abraham G, Mathew M, Lalitha MK, Srinivasan CN. Secondary sternal aspergillus OM in a diabetic hemodialysis patient with previous allograft rejection. Hemodialysis International 2007;11:403–5. [5] Allen D, Ng S, Taussig D. Sternal OM caused by A. fumigatus in a patient with previously treated Hodgkin’s disease. Journal of Clinical Pathology 2002;55:616–8. [6] Barzaghi N, Emmi V, Marone P, Mencherini S, Minoli L, Minzioni G. Sternal OM due to A. fumigatus after cardiac surgery. Chest 1994;105(4):1275. [7] Pasqualotto AC, Denning DW. Post-operative aspergillosis. Clinical Microbiology and Infection 2006;12:1060–76.
[8] Florio M, Marroni M, Morosi S, Stagni G. Nosocomial Aspergillus flavus wound infections following cardiac surgery. Le Infezioni in Medicina 2004;12(4):270–3. [9] Vandecasteele SJ, Boelaert JR, Verrelst P, Graulus E, Gordts BZ. Diagnosis and treatment of Aspergillus flavus sterna wound infections after cardiac surgery. Clinical Infectious Diseases 2002;35:887–90. [10] Singh N, Paterson DL. Aspergillus infections in transplant patients. Clinical Microbiology Reviews 2005;18:44–69. [11] Hezbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of Invasive aspergillosis. The New England Journal of Medicine 2002;347:408–15.
