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Clinical microbiological case: refractory chest wall infection following reconstructive surgery in a patient with relapsed lung cancer
ANSWER S TO CONTINUING MEDICAL EDUCATION QUESTIONS
Diagnosis at first glance: nodular hepatic lesions in persons with AIDS R. Colebunders and P. Michielsen Please refer to the article on pages 562–563 of this issue to view the questions to which these answers refer. AN S W ER S 1. Diagnosis: large cell non-Hodgkin lymphoma (NHL) of the liver. Differential diagnosis in this patient includes: Kaposi’s sarcoma (KS), NHL, bacterial (including mycobacterial) abscesses, fungal abscesses, amoebiasis and liver metastases or hepatoma [1]. In a homosexual man presenting with multiple lesions in the liver, a diagnosis of Kaposi’s sarcoma should be suspected. However, the fact that our patient did not present KS lesions on the skin or KS lesions in other organs is an argument against such a diagnosis. Furthermore, two different ultrasonic patterns of KS in the liver are reported: a nodular pattern with small, hyperechoic nodules scattered close to the portal branches, and an infiltrative pattern, with thickened and hyperechoic periportal connective tissue [2,3]. The ultrasonic aspects of the lesions of our patient were hypoechoic. Bacterial (including mycobacterial) and fungal abscesses of the liver in persons with HIV infection are not considered as frequent complications, certainly not in European patients with HIV infection. When such abscesses occur, they are generally the consequence of an intra-abdominal infection or a surgical intervention (bacterial abscesses) or associated with a disseminated infection (mycobacterial and fungal abscesses). Liver amoebiasis is also not known to occur with increased frequency in patients with HIV infection. Moreover, the patient never resided in a country where amoebiasis is endemic. In persons without HIV infection, a negative serologic test for amoebiasis is a strong argument against liver abscesses caused by amoebiasis. However, in persons with HIV infection, it is known that serologic tests have a lower predictive value (because of abnormally functioning Blymphocytes). Liver metastases should always be excluded even when there are no clinical arguments that the patient has cancer. A hepatoma is unlikely in the absence of chronic hepatitis B or C infection or alcoholic liver disease. Clinically, the most likely diagnosis is NHL. The treatment of persons with HIV infection with highly active antiretroviral treatment (HAART) resulted in a sharp decrease in the incidence of opportunistic infections [4]. A similar decrease in systemic NHL, however, has not been observed [4], only a decrease in the incidence of primary central nervous system lymphoma [5]. Large cell NHL is a well known complication of HIV infection. It generally occurs when the CD4þ lymphocyte count is below
200 109/L. Only Burkitt’s lymphoma (small cell NHL) may occur earlier. Hepatic involvement is common in patients with advanced NHL; over 50% of patients with known systemic lymphomas show liver involvement at autopsy [6]. Hepatic NHL in patients with AIDS usually presents with multiple large hepatic masses and involvement of other abdominal organs or lymph nodes [7]. NHL localized only in the liver in patients with HIV infection is exceptional [8–12]. Most of these cases present with multiple hypodense mass lesions larger than those seen with opportunistic infections or Kaposi’s sarcoma [13]. 2. The diagnosis of NHL was made by histologic examination of a liver biopsy. Cultures of liver tissue did not grow any organism. No other localizations of lymphoma were found on CT scan and bone marrow biopsy. This patient had a relatively high CD4þ lymphocyte count at the time when the NHL was diagnosed. It is, however, likely that the NHL was already present earlier before the HAARTwas started, when his CD4þ lymphocyte count was below 100 109/L. 3. NHL in persons with HIV infection should be treated in a similar way as in non-HIV-infected individuals [14]. Our patient received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). A problem in persons with HIV infection is how to combine HAART with chemotherapy. It is advisable to treat patients concomitantly with chemotherapy and HAART, but to choose antiretrovirals that do not increase the potential toxicity of the chemotherapy [14]. For example, zidovudine is contraindicated because of its hematoxicity. Administering stavudine and didanosine may increase the potential neurotoxicity of vincristine [15]. Certain patients may not tolerate HAART regimens during chemotherapy because of gastrointestinal problems/side-effects. In our patient, we were able to continue HAART, but the stavudine was switched to nevirapine. During chemotherapy, his clinical condition rapidly improved. Now, 1 year later, he is in good health. His CD4þ lymphocyte count is 214 109/L, his viral load is undetectable (below 50 copies/mL plasma) and ultrasound examination of the abdomen no longer shows focal liver lesions. HAART has considerably improved the prognosis of patients with HIV infection [16]. It is therefore becoming increasingly important to detect infectious and malignant complications as early as possible in order to treat these conditions in an optimal way.
R EFER E NCE S 1. Poles MA, Dieterich DT, Schwarz ED et al. Liver biopsy findings in 501 patients infected with human immunodeficiency virus (HIV). J Acquir Immune Defic Syndr Hum Retrovirol 1996; 11(2): 170–7. 2. Defalque D, Menu Y, Matheron S, Girard PM, Nahum H. Sarcome de Kaposi et SIDA. Aspect echographique et tomodensitome´trique. J Radiol 1988; 69(2): 617–20.
ß 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases
Answers to Continuing Medical Education Questions
3. Luburich P, Bru C, Ayuso MC, Azon A, Condom E. Hepatic Kaposi sarcoma in AIDS. US CT Findings Radiol 1990; 175(1): 172–4. 4. Buchbinder SP, Holmberg SD, Scheer S, Colfax G, O’Malley P, Vittinghoff E. Combination antiretroviral therapy and incidence of AIDS-related malignancies. J AIDS 1999; 21(Suppl 1): S23–6. 5. Jacobson LP, Yamashita TE, Detels R et al. Impact of potent antiretroviral therapy on the incidence of Kaposi’s sarcoma and non-Hodgkin’s lymphomas among HIV-1-infected individuals. Multicenter AIDS Cohort Study. J AIDS 1999; 21(Suppl 1): S34–41. 6. Edmonson M, Peters R. Neoplasms of the liver. In: Schiff L, Schiff E, eds. Diseases of the liver. New York: JB Lippincott, 1982: 1101–58. 7. Reichert CM, O’Leary TJ, Levens DL, Simrell CR, Macher AM. Autopsy pathology in the acquired immune deficiency syndrome. Am J Pathol 1983; 112(3): 357–82. 8. Bauduer F, Marty F, Gemain MC, Dulubac E, Bordahandy R. Primary non-Hodgkin’s lymphoma of the liver in a patient with hepatitis B, C, HIV infections. Am J Hematol 1997; 54(3): 265. 9. Caccamo D, Pervez NK, Marchevsky A. Primary lymphoma of the liver in the acquired immunodeficiency syndrome. Arch Pathol Lab Med 1986; 110(6): 553–5. 10. Lisker-Melman M, Pittaluga S, Pluda JM et al. Primary lymphoma of the liver in a patient with acquired immune deficiency syndrome and chronic hepatitis B. Am J Gastroenterol 1989; 84(11): 1445–8. 11. Mossad SB, Tomford JW, Avery RK, Hussein MA, Vaughn KW. Isolated primary hepatic lymphoma in a patient with acquired immunodeficiency syndrome. Int J Infect Dis 2000; 4(1): 57–8. 12. Scerpella EG, Villareal AA, Casanova PF, Moreno JN. Primary lymphoma of the liver in AIDS. Report of one new case and review of the literature. J Clin Gastroenterol 1996; 22(1): 51–3. 13. Radin DR, Esplin JA, Levine AM, Ralls PW. AIDS-related nonHodgkin’s lymphoma: abdominal CT findings in 112 patients. AJR Am J Roentgenol 1993; 160(5): 1133–9. 14. Tirelli U, Spina M, Gaidano G, Vaccher E, Franceschi S, Carbone A. Epidemiological, biological and clinical features of HIV-related lymphomas in the era of highly active antiretroviral therapy. AIDS 2000; 14(12): 1675–88. 15. Gisselbrecht C, Oksenhendler E, Tirelli U et al. Human immunodeficiency virus-related lymphoma treatment with intensive combination chemotherapy. French-Italian Cooperative Group. Am J Med 1993; 95(2): 188–96. 16. Kaplan LD, Straus DJ, Testa MA et al. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin’s lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 1997; 336(23): 1641–8.
577
Figure 2 The left anterio-lateral chest wall wound following surgical debridement and prolene mesh removal.
CL INIC AL OU TCOME Ten weeks following the start of empirical therapy for Mycobacterium tuberculosis (isoniazid 300 mg, rifampin 600 mg, ethambutol 1200 mg and pyrizinamide 1500 mg daily), the patient’s symptoms progressed. A second chest wall exploration, including extensive debridement and removal of the infected prolene mesh, was performed 12 weeks later. Fibroadipose tissue, breast and skeletal muscle specimens revealed acute and chronic (dimorphic) inflammation, with foreign body giant cell reaction. Acid-fast bacilli and granuloma were conspicuously absent, and the chest wound was left to heal by secondary intention (Figure 2). Three weeks after surgery, M. fortuitum and M. abscessus were isolated from all surgical specimens. Treatment was changed to oral ciprofloxacin (500 mg) and clarithromycin (500 mg) twice daily and continued for 6 months. The chest wound healed completely, and mastitis resolved (Figure 3). No recurrence was reported on 18-month follow-up. DI AGNO S I S
Clinical microbiological case: refractory chest wall infection following reconstructive surgery in a patient with relapsed lung cancer A. Safdar, M. Bains and B. Polsky Please refer to the article on pages 563–564 of this issue to view the questions to which these answers refer.
M. fortuitum and M. abscessus prosthetic device infection. DI SC US S ION 1. Infections due to the rapidly growing mycobacteria (RGM) have emerged as an important cause of morbidity and mortality for humans, and are often seen in patients following penetrating trauma and reconstructive surgery [1–3]. M. chelonae, M. fortuitum
ß 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 7, 576–579
578 Clinical Microbiology and Infection, Volume 7 Number 10, October 2001
Figure 3 Complete bridging of the large wound by granulation tissue and resolution of mastitis observed 6 months following combination therapy with ciprofloxacin and clarithromycin.
and M. abscessus are commonly isolated in this setting, and human infections are sporadic [2,3]. Integument, muscles, bone and joints are frequently involved. Pulmonary infections are uncommon and clinically indistinguishable from other causes of mycobacterial lung disease due to M. tuberculosis, M. avium and M. kansasii [4]. 2. Tissue contamination during surgical procedures or implantation of an infected prosthetic device are considered to be common mechanisms for postoperative wound and deep tissue infections due to RGM. Infections following augmentation mammoplasty, reconstructive cosmetic surgery, and postthoracotomy sternal osteomyelitis, and late prosthetic joint infections, are such examples [5–8]. We suspect that placement of an infected prolene mesh was associated with this locally progressive infection in our patient that presented as a refractory early postsurgical wound infection. 3. Generally, infections due to M. chelonae, M. fortuitum and M. abscessus are insidious, and often remain localized to the initial site of infection. However, in patients with severe cellular immune dysfunction, such as those with profound CD3þCD4þ lymphocytopenia due to HIV infection or hematologic malignancy, a more fulminant course may be expected, and systemic dissemination is not uncommon [9].
4. Clinically, M. tuberculosis infection is indistinguishable from infections due to RGM. In patients with skin and soft tissue infections, a plethora of acid-fast bacilli arranged in clusters among granulocytic intradermal microabscesses is highly suggestive of a process due to M. fortuitum or M. chelonae [9–12]. Similarly, dimorphic inflammation (acute and chronic), granulocytic microabscesses and occasional non-necrotizing granuloma are rarely seen in patients with pulmonary tuberculosis [2,13]. 5. The ability of these microorganisms to form biofilms on semi-implantable and implantable foreign devices appears to play a central role in promoting refractory disease, by allowing them to escape host immune surveillance, and by leading to suboptimal antimicrobial drug penetration [13]. The partial, subtherapeutic exposure to antimicrobials may also lead to drug resistance and treatment failure. It is critical to remove these infected prosthetic devices, as antimicrobial therapy alone is often inadequate in successfully eradicating infections. 6. Therapy with two or more antimycobacterial agents is often recommended. Trimethoprim–sulfamethoxazole, doxycycline, minocycline and amikacin show the highest in vitro activity against M. fortuitum and M. chelonae [14]. Most RGM show variable (in vitro) resistance to the conventional anti-M. tuberculosis agents, such as isoniazid, rifampin, pyrazinamide, and ethambutol [2]. Clinical experience with ciprofloxacin, imipenem and clarithromycin is promising [15,16]. Our patient responded favorably to a combination of ciprofloxacin and clarithromycin therapy.
R EFER E NCE S 1. Wallace RJ Jr, Swenson JM, Silcox VA, Good RC, Tschen JA, Stone MS. Spectrum of disease due to rapidly growing mycobacteria. Rev Infect Dis 1983; 5: 657–79. 2. Wolinsky E. Nontuberculous mycobacteria and associated disease. Am Rev Respir 1979; 119: 107–59. 3. Centers for Disease Control. Atypical mycobacteria wound infections — North Carolina, Colorado. MMWR 1976; 25: 238–43. 4. Jacobson K, Garcia R, Libshitz H et al. Clinical and radiological features of pulmonary disease caused by rapidly growing mycobacteria in cancer patients. Eur J Clin Microbiol Infect Dis 1998; 17: 615–21. 5. Clegg HW, Foster MT, Sanders WE, Baine WB. Infection due to organisms of the Mycobacterium fortuitum-complex after augmentation mammaplasty: clinical and epidemiologic features. J Infect Dis 1983; 147: 427–33. 6. Centers for Disease Control. Mycobacterial infections associated with augmentation mammoplasty — Florida, North Carolina, Taxes. MMWR 1978; 27: 513. 7. Hoffman PC, Fraser DW, Robicsek F, O’Bar PR, Mauney CU. Two outbreaks of sternal wound infections due to organisms of the Mycobacterium fortuitum complex. J Infect Dis 1981; 143: 533–42. 8. Kuritsky JN, Bullen MG, Broome CV, Silcox VA, Good RC, Wallace RJ Jr. Sternal wound infections and endocarditis due to organisms of the Mycobacterium fortuitum complex. Ann Intern Med 1983; 98: 938–9.
ß 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 7, 576–579
Answers to Continuing Medical Education Questions
9. Graybill JR, Silva J Jr, Fraser DW, Lordon R, Rogers E. Disseminated mycobacteriosis due to Mycobacterium abscessus in two recipients of renal homografts. Am Rev Respir Dis 1974; 109: 4–10. 10. Jauregui L, Arbulu A, Wilson F. Osteomyelitis, pericarditis, mediastinitis, and vasculitis due to Mycobacterium chelonei. Am Rev Respir Dis 1977; 115: 699–703. 11. Greer KE, Gross GP, Martensen SH. Sporotrichoid cutaneous infection due to Mycobacterium chelonei. Arch Dermatol 1979; 115: 738–9. 12. Foz A, Roy C, Jurado J, Arteaga E, Ruiz JM, Moragas A. Mycobacterium chelonei iatrogenic infections. J Clin Microbiol 1978; 7: 319–21.
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13. Hall-Stoodley L, Lappin-Scott H. Biofilm formation by the rapidly growing mycobacterial species Mycobacterium fortuitum. FEMS Microbiol Lett 1998; 168: 77–84. 14. Swenson JM, Thornsberry C, Silcox VA. Rapidly growing mycobacteria: testing of susceptibility to 34 antimicrobial agents by broth microdilution. Antimicrob Agents Chemother 1982; 22: 186–92. 15. Pfuetze KH, Vo LV, Reimann AF, Berg GS, Lester W. Photochromogenic mycobacterial pulmonary disease. Am Rev Respir Dis 1965; 92: 470–5. 15. Cooke FJ, Friedland JS. Spontaneous breast abscess due to Mycobacterium fortuitum. Clin Infect Dis 1998; 26: 760–1.
ß 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 7, 576–579
Diagnosis at first glance: nodular hepatic lesions in persons with AIDS R. Colebunders and P. Michielsen Please refer to the article on pages 562–563 of this issue to view the questions to which these answers refer. AN S W ER S 1. Diagnosis: large cell non-Hodgkin lymphoma (NHL) of the liver. Differential diagnosis in this patient includes: Kaposi’s sarcoma (KS), NHL, bacterial (including mycobacterial) abscesses, fungal abscesses, amoebiasis and liver metastases or hepatoma [1]. In a homosexual man presenting with multiple lesions in the liver, a diagnosis of Kaposi’s sarcoma should be suspected. However, the fact that our patient did not present KS lesions on the skin or KS lesions in other organs is an argument against such a diagnosis. Furthermore, two different ultrasonic patterns of KS in the liver are reported: a nodular pattern with small, hyperechoic nodules scattered close to the portal branches, and an infiltrative pattern, with thickened and hyperechoic periportal connective tissue [2,3]. The ultrasonic aspects of the lesions of our patient were hypoechoic. Bacterial (including mycobacterial) and fungal abscesses of the liver in persons with HIV infection are not considered as frequent complications, certainly not in European patients with HIV infection. When such abscesses occur, they are generally the consequence of an intra-abdominal infection or a surgical intervention (bacterial abscesses) or associated with a disseminated infection (mycobacterial and fungal abscesses). Liver amoebiasis is also not known to occur with increased frequency in patients with HIV infection. Moreover, the patient never resided in a country where amoebiasis is endemic. In persons without HIV infection, a negative serologic test for amoebiasis is a strong argument against liver abscesses caused by amoebiasis. However, in persons with HIV infection, it is known that serologic tests have a lower predictive value (because of abnormally functioning Blymphocytes). Liver metastases should always be excluded even when there are no clinical arguments that the patient has cancer. A hepatoma is unlikely in the absence of chronic hepatitis B or C infection or alcoholic liver disease. Clinically, the most likely diagnosis is NHL. The treatment of persons with HIV infection with highly active antiretroviral treatment (HAART) resulted in a sharp decrease in the incidence of opportunistic infections [4]. A similar decrease in systemic NHL, however, has not been observed [4], only a decrease in the incidence of primary central nervous system lymphoma [5]. Large cell NHL is a well known complication of HIV infection. It generally occurs when the CD4þ lymphocyte count is below
200 109/L. Only Burkitt’s lymphoma (small cell NHL) may occur earlier. Hepatic involvement is common in patients with advanced NHL; over 50% of patients with known systemic lymphomas show liver involvement at autopsy [6]. Hepatic NHL in patients with AIDS usually presents with multiple large hepatic masses and involvement of other abdominal organs or lymph nodes [7]. NHL localized only in the liver in patients with HIV infection is exceptional [8–12]. Most of these cases present with multiple hypodense mass lesions larger than those seen with opportunistic infections or Kaposi’s sarcoma [13]. 2. The diagnosis of NHL was made by histologic examination of a liver biopsy. Cultures of liver tissue did not grow any organism. No other localizations of lymphoma were found on CT scan and bone marrow biopsy. This patient had a relatively high CD4þ lymphocyte count at the time when the NHL was diagnosed. It is, however, likely that the NHL was already present earlier before the HAARTwas started, when his CD4þ lymphocyte count was below 100 109/L. 3. NHL in persons with HIV infection should be treated in a similar way as in non-HIV-infected individuals [14]. Our patient received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). A problem in persons with HIV infection is how to combine HAART with chemotherapy. It is advisable to treat patients concomitantly with chemotherapy and HAART, but to choose antiretrovirals that do not increase the potential toxicity of the chemotherapy [14]. For example, zidovudine is contraindicated because of its hematoxicity. Administering stavudine and didanosine may increase the potential neurotoxicity of vincristine [15]. Certain patients may not tolerate HAART regimens during chemotherapy because of gastrointestinal problems/side-effects. In our patient, we were able to continue HAART, but the stavudine was switched to nevirapine. During chemotherapy, his clinical condition rapidly improved. Now, 1 year later, he is in good health. His CD4þ lymphocyte count is 214 109/L, his viral load is undetectable (below 50 copies/mL plasma) and ultrasound examination of the abdomen no longer shows focal liver lesions. HAART has considerably improved the prognosis of patients with HIV infection [16]. It is therefore becoming increasingly important to detect infectious and malignant complications as early as possible in order to treat these conditions in an optimal way.
R EFER E NCE S 1. Poles MA, Dieterich DT, Schwarz ED et al. Liver biopsy findings in 501 patients infected with human immunodeficiency virus (HIV). J Acquir Immune Defic Syndr Hum Retrovirol 1996; 11(2): 170–7. 2. Defalque D, Menu Y, Matheron S, Girard PM, Nahum H. Sarcome de Kaposi et SIDA. Aspect echographique et tomodensitome´trique. J Radiol 1988; 69(2): 617–20.
ß 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases
Answers to Continuing Medical Education Questions
3. Luburich P, Bru C, Ayuso MC, Azon A, Condom E. Hepatic Kaposi sarcoma in AIDS. US CT Findings Radiol 1990; 175(1): 172–4. 4. Buchbinder SP, Holmberg SD, Scheer S, Colfax G, O’Malley P, Vittinghoff E. Combination antiretroviral therapy and incidence of AIDS-related malignancies. J AIDS 1999; 21(Suppl 1): S23–6. 5. Jacobson LP, Yamashita TE, Detels R et al. Impact of potent antiretroviral therapy on the incidence of Kaposi’s sarcoma and non-Hodgkin’s lymphomas among HIV-1-infected individuals. Multicenter AIDS Cohort Study. J AIDS 1999; 21(Suppl 1): S34–41. 6. Edmonson M, Peters R. Neoplasms of the liver. In: Schiff L, Schiff E, eds. Diseases of the liver. New York: JB Lippincott, 1982: 1101–58. 7. Reichert CM, O’Leary TJ, Levens DL, Simrell CR, Macher AM. Autopsy pathology in the acquired immune deficiency syndrome. Am J Pathol 1983; 112(3): 357–82. 8. Bauduer F, Marty F, Gemain MC, Dulubac E, Bordahandy R. Primary non-Hodgkin’s lymphoma of the liver in a patient with hepatitis B, C, HIV infections. Am J Hematol 1997; 54(3): 265. 9. Caccamo D, Pervez NK, Marchevsky A. Primary lymphoma of the liver in the acquired immunodeficiency syndrome. Arch Pathol Lab Med 1986; 110(6): 553–5. 10. Lisker-Melman M, Pittaluga S, Pluda JM et al. Primary lymphoma of the liver in a patient with acquired immune deficiency syndrome and chronic hepatitis B. Am J Gastroenterol 1989; 84(11): 1445–8. 11. Mossad SB, Tomford JW, Avery RK, Hussein MA, Vaughn KW. Isolated primary hepatic lymphoma in a patient with acquired immunodeficiency syndrome. Int J Infect Dis 2000; 4(1): 57–8. 12. Scerpella EG, Villareal AA, Casanova PF, Moreno JN. Primary lymphoma of the liver in AIDS. Report of one new case and review of the literature. J Clin Gastroenterol 1996; 22(1): 51–3. 13. Radin DR, Esplin JA, Levine AM, Ralls PW. AIDS-related nonHodgkin’s lymphoma: abdominal CT findings in 112 patients. AJR Am J Roentgenol 1993; 160(5): 1133–9. 14. Tirelli U, Spina M, Gaidano G, Vaccher E, Franceschi S, Carbone A. Epidemiological, biological and clinical features of HIV-related lymphomas in the era of highly active antiretroviral therapy. AIDS 2000; 14(12): 1675–88. 15. Gisselbrecht C, Oksenhendler E, Tirelli U et al. Human immunodeficiency virus-related lymphoma treatment with intensive combination chemotherapy. French-Italian Cooperative Group. Am J Med 1993; 95(2): 188–96. 16. Kaplan LD, Straus DJ, Testa MA et al. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin’s lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 1997; 336(23): 1641–8.
577
Figure 2 The left anterio-lateral chest wall wound following surgical debridement and prolene mesh removal.
CL INIC AL OU TCOME Ten weeks following the start of empirical therapy for Mycobacterium tuberculosis (isoniazid 300 mg, rifampin 600 mg, ethambutol 1200 mg and pyrizinamide 1500 mg daily), the patient’s symptoms progressed. A second chest wall exploration, including extensive debridement and removal of the infected prolene mesh, was performed 12 weeks later. Fibroadipose tissue, breast and skeletal muscle specimens revealed acute and chronic (dimorphic) inflammation, with foreign body giant cell reaction. Acid-fast bacilli and granuloma were conspicuously absent, and the chest wound was left to heal by secondary intention (Figure 2). Three weeks after surgery, M. fortuitum and M. abscessus were isolated from all surgical specimens. Treatment was changed to oral ciprofloxacin (500 mg) and clarithromycin (500 mg) twice daily and continued for 6 months. The chest wound healed completely, and mastitis resolved (Figure 3). No recurrence was reported on 18-month follow-up. DI AGNO S I S
Clinical microbiological case: refractory chest wall infection following reconstructive surgery in a patient with relapsed lung cancer A. Safdar, M. Bains and B. Polsky Please refer to the article on pages 563–564 of this issue to view the questions to which these answers refer.
M. fortuitum and M. abscessus prosthetic device infection. DI SC US S ION 1. Infections due to the rapidly growing mycobacteria (RGM) have emerged as an important cause of morbidity and mortality for humans, and are often seen in patients following penetrating trauma and reconstructive surgery [1–3]. M. chelonae, M. fortuitum
ß 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 7, 576–579
578 Clinical Microbiology and Infection, Volume 7 Number 10, October 2001
Figure 3 Complete bridging of the large wound by granulation tissue and resolution of mastitis observed 6 months following combination therapy with ciprofloxacin and clarithromycin.
and M. abscessus are commonly isolated in this setting, and human infections are sporadic [2,3]. Integument, muscles, bone and joints are frequently involved. Pulmonary infections are uncommon and clinically indistinguishable from other causes of mycobacterial lung disease due to M. tuberculosis, M. avium and M. kansasii [4]. 2. Tissue contamination during surgical procedures or implantation of an infected prosthetic device are considered to be common mechanisms for postoperative wound and deep tissue infections due to RGM. Infections following augmentation mammoplasty, reconstructive cosmetic surgery, and postthoracotomy sternal osteomyelitis, and late prosthetic joint infections, are such examples [5–8]. We suspect that placement of an infected prolene mesh was associated with this locally progressive infection in our patient that presented as a refractory early postsurgical wound infection. 3. Generally, infections due to M. chelonae, M. fortuitum and M. abscessus are insidious, and often remain localized to the initial site of infection. However, in patients with severe cellular immune dysfunction, such as those with profound CD3þCD4þ lymphocytopenia due to HIV infection or hematologic malignancy, a more fulminant course may be expected, and systemic dissemination is not uncommon [9].
4. Clinically, M. tuberculosis infection is indistinguishable from infections due to RGM. In patients with skin and soft tissue infections, a plethora of acid-fast bacilli arranged in clusters among granulocytic intradermal microabscesses is highly suggestive of a process due to M. fortuitum or M. chelonae [9–12]. Similarly, dimorphic inflammation (acute and chronic), granulocytic microabscesses and occasional non-necrotizing granuloma are rarely seen in patients with pulmonary tuberculosis [2,13]. 5. The ability of these microorganisms to form biofilms on semi-implantable and implantable foreign devices appears to play a central role in promoting refractory disease, by allowing them to escape host immune surveillance, and by leading to suboptimal antimicrobial drug penetration [13]. The partial, subtherapeutic exposure to antimicrobials may also lead to drug resistance and treatment failure. It is critical to remove these infected prosthetic devices, as antimicrobial therapy alone is often inadequate in successfully eradicating infections. 6. Therapy with two or more antimycobacterial agents is often recommended. Trimethoprim–sulfamethoxazole, doxycycline, minocycline and amikacin show the highest in vitro activity against M. fortuitum and M. chelonae [14]. Most RGM show variable (in vitro) resistance to the conventional anti-M. tuberculosis agents, such as isoniazid, rifampin, pyrazinamide, and ethambutol [2]. Clinical experience with ciprofloxacin, imipenem and clarithromycin is promising [15,16]. Our patient responded favorably to a combination of ciprofloxacin and clarithromycin therapy.
R EFER E NCE S 1. Wallace RJ Jr, Swenson JM, Silcox VA, Good RC, Tschen JA, Stone MS. Spectrum of disease due to rapidly growing mycobacteria. Rev Infect Dis 1983; 5: 657–79. 2. Wolinsky E. Nontuberculous mycobacteria and associated disease. Am Rev Respir 1979; 119: 107–59. 3. Centers for Disease Control. Atypical mycobacteria wound infections — North Carolina, Colorado. MMWR 1976; 25: 238–43. 4. Jacobson K, Garcia R, Libshitz H et al. Clinical and radiological features of pulmonary disease caused by rapidly growing mycobacteria in cancer patients. Eur J Clin Microbiol Infect Dis 1998; 17: 615–21. 5. Clegg HW, Foster MT, Sanders WE, Baine WB. Infection due to organisms of the Mycobacterium fortuitum-complex after augmentation mammaplasty: clinical and epidemiologic features. J Infect Dis 1983; 147: 427–33. 6. Centers for Disease Control. Mycobacterial infections associated with augmentation mammoplasty — Florida, North Carolina, Taxes. MMWR 1978; 27: 513. 7. Hoffman PC, Fraser DW, Robicsek F, O’Bar PR, Mauney CU. Two outbreaks of sternal wound infections due to organisms of the Mycobacterium fortuitum complex. J Infect Dis 1981; 143: 533–42. 8. Kuritsky JN, Bullen MG, Broome CV, Silcox VA, Good RC, Wallace RJ Jr. Sternal wound infections and endocarditis due to organisms of the Mycobacterium fortuitum complex. Ann Intern Med 1983; 98: 938–9.
ß 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 7, 576–579
Answers to Continuing Medical Education Questions
9. Graybill JR, Silva J Jr, Fraser DW, Lordon R, Rogers E. Disseminated mycobacteriosis due to Mycobacterium abscessus in two recipients of renal homografts. Am Rev Respir Dis 1974; 109: 4–10. 10. Jauregui L, Arbulu A, Wilson F. Osteomyelitis, pericarditis, mediastinitis, and vasculitis due to Mycobacterium chelonei. Am Rev Respir Dis 1977; 115: 699–703. 11. Greer KE, Gross GP, Martensen SH. Sporotrichoid cutaneous infection due to Mycobacterium chelonei. Arch Dermatol 1979; 115: 738–9. 12. Foz A, Roy C, Jurado J, Arteaga E, Ruiz JM, Moragas A. Mycobacterium chelonei iatrogenic infections. J Clin Microbiol 1978; 7: 319–21.
579
13. Hall-Stoodley L, Lappin-Scott H. Biofilm formation by the rapidly growing mycobacterial species Mycobacterium fortuitum. FEMS Microbiol Lett 1998; 168: 77–84. 14. Swenson JM, Thornsberry C, Silcox VA. Rapidly growing mycobacteria: testing of susceptibility to 34 antimicrobial agents by broth microdilution. Antimicrob Agents Chemother 1982; 22: 186–92. 15. Pfuetze KH, Vo LV, Reimann AF, Berg GS, Lester W. Photochromogenic mycobacterial pulmonary disease. Am Rev Respir Dis 1965; 92: 470–5. 15. Cooke FJ, Friedland JS. Spontaneous breast abscess due to Mycobacterium fortuitum. Clin Infect Dis 1998; 26: 760–1.
ß 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 7, 576–579