- Email: [email protected]
Tocilizumab-associated cutaneous reactive endotheliomatosis in a patient with rheumatoid arthritis
132
Letters to the Editor / Joint Bone Spine 82 (2015) 129–137 [4] Isenberg D, Socci A. Images in emergency medicine. Woman with leg swelling. Dissecting Baker’s cyst. Ann Emerg Med 2010;56:582.
Bradley Sevy a Dirk P. Stanley b Nathan E. Doctry c Ivan Chernev a,∗,b a West Virginia School of Osteopathic Medicine, Lewisburg, WV, USA b Department of Medicine, Appalachian Regional Healthcare, Beckley, WV, USA c Department of Surgery, Appalachian Regional Healthcare, Beckley, WV, USA ∗ Corresponding author. Tel.: +304 254 2646, 304 254 2650; fax: +304 254 2794. E-mail address: [email protected] (I. Chernev)
Accepted 22 April 2014 Available online 21 June 2014 http://dx.doi.org/10.1016/j.jbspin.2014.04.008
Tocilizumab-associated cutaneous reactive endotheliomatosis in a patient with rheumatoid arthritis
a r t i c l e
Fig. 1. A–F. Axial T1 (A), axial T2 FS FRFSE (B) and frontal T2 FS FRFSE (C) MRI showing well-defined, capsulated mass which is hyperintense on T1 and with (remove) hypointense on T2 with hypointense capsule on both sequences. Note some heterogeneity noticed on T2 images. Longitudinal (D) and transverse (E) US images taken with high frequency linear transducer showing a complex cystic lesion in the right posteromedial calf with internal echoes. Intraoperative photograph (F) showing a cystic lesion with a capsule closely adhering to the superficial fascia.
reported on the histopathology report. There was no evidence of malignancy. Although the precise mechanism of the development of the CEH in our patient is not exactly known, we believe that the initial trauma caused hemorrhagic rupture of a previously existed Baker’s cyst which subsequently was encapsulated and slowly enlarged in a manner similar to the CEH. We suggest that CEH due to ruptured hemorrhagic Baker’s cyst should be included as rare cause of slowly enlarging mass in the calf region.
Disclosure of interest
i n f o
Keywords: Rheumatoid arthritis Tocilizumab Cutaneous vasculitis Endotheliomatosis
Tocilizumab (TCZ) is a humanized antibody against the IL-6 receptor (IL-6R) approved for the treatment of adult patients with rheumatoid arthritis (RA) [1,2]. The most serious adverse events reported during treatment with TCZ were infectious complications [3]. Although TCZ could induce non-specific cutaneous rash and psoriasis [4], TCZ-associated cutaneous vasculitis in RA patients has never been reported. A 67-year-old woman was diagnosed to have seropositive RA with cutaneous vasculitis (no available skin biopsy), presenting with purpura over lower legs which first developed at the age of 58. The autoimmune profiles were negative for anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, and anticardiolipin antibody, but low titers of rheumatoid factor were found (59.1 IU/ml, normal range: <15 IU/ml). Serum C4 level was within the normal limit. She had a history of chronic hepatitis C without cryoglobulinemia, but she had never received treatment for hepatitis C. Her skin purpura went into remission soon after use of oral methylprednisolone (8 mg/day) and methotrexate (7.5 mg/week).
The authors declare that they have no conflicts of interest concerning this article. References [1] Reid JD, Kommareddi S, Park MC. Chronic expanding hematomas: a clinicopathologic entity. JAMA 1980;244:2441–2. [2] Negor K, Uchida K, Yayama T, et al. Chronic expanding hematoma of the thigh. Joint Bone Spine 2012;79:192–4. [3] Krinas G, Nikolopoulos I, Ilias AP, et al. Complicated haemorragic baker cyst. An all-time classic diagnostic dilemma. An interesting case report and a thorough review of the literature. EEXOT 2012;63:79–85.
Fig. 1. Treatment course of rheumatoid arthritis in this patient.
Letters to the Editor / Joint Bone Spine 82 (2015) 129–137
133
occurred on both lower legs. Her laboratory data showed normal renal function, and no neutropenia or cryoglobulinemia. The abdominal sonography demonstrated no splenomegaly. Aggressive antibiotic treatment was given for suspected cellulitis. Unfortunately, the skin ulcers progressed to dry gangrene, and the patient died within four months. The pathological findings of skin biopsy revealed lobulated neovascularization with red blood cell extravasation in the upper and deep dermis (Fig. 2). Also, the involved vessels manifested focal mural fibrin and intraluminal thrombi. No precipitated cryoglobulin was found within the dermal vessels. Based on her clinical and pathologic findings, the final diagnosis was TCZ-associated cutaneous reactive endotheliomatosis, complicated with septic shock. Rheumatoid vasculitis may be considered to be a clinicopathologic manifestation of RA characterized by vascular inflammation or ischemia. Magro and Crowson [5] proposed three main histologic cutaneous reaction patterns in 43 RA patients, as follows: palisading granulomatous inflammation (21 cases, 49%), dominant vasculopathic lesions (13 cases, 30%), and prominent extravascular neutrophilic inflammation (9 cases, 21%). In our case, the cutaneous pathological report revealed dominant vasculopathic lesions (cutaneous reactive endotheliomatosis), including glomeruloid neovascularization. We postulate that TCZ might have aggravated her previous cutaneous vasculitis, and triggered the emergence of cutaneous reactive endotheliomatosis. Nevertheless, the definite pathogenesis is unclear. TCZ could induce cutaneous infectious complications, which tend to be less fatal. Although the definite pathogenesis of TCZassociated cutaneous vasculitis remained unclear, this disorder is potentially life-threatening without early diagnosis and treatment. The physician should exercise caution when prescribing TCZ in RA patients who have a previous history of cutaneous vasculitis. Furthermore, TCZ-associated cutaneous vasculitis in RA patients should be considered when antibiotic-resistant cellulitis or chronic ulcers develop. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References
Fig. 2. A. Histological picture of skin specimen over right leg, stained with haematoxylin and eosin (original magnification 100×). Lobulated neovascularization with red blood cell extravasation in the upper and deep dermis (arrow). B. Dermal glomeruloid neovascularization (original magnification 400×). C. CD34 immunohistochemical stain (endothelial cell marker). Neovascularization in the upper and deep dermis (original magnification 100×) (arrowhead).
However, the disease activity of RA remained high, and she had severe mucositis after use of methotrexate. Therefore, etanercept (25 mg, twice a week) was prescribed from March 2010 to January 2013 (Fig. 1). The disease activity of RA remained low during this period. Nevertheless, she developed painful swelling of joints after three years of etanercept treatment. She then started to receive TCZ. After receiving two doses of TCZ, multiple chronic skin ulcers
[1] Navarro-Millán I, Singh JA, Curtis JR. Systematic review of tocilizumab for rheumatoid arthritis: a new biologic agent targeting the interleukin-6 receptor. Clin Ther 2012;34:788–802. [2] Ogata A, Tanaka T. Tocilizumab for the treatment of rheumatoid arthritis and other systemic autoimmune diseases: current perspectives and future directions. Int J Rheumatol 2012;2012:946048, doi:10.1155/2012/946048. [3] Campbell L, Chen C, Bhagat SS, et al. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatology 2011;50:552–62. [4] Grasland A, Mahé E, Raynaud E, et al. Psoriasis onset with tocilizumab. Joint Bone Spine 2013;80:541–2. [5] Magro CM, Crowson AN. The spectrum of cutaneous lesions in rheumatoid arthritis: a clinical and pathological study of 43 patients. J Cutan Pathol 2003;30:1–10.
Cheng-Pin Wu a Chia-Wei Hsieh b,c,∗ Der-Yuan Chen b,c,d Bor-Jen Lee a,c Chii-Shuenn Yang e a Intensive Care Unit, Taichung Veterans General Hospital, Taichung, Taiwan, ROC b Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung 40705, Taiwan, ROC
134
Letters to the Editor / Joint Bone Spine 82 (2015) 129–137 c
Chung Shan Medical University, Taichung, Taiwan, ROC d Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC e Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC ∗ Corresponding
author at: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung 40705, Taiwan, ROC. Tel.: +886 4 23592525x3354; fax: +886 4 23503285. E-mail address: [email protected] (C.-W. Hsieh) Accepted 6 April 2014 Available online 29 December 2014
Table 1 Characteristics and comorbidities of the 238 patients presenting with staphylococcal bone and joint infections. Characteristics Age (years mean ± SD) Sex ratio (male/female) Cardiovascular disease Diabetes mellitus Hepatic disorder Nervous system disorder Renal disorder Neoplasm HIV infection Bone and joint infections Prosthesis or device-related infection Spondylodiscitis Other BJI
62 ± 17 2.01 (159/79) 100 (42%) 44 (18%) 32 (13%) 30 (13%) 28 (12%) 14 (6%) 4 (1.7%) 108 (45%) 47 (20%) 83 (35%)
BJI: bone and joint infections.
significant variables (P < 0.1) were then entered into stepwise logistic regression analyses.
http://dx.doi.org/10.1016/j.jbspin.2014.04.004
3. Results Safety of antibiotics combinations against Staphylococcal bone and joint infections
a r t i c l e
i n f o
Keywords: Bone and joint infection Antibiotics associations Tolerance Staphylococcus spp.
1. Introduction Nowadays, there is an increasing incidence of bone and joint infections (BJI). [1]. Staphylococci are the predominant etiologic agent [2]. Our aim was to examine the rate of antibiotic adverse events (AE) concerning different antibiotics associations (ATB-A) in Staphylococcal BJI. 2. Methods Patients were selected through the dashboard of our department (Nice, France), based on a specific software (Statview® version 4.5) [3]. Comorbidities, length of hospitalization, precise diagnosis, microbiological results, antibiotics prescribed and AE were recorded prospectively during hospitalization. All the monobacterial Staphylococcal BJI from July 2005 to December 2012, defined by microbiologic harvesting or positive blood cultures, were selected. Isolated monoarthritis were excluded (because antibiotic management was different). During ambulatory care, occurrence of any antibiotic-related AE, modification of ATB-A prescribed, evolution and duration of follow-up were retrospectively recorded. In our department, rifampin dosage was 10 mg/kg twice a day. Aerobic and anaerobic cultures were performed, with blood cultures, and in few cases 16s rRNA gene sequencing was used. Only AE requiring ATB discontinuations were considered here. Evolution was classified as recovery in the absence of clinical and/or microbiological relapse over the period of care. Relationship between variables was evaluated using the 2 statistic (categorical variables), Student’s t-test (normally distributed continuous variables), and the Mann–Whitney U test (non-parametric comparisons). Univariate correlates and clinically
Finally, 238 patients with Staphylococcus BJI were treated, with 186 (78%) Staphylococcus aureus (17% methicillin-resistant), and 52 (22%) coagulase negative Staphylococcus (40% methicillinresistant). The main clinical characteristics and repartition of BJI are presented in Table 1. The 3 main ATB-A prescribed were fluoroquinolones and rifampin (FQ + RF), rifampin and clindamycin (RF + CD) and clindamycin and fluoroquinolones (CD + FQ). All other ATB-As were classified as “other associations”. The mean duration of total antibiotic treatment was 6 weeks. Among the 61 AE leading to ATB discontinuation, 41 (67%) concerned hospitalization’s period and 20 (33%) concerned ambulatory care. Classification of the AE is presented in Table 2. RF + FQ was the leading ATB-A source of AE followed by RF + CD and FQ + CD. Gastrointestinal disorders represented 13/33 (39%) of the AE. There was no Clostridium difficile-associated diarrhea. The mean time of follow-up (± SD) was 11 ± 12 months. At the end of the study, 160 patients recovered, while 40 patients relapsed (17%), 31 patients (13%) were lost to follow-up and 7 patients died. In univariate and then multivariable analysis, AE related to ATB-A were associated with female gender (OR [95% CI]) 1.99 [1.07–3.69], P = 0.028, but not with comorbidities, presence of material, duration of hospital stay and outcomes. 4. Discussion The best-tolerated ATB-A in monobacterial Staphylococcal BJI was FQ + CD. Rifampicin [4–7], clindamycin [8] and fluoroquinolones [9,10] have already been studied in Staphylococcal BJI, but our study is the first to compare 3 ATB-As in this indication. One third of the AE were recorded during ambulatory care, underlying the importance of a regular follow-up by specialists. Prospective studies are required to determine the real place of clindamycin for Staphylococcal BJI, in terms of cure rate and AE. Clindamycin could be the first drug to consider as an alternative companion for FQ when RF is not tolerated or contraindicated.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
Letters to the Editor / Joint Bone Spine 82 (2015) 129–137 [4] Isenberg D, Socci A. Images in emergency medicine. Woman with leg swelling. Dissecting Baker’s cyst. Ann Emerg Med 2010;56:582.
Bradley Sevy a Dirk P. Stanley b Nathan E. Doctry c Ivan Chernev a,∗,b a West Virginia School of Osteopathic Medicine, Lewisburg, WV, USA b Department of Medicine, Appalachian Regional Healthcare, Beckley, WV, USA c Department of Surgery, Appalachian Regional Healthcare, Beckley, WV, USA ∗ Corresponding author. Tel.: +304 254 2646, 304 254 2650; fax: +304 254 2794. E-mail address: [email protected] (I. Chernev)
Accepted 22 April 2014 Available online 21 June 2014 http://dx.doi.org/10.1016/j.jbspin.2014.04.008
Tocilizumab-associated cutaneous reactive endotheliomatosis in a patient with rheumatoid arthritis
a r t i c l e
Fig. 1. A–F. Axial T1 (A), axial T2 FS FRFSE (B) and frontal T2 FS FRFSE (C) MRI showing well-defined, capsulated mass which is hyperintense on T1 and with (remove) hypointense on T2 with hypointense capsule on both sequences. Note some heterogeneity noticed on T2 images. Longitudinal (D) and transverse (E) US images taken with high frequency linear transducer showing a complex cystic lesion in the right posteromedial calf with internal echoes. Intraoperative photograph (F) showing a cystic lesion with a capsule closely adhering to the superficial fascia.
reported on the histopathology report. There was no evidence of malignancy. Although the precise mechanism of the development of the CEH in our patient is not exactly known, we believe that the initial trauma caused hemorrhagic rupture of a previously existed Baker’s cyst which subsequently was encapsulated and slowly enlarged in a manner similar to the CEH. We suggest that CEH due to ruptured hemorrhagic Baker’s cyst should be included as rare cause of slowly enlarging mass in the calf region.
Disclosure of interest
i n f o
Keywords: Rheumatoid arthritis Tocilizumab Cutaneous vasculitis Endotheliomatosis
Tocilizumab (TCZ) is a humanized antibody against the IL-6 receptor (IL-6R) approved for the treatment of adult patients with rheumatoid arthritis (RA) [1,2]. The most serious adverse events reported during treatment with TCZ were infectious complications [3]. Although TCZ could induce non-specific cutaneous rash and psoriasis [4], TCZ-associated cutaneous vasculitis in RA patients has never been reported. A 67-year-old woman was diagnosed to have seropositive RA with cutaneous vasculitis (no available skin biopsy), presenting with purpura over lower legs which first developed at the age of 58. The autoimmune profiles were negative for anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, and anticardiolipin antibody, but low titers of rheumatoid factor were found (59.1 IU/ml, normal range: <15 IU/ml). Serum C4 level was within the normal limit. She had a history of chronic hepatitis C without cryoglobulinemia, but she had never received treatment for hepatitis C. Her skin purpura went into remission soon after use of oral methylprednisolone (8 mg/day) and methotrexate (7.5 mg/week).
The authors declare that they have no conflicts of interest concerning this article. References [1] Reid JD, Kommareddi S, Park MC. Chronic expanding hematomas: a clinicopathologic entity. JAMA 1980;244:2441–2. [2] Negor K, Uchida K, Yayama T, et al. Chronic expanding hematoma of the thigh. Joint Bone Spine 2012;79:192–4. [3] Krinas G, Nikolopoulos I, Ilias AP, et al. Complicated haemorragic baker cyst. An all-time classic diagnostic dilemma. An interesting case report and a thorough review of the literature. EEXOT 2012;63:79–85.
Fig. 1. Treatment course of rheumatoid arthritis in this patient.
Letters to the Editor / Joint Bone Spine 82 (2015) 129–137
133
occurred on both lower legs. Her laboratory data showed normal renal function, and no neutropenia or cryoglobulinemia. The abdominal sonography demonstrated no splenomegaly. Aggressive antibiotic treatment was given for suspected cellulitis. Unfortunately, the skin ulcers progressed to dry gangrene, and the patient died within four months. The pathological findings of skin biopsy revealed lobulated neovascularization with red blood cell extravasation in the upper and deep dermis (Fig. 2). Also, the involved vessels manifested focal mural fibrin and intraluminal thrombi. No precipitated cryoglobulin was found within the dermal vessels. Based on her clinical and pathologic findings, the final diagnosis was TCZ-associated cutaneous reactive endotheliomatosis, complicated with septic shock. Rheumatoid vasculitis may be considered to be a clinicopathologic manifestation of RA characterized by vascular inflammation or ischemia. Magro and Crowson [5] proposed three main histologic cutaneous reaction patterns in 43 RA patients, as follows: palisading granulomatous inflammation (21 cases, 49%), dominant vasculopathic lesions (13 cases, 30%), and prominent extravascular neutrophilic inflammation (9 cases, 21%). In our case, the cutaneous pathological report revealed dominant vasculopathic lesions (cutaneous reactive endotheliomatosis), including glomeruloid neovascularization. We postulate that TCZ might have aggravated her previous cutaneous vasculitis, and triggered the emergence of cutaneous reactive endotheliomatosis. Nevertheless, the definite pathogenesis is unclear. TCZ could induce cutaneous infectious complications, which tend to be less fatal. Although the definite pathogenesis of TCZassociated cutaneous vasculitis remained unclear, this disorder is potentially life-threatening without early diagnosis and treatment. The physician should exercise caution when prescribing TCZ in RA patients who have a previous history of cutaneous vasculitis. Furthermore, TCZ-associated cutaneous vasculitis in RA patients should be considered when antibiotic-resistant cellulitis or chronic ulcers develop. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References
Fig. 2. A. Histological picture of skin specimen over right leg, stained with haematoxylin and eosin (original magnification 100×). Lobulated neovascularization with red blood cell extravasation in the upper and deep dermis (arrow). B. Dermal glomeruloid neovascularization (original magnification 400×). C. CD34 immunohistochemical stain (endothelial cell marker). Neovascularization in the upper and deep dermis (original magnification 100×) (arrowhead).
However, the disease activity of RA remained high, and she had severe mucositis after use of methotrexate. Therefore, etanercept (25 mg, twice a week) was prescribed from March 2010 to January 2013 (Fig. 1). The disease activity of RA remained low during this period. Nevertheless, she developed painful swelling of joints after three years of etanercept treatment. She then started to receive TCZ. After receiving two doses of TCZ, multiple chronic skin ulcers
[1] Navarro-Millán I, Singh JA, Curtis JR. Systematic review of tocilizumab for rheumatoid arthritis: a new biologic agent targeting the interleukin-6 receptor. Clin Ther 2012;34:788–802. [2] Ogata A, Tanaka T. Tocilizumab for the treatment of rheumatoid arthritis and other systemic autoimmune diseases: current perspectives and future directions. Int J Rheumatol 2012;2012:946048, doi:10.1155/2012/946048. [3] Campbell L, Chen C, Bhagat SS, et al. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatology 2011;50:552–62. [4] Grasland A, Mahé E, Raynaud E, et al. Psoriasis onset with tocilizumab. Joint Bone Spine 2013;80:541–2. [5] Magro CM, Crowson AN. The spectrum of cutaneous lesions in rheumatoid arthritis: a clinical and pathological study of 43 patients. J Cutan Pathol 2003;30:1–10.
Cheng-Pin Wu a Chia-Wei Hsieh b,c,∗ Der-Yuan Chen b,c,d Bor-Jen Lee a,c Chii-Shuenn Yang e a Intensive Care Unit, Taichung Veterans General Hospital, Taichung, Taiwan, ROC b Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung 40705, Taiwan, ROC
134
Letters to the Editor / Joint Bone Spine 82 (2015) 129–137 c
Chung Shan Medical University, Taichung, Taiwan, ROC d Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC e Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC ∗ Corresponding
author at: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung 40705, Taiwan, ROC. Tel.: +886 4 23592525x3354; fax: +886 4 23503285. E-mail address: [email protected] (C.-W. Hsieh) Accepted 6 April 2014 Available online 29 December 2014
Table 1 Characteristics and comorbidities of the 238 patients presenting with staphylococcal bone and joint infections. Characteristics Age (years mean ± SD) Sex ratio (male/female) Cardiovascular disease Diabetes mellitus Hepatic disorder Nervous system disorder Renal disorder Neoplasm HIV infection Bone and joint infections Prosthesis or device-related infection Spondylodiscitis Other BJI
62 ± 17 2.01 (159/79) 100 (42%) 44 (18%) 32 (13%) 30 (13%) 28 (12%) 14 (6%) 4 (1.7%) 108 (45%) 47 (20%) 83 (35%)
BJI: bone and joint infections.
significant variables (P < 0.1) were then entered into stepwise logistic regression analyses.
http://dx.doi.org/10.1016/j.jbspin.2014.04.004
3. Results Safety of antibiotics combinations against Staphylococcal bone and joint infections
a r t i c l e
i n f o
Keywords: Bone and joint infection Antibiotics associations Tolerance Staphylococcus spp.
1. Introduction Nowadays, there is an increasing incidence of bone and joint infections (BJI). [1]. Staphylococci are the predominant etiologic agent [2]. Our aim was to examine the rate of antibiotic adverse events (AE) concerning different antibiotics associations (ATB-A) in Staphylococcal BJI. 2. Methods Patients were selected through the dashboard of our department (Nice, France), based on a specific software (Statview® version 4.5) [3]. Comorbidities, length of hospitalization, precise diagnosis, microbiological results, antibiotics prescribed and AE were recorded prospectively during hospitalization. All the monobacterial Staphylococcal BJI from July 2005 to December 2012, defined by microbiologic harvesting or positive blood cultures, were selected. Isolated monoarthritis were excluded (because antibiotic management was different). During ambulatory care, occurrence of any antibiotic-related AE, modification of ATB-A prescribed, evolution and duration of follow-up were retrospectively recorded. In our department, rifampin dosage was 10 mg/kg twice a day. Aerobic and anaerobic cultures were performed, with blood cultures, and in few cases 16s rRNA gene sequencing was used. Only AE requiring ATB discontinuations were considered here. Evolution was classified as recovery in the absence of clinical and/or microbiological relapse over the period of care. Relationship between variables was evaluated using the 2 statistic (categorical variables), Student’s t-test (normally distributed continuous variables), and the Mann–Whitney U test (non-parametric comparisons). Univariate correlates and clinically
Finally, 238 patients with Staphylococcus BJI were treated, with 186 (78%) Staphylococcus aureus (17% methicillin-resistant), and 52 (22%) coagulase negative Staphylococcus (40% methicillinresistant). The main clinical characteristics and repartition of BJI are presented in Table 1. The 3 main ATB-A prescribed were fluoroquinolones and rifampin (FQ + RF), rifampin and clindamycin (RF + CD) and clindamycin and fluoroquinolones (CD + FQ). All other ATB-As were classified as “other associations”. The mean duration of total antibiotic treatment was 6 weeks. Among the 61 AE leading to ATB discontinuation, 41 (67%) concerned hospitalization’s period and 20 (33%) concerned ambulatory care. Classification of the AE is presented in Table 2. RF + FQ was the leading ATB-A source of AE followed by RF + CD and FQ + CD. Gastrointestinal disorders represented 13/33 (39%) of the AE. There was no Clostridium difficile-associated diarrhea. The mean time of follow-up (± SD) was 11 ± 12 months. At the end of the study, 160 patients recovered, while 40 patients relapsed (17%), 31 patients (13%) were lost to follow-up and 7 patients died. In univariate and then multivariable analysis, AE related to ATB-A were associated with female gender (OR [95% CI]) 1.99 [1.07–3.69], P = 0.028, but not with comorbidities, presence of material, duration of hospital stay and outcomes. 4. Discussion The best-tolerated ATB-A in monobacterial Staphylococcal BJI was FQ + CD. Rifampicin [4–7], clindamycin [8] and fluoroquinolones [9,10] have already been studied in Staphylococcal BJI, but our study is the first to compare 3 ATB-As in this indication. One third of the AE were recorded during ambulatory care, underlying the importance of a regular follow-up by specialists. Prospective studies are required to determine the real place of clindamycin for Staphylococcal BJI, in terms of cure rate and AE. Clindamycin could be the first drug to consider as an alternative companion for FQ when RF is not tolerated or contraindicated.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.