- Email: [email protected]
Rhodococcus equi infection in a patient with Crohn's disease treated with infliximab
Letters to the Editor
689
8. Mukhopadhyay C, Chawla K, Sharma Y, Bairy I. Emerging extraintestinal infections with Aeromonas hydrophila in coastal region of southern Karnataka. J Postgrad Med 2008;54(3): 199e202. 9. Janda JM, Abbott SL. The genus Aeromonas: taxonomy, pathogenicity, and infection. Clin Microbiol Rev 2010;23:35e73. 10. Ling TK, Tam PC, Liu ZK, Cheng AF. Evaluation of VITEK 2 rapid identification and susceptibility testing system against gramnegative clinical isolates. J Clin Microbiol 2001;39:2964e6.
Priyam Batra Purva Mathur* M.C. Misra All India Institute of Medical Sciences, New Delhi 110029, India *Corresponding author. Tel.: þ91 9810350650.
E-mail address: [email protected] (P. Mathur) Accepted 13 December 2014 http://dx.doi.org/10.1016/j.jinf.2014.12.004 ª 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Rhodococcus equi infection in a patient with Crohn’s disease treated with infliximab
Dear Editor, Loulerque et al., in this Journal recently reported a large prospective survey of bacteremias in patients on TNF immunomodulators.1 We encountered a patient with bacteremia due to Rhodococcus equi while receiving treatment with infliximab. A 41-year-old man was admitted to the hospital because of fever up to 40 C, cough, and malaise during the last week. A diagnostic of Crohn’s disease had been made seventeen years earlier and the patient had been treated with infliximab every other month in the last three years, during which he had suffered no flare-up of the disease. At the time of admission to the hospital the white-cell count was 27,180 per cubic millimetre (neutrophils 84%, lymphocytes 8%, monocytes 8%) and the serum creatinine level was 125 mmol per litre. Arterial blood gas measurements while the patient was breathing ambient air revealed a partial pressure of oxygen of 55.2 mm Hg and a partial pressure of carbon dioxide of 33.0 mm Hg, with a pH of 7.51. Results of an HIV screening test were negative. A chest radiograph revealed a pulmonary consolidation in the right upper lobe and the right lower lobe, with minimal right pleural effusion. Two sets of blood cultures became positive for mucoid Gram-positive cocobacillary rods. After 48 h of incubation, rieux, France) identified the the API Coryne system (BioMe organism as R. equi. The patient was treated with
vancomycin and rifampin. Vancomycin was replaced by meropenem due to an allergic reaction to vancomycin. The clinical response was favourable, with abatement of fever and respiratory symptoms two weeks after the initiation of therapy. Three weeks later, the patient was switched to the combination of oral clarithromycin and rifampin. This treatment was continued for five months, until the normalization of the chest radiograph. Treatment with infliximab was restarted. The patient has remained asymptomatic for the next four years. The introduction of biological agents, such as infliximab, acting against tumour necrosis factor-a (TNF-a) was a major advance for the treatment of an increasing number of chronic diseases. The use of infliximab has greatly improved the treatment of Crohn’s disease, reducing the rate of complications, hospitalizations and surgical procedures. TNF-a plays an important role in cellular immunity, The clinical use of TNF antagonists can increase the risk of infections caused by intracellular microorganisms, including Mycobacterium tuberculosis, nontuberculous mycobacteria, Aspergillus species, Histoplama capsulatum, Candida species, Listeria, Cryptococcus neoformans, Nocardia species, Salmonella species, Staphylococcus aureus, Pseudomonas aeruginosa, Toxoplasma gondii, Brucella species, Bartonella species, Pneumocystis jirovecci, Leishmania donovani, Coccidiodes immitis, Mycobacterium leprae and cytomegalovirus.1e3 Until now, Rhodococcus equi has not been included among the opportunistic microorganisms causing infections in patients treated with TNF-a inhibitors.1e3 A PubMed search using the MeSH terms infliximab, tumour necrosis factor-alpha, biologic therapy and Rhodococcus equi revealed no cases of R. equi infection in patients treated with infliximab. R. equi is a Gram-positive pleomorphic coccobacillus. It is a facultative intracellular pathogen that can survive inside macrophages, producing a necrotizing granulomatous reaction.4,5 R equi primarily causes zoonotic infection in grazing animals, mainly horses and foals. Human infections are rather uncommon. They usually occur in persons with diminished cellular immunity, especially those with AIDS.4 It is amazing the lack of reports about R. equi infection in patients receiving infliximab, since it is well known that TNF plays a major role in innate immune response to R. equi.6 Based on our observation, we suggest that R. equi should be included among the microorganisms that can cause opportunistic infections in patients receiving infliximab.
Conflicts of interest None.
References 1. Loulergue P, Tubach F, Salmon D, Dellamonica P, Taillan B, Thorel JB, et al. Bacteremia in patients receiving TNF-alpha antagonistsda prospective multicenter study. J Infect 2013; 67:524e8. http://dx.doi.org/10.1016/j.jinf.2013.07.027. 2. Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 2004;38:1261e5.
690
Letters to the Editor
3. Salvana EM, Salata RA. Infectious complications associated with monoclonal antibodies and related small molecules. Clin Microbiol Rev 2009;22:274e90. http: //dx.doi.org/10.1128/CMR.00040-08. 4. Verville TD, Huycke MM, Greenfield RA, Fine DP, Kuhls TL, Slater LN. Rhodococcus equi infections of humans. 12 cases and a review of the literature. Med Baltim 1994;73:119e32. 5. Yamshchikov AV, Schuetz A, Lyon GM. Rhodococcus equi infection. Lancet Infect Dis 2010;10:350e9. http: //dx.doi.org/10.1016/S1473-3099(10)70068-2. 6. Darrah PA, Monaco MC, Jain S, Hondalus MK, Golenbock DT, Mosser DM. Innate immune responses to Rhodococcus equi. J Immunol 2004;173:1914e24.
Carolina Guerrero Internal Medicine Service, Consorci Sanitari de Terrassa, Ctra. Torrebonica s/n, 08227 Terrassa, Spain Joan Tort Internal Medicine Service, Consorci Sanitari de Terrassa, Ctra. Torrebonica s/n, 08227 Terrassa, Spain rez Josefa Pe Microbiology Laboratory, Catlab, Vial Sant Jordi s/n, Pol. Ind. Can Mitjans, 08232 Viladecavalls, Spain s Marta Andre Infectious Diseases Unit, Internal Medicine Service, Consorci Sanitari de Terrassa, Ctra. Torrebonica s/n, 08227 Terrassa, Spain Elena Espejo* Infectious Diseases Unit, Internal Medicine Service, Consorci Sanitari de Terrassa, Ctra. Torrebonica s/n, 08227 Terrassa, Spain *Corresponding author. Infectious Diseases Unit, Consorci Sanitari de Terrassa Ctra. Torrebonica s/n. 08227 Terrassa, Spain. Tel.: þ34 937839488; fax: þ34 937003614.
E-mail address: [email protected] Accepted 21 December 2014 http://dx.doi.org/10.1016/j.jinf.2014.12.008 ª 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Inpatient admissions of patients living with HIV in two European centres (UK and Italy); comparisons and contrasts
Dear Sirs, In this journal Sogard and colleagues described HIV comorbidities across in a very large pan-european population. However we think there may be striking differences between individual countries in Europe,1 so we are reporting our experience.
Combined antiretroviral treatment (cART) has reduced morbidity and mortality rates2 in people living with HIV (PLWH) because of fewer opportunists infections, but premature age related co-morbidities3 and increased hospitalisation still occur.4 The future impact of non-infectious comorbidities (NICMs) on patient care and service provision is still unfolding and information on current admissions may be helpful in planning future services. This article gives a description of the clinical conditions and patient demographics of inpatient admissions in two HIV specialist centres. Chelsea and Westminster Hospital, London (UK) and four infectious disease departments (Sanremo, Galliera, San Martino, La Spezia) in Liguria, Italy (IT) known collectively as the Analisi Costi Terapia Antivirale network (ACTeA) have local populations of 470,000 and 700,000 respectively. All HIV medical admissions throughout 2012 were reviewed (surgical, paediatric, obstetrics and gynaecological admissions excluded); UK HIV cohort is 7400 and 3000 in IT. The principal clinical condition was prospectively collected from ACTeA onto an online platform by the lead clinician. In the UK electronic medical records and clinical coding were retrospectively reviewed by Italian and UK researchers, to reduce bias in the data collection. The International Classification of Diseases (ICD) 9 (IT)/10 (UK) were used in the centres involved and data was anonymised and stored securely. For standardisation, viral load <400 copies/ml was classed as viral suppression and cART status was defined as new starters (<6 months), stable (>6 months), poor adherence (<80%, clinician recorded or self-suspended) or failing regimen on admission. The following opportunistic infections were coded: Cytomegalovirus, Toxoplasma, Pneumocystis jirovecii, Mycobacterium tuberculosis (pulmonary, disseminated and lymphadenitis), Mycobacterium avium complex (MAC), Cryptococcosis and recurrent pneumonia.5 The discharging diagnoses were grouped according to ICD categories. Categories exceeding 3% admissions were reviewed, within each category conditions constituting 50% of the total ICD are discussed. Fisher’s exact or Pearson chi square tests were used to compare categorical variables, while ManneWhitney U test was used for continuous variables. Two-tailed probabilities were reported. Admission rates by country were estimated by negative-binomial regression, modelling and the likelihood ratio test. Analyses used SPSS software and STATA. 731 admissions were identified (see Table 1). Rate of patient admissions per 100 years was 6.12 IT and 12.91 UK Over 60% of admissions had suppressed viral loads and CD4 counts >200 cells/ml (median CD4 302 IT, 368 UK), reflecting the number of patients on cART (86.4% IT, 82.1% UK). This suggests that the majority of admissions would not be AIDS related, but due to other co-morbidities and non opportunistic infections at the median age of 47 years old. Rate of patient admissions per 100 years (6.12 IT vs 12.91 UK) is lower than in earlier studies,6 likely relating to continue improvement and survival with cART. The difference in mode of HIV transmission (IVDU: 64.4% IT vs 6.3% UK, MSM: 12.2% IT vs 59.5% UK, pZ<0.001) explains why Hepatitis C virus (HCV) co-infection is higher
689
8. Mukhopadhyay C, Chawla K, Sharma Y, Bairy I. Emerging extraintestinal infections with Aeromonas hydrophila in coastal region of southern Karnataka. J Postgrad Med 2008;54(3): 199e202. 9. Janda JM, Abbott SL. The genus Aeromonas: taxonomy, pathogenicity, and infection. Clin Microbiol Rev 2010;23:35e73. 10. Ling TK, Tam PC, Liu ZK, Cheng AF. Evaluation of VITEK 2 rapid identification and susceptibility testing system against gramnegative clinical isolates. J Clin Microbiol 2001;39:2964e6.
Priyam Batra Purva Mathur* M.C. Misra All India Institute of Medical Sciences, New Delhi 110029, India *Corresponding author. Tel.: þ91 9810350650.
E-mail address: [email protected] (P. Mathur) Accepted 13 December 2014 http://dx.doi.org/10.1016/j.jinf.2014.12.004 ª 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Rhodococcus equi infection in a patient with Crohn’s disease treated with infliximab
Dear Editor, Loulerque et al., in this Journal recently reported a large prospective survey of bacteremias in patients on TNF immunomodulators.1 We encountered a patient with bacteremia due to Rhodococcus equi while receiving treatment with infliximab. A 41-year-old man was admitted to the hospital because of fever up to 40 C, cough, and malaise during the last week. A diagnostic of Crohn’s disease had been made seventeen years earlier and the patient had been treated with infliximab every other month in the last three years, during which he had suffered no flare-up of the disease. At the time of admission to the hospital the white-cell count was 27,180 per cubic millimetre (neutrophils 84%, lymphocytes 8%, monocytes 8%) and the serum creatinine level was 125 mmol per litre. Arterial blood gas measurements while the patient was breathing ambient air revealed a partial pressure of oxygen of 55.2 mm Hg and a partial pressure of carbon dioxide of 33.0 mm Hg, with a pH of 7.51. Results of an HIV screening test were negative. A chest radiograph revealed a pulmonary consolidation in the right upper lobe and the right lower lobe, with minimal right pleural effusion. Two sets of blood cultures became positive for mucoid Gram-positive cocobacillary rods. After 48 h of incubation, rieux, France) identified the the API Coryne system (BioMe organism as R. equi. The patient was treated with
vancomycin and rifampin. Vancomycin was replaced by meropenem due to an allergic reaction to vancomycin. The clinical response was favourable, with abatement of fever and respiratory symptoms two weeks after the initiation of therapy. Three weeks later, the patient was switched to the combination of oral clarithromycin and rifampin. This treatment was continued for five months, until the normalization of the chest radiograph. Treatment with infliximab was restarted. The patient has remained asymptomatic for the next four years. The introduction of biological agents, such as infliximab, acting against tumour necrosis factor-a (TNF-a) was a major advance for the treatment of an increasing number of chronic diseases. The use of infliximab has greatly improved the treatment of Crohn’s disease, reducing the rate of complications, hospitalizations and surgical procedures. TNF-a plays an important role in cellular immunity, The clinical use of TNF antagonists can increase the risk of infections caused by intracellular microorganisms, including Mycobacterium tuberculosis, nontuberculous mycobacteria, Aspergillus species, Histoplama capsulatum, Candida species, Listeria, Cryptococcus neoformans, Nocardia species, Salmonella species, Staphylococcus aureus, Pseudomonas aeruginosa, Toxoplasma gondii, Brucella species, Bartonella species, Pneumocystis jirovecci, Leishmania donovani, Coccidiodes immitis, Mycobacterium leprae and cytomegalovirus.1e3 Until now, Rhodococcus equi has not been included among the opportunistic microorganisms causing infections in patients treated with TNF-a inhibitors.1e3 A PubMed search using the MeSH terms infliximab, tumour necrosis factor-alpha, biologic therapy and Rhodococcus equi revealed no cases of R. equi infection in patients treated with infliximab. R. equi is a Gram-positive pleomorphic coccobacillus. It is a facultative intracellular pathogen that can survive inside macrophages, producing a necrotizing granulomatous reaction.4,5 R equi primarily causes zoonotic infection in grazing animals, mainly horses and foals. Human infections are rather uncommon. They usually occur in persons with diminished cellular immunity, especially those with AIDS.4 It is amazing the lack of reports about R. equi infection in patients receiving infliximab, since it is well known that TNF plays a major role in innate immune response to R. equi.6 Based on our observation, we suggest that R. equi should be included among the microorganisms that can cause opportunistic infections in patients receiving infliximab.
Conflicts of interest None.
References 1. Loulergue P, Tubach F, Salmon D, Dellamonica P, Taillan B, Thorel JB, et al. Bacteremia in patients receiving TNF-alpha antagonistsda prospective multicenter study. J Infect 2013; 67:524e8. http://dx.doi.org/10.1016/j.jinf.2013.07.027. 2. Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 2004;38:1261e5.
690
Letters to the Editor
3. Salvana EM, Salata RA. Infectious complications associated with monoclonal antibodies and related small molecules. Clin Microbiol Rev 2009;22:274e90. http: //dx.doi.org/10.1128/CMR.00040-08. 4. Verville TD, Huycke MM, Greenfield RA, Fine DP, Kuhls TL, Slater LN. Rhodococcus equi infections of humans. 12 cases and a review of the literature. Med Baltim 1994;73:119e32. 5. Yamshchikov AV, Schuetz A, Lyon GM. Rhodococcus equi infection. Lancet Infect Dis 2010;10:350e9. http: //dx.doi.org/10.1016/S1473-3099(10)70068-2. 6. Darrah PA, Monaco MC, Jain S, Hondalus MK, Golenbock DT, Mosser DM. Innate immune responses to Rhodococcus equi. J Immunol 2004;173:1914e24.
Carolina Guerrero Internal Medicine Service, Consorci Sanitari de Terrassa, Ctra. Torrebonica s/n, 08227 Terrassa, Spain Joan Tort Internal Medicine Service, Consorci Sanitari de Terrassa, Ctra. Torrebonica s/n, 08227 Terrassa, Spain rez Josefa Pe Microbiology Laboratory, Catlab, Vial Sant Jordi s/n, Pol. Ind. Can Mitjans, 08232 Viladecavalls, Spain s Marta Andre Infectious Diseases Unit, Internal Medicine Service, Consorci Sanitari de Terrassa, Ctra. Torrebonica s/n, 08227 Terrassa, Spain Elena Espejo* Infectious Diseases Unit, Internal Medicine Service, Consorci Sanitari de Terrassa, Ctra. Torrebonica s/n, 08227 Terrassa, Spain *Corresponding author. Infectious Diseases Unit, Consorci Sanitari de Terrassa Ctra. Torrebonica s/n. 08227 Terrassa, Spain. Tel.: þ34 937839488; fax: þ34 937003614.
E-mail address: [email protected] Accepted 21 December 2014 http://dx.doi.org/10.1016/j.jinf.2014.12.008 ª 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Inpatient admissions of patients living with HIV in two European centres (UK and Italy); comparisons and contrasts
Dear Sirs, In this journal Sogard and colleagues described HIV comorbidities across in a very large pan-european population. However we think there may be striking differences between individual countries in Europe,1 so we are reporting our experience.
Combined antiretroviral treatment (cART) has reduced morbidity and mortality rates2 in people living with HIV (PLWH) because of fewer opportunists infections, but premature age related co-morbidities3 and increased hospitalisation still occur.4 The future impact of non-infectious comorbidities (NICMs) on patient care and service provision is still unfolding and information on current admissions may be helpful in planning future services. This article gives a description of the clinical conditions and patient demographics of inpatient admissions in two HIV specialist centres. Chelsea and Westminster Hospital, London (UK) and four infectious disease departments (Sanremo, Galliera, San Martino, La Spezia) in Liguria, Italy (IT) known collectively as the Analisi Costi Terapia Antivirale network (ACTeA) have local populations of 470,000 and 700,000 respectively. All HIV medical admissions throughout 2012 were reviewed (surgical, paediatric, obstetrics and gynaecological admissions excluded); UK HIV cohort is 7400 and 3000 in IT. The principal clinical condition was prospectively collected from ACTeA onto an online platform by the lead clinician. In the UK electronic medical records and clinical coding were retrospectively reviewed by Italian and UK researchers, to reduce bias in the data collection. The International Classification of Diseases (ICD) 9 (IT)/10 (UK) were used in the centres involved and data was anonymised and stored securely. For standardisation, viral load <400 copies/ml was classed as viral suppression and cART status was defined as new starters (<6 months), stable (>6 months), poor adherence (<80%, clinician recorded or self-suspended) or failing regimen on admission. The following opportunistic infections were coded: Cytomegalovirus, Toxoplasma, Pneumocystis jirovecii, Mycobacterium tuberculosis (pulmonary, disseminated and lymphadenitis), Mycobacterium avium complex (MAC), Cryptococcosis and recurrent pneumonia.5 The discharging diagnoses were grouped according to ICD categories. Categories exceeding 3% admissions were reviewed, within each category conditions constituting 50% of the total ICD are discussed. Fisher’s exact or Pearson chi square tests were used to compare categorical variables, while ManneWhitney U test was used for continuous variables. Two-tailed probabilities were reported. Admission rates by country were estimated by negative-binomial regression, modelling and the likelihood ratio test. Analyses used SPSS software and STATA. 731 admissions were identified (see Table 1). Rate of patient admissions per 100 years was 6.12 IT and 12.91 UK Over 60% of admissions had suppressed viral loads and CD4 counts >200 cells/ml (median CD4 302 IT, 368 UK), reflecting the number of patients on cART (86.4% IT, 82.1% UK). This suggests that the majority of admissions would not be AIDS related, but due to other co-morbidities and non opportunistic infections at the median age of 47 years old. Rate of patient admissions per 100 years (6.12 IT vs 12.91 UK) is lower than in earlier studies,6 likely relating to continue improvement and survival with cART. The difference in mode of HIV transmission (IVDU: 64.4% IT vs 6.3% UK, MSM: 12.2% IT vs 59.5% UK, pZ<0.001) explains why Hepatitis C virus (HCV) co-infection is higher