Infectious Diseases Society of America
8/15/07
Infectious Diseases Society of America
Emerging Infections Network
Report for Query:
‘Mycobacteria and Other Serious Infections Associated with Biologic Therapies’
Page 1 of 6
8/15/07
Overall response rate: 426/871 (48.9%) physicians with adult practices responded from 6/14/07 to 7/29/07.
Note: Not all respondents answered all questions, so totals for individual questions vary.
Responders as percent of overall members in each category:
Practice type: Academic institution 178 (62% of 287 members)
Private practice 134 (53% of 254 members)
Other 28 (52% of 54 members)
Question 1. Cases of mycobacterial infections in last 6 months [answered by 317 members]:
• 38 members answered none for both NTM and TB
• 249 members had seen at least one case of NTM; 239 members had seen at least 1 case of TB
Mean, median (std deviation), range
Non-tuberculous mycobacteria 3.22, 2 (6.20), 0-100†
Tuberculosis 2.70, 1 (6.50), 0-98†
†Both of the individuals who reported 100 cases (NTM) and 98 cases (TB) specialize in these respective entities.
Question 2: Were any cases associated with anti-TNF therapy or other biologics?
Yes (range of 1-3 cases per member) 35 (8%)
No 353 (83%)
N/A (no cases of mycobacterial infections seen) 38 (9%)
Question 3: Patient information for each of the 50 cases associated with biologics therapy:
Organism: M. tuberculosis 18 (36%)
M. avium complex 16 (32%)
M. chelonae 5 (10%)
M. abscessus 3 (6%)
M. marinum 3 (6%)
1 each: M. fortuitum, M. haemophilum, M. kansasii, M. scrofulaceum, and non-TB AFB
Biologic drug used (provided for 44/50 cases):
Infliximab 18 (36%)
Etanercept 12 (24%)
Rituximab 8 (16%)
Adalimumab 3 (6%)
Other (not specified) 3 (6%)
Unknown or missing 6 (12%)
Age: Mean 57 y, range 11-82 y
Other immunosuppressive drugs:
None or unknown 27 (54%)
Steroids 11 (22%)
Methotrexate 4 (8%)
Steroids and methotrexate 6 (12%)
Cyclosporine 1 (2%)
Azathioprine 1 (2%)
Was biologic drug stopped?
No 2 (4%)
Yes 43 (86%)
Unknown or missing 5 (10%)
The numbers were too small to permit analysis of associations between specific organisms and biologic drugs.
Question 4. When biologic was stopped, how many patients suffered IRIS?
None 43 (86%)
One 2 (4%)
No answer 5 (10%)
Question 5. How many died during therapy for mycobacterial infection?
None 44 (88%)
One 5 (10%)
Three 1 (2%)
Question 6. Have you seen other infections associated with these biologics?
No 188 (59%)
Yes 130 (41%) (specified below)
Infection (No. who answered) Mean (std dev), range # infections reported by # members
Invasive S. aureus (268) 0.272 (0.75), 0-6 73 by 47 members
Histoplasmosis (263) 0.213 (0.62), 0-5 56 by 40 members
Severe pneumococcal disease (267) 0.075 (0.33), 0-3 20 by 16 members
CMV (270) 0.067 (0.32), 0-3 18 by 14 members
Aspergillosis (263) 0.061 (0.32), 0-4 16 by 13 members
Parasitic infections (269) 0.037 (0.38), 0-6 10 by 5 members
Listeriosis (268) 0.019 (0.14), 0-1 5 by 5 members
Legionellosis (262) 0.015 (0.12), 0-1 4 by 4 members
Blastomycosis (268) 0.007 (0.09), 0-1 2 by 2 members
Coccidioidomycosis (268) 0.007 (0.09), 0-1 2 by 2 members
Salmonellosis (268) 0.007 (0.09), 0-1 2 by 2 members
Other (271) 0.140 (0.45), 0-4 38 by 30 members
Other specified as:
7 cases: Cryptococcus (both pulmonary and CNS)
4 cases each: postop surgical infections with various agents, PCP/Pneumocystis jiroveci
3 cases each: streptococcal disease including other beta-hemolytic strep and group A beta-hemolytic streptococci, varicella zoster/herpes zoster, osteomyelitis (specified as pseudomonas in 2 cases)
2 cases: falciparum malaria
1 case each: Q fever, severe facial cellulitis, Actinomyces turensis pneumonia, HSV esophagitis post Remicade 4 y ago, more SST problems like infectious olecranon bursitis due to SA or pseudomonas, persistent peritonitis/intra-abdominal polymicrobial abscesses with Humira, fever, Fusarium, wound infections with S. aureus that are difficult to heal, 50 yo RA guy with recurrent MRSA boils while on Humira
Comments about mycobacteria or this survey:
Specific biologic/infection associations:
• Q fever with Remicade; several MRSA infections following Remicade. One diverticular abscess in a retired surgeon who queried colleagues at MGH who told him they have a lot of problems with diverticular disease that cannot be resolved without surgery when Remicade is involved. I am aware of one case of neglected M. marinum finger infection that disseminated on steroids and Remicade which also could not be eradicated with drugs and relapses without Rx even after stopping Remicade.
• Infliximab was used in this case [of histo]. I had another case of histoplasmosis and infliximab about 2004.
• We have seen MDR TB with Remicade for Crohns
• Patients on methotrexate + Enbrel (Histo case) and MTx + Remicade (Aspergillus case)
• Fatal infection in a 9 y/o child with sickle cell anemia and Crohn's disease receiving Remicade who developed florid CMV colitis and probable disseminated disease (hepatitis)
• 58 yo woman w/ RA, Rx Orencia, dvp'd pneumonia, bronchoscopy showed Acinomyces turensis which I felt was a pathogen (vs. colonization), improved on pcn and off Orencia
• Dramatic case of S. aureus toxic shock syndrome due to S. aureus enterotoxin serotype c in patient who received infliximab for psoriasis. TSS is due to TNF in excess and yet this patient developed severe TSS (she died) 2 weeks after her last dose of TNF-inhibitor.
• About 2 years ago we saw a case of pulmonary actinomycosis in a man on infliximab for severe Crohn's. He did well on standard therapy. His infliximab was withheld for several months but has been re-started.
• 1 case of CMV w/ Remicade 5 y ago; +HSV esophagitis post Remicade 4 y ago; 2 cases M. chelonae after Remicade 2 y ago.
• PCP (Pneumocystis jiroveci) assoc with Remicade in elderly cauc woman being treated by a rheumatologist for rheumatoid arthritis. Delay in dx as pt was not viewed as at risk for opportunistic infection by her treating physician.
• Histoplasmosis/infliximab, S. aureus/infliximab, persistent peritonitis/intra-abdominal abscesses(polymicrobial)/Humira
• Infliximab [associated with invasive S. aureus]
• [Invasive S. aureus associated with] etanercept for RA
• The aspergillosis case was 5 y ago; pt lost 1/2 his face to surgery. This one case was horrible. Pt was on infliximab for RA & developed severe invasive aspergillosis of sinuses.
• I had a terrible outcome of M. avium pulmonary disease after restarting Arava.
• Remicade [associated with invasive S. aureus]
• I have seen 2 pts with miliary disseminated TV related to Remicade - last in 2003 or 2004. Expired from a tuberculosis mycotic aneurysm of descending thoracic aorta adjacent to mediastinal node - contiguous spread from note to aorta in 85yo non-surgical candidate.
• I have a 55yo woman with rheumatoid arthritis on Remicade who developed "B" symptoms & a miliary pattern on chest radiograph
• CAP complicated by empyema and/or necessitating hospitalization appears higher frequency with infliximab and etanercept.
• I treated a case of disseminated histoplasmosis in a Humira recipient. I describe the case in my "Cases of the Month." Here is the link: http://www.infdiseasesconsultants.com/idcase6.php
• One RA patient on Humira had M. gordonae grow from an AFB culture throat swab
• I saw a woman with disseminated histoplasmosis shortly after being started on Enbrel for Crohn's disease. She responded promptly to itraconazole and has remained free of Crohn's after being off TNF inhibitors for over one year.
• Few yrs ago I saw 2 pts who developed active Tb on infliximab.
• One TB and one disseminated histo – both 2 or 3 years ago with Remicade
• Infliximab related [case of histo]
• Septic arthritis with MSSA in pt on Enbrel.
• In November 2005, I consulted on a patient who developed Listeria brain abscesses while being treated for Crohn's disease with infliximab and prednisone.
• Had one patient (50's) greater than 6 months ago with MAC likely related to Enbrel
• Pulmonary and disseminated histoplasmosis due to long term use of Remicade in a patient with Crohn's disease.
• I saw a case of pulmonary histoplasmosis in patient on etanercept for RA in 2006.
• Have seen cryptococcal pulmonary reactivation with adalimumab
• Other case= 50 yo RA guy with recurrent MRSA boils while on Humira.
• Disseminated histo in patient with Crohn's on Remicade.
• I had seen 2 cases of disseminated histoplasmosis in patients on Remicade for IBD.
• Saw a fascinating case several years ago when infliximab had just been introduced. Middle aged male being tx’ed for Crohn's developed fevers, eventually an ARDS-like picture
Comments about mycobacteria and TNF inhibitors:
• Not in last 6 months, but have seen serious NTM infection and other bacterial infections with anti-TNF rx.
• Recent increase in anti-TNF life-threatening infection has been worrisome
• So far none seen-certainly a concern. I have an HIV/HCV coinfection pt about to be treated but his HCV is treated with remission and HIV control is exemplary.
• Histo 18 mo ago (1 case), S. aureus 1 yr ago (2 cases), pneumococcal w/in 6 mon (1 case)
• Increasing incidence in the elderly with underlying bronchiectasis/COPD
• Not commonly used agents in our setting.
• My patient [NTM case not associated with TNF inhibitors] developed her facial infection after dermabrasion for facial cancer
• Severe group a beta strep infection - patient had group A beta strep pharyngitis presenting with septic shock and multi-organ dysfunction
• I saw one case on NTM about 1 and 1/2 yrs ago but did not treat with any med only total resection, and last month we just had one TB lymphadenitis which we treated.
• Massive increase suddenly in NON-immunosuppressed hosts - one coinfected with MAC, M. kansasii, another atypical still being ID'd.
• Rapid grower AFB associated with silicone injections from Dominican Republic
• Importance of TST plus controls before AND updating immunizations before!
• No infections in the past 6 months but severe S. aureus disease in a patient on a TNF inhibitor 3 years ago.
• I have seen more skin and soft tissue problems like infectious olecranon bursitis due to S. aureus or pseudomonas
• It must be rare [by a member who reported having seen no infections]
• Very concerned about over-exuberant use by rheumatologists. How does one control the rheumatologists???
• Had a case of Crohn’s with lung cysts of unknown etiology
• 1 case of Fusarium -? association; I am seeing more cases of nontuberculous mycobacteria in other patients
• TB is screened for prior to biologics starting (usually)
• See disseminated histoplasmosis frequently with these drugs
• We have seen about 5 or 6 cases of rapidly growing mycobacterial infections associated with these agents in the past 5 years however [reported by a member who had seen no infections in the last 6 months].
• Risks have been underestimated.
• Saw 2 cases of NTM in pts not on biologic therapies (1 was HIV pt who had IRIS 2nd to better HIV Rx).
• Rheumatology often refers us patients prior to starting biologic agents
• Probable underestimate [by member who reported 3 cases of invasive S. aureus]
• I have seen 2 cases of pseudomonas osteomyelitis in patients on TNF inhibitors.
• I don't think I would remember a severe staph or pneumococcus infection just b/c the pt was on an immunomodulator and these infections are so common.
• I have seen many more of these in prior years [by a member who reported one case of TB in patient on infliximab]
• I usually treat latent TB infection first before treatment with biologic agents
• The NTM kids I have seen have typically had positive tuberculin skin tests
• We have a high incidence of histo and blasto in middle TN [by a member who reported 1 case of each related to TNF inhibitors]
• CMV colitis in a patient with rheumatoid arthritis being treated with prednisone
• I have seen disseminated histoplasmosis in patient 2 months after starting anti TNF therapy. We are in Indiana. I am interested in the occurrence of reactivation of the endemic fungi in these situations - especially in endemic/hyperendemic areas.
• Have seen invasive aspergillosis in patients on TNF-inhibiting Rx, but not during the last 6 months.
• The MAC infection was rather severe [by a member who reported a case of M. avium infection in a patient on infliximab and methotrexate].
• We haven't seen any of these types of infections
• Have seen two or 3 cases of severe pneumococcal dz in pts on these agents
• How long should a PPD+ patient be on INH prophylaxis before a biologic agent is used?
• We documented CD4+ lymphocytopenia in both of the above patients as well [One with TB on infliximab and one with M. abscessus on infliximab].
• In previous years I have seen two cases of disseminated TB in patients on TNF inhibitors. Both women responded well to TB drugs.
• We have had a couple of cases of severe CMV disease in the last two years (but not in the past 6 months) that occurred in patients who were not receiving other substantial immunosuppression and I was convinced the severity of disease was related to anti-TNF drugs.
• Consider the frequency of previous viral infections in patients who will be on anti-TNF.
• I have to evaluate the occasional patient pre-antiTNF-therapy. Anyone using Quantiferon testing for this? No labs in this state [Oklahoma].
• Is everyone seeing increased atypical mycobacteria?
• Definitely seeing more nodular lung disease with MAC in non-HIV patients.
• How often do you find M. fortuitum as isolated lung granuloma (RML) not involving the subcutaneous chest (soft-tissue) area?
• Don't recall specifics of cases for Q3
• In the last few years we have seen Tbc
General comments
• A lot of aseptic meningitis in the last 2 weeks [on June 14, 2007]. Still waiting for labs to see what it is.
• Case of fulminant anaerobic pericarditis of unknown source.
• Every June we see parainfluenza in our BMT/leukemia patients - 13 last year.
• I am seeing increased numbers of patients with histoplasmosis
• Increasing complexity of counseling/discussion for vaccinations in general