Rapid Responses to:
|
|
Rapid Responses: Rapid Responses published:
-
![[Read Rapid Response]](/icons/misc/sectionDOWN.gif)
MDR-TB or Brucellosis?
- James, Philip Harris (16 April 2008)
-
Re: MDR-TB or Brucellosis?
- Georgios Pappas (17 April 2008)
-
Re: MDR-TB or Brucellosis?
- Mile Bosilkovski, Jovanka Andonovska (1 May 2008)
|
|
|||
|
James, Philip Harris, SHO/ST1 Medicine. Currently taking the Diploma in Tropical Medicine and Hygiene at the LSTM. Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA
Send response to journal:
|
Having just read the BMJ editorial (March 2008)[1] and subsequent systematic review on the treatment of Brucellosis[2], I am somewhat surprised at the unfortunate ambiguity and omissions from the editorial. There is good evidence for treating Brucellosis using an aminoglycoside with doxycycline[2] but I do not believe triple or other therapy containing rifampacin or streptomycin should be considered as a viable alternative. Indeed, Brucellosis can by various accounts be clinically similar to Tuberculosis (TB)[3]. Fever, weight loss, joint pain and cough are common features of both. Spinal Brucellosis syndromes also bare resemblance to spinal-TB. Alternatively, where the burden of Brucellosis exists in developing countries co-existence of TB will also be common. Furthermore, Brucellosis is notoriously difficult to diagnose[4]. Serological tests are not especially sensitive and cannot differentiate between acute infection and that previously “cured”. Culture techniques are also problematic. Similarly, TB can also be a diagnostic problem. Therefore, given TB (and multi-drug-resistance [MDR]) is a growing international public health challenge, should we be condoning the usage of mono-therapeutic anti-TB drugs for a disease that could potentially be a misdiagnosis and is instead TB? When I say “mono-therapy”, I mean the use of rifampacin in addition to doxycycline and an aminoglycoside (two drugs of minimal usage against TB); this is essentially a TB mono-therapy. Such a regimen would have grave potential to seed the emergence of a MDR-TB strain. Making a clinical diagnosis of Brucellosis is certainly more likely in a developing health care setting where diagnostic tests are unavailable. But there is no reason why diagnosis should not prove a conundrum in a more resource rich health system. In either case TB may have been excluded by sputum microscopy and culture. But again, whichever technique used will not be 100% sensitive[5]. Surely when the diagnosis of Brucellosis is not cast in iron (or TB cannot be excluded), doxycycline and an aminoglycoside (gentamycin) should be used as first line therapy. If clinical improvement is not forthcoming serious consideration should be given towards whether the symptoms being treated are actually related to TB or whether TB has been ruled out. Then, the decision to treat with either 2nd-line therapy for Brucellosis or commence appropriate 1st-line TB therapy (e.g. isoniazid, rifampacin, pyrazinamide and ethambutol) can be made. While the use of an aminoglycoside in the first instance probably commits the patient to a lengthy inpatient stay, I do not believe the more convenient alternative of oral rifampacin outweighs the risk of MDR-TB. This issue has certainly been discussed before[6] and I hope the BMJ will continue promoting sensible public health practice. In due course we eagerly await the emergence of new diagnostic techniques with sufficient sensitivity and specificity for Brucellosis coupled with effective oral treatment regimens without the risks as stated. 1. Georgious Pappas. Editorial: Treatment of Brucellosis. BMJ, 2008; 336: 678-9. 2. Keren Skalsky et al. Treatment of human Brucellosis: systematic review and meta-analysis of randomised control trials. BMJ, 2008; 336: 701 -4. 3. Young EJ. Human Brucellosis. Rev Infect Dis, 1983; 5: 821-42. 4. Franco MP et al. Human Brucellosis. Lancet Inf Disease, 2007; 7: 775-86. 5. Coulter JBS. Diagnosis of pulmonary tuberculosis in young children. Ann Trop Paediatr, 2008; 28: 3-12. 6. Al-Hajjaj MS et al. Progressive rise of Mycobacterium tuberculosis resistance to rifampicin and streptomycin in Riyadh, Saudi Arabia. Respirology. 2001;6:317–322. Competing interests: None declared |
|||
|
|
|||
|
Georgios Pappas, Head Institue for Continuing Medical Education of Ioannina
Send response to journal:
|
I have read with interest the concerns of Dr. Harris regarding the co -existence of brucellosis and tuberculosis, and the potential effect of rifampicin-containing brucellosis treatment on TB in such areas. This is an issue that has been discussed in the document called The Ioannina Recommendations, the expert guidelines published recently [1]. There is indeed concern about this issue and the need for more studies on the actual burden of this effect has been stressed. Regarding triple therapy, the editorial [2] is clear against it. What was underlined though was that convenience often reigns over science: two studies showed that both patients and physicians, even when informed, among others about the potential community risks of a rifampicin-containing double regimen, still preferred the convenient, inferior, all oral regimen of doxycycline and rifampicin [3,4]. Diagnostic progress has been made and will surely reach the developing countries in the near future [5]. The quest for a safer oral regimen is indeed a target to be pursued aggressively. Interventions at all medical and veterianrian levels of awareness could buy us some time though. References 1. Ariza J, Bosilkovski M, Cascio A, et al. Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations. PLoS Med. 2007;4:e317. 2. Pappas G. Editorial: Treatment of Brucellosis. BMJ. 2008;336:678-9. 3. Pappas G, Siozopoulou V, Akritidis N, Falagas ME. Doxycycline- rifampicin: physicians' inferior choice in brucellosis or how convenience reigns over science. J Infect. 2007;54:459-62 4.Pappas G, Siozopoulou V, Saplaoura K, et al. Health literacy in the field of infectious diseases: the paradigm of brucellosis. J Infect. 2007;54:40-5. 5. Franco MP, Mulder M, Gilman RH, Smits HL. Human Brucellosis. Lancet Inf Diseases. 2007;7:775-86. Competing interests: None declared |
|||
|
|
|||
|
Mile Bosilkovski, MD, specialist Infectious diseases Clinic for Infectious Diseases and Febrile Conditions, 1000, Skopje, FYROM, Jovanka Andonovska
Send response to journal:
|
Personally, I do not agree with the comment that “Brucellosis is notoriously difficult to diagnose” and that “Serological tests are not specifically sensitive…”, although one can’t neglect the drawbacks of these diagnostic procedures. Agglutination tests currently used in the diagnosis of brucellosis are very sensitive and specific, and brucellosis can be effectively excluded from the diseases having similar clinical features by the use of these tests (1).Also, these tests are mainly available in endemic regions of developing countries. The addition of Coombs and ELISA as diagnostic methods helps to overcome some of their weaknesses, improving the diagnosis and the management of the disease (2,3). Because of these reasons in the clinical practice (although theoretically possible): a) the probability of overlooking the diagnosis of brucellosis is very little, especially in endemic regions, where one has the disease always in mind; b) brucellosis is not a serious differential-diagnostic problem to tuberculosis. The clinical practice (from the literature and our own experience) rarely identifies both of the diseases in the same patient. Harris justifies the theoretical possibility that the extended use of rifampin in the treatment of brucellosis would increase the number of MDR Mycobacterium TB. What is the knowledge from the clinical practice, except the one quoted (4)? In the Republic of Macedonia, during the period of 1997-2007, over 4700 patients have been treated with brucellosis, out of which retreatment was given to approximately 15% due to relapses. In more than 85% of the treated patients, rifampin was used in the antibrucellar therapy. The available data of mycobacterial resistance toward rifampin during this period was as follows: 1997-2,9%, 1999-4,5%, 2000-3,3%, 2003- 4,1%, 2005-5,6%, 2007-4,3%. The clinical practice in the patients with brucellosis in this endemic region, so far, has indicated the need of frequent use of rifampin. A large portion of those patients suffer mild to moderate illness, avoid the parenteral route of drug application, need to be near their herds during the period of treatment, live miles away from the medical institutions. Which therapy can be advised for them, having in mind that only the tetracycline and rifampin (for now) have a proven activity in the acidic phagolysosomal environment (5)? Except that, the use of rifampin in the treatment of brucellosis in children, during pregnancy and in the cases of neurobrucellosis, cannot be avoided. References: 1. Mert A et al. The sensitivity and specificity of Brucella agglutination tests. Diagn Microbiol Inf Dis 2003;46:241-3. 2. Al-Dahouk S et al. Laboratory-based Diagnosis of Brucellosis- A review of the Literature. Clin Lab 2003;49:577-89. 3. Araj G. Human Brucellosis: A Classical Infectious Disease with Persistent Diagnostic Challenges. Clin Lab Sci 1999;12:207-12. 4. Al-Hajjaj MS et al. Progressive rise of Mycobacterium tuberculosis resistance to rifampicin and streptomycin in Riyadh, Saudi Arabia. Respirology. 2001;6:317–322. 5. Akova M, Gur D, Livermore DM et al.goz T, Livemore DM. In Vitro Activities of Antibiotics Alone and Combinations against Brucella melitensis at Neutral and Acidic pHs Levels. Antimicrob Agents Chemother 1999; 43:1298-300. Competing interests: None declared |
|||