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RESEARCH: Keren Skalsky, Dafna Yahav, Jihad Bishara, Silvio Pitlik, Leonard Leibovici, and Mical Paul Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials BMJ 2008; 336: 701-704 [Abstract] [Full text]

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Treatment of brucellosis nowadays

Mile Bosilkovski, Marija Dimzova   (17 April 2008)

Treatment of brucellosis nowadays 17 April 2008
Mile Bosilkovski, MD, specialist Infectious diseases Clinic for Infectious Diseases and Febrile Conditions, 1000, Skopje, FYROM, Marija Dimzova Send response to journal: Re: Treatment of brucellosis nowadays	We are all aware that prompt beginning and appropriate implementation of the treatment of human brucellosis is one of the most important (unfortunately, not always the sine qua non) factor which determines the symptoms and complications of the disease, prevents the emergence of relapses and progression to chronic disease. Nowadays, there are well defined principles for treatment of brucellosis, which are based upon extended employment of combined antimicrobial agents, having in mind that there must be an antimicrobial agent/s which exhibit good intracellular penetration and efficacy in intracellular milieu of low pH (1). In spite of this, the dilemmas surrounding the treatment of human brucellosis are constantly re-emerging, more as a result of the aspiration for improving the existing results (to reduce the rates of therapeutic failure and relapses), without neglecting the commodity of the patients (safety of the drugs, the way of administration, compliance) and the optimal economic effects (cost-benefit) of the treatment. The 1986 WHO declaration was a major breakthrough of the existing knowledge on the disease, and gave valuable guidelines how to treat the illness. Twenty years later, in Ioannina, 2006, the guiding principles about brucellosis (2) were modified and shaped by established clinicians from various parts of the world with the aspiration to incorporate the additional knowledge (mostly based upon personal experiences). As was expected, numerous modifications of the treatment existed and will further exist in different regions of the globe, depending upon the economic, political and social situation, mentality of the population, the ability and motivation for continuing medical education and implementation of new facts about the disease, as well as on personal clinical experience, without neglecting the tradition and the ego of the physicians. The manuscript by Skalsky K et al (3) is impressively designed and analyzed; still we see it as a presumptuous attempt to recommend some options in the treatment of brucellosis for which there is still not enough relevant knowledge. The triple antimicrobial therapy (not well defined which antimicrobials and at times combined with surgical treatment) nowadays is only used in treatment of certain well defined conditions in human brucellosis (endocarditis, neurobrucellosis, abscess forms..). In the “Recommendations for the treatment of uncomplicated brucellosis...of the current study” for first line regimen is recommended doxycycline 6 weeks+rifampicin 6 weeks+gentamicin 2 weeks or doxycycline 6 weeks+gentamicin 2 weeks”. This study does not indicate not one previous manuscript with this kind of triple therapeutic regimen which comprises the conditions mentioned in their recommendations: a) treatment which lasts for 6 weeks; b) gentamicin as an aminoglycoside choice; c) use of gentamicin for two weeks. We presume that the authors recall upon the results gathered in two research studies (4, 5), but in these studies the aminoglycoside used were streptomycin and amikacin, respectively. By the way, the first study elaborates patients with brucellar spondylitis (a serious complication) which was treated for ONLY 6 weeks, while the treatment in the second study was designed for 8 weeks duration. In most of the studies where gentamicin used, was applied for 7 days. In addition, in today’s era of antimicrobial drugs to recommend that “tetracycline 6 weeks+…” as is done in “Second line regimen” is nonsence considering all pharmacodynamic, pharmacokinetic characteristics, adverse reactions, cost and availability of doxycycline. At the end, we think that the well known facts for at least two decades that “doxycycline-aminoglycoside regimens are superior to doxycycline-rifampicin”, and “six weeks treatment is associated with a lower rate of relapse than shorter regimens” represent only “What this study confirms” and in no way “What this study adds”. References 1. Pappas G, Akritidis N, Tsianos E. Effective treatments in the management of brucellosis. Expert Opin Pharmacother. 2005;6(2):201-9. 2. Ariza J, Bosilkovski M, Cascio A, Colmenero JD, Corbel MJ, Falagas ME, et al. Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations. PLoS Med. 2007;4(12):e317. 3. Skalsky K, Yahav D, Bishara J, Pitlik S, Leibovici L, Paul M. Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials. BMJ. 2008;336(7646):701-4. 4. Bayindir Y, Sonmez E, Aladag A, Buyukberber N. Comparison of five antimicrobial regimens for the treatment of brucellar spondylitis: a prospective, randomized study. J Chemother. 2003;15(5):466-71. 5. Ranjbar M, Keramat F, Mamani M, Kia AR, Khalilian FO, Hashemi SH, Nojomi M. Comparison between doxycycline-rifampin-amikacin and doxycycline -rifampin regimens in the treatment of brucellosis. Int J Infect Dis. 2007;11(2):152-6. Competing interests: MB is one of the authors of the work (2) cited in refferences