Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trialsBMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39497.500903.25 (Published 27 March 2008) Cite this as: BMJ 2008;336:701
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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”.
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.
MB is one of the authors of the work (2) cited in refferences
Competing interests: No competing interests