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Doxycycline versus Azithromycin for Treatment of Leptospirosis (and Scrub Typhus)

http://jac.oxfordjourna
ls.org/content/59/1/14
8.full.pdf

Effect of timing and duration of azithromycin therapy of leptospirosis in a hamster model

Objectives: Azithromycin is not associated with significant adverse effects or restricted
usage in certain populations unlike standard antileptospirosis agents. In this study, the utility
of short courses of azithromycin in treating or preventing leptospirosis was investigated in a
lethal hamster model. Methods: All hamsters were infected intraperitoneally with 105
leptospires. In experiment one, animals received 5 mg/kg of doxycycline or 10 mg/kg of
azithromycin via intraperitoneal injection beginning on the second day after infection and
continuing once daily for 1, 2, 3 or 5 days. In experiment two, animals received 1 or 2 day
courses of azithromycin initiated 2 or 4 days following infection, or 4 days prior to infection.
Results: All untreated control animals died between the sixth and ninth day following
infection. In experiment one, survival rates in the doxycycline groups were 0, 50, 80 and
100% for those animals treated for 1, 2, 3 and 5 days, respectively. Except for the 1 day
treatment group (which had an 80% survival), there was 100% survival in all azithromycintreated groups. In experiment two, all animals treated after infection survived until study

ABSTRACT
Leptospirosis and scrub typhus are important causes of acute fever in Southeast Asia.
Options for empirical therapy include doxycycline and azithromycin, but it is unclear whether
their efficacies are equivalent. We conducted a multicenter, open, randomized controlled trial
with adult patients presenting with acute fever (<15 days), without an obvious focus of
infection, at four hospitals in Thailand between July 2003 and January 2005. Patients were
randomly allocated to receive either a 7-day course of doxycycline or a 3-day course of
azithromycin. The cure rate, fever clearance time, and adverse drug events were compared
between the two study groups. A total of 296 patients were enrolled in the study. The cause
of acute fever was determined for 151 patients (51%): 69 patients (23.3%) had leptospirosis;
57 patients (19.3%) had scrub typhus; 14 patients (4.7%) had murine typhus; and 11
patients (3.7%) had evidence of both leptospirosis and a rickettsial infection. The efficacy of
azithromycin was not inferior to that of doxycycline for the treatment of both leptospirosis
and scrub typhus, with comparable fever clearance times in the two treatment arms. Adverse
events occurred more frequently in the doxycycline group than in the azithromycin group
(27.6% and 10.6%, respectively; P = 0.02). In conclusion, doxycycline is an affordable and
effective choice for the treatment of both leptospirosis and scrub typhus. Azithromycin was
better tolerated than doxycycline but is more expensive and less readily available.

http://pajooheshi.maz
ums.ac.ir/Dorsapax/u
serfiles/file/pajoohesh
i/tabe
%20shalizar/36.pdf

http://medind.nic.in/ia
u/t06/i4/iaut06i4p345.
pdf

completion. No animals survived with 1 day of therapy started 4 days prior to infection while
only 20% survived if they received 2 days. Conclusions: These results suggest short-course
therapy with azithromycin, even started well after infection, is efficacious in preventing
mortality from acute leptospirosis.
Antibiotics have been used to treat leptospirosis since penicillin first became available. The
current choices of treatment for leptospirosis include penicillin, doxycycline, cefotaxime,
ceftriaxone and azithromycin. Penicillin has long been considered the treatment of choice.
Doxycycline is a reasonable alternative, but concerns exist regarding its use in all patients.
In milder cases, oral treatment with tetracycline, doxycycline, ampicillin, or amoxicillin
should be considered. For severe cases of Leptospirosis, intravenous administration of
penicillin G, amoxicillin, ampicillin, or erythromycin is recommended. One comparative trial
of the efficacy of ceftriaxone and penicillin for the treatment of severe Leptospirosis found
no significant differences between the two drugs in terms of complications or mortality rates.
Another open-label randomized study compared parenteral cefotaxime, penicillin G, and
doxycycline for the treatment of suspected severe Leptospirosis. Among 264 patients with
Leptospirosis confirmed by serologic testing or culture, the mortality rate was 5%. There
were no significant differences between antibiotics with regard to associated mortality,
defervescence, or time to resolution of abnormal laboratory findings. Thus doxycycline,
cefotaxime, or ceftriaxone is a satisfactory alternative to penicillin G for the treatment of
severe leptospirosis. Once-daily ceftriaxone has been shown to be as effective as penicillin.
A two-year study of the efficacy of azithromycin in the treatment of leptospirosis in humans

http://pcp.org.ph/dati/i
ndex.php?
option=com_content
&view=article&id=94
%3Aleptospirosis&ca
tid=64%3Apcpstatements

Philippine College of Physicians

Interim Recommendation on Clinical Recognition and Treatment of Leptospirosis (PSMID)
What antibiotics are recommended for patients suspected to have leptospirosis?
For mild leptospirosis, doxycycline (hydrochloride, hyclate) is the drug of choice. Alternative drugs include
amoxicillin and azithromycin dihydrate. For moderate-severe leptospirosis, penicillin G remains the drug of
choice. Alternative drugs include parenteral ampicillin, 3rd generation cephalosporin (cefotaxime, ceftriaxone),
and parenteral azithromycin dihydrate. Antibiotic therapy should be completed for 7 days, except for
azithromycin dihydrate which could be given for 3 days.

Hunter's Tropical Medicine and Emerging Infectious Disease

http://journals.plos.or
g/plosntds/article?
id=10.1371%2Fjourn
al.pntd.0000610

http://onlinelibrary.wil
ey.com/doi/10.1002/1
4651858.CD008264.
pub2/abstract;jsessio
nid=252A985B0EAA
B602DC4044828A16
B0C5.f02t01?
userIsAuthenticated=
false&deniedAccess

Strategies for Diagnosis and Treatment of Suspected Leptospirosis: A Cost-Benefit Analysis (2010 study)
Empirical doxycycline treatment was the most efficient strategy, being both the least costly alternative and the
one that resulted in the shortest duration of fever. The limited sensitivity of all three diagnostic tests implied that
their use to guide treatment was not cost-effective. The most influential parameter driving these results was the
cost of treating patients with complications for patients who did not receive adequate treatment as a result of
incorrect diagnosis or a strategy of no-antibiotic-treatment.
012 study: Antibiotics for leptospirosis
David M Brett-Major1,*, Rodney Coldren2
Editorial Group: Cochrane Hepato-Biliary Group
Insufficient evidence is available to advocate for or against the use of antibiotics in the therapy for leptospirosis.
Among survivors who were hospitalised for leptospirosis, use of antibiotics for leptospirosis may have decreased
the duration of clinical illness by two to four days, though this result was not statistically significant. When
electing to treat with an antibiotic, selection of penicillin, doxycycline, or cephalosporin does not seem to impact
mortality nor duration of fever. The benefit of antibiotic therapy in the treatment of leptospirosis remains unclear,

Received
25 July
2012
Accepted
10 Sept.
2012
Available
online 01
October
2012

CustomisedMessage

particularly for severe disease. Further clinical research is needed to include broader panels of therapy tested
against placebo.

http://www.ijarst.com/
journals/Volume
%201_Issue1/IJARS
T-01-01-03.pdf

Every disease can be cured if its roots are traced; means there is cure for every disease.
Leptospirosis is a hidden and emerging public health problem as it causes fever, acute renal
failure and jaundice. The major outer membrane lipoprotein LipL32 is expressed during
infection which is highly conserved among pathogenic leptospira. It is absent in nonpathogenic avirulent leptospira. Insilico comparison of amino acid sequences of LipL32
showed 97.8% average sequence identity among the pathogenic species. In this study
some 3D model were built for LipL32 protein using molecular modelling. Protein
hydrophobicity plots were utilized to locate the antigenic sites. Docking studies of retrieved
structures and modeled LipL32 proteins with doxycycline revealed that doxycycline can
inhibit LipL32 proteins of Leptospira santarosai, Leptospira weilii and Leptospira kirschner
as they have bound docking with doxycycline. They share a common pharmacopore within
a genus and a common drug may be utilized to combat all the related species.