An Open, Randomized, Controlled Trial of Penicillin, Doxycycline, and Cefotaxime for Patients with Severe Leptospirosis

Suputtamongkol, Yupin; Niwattayakul, Kanigar; Suttinont, Chuanpit; Losuwanaluk, Kitti; Limpaiboon, Roongroeng; Chierakul, Wirongrong; Wuthiekanun, Vanaporn; Triengrim, Surapee; Chenchittikul, Mongkol; White, Nicholas J.

doi:10.1086/425001

Cited by 168 publications

(113 citation statements)

References 24 publications

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“…28 However, in several studies reporting serologic surveys in local populations in Southeast Asia, serogroup Icterohaemorrhagiae was not shown to be the dominant serogroup. [29][30][31][32] Leptospirosis was seen as multi-organ failure and a potentially life-threatening disease in many of our patients. This type of manifestation was significantly more common in patients presumptively infected with serogroup Icterohaemorrhagiae.…”

Section: Discussionmentioning

confidence: 87%

Travel-Related Leptospirosis in Israel: A Nationwide Study

Leshem¹,

Segal²,

Barnea³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Abstract. Leptospirosis is re-emerging in developed countries as a travel-related infection. In this nationwide study of travel-related leptospirosis in Israel, all cases diagnosed at the Central Reference Laboratory for Leptospirosis, during 2002Leptospirosis, during -2008 were retrospectively reviewed and only travel-related cases were included. During the study years, 20 (42%) of 48 leptospirosis cases in Israel were travel-related. Exposure occurred in Southeast Asia in 15 (75%) of 20 cases. The estimated yearly incidence of travel-related leptospirosis was 1.78/100,000 travelers compared with an incidence of endemic cases of 0.06/100,000 inhabitants (risk ratio = 29.6, 95% confidence interval = 16.7-52.4). Most patients (89%) were infected during water-related activities. Severe disease was present in 10 (55%) of 18 patients; 7 of them were presumptively infected with the Icterohaemorrhagiae serogroup. Thus, travel-related leptospirosis is becoming increasingly important in the epidemiology of leptospirosis in Israel. Leptospirosis should be suspected in any traveler with undifferentiated febrile illness, especially when water exposure is reported.

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Section: Discussionmentioning

confidence: 87%

Travel-Related Leptospirosis in Israel: A Nationwide Study

Leshem¹,

Segal²,

Barnea³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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“…These samples were collected as part of studies investigating the causes of fever. 4,7 This clinical study was approved by the Ethical Review Subcommittee of the Public Health Ministry of Thailand, and Siriraj Institutional Review Board Faculty of Medicine Siriraj Hospital, Mahidol University.…”

Section: Methodsmentioning

confidence: 99%

“…For this study, the diagnosis of scrub typhus was confirmed by either 1) nested polymerase chain reaction (PCR) detection of the 16S ribosomal RNA gene or 56-kD protein gene 8,9 ; or 2) IFA detection of an IgM O. tsutsugamushi titer 1:400 or a 4-fold increase in IFA IgM titer, or an IgG titer 1:800 or a 4-fold increase in IFA IgG titer. 7,8 Non-scrub typhus patient samples. Serum samples (n = 62) from patients with laboratory-confirmed diagnosis of other tropical febrile illness were collected at the same study hospitals.…”

Section: Methodsmentioning

confidence: 99%

Development of New, Broadly Reactive, Rapid IgG and IgM Lateral Flow Assays for Diagnosis of Scrub Typhus

Silpasakorn¹,

Srisamut²,

Ekpo³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. We evaluated the diagnostic accuracy of two broadly reactive rapid immunochromatographic tests (ICTs) for detection of IgM and IgG against Orientia tsutsugamushi by using archived acute-phase serum samples from 102 patients with laboratory-confirmed scrub typhus, and from 62 archived serum samples from patients with other causes of fever as a negative control. These ICTs were constructed by using a mixture of recombinant proteins: 1) C1, a chimeric protein containing epitopes of the 56-kD antigen from Karp and TA763 strains; 2) Ktr56; and 3) Gmr56. Sensitivities of the ICTs for detection of IgM and IgG were 90.2% (95% confidence interval [CI] = 84.4-96.0%) and 86.3% (95% CI = 80.9-93.8%), respectively. Specificities were 85.5% (95% CI = 73.9-92.2%) and 96.8% (95% CI = 90.3-100%), respectively. Both assays were more sensitive and specific than the standard immune immunofluorescence assay for the early diagnosis of scrub typhus.

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“…6 Subsequent clinical trials from Thailand support the use of ceftriaxone, cefotaxime, and azithromycin as well in this zoonotic infection. [7][8][9] Intravenous third generation cephalosporins have become the preferred agents for severe leptospirosis based on their proven efficacy, ease of use, availability, and ability to cover other etiologies of acute febrile illness when the diagnosis is in doubt. The potential efficacy of other cephalosporins in leptospirosis is less clear.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Activity of First Generation Cephalosporins Against Leptospira

Harris

Blatz²,

Hinkle³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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Third generation cephalosporins are commonly used in the treatment of leptospirosis. The efficacy of first generation cephalosporins has been less well-studied. Susceptibility testing of 13 Leptospira strains (11 serovars) to cefazolin and cephalexin was conducted using broth microdilution. Median minimal inhibitory concentration (MIC) for cefazolin and cephalexin ranged from < 0.016 to 2 μg/mL (MIC90 = 0.5 μg/mL) and from 1 to 8 μg/mL (MIC90 = 8 μg/mL), respectively. Efficacy of cefazolin and cephalexin in an acute lethal hamster model of leptospirosis was studied. Survival rates for cefazolin were 80%, 100%, and 100%, and survival rates for cephalexin were 50%, 80%, and 100% (treated with 5, 25, and 50 mg/kg per day for 5 days, respectively). Each treatment group showed improved survival compared with no treatment (P < 0.01), and none of the therapies, regardless of dose, was statistically significantly different than doxycycline. These results support a potential role for first generation cephalosporins as alternative therapies for leptospirosis.

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An Open, Randomized, Controlled Trial of Penicillin, Doxycycline, and Cefotaxime for Patients with Severe Leptospirosis

Abstract: Doxycycline or cefotaxime is a satisfactory alternative to penicillin G for the treatment of severe leptospirosis.

Cited by 168 publications

References 24 publications

Travel-Related Leptospirosis in Israel: A Nationwide Study

Travel-Related Leptospirosis in Israel: A Nationwide Study

Development of New, Broadly Reactive, Rapid IgG and IgM Lateral Flow Assays for Diagnosis of Scrub Typhus

In Vitro and In Vivo Activity of First Generation Cephalosporins Against Leptospira

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