Bichat guidelines for the clinical management of tularaemia and bioterrorism-related tularaemia

Bossi, Philippe; Tegnell, Anders; Baka, A; Loock, F van; Werner, A; Hendriks, J.; Maidhof, H; Gouvras, G

doi:10.2807/esm.09.12.00503-en

Cited by 29 publications

(45 citation statements)

References 11 publications

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“…and oral) and 14 to 21 days for doxycycline (i.v. and oral); oral options are used when clinically indicated or for PEP (2,22). TP-271 is currently in phase 1 clinical development, evaluating safety and exposures in healthy volunteers when administered i.v.…”

Section: Discussionmentioning

confidence: 99%

The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Francisella tularensis SCHU S4 Infection in BALB/c Mice and Cynomolgus Macaques

Grossman

Anderson

Christ³

et al. 2017

Antimicrob Agents Chemother

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TP-271 is a novel, fully synthetic fluorocycline in development for complicated bacterial respiratory infections. TP-271 was active in vitro against a panel of 29 Francisella tularensis isolates, showing MICs against 50% and 90% of isolates of 0.25 and 0.5 g/ml, respectively. In a mouse model of inhalational tularemia, animals were exposed by aerosol to 91 to 283 50% lethal doses (LD 50 )/mouse of F. tularensis SCHU S4. Following 21 days of once-daily intraperitoneal dosing with TP-271 at 3, 6, 12, and 18 mg/kg of body weight/day, initiating at 24 h postchallenge, survival was 80%, 100%, 100%, and 100%, respectively. When treatment was initiated at 72 h postchallenge, survival was 89%, 100%, 100%, and 100% in the 3-, 6-, 12-, and 18-mg/kg/day TP-271 groups, respectively. No mice treated with the vehicle control survived. Surviving mice treated with TP-271 showed little to no relapse during 14 days posttreatment. In a nonhuman primate model of inhalational tularemia, cynomolgus macaques received an average aerosol exposure of 1,144 CFU of F. tularensis SCHU S4. Once-daily intravenous infusion with 1 or 3 mg/kg TP-271, or vehicle control, for 21 days was initiated within 6 h of confirmed fever. All animals treated with TP-271 survived to the end of the study, with no relapse during 14 days after the last treatment, whereas no vehicle control-treated animals survived. The protection and low relapse afforded by TP-271 treatment in these studies support continued investigation of TP-271 for use in the event of aerosolized exposure to F. tularensis.KEYWORDS TP-271, fluorocycline, tularemia, Francisella tularensis F rancisella tularensis, the causative agent of tularemia, is a small aerobic nonmotile Gram-negative coccobacillus capable of causing the zoonotic disease tularemia, naturally spread among mammals by ticks, flies, and mosquitoes (1, 2). Humans can become infected with F. tularensis by insect bites, handling infectious animal materials, direct contact with or ingestion of contaminated water, food, or soil, and inhalation of infective aerosols. Inhalation of as few as 10 organisms can cause disease, making F. tularensis subsp. tularensis (type A subspecies) one of the most infectious pathogenic bacteria known and a likely agent for a bioterrorist attack (3). Accordingly, this pathogen is categorized as a priority category A (tier 1) threat agent by the Centers for Disease Control and Prevention (CDC) because of the high likelihood that F. tularensis will be used as a bioweapon (2).Inhalation of F. tularensis bacteria causes pneumonia, respiratory failure, shock, and a high incidence of mortality (2, 4). Aerosol dispersion of F. tularensis is predicted to be

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Section: Discussionmentioning

confidence: 99%

The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Francisella tularensis SCHU S4 Infection in BALB/c Mice and Cynomolgus Macaques

Grossman

Anderson

Christ³

et al. 2017

Antimicrob Agents Chemother

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“…This highly infectious bacterial pathogen can be transmitted to humans in numerous ways (4), including direct contact with sick animals, inhalation, ingestion of contaminated water or food, or bites from ticks, mosquitoes, or flies. Four different subspecies of F. tularensis that differ in virulence and geographic distribution exist, designated F. tularensis subsp.…”

mentioning

confidence: 99%

Identification of a Putative Chaperone Involved in Stress Resistance and Virulence in Francisella tularensis

et al. 2011

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Francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularemia. This facultative intracellular bacterium replicates in vivo mainly inside macrophages and therefore has developed strategies to resist this stressful environment. Here, we identified a novel genetic locus that is important for stress resistance and intracellular survival of F. tularensis. In silico and transcriptional analyses suggest that this locus (genes FTL_0200 to FTL_0209 in the live vaccine strain [LVS]) constitutes an operon controlled by the alternative sigma factor 32 . The first gene, FTL_0200, encodes a putative AAA؉ ATPase of the MoxR subfamily. Insertion mutagenesis into genes FTL_0200, FTL_0205, and FTL_0206 revealed a role for the locus in both intracellular multiplication and in vivo survival of F. tularensis. Deletion of gene FTL_0200 led to a mutant bacterium with increased vulnerability to various stress conditions, including oxidative and pH stresses. Proteomic analyses revealed a pleiotropic impact of the ⌬FTL_0200 deletion, supporting a role as a chaperone for FTL_0200. This is the first report of a role for a MoxR family member in bacterial pathogenesis. This class of proteins is remarkably conserved among pathogenic species and may thus constitute a novel player in bacterial virulence.

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“…Vol. 63,2006 Multi-author Review Article 2205 of as few as 10 organisms to initiate human infection [43,44]. Tularaemia is distributed worldwide but occurs especially in the northern hemisphere, in Europe, North America, the Middle East, the former Soviet Union, China and Japan.…”

Section: Tularaemiamentioning

confidence: 99%

Biological weapons

Bossi

Garín²,

Guihot

et al. 2006

Cell. Mol. Life Sci.

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Bioterrorism is defined by the intentional or threatened of microorganisms or toxins derived from living organisms to cause death or diseases in humans, animals or plants on which we depend. The other major point is to generate fear in the population. More than 180 pathogens have been reported to be potential agents for bioterrorism. The following is an overview of several agents that could be involved in a biological attack.

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Bichat guidelines for the clinical management of tularaemia and bioterrorism-related tularaemia

Cited by 29 publications

References 11 publications

The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Francisella tularensis SCHU S4 Infection in BALB/c Mice and Cynomolgus Macaques

The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Francisella tularensis SCHU S4 Infection in BALB/c Mice and Cynomolgus Macaques

Identification of a Putative Chaperone Involved in Stress Resistance and Virulence in Francisella tularensis

Biological weapons

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