Treatment of murine pneumonic Francisella tularensis infection with gatifloxacin, moxifloxacin or ciprofloxacin

Steward, J.; Piercy, T.; Lever, Mark S.; Simpson, Andrew J. H.; Brooks, Timothy

doi:10.1016/j.ijantimicag.2006.02.006

Cited by 23 publications

(20 citation statements)

References 24 publications

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“…Animal models of tularemia have principally been developed in the mouse and have proved to be very helpful tools in elucidating several aspects of disease pathogenesis, including the characterization of innate and adaptive immunity to F. tularensis, in testing the efficacy of antibiotics and other therapies (30,32,33,39) and vaccine candidates against the disease (7,13,34). Various methods of inducing disease have been used, and the respiratory route is of particular interest (11,42) due to the severity of pneumonic tularemia and the impact that aerosol spread might have in a bioterrorist attack.…”

Section: Discussionmentioning

confidence: 99%

Identification of Immunologic and Pathologic Parameters of Death versus Survival in Respiratory Tularemia

et al. 2008

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Francisella tularensis can cause severe disseminated disease after respiratory infection. The identification of factors involved in mortality or recovery following induction of tularemia in the mouse will improve our understanding of the natural history of this disease and facilitate future evaluation of vaccine candidate preparations. BALB/c mice were infected intranasally with the live vaccine strain (LVS) of F. tularensis subsp. holarctica and euthanized at different stages of disease to analyze the induction of immune molecules, gross anatomical features of organs, bacterial burdens, and progression of the histopathological changes in lung and spleen. Tissue-specific interleukin-6 (IL-6), macrophage inflammatory protein 2, and monocyte chemotactic protein 1 were immune markers of mortality, while anti-LVS immunoglobulin M and IL-1␤ were associated with survival. Moribund mice had enlarged spleens and lungs, while surviving mice had even more prominent splenomegaly and normal-appearing lungs. Histopathology of the spleens of severely ill mice was characterized by disrupted lymphoid follicles and fragmented nuclei, while the spleens of survivors appeared healthy but with increased numbers of megakaryocytes and erythrocytes. Histopathology of the lungs of severely ill mice indicated severe pneumonia. Lungs of survivors at early time points showed increased inflammation, while at late times they appeared healthy with peribronchial lymphoid aggregates. Our results suggest that host immune factors are able to affect bacterial dissemination after respiratory tularemia, provide new insights regarding the pathological characteristics of pulmonary tularemia leading to systemic disease, and potentially identify immune markers associated with recovery from the disease.

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Section: Discussionmentioning

confidence: 99%

Identification of Immunologic and Pathologic Parameters of Death versus Survival in Respiratory Tularemia

et al. 2008

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“…However, perhaps somewhat surprisingly, a single dose of oral ciprofloxacin also gave full protection against F. tularensis LVS, preventing differentiation between the efficacies of the antibiotics given by either route of administration. Oral ciprofloxacin treatment for 14 days does not fully protect against F. tularensis Schu S4 infection in mice (3), suggesting that the efficacy of the short treatment regimen used in this study against LVS does not reflect the efficacy against more virulent F. tularensis strains. The shortcomings of F. tularensis LVS as a model for understanding the gene function of more virulent strains has been highlighted previously (25).…”

Section: Discussionmentioning

confidence: 70%

“…Ideally, this prophylaxis would be highly effective and could be taken by patients without medical supervision. The currently recommended prophylactic options, oral ciprofloxacin and oral doxycycline, although easy to administer, have been associated with relapse in murine prophylaxis studies (3,23) and in some cases of human therapy (4,6). Therefore, there is the need for a new antibiotic, or a new presentation of an existing antibiotic, such as an alternative formulation and administration method, that can offer a higher level of protection against F. tularensis without the need for delivery by injection.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, the recommended F. tularensis prophylaxis is orally delivered ciprofloxacin or doxycycline for 14 days (1). However, in a murine model of pneumonic F. tularensis Schu S4 infection, 14 days of oral ciprofloxacin therapy resulted in all treated mice succumbing to the infection after the treatment regimen had finished (3). In addition, relapse has been reported in humans treated with ciprofloxacin or doxycycline (4).…”

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confidence: 99%

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Liposome Encapsulation of Ciprofloxacin Improves Protection against Highly Virulent Francisella tularensis Strain Schu S4

Hamblin

Armstrong

Barnes

et al. 2014

Antimicrob Agents Chemother

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c Liposome-encapsulated ciprofloxacin for inhalation (CFI) was investigated as a putative postexposure therapeutic for two strains of Francisella tularensis. The efficacies of oral ciprofloxacin and intranasally instilled CFI could not be distinguished in a mouse model of infection with the F. tularensis live vaccine strain (LVS), where a single dose of either formulation offered full protection against a lethal challenge. However, mouse studies with the more virulent Schu S4 strain of F. tularensis demonstrated that a higher level of protection against a lethal aerosol infection is provided by CFI than by oral ciprofloxacin. In addition, using this infection model, it was possible to discriminate the efficacy of intranasally instilled CFI from that of aerosolized CFI, with aerosolized CFI providing full protection after just a single dose. The improved efficacy of CFI compared to oral ciprofloxacin is likely due to the high sustained concentrations of ciprofloxacin in the lung. In summary, CFI may be a promising therapy, perhaps enabling the prophylactic regimen to be shortened, for use in the event of a deliberate release of F. tularensis. The prophylactic efficacy of CFI against other biological warfare (BW) threat agents also warrants investigation.

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“…Studies in mice have verified the successful use of fluoroquinolones in treating experimental tularemia, [69] including newer fluoroquinolones such as gatifloxacin and moxifloxacin [73,74]. One retrospective review described the successful treatment of 41 out of 43 patients with ciprofloxacin during a tularemia outbreak in Sweden [75].…”

Section: Review Hepburn and Simpsonmentioning

confidence: 99%

Tularemia: current diagnosis and treatment options

Hepburn

Simpson

2008

Expert Review of Anti-infective Therapy

115

117

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Tularemia is an infection caused by Francisella tularensis with a worldwide distribution and diverse clinical manifestations. Limitations in both culture and serologic testing have led to substantial research into new diagnostic techniques and their clinical application, with PCR testing as the best example. This review focuses on the utility of culture, PCR and serologic testing for tularemia. In addition, we also review the evidence to support different therapeutic options for tularemia, highlighting both the most effective supporting evidence for therapeutic recommendations as well as gaps in current knowledge. We conclude the article with suggestions regarding potential areas for future research.

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Treatment of murine pneumonic Francisella tularensis infection with gatifloxacin, moxifloxacin or ciprofloxacin

Cited by 23 publications

References 24 publications

Identification of Immunologic and Pathologic Parameters of Death versus Survival in Respiratory Tularemia

Identification of Immunologic and Pathologic Parameters of Death versus Survival in Respiratory Tularemia

Liposome Encapsulation of Ciprofloxacin Improves Protection against Highly Virulent Francisella tularensis Strain Schu S4

Tularemia: current diagnosis and treatment options

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