Abstract
The Centers for Disease Control and Prevention (CDC) recommend oral or intravenous doxycycline plus a third-generation cephalosporin or fluoroquinolone alone for the treatment of Vibrio vulnificus infections. Until now, no study has compared oral with parenteral administered doxycycline with respect to their in vivo efficacy. In the present work, ICR mice infected with a high dose of V. vulnificus were administered ciprofloxacin, ceftriaxone, and doxycycline. The bacterial DNA copy number in surviving and non-surviving mice was determined using quantitative polymerase chain reaction (qPCR). In this setting, ciprofloxacin was the most effective monotherapeutic drug, but a higher survival rate (50%) was achieved using the combination therapy of intraperitoneal doxycycline plus ceftriaxone. The blood of non-surviving mice at 12 h post-infection contained at least 104 DNA copies/μL, in contrast to 102 to 103 DNA copies/μL in surviving mice. Thus, in the treatment of V. vulnificus infections in humans, when the intravenous form of doxycycline is unavailable, ciprofloxacin might be a better option than oral doxycycline to lower mortality. In addition, our results demonstrate that qPCR can be a useful tool for identifying the V. vulnificus load in infected patients, with the DNA copy number providing a marker of either disease severity or mortality.
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References
Bross MH, Soch K, Morales R, Mitchell RB (2007) Vibrio vulnificus infection: diagnosis and treatment. Am Fam Physician 76(4):539–544
Neupane GP, Kim DM (2009) Comparison of the effects of Deferasirox, deferiprone, and deferoxamine on the growth and virulence of Vibrio vulnificus. Transfusion 49:1762–1769
Starks AM, Schoeb TR, Tamplin ML, Parveen S, Doyle TJ, Bomeisl PE, Escudero GM, Gulig PA (2000) Pathogenesis of infection by clinical and environmental strains of Vibrio vulnificus in iron-dextran-treated mice. Infect Immun 68:5785–5793
Chiang SR, Chuang YC (2003) Vibrio vulnificus infection: clinical manifestations, pathogenesis, and antimicrobial therapy. J Microbiol Immunol Infect 36(2):81–88
Wormser GP, Halperin JJ (2008) Oral doxycycline for neuroborreliosis. Lancet Neurol 7:665–666
Oliver JD (2005) Wound infections caused by Vibrio vulnificus and other marine bacteria. Epidemiol Infect 133:383–391
Centers for Disease Control and Prevention (CDC) (1993) Vibrio vulnificus infections associated with raw oyster consumption—Florida, 1981–1992. MMWR Morb Mortal Wkly Rep 42(21):405–407. Available online at: http://www.cdc.gov/mmwr/preview/mmwrhtml/00020736.htm. Accessed October 12, 2010
Neupane GP, Kim DM (2010) In vitro time–kill activities of ciprofloxacin alone and in combination with the iron chelator Deferasirox against Vibrio vulnificus. Eur J Clin Microbiol Infect Dis 29:407–410
Bowdre JH, Hull JH, Cocchetto DM (1983) Antibiotic efficacy against Vibrio vulnificus in the mouse: superiority of tetracycline. J Pharmacol Exp Ther 225(3):595–598
Morris JG Jr, Tenney JH, Drusano GL (1985) In vitro susceptibility of pathogenic Vibrio species to norfloxacin and six other antimicrobial agents. Antimicrob Agents Chemother 28:442–445
Morris JG Jr, Black RE (1985) Cholera and other vibrioses in the United States. N Engl J Med 312:343–350
Tang HJ, Chang MC, Ko WC, Huang KY, Lee CL, Chuang YC (2002) In vitro and in vivo activities of newer fluoroquinolones against Vibrio vulnificus. Antimicrob Agents Chemother 46:3580–3584
Kim DM, Lym Y, Jang SJ, Han H, Kim YG, Chung CH, Hong SP (2005) In vitro efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus. Antimicrob Agents Chemother 49:3489–3491
Chiang SR, Tang HJ, Chang PC, Cheng KC, Ko WC, Chen CH, Chuang YC (2007) Synergistic antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of Vibrio vulnificus infection. J Microbiol Immunol Infect 40:123–133
Liu JW, Lee IK, Tang HJ, Ko WC, Lee HC, Liu YC, Hsueh PR, Chuang YC (2006) Prognostic factors and antibiotics in Vibrio vulnificus septicemia. Arch Intern Med 166(19):2117–2123
Reed LJ, Muench H (1938) A simple method of estimating fifty per cent endpoints. Am J Hyg 27(3):493–497
Takahashi H, Hara-Kudo Y, Miyasaka J, Kumagai S, Konuma H (2005) Development of a quantitative real-time polymerase chain reaction targeted to the toxR for detection of Vibrio vulnificus. J Microbiol Methods 61(1):77–85
Kim HS, Kim DM, Neupane GP, Lee YM, Yang NW, Jang SJ, Jung SI, Park KH, Park HR, Lee CS, Lee SH (2008) Comparison of conventional, nested, and real-time PCR assays for rapid and accurate detection of Vibrio vulnificus. J Clin Microbiol 46:2992–2998
Wang S, Levin RE (2006) Discrimination of viable Vibrio vulnificus cells from dead cells in real-time PCR. J Microbiol Methods 64:1–8
Lee JL, Levin RE (2009) Discrimination of viable and dead Vibrio vulnificus after refrigerated and frozen storage using EMA, sodium deoxycholate and real-time PCR. J Microbiol Methods 79:184–188
Rhee JH, Choi SN, Chung SS (1987) Bactericidal activity of tetracycline against Vibrio vulnificus. J Korean Med Assoc 30:769–777
Deppermann KM, Lode H, Höffken G, Tschink G, Kalz C, Koeppe P (1989) Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin–clavulanic acid. Antimicrob Agents Chemother 33(11):1901–1907
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The present study was supported by grants from the Clinical Medicine Research Institute at Chosun University Hospital (2008).
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Neupane, G.P., Kim, DM., Yun, N.R. et al. Quantitative PCR and in vivo efficacy of antibiotics in the treatment of Vibrio vulnificus infection in a mouse model. Eur J Clin Microbiol Infect Dis 31, 2461–2467 (2012). https://doi.org/10.1007/s10096-012-1592-z
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DOI: https://doi.org/10.1007/s10096-012-1592-z