\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{Biofilm-Associated Candidal Thrombophlebitis}



\author[1]{Shinnosuke Fukushima}%
\author[2]{Koichiro Yamamoto}%
\author[2]{Yasuhiro  Nakano}%
\author[3]{Hideharu Hagiya}%
\author[4]{Fumio Otsuka}%
\affil[1]{Okayama University}%
\affil[2]{Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences}%
\affil[3]{Okayama University Hospital}%
\affil[4]{Okayama Daigaku - Shikata Campus}%


\vspace{-1em}



  
  \date{June 03, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Candidemia is possibly complicated with a biofilm formation, and the
mortality rate of biofilm-associated candidemia is reported very high.
Herein, we described candida biofilm-related thrombophlebitis, which was
successfully treated with micafungin. This case suggested that biofilm
targeted therapy may be warranted in the presence of thrombus formation.%
\end{abstract}%



\sloppy


Case Image

\textbf{Biofilm-Associated Candidal Thrombophlebitis}

Shinnosuke Fukushima\textsuperscript{1}, Koichiro
Yamamoto\textsuperscript{1}, Yasuhiro Nakano\textsuperscript{1},
Hideharu Hagiya\textsuperscript{1}\#, Fumio Otsuka\textsuperscript{1}

\textsuperscript{1}Department of General Medicine, Okayama University
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,
2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan.

\textbf{\#Corresponding author}

Hideharu Hagiya. M.D., Ph.D.

Department of General Medicine, Okayama University Graduate School of
Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho,
Kitaku, Okayama 700-8558, Japan. Phone number: +81-86-234-7342, Fax
number: +81-86-234-7345

E-mail address: \emph{hagiya@okayama-u.ac.jp}

\textbf{Keywords:} biofilm, thrombophlebitis, \emph{Candida albicans} ,
central-line associated bloodstream infection, candidemia

\textbf{Author Contributions} : SF and YN contributed to patient care.
SF wrote the manuscript, and KY and HH revised, and FO organized it.

\textbf{Conflicts of interest}

No authors have any competing interests in this case.

\textbf{Informed Consent}

Written informed consent was obtained from the patient to publish this
case report.

\textbf{Case}

A 45-year-old Japanese woman receiving parenteral nutrition via a
peripherally inserted central catheter (PICC) was hospitalized for
hypopharyngeal cancer. Blood culture detected \emph{Candida albicans}and
plain computed tomography (CT) revealed gas production surrounding the
catheter in the brachiocephalic vein (\textbf{Figure 1a} ). We extracted
the PICC and administered fosfluconazole, but candidemia persisted for 2
weeks. A follow-up contrast-enhanced CT showed the disappearance of gas
while a blood clot remained (\textbf{Figure 1b} ). Considering candida
biofilm-related thrombophlebitis, we additionally administered
micafungin and the recurrent candidemia promptly withdrew with a good
clinical course thereafter.

Biofilm-associated candidemia is rare but possibly results in a high
mortality rate estimated at at aroud 70\% {[}1{]}. Candida biofilm
provides resistance to azole-class antifungals, wherein treatment with
echinocandins or amphotericin B is reportedly promising {[}2{]}.
Clinical course of the present case suggested the effectiveness of
micafungin treatment in candidal thrombophlebitis, with which biofilm
formation was associated. In case candidemia persisted with thrombus
formation, a candida biofilm targeted therapy may be required.

\textbf{References}

{[}1{]} Atiencia-Carrera MB, Cabezas-Mera FS, Tejera E, Machado A.
Prevalence of biofilms in Candida spp. bloodstream infections: A
meta-analysis. PLoS One. 2022 Feb 3;17(2):e0263522. doi:
10.1371/journal.pone.0263522. PMID: 35113972; PMCID: PMC8812928.

{[}2{]} Taff HT, Mitchell KF, Edward JA, Andes DR. Mechanisms of Candida
biofilm drug resistance. Future Microbiol. 2013 Oct;8(10):1325-37. doi:
10.2217/fmb.13.101. PMID: 24059922; PMCID: PMC3859465.

\textbf{Figure legend}

\textbf{Figure 1. Computed tomography revealing candida
thrombophlebitis} \textbf{in the brachiocephalic vein}

Gas production surrounding a peripherally inserted central catheter

Residual thrombus after catheter removal\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure1/Figure1}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

