\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[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Infective endocarditis caused by K. oxytoca: A Case Report}



\author[1]{Suju Jamarkattel}%
\author[2]{Sujan Jamarkattel}%
\author[3]{Sajan Ngakhusi}%
\affil[1]{Matrisishu Miteri Hospital}%
\affil[2]{Providence Medford Medical Center}%
\affil[3]{Bhaktapur Cancer Hospital}%


\vspace{-1em}



  
  \date{May 28, 2024}


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








\sloppy


\textbf{Infective endocarditis caused by K. oxytoca: A Case Report}

\textbf{Key Clinical Message:}

Infective endocarditis caused by Klebsiella species is rare, with K.
oxytoca contributing to only a tiny fraction of cases. This case
highlights the role of advanced imaging and molecular techniques in the
diagnosing and managing it.

\textbf{KEYWORDS:} Gram-negative bacteria; heart valves; infective
endocarditis; \emph{K. oxytoca} , septicemia.

\textbf{Introduction:}

Infective endocarditis (IE) caused by \emph{Klebsiella} species is an
infrequent occurrence, comprising less than 1.2\% of native valve
endocarditis cases and up to 4.1\% of prosthetic valve endocarditis
cases. \textsuperscript{1,2} The majority of such cases are caused
by\emph{K. pneumoniae.} \textsuperscript{3,4} \emph{K. oxytoca} is an
extremely rare species that can rarely cause endocarditis. Here, we
present a case of \emph{K. oxytoca} endocarditis to highlight the need
for careful evaluation during the entire course of therapy and the role
of advanced imaging and molecular techniques.

\textbf{Case presentation:}

A 77-year-old Caucasian male with no known past medical history except
for benign prostatic hypertrophy presented to the emergency department
with a one-week history of acute onset of progressive dyspnea and
generalized swelling. Approximately three weeks prior to this emergency
room visit, he had been admitted to the intensive care unit in our
hospital for an episode of septic shock secondary to \emph{K.
oxytoca}bacteremia. 1 out of 2 sets of blood cultures were positive for
\emph{K. oxytoca} . He was then diagnosed and treated for two weeks for
a complicated urinary tract infection. He was initially treated with
intravenous ceftriaxone but later switched to oral levofloxacin given
susceptibilities as reported below in \textbf{figure 1a.}

On initial evaluation in the emergency department, the patient appeared
in mild distress. He was placed on a low flow nasal cannula, with oxygen
saturation of 94 percent on 2 liters of supplemental oxygen. Initial
vital signs were recorded as follows: Blood pressure was 116/75 mm Hg,
pulse 96 beats per minute, axillary temperature 98.7 Fahrenheit and
respiration 24 per minute. Physical examination was remarkable for
bibasilar crackles on chest auscultation and grade 2+ pitting peripheral
edema in bilateral lower extremities. He also had a grade 3 systolic
murmur best heard in the 2nd left intercostal space, loudest on
expiration.~ Otherwise, he was awake, alert and oriented to time, place
and person. No Janeway lesions, no splinter hemorrhages, no Osler's
nodes were noted on the rest of the clinical exam.

His laboratory studies were remarkable for leukocytosis, white blood
cell count on admission was 15.6 x 10\textsuperscript{3}~cells/uL.
(Reference range 4.4-11.0 x10\textsuperscript{3~}/uL). His aspartate
transaminase was 78 Unit/L (reference range: 6-42 U/L) and alanine
transaminase was 60 Unit/L (reference range: 0-55 U/L). C-reactive
protein was 2.5 mg/dL (reference range: Less than 0.3mg/dL). Chest
radiograph showed bilateral vascular congestion, bilateral pleural
effusions and enlarged cardiac silhouette as depicted in \textbf{Figure
1b} . Multiple sets of blood cultures were negative. \emph{Bartonella}
,\emph{Brucella} and \emph{Coxiella} specific antibodies were negative.\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Figure 1a: Blood culture report and susceptibility profile from
patient's recent hospitalization, which isolated K. oxytoca & Figure 1b:
Plain chest radiograph showing bilateral interstitial infiltrates and
enlarged cardiac silhouette\tabularnewline
\midrule
\endhead
Figure 1c: The picture in upper row showing pseudoaneurysm of aortic
root and the picture in the bottom revealed the presence of severely
thickened aortic valve & Figure 1d: Ribosomal DNA amplification and
direct sequencing of DNA from excised cardiac valve, which identified K.
oxytoca\tabularnewline
\bottomrule
\end{longtable}

During hospitalization, he continued to have persistently elevated white
blood cell count, with no clear explanation on workup. He was needing
aggressive diuresis for his clinical picture of cardiogenic shock and
associated fluid overload. Multiple sets of blood cultures remained
negative after more than 72 hours of incubation. Computed tomography of
abdomen and pelvis scan revealed no abscess or foci of infection.

He was started on empiric intravenous ceftriaxone given his recent
history of \emph{K. oxytoca} septicemia. Echocardiograms via both
transthoracic and transesophageal approaches were pursued which showed
preserved left ventricular ejection fraction however was concerning for
native aortic valve endocarditis with severely thickened aortic valve
and a pseudoaneurysm of aortic root.

Cardiothoracic surgery was consulted given findings of valvular
endocarditis with symptoms and signs of left ventricular failure. He
subsequently underwent surgical debridement of aortic annulus and left
ventricular outflow tract with aortic valve replacement.
Intraoperatively, chronic vegetation at the base of the right coronary
cusp with fibrosis of the left ventricular outflow tract was found.
Debrided valve tissue was sent for bacterial, acid-fast bacilli (AFB)
test, fungal cultures and direct DNA sequencing by PCR. Gram stain and
routine bacterial, mycobacterial and fungal cultures of the operative
specimens were negative. However,~\emph{K. oxytoca} ~specific DNA was
detected on the ribosomal DNA amplification by polymerase chain reaction
of diseased valve/tissue.

The patient clinically improved after a few days' stay in the cardiac
care unit post-surgery and was continued on intravenous ceftriaxone. He
was able to be discharged home after eleven days of hospitalization and
was continued on intravenous antibiotics via a peripherally inserted
central catheter to complete a four-week course. On a post-hospital
discharge visit to the cardiology clinic, he clinically improved and
continued to participate in physical therapy sessions.

\textbf{Discussion:}

\emph{K. oxytoca} ~endocarditis is an uncommon entity that can
infrequently cause endocarditis and is associated with poor outcome. In
comparison to more virulent organisms like \emph{Staphylococci} ,
gram-negative bacteria have a lower tendency to infect native heart
valves due to their reduced ability to adhere to the
endocardium.\textsuperscript{4} However, \emph{Klebsiella} species
endocarditis are responsible for high rates of complications and
mortality. \textsuperscript{2} We report a case of~\emph{K. oxytoca}
~endocarditis in an elderly man who presented with heart failure and
severe aortic stenosis secondary to infective endocarditis.

\emph{K. oxytoca} bacteremia is commonly seen in the setting of
hepatobiliary tract, urinary tract, skin and soft tissue, and peritoneal
infection\textsuperscript{.} \textsuperscript{2,5} The documented
pathways through which K. oxytoca enters the bloodstream in cases of
bacteremia are ranked in descending order as follows: the hepatobiliary
tract (50\%-55\%), intravascular or urinary catheters (7\%-16\%), the
urinary tract (5\%-6\%), skin and soft tissues (3\%-5\%), and the
peritoneal cavity (2\%-6\%). Moreover, in 23\% to 34\% of infections,
the specific entry points remain
unidentified.\textsuperscript{6,7}Although our patient didn't have any
history of immunosuppression, he had other risk factors for developing
gram-negative infective endocarditis including his advanced age and
history of recent prolonged hospitalization for septic shock secondary
to \emph{K. oxytoca}bacteremia of urinary source.

It is well known that echocardiography is the mainstay of cardiac
imaging for diagnosis of infective
endocarditis.\textsuperscript{8}Transesophageal echocardiography (TEE)
is a more sensitive test compared to transthoracic echocardiogram (TTE)
which is generally the first diagnostic test for patients with suspected
infective endocarditis. In addition, TEE is superior to TTE for
detection of cardiac complications including abscess, leaflet
perforation, and aortic pseudoaneurysm or intracardiac fistula.
\textsuperscript{9,10} As in our patient, early complications were
better visualized on TEE, and the surgical intervention followed soon
after. Given the high morbidity and mortality rates associated with
these infections, timely surgical consultation is of paramount
importance. \textsuperscript{11}

Similarly, microbiological diagnosis of infective endocarditis is
primarily based on blood culture, excised cardiac valve tissue, or
infected emboli. This conventional approach has been shown to be
successful in 92 to 95\% of cases in which a microorganism is
present.\textsuperscript{11} In regard to our patient, a chronic
vegetation at the base of the right coronary cusp with fibrosis of the
left ventricular outflow tract was found on histopathological analysis
confirming the diagnosis of infective endocarditis as per modified
Duke's criteria. Although, the conventional microbiological analysis of
cardiac valve tissue was unremarkable, \emph{K. oxytoca} ~specific DNA
was detected on a broad-range polymerase chain reaction technique of
affected valve/tissue.

The patient in our case report had no history of intravenous drug use,
nor he had any exposure to animal farms, or any active exposure to pet
animals. Culture negative endocarditis due to fastidious organisms was
initially considered among the differential diagnoses, however
serological titer tests and automated testing of blood cultures, in
addition to the use of specialized culture media (enriched broth) were
unremarkable. This also highlights the fact that molecular based
techniques could potentially be helpful for the identification and
analysis of this life-threatening infection.

The most effective drugs against these microorganisms include third
generation cephalosporins and aminoglycosides, which are generally
administered together. While the ideal period for treatment is not
clearly established, a recommended duration of around 6 weeks is
advisable. Additional antibiotics like imipenem, aztreonam, and
fluoroquinolones have also shown effectiveness against gram-negative
bacteria. \textsuperscript{12} Our patient showed clinical improvement
with a four-week course of intravenous ceftriaxone.

\textbf{Conclusion}

This case report highlights the importance of careful evaluation and
aggressive treatment of \emph{K. oxytoca} endocarditis due to its severe
complications, overall poor prognosis, and associated high mortality
rate. Similarly, molecular-based techniques including universal PCR
techniques can be a useful tool in certain scenarios when the standard
microbiological analysis is unrevealing.

\textbf{Declaration of Conflicting Interests}

The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

\textbf{Funding}

The author(s) received no financial support for the research,
authorship, and/or publication of this article. This case report
received no specific grant.

\textbf{ACKNOWLEDGMENT}

We gratefully acknowledge the work of members of our hospital and the
patient.

\textbf{CONFLICT OF INTEREST STATEMENT}

The authors declare that there is no conflict of interest.

\textbf{ETHICS STATEMENT}

None

\textbf{WRITTEN CONSENT FROM THE PATIENT}

Written informed consent was obtained from the patient before the
submission of the report. The patient understands that his name and
initials won't be mentioned and only the images of diagnostics tests
will be used.

\textbf{DETAILED AUTHORS' CONTRIBUTIONS}

Suju J, Sajan N collected the required case information, images,
reports, and contributed to writing the original drafts of the
manuscript. Sujan J contributed to conceptualize and describe the case.
Suju J, Sajan N and Sujan J reviewed the literature and contributed to
writing and editing the manuscript. All authors read and approved the
final manuscript.

\textbf{DATA AVAILABILITY STATEMENT}

The data supporting the findings in this case report is available within
the article and its supplementary materials.

\textbf{References:}

1. Slipczuk L, Codolosa JN, Davila CD, et al. Infective Endocarditis
Epidemiology Over Five Decades: A Systematic Review. \emph{PLOS ONE} .
2013;8(12):e82665. doi:10.1371/journal.pone.0082665

2. Anderson MJ, Janoff EN. Klebsiella Endocarditis: Report of Two Cases
and Review. \emph{Clinical Infectious Diseases} . 1998;26(2):468-474.
doi:10.1086/516330

3. Ioannou P, Miliara E, Baliou S, Kofteridis DP. Infective endocarditis
by Klebsiella species: a systematic review. \emph{J Chemother} .
2021;33(6):365-374. doi:10.1080/1120009X.2021.1888025

4. Raza SS, Sultan OW, Sohail MR. Gram-negative bacterial endocarditis
in adults: state-of-the-heart. \emph{Expert Rev Anti Infect Ther} .
2010;8(8):879-885. doi:10.1586/eri.10.76

5. Chen JY, Chen PS, Chen YP, Lee WT, Lin LJ. Community-acquired
Klebsiella oxytoca endocarditis: a case report. \emph{J Infect} .
2006;52(5):e129-131. doi:10.1016/j.jinf.2005.08.015

6. Lin RD, Hsueh PR, Chang SC, Chen YC, Hsieh WC, Luh KT. Bacteremia due
to Klebsiella oxytoca: clinical features of patients and antimicrobial
susceptibilities of the isolates. \emph{Clin Infect Dis} .
1997;24(6):1217-1222. doi:10.1086/513637

7. Kim BN, Ryu J, Kim YS, Woo JH. Retrospective analysis of clinical and
microbiological aspects of Klebsiella oxytoca bacteremia over a 10-year
period. \emph{Eur J Clin Microbiol Infect Dis} . 2002;21(6):419-426.
doi:10.1007/s10096-002-0738-9

8. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke
criteria for the diagnosis of infective endocarditis. \emph{Clin Infect
Dis} . 2000;30(4):633-638. doi:10.1086/313753

9. Daniel WG, M\selectlanguage{ngerman}ügge A, Martin RP, et al. Improvement in the diagnosis of
abscesses associated with endocarditis by transesophageal
echocardiography. \emph{N Engl J Med} . 1991;324(12):795-800.
doi:10.1056/NEJM199103213241203

10. Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in
Adults: Diagnosis, Antimicrobial Therapy, and Management of
Complications: A Scientific Statement for Healthcare Professionals From
the American Heart Association. \emph{Circulation} .
2015;132(15):1435-1486. doi:10.1161/CIR.0000000000000296

11. Cahill TJ, Prendergast BD. Infective endocarditis. \emph{Lancet} .
2016;387(10021):882-893. doi:10.1016/S0140-6736(15)00067-7

12. Habib G, Lancellotti P, Antunes MJ, et al. 2015 ESC Guidelines for
the management of infective endocarditis: The Task Force for the
Management of Infective Endocarditis of the European Society of
Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic
Surgery (EACTS), the European Association of Nuclear Medicine
(EANM).\emph{Eur Heart J} . 2015;36(44):3075-3128.
doi:10.1093/eurheartj/ehv319

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

