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<article article-type="research-article" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xml:lang="en">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">JRENHEP</journal-id>
<journal-title-group>
<journal-title>Journal of Renal and Hepatic Disorders</journal-title>
<abbrev-journal-title>JRENHEP</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">2207-3744</issn>
<publisher>
<publisher-name>Troika Publisher</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.63268/jrenhp.v9i1.211</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Research</subject>
</subj-group>
</article-categories>
      <title-group>
        <article-title>Emergence of antibiotic resistance in bloodstream infections associated with catheters in hemodialysis patients: a prospective observational study</article-title>
      </title-group>
	  
	  
	  <contrib-group content-type="authors">

 <contrib contrib-type="author">
          <name>
            <surname>Bhat</surname>
            <given-names>Mohammad</given-names>
          </name>
		  <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Muqbool</surname>
            <given-names>Danish</given-names>
          </name>
		  <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Yousuf</surname>
            <given-names>Rayees</given-names>
          </name>
		  <xref ref-type="aff" rid="aff1">1</xref>
		  <xref ref-type="corresp" rid="cor1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Parry</surname>
            <given-names>Manzoor</given-names>
          </name>
		  <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Farooq</surname>
            <given-names>Amir</given-names>
          </name>
		  <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wani</surname>
            <given-names>Muzamil</given-names>
          </name>
		  <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Khan</surname>
            <given-names>Imran</given-names>
          </name>
		  <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wani</surname>
            <given-names>Imtiyaz</given-names>
          </name>
		  <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Wani</surname>
            <given-names>Muzafar</given-names>
          </name>
		  <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>


<aff id="aff1"><label>1</label>Department of Nephrology, Sheri-Kashmir Institute of Medical Sciences, 190011 Srinagar, India</aff>

</contrib-group>
	  
	  <author-notes>
<corresp id="cor1"><italic>Author for correspondence:</italic> <email>Rayees.yousuf@skims.ac.in</email></corresp>

</author-notes>



<pub-date pub-type="epub">
<day>20</day>
<month>06</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection"><year>2025</year></pub-date>
<volume>9</volume>
<issue>1</issue>
<fpage>12</fpage>
<lpage>17</lpage>
<history>
<date date-type="received">
<day>02</day>
<month>12</month>
<year>2024</year></date> 
<date date-type="accepted">
<day>30</day>
<month>04</month>
<year>2025</year></date> 
</history>
<permissions>
<copyright-statement><italic>Copyright:</italic> The Author(s). Published by Troika Publisher.</copyright-statement>
<copyright-year>2025</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p><italic>License:</italic> This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0">http://creativecommons.org/licenses/by/4.0</ext-link></license-p>
</license>
</permissions>
	  
      <abstract>
<p><bold>Background</bold>: Catheter-related bloodstream infections (CRBSIs) are a 
significant cause of hospitalization and mortality among hemodialysis patients. 
Incidence rates and resistance patterns vary widely. Recent studies show a rise 
in CRBSIs caused by multidrug-resistant organisms (MDROs). This study aims to 
determine the incidence, microbiological profile, antibiogram and outcomes of 
CRBSIs in hemodialysis patients at our institution. <bold>Methods</bold>: This 
prospective single center observational study included all patients initiating 
hemodialysis with central venous double-lumen catheters. <bold>Results</bold>: During 
the study, 240 catheters were inserted in 240 patients. A total of 48/240 (20%) 
developed CRBSI with 41/48 (85.4%) having culture-positive probable CRBSI and 
07/48 (14.6%) having culture-negative possible CRBSI. Concomitant exit site 
infection was present in 09/48 (18.8%). The CRBSI incidence rate was 1.46 
episodes per 1000 catheter days, based on 48 episodes over 32,782 catheter days. 
The mean time to CRBSI was 204.6 &#xB1; 87.1 days. Gram-positive bacteria were 
cultured in 15 cases (31.3%), Gram-negative bacteria in 26 cases (54.2%), and 7 
cases (14.6%) had negative culture. Coagulase negative Staphylococcus Aureus 
(CoNS) was the most common Gram-positive pathogens isolated, making up 46.7% of 
the cases. Klebsiella pneumonia, Pseudomonas, and Acinetobacter species were 
identified as the most prevalent Gram-negative pathogens (n = 06/26 each; 23.1%. 
Among 8 cultured Gram-negative bacterial species, resistance patterns observed 
was Ampicillin: 4/4 tested (100.0%), Quinolones: 4/6 tested (66.7%), 
Clotrimazole: 3/5 tested (60.0%), Carbapenems: 3/6 tested (50.0%), Gentamicin: 
2/5 tested (40.0%), Amikacin: 1/3 tested (33.3%), and Piperacillin-Tazobactam: 
1/5 tested (20.0%). A total of 39/48 catheters were salvaged. 
<bold>Conclusions</bold>: CRBSI remains a significant issue in patients using central 
venous catheters. The rise of multidrug-resistant Gram-negative infections 
necessitates stricter measures, including improved hygiene, surveillance and 
long-term vascular access. Proper cultures should precede empirical antibiotic 
therapy, and healthcare centers should tailor their antibiotic policies to local 
susceptibility patterns.</p>
</abstract>
<kwd-group>
<kwd>Catheter related blood stream infection</kwd>
<kwd>Cuffed dialysis catheter</kwd>
<kwd>Un-cuffed dialysis catheter</kwd>
<kwd>Hemodialysis</kwd>
</kwd-group>
</article-meta>
</front>
<body>




<sec id="S1" sec-type="intro">
<title>Introduction</title>
  <p>Hemodialysis (HD) catheters are crucial for initiating treatment in most 
patients with end-stage renal disease (ESRD). Central venous catheters (CVCs) 
used in HD are linked to a significant proportion of infections, with 
catheter-related bloodstream infections (CRBSIs) being a leading cause of 
mortality among these patients [<xref ref-type="bibr" rid="b1">1</xref>, <xref ref-type="bibr" rid="b2">2</xref>, <xref ref-type="bibr" rid="b3">3</xref>, <xref ref-type="bibr" rid="b4">4</xref>]. The incidence of CRBSI ranges from 
0.6 to 6.5 episodes per 1000 catheter days, influenced by factors such as the 
definition used, local catheter placement and care policies, and the duration of 
catheter use [<xref ref-type="bibr" rid="b1">1</xref>, <xref ref-type="bibr" rid="b5">5</xref>, <xref ref-type="bibr" rid="b6">6</xref>, <xref ref-type="bibr" rid="b7">7</xref>], highlighting the importance of local epidemiological data 
for guiding prevention strategies. A recent study has highlighted a notable 
escalation in the incidence of catheter-related bloodstream infections (CRBSIs) 
caused by multidrug-resistant organisms (MDROs), with a prevalence of 44.5% [<xref ref-type="bibr" rid="b8">8</xref>]. 
This study addresses the limited regional data on antimicrobial resistance 
patterns in catheter-related bloodstream infections (CRBSI) among hemodialysis 
patients, focusing on a tertiary care center in Northern India.</p>  
     <p>This prospective observational study was conducted at the Department of 
Nephrology, a tertiary care center in Northern India, over a one-year period from 
September 2023 to September 2024. All patients initiated on hemodialysis through 
central venous double-lumen catheters (both cuffed and non-cuffed) were enrolled. 
Demographic data, clinical variables including age, gender, type of catheter 
placed (cuffed or non-cuffed), site and date of catheter insertion, and cause of 
ESRD were collected at the initial visit. Patients who developed symptoms and 
signs of CRBSI like fever, chills, hypotension, and /or catheter exit site 
discharge on follow-up, were hospitalized and evaluated using peripheral 
vein and central venous catheter blood cultures, alongside baseline blood tests. 
The 2006 National Kidney Foundation Kidney Disease Outcomes Quality Initiative 
(NKF KDOQI) Clinical Practice Guidelines for Vascular Access classification were 
followed for classifying culture-positive probable CRBSI and culture-negative 
possible CRBSI. All patients received empirical intravenous antibiotics targeting 
both Gram-positive (including Methicillin resistant Staphylococcus Aureus MRSA) 
and Gram-negative organisms, reflecting global guidelines for CRBSI management. 
Empirical Gram-positive cover was given by vancomycin or teicoplanin depending on 
physician discretion and empirical Gram-negative cover was given by piperacillin 
tazobactam or meropenem A 2D Echocardiography was done to rule out infective 
endocarditis when clinically indicated.</p>  
</sec>



<sec id="S2">
<title>Statistical methods</title>
   <p>Continuous variables were reported as mean &#xB1; standard deviation (SD), 
while categorical variables were expressed as percentages 
(proportions). Chi-square tests assessed associations between categorical 
variables. Mann-Whitney U tests compared non-normally distributed continuous 
variables. All analyses were performed using IBM SPSS Statistics for Windows 
(version 25, Armonk, NY, USA).</p>  

</sec>



<sec id="S3" sec-type="results">
<title>Results</title>
     <p>A total of 240 catheters (in 240 patients) were inserted during the study 
period, cuffed and non-cuffed dialysis catheters accounted for 195/240 (81.3%) 
and 45/240 (18.8%) respectively. Men and women accounted for 141 (58.8%) and 99 
(41.3%) respectively. Hypertension and diabetes mellitus were the most common 
comorbidities, present in 212 (88.3%) and 189 (78.8% respectively). The mean 
age was 52.5 &#xB1; 15.7 years. Most patients were in the 30 to 60-year age 
group, followed by 60 to 90 years, accounting for 142/240 (59.2%) and 75/240 
(31.3%). A total of 48/240 (20%) developed CRBSI with 41/48 (85.4%) having 
culture-positive probable CRBSI and 07/48 (14.6%) having culture-negative 
possible CRBSI, as defined by the 2006 NKF-KDOQI criteria. Intradialytic chills 
followed by fever were the most common presenting complaints present in 91.7% 
(44/48) and, 89.5% (43/48) patients respectively Mean Age of CRBSI <italic>vs. 
</italic>Non-CRBSI Patients was 51.6 &#xB1; 15.6 and 56.1 &#xB1; 15.8 years 
respectively; <italic>p</italic>-value 0.15. Out of 48 cases of CRBSI, men and women 
accounted for 23 (48%) and 25 (52%) cases respectively; <italic>p</italic>-value 0.09. 
A total of 41/48 (85.4%) episodes occurred in patients with cuffed dialysis 
catheters and 07/48 (14.6%) in non-cuffed dialysis catheters; <italic>p</italic>-value 
0.536. The mean catheter days were 177.5 &#xB1; 94.9 days. The median catheter 
days for un-cuffed and cuffed dialysis lines were 28 days and 210 days 
respectively<italic> p</italic>-value &lt; 0.001. The mean and median time to CRBSI were 
204.6 &#xB1; 87.1 days and 231.5 days respectively. The incidence rate for 
un-cuffed and cuffed dialysis lines was 4.31 and 1.32 episodes per thousand 
catheter days. Concomitant exit site infection was present in 09/48 (18.8%). The 
overall CRBSI incidence was 1.46 episodes per 1000 catheter days (48 cases/32,782 
catheter days &#xD7; 1000). When stratified by classification, 
culture-positive probable CRBSIs (n = 41) occurred at a rate of 1.25 per 1000 
catheter days, while culture-negative possible CRBSIs (n = 7) had a lower 
incidence of 0.213 per 1000 catheter days. Hypertension and diabetes were the 
most common comorbidity present in 45/48 (93.8%) and 40/48 (83.3%) of CRBSI 
patients respectively. Gram-positive organisms were isolated in 15/48 cases 
(31.3%), while Gram-negative bacteria accounted for 26/48 cases (54.2%), and 
7/48 cases (14.6%) had negative cultures. Coagulase-negative Staphylococcus 
aureus (CoNS) was the most common Gram-positive pathogen isolated (07/15; 
46.7%), all were methicillin-resistant. Among the remaining Gram-positive 
isolates, methicillin-sensitive <italic>Staphylococcus-aureus</italic> (MSSA), 
methicillin resistant <italic>Staphylococcus aureus</italic> (MRSA), and Enterococcus 
species were identified. Klebsiella pneumonia, Pseudomonas, and Acinetobacter 
were the most common among Gram-negative organisms grown (n = 6 each; 23.1%), 
followed by Escherichia coli, Pantoea agglomerans, Stenotrophomonas Maltophillia 
and Serratia Marcescens. Among 8 cultured Gram-negative bacterial species, 
resistance patterns observed was Ampicillin: 4/4 tested (100.0%), Quinolones: 
4/6 tested (66.7%), Cotrimoxazole: 3/5 tested (60.0%), Carbapenems: 3/6 tested 
(50.0%), Gentamicin: 2/5 tested (40.0%), Amikacin: 1/5 tested (20%), and 
Piperacillin-Tazobactam: 1/5 tested (20.0%). Most Gram-positive isolates 
demonstrated susceptibility to the empirically administered antibiotics, while a 
predominant proportion of Gram-negative organisms were identified as 
extended-spectrum beta-lactamase (ESBL)-producing strains. The CRBSI group had a 
mean age of 56.1 &#xB1; 15.8 years, while the non-CRBSI group averaged 51.6 
&#xB1; 15.6 years; <italic>p</italic>-value 0.150. In 60 to 90-year age group, 17/75 
(22.7%) developed CRBSI followed by 29/142 (20.4%) in 30 to 60-year age group. 
Men and women accounted for 23/48 (47.9%) and 25/48 (52.1%) of CRBSI cases 
respectively; <italic>p</italic>-value 0.08. Leukocytosis (&gt;11,000 cells/mm<sup>3</sup>) was 
present in 44/48 (91.7%) patients and 3/48 (6.3%) had normal total leucocyte 
count.</p>  
     <p>Catheter salvage was achieved in 39 of 48 cases (81.3%). Concurrent exit-site 
infections requiring catheter removal occurred in 9 patients (18.8%) with CRBSI. 
No mortality was reported during the study period. The results are summarized in 
<xref ref-type="table" rid="T1">Tables 1</xref>,<xref ref-type="table" rid="T2">2</xref>,<xref ref-type="table" rid="T3">3</xref>,<xref ref-type="table" rid="T4">4</xref>,<xref ref-type="table" rid="T5">5</xref>,<xref ref-type="table" rid="T6">6</xref>.</p>  



<table-wrap id="T1" orientation="portrait" position="float">
<label>Table 1.</label>
<caption>
<p>Baseline characteristics of CRBSI group.</p></caption>

<table frame="border" rules="all">
<thead valign="top">
<tr>
<td>Parameter</td> 
<td align="center">Minimum</td> 
<td align="center">Maximum</td> 
<td align="center">Mean &#xB1; SD</td></tr> 
</thead>
<tbody valign="top">
<tr>
<td>Hemoglobin (g/dL)</td> 
<td align="center">4.90</td> 
<td align="center">11.30</td> 
<td align="center">8.0 &#xB1; 1.5</td></tr> 
<tr>
<td>WBC/&#xB5;L</td> 
<td align="center">2.30</td> 
<td align="center">28.00</td> 
<td align="center">14.8 &#xB1; 4.5</td></tr> 
<tr>
<td>Neutrophils (%)</td> 
<td align="center">65.20</td> 
<td align="center">98.00</td> 
<td align="center">84.8 &#xB1; 7.2</td></tr> 
<tr>
<td>Creatinine (mg/dL)</td> 
<td align="center">4.73</td> 
<td align="center">13.09</td> 
<td align="center">8.12 &#xB1; 1.96</td></tr> 
<tr>
<td>Urea (mg/dL)</td> 
<td align="center">79.00</td> 
<td align="center">299.00</td> 
<td align="center">176.83 &#xB1; 50.14</td></tr> 
<tr>
<td>Uric acid (mg/dL)</td> 
<td align="center">2.68</td> 
<td align="center">12.00</td> 
<td align="center">7.11 &#xB1; 2.15</td></tr> 
<tr>
<td>Albumin (g/dL)</td> 
<td align="center">1.57</td> 
<td align="center">3.90</td> 
<td align="center">2.71 &#xB1; 0.55</td></tr> 
<tr>
<td>No. of catheter days</td> 
<td align="center">25.00</td> 
<td align="center">319.00</td> 
<td align="center">204.6 &#xB1; 87.1</td></tr> 
<tr>
<td>Empiric therapy (d)</td> 
<td align="center">1.00</td> 
<td align="center">3.00</td> 
<td align="center">1.65 &#xB1; 0.67</td></tr> 
<tr>
<td>Culture positivity (d)</td> 
<td align="center">0.00</td> 
<td align="center">3.00</td> 
<td align="center">1.02 &#xB1; 1.01</td></tr> 
</tbody> 
</table>
<table-wrap-foot>
<fn id="TF1-1"><p>SD: standard deviation; WBC: White blood cells.</p></fn></table-wrap-foot>
</table-wrap>


<table-wrap id="T2" orientation="portrait" position="float">
<label>Table 2.</label>
<caption>
<p>Comparison between CRBSI and Non-CRBSI group.</p></caption>

<table frame="border" rules="all">
<thead valign="top">

<tr>
<td>Characteristics</td> 
<td align="center">No CRBSI</td> 
<td align="center">CRBSI</td> 
<td align="center"><italic>p</italic>-value</td></tr> 
</thead>
<tbody valign="top">
<tr>
<td>Percentage of events</td> 
<td align="center">192/240 (80%)</td> 
<td align="center">48/240 (20%)</td> 
<td/></tr> 
<tr>
<td>Age mean &#xB1; SD in years</td> 
<td align="center">56.1 &#xB1; 15.8</td> 
<td align="center">51.6 &#xB1; 15.6</td> 
<td align="center">0.150</td></tr> 
<tr>
<td>Gender (M/F)</td> 
<td align="center">118/74</td> 
<td align="center">23/25</td> 
<td align="center">0.088</td></tr> 
<tr>
<td>DM (Yes/No)</td> 
<td align="center">149/43</td> 
<td align="center">40/08</td> 
<td align="center">0.385</td></tr> 
<tr>
<td>HTN (Yes/No)</td> 
<td align="center">167/25</td> 
<td align="center">45/03</td> 
<td align="center">0.191</td></tr> 
<tr>
<td>Type of catheter (Cuffed/un-cuffed)</td> 
<td align="center">154/38</td> 
<td align="center">41/7</td> 
<td align="center">0.408</td></tr> 
</tbody> 
</table>
<table-wrap-foot>
<fn id="TF1-1"><p>M/F: Male/Female; DM: Diabetes mellitus; HTN: Hypertension; SD: standard 
deviation; CRBSI: Catheter-related bloodstream infections.</p></fn></table-wrap-foot>
</table-wrap>

 
 
<table-wrap id="T3" orientation="portrait" position="float">
<label>Table 3.</label>
<caption>
<p>Incidence of CRBSI per 1000 catheter days.</p></caption>

<table frame="border" rules="all">
<thead valign="top">

<tr> 
<td colspan="2">Variable</td> 
<td align="center">Catheters</td> 
<td align="center">Catheter days</td> 
<td align="center">Incidence rate (per 1000 catheter days)</td></tr> 
</thead>
<tbody valign="top">
<tr> 
<td colspan="2">Total</td> 
<td align="center">240</td> 
<td align="center">32,782</td> 
<td/></tr> 
<tr> 
<td colspan="2">No CRBSI</td> 
<td align="center">192 (80%)</td> 
<td align="center">23,083</td> 
<td/></tr> 
<tr> 
<td colspan="5">CRBSI</td></tr> 
<tr> 
<td/> 
<td align="center">Total</td> 
<td align="center">48/240 (20%)</td> 
<td align="center">9699</td> 
<td align="center">1.46</td></tr> 
<tr> 
<td/> 
<td align="center">Probable</td> 
<td align="center">41 (85.41%)</td> 
<td align="center">8705</td> 
<td align="center">1.25</td></tr> 
<tr> 
<td/> 
<td align="center">Possible</td> 
<td align="center">7 (14.58%)</td> 
<td align="center">994</td> 
<td align="center">0.21</td></tr> 
</tbody> 
</table>
<table-wrap-foot>
<fn id="TF1-1"><p>CRBSI: Catheter related blood stream infection.</p></fn></table-wrap-foot>
</table-wrap>



<table-wrap id="T4" orientation="portrait" position="float">
<label>Table 4.</label>
<caption>
<p>Microbiological spectrum of CRBSI.</p></caption>

<table frame="border" rules="all">
<thead valign="top">

<tr>
<td>Gram positive</td> 
<td align="center">Frequency (%)</td> 
<td align="center">Gram negative</td> 
<td align="center">Frequency (%)</td></tr> 
</thead>
<tbody valign="top">
<tr>
<td>CoNS</td> 
<td align="center">07 (46.7)</td> 
<td align="center">Pseudomonas</td> 
<td align="center">06 (23.1)</td></tr> 
<tr>
<td>MRSA</td> 
<td align="center">04 (26.7)</td> 
<td align="center">Acinetobacter</td> 
<td align="center">06 (23.1)</td></tr> 
<tr>
<td>MSSA</td> 
<td align="center">03 (20)</td> 
<td align="center">Klebsiella pneumoniae</td> 
<td align="center">06 (23.1)</td></tr> 
<tr>
<td>Enterococcus</td> 
<td align="center">01 (6.7)</td> 
<td align="center">E. Coli</td> 
<td align="center">02 (7.7)</td></tr> 
<tr> 
<td/> 
<td/> 
<td align="center">Pantoea agglomerans</td> 
<td align="center">02 (7.7)</td></tr> 
<tr> 
<td/> 
<td/> 
<td align="center">Stenotrophomonas maltophilia</td> 
<td align="center">02 (7.7)</td></tr> 
<tr> 
<td/> 
<td/> 
<td align="center">Serratia marcescens</td> 
<td align="center">01 (3.84)</td></tr> 
<tr> 
<td/> 
<td/> 
<td align="center">Enterobacter cloacae</td> 
<td align="center">01 (3.84)</td></tr> 
<tr>
<td>Total</td> 
<td align="center">15/48 (31.3%)</td> 
<td align="center">Total</td> 
<td align="center">26/48 (54.2%)</td></tr> 
</tbody> 
</table>
<table-wrap-foot>
<fn id="TF1-1"><p>CoNS: Coagulase negative staphylococcus aureus; MRSA: Methicillin resistant 
Staphylococcus aureus; MSSA: Methicillin sensitive staphylococcus aureus; E. 
Coli: Escherichia Coli.</p></fn></table-wrap-foot>
</table-wrap>




<table-wrap id="T5" orientation="portrait" position="float">
<label>Table 5.</label>
<caption>
<p>Antibiogram of Gram-positive organisms.</p></caption>

<table frame="border" rules="all">
<thead valign="top">

<tr>
<td>Antibiotics</td> 
<td align="center">CoNS (N = 7)</td> 
<td align="center">MRSA (N = 4)</td> 
<td align="center">MSSA (N = 3)</td> 
<td align="center">Enterococcus (N = 1)</td></tr> 
</thead>
<tbody valign="top">
<tr>
<td>Vancomycin</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">R</td></tr> 
<tr>
<td>Linezolid</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">S</td></tr> 
<tr>
<td>Teicoplanin</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">R</td></tr> 
<tr>
<td>Ciprofloxacin</td> 
<td align="center">S</td> 
<td align="center">R</td> 
<td align="center">S</td> 
<td align="center">ND</td></tr> 
<tr>
<td>Clindamycin</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">ND</td></tr> 
<tr>
<td>Tigecycline</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">ND</td></tr> 
<tr>
<td>All beta lactams</td> 
<td align="center">R</td> 
<td align="center">R</td> 
<td align="center">S</td> 
<td align="center">R</td></tr> 
<tr>
<td>Gentamicin</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">R</td> 
<td align="center">ND</td></tr> 
<tr>
<td>Erythromycin</td> 
<td align="center">R</td> 
<td align="center">R</td> 
<td align="center">R</td> 
<td align="center">ND</td></tr> 
</tbody> 
</table>
<table-wrap-foot>
<fn id="TF1-1"><p>S: Sensitive; R: Resistant; ND: Not done; CoNS: Coagulase negative staphylococcus aureus; MRSA: Methicillin resistant 
Staphylococcus aureus; MSSA: Methicillin sensitive staphylococcus aureus.</p></fn></table-wrap-foot>
</table-wrap>


   
<table-wrap id="T6" orientation="portrait" position="float">
<label>Table 6.</label>
<caption>
<p>Antibiogram of Gram-negative organisms.</p></caption>

<table frame="border" rules="all">
<thead valign="top">


<tr>
<td>Antibiotics</td> 
<td align="center">PM (N = 6)</td> 
<td align="center">KP (N = 6)</td> 
<td align="center">E. Coli (N = 2)</td> 
<td align="center">AB (N = 6)</td> 
<td align="center">PA (N = 2)</td> 
<td align="center">SM (N = 2)</td> 
<td align="center">SMA (N = 1)</td> 
<td align="center">EC (N = 1)</td></tr> 
</thead>
<tbody valign="top">
<tr>
<td>Amikacin</td> 
<td align="center">ND</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">R</td></tr> 
<tr>
<td>Gentamicin</td> 
<td align="center">R</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">S</td> 
<td align="center">R</td></tr> 
<tr>
<td>Ampicillin</td> 
<td align="center">R</td> 
<td align="center">R</td> 
<td align="center">R</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">R</td></tr> 
<tr>
<td>Ceftriaxone</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td></tr> 
<tr>
<td>Cefepime</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">S</td> 
<td align="center">R</td></tr> 
<tr>
<td>Piperacillin-tazobactam</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">R</td></tr> 
<tr>
<td>Cefaperazone-sulbactam</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">R</td></tr> 
<tr>
<td>Imipenem/meropenem</td> 
<td align="center">R</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">R</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">S</td> 
<td align="center">R</td></tr> 
<tr>
<td>Colistin</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">R</td> 
<td align="center">S</td></tr> 
<tr>
<td>Cotrimoxazole</td> 
<td align="center">R</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">R</td> 
<td align="center">S</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">R</td></tr> 
<tr>
<td>Ciprofloxacin/Levofloxacin</td> 
<td align="center">R</td> 
<td align="center">R</td> 
<td align="center">S</td> 
<td align="center">R</td> 
<td align="center">ND</td> 
<td align="center">S</td> 
<td align="center">ND</td> 
<td align="center">R</td></tr> 
<tr>
<td>Tigecycline</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">ND</td> 
<td align="center">S</td></tr> 
</tbody> 
</table>
<table-wrap-foot>
<fn id="TF1-1"><p>PM: Pseudomonas species; KP: Klebsiella Pneumoniae; AB: Acinetobacter Baumanii; 
PA: Pantoea Agglomerans; SM: Stenotrophomonas Maltophillia; SMA: Serratia 
Marcescens; EC: Enterobacter Cloacae; S: Sensitive; R: Resistant; ND: Not done; E. Coli: Escherichia Coli.</p></fn></table-wrap-foot>
</table-wrap>



</sec>


<sec id="S4" sec-type="discussion">
<title>Discussion</title>
     <p>In resource-limited settings, low socioeconomic status, limited health literacy, 
and inadequate reimbursement systems contribute to delayed medical care and late 
referrals for arteriovenous fistula (AVF) creation, often leading to emergent 
dialysis initiation via central venous catheters (CVCs). This is reflected by the 
historical data where non-cuffed dialysis catheters accounted for about 80 to 
100% of all central venous hemodialysis catheters in developing nations [<xref ref-type="bibr" rid="b9">9</xref>, <xref ref-type="bibr" rid="b10">10</xref>, <xref ref-type="bibr" rid="b11">11</xref>]. 
In our study cuffed tunneled double-lumen catheters accounted for 81.3% of all 
central venous hemodialysis catheters. These results are favorable reflecting a 
trend towards more use of tunneled cuffed double-lumen HD catheters. Non-tunneled 
catheters exhibit a 2&#x2013;3 times higher CRBSI incidence compared to tunneled 
catheters, as demonstrated by multiple studies [<xref ref-type="bibr" rid="b12">12</xref>, <xref ref-type="bibr" rid="b13">13</xref>] and Cuffed double-lumen 
hemodialysis catheters (<italic>e.g.</italic>, PermCath) serve as effective 
intermediate-term vascular access while awaiting arteriovenous fistula (AVF) 
creation and maturation. A total of 48/240 (20%) patients developed CRBSI during 
the study period. Our results are better than Shingarev R <italic>et al</italic>. [<xref ref-type="bibr" rid="b14">14</xref>] 
where 54% had a CRBSI by six months of a newly placed tunneled hemodialysis 
catheter. This reflects improvement in aseptic technique and better catheter care 
over the years. However, the study by Shingarev R <italic>et al</italic>. [<xref ref-type="bibr" rid="b14">14</xref>] included 
more than 450 participants and all the patients had cuffed dialysis catheters as 
against our study which included both cuffed and non cuffed dialysis catheters. 
In our study 41/48 (85.4%) had culture-positive probable CRBSI and 07/48 
(14.6%) had culture-negative possible CRBSI. Our culture positivity rate is 
better than the study done by Sethi <italic>et al</italic>. [<xref ref-type="bibr" rid="b15">15</xref>] where the culture 
positivity rate was only 62.2%. The improvement in culture positivity rates 
reflects early recognition of symptoms and appropriate collection of septic 
screens before empirical antibiotic exposure. All patients with culture-negative 
CRBSI in our cohort had received IV antibiotics in the community before the 
collection of septic screens which was the most likely reason for negative 
cultures. Intradialytic chills followed by fever were the most common presenting 
complaints present in 91.7% (44/48) and, 89.5% (43/48) of our patients 
respectively. The most common age group involved in our study was 60&#x2013;90 years 
which is similar to a study reported by Tao <italic>et al</italic>. [<xref ref-type="bibr" rid="b16">16</xref>] and Murea 
<italic>et al</italic>. [<xref ref-type="bibr" rid="b17">17</xref>]. This phenomenon may stem from factors such 
as immune-senescence, atypical clinical presentations in older adults, and delays 
in diagnosis. Cuffed catheters showed numerically higher CRBSI rates but the 
difference was not statistically significant (<italic>p</italic>-value 0.536). This looks 
contrary to the expected. The likely reason for such a discrepancy in our study 
is the under-representation of patients with non-cuffed dialysis catheters and 
significantly fewer at-risk catheter days in non-cuffed dialysis catheters. This 
underscores the need for larger studies and risk-stratified protocols to clarify 
this association. The median catheter days for un-cuffed and cuffed dialysis 
lines were 28 days and 210 days respectively (<italic>p</italic>-value &lt; 0.001). The 
historical incidence of CRBSIs associated with hemodialysis catheters falls 
within the range of 3&#x2013;6 per 1000 catheter-days [<xref ref-type="bibr" rid="b18">18</xref>]. Studies report widely 
differing CRBSI rates, from 0.4 to 1.27 cases per 1000 catheter-days [<xref ref-type="bibr" rid="b19">19</xref>, <xref ref-type="bibr" rid="b20">20</xref>, <xref ref-type="bibr" rid="b21">21</xref>]. 
The CRBSI incidence rate in our cohort is 1.46 episodes/1000 catheter days 
(48/32,782 &#xD7; 1000) compared to an incidence of 1.30 episodes/1000 catheter days by 
Mark A. Little <italic>et al</italic>. [<xref ref-type="bibr" rid="b22">22</xref>]. The high incidence rate can be decreased by 
implementation of standard catheter insertion and catheter care protocol. The 
median time to CRBSI in our cohort was 136.5 days, higher as compared to 24.5 
days reported by Agrawal <italic>et al</italic>. [<xref ref-type="bibr" rid="b23">23</xref>]. The main reason for this 
discrepancy could be partly due to better infection control practices in our 
center and the fact that study of Agrawal <italic>et al</italic>. [<xref ref-type="bibr" rid="b23">23</xref>] is done in 
patients on non-tunneled catheters which are at higher risk of infection and have 
less longevity. While most of the centers in the world encounter predominantly 
Gram-positive CRBSIs [<xref ref-type="bibr" rid="b14">14</xref>, <xref ref-type="bibr" rid="b24">24</xref>, <xref ref-type="bibr" rid="b25">25</xref>], Gram-negative organisms accounted for the 
majority of catheter-associated bloodstream infections (CRBSIs) in our study. 
Similar results have been reported from many other Indian studies [<xref ref-type="bibr" rid="b9">9</xref>, <xref ref-type="bibr" rid="b26">26</xref>]. Given 
the fecal origin of most Gram-negative pathogens, we hypothesize that suboptimal 
hygiene practices contribute to the high incidence of Gram-negative CRBSIs. The 
other reason for increased incidence of Gram negative CRBSI could be due to 
indiscriminate use of broad-spectrum antibiotics. Staphylococcus aureus emerged 
as the most frequently isolated pathogen in the study cohort. The most prevalent 
Gram-negative pathogens isolated included Klebsiella pneumoniae, Acinetobacter 
spp. and Pseudomonas spp. While Western literature frequently associates 
percutaneously inserted catheters with Staphylococcus-aureus and 
Enterobacteriaceae-related CRBSIs, this study observed a Gram-negative 
predominance alongside notable Gram-positive contributions.</p>  
     <p>Among Gram-positive isolates, coagulase-negative staphylococci (CoNS) were 
predominant, with all exhibiting methicillin resistance. Additional Gram-positive 
pathogens included methicillin-sensitive Staphylococcus-aureus (MSSA), 
methicillin resistant Staphylococcus-aureus (MRSA), and Enterococcus species.</p>  
     <p>A majority of Gram-negative isolates demonstrated extended-spectrum 
beta-lactamase (ESBL) production, aligning with global trends of rising ESBL 
prevalence in Gram-negative infections.</p>  
     <p>The variations in microbiological profiles and antibiotic susceptibility 
patterns underscore the necessity for individual centers to analyze their local 
pathogen distribution and integrate these findings into empirical antibiotic 
selection protocols.</p>  
     <p>Our study has certain limitations. It is a single-center study with a limited 
sample size, a larger multicenter study needs to be done to reproduce the 
results.</p>  
</sec>


<sec id="S5" sec-type="conclusions">
<title>Conclusions</title>


     <p>CRBSI remains a major clinical challenge in patients receiving hemodialysis via 
central venous catheters, compounded by the growing prevalence of multi-drug 
resistant Gram-negative infections. This evolving resistance landscape 
necessitates enhanced preventive strategies, including rigorous sterile 
protocols, improved hygiene, ongoing surveillance, and accelerated transition to 
long-term vascular access (<italic>e.g.</italic>, AV fistulas). Appropriate cultures 
should be taken before starting empirical antimicrobial therapy and every center 
should frame its antibiotic policy based on regional antibiotic susceptibility 
patterns.</p>  
   </sec>  
   
    </body>  
 <back>  
   <ack>  
 
 <sec id="S6">  
   
     <title>Abbreviations</title>  
     <p>CRBSI, Catheter related blood stream infection; ESRD, End stage renal disease; 
ESBL, Extended spectrum beta-lactamase; NKF KDOQI, National kidney 
foundation-kidney disease outcomes quality initiative; MDROs, multidrug-resistant 
organisms; CoNS, Coagulase-negative Staphylococcus aureus; HD, Hemodialysis; 
CVCs, Central venous catheters; MRSA, methicillin resistant 
<italic>Staphylococcus aureus</italic>; SD, standard deviation; AVF, arteriovenous 
fistula; MSSA, methicillin-sensitive <italic>Staphylococcus-aureus</italic>; TLC, Total 
leucocyte count; WBC, White blood cells.</p>  
   </sec>  
   <sec id="S7">  
     
     <title>Availability of data and materials</title>  
     <p>The data presented in this study are available on reasonable request from the 
corresponding author.</p>  
   </sec>  
   <sec id="S8">  
    
     <title>Author contributions</title>  
     <p>MB, DM, RY, MP, IW and Muzafar W&#x2014;contributed to the design and development of the study; contributed data analysis and interpretation. DM, RY, MP, AF, Muzamil W and IK&#x2014;contributed to data collection; participated in the writing of the manuscript. MB, IW and Muzafar W&#x2014;participated in the critical review. All authors contributed to editorial changes in the manuscript; provided approval for the final manuscript.</p>  
   </sec>  
   <sec id="S9">  
  
     <title>Ethics approval and consent to participate</title>  
     <p>The study is approved by Institutional Ethics Committee SKIMS under no: 
SIMS131/IEC-SKIMS/2023-369. The consent has been taken from all participants of 
the study.</p>  
   </sec>  
   <sec id="S10">  
   
     <title>Acknowledgment</title>  
     <p>Sincere thanks to all the patients who participated in the study.</p>  
   </sec>  
   <sec id="S11">  
   
     <title>Funding</title>  
     <p>This research received no external funding.</p>  
   </sec>  
   <sec id="S12">  
  
     <title>Conflict of interest</title>  
     <p>The authors declare no conflict of interest.</p>  
   </sec>  

</ack>   
   
   
   <fn-group>
<fn id="fn1"><p><italic>How to cite:</italic> Mohammad Bhat, Danish Muqbool, Rayees Yousuf, Manzoor Parry, Amir Farooq, Muzamil Wani, <italic>et al</italic>. Emergence of antibiotic resistance
in bloodstream infections associated with catheters in hemodialysis patients: a prospective observational study. Journal of Renal and Hepatic Disorders.
2025; 9(1): 12-17. doi: 10.63268/jrenhp.v9i1.211.</p></fn></fn-group>
   
   
  
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