Infectivity in the clinical hematology department of a University Hospital in Tlemcen-Algeria: Involvement of microbial biofilms in catheters alteration

Infectivity in the clinical hematology department of a University Hospital in Tlemcen-Algeria: Involvement of microbial biofilms in catheters alteration | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Infectivity in the clinical hematology department of a University Hospital in Tlemcen-Algeria: Involvement of microbial biofilms in catheters alteration Wafaa Kendil, Moustapha Yassine Mahdad, Rida Mohammed Mediouni, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8457760/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The use of catheters in hematology departments, particularly over extended periods, can lead to significant complications for patients. Microbiological alteration of these devices may result in various types of infectivity. Central venous catheters (CVC), as invasive medical devices, are particularly susceptible to colonization by bacteria capable of forming biofilms, thereby increasing the risk of associated infections. The aim of this study was to characterize the types of infectivity observed in the clinical hematology department of the University Hospital of Tlemcen (Algeria), identify the microbial species involved, and to examine the inner surfaces of altered CVC for the presence of bacterial biofilms using scanning electron microscopy. Hematology Infectivity Catheters Biofilms Scanning electron microscopy Algeria Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction According to World Health Organization [ 1 ], 5 to 15% of hospitalized patients experience an infection related to their care. In developing countries, the risk is 2 to 20 times higher; in 2023, Raoofi et al. [ 2 ] claimed that compared to other regions of the world, African nations have a higher occurrence of a factor of 0.27. In the hospital environment, the invasive procedure of using catheters plays a dual role; the first is to makes it easier to transfuse different physiological fluids, unfortunately the second is the alteration of these devices by microbial colonizers [ 3 , 4 ], hence the infectivity of catheters which varies according to the level of their infectiosity [ 5 ]. According to Brun-Buisson et al. [ 6 ], three types of catheter infectivity are known: contamination, colonization, and infection. It is therefore imperative to distinguish catheter infection from simple contamination before initiating antibiotic treatment [ 7 ]. Brun-Buisson et al. [ 6 ] defined contamination as a non-significant positive culture (significance threshold ≥ 10 3 ) without any local or general signs of infection, while colonization is characterized by a significant positive culture without any signs of infection. Conversely, infection is defined by a significant positive culture with the presence of signs of infection. In addition, catheters provide a gateway and prime surface for the adhesion of various pathogens. This leads to infections, affecting the lives of hospitalized patients, especially those with immune deficiencies [ 8 ]. Actually, catheters offer the perfect surface for the long-term adhesion of microorganisms, which promotes the development of biofilms [ 9 ]. This factor is essential for the persistence and severity of healthcare-associated infections, thereby limiting the range of possible treatments; due to the difficulty of removing a microbial biofilm once it has settled on a catheter [ 10 ], despite prospects highlighting substances with inhibitory effects against these complex structures [ 11 ]. On the other hand, acute myeloid leukemia (AML) is a serious disease that affects the hematopoietic system; affected patients are very often victims of embolism [ 12 , 13 ]. The use of catheters is known to increase the risk of embolism and constitutes an ideal platform for the adhesion of microorganisms [ 14 , 15 ], especially since the sessile lifestyle is the most widespread form of microbial existence in nature [ 16 ]. Considering the invasive risk of infection associated with intravascular thrombosis of catheters, as well as their different infectivities [ 6 , 17 ], this study aimed to identify the different forms of catheter infectivity and to examine the biofilms that develop on their surfaces. This was achieved by including patients who were hospitalized to a university hospital in Algeria's clinical hematology department. Materials and methods Catheters collection The samples were taken between October 2021 and June 2022. Thirty-six (36) venous catheters were collected from inpatients in the clinical hematology department of a university hospital in Tlemcen. It should be noted that only catheters implanted for 48 hours or more were included [18]. In order to complete the data relating to each sample, the clinical and personal information of each patient was taken into consideration, including their age, gender, reason for admission to hospital, body temperature at the time of sampling and other related data. Determination of catheter infectivity types After its removal, the distal end of each catheter was aseptically cut into a tube containing 5 mL of sterile saline solution. In order to detach microbial cells adhering to the catheters, the tubes were vortexed for one minute [6]. However, it has been reported that agitation alone cannot detach all microorganisms from catheters [19]; therefore, samples were subjected to ultrasonication (40 kHz, 100 W) for one minute. This approach was supported by Karbysheva et al. [20] for its effectiveness in diagnosing catheter-associated infections. Determination of catheter infectivity types was based on the presence or absence of a significant microbial load, as well as on associated signs of infection [6]. For this, 100 μL were inoculated from each decimal dilution of the sample (1/10, 1/100, and 1/1000). Bacteria were grown on nutrient agar and yeasts on Sabouraud dextrose agar; however, the inoculation of the agar allows just the active microbial flora to be assessed [21]. Simultaneously, a direct count of yeasts under the microscope, using Thoma cells, was carried out in order to determine their total number. Petri dishes were incubated at 37°C for 24 hours. The isolation of microorganisms, yeasts and bacteria, was approached extemporaneously with the study of catheters infectivity. The automated VITEK2 system (BioMérieux) and CHROM-Agar TM (Sigma) were used to identify the fungal isolates. Bacteria identification was performed using Api 20E®, Api 20NE®, Api Staph® and VITEK2 (BioMérieux). Microscopic a nalysis of c atheters Microbial biofilms adhering to the surface of sampled catheters were examined using scanning electron microscopy (SEM), which offers high-resolution three-dimensional imaging of the observed structure [22]. For this purpose, a central venous catheter (CVC), taken from a 44-year-old patient, was examined under a microscope without being subjected to vortexing or sonication procedures, in order to preserve any possible microbial biofilm structures. This patient was admitted to the hospital for acute myeloid leukemia (AML), she was undergoing chemotherapy and had a CVC implanted in internal jugular line, which was inserted for ten days before it was removed for examination. It is important to note that this patient did not receive any anticoagulant, platelet or antibiotic treatment, but she was the victim of a previous SARS-Cov-2 infection six months prior. Briefly, the catheter was dehydrated in a succession of ethanol concentrations (30%, 50%, 75%, and 100%) after being washed twice with sterile PBS and preserved overnight at 4°C using a 2.5% glutaraldehyde solution (Sigma-Aldrich, St. Louis, MO, USA). The catheter was then critical point dried, coated with palladium, and examined using a scanning electron microscope (ThermoFisher Scientific Apreo 2S). Statistical analysis Statistical analysis was performed using SPSS version 27.0.1 A multiple correspondence analysis (MCA) was conducted to explore the associations between the categorical variables of the study. Results and discussion Catheter collection Among all collected catheters, 69.44% yielded a positive microbial culture. Given that 13% of patients died in the Clinical Hematology service during the collection period, this reflects the magnitude of the risk associated with catheter use in this department; whereas a rate close to that of the present study (61.8%) has been reported in this context [23]. Microbial analysis of the catheters revealed various alterations. Figure 1 summarizes the results of the microbial alteration profile of the catheters. Microbiological analysis of the catheters revealed a predominance of mixed microbial alterations, bacteria-bacteria or bacteria-yeast. Notably, 44% of the associations concerned bacteria, compared to 8% for bacteria-yeast associations. In contrast, single-species alterations were exclusively represented by bacteria. These results reflect the increasing complexity of infections associated with catheter use. It is important to emphasize that all patients included in this study received antibiotic treatment, exclusively antibacterial (vancomycin, metronidazole, imipenem/cilastatin, and ceftazidime). However, no antifungal treatment was initiated during the sampling period. Six strains belonging to the genus Candida were identified; five isolates were determined to be C andida albicans and one was C. kefyr . C. albicans is classified as a critical pathogen that poses a significant risk to public health [1], the predominance of this species is highlighted in scientific literature, which identifies this species as the most frequently isolated human pathogenic yeast on medical devices [24,25]. The isolation of C. kefyr is noteworthy. As is the case in the present study, this species, generally considered a commensal organism, has recently emerged as an opportunistic pathogen, particularly in immunocompromised patients in a post-COVID-19 context [26]. Likewise, Ahmad et al. [27] indicated that this species can cause invasive infections. The identification of the isolated bacteria revealed a slight predominance of Gram-positive (56%) compared to Gram-negative bacteria. Staphylococcus sp . was the most frequently isolated species (57,69%), a result also observed by Pietrocola et al. [28]. S. haemolyticus , a coagulase-negative Staphylococcus known for its pathogenic potential [10], was the most prevalent species within this group. Regarding S. aureus and S. epidermidis , the isolation rates were relatively low, given their clinical and epidemiological importance [29]. It should be noted that other species were also isolated, including S. lentus and S. hominis . Further Gram-positive bacteria have been isolated, including Micrococcus luteus, Bacillus sp., Dermacoccus nishinomiyaensis, and Kocuria kristinae . These species are commensal of the skin and emerging pathogens [30-33]. Regarding Gram-negative bacteria, Enterobacter cloacae and Sphingomonas paucimobilis were the most commonly isolated species (20% each), which reflects their capacity to survive on medical devices. The opportunistic enterobacterium is frequently associated with nosocomial infections, particularly bloodstream and respiratory infections [34]. However, S. paucimobilis , an environnemental bacterium that rarely causes infection in human [35], was isolated for the first time from a hospital environment in Algeria. This is an intriguing discovery that particularly attracts attention. Other Gram-negative species were also identified, including Klebsiella pneumoniae , Pseudomonas aeruginosa , Pseudomonas fluorescens , Pasteurella testudinis , Rhizobium radiobacter, Pantoea sp , Serratia marcescens , and Kluyvera sp . Considering bacteria-fungus associations, only the following Gram-negative bacteria were co-isolated with Candida albicans from the same catheter; Klebsiella pneumoniae, Pseudomonas aeruginosa, and Pasteurella testudinis . In fact, serious co-infections are known to be exacerbated by catheter colonization caused by C. albicans / P. aeruginosa / K. pneumoniae association [36]. Although rare, the isolation of Rhizobium radiobacter requires particular clinical attention. Initially identified as a plant pathogen and soil saprophyte, this species is now recognized as an opportunistic pathogen in humans, often associated with immunosuppression and the use of invasive medical devices [37]. Moreover, cases of ceftazidime resistance in R. radiobacter have recently been reported, highlighting the need to control its spread [38], because resistant bacteria linked to biofilm formation are one of the main clinical concerns [39]. Determination of catheter infectivity types Analysis of culture-positive catheters (76%) highlighted three types of catheter infectivity. According to the results obtained, colonization was identified as the most frequent (32%), closely followed by contamination (26%), infection was responsible for 18% of cases of infectivity (figure 2). According to Quinet [18], a bacterial strain that colonizes a catheter causes an infection in 20% of cases. The results of this investigation, however, are not consistent with those of Touil et al. [40], who found that infection was the most common type of catheter-related contamination in the intensive care departments of the same university hospital in Tlemcen. On the other hand, it was found that the infectivity type was closely linked to the type of catheter used. Contamination was primarily associated with peripheral venous catheters, accounting for 45.83% of cases. In contrast, this type of infectivity was observed in only one-sixth (1/6) of cases involving central venous catheters. However, both central and peripheral venous catheters showed the same colonization rate (41.66%). Additionally, compared to peripheral venous catheters (12.5%), the infection rate observed with central venous catheters (41.66%) was more than three times greater. The confidence ellipses obtained through multiple correspondence analysis (MCA) illustrate the confidence ellipses around the variables studied, namely the type of infectivity and the catheter insertion time (Figure 3). MCA revealed a link between the three types of infectivity, specifically between colonization and contamination. Furthermore, the risk of infection associated with a medical device significantly impacted by how long it is in use. MCA highlighted a correlation with the catheter insertion time, thus emphasizing the importance of this variable. In fact, more than half (52.63%) of the catheters used for less than three days showed signs of contamination, this rate dropped to only 16.66% after this 3-day period. In contrast, for catheters used for three days or more, the colonization and infection rates were 61.11% and 27.77%, respectively. Regardless of the time of catheter insertion, once the catheter becomes contaminated, the risk of infection generally follows two mathematical models. The statistical study revealed that during the first three days, the progressive infectivity rate respects the following second-degree mathematical equation, y = 10.53 x 2 - 57.91 x + 100.01 . Beyond this period, it becomes y = - 38.895 x 2 + 161.14 x - 105.58 (Figure 4). The mathematical model highlights the importance of catheter insertion time in relation to the type of infectivity, hence its evolution from simple contamination to infection. According to this model, contamination is more pronounced before the third day following catheter insertion. But after this point, the colonization rate increases. Conversely, infection rate remains around 20 and 26 % regardless of the catheter insertion time. Seghir et al. [41], found that catheters left in place for three days or more were responsible for 75% of infections. This highlights the significant impact of catheter insertion time on their microbial alteration. In this same context, a prospective study conducted by Pitiriga et al. [42] in a Greek hospital revealed that, even with a comprehensive set of preventive measures in place, a longer catheter insertion time is associated with a higher infection rate. Furthermore, Fukuoka et al. [43] reported in their study that the risk of infection increases by 5% for each additional day of catheterization. Otherwise, an analysis of the distribution of infection types across different age groups of patients was conducted to determine whether there is a relationship between these two factors. It should be noted that the age groups were defined according to the classification proposed by Statistics Canada (n.d.) as follows: adolescents (15 to 24 years), adults (25 to 64 years), and older adults (65 years and older). The results indicate that catheter-related infections vary depending on the age of the patients. In adults, catheter colonization was significantly more frequent (46.15%), followed by contamination (34.62%) and infection (19.23%). In older adults patients, the infection rate reached 25%, while the rates of colonization and contamination were identical, at 37.5% each. These differences can be explained by the specific characteristics of each patient group studied, such as the presence of comorbidities, immunosuppression, or differences in healthcare practices. Contrary to what is generally reported in the literature, which often associates advanced age with increased vulnerability to catheter-related infections [44,45], our observations indicate that infection is the leading cause of catheter-related complications in adolescents, accounting for 50% of all cases. This high rate could be explained in part by the specific care practices used for this patient group, which is often perceived as being at lower risk. Microscopic a nalysis of c atheters The patient who was admitted to the hospital for AML, developed an embolism in the central venous catheter (CVC), which was removed after 18 days of placement. Scanning electron microscopy allowed for detailed observation of the inside of the CVC used. It showed a visible blood clot (Figure 5.1), and revealed echinocytes, or burr cells, as well as bacteria (Figure 5.2A). It also revealed red blood cells attached to each other by platelet filaments (Figure 5.2B). The CVC appears to play a role in the occurrence of the embolism in the patient described above, suggesting that a stimulus had caused platelet activation. These platelet filaments appear to hold the blood cells tightly attached, consequently causing the embolism. In addition, the red blood cells attached to each other by platelet filaments could partly explain the risk of embolism. The risk of venous embolism, indeed, increases in patients with AML due to prolonged hospitalization and the need for central venous access [14,46]. Embolism problems associated with CVC use are common and result in an increased risk of infections [47-49], as microorganisms can be deposited on catheter surfaces [50]. On the other hand, the microbiological examination of the same CVC revealed the existence of microbial biofilm. As shown in figure 6, this complex structure of the microbial sessile cells was surrounded by a dense cluster of red blood cells. This figure shows the infection risk associated with bacterial aggregation, leading to biofilm formation. This suggests that the formation of bacterial biofilms on the internal surface of the CVC substantially favors infection. The maintenance of a central venous catheter was associated with increased mortality [51]. Several researchers highlighted microbial biofilms in the inner surfaces of inpatients inserted catheters. All of them demonstrated the infectious risk regardless the use of CVC [5,52,53]. As soon as clinical signs and symptoms of infection appear in patients with CVC, diagnostic procedures for the detection of catheter-related infections should be initiated [54]. Conclusion This study examined the microbiological and clinical risks associated with catheter use in the clinical hematology department of the University Hospital - Tlemcen, Algeria. It revealed that nearly 70% of removed catheters had positive cultures. A high mortality rate of 13% was observed among patients during the study period. Mixed infections were frequent, with 44% being bacterial-bacterial and 8% bacterial-yeast combinations. More than half of the isolated bacteria were Gram-positive, primarily Staphylococcus sp . Among the Gram-negative bacteria, Enterobacter cloacae and Sphingomonas paucimobilis were notable, the latter being the first species isolated in an Algerian hospital. Klebsiella pneumoniae and Pseudomonas aeruginosa were also identified. The results revealed three types of infectivity; colonization (32%), contamination (26%) and infection (18%). Statistical analysis revealed a correlation between the type of infectivity and the duration of catheter insertion. This correlation was underscored by the mathematical model. Furthermore, the type of infectivity varied according to the patient's age. SEM examination of the inside of a CVC disclosed a clot of blood cells bound together by platelet filaments, as well as echinocytes. The analysis revealed the presence of a microbial biofilm surrounded by a dense cluster of red blood cells. This bacterial aggregate suggests that biofilm formation on the internal surface of the catheter significantly increases the likelihood of infection. Declarations Ethics and Consent statement. This study, entitled “ Infectivity in the clinical hematology department of a University Hospital in Tlemcen-Algeria: Involvement of microbial biofilms in catheters alteration ” was conducted in accordance with ethical standards. It received approval from the Ethics Committee of the University of Naama on September 25, 2021. All participants provided their informed consent in writing before being included in the study. They were clearly informed that their participation was voluntary and that they had the right to withdraw at any time, without having to provide a reason. To protect the privacy of participants, all data has been anonymized. Competing Interests The authors have no relevant financial or non-financial interests to disclose. No potential conflict of interest was reported by the authors. Funding The authors reported there is no funding associated with the work featured in this article. Author Contribution W.K. and S.M.L.S. Conceptualization, Investigation, Methodology, Writing -original draft.M.Y.M. and R.M.M. Formal analysis, Software.M.G., K.R. and .R. Investigation, Resources.A.F.B. Investigation. Acknowledgement The authors would like to thank Tugce Karakulak Uz, research engineer at the Swagelok Center for Surface Analysis of Materials at CWRU-USA, for his assistance. References Casalini G., Giacomelli A., Antinori S. 2024. 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Peripherally inserted central catheter in patients with acute myeloid leukemia: incidence and risk factors for premature removal. Leukemia & Lymphoma. 61(9): 2265-2267. Sivera P. 2022. Emerging data for cancer associated thrombosis treatment. Hematol Transfus Cell Ther. 44(S1): S1−S9. Ikram S, Heikal A, Finke S, Hofgaard A, Rehman Y, Sabri AN, & Økstad OA. 2019. Bacillus cereus biofilm formation on central venous catheters of hospitalised cardiac patients. Biofouling, 35(2): 204–216. Ngo Bell EC, Chapon V, Bessede E, Meriglier E, Issa N, Domblides C, Bonnet F, Vandenhende MA. (2024). Central venous catheter-related bloodstream infections: Epidemiology and risk factors for hematogenous complications. Infect Dis Now. 54(3): 104859. Yadav MK, Vidal JE, Song J-J. 2020. Microbial biofilms on medical indwelling devices. In : Yadav MK, Singh BP, New and Future Developments in Microbial Biotechnology and Bioengineering: Microbial Biofilms. Elsevier, 15-28. Sharma S, Mohler J, Mahajan SD, Schwartz SA, Bruggemann L, Aalinkeel R. 2023. Microbial Biofilm: A Review on Formation, Infection, Antibiotic Resistance, Control Measures, and Innovative Treatment. Microorganisms. 11(6):1614. Böll B, Schalk E, Buchheidt D, Hasenkamp J, Kiehl M, Kiderlen TR, et al. 2020. Central venous catheter–related infections in hematology and oncology: 2020 updated guidelines on diagnosis, management, and prevention by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol.100(1): 239-259. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8457760","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":568022107,"identity":"08061260-a555-47ff-bf74-57c01c84b192","order_by":0,"name":"Wafaa Kendil","email":"","orcid":"","institution":"University of Tlemcen","correspondingAuthor":false,"prefix":"","firstName":"Wafaa","middleName":"","lastName":"Kendil","suffix":""},{"id":568022108,"identity":"a8d3dc4c-7e30-4faa-a7ec-330aa0e8e27b","order_by":1,"name":"Moustapha Yassine Mahdad","email":"","orcid":"","institution":"University of Naama","correspondingAuthor":false,"prefix":"","firstName":"Moustapha","middleName":"Yassine","lastName":"Mahdad","suffix":""},{"id":568022109,"identity":"b5ad2edb-4ed2-42e9-9c50-169200bf4a87","order_by":2,"name":"Rida Mohammed Mediouni","email":"","orcid":"","institution":"University of Naama","correspondingAuthor":false,"prefix":"","firstName":"Rida","middleName":"Mohammed","lastName":"Mediouni","suffix":""},{"id":568022110,"identity":"d2e101ab-3c5a-457d-be17-edc12b3d8b81","order_by":3,"name":"Mahmoud Ghannoum","email":"","orcid":"","institution":"Case Western Reserve University","correspondingAuthor":false,"prefix":"","firstName":"Mahmoud","middleName":"","lastName":"Ghannoum","suffix":""},{"id":568022111,"identity":"a9f17eb1-71b7-4170-a03d-bcd960ae8c1a","order_by":4,"name":"Kyle Roberts","email":"","orcid":"","institution":"Case Western Reserve University","correspondingAuthor":false,"prefix":"","firstName":"Kyle","middleName":"","lastName":"Roberts","suffix":""},{"id":568022112,"identity":"add8a85a-9420-467c-8704-e21169b51f8e","order_by":5,"name":"Mauricio Retuerto","email":"","orcid":"","institution":"Case Western Reserve University","correspondingAuthor":false,"prefix":"","firstName":"Mauricio","middleName":"","lastName":"Retuerto","suffix":""},{"id":568022113,"identity":"d3a8a31c-aa27-4480-808c-bc581fc99ab1","order_by":6,"name":"Ahmed Fouad BENDAHMANE","email":"","orcid":"","institution":"University of Tlemcen","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"Fouad","lastName":"BENDAHMANE","suffix":""},{"id":568022114,"identity":"71e6d5cd-a043-45ee-b334-04b8bf9dda7c","order_by":7,"name":"Sidi Mohammed Lahbib Seddiki","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIie2QsQrCMBCGI64B15vsK0QEcRFfJSK0SyqCuwgOHd0kQtFXaN+gJeDUB4jEoZNTh44OIqYOgiCHbg75pnDk47//CHE4/hMGPINu88peM/qF0v9RsX8nq7cZpnjROtVlMQw2MswVJWevs1UlqW5IRHFcDLmGUOoZt8qlJ43PWjESw0AMgNcQJiBYvrur1spw1qaALHaonkrAGkUSNT6YoG5ThpTR1CoaeKNkNVGTxAibwrEuvu1SQE8W1VOZpkbM8zhDFotUeroel14nEv2aEzXamyAtsYt9BslwOBwOxzc8AIqaWCO/NR/fAAAAAElFTkSuQmCC","orcid":"","institution":"University of Naama","correspondingAuthor":true,"prefix":"","firstName":"Sidi","middleName":"Mohammed Lahbib","lastName":"Seddiki","suffix":""}],"badges":[],"createdAt":"2025-12-26 22:23:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8457760/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8457760/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100004337,"identity":"122cc70a-4404-4aa3-be99-d5e5835ca951","added_by":"auto","created_at":"2026-01-12 05:25:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":83750,"visible":true,"origin":"","legend":"\u003cp\u003eMicrobial alteration profile of catheters collected in the clinical hematology department of the University Hospital, Tlemcen-Algeria.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8457760/v1/947be3d4a24fc8ef9994567f.png"},{"id":100360192,"identity":"99b3f222-c65d-47ff-90e6-775d45849044","added_by":"auto","created_at":"2026-01-16 07:37:56","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":120687,"visible":true,"origin":"","legend":"\u003cp\u003eTypes of catheter infectivities based on positive microbiological tests results.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8457760/v1/919677d485cf6c7dc88c0175.png"},{"id":100361185,"identity":"ece01fc2-0619-404a-953a-585839c16f26","added_by":"auto","created_at":"2026-01-16 07:44:36","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":116873,"visible":true,"origin":"","legend":"\u003cp\u003ePlotellipses from multiple correspondence analysis illustrating confidence ellipses around the modalities of infectivity types and catheter insertion time (CIT).\u003c/p\u003e","description":"","filename":"33.png","url":"https://assets-eu.researchsquare.com/files/rs-8457760/v1/7474f18a481eae0948aa0a20.png"},{"id":100004338,"identity":"bf73c6a5-254e-4335-9c71-b93670364c64","added_by":"auto","created_at":"2026-01-12 05:25:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":45519,"visible":true,"origin":"","legend":"\u003cp\u003eMathematical simulation of the impact of catheter insertion time on the infectivity rate. The colors indicate: Blue ≤ 3 days, Orange \u0026gt; 3 days.\u003c/p\u003e","description":"","filename":"44.png","url":"https://assets-eu.researchsquare.com/files/rs-8457760/v1/f463a46089d2e568ec8c5bd5.png"},{"id":100004341,"identity":"cb92767e-05d1-47c9-8268-f490d59bfd41","added_by":"auto","created_at":"2026-01-12 05:25:45","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":717034,"visible":true,"origin":"","legend":"\u003cp\u003eSEM observation of the inside of a CVC. (1) Embolism in the catheter of a patient admitted to the clinical hematology department for treatment of acute myeloid leukemia. (2A) Echinocyte (large arrow) and microbial cells (small arrows). (2B) Blood cells linked together by platelet filaments. Image made with ThermoFisher Apreo 2S SEM.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8457760/v1/1e2095297e4e5b14fd7bf121.png"},{"id":100004340,"identity":"71eb7086-3d19-4ee9-800c-6487296cc00e","added_by":"auto","created_at":"2026-01-12 05:25:45","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":514450,"visible":true,"origin":"","legend":"\u003cp\u003eSEM observation of an embolism in the CVC associated with bacterial biofilm. The arrow indicates an echinocyte.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-8457760/v1/f0d1c1ce86316fc2ca7a9c2d.png"},{"id":100380800,"identity":"f2038b78-ba65-4135-9913-7f1043d98093","added_by":"auto","created_at":"2026-01-16 10:34:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2301703,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8457760/v1/4a9a9751-785d-4aab-8a5e-81f3888d7683.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Infectivity in the clinical hematology department of a University Hospital in Tlemcen-Algeria: Involvement of microbial biofilms in catheters alteration","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAccording to World Health Organization [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], 5 to 15% of hospitalized patients experience an infection related to their care. In developing countries, the risk is 2 to 20 times higher; in 2023, Raoofi et al. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] claimed that compared to other regions of the world, African nations have a higher occurrence of a factor of 0.27. In the hospital environment, the invasive procedure of using catheters plays a dual role; the first is to makes it easier to transfuse different physiological fluids, unfortunately the second is the alteration of these devices by microbial colonizers [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], hence the infectivity of catheters which varies according to the level of their infectiosity [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to Brun-Buisson et al. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], three types of catheter infectivity are known: contamination, colonization, and infection. It is therefore imperative to distinguish catheter infection from simple contamination before initiating antibiotic treatment [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Brun-Buisson et al. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] defined contamination as a non-significant positive culture (significance threshold\u0026thinsp;\u0026ge;\u0026thinsp;10\u003csup\u003e3\u003c/sup\u003e) without any local or general signs of infection, while colonization is characterized by a significant positive culture without any signs of infection. Conversely, infection is defined by a significant positive culture with the presence of signs of infection. In addition, catheters provide a gateway and prime surface for the adhesion of various pathogens. This leads to infections, affecting the lives of hospitalized patients, especially those with immune deficiencies [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eActually, catheters offer the perfect surface for the long-term adhesion of microorganisms, which promotes the development of biofilms [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This factor is essential for the persistence and severity of healthcare-associated infections, thereby limiting the range of possible treatments; due to the difficulty of removing a microbial biofilm once it has settled on a catheter [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], despite prospects highlighting substances with inhibitory effects against these complex structures [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOn the other hand, acute myeloid leukemia (AML) is a serious disease that affects the hematopoietic system; affected patients are very often victims of embolism [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The use of catheters is known to increase the risk of embolism and constitutes an ideal platform for the adhesion of microorganisms [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], especially since the sessile lifestyle is the most widespread form of microbial existence in nature [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Considering the invasive risk of infection associated with intravascular thrombosis of catheters, as well as their different infectivities [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], this study aimed to identify the different forms of catheter infectivity and to examine the biofilms that develop on their surfaces. This was achieved by including patients who were hospitalized to a university hospital in Algeria's clinical hematology department.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003ch2\u003e\u003cem\u003eCatheters collection\u0026nbsp;\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eThe samples were taken between October 2021 and June 2022. Thirty-six (36) venous catheters were collected from inpatients in the clinical hematology department of a university hospital in Tlemcen. It should be noted that only catheters implanted for 48 hours or more were included [18]. In order to complete the data relating to each sample, the clinical and personal information of each patient was taken into consideration, including their age, gender, reason for admission to hospital, body temperature at the time of sampling and other related data.\u003c/p\u003e\n\u003ch2\u003e\u003cem\u003eDetermination of catheter infectivity types\u003c/em\u003e\u003c/h2\u003e\n\u003cp\u003eAfter its removal, the distal end of each catheter was aseptically cut into a tube containing 5 mL of sterile saline solution. In order to detach microbial cells adhering to the catheters, the tubes were vortexed for one minute [6]. However,\u0026nbsp;it has been reported that agitation alone cannot detach all microorganisms from catheters\u0026nbsp;[19]; therefore, samples were subjected to ultrasonication (40 kHz, 100 W) for one minute. This approach was supported by Karbysheva et al.\u0026nbsp;[20]\u0026nbsp;for its effectiveness in diagnosing catheter-associated infections.\u003c/p\u003e\n\u003cp\u003eDetermination of catheter infectivity types was based on the presence or absence of a significant microbial load, as well as on associated signs of infection [6]. For this, 100 \u0026mu;L were inoculated from each decimal dilution of the sample (1/10, 1/100, and 1/1000). Bacteria were grown on nutrient agar and yeasts on Sabouraud dextrose agar; however, the inoculation of the agar allows just the active microbial flora to be assessed [21]. Simultaneously, a direct count of yeasts under the microscope, using Thoma cells, was carried out in order to determine their total number. Petri dishes were incubated at 37\u0026deg;C for 24 hours.\u003c/p\u003e\n\u003cp\u003eThe isolation of microorganisms, yeasts and bacteria, was approached extemporaneously with the study of catheters infectivity. The automated VITEK2 system (BioM\u0026eacute;rieux) and CHROM-Agar\u003csup\u003eTM\u003c/sup\u003e (Sigma) were used to identify the fungal isolates. Bacteria identification was performed using Api 20E\u0026reg;, Api 20NE\u0026reg;, Api Staph\u0026reg; and VITEK2 (BioM\u0026eacute;rieux).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMicroscopic\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003ea\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003enalysis of\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003ec\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eatheters\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMicrobial biofilms adhering to the surface of sampled catheters were examined using scanning electron microscopy (SEM), which offers high-resolution three-dimensional imaging of the observed structure\u0026nbsp;[22].\u003c/p\u003e\n\u003cp\u003eFor this purpose, a central venous catheter (CVC), taken from a 44-year-old patient, was examined under a microscope without being subjected to vortexing or sonication procedures, in order to preserve any possible microbial biofilm structures.\u003c/p\u003e\n\u003cp\u003eThis patient was admitted to the hospital for acute myeloid leukemia (AML), she was undergoing chemotherapy and had a CVC implanted in internal jugular line, which was inserted for ten days before it was removed for examination. It is important to note that this patient did not receive any anticoagulant, platelet or antibiotic treatment, but she was the victim of a previous SARS-Cov-2 infection six months prior.\u003c/p\u003e\n\u003cp\u003eBriefly, the catheter was dehydrated in a succession of ethanol concentrations (30%, 50%, 75%, and 100%) after being washed twice with sterile PBS and preserved overnight at 4\u0026deg;C using a 2.5% glutaraldehyde solution (Sigma-Aldrich, St. Louis, MO, USA). The catheter was then critical point dried, coated with palladium, and examined using a scanning electron microscope (ThermoFisher Scientific Apreo 2S).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed using SPSS version 27.0.1 A multiple correspondence analysis (MCA) was conducted to explore the associations between the categorical variables of the study.\u003c/p\u003e"},{"header":"Results and discussion","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCatheter collection\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong all collected catheters, 69.44% yielded a positive microbial culture. Given that 13% of patients died in the Clinical Hematology service during the collection period, this reflects the magnitude of the risk associated with catheter use in this department; whereas a rate close to that of the present study (61.8%) has been reported in this context\u0026nbsp;[23].\u003c/p\u003e\n\u003cp\u003eMicrobial analysis of the catheters revealed various alterations. Figure 1 summarizes the results of the microbial alteration profile of the catheters.\u003c/p\u003e\n\u003cp\u003eMicrobiological analysis of the catheters revealed a predominance of mixed microbial alterations, bacteria-bacteria or bacteria-yeast. Notably, 44% of the associations concerned bacteria, compared to 8% for bacteria-yeast associations. In contrast, single-species alterations were exclusively represented by bacteria. These results reflect the increasing complexity of infections associated with catheter use. It is important to emphasize that all patients included in this study received antibiotic treatment, exclusively antibacterial (vancomycin, metronidazole, imipenem/cilastatin, and ceftazidime). However, no antifungal treatment was initiated during the sampling period.\u003c/p\u003e\n\u003cp\u003eSix strains belonging to the genus \u003cem\u003eCandida\u0026nbsp;\u003c/em\u003ewere identified; five isolates were determined to be \u003cem\u003eC\u003c/em\u003e\u003cem\u003eandida\u003c/em\u003e\u003cem\u003e\u0026nbsp;albicans\u003c/em\u003e and one was \u003cem\u003eC. kefyr\u003c/em\u003e. \u003cem\u003eC. albicans\u003c/em\u003e is classified as a critical pathogen that poses a significant risk to public health [1], the predominance of this species is highlighted in scientific literature, which identifies this species as the most frequently isolated human pathogenic yeast on medical devices [24,25].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe isolation of \u003cem\u003eC. kefyr\u003c/em\u003e is noteworthy. As is the case in the present study, this species, generally considered a commensal organism, has recently emerged as an opportunistic pathogen, particularly in immunocompromised patients in a post-COVID-19 context [26]. Likewise, Ahmad et al. [27] indicated that this species can cause invasive infections.\u003c/p\u003e\n\u003cp\u003eThe identification of the isolated bacteria revealed a slight predominance of Gram-positive (56%) compared to Gram-negative bacteria. \u003cem\u003eStaphylococcus sp\u003c/em\u003e. was the most frequently isolated species (57,69%), a result also observed by Pietrocola et al. [28]. \u003cem\u003eS. haemolyticus\u003c/em\u003e, a coagulase-negative \u003cem\u003eStaphylococcus\u003c/em\u003e known for its pathogenic potential [10], was the most prevalent species within this group.\u003c/p\u003e\n\u003cp\u003eRegarding \u003cem\u003eS. aureus\u0026nbsp;\u003c/em\u003eand \u003cem\u003eS. epidermidis\u003c/em\u003e, the isolation rates were relatively low, given their clinical and epidemiological importance [29]. It should be noted that other species were also isolated, including \u003cem\u003eS. lentus\u0026nbsp;\u003c/em\u003eand \u003cem\u003eS. hominis\u003c/em\u003e. Further Gram-positive bacteria have been isolated, including \u003cem\u003eMicrococcus luteus, Bacillus sp., Dermacoccus nishinomiyaensis,\u0026nbsp;\u003c/em\u003eand \u003cem\u003eKocuria kristinae\u003c/em\u003e. These species are commensal of the skin and emerging pathogens\u0026nbsp;[30-33].\u003c/p\u003e\n\u003cp\u003eRegarding Gram-negative bacteria, \u003cem\u003eEnterobacter cloacae\u003c/em\u003e and \u003cem\u003eSphingomonas\u0026nbsp;\u003c/em\u003e\u003cem\u003epaucimobilis\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003ewere the most commonly isolated species (20% each), which reflects their capacity to survive on medical devices. The opportunistic enterobacterium is frequently associated with nosocomial infections, particularly bloodstream and respiratory infections [34]. However, \u003cem\u003eS.\u0026nbsp;\u003c/em\u003e\u003cem\u003epaucimobilis\u003c/em\u003e, an environnemental bacterium that rarely causes infection in human [35], was isolated for the first time from a hospital environment in Algeria. This is an intriguing discovery that particularly attracts attention.\u003c/p\u003e\n\u003cp\u003eOther Gram-negative species were also identified, including \u003cem\u003eKlebsiella\u0026nbsp;\u003c/em\u003e\u003cem\u003epneumoniae\u003c/em\u003e\u003cem\u003e, Pseudomonas\u0026nbsp;\u003c/em\u003e\u003cem\u003eaeruginosa\u003c/em\u003e\u003cem\u003e,\u0026nbsp;\u003c/em\u003e\u003cem\u003ePseudomonas fluorescens\u003c/em\u003e\u003cem\u003e,\u003c/em\u003e\u003cem\u003e\u0026nbsp;Pasteurella\u0026nbsp;\u003c/em\u003e\u003cem\u003etestudinis\u003c/em\u003e\u003cem\u003e, Rhizobium radiobacter, Pantoea\u0026nbsp;\u003c/em\u003e\u003cem\u003esp\u003c/em\u003e\u003cem\u003e, Serratia\u0026nbsp;\u003c/em\u003e\u003cem\u003emarcescens\u003c/em\u003e\u003cem\u003e,\u0026nbsp;\u003c/em\u003eand \u003cem\u003eKluyvera\u0026nbsp;\u003c/em\u003e\u003cem\u003esp\u003c/em\u003e. Considering bacteria-fungus associations, only the following Gram-negative bacteria were co-isolated with \u003cem\u003eCandida albicans\u003c/em\u003e from the same catheter; \u003cem\u003eKlebsiella pneumoniae, Pseudomonas aeruginosa,\u0026nbsp;\u003c/em\u003eand \u003cem\u003ePasteurella testudinis\u003c/em\u003e. In fact, serious co-infections are known to be exacerbated by catheter colonization caused by \u003cem\u003eC. albicans\u003c/em\u003e/\u003cem\u003eP. aeruginosa\u003c/em\u003e/\u003cem\u003eK. pneumoniae\u003c/em\u003e association [36].\u003c/p\u003e\n\u003cp\u003eAlthough rare, the isolation of \u003cem\u003eRhizobium radiobacter\u003c/em\u003e requires particular clinical attention. Initially identified as a plant pathogen and soil saprophyte, this species is now recognized as an opportunistic pathogen in humans, often associated with immunosuppression and the use of invasive medical devices [37]. Moreover, cases of ceftazidime resistance in \u003cem\u003eR. radiobacter\u003c/em\u003e have recently been reported, highlighting the need to control its spread [38], because resistant bacteria linked to biofilm formation are one of the main clinical concerns [39].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDetermination of catheter infectivity types\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnalysis of culture-positive catheters (76%) highlighted three types of catheter infectivity. According to the results obtained, colonization was identified as the most frequent (32%), closely followed by contamination (26%), infection was responsible for 18% of cases of infectivity (figure 2).\u003c/p\u003e\n\u003cp\u003eAccording to Quinet\u0026nbsp;[18], a bacterial strain that colonizes a catheter causes an infection in 20% of cases. The results of this investigation, however, are not consistent with those of Touil et al. [40], who found that infection was the most common type of catheter-related contamination in the intensive care departments of the same university hospital in Tlemcen.\u003c/p\u003e\n\u003cp\u003eOn the other hand, it was found that the infectivity type was closely linked to the type of catheter used. Contamination was primarily associated with peripheral venous catheters, accounting for 45.83% of cases. In contrast, this type of infectivity was observed in only one-sixth (1/6) of cases involving central venous catheters. However, both central and peripheral venous catheters showed the same colonization rate (41.66%). Additionally, compared to peripheral venous catheters (12.5%), the infection rate observed with central venous catheters (41.66%) was more than three times greater.\u003c/p\u003e\n\u003cp\u003eThe confidence ellipses obtained through multiple correspondence analysis (MCA) illustrate the confidence ellipses around the variables studied, namely the type of infectivity and the catheter insertion time (Figure 3). MCA revealed a link between the three types of infectivity, specifically between colonization and contamination.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, the risk of infection associated with a medical device significantly impacted by how long it is in use. MCA highlighted a correlation with the catheter insertion time, thus emphasizing the importance of this variable. In fact, more than half (52.63%) of the catheters used for less than three days showed signs of contamination, this rate dropped to only 16.66% after this 3-day period. In contrast, for catheters used for three days or more, the colonization and infection rates were 61.11% and 27.77%, respectively.\u003c/p\u003e\n\u003cp\u003eRegardless of the time of catheter insertion, once the catheter becomes contaminated, the risk of infection generally follows two mathematical models. The statistical study revealed that during the first three days, the progressive infectivity rate respects the following second-degree mathematical equation, \u003cstrong\u003ey = 10.53 x\u003csup\u003e2\u003c/sup\u003e - 57.91 x + 100.01\u003c/strong\u003e. Beyond this period, it becomes \u003cstrong\u003ey = - 38.895 x\u003csup\u003e2\u003c/sup\u003e + 161.14 x - 105.58\u003c/strong\u003e (Figure 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe mathematical model highlights the importance of catheter insertion time in relation to the type of infectivity, hence its evolution from simple contamination to infection. According to this model, contamination is more pronounced before the third day following catheter insertion. But after this point, the colonization rate increases. Conversely, infection rate remains around 20 and 26 % regardless of the catheter insertion time.\u003c/p\u003e\n\u003cp\u003eSeghir et al. [41], found that catheters left in place for three days or more were responsible for 75% of infections. This highlights the significant impact of catheter insertion time on their microbial alteration. In this same context, a prospective study conducted by Pitiriga et al.\u0026nbsp;[42]\u0026nbsp;in a Greek hospital revealed that, even with a comprehensive set of preventive measures in place, a longer catheter insertion time is associated with a higher infection rate. Furthermore, Fukuoka et al.\u0026nbsp;[43]\u0026nbsp;reported in their study that the risk of infection increases by 5% for each additional day of catheterization.\u003c/p\u003e\n\u003cp\u003eOtherwise, an analysis of the distribution of infection types across different age groups of patients was conducted to determine whether there is a relationship between these two factors. It should be noted that the age groups were defined according to the classification proposed by Statistics Canada (n.d.)\u0026nbsp;as follows: adolescents (15 to 24 years), adults (25 to 64 years), and older adults (65 years and older).\u003c/p\u003e\n\u003cp\u003eThe results indicate that catheter-related infections vary depending on the age of the patients. In adults, catheter colonization was significantly more frequent (46.15%), followed by contamination (34.62%) and infection (19.23%). In older adults patients, the infection rate reached 25%, while the rates of colonization and contamination were identical, at 37.5% each. These differences can be explained by the specific characteristics of each patient group studied, such as the presence of comorbidities, immunosuppression, or differences in healthcare practices.\u003c/p\u003e\n\u003cp\u003eContrary to what is generally reported in the literature, which often associates advanced age with increased vulnerability to catheter-related infections\u0026nbsp;[44,45], our observations indicate that infection is the leading cause of catheter-related complications in adolescents, accounting for 50% of all cases. This high rate could be explained in part by the specific care practices used for this patient group, which is often perceived as being at lower risk.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMicroscopic\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003ea\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003enalysis of\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003ec\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eatheters\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient who was admitted to the hospital for AML, developed an embolism in the central venous catheter (CVC), which was removed after 18 days of placement. Scanning electron microscopy allowed for detailed observation of the inside of the CVC used. It showed a visible blood clot (Figure 5.1), and revealed echinocytes, or burr cells, as well as bacteria (Figure 5.2A). It also revealed red blood cells attached to each other by platelet filaments (Figure 5.2B).\u003c/p\u003e\n\u003cp\u003eThe CVC appears to play a role in the occurrence of the embolism in the patient described above, suggesting that a stimulus had caused platelet activation. These platelet filaments appear to hold the blood cells tightly attached, consequently causing the embolism. In addition, the red blood cells attached to each other by platelet filaments could partly explain the risk of embolism. The risk of venous embolism, indeed, increases in patients with AML due to prolonged hospitalization and the need for central venous access [14,46]. Embolism problems associated with CVC use are common and result in an increased risk of infections [47-49], as microorganisms can be deposited on catheter surfaces [50].\u003c/p\u003e\n\u003cp\u003eOn the other hand, the microbiological examination of the same CVC revealed the existence of microbial biofilm. As shown in figure 6, this complex structure of the microbial sessile cells was surrounded by a dense cluster of red blood cells. This figure shows the infection risk associated with bacterial aggregation, leading to biofilm formation. This suggests that the formation of bacterial biofilms on the internal surface of the CVC substantially favors infection.\u003c/p\u003e\n\u003cp\u003eThe maintenance of a central venous catheter was associated with increased mortality [51]. Several researchers highlighted microbial biofilms in the inner surfaces of inpatients inserted catheters. All of them demonstrated the infectious risk regardless the use of CVC [5,52,53]. As soon as clinical signs and symptoms of infection appear in patients with CVC, diagnostic procedures for the detection of catheter-related infections should be initiated [54].\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study examined the microbiological and clinical risks associated with catheter use in the clinical hematology department of the University Hospital - Tlemcen, Algeria. It revealed that nearly 70% of removed catheters had positive cultures. A high mortality rate of 13% was observed among patients during the study period. Mixed infections were frequent, with 44% being bacterial-bacterial and 8% bacterial-yeast combinations. More than half of the isolated bacteria were Gram-positive, primarily \u003cem\u003eStaphylococcus sp\u003c/em\u003e. Among the Gram-negative bacteria, \u003cem\u003eEnterobacter cloacae\u003c/em\u003e and \u003cem\u003eSphingomonas paucimobilis\u003c/em\u003e were notable, the latter being the first species isolated in an Algerian hospital. \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e were also identified.\u003c/p\u003e \u003cp\u003eThe results revealed three types of infectivity; colonization (32%), contamination (26%) and infection (18%). Statistical analysis revealed a correlation between the type of infectivity and the duration of catheter insertion. This correlation was underscored by the mathematical model. Furthermore, the type of infectivity varied according to the patient's age.\u003c/p\u003e \u003cp\u003eSEM examination of the inside of a CVC disclosed a clot of blood cells bound together by platelet filaments, as well as echinocytes. The analysis revealed the presence of a microbial biofilm surrounded by a dense cluster of red blood cells. This bacterial aggregate suggests that biofilm formation on the internal surface of the catheter significantly increases the likelihood of infection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cspan\u003eEthics and Consent statement. This study, entitled \u0026ldquo; Infectivity in the clinical hematology department of a University Hospital in Tlemcen-Algeria: Involvement of microbial biofilms in catheters alteration \u0026rdquo; was conducted in accordance with ethical standards. It received approval from the Ethics Committee of the University of Naama on September 25, 2021. All participants provided their informed consent in writing before being included in the study. They were clearly informed that their participation was voluntary and that they had the right to withdraw at any time, without having to provide a reason. To protect the privacy of participants, all data has been anonymized.\u003c/span\u003e\u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose. No potential conflict of interest was reported by the authors.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors reported there is no funding associated with the work featured in this article.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eW.K. and S.M.L.S. Conceptualization, Investigation, Methodology, Writing -original draft.M.Y.M. and R.M.M. Formal analysis, Software.M.G., K.R. and .R. Investigation, Resources.A.F.B. Investigation.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors would like to thank Tugce Karakulak Uz, research engineer at the Swagelok Center for Surface Analysis of Materials at CWRU-USA, for his assistance.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eCasalini G.,\u0026ensp;Giacomelli A.,\u0026ensp;Antinori S. 2024. The WHO fungal priority pathogens list: a crucial reappraisal to review the prioritisation. 5(7): 717-724.\u003c/li\u003e\n \u003cli\u003eRaoofi S, Kan FP, Rafiei S, Hosseinipalangi Z, Mejareh ZN, Khani S, et al. 2023. Global prevalence of nosocomial infection: A systematic review and meta-analysis. \u003cem\u003ePLoSONE\u003c/em\u003e, \u003cem\u003e18\u003c/em\u003e(1), 1\u0026ndash;17.\u003c/li\u003e\n \u003cli\u003eSeddiki SML, Boucherit-Otmani Z, Boucherit K, \u0026amp; Kunkel D. 2015. Fungal infectivities of implanted catheters due to \u003cem\u003eCandida sp\u003c/em\u003e. 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Multidrug-Resistant \u003cem\u003eEnterobacter cloacae complex\u003c/em\u003e emerging as a global, diversifying threat. Frontiers in Microbiology. 10(1): 439849.\u003c/li\u003e\n \u003cli\u003eMarincu I, Bratosin F, Bogdan I, Dumitru C, Stoica CN, Csep AN, et al. 2023. Concurrent \u003cem\u003eSphingomonas paucimobilis\u003c/em\u003e and \u003cem\u003eMycobacterium tuberculosis Meningitis\u003c/em\u003e in an Immunocompromised Patient: A Rare Case Report and Comprehensive Review of Literature. Medicine. 59(4): 687.\u003c/li\u003e\n \u003cli\u003eSophonsri A, Kelsom C, Lou M, Nieberg P, \u0026amp; Wong-Beringer A. 2023. Risk Factors and outcome associated with coinfection with carbapenem-resistant \u003cem\u003eKlebsiella pneumonia\u003c/em\u003e and carbapenem-resistant \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e or \u003cem\u003eAcinetobacter baumanii\u003c/em\u003e: a descriptive analysis. 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Microbial biofilms on medical indwelling devices. \u003cem\u003eIn\u003c/em\u003e: Yadav MK, Singh BP, New and Future Developments in Microbial Biotechnology and Bioengineering: Microbial Biofilms. Elsevier, 15-28.\u003c/li\u003e\n \u003cli\u003eSharma S, Mohler J, Mahajan SD, Schwartz SA, Bruggemann L, Aalinkeel R. 2023. Microbial Biofilm: A Review on Formation, Infection, Antibiotic Resistance, Control Measures, and Innovative Treatment. Microorganisms. 11(6):1614.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eB\u0026ouml;ll B, Schalk E, Buchheidt D, Hasenkamp J, Kiehl M, Kiderlen TR, et al. 2020. Central venous catheter\u0026ndash;related infections in hematology and oncology: 2020 updated guidelines on diagnosis, management, and prevention by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol.100(1): 239-259.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hematology, Infectivity, Catheters, Biofilms, Scanning electron microscopy, Algeria","lastPublishedDoi":"10.21203/rs.3.rs-8457760/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8457760/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe use of catheters in hematology departments, particularly over extended periods, can lead to significant complications for patients. Microbiological alteration of these devices may result in various types of infectivity. Central venous catheters (CVC), as invasive medical devices, are particularly susceptible to colonization by bacteria capable of forming biofilms, thereby increasing the risk of associated infections. The aim of this study was to characterize the types of infectivity observed in the clinical hematology department of the University Hospital of Tlemcen (Algeria), identify the microbial species involved, and to examine the inner surfaces of altered CVC for the presence of bacterial biofilms using scanning electron microscopy.\u003c/p\u003e","manuscriptTitle":"Infectivity in the clinical hematology department of a University Hospital in Tlemcen-Algeria: Involvement of microbial biofilms in catheters alteration","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 05:25:40","doi":"10.21203/rs.3.rs-8457760/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2a1ce0a3-4fd4-49ed-9885-26852d751b91","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T05:25:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-12 05:25:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8457760","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8457760","identity":"rs-8457760","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}