Surveillance of Antimicrobial resistance among organism causing Bacteremia in patients admitted in Mbarara Regional Referral Hospital, Mbarara, Southwestern Uganda

Surveillance of Antimicrobial resistance among organism causing Bacteremia in patients admitted in Mbarara Regional Referral Hospital, Mbarara, Southwestern Uganda | 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 Article Surveillance of Antimicrobial resistance among organism causing Bacteremia in patients admitted in Mbarara Regional Referral Hospital, Mbarara, Southwestern Uganda Joel bazira, Nalumaga Pauline Petra, Jacob Iramiot, Baluku Kuraishi, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4384837/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 Blood stream infections are the major cause of fevers of undetermined origin in Africa. The continuing emergence of pathogenic microorganisms that are resistant to first-line antimicrobials is a cause of increasing Anti-Microbial Resistance concern. This study aimed at understanding the surveillance of antimicrobial resistance in order to serve as a quality assurance tool to determine common pathogens causing bacteremia, trends of antimicrobial resistance which will guide drug-policy decisions and facilitate rational use of drugs to prevent the further emergence of antimicrobial resistance. This study analyzed results of blood cultures that were routinely taken from patients of different age groups with fever or suspicion of sepsis among patients admitted in different wards of Mbarara Regional Referral Hospital and transported to Mbarara University of Science and Technology, the microbiology laboratory between 2015 and 2022. Bacterial isolates of clinical significance from specimens received during the study period were recorded in WHONET (surveillance software) and exported to STATA for analysis. Bloodstream infections were confirmed in 259 cases over the seven-year study period. Gram positive pathogens accounted for 160 (61.7%) in the confirmed infections while gram negative pathogens accounted for 99 (38.2%) of the cases. Staphylococcus aureus was the most isolated pathogen accounting for 57.1% (n=148) of the blood stream infections. Both the Gram positive and gram negative bacteria demonstrated increasing resistance towards among Ceftriaxone and Ampicillin. Using advanced information technology to study antimicrobial susceptibility patterns of resistant bacteria in blood culture isolates will be useful in directing empiric antibiotic therapy of severe sepsis in Uganda because laboratory data being will be collected and analyzed rapidly. Biological sciences/Microbiology Biological sciences/Microbiology/Bacteriology surveillance blood stream infections antibiotic resistance Mbarara Uganda. Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction In Africa, fever is usually a synonym for malaria. However, there is evidence that a significant number of fevers of undetermined origin (FUO) are caused by bacterial bloodstream infections (BBSI). FUO is frequently treated in Africa with antimalarial medications and antibacterial drugs such as chloramphenicol that have frequently proven ineffective ( 1 ). This shows the continuous evolving public health crisis of Antimicrobial resistance because of the global spread of multi and pan-resistant microbes that are resistant to the commonly available antibiotics ( 2 ). In the WHO African region in 2019, there were an estimated 1.05 million deaths (95% UI 829 000–1 316 000) associated with bacterial AMR and 250 000 deaths (192 000–325 000) with bloodstream infections (56 000 deaths [37 000–82 000], or 22%) attributed to of all estimated bacterial pathogen AMR deaths ( 3 ). Although Staphylococcus aureus is the predominant cause of BBSI in industrialized countries ( 4 ), in African countries such as Ghana or Kenya, gram-negative bacteria are identified most often in BBSI ( 5 , 6 ). The continuing emergence of pathogenic microorganisms that are resistant to first-line antimicrobials is a cause of increasing concern in Uganda. The facilitators of this growing resistance include; Uganda’s pharmaceutical gaps, poverty, increased empiric poly-antimicrobial use and poor adherence of dosage regimens ( 7 ). Preliminary studies carried out in the hospital on small sample sizes indicate an increase in the resistance to the commonly used antibiotics. These studies show the increased incidence of ESBL producing bacteria, Vancomycin resistant bacteria, MRSA, and the emergence of ESKAPE pathogens ( 8 ). This increased rate of resistance is associated with higher levels of mortality and morbidity which not only impacts on patients but also increases the burden on health care services leading to additional diagnostic testing, prolonged hospital stay and increased intensity and duration of treatment. Although the mechanisms by which organisms acquire resistance are often well understood such as the selective pressures arising from exposure to antimicrobials, the precise role of drug usage in selection of drug resistance has yet to be fully elucidated. There is evidence to suggest that more prudent usage of antimicrobials in human disease, animal husbandry and agriculture, could make a significant impact on the pace and extent to which resistance emerges in microorganisms pathogenic to man ( 9 ). It is imperative to preserve the effectiveness of common antibiotics by promoting rational use of antibiotics based on sound knowledge of local resistance patterns. In a hospital with bacteriology services, the implementation of a computerized surveillance system is a low-cost tool to make use of available resistance data. The objective of surveillance of antimicrobial resistance is to serve as a quality assurance tool to determine common pathogens causing bacteremia, trends of antimicrobial resistance which will guide drug-policy decisions and facilitate rational use of drugs to prevent the further emergence of antimicrobial resistance. Methods This was a retrospective study that examined the results of blood cultures that were routinely taken from patients of all age groups with fever or suspicion of sepsis admitted in different wards of Mbarara Regional Referral Hospital and transported to Mbarara University of Science and Technology, the microbiology laboratory from 2015 to 2022 from the microbiology laboratory of the Department of Microbiology, MUST, which receives samples from both the outpatient and inpatient departments of Mbarara Regional Referral Hospital (MRRH). MRRH is located in Mbarara, western Uganda, about 260 kilometers from Kampala capital city, and is also a teaching hospital for Mbarara University of Science and Technology. The hospital has 300 beds and provides a wide range of health services through its departments of pediatrics, obstetrics and gynecology, internal medicine, surgery, cancer unit, emergency and critical care, imaging, pathology, laboratories, and outpatient department. A recommended 7–10 mL of blood were taken for culture under aseptic conditions from all adult patients while 3–10 mL was collected from children admitted to the hospital with clinical suspicion of sepsis, severe sepsis, or septic shock ( 10 – 12 ). The blood samples were incubated for five days at 37℃ in the incubator followed by manually culturing on Blood agar, Maconkey agar and Chocolate agar ( 12 ). The isolated bacterial colonies were identified through Gram staining, colony morphology ( 13 ), Biochemical testing that included Citrate utilization test, Urease test, Triple sugar iron agar (TSI) test, Indole test, Sulphur indole motility, Catalase and coagulase tests ( 14 , 15 ) Susceptibility testing was performed on Muller Hinton Agar using the relevant antimicrobial agents basing on their availability to clinicians was determined by the modified Bauer-Kirby disc diffusion method. The breakpoint zone sizes were interpreted according to CLSI guidelines ( 16 ). The bacteria were tested with discs containing Cefuroxime (30µg), ampicillin (10 µg), ciprofloxacin (5 µg), ceftriaxone (30 µg), and gentamicin (10 µg). The control strains used were S. aureus ATCC 25923 and Klebsiella pneumoniae ATCC 700603. Ethical Clearance The study is under a big project “AMR surveillance, Modelling Antimicrobial pharmaceutical needs and PCR/Herbal/Biotechnological products development” in Uganda where an approval was obtained from Busitema University Faculty of Health Sciences REC with REC number BUFHS-2022-15. Upon clearance, informed consent was sought from the department of microbiology, Mbarara university of science and technology to access the isolates and corresponding information. All procedures performed were in accordance with relevant guidelines and regulations. Data Analysis plan All bacterial isolates of clinical significance from specimens received during the study period were recorded and analyzed. The captured data in the WHONET (surveillance software) was exported to STATA 17.0 software SE (StataCorp. LP, 2013, College Station, Texas, United States) for analysis. Results Prevalence of significant pathogens Bloodstream infections were confirmed in 259 cases over the ten-year study period. Gram positive pathogens accounted for 160 (61.7%) in the confirmed infections while gram negative pathogens accounted for 99 (38.2%) of the cases. Staphylococcus aureus was the most isolated pathogen accounting for 57.1% (n = 148) of the blood stream infections. The most isolated gram negative bacteria isolated was Salmonella spp which accounted for 15.4% (n = 40) of the infections followed by E.coli 13.9% (n = 36). Other isolated organisms included Klebsiella spp (n = 9), Enterobacter (n = 8), Streptococcus pneumoniae (n = 7), Citrobacter sp (n = 6) and Enterococcus sp (n = 5) (Table 1 and Fig. 1 ). S.aureus was the most isolated gram positive organism in confirmed blood stream infections. The trends of Staphylococcal blood stream infections increased gradually from 1.4% in 2015 to 1.9% in 2022. Trends in Salmonella sp . bloodstream infection showed fluctuating incidence from 6.5% in 2015 to 17.7% in 2019 and declined to 6.5% in 2020. In 2015, no confirmed cases of blood stream infections was caused by Escherichia coli. However, during the surveillance, it was noted that there was gradual increase of E.coli infections from 1.3% in 2016 to 13.3% in 2018, followed by a decline of these infections to 6.7% in 2019 until 2022. Although many organisms were isolated during the surveillance, there was no significant change of blood stream infections caused by Streptococcus sp , Klebsiella sp , Enterococci , Citrobacter sp and Enterobacter sp. Table 1 prevalence of significant pathogens isolated from 2015 to 2022 Organism 2015 2016 2017 2018 2019 2020 2021 2022 S.aureus 20(1.4%) 13(0.9%) 2(0.1%) 24(1.7%) 10(1.7%) 24(1.7%) 21(1.4%) 28(1.9%) E.coli 1(1.3%) 3(4.0%) 10(13.3%) 5(6.7%) 7(9.3%) 6(8.0%) 4(5.3%) Klebsiella sp 2(22.2%) 2(22.2%) 5(55.6%) Enterococcus sp 2(40%) 1(20%) 2(40%) Enterobacter sp 4(50%) 1(12.5%) 1(12.5%) 2(25%) Streptococcus pneumoniae 1(2.5%) 1(2.5%) 1(2.5%) 3(7.5%) 1(2.5%) Salmonella sp 4(6.5%) 11(17.7%) 6(9.7%) 4(6.5%) 11(17.7%) 4(6.5%) Citrobacter sp 1(16.7%) 2(33.3%) 3(50%) Trends of Antibiotic susceptibility Trends of antimicrobial resistance of the commonest causing pathogens was evaluated over the seven years of surveillance. A linear trend of increasing resistance was observed among gram positive pathogens causing blood stream infections against Ceftriaxone, Ampicillin and Ciprofloxacin as shown in Table 2 and Fig. 1 . Increase in Ceftriaxone resistance was observed from 48.1% in 2015 to 56.7% in 2022. Resistance towards Ampicillin increased from 62.5% in 2015 to 86.7% in 2022. Resistance towards gentamycin and pencillin showed decreasing trends from 51.6–35.6% and 100–88.6% respectively (Table 2 , Fig. 1 ). Table 2 Frequencies of resistance in gram positive organisms. Antibiotic 2015 2016 2017 2018 2019 2020 2021 2022 Ceftriaxone 48.1 54.1 33.3 48.8 43.8 61.9 50.0 56.7 Ampicillin 62.5 70.8 76.7 73.2 91.4 77.9 66.0 86.7 Cefuroxime 57.1 60.4 48.6 51.3 59.1 90.0 9.1 Ciprofloxacin 42.3 45.7 41.7 55.8 58.6 45.0 49.1 60.9 Gentamycin 51.6 50.0 58.2 43.1 36.4 35.1 28.7 35.6 Penicillin 100 100 100 84.9 80.9 85.9 71.4 88.6 However, in gram negative bacteria causing blood stream infections, a linear trend of increasing resistance was observed among Ceftriaxone (from 62.3% in 2015 to 73.7% in 2022) and Ampicillin (from 77.8% in 2015 to 95% in 2022) while decreasing trends of resistance were observed in cefuroxime (from 100% in 2015 to 33.3% in 2022) and gentamycin (from 62% in 2015 to 46.2% in 2022) (Table 3, Fig. 2 ). Trends of antibiotic susceptibility of the most isolated bacteria causing blood infections were evaluated. Staphylococcus aureus showed increasing susceptibility towards Vancomycin (44.4% in 2015 to 14.8% in 2022) and gentamycin (from 50.9% in 2015 to 35.2% in 2022). However, S.aureus showed gradual increase in resistance towards Ciprofloxacin (from 43.8% in 2015 to 61.7% in 2022) and Ampicillin (from 61.5% 2015 to 97.1% in 2022) as illustrated in Table 4 and Fig. 3 . E.coli demonstrated fluctuating resistance against all antibiotics (Table 5 , Fig. 4 ). Table 4 Susceptibility patterns of Staphylococcus aureus from 2015 to 2022 Antibiotic 2015 2016 2017 2018 2019 2020 2021 2022 Vancomycin 44.4 48.5 50.6 36.5 27.4 10.3 100 14.8 Penicillin 100 100 100 84.0 78.0 88.0 71.4 92.1 Ceftriaxone 59.5 71.4 60.0 45.7 50.0 100 58.8 Ampicillin 61.5 66.7 86.7 76.5 90.2 81.8 72.2 97.1 Cefuroxime 60.0 59.2 52.6 51.4 52.9 100 10.0 Ciprofloxacin 43.8 54.9 45.2 51.2 56.5 47.9 50.3 61.7 Gentamycin 50.9 51.6 58.3 46.9 37.5 34.5 28.8 35.2 Table 5 ; Susceptibility patterns of E.coli from 2015 to 2022 Antibiotic 2015 2016 2017 2018 2019 2020 2021 2022 Ceftriaxone 80.0 50.0 76.5 33.3 70.6 86.5 81.3 74.1 Ampicillin 100 88.9 91.8 88.3 95.7 91.5 83.1 97.2 Cefuroxime 100 100 81.5 76.6 81.2 92.3 90.5 40.0 Ciprofloxacin 81.3 43.5 50.0 45.1 68.8 54.2 64.5 62.7 Gentamycin 62.5 30.0 67.7 42.6 50.7 38.2 40.3 48.9 Discussion The seven-year surveillance of blood stream infections in Mbarara Regional Referral Hospital shows a marked increase in the incidence of bloodstream infection caused by all pathogens as well as increased prevalence of antimicrobial resistance amongst commonly used antibiotics from 2015 to 2022. Over the past years, the government of Uganda has had campaigns of food security, malaria control interventions, and increased use of antiretroviral therapy to try and improve the livelihood of its citizens. However, the increasing prevalence of Human Immunodeficiency Virus (HIV) infection in patients with sepsis in Uganda among other factors may have an impact in the rising blood stream infections (17-20). Generally, the isolated gram positive and gram negative bacteria showed increasing resistance towards ampicillin. This was similar to some findings (21, 22). Bacterial resistance is due to genetic mutations and acquired genomes (23). Furthermore, the incidence of ESBL producing bacteria and methicillin resistant Staphylococcus aureus in both community and hospital acquired infections has significantly increased (22, 24, 25). A predominance of gram-positive pathogens, in particular S. aureus , during the years of the study was noted. Staphylococcus aureus is a leading national and international cause of community-acquired and health care associated bacteremia (26). The predominance of this pathogen during the years of this study are consistent with findings from other studies in Uganda and other parts of the world (27-30). The increased prevalence of staphylococcal blood stream infections may be attributed to the social and economic factors that enable the easy community spread (31).a significant increase in S.aureus resistance towards Ampicillin and Ciprofloxacin during the surveillance was observed. These high rates of ciprofloxacin and Ampicillin resistance have been observed in other similar studies (32-34). The high rates of ciprofloxacin and ampicillin resistance may be due to the constant use and/or misuse of penicillins and fluoroquinolones in both animal and human consumption. The increased susceptibility was also observed in vancomycin, and these findings were similar to a study performed in South Korea (30). Pneumococcal bacteremia has greatly reduced globally due to the dramatically conjugant pneumococcal vaccination that was introduced in Uganda (35). However, a retrospective analysis of local surveillance data from three regions in Uganda highlighted an increased prevalence of 40.6% (36). Salmonella blood stream infections were observed 2015 to 2022, and had the peak infections in 2016 and 2019. This may be attributed to the poor waste management, and infections from animal sources that was observed in studies carried out during that time period (37, 38). These findings were consisted with other studies in Uganda (39, 40) The reduced incidence of Salmonella infections may be as a result of proper sanitation practices that have started being adopted as a result of government policies (41). The emergence and expansion of the MDR H58 haplotype (genotype 4.3.1) from South Asia into East Africa has led to the regional heterogeneity in the resistance patterns of Salmonella towards fluoroquinolones, raising concern for the rapid spread of ciprofloxacin-resistant salmonella strains in East Africa (42, 43). Escherichia coli bloodstream infections were observed throughout the study period. These findings were similar to other studies (44, 45). Therefore E.coli blood stream infections are common in Uganda and these infections are usually associated with onset UTIs (46). E.coli bacteremia may also be as a result of liver disease, immunosuppressant use, recent surgery, and prior use of cephalosporins or fluoroquinolones (47). The seven year surveillance has revealed a substantial shift in the types of bloodstream pathogens most commonly identified in our setting. Staphylococcus aureus bacteremia has remained the highest cause of blood stream infections possibly due to the hospital and community-based infection control and prevention interventions not being enhanced. Prospective studies on antimicrobial susceptibility patterns observing ESBL producing organisms, MRSA, Vancomycin resistant bacteria in blood culture isolates will be useful for directing empiric antibiotic therapy of severe sepsis in Uganda especially while using advanced information technology to aid in laboratory data being collected and analyzed rapidly. Declarations Data Availability The datasets used and analyzed during the current study available from the corresponding author on reasonable request. Conflicts of interest The authors confirm that they had no conflicts of interest. Funding The study obtained funding by the government of Uganda for the study entitled Pathogen Epidemiological studies no OP-STI-PRESIDEPATHOGEN-2021/2022/21 Authors’ contributions JB drafted the concept, BK participated in data collection and analysis. JB and NPP drafted the manuscript. HD, ML, AW, JI revised the manuscript. All authors read and approved the final version of the manuscript. References Tenover FC, Hughes JM. The challenges of emerging infectious diseases: development and spread of multiply-resistant bacterial pathogens. Jama. 1996;275(4):300-4. Sirijatuphat R, Sripanidkulchai K, Boonyasiri A, Rattanaumpawan P, Supapueng O, Kiratisin P, et al. Implementation of global antimicrobial resistance surveillance system (GLASS) in patients with bacteremia. PloS one. 2018;13(1):e0190132. Sartorius B, Gray AP, Weaver ND, Aguilar GR, Swetschinski LR, Ikuta KS, et al. 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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-4384837","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":306031123,"identity":"12ec634a-106b-41bd-b937-a96d2bad1130","order_by":0,"name":"Joel bazira","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIiWNgGAWjYBACxhlAIoGBQY50LcYgdgNxeiQgVGID0VqYZzc//vBwj1362hnpzx8w1NgxGJxfQMBhc44ZGCQ8S87ddiPHsIHhWDKDwY0HBLTMSDBISDjADNICdBjbAaCWA4S0pH84kHCgPt3sRvrDBoZ/RGkBuifhwOEEsxsJhg2MbUAt5xsI+eVMMUPCgeOG2868MZyR2JfMI3kDvw4Gw9ntmz/+OFAtb3Y8/cGHD9/s5PjOE3CYIYorEhgYeBgkEvBrkccU4idgyygYBaNgFIw4AACu5k1B1e1olQAAAABJRU5ErkJggg==","orcid":"","institution":"Mbarara University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Joel","middleName":"","lastName":"bazira","suffix":""},{"id":306031124,"identity":"67f640b4-9f20-49ef-b97c-19dcf44cd46f","order_by":1,"name":"Nalumaga Pauline Petra","email":"","orcid":"","institution":"Mbarara University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Nalumaga","middleName":"Pauline","lastName":"Petra","suffix":""},{"id":306031125,"identity":"c826e5ce-516e-4f1e-9cd5-15be945cf024","order_by":2,"name":"Jacob Iramiot","email":"","orcid":"","institution":"Busitema University","correspondingAuthor":false,"prefix":"","firstName":"Jacob","middleName":"","lastName":"Iramiot","suffix":""},{"id":306031126,"identity":"9498f8bd-2ee1-4489-8470-bdbf4350fb72","order_by":3,"name":"Baluku Kuraishi","email":"","orcid":"","institution":"Mbarara University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Baluku","middleName":"","lastName":"Kuraishi","suffix":""},{"id":306031127,"identity":"770e4822-aadb-46fa-9de9-c0fca8a8c94e","order_by":4,"name":"Abel Walekhwa","email":"","orcid":"","institution":"University of Cambridge","correspondingAuthor":false,"prefix":"","firstName":"Abel","middleName":"","lastName":"Walekhwa","suffix":""},{"id":306031128,"identity":"927064e0-f6b6-46fc-9205-edd40e986d86","order_by":5,"name":"Hope Derick","email":"","orcid":"","institution":"Muni University","correspondingAuthor":false,"prefix":"","firstName":"Hope","middleName":"","lastName":"Derick","suffix":""},{"id":306031130,"identity":"e3617284-abf3-4587-99dd-1d151e6a7e22","order_by":6,"name":"Lawrence Mugisha","email":"","orcid":"","institution":"Makerere University","correspondingAuthor":false,"prefix":"","firstName":"Lawrence","middleName":"","lastName":"Mugisha","suffix":""}],"badges":[],"createdAt":"2024-05-07 18:26:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4384837/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4384837/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57518398,"identity":"707448cf-97fc-4d30-bccb-2da52b7069da","added_by":"auto","created_at":"2024-05-31 20:33:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":57354,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003etrends of resistance of Gram positive bacteria towards commonly used antibiotics.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4384837/v1/38db3e2d690a232bd40d6d57.jpg"},{"id":57517803,"identity":"e3a761b5-4d61-4ec7-beb0-f4443e0c9c16","added_by":"auto","created_at":"2024-05-31 20:25:19","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":57713,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003etrends of resistance of Gram negative bacteria towards commonly used antibiotics.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4384837/v1/d2d12108917d5e488fa51950.jpg"},{"id":57517806,"identity":"5e92eb12-c978-44ec-b120-5f6714ea078a","added_by":"auto","created_at":"2024-05-31 20:25:19","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":69977,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSusceptibility patterns of Staphylococcus aureus in %age from 2015 to 2022\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4384837/v1/7befd82abd8343a9fa66bce3.jpg"},{"id":57517807,"identity":"38fa07cc-c9d4-4f1c-ac2a-91d250dfbe39","added_by":"auto","created_at":"2024-05-31 20:25:19","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":77222,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSusceptibility pattern of \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eE.coli\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003efrom 2015 to 2022\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4384837/v1/161c323fc31d36e48ef15d47.jpg"},{"id":70347133,"identity":"3995e812-18e3-41bb-a99e-dbf0ce0af410","added_by":"auto","created_at":"2024-12-02 11:17:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":879587,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4384837/v1/2d5218a4-4b87-477f-88de-62181efe3282.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Surveillance of Antimicrobial resistance among organism causing Bacteremia in patients admitted in Mbarara Regional Referral Hospital, Mbarara, Southwestern Uganda","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn Africa, fever is usually a synonym for malaria. However, there is evidence that a significant number of fevers of undetermined origin (FUO) are caused by bacterial bloodstream infections (BBSI). FUO is frequently treated in Africa with antimalarial medications and antibacterial drugs such as chloramphenicol that have frequently proven ineffective (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). This shows the continuous evolving public health crisis of Antimicrobial resistance because of the global spread of multi and pan-resistant microbes that are resistant to the commonly available antibiotics (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the WHO African region in 2019, there were an estimated 1.05\u0026nbsp;million deaths (95% UI 829 000\u0026ndash;1 316 000) associated with bacterial AMR and 250 000 deaths (192 000\u0026ndash;325 000) with bloodstream infections (56 000 deaths [37 000\u0026ndash;82 000], or 22%) attributed to of all estimated bacterial pathogen AMR deaths (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Although \u003cem\u003eStaphylococcus aureus\u003c/em\u003e is the predominant cause of BBSI in industrialized countries (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), in African countries such as Ghana or Kenya, gram-negative bacteria are identified most often in BBSI (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe continuing emergence of pathogenic microorganisms that are resistant to first-line antimicrobials is a cause of increasing concern in Uganda. The facilitators of this growing resistance include; Uganda\u0026rsquo;s pharmaceutical gaps, poverty, increased empiric poly-antimicrobial use and poor adherence of dosage regimens (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Preliminary studies carried out in the hospital on small sample sizes indicate an increase in the resistance to the commonly used antibiotics. These studies show the increased incidence of ESBL producing bacteria, Vancomycin resistant bacteria, MRSA, and the emergence of ESKAPE pathogens (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This increased rate of resistance is associated with higher levels of mortality and morbidity which not only impacts on patients but also increases the burden on health care services leading to additional diagnostic testing, prolonged hospital stay and increased intensity and duration of treatment. Although the mechanisms by which organisms acquire resistance are often well understood such as the selective pressures arising from exposure to antimicrobials, the precise role of drug usage in selection of drug resistance has yet to be fully elucidated. There is evidence to suggest that more prudent usage of antimicrobials in human disease, animal husbandry and agriculture, could make a significant impact on the pace and extent to which resistance emerges in microorganisms pathogenic to man (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIt is imperative to preserve the effectiveness of common antibiotics by promoting rational use of antibiotics based on sound knowledge of local resistance patterns. In a hospital with bacteriology services, the implementation of a computerized surveillance system is a low-cost tool to make use of available resistance data. The objective of surveillance of antimicrobial resistance is to serve as a quality assurance tool to determine common pathogens causing bacteremia, trends of antimicrobial resistance which will guide drug-policy decisions and facilitate rational use of drugs to prevent the further emergence of antimicrobial resistance.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis was a retrospective study that examined the results of blood cultures that were routinely taken from patients of all age groups with fever or suspicion of sepsis admitted in different wards of Mbarara Regional Referral Hospital and transported to Mbarara University of Science and Technology, the microbiology laboratory from 2015 to 2022 from the microbiology laboratory of the Department of Microbiology, MUST, which receives samples from both the outpatient and inpatient departments of Mbarara Regional Referral Hospital (MRRH).\u003c/p\u003e \u003cp\u003eMRRH is located in Mbarara, western Uganda, about 260 kilometers from Kampala capital city, and is also a teaching hospital for Mbarara University of Science and Technology. The hospital has 300 beds and provides a wide range of health services through its departments of pediatrics, obstetrics and gynecology, internal medicine, surgery, cancer unit, emergency and critical care, imaging, pathology, laboratories, and outpatient department.\u003c/p\u003e \u003cp\u003eA recommended 7\u0026ndash;10 mL of blood were taken for culture under aseptic conditions from all adult patients while 3\u0026ndash;10 mL was collected from children admitted to the hospital with clinical suspicion of sepsis, severe sepsis, or septic shock (\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The blood samples were incubated for five days at 37℃ in the incubator followed by manually culturing on Blood agar, Maconkey agar and Chocolate agar (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The isolated bacterial colonies were identified through Gram staining, colony morphology (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), Biochemical testing that included Citrate utilization test, Urease test, Triple sugar iron agar (TSI) test, Indole test, Sulphur indole motility, Catalase and coagulase tests (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eSusceptibility testing was performed on Muller Hinton Agar using the relevant antimicrobial agents basing on their availability to clinicians was determined by the modified Bauer-Kirby disc diffusion method. The breakpoint zone sizes were interpreted according to CLSI guidelines (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The bacteria were tested with discs containing Cefuroxime (30\u0026micro;g), ampicillin (10 \u0026micro;g), ciprofloxacin (5 \u0026micro;g), ceftriaxone (30 \u0026micro;g), and gentamicin (10 \u0026micro;g). The control strains used were \u003cem\u003eS. aureus\u003c/em\u003e ATCC 25923 and \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e ATCC 700603.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthical Clearance\u003c/h2\u003e \u003cp\u003e The study is under a big project \u0026ldquo;AMR surveillance, Modelling Antimicrobial pharmaceutical needs and PCR/Herbal/Biotechnological products development\u0026rdquo; in Uganda where an approval was obtained from Busitema University Faculty of Health Sciences REC with REC number BUFHS-2022-15. Upon clearance, informed consent was sought from the department of microbiology, Mbarara university of science and technology to access the isolates and corresponding information. All procedures performed were in accordance with relevant guidelines and regulations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis plan\u003c/h2\u003e \u003cp\u003eAll bacterial isolates of clinical significance from specimens received during the study period were recorded and analyzed. The captured data in the WHONET (surveillance software) was exported to STATA 17.0 software SE (StataCorp. LP, 2013, College Station, Texas, United States) for analysis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003ePrevalence of significant pathogens\u003c/h2\u003e\n \u003cp\u003eBloodstream infections were confirmed in 259 cases over the ten-year study period. Gram positive pathogens accounted for 160 (61.7%) in the confirmed infections while gram negative pathogens accounted for 99 (38.2%) of the cases. \u003cem\u003eStaphylococcus aureus\u003c/em\u003e was the most isolated pathogen accounting for 57.1% (n\u0026thinsp;=\u0026thinsp;148) of the blood stream infections. The most isolated gram negative bacteria isolated was \u003cem\u003eSalmonella spp\u003c/em\u003e which accounted for 15.4% (n\u0026thinsp;=\u0026thinsp;40) of the infections followed by \u003cem\u003eE.coli\u003c/em\u003e 13.9% (n\u0026thinsp;=\u0026thinsp;36). Other isolated organisms included \u003cem\u003eKlebsiella spp\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;9), \u003cem\u003eEnterobacter\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;8), \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;7), \u003cem\u003eCitrobacter sp\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;6) and \u003cem\u003eEnterococcus sp\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;5) (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eS.aureus\u003c/em\u003e was the most isolated gram positive organism in confirmed blood stream infections. The trends of Staphylococcal blood stream infections increased gradually from 1.4% in 2015 to 1.9% in 2022. Trends in \u003cem\u003eSalmonella sp\u003c/em\u003e. bloodstream infection showed fluctuating incidence from 6.5% in 2015 to 17.7% in 2019 and declined to 6.5% in 2020. In 2015, no confirmed cases of blood stream infections was caused by \u003cem\u003eEscherichia coli.\u003c/em\u003e However, during the surveillance, it was noted that there was gradual increase of \u003cem\u003eE.coli\u003c/em\u003e infections from 1.3% in 2016 to 13.3% in 2018, followed by a decline of these infections to 6.7% in 2019 until 2022. Although many organisms were isolated during the surveillance, there was no significant change of blood stream infections caused by \u003cem\u003eStreptococcus sp\u003c/em\u003e, \u003cem\u003eKlebsiella sp\u003c/em\u003e, \u003cem\u003eEnterococci\u003c/em\u003e, \u003cem\u003eCitrobacter sp\u003c/em\u003e and \u003cem\u003eEnterobacter sp.\u003c/em\u003e\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eprevalence of significant pathogens isolated from 2015 to 2022\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"9\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOrganism\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eS.aureus\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13(0.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2(0.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24(1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24(1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21(1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(1.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eE.coli\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1(1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3(4.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10(13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(9.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6(8.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(5.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eKlebsiella sp\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(22.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(22.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(55.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEnterococcus sp\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEnterobacter sp\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1(12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1(12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1(2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1(2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eSalmonella sp\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11(17.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6(9.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4(6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(17.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(6.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eCitrobacter sp\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1(16.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2(33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003eTrends of Antibiotic susceptibility\u003c/h2\u003e\n \u003cp\u003eTrends of antimicrobial resistance of the commonest causing pathogens was evaluated over the seven years of surveillance. A linear trend of increasing resistance was observed among gram positive pathogens causing blood stream infections against Ceftriaxone, Ampicillin and Ciprofloxacin as shown in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Increase in Ceftriaxone resistance was observed from 48.1% in 2015 to 56.7% in 2022. Resistance towards Ampicillin increased from 62.5% in 2015 to 86.7% in 2022. Resistance towards gentamycin and pencillin showed decreasing trends from 51.6\u0026ndash;35.6% and 100\u0026ndash;88.6% respectively (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eFrequencies of resistance in gram positive organisms.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"9\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAntibiotic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCeftriaxone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e48.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e56.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmpicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e77.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCefuroxime\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e48.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCiprofloxacin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e55.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e60.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGentamycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e35.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e35.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePenicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e84.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e80.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e85.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e88.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eHowever, in gram negative bacteria causing blood stream infections, a linear trend of increasing resistance was observed among Ceftriaxone (from 62.3% in 2015 to 73.7% in 2022) and Ampicillin (from 77.8% in 2015 to 95% in 2022) while decreasing trends of resistance were observed in cefuroxime (from 100% in 2015 to 33.3% in 2022) and gentamycin (from 62% in 2015 to 46.2% in 2022) (Table 3, Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003e\u003cimg 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\" style=\"width: 675px; height: 333.206px;\" width=\"675\" height=\"333.206\"\u003e\u003c/p\u003e\n \u003cp\u003eTrends of antibiotic susceptibility of the most isolated bacteria causing blood infections were evaluated. \u003cem\u003eStaphylococcus aureus\u003c/em\u003e showed increasing susceptibility towards Vancomycin (44.4% in 2015 to 14.8% in 2022) and gentamycin (from 50.9% in 2015 to 35.2% in 2022). However, S.aureus showed gradual increase in resistance towards Ciprofloxacin (from 43.8% in 2015 to 61.7% in 2022) and Ampicillin (from 61.5% 2015 to 97.1% in 2022) as illustrated in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. \u003cem\u003eE.coli\u003c/em\u003e demonstrated fluctuating resistance against all antibiotics (Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSusceptibility patterns of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e from 2015 to 2022\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"9\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAntibiotic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVancomycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePenicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e84.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e78.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e92.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCeftriaxone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmpicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e97.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCefuroxime\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCiprofloxacin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e56.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGentamycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e46.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e35.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e; Susceptibility patterns of \u003cem\u003eE.coli\u003c/em\u003e from 2015 to 2022\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"9\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAntibiotic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCeftriaxone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e81.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmpicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e88.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e95.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e83.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e97.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCefuroxime\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e81.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e81.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e92.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCiprofloxacin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e62.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGentamycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e67.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e42.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e50.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e48.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe seven-year surveillance of blood stream infections in Mbarara Regional Referral Hospital shows a marked increase in the incidence of bloodstream infection caused by all pathogens as well as increased prevalence of antimicrobial resistance amongst commonly used antibiotics from 2015 to 2022. Over the past years, the government of Uganda has had campaigns of food security, malaria control interventions, and increased use of antiretroviral therapy to try and improve the livelihood of its citizens. However, the increasing prevalence of Human Immunodeficiency Virus (HIV) infection in patients with sepsis in Uganda among other factors may have an impact in the rising blood stream infections (17-20).\u003c/p\u003e\n\u003cp\u003eGenerally, the isolated gram positive and gram negative bacteria showed increasing resistance towards ampicillin. This was similar to some findings (21, 22). Bacterial resistance is due to genetic mutations and acquired genomes (23). Furthermore, the incidence of ESBL producing bacteria and methicillin resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e in both community and hospital acquired infections has significantly increased (22, 24, 25). \u003c/p\u003e\n\u003cp\u003eA predominance of gram-positive pathogens, in particular \u003cem\u003eS. aureus\u003c/em\u003e, during the years of the study was noted. \u003cem\u003eStaphylococcus aureus\u003c/em\u003e is a leading national and international cause of community-acquired and health care associated bacteremia (26). The predominance of this pathogen during the years of this study are consistent with findings from other studies in Uganda and other parts of the world (27-30). The increased prevalence of staphylococcal blood stream infections may be attributed to the social and economic factors that enable the easy community spread (31).a significant increase in \u003cem\u003eS.aureus\u003c/em\u003e resistance towards Ampicillin and Ciprofloxacin during the surveillance was observed. These high rates of ciprofloxacin and Ampicillin resistance have been observed in other similar studies (32-34). The high rates of ciprofloxacin and ampicillin resistance may be due to the constant use and/or misuse of penicillins and fluoroquinolones in both animal and human consumption. The increased susceptibility was also observed in vancomycin, and these findings were similar to a study performed in South Korea (30). \u003c/p\u003e\n\u003cp\u003ePneumococcal bacteremia has greatly reduced globally due to the dramatically conjugant pneumococcal vaccination that was introduced in Uganda (35). However, a retrospective analysis of local surveillance data from three regions in Uganda highlighted an increased prevalence of 40.6% (36).\u003c/p\u003e\n\u003cp\u003eSalmonella blood stream infections were observed 2015 to 2022, and had the peak infections in 2016 and 2019. This may be attributed to the poor waste management, and infections from animal sources that was observed in studies carried out during that time period (37, 38). These findings were consisted with other studies in Uganda (39, 40) The reduced incidence of Salmonella infections may be as a result of proper sanitation practices that have started being adopted as a result of government policies (41). The emergence and expansion of the MDR H58 haplotype (genotype 4.3.1) from South Asia into East Africa has led to the regional heterogeneity in the resistance patterns of Salmonella towards fluoroquinolones, raising concern for the rapid spread of ciprofloxacin-resistant salmonella strains in East Africa (42, 43).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e bloodstream infections were observed throughout the study period. These findings were similar to other studies (44, 45). Therefore \u003cem\u003eE.coli\u003c/em\u003e blood stream infections are common in Uganda and these infections are usually associated with onset UTIs (46). \u003cem\u003eE.coli\u003c/em\u003e bacteremia may also be as a result of liver disease, immunosuppressant use, recent surgery, and prior use of cephalosporins or fluoroquinolones (47). \u003c/p\u003e\n\u003cp\u003eThe seven year surveillance has revealed a substantial shift in the types of bloodstream pathogens most commonly identified in our setting. \u003cem\u003eStaphylococcus aureus\u003c/em\u003e bacteremia has remained the highest cause of blood stream infections possibly due to the hospital and community-based infection control and prevention interventions not being enhanced. \u003c/p\u003e\n\u003cp\u003eProspective studies on antimicrobial susceptibility patterns observing ESBL producing organisms, MRSA, Vancomycin resistant bacteria in blood culture isolates will be useful for directing empiric antibiotic therapy of severe sepsis in Uganda especially while using advanced information technology to aid in laboratory data being collected and analyzed rapidly.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that they had no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study obtained funding by the government of Uganda for the study entitled Pathogen Epidemiological studies no OP-STI-PRESIDEPATHOGEN-2021/2022/21\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJB drafted the concept, BK participated in data collection and analysis. JB and NPP drafted the manuscript. HD, ML, AW, JI revised the manuscript. All authors read and approved the final version of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTenover FC, Hughes JM. The challenges of emerging infectious diseases: development and spread of multiply-resistant bacterial pathogens. Jama. 1996;275(4):300-4.\u003c/li\u003e\n\u003cli\u003eSirijatuphat R, Sripanidkulchai K, Boonyasiri A, Rattanaumpawan P, Supapueng O, Kiratisin P, et al. Implementation of global antimicrobial resistance surveillance system (GLASS) in patients with bacteremia. PloS one. 2018;13(1):e0190132.\u003c/li\u003e\n\u003cli\u003eSartorius B, Gray AP, Weaver ND, Aguilar GR, Swetschinski LR, Ikuta KS, et al. The burden of bacterial antimicrobial resistance in the WHO African region in 2019: a cross-country systematic analysis. The Lancet Global Health. 2024;12(2):e201-e16.\u003c/li\u003e\n\u003cli\u003eStamm W, Grayson M, Nicolle L, Powell M. WHO Global Strategy for Containment of Antimicrobial Resistance (Document no: WHO/CDS/CSR/DRS/2001.2). Geneva, World Health Organization. 2001.\u003c/li\u003e\n\u003cli\u003eO\u0026apos;Brien TF. The global epidemic nature of antimicrobial resistance and the need to monitor and manage it locally. Clinical Infectious Diseases. 1997;24(Supplement_1):S2-S8.\u003c/li\u003e\n\u003cli\u003eCohen ML. Epidemiology of drug resistance: implications for a post\u0026mdash;antimicrobial era. Science. 1992;257(5073):1050-5.\u003c/li\u003e\n\u003cli\u003eVikesland P, Garner E, Gupta S, Kang S, Maile-Moskowitz A, Zhu N. Differential drivers of antimicrobial resistance across the world. Accounts of chemical research. 2019;52(4):916-24.\u003c/li\u003e\n\u003cli\u003eWang H, Chen M, Group CNPRSS. Surveillance for antimicrobial resistance among clinical isolates of gram-negative bacteria from intensive care unit patients in China, 1996 to 2002. 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Neonatal sepsis at Mulago national referral hospital in Uganda: Etiology, antimicrobial resistance, associated factors and case fatality risk. PloS one. 2020;15(8):e0237085.\u003c/li\u003e\n\u003cli\u003eBaguma A, Musinguzi B, Kagirita AA, Bazira J. Antimicrobial resistance profile among bacteria isolated from patients presenting with wounds at Kabale Regional Referral Hospital, South western Uganda. 2020.\u003c/li\u003e\n\u003cli\u003eLwigale F. Antimicrobial resistance patterns of bacterial isolates from bloodstream infections at Jinja regional referral hospital: A cross-sectional study. medRxiv. 2023:2023.08. 09.23293917.\u003c/li\u003e\n\u003cli\u003eKim D, Yoon E-J, Hong JS, Choi MH, Kim HS, Kim YR, et al. Major bloodstream infection-causing bacterial pathogens and their antimicrobial resistance in South Korea, 2017\u0026ndash;2019: Phase i report from kor-glass. 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IJID regions. 2022;5:72-8.\u003c/li\u003e\n\u003cli\u003eLubwama M, Kateete DP, Katende G, Kigozi E, Orem J, Phipps W, et al. CTX-M, TEM, and SHV Genes in Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp Isolated from Hematologic Cancer Patients with Bacteremia in Uganda. Infection and Drug Resistance. 2024;17(null):641-53.\u003c/li\u003e\n\u003cli\u003ePitout JD, Laupland KB. Extended-spectrum \u0026beta;-lactamase-producing Enterobacteriaceae: an emerging public-health concern. The Lancet infectious diseases. 2008;8(3):159-66.\u003c/li\u003e\n\u003cli\u003eHa YE, Kang C-I, Cha MK, Park SY, Wi YM, Chung DR, et al. Epidemiology and clinical outcomes of bloodstream infections caused by extended-spectrum \u0026beta;-lactamase-producing Escherichia coli in patients with cancer. International journal of antimicrobial agents. 2013;42(5):403-9.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"surveillance, blood stream infections, antibiotic resistance, Mbarara, Uganda.","lastPublishedDoi":"10.21203/rs.3.rs-4384837/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4384837/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBlood stream infections are the major cause of fevers of undetermined origin in Africa. The continuing emergence of pathogenic microorganisms that are resistant to first-line antimicrobials is a cause of increasing Anti-Microbial Resistance concern. This study aimed at understanding the surveillance of antimicrobial resistance in order to serve as a quality assurance tool to determine common pathogens causing bacteremia, trends of antimicrobial resistance which will guide drug-policy decisions and facilitate rational use of drugs to prevent the further emergence of antimicrobial resistance.\u003c/p\u003e\n\u003cp\u003eThis study analyzed results of blood cultures that were routinely taken from patients of different age groups with fever or suspicion of sepsis among patients admitted in different wards of Mbarara Regional Referral Hospital and transported to Mbarara University of Science and Technology, the microbiology laboratory between 2015 and 2022. Bacterial isolates of clinical significance from specimens received during the study period were recorded in WHONET (surveillance software) and exported to STATA for analysis.\u003c/p\u003e\n\u003cp\u003eBloodstream infections were confirmed in 259 cases over the seven-year study period. Gram positive pathogens accounted for 160 (61.7%) in the confirmed infections while gram negative pathogens accounted for 99 (38.2%) of the cases. \u003cem\u003eStaphylococcus aureus\u003c/em\u003e was the most isolated pathogen accounting for 57.1% (n=148) of the blood stream infections. Both the Gram positive and gram negative bacteria demonstrated increasing resistance towards among Ceftriaxone and Ampicillin. Using advanced information technology to study antimicrobial susceptibility patterns of resistant bacteria in blood culture isolates will be useful in directing empiric antibiotic therapy of severe sepsis in Uganda because laboratory data being will be collected and analyzed rapidly.\u003c/p\u003e","manuscriptTitle":"Surveillance of Antimicrobial resistance among organism causing Bacteremia in patients admitted in Mbarara Regional Referral Hospital, Mbarara, Southwestern Uganda","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-31 20:25:15","doi":"10.21203/rs.3.rs-4384837/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":"fe83320e-326f-41bc-a729-1dcc08cc8348","owner":[],"postedDate":"May 31st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":32322865,"name":"Biological sciences/Microbiology"},{"id":32322866,"name":"Biological sciences/Microbiology/Bacteriology"}],"tags":[],"updatedAt":"2024-12-02T11:09:10+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-31 20:25:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4384837","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4384837","identity":"rs-4384837","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}