{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T19:55:08Z","timestamp":1790452508872,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T00:00:00Z","timestamp":1666396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012283","name":"Chang Gung Memorial Hospital in Taiwan","doi-asserted-by":"publisher","award":["CMRPG6L0071"],"award-info":[{"award-number":["CMRPG6L0071"]}],"id":[{"id":"10.13039\/501100012283","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012283","name":"Chang Gung Memorial Hospital in Taiwan","doi-asserted-by":"publisher","award":["CMRPG6H0641"],"award-info":[{"award-number":["CMRPG6H0641"]}],"id":[{"id":"10.13039\/501100012283","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Necrotizing fasciitis (NF) is an uncommon life-threatening necrotizing skin and soft tissue infection. The formation of hemorrhagic bullae is a special skin sign of NF. The purposes of this study were to investigate the incidence of hemorrhagic bullae formation and bacteremia associated with different organisms, to appraise the appropriate use of ceftriaxone, and to compare the clinical and laboratory risk indicators of NF patients with Gram-positive and Gram-negative infections on the initial examination. Methods: From March 2018 to December 2020, there were seventy-four NF patients with positive monomicrobial bacterial cultures enrolled based on surgical confirmation, and were categorized into two groups: the Gram-positive group and the Gram-negative group. Ceftriaxone susceptibility tests were carried out using the standard disk diffusion technique. Data, such as demographics, clinical outcomes, microbiological results, presentations of hemorrhagic bullae, and laboratory findings, were compared among these two groups. Results: The Gram-negative group included 52 patients, of whom 6 patients died, resulting in a mortality rate of 11.5%. The Gram-positive group included 22 patients and none died. Patients with bacteremia, hemorrhagic bullae, shock, fever, higher segmented forms and banded forms, and lower platelet counts constituted higher proportions in the Gram-negative group than in the Gram-positive group. The multivariate analysis identified six variables for the differentiation of Gram-negative and Gram-positive NF: the presentation of bacteremia, hemorrhagic bullae, shock at first consultation, fever with body temperature &gt; 38.5 \u00b0C, band forms &gt; 0%, and segmented forms \u2266 74%. A total of 66 isolates (89.2%) was susceptible to ceftriaxone. Conclusions: Gram-negative NF patients were significantly associated with hemorrhagic bullae presentation, blood stream infection, and mortality. Physicians should be alert to NF patients with the appearance of bacteremia, shock, fever, higher WBC banded and segmented forms, and lower platelet counts at the emergency department, with patients revealed to more likely have Gram-negative infections. Ceftriaxone with\/without other appropriate antibiotics under the supervision of infectious doctors appeared to be clinically effective for the treatment of NF and blood stream infections.<\/jats:p>","DOI":"10.3390\/antibiotics11111454","type":"journal-article","created":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T20:43:50Z","timestamp":1666557830000},"page":"1454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Rational Use of Ceftriaxone in Necrotizing Fasciitis and Mortality Associated with Bloodstream Infection and Hemorrhagic Bullous Lesions"],"prefix":"10.3390","volume":"11","author":[{"given":"Hung-Yen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Chia-Yi Chang Gung Memorial Hospital, Taiwan 613, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1998-5631","authenticated-orcid":false,"given":"Tsung-Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Chia-Yi Chang Gung Memorial Hospital, Taiwan 613, China"},{"name":"College of Medicine, Chang Gung University at Taoyuan, Taiwan 333, China"},{"name":"Microbiology Research and Treatment Center, Chia-Yi Chang Gung Memorial Hospital, Taiwan 613, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiun-Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Chia-Yi Chang Gung Memorial Hospital, Taiwan 613, China"},{"name":"College of Medicine, Chang Gung University at Taoyuan, Taiwan 333, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5507-8396","authenticated-orcid":false,"given":"Liang-Tseng","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Chia-Yi Chang Gung Memorial Hospital, Taiwan 613, China"},{"name":"College of Medicine, Chang Gung University at Taoyuan, Taiwan 333, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Chin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Chia-Yi Chang Gung Memorial Hospital, Taiwan 613, China"},{"name":"College of Medicine, Chang Gung University at Taoyuan, Taiwan 333, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Hung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Chia-Yi Chang Gung Memorial Hospital, Taiwan 613, China"},{"name":"College of Medicine, Chang Gung University at Taoyuan, Taiwan 333, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.2106\/00004623-200308000-00005","article-title":"Necrotizing fasciitis: Clinical presentation, microbiology, and determinants of mortality","volume":"85A","author":"Wong","year":"2003","journal-title":"JBJS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.5435\/00124635-200005000-00002","article-title":"Necrotizing soft-tissue infections","volume":"8","author":"Fontes","year":"2000","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0002-9610(00)00360-3","article-title":"The microbiology of necrotizing soft tissue infections","volume":"179","author":"Elliott","year":"2000","journal-title":"Am. J. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jhin.2010.01.028","article-title":"Diagnosis and management of necrotising fasciitis: A multiparametric approach","volume":"75","author":"Morgan","year":"2010","journal-title":"J. Hosp. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1111\/j.1365-4632.2007.03201.x","article-title":"Staging of necrotising fasciitis based on the evolving cutaneous features","volume":"46","author":"Wang","year":"2007","journal-title":"Int. J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4103\/JETS.JETS_42_17","article-title":"Necrotizing fasciitis: How reliable are the cutaneous signs?","volume":"10","author":"Kiat","year":"2017","journal-title":"J. Emerg. Trauma. Shock."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.ajem.2007.07.014","article-title":"Hemorrhagic bullae are not only skin deep","volume":"26","author":"Hsiao","year":"2008","journal-title":"Am. J. Emerg. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jemermed.2007.02.047","article-title":"Hemorrhagic bullae represent an ominous sign for cirrhotic patients","volume":"34","author":"Liu","year":"2008","journal-title":"J. Emerg. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s15010-020-01559-5","article-title":"Different types of bullae of limbs with necrotizing fasciitis predict different outcome: A prospective study","volume":"49","author":"Huang","year":"2021","journal-title":"Infection"},{"key":"ref_10","first-page":"e17806","article-title":"Differentiating upper extremity necrotizing soft tissue infection frome serious cellulitis and abscess","volume":"13","author":"Cohen","year":"2021","journal-title":"Cureus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1097\/SLA.0000000000002774","article-title":"Necrotizing soft tissue infections: Diagnostic accuracy of physical examination, imaging, and LRINEC score","volume":"269","author":"Fernando","year":"2019","journal-title":"Ann. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1007\/s11999-010-1311-y","article-title":"Laboratory indicators for early detection and surgical treatment of Vibrio necrotizing fasciitis","volume":"468","author":"Tsai","year":"2010","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Tsai, Y.H., Huang, T.Y., Chen, J.L., Hsiao, C.T., Kuo, L.T., and Huang, K.C. (2021). Bacteriology and mortality of necrotizing fasciitis in a tertiary coastal hospital with comparing risk indicators of methicillin-resistant Staphylococcus aureus and Vibrio vulnifcus infections: A prospective study. BMC. Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06518-5"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ajem.2007.04.023","article-title":"Predictors of mortality in patients with necrotizing fasciitis","volume":"26","author":"Hsiao","year":"2008","journal-title":"Am. J. Emerg. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7716","DOI":"10.1038\/s41598-020-64741-7","article-title":"Independent Predictors of Mortality for Aeromonas Necrotizing Fasciitis of Limbs: An 18-year Retrospective Study","volume":"10","author":"Huang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1089\/sur.2021.337","article-title":"Comparison of surgical outcomes and predictors in patients with monomicrobial necrotizing fasciitis caused by Vibrio vulnificus, Aeromonas hydrophila and Aeromonas sobria","volume":"23","author":"Tsai","year":"2022","journal-title":"Surg. Infect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"274","DOI":"10.2106\/JBJS.I.01679","article-title":"Comparison of necrotizing fasciitis and sepsis caused by Vibrio vulnificus and Staphylococcus aureus","volume":"93","author":"Tsai","year":"2011","journal-title":"JBJS"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e159","DOI":"10.1016\/j.ijid.2011.11.001","article-title":"Microbiology and surgical indicators of necrotizing fasciitis in a tertiary hospital of southwest Taiwan","volume":"16","author":"Tsai","year":"2012","journal-title":"Int. J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1056\/NEJMra1600673","article-title":"Necrotizing soft-tissue infections","volume":"377","author":"Stevens","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.jemermed.2021.12.012","article-title":"Necrotizing soft tissue infections (NSTI): Pearls and pitfalls for the emergency clinician","volume":"62","author":"Pelletier","year":"2022","journal-title":"J. Emerg. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/QCO.0000000000000242","article-title":"Current guidelines and recommendations for the management of skin and soft tissue infections","volume":"29","author":"Montravers","year":"2016","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Urbina, T., Razazi, K., Ourghanlian, C., Woerther, P.L., Chosidow, O., Lepeule, R., and de Prost, N. (2021). Antibiotics in Necrotizing Soft Tissue Infections. Antibiotics, 10.","DOI":"10.3390\/antibiotics10091104"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rampal, S., Ganesan, T., Sisubalasingam, N., Neela, V.K., Tokg\u00f6z, M.A., Arunasalam, A., Halim, M.A.H.A., Shamsudin, Z.B., Kumar, S., and Sinniahet, A. (2021). Local trends of antibiotic prescriptions for necrotizing fasciitis patients in two tertiary care hospitals in central malaysia. Antibiotics, 10.","DOI":"10.3390\/antibiotics10091120"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1093\/jac\/dkz279","article-title":"Antibiotics with activity against intestinal anaerobes and the hazard of acquired colonization with ceftriaxone-resistant Gram-negative pathogens in ICU patients: A propensity score-based analysis","volume":"74","author":"Boutrot","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12000","DOI":"10.1038\/s41598-022-16132-3","article-title":"Ceftriaxone resistance among patients at GAMBY teaching general hospital","volume":"12","author":"Gelaw","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00849","DOI":"10.1002\/prp2.849","article-title":"The Contribution of nano-based strategies in overcoming ceftriaxone resistance: A literature review","volume":"9","author":"Tewabe","year":"2021","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ijid.2014.05.024","article-title":"Monomicrobial necrotizing fasciitis in a single center: The emergence of Gram-negative bacteria as a common pathogen","volume":"28","author":"Yahav","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.cmi.2018.05.008","article-title":"Monomicrobial Klebsiella pneumoniae necrotizing fasciitis: An emerging life-threatening entity","volume":"25","author":"Rahim","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.diagmicrobio.2018.12.013","article-title":"Monomicrobial gram-negative necrotizing fasciitis: An uncommon but fatal syndrome","volume":"94","author":"Park","year":"2019","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Huang, T.Y., Peng, K.T., Hsiao, C.T., Fann, W.C., Tsai, Y.H., Li, Y.Y., Hung, C.H., Chuang, F.Y., and Hsu, W.H. (2020). Predictors for gram-negative monomicrobial necrotizing fasciitis in southern Taiwan. BMC. Infect. Dis., 20.","DOI":"10.1186\/s12879-020-4796-3"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/s00134-020-05950-6","article-title":"Bloodstream infections in critically ill patients: An expert statement","volume":"46","author":"Timsit","year":"2020","journal-title":"Intensive. Care Med."},{"key":"ref_32","first-page":"429","article-title":"\u03b2-Lactam pharmacodynamics in gram-negative bloodstream infections in the critically ill","volume":"75","author":"Wong","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s11096-012-9637-z","article-title":"Outpatient parenteral antimicrobial therapy with ceftriaxone, a review","volume":"34","author":"Duncan","year":"2012","journal-title":"Int. J. Clin. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kamfose, M.M., Muriithi, F.G., Knight, T., Lasserson, D., and Hayward, G. (2020). Intravenous ceftriaxone versus multiple dosing regimes of intravenous anti-staphylococcal antibiotics for methicillin-susceptible Staphylococcus aureus (MSSA): A systematic review. Antibiotics, 9.","DOI":"10.3390\/antibiotics9020039"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Alsowaida, Y.S., Saleh, Y., Benitez, G., Saleh, K.B., Almangour, T.A., Shehadeh, F., and Mylonakis, E. (2022). Effectiveness and safety of ceftriaxone compared to standard of care for treatment of bloodstream infections due to Methicillin-susceptible Staphylococcus aureus: A systematic review and meta-analysis. Antibiotics, 11.","DOI":"10.3390\/antibiotics11030375"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"106486","DOI":"10.1016\/j.ijantimicag.2021.106486","article-title":"Ceftriaxone versus antistaphylococcal antibiotics for definitive treatment of methicillin-susceptible Staphylococcus aureus infections: A systematic review and meta-analysis","volume":"59","author":"Yetmar","year":"2022","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_37","first-page":"215","article-title":"Treatment options for gram-positive and gram-negative bacteria: Focus on ceftriaxone","volume":"3","author":"Hirai","year":"2011","journal-title":"Clin. Med. Rev. Ther."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/11\/1454\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:00:47Z","timestamp":1760144447000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/11\/1454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,22]]},"references-count":37,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["antibiotics11111454"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics11111454","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,22]]}}}