Empyema Thoracis caused by Aggregatibacter aphrophilus: two cases report

Empyema Thoracis caused by Aggregatibacter aphrophilus: two cases report | 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 Case Report Empyema Thoracis caused by Aggregatibacter aphrophilus: two cases report Deng-Wei Chou, Chao-Tai Lee, Shu-Ling Wu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8831766/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background: Aggregatibacter aphrophilus is a normal commensal of the human oropharynx and a member of the HACEK group of organisms. This microorganism can cause a wide variety of infections mainly including endocarditis and osteoarticular infections. However, empyema thoracis caused by A. aphrophilus is very rare. The information about this rare disease is very limited. We herein report 2 rare cases having empyema thoracis due to A. aphrophilus . Case presentation: An 88-year-old man with a history of bronchiectasis and periodontitis was admitted for a 2-week history of right lower chest pain, a low-grade fever, and productive cough. Another 51-year-old man with a history of alcoholic liver cirrhosis was admitted with complaint of right chest pain for one week. The cultures of the pleural effusion in both cases were positive for A. aphrophilus which was confirmed by the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The former case responded to a 2-week course of intravenous piperacillin/tazobactam. The latter case died from shock and progressive deterioration of liver function. Conclusions: The effective treatment of A. aphrophilus empyema thoracis should comprise (i) accurate causative pathogen identification by conforming with MALDI-TOF MS , (ii) adequate empyema drainage, (iii) appropriate antimicrobial therapy with penicillin/β-lactam inhibitor combinations or the third-generation cephalosporins, and (iv) underlying diseases management especially malignancy and alcoholism. Aggregatibacter aphrophilus HACEK Empyema Thoracis Matrix-assisted laser desorption ionization time-of-flight mass spectrometry Figures Figure 1 Background Aggregatibacter aphrophilus (formerly named as Haemophilus aphrophilus and H. paraphrophilus ) is a small, pleomorphic, nonmotile, nonsporting Gram-negative coccobacillus that is a normal commensal of the human oropharynx [1]. It is a member of the HACEK group of organisms ( Haemophilus species, Aggregatibacter species, Cardiobacterium hominis , Eikenella corrodens , and Kingella species) [1]. This organism does not require X factor (hemin) and V factor (nicotinamide adenine dinucleotide) for growth and its growth is enhanced in a carbon dioxide (CO 2 )-enriched atmosphere [2]. Although A. aphrophilus with a level of pathogenicity is a rare cause of human infection [3], this microorganism can cause a wide variety of infections [4]. Invasive A. aphrophilus infections mainly cause endocarditis and osteoarticular infections [3, 4]. Other manifestations include pneumonitis, peritonitis, sinusitis, wound infection, ophthalamic infections, bacteremia, meningitis, brain abscess, cervical lymphadenitis, facial cellulitis, empyema, and pericarditis [3, 4]. Among these infections, empyema thoracis caused by A. aphrophilus is very rare. According to our review of relevant studies, only 6 cases of empyema thoracis caused by this microorganism have been reported from 1965 to 2025. The information about this rare disease is very limited. Herein, we report 2 cases having empyema thoracis due to A. aphrophilus and present a literature review to better understand this rare disease. Case Presentation Case 1 An 88-year-old man with a history of bronchiectasis and periodontitis was admitted to our hospital with a 2-week history of right lower chest pain, a low-grade fever, and productive cough. On admission, his blood pressure was 150/62 mmHg, body temperature was 37.5 ℃, pulse rate was 80 beats/min, respiratory rate was 20 breaths/min, and oxygen saturation was 94% on room air. Chest auscultation revealed decreased breath sounds in the right lower lung field, and crackles in the left lower lung field. Laboratory examinations showed the following values: white blood cell count, 18,250/μL (with 80% neutrophils); hemoblobin 9.4 g/dL; and C-reactive protein, 24 mg/dL (reference range ＜ 0.3 mg/dL). A chest radiograph (Figure 1A) showed blunting of the right costophrenic sulcus and hazy increased opacity overlying the right lower lung (white arrow). In addition, branching tubular and nodular opacities were seen in the left lower lobe (black arrow), which was suggestive of mucoid impaction in ectatic bronchi. Contrast-enhanced computed tomography (CT) of the chest (Figure 1B) showed loculated fluid collection (white arrow) between the thickening parietal and visceral pleura, which was suggestive of empyema. Thoracentesis was performed, and 10 mL of pus-like pleural effusion was obtained. Pleural effusion was turbid color and contained 0 mg/dL glucose (serum glucose: 120 mg/dL), 5.4 mg/dL total protein (serum total protein: 5.6 mg/dL), 984 U/L lactate dehydrogenase (serum lactate dehydrogenase: 304 U/L), 3,700/μL red blood cells, and 12,000/μL white blood cells with 98 % neutrophils. Gram staining for pleural effusion showed Gram-negative coccobacilli. Ziehl-Neelsen staining showed negative. Pleural effusion was cultured on blood agar, eosin-methylene blue agar and chocolate agar plates. After incubation in 5% CO 2 at 35ºC up to 48 hours, there was no growth on eosin-methylene blue agar, but the blood agar and chocolate agar plates showed profuse growth of convex and opaque colonies which were identified as gram-negative coccobacilli. Biochemical tests showed the isolate was catalase-negative, oxidase-negative and indole-negative. The isolate was identified A. aphrophilus/A. paraphrophilus (code, 2777577770; confidence, 0.99993)by the BBL Crystal NH Identification System (Becton Dickinson Microbiology System, Sparks, MD). The Haemophilus ID Quad agar plate (Becton Dickinson Microbiology System, Sparks, MD) revealed the isolate was X factor and V factor independent, indicating it was A. aphrophilus . The isolate was confirmed as A. aphrophilus (score value, 1.919) by the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) using BioTyper 2.3 software package (Bruker Daltonics). Negative for β-lactmase production of this strain was detected by the Cefinase paper disc (Becton Dickinson Microbiology System, Sparks, MD). The antimicrobial susceptibility test was determined by applying antimicrobial dilution and disk susceptibility testing used for HACEK group by the Clinical and Laboratory Standards Institute [5]. The isolate was susceptible to co-trimoxazole, gentamicin, amikacin, cefazolin, cefuroxime, flomoxef, ceftriaxone, ceftazidime, amoxicillin plus sulbactam , piperacillin plus tazobactam, levofloxacin, and tigecycline. Sputum cultures were positive for Pseudomonas aeruginosa . Blood cultures did not grow any pathogen. The patient responded to a 2-week course of intravenous piperacillin/tazobactam followed by a 2-week course of oral ceftibuten. Case 2 A 51-year-old man with a history of alcoholic liver cirrhosis (Child-Pugh C) and periodontitis visited our emergency department with complaint of right chest pain for one week. On arrival, his blood pressure was 90/48 mmHg, body temperature was 36.5 ℃, pulse rate was 105 beats/min, respiratory rate was 16 breaths/min, and oxygen saturation was 90% on room air. Chest auscultation revealed decreased breath sounds in the right lung. Laboratory examinations showed the following values: white blood cell count, 30,550/μL (with 91% neutrophils); ammonia 139 μg/dL (normal, 12-66 μg/dL); total bilirubin 5.1 mg/dL (normal, 0.2-1.0 mg/dL); direct bilirubin 4.1 mg/dL (normal, 0.1-0.5 mg/dL); albumin 1.6 gm/dL (normal, 3.5-5.0 gm/dL); and creatinine, 3.4 mg/dL. A chest radiograph (Figure 1C) showed a nearly total opacification of the right hemithorax (white arrow) with tracheal deviation to the left side. Non-contrast-enhanced CT of the chest (Figure 1D) showed the right hemithorax was filled with thick multiloculated pleural effusion (white arrows) with air bubbles , which was indicative of empyema. The patient immediately underwent tube thoracotomy, and 1,500 mL of pus-like pleural effusion was obtained. Pleural effusion was milky color and contained 5 mg/dL glucose (serum glucose: 149 mg/dL), 3.8 mg/dL total protein (serum total protein: 4.8 mg/dL), 11,684 U/L lactate dehydrogenase (serum lactate dehydrogenase: 292 U/L), 5,000/μL red blood cells, and 350,000/μL white blood cells with 100 % neutrophils. Ziehl-Neelsen staining for pleural effusion showed negative finding. Empirical vancomycin and imipenem were initiated. Pleural effusion was sent for further work-up. Methods of culture and identification for isolate from pleural effusion were the same as described in the first case. The bacterial isolate was identified as A. aphrophilus , and the r esults of antibiotic susceptibility testing indicated susceptibility to co-trimoxazole, ampicillin, β-lactmase, ampicillin plus sulbactam , cefuroxime, ceftriaxone, ceftazidime, imipenem, and levofloxacin. Sputum and blood cultures did not grow any pathogen. Due to shock and progressive deterioration of liver function, the patient expired on hospital Day 8. Review of the literature We searched PubMed for papers published in English from 1965 to December 2025 using the following terms: (" Aggregatibacter aphrophilus " OR " Haemophilus aphrophilus " AND ("empyema"). Four cases with empyema were reported [4, 6, 7, 8]. In addition, we used search terms of " Aggregatibacter aphrophilus OR Haemophilus aphrophilus " with limitation in review article. One article with 2 cases was relevant [3]. According to our review of relevant studies, only a total of 8 cases (Table 1), including our 2 patients had been diagnosed in the English literature. There were 5 men (63%) and 3 women (37%) with a mean age of 55 years, ranging from 26 to 88 years. Six cases (75%) were less than 65 years old. The majority of cases had underlying diseases (5 cases, 63%) including malignancies (2 cases, 25%), excessive alcoholic consumption (2 cases, 25%), and bronchiectasis (1 case, 13%). Cough, dyspnea, fever and pleuritic chest pain were the common symptoms at initial presentation. All patients underwent thoracentesis or tube thoracostomy therapy. All pleural effusion cultures grew A. aphrophilus . Sputum and blood cultures from all patients were negative for A. aphrophilus . Three cases (patients 1-3) reported before 1978 were treated with penicillin. Three cases (patients 4-6) reported after 2005 were treated with amoxicillin-clavulanate or amoxicillin. One case (patient 7) reported after 2005 were treated with piperacillin/tazobactam. Although appropriate antibiotic therapy, 2 cases (25%) with intractable underlying diseases including lung cancer and alcoholic cirrhosis of liver died during hospitalization. Discussion A. aphrophilus bundles together two previously separate species, H. aphrophilus and H. paraphrophilus [1]. This micro-organism requires 5% CO 2 for primary isolation and grows best on the chocolate blood agar. A. aphrophilus is oxidase-negative, catalase-negative and X and V independent, in contrast to the common isolated H. influenzae and H. para influenzae , which are both oxidase-positive and catalase-positive [2]. Because A. aphrophilus has been misidentified as Pasteurella species using commercial identification kits [9, 10], diagnostic laboratories may have difficulty identifying this microorganism correctly. Therefore, the combination of commercial identification kits with a real-time PCR assay [11] or MALDI-TOF [12] could improve microbiological documentation. The Clinical and Laboratory Standards Institute has published consensus guidelines for antimicrobial susceptibility testing for infrequently isolated or fastidious bacteria [5] including A. aphrophilus . In a case series study, antimicrobial therapy for A. aphrophilus including amoxicillin or ampicillin with a β-lactmase inhibitor, the third-generation cephalosporins, or the fluoroquinolones can lead to a favorable outcome [4]. Despite this microorganism is susceptible to doxycycline, which was ineffective for the treatment of empyema in a case report [6]. The initial presentation, radiological pattern and clinical course of patients with A. aphrophilus empyema thoracis are indistinguishable from infections caused by other microorganisms. C ommercial identification kits may have difficulty identifying A. aphrophilus correctly. The combination of commercial identification kits with MALDI-TOF MS could improve microbiological documentation. The leading underlying diseases of death are malignancies and excessive alcoholic consumption . The first-choice antibiotics for treating A. aphrophilus empyema thoracis are penicillin/β-lactam inhibitor combinations and the third-generation cephalosporins. Other effective options, according to antimicrobial sensitivity, include fluoroquinolones and meropenem. A. aphrophilus empyema thoracis can be a life-threatening opportunistic infection in immunocompromised patients. The empirical antimicrobial therapy for A. aphrophilus empyema thoracis should cover potential infections according to the patients’ underlying diseases especially malignancy and alcoholism. Conclusion The effective treatment of A. aphrophilus empyema thoracis should comprise (i) accurate causative pathogen identification by conforming with a combination of a commercial identification system and MALDI-TOF MS , (ii) adequate empyema drainage, (iii) appropriate antimicrobial therapy with penicillin/β-lactam inhibitor combinations or the third-generation cephalosporins, and (iv) underlying diseases management especially malignancy and alcoholism. Abbreviations CO 2 : Carbon dioxide CT: Computed tomography MALDI-TOF MS: Matrix-assisted laser desorption ionization time-of-flight mass spectrometry Declarations Ethics approval and consent to participate This study follows the ethical principles of the Declaration of Helsinki and has been approved by the Institutional Review Board of Tainan Municipal Hospital (No. 1141201). Written informed consent for publication was obtained from the next of kin of all patients. Consent for publication Consent for publication was obtained from the next of kin of all patients. Written consent is available upon request. Availability of data and materials No datasets were generated or analysed during the current study. Competing interests The authors declare no competing interests. Funding There is no source of funding in submission of this report. Authors’ contributions DW C was responsible for diagnosing and managing the patients. He also participated in the editing and writing of the manuscript. CT L participated in laboratory examinations. SL W participated in the data organization. All authors have reviewed the manuscript. Acknowledgements Not applicable. Authors and Affiliations (optional) Not applicable References Nørskov-Lauritsen N, Kilian M. Reclassification of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis as Aggregatibacter actinomycetemcomitans gen. nov., comb. nov., Aggregatibacter aphrophilus comb. nov. and Aggregatibacter segnis comb. nov., and emended description of Aggregatibacter aphrophilus to include V factor-dependent and V factor-independent isolates. Int J Syst Evol Microbiol. 2006;56(Pt 9):2135-46; doi: 10.1099/ijs.0.64207-0. Murphy TF. Haemophilus species (including H. influenzae and chancroid). In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. Philadelphia, Pennsylvania: Churchill Livingstone Elsevier; 2010. p. 2917-18. Bieger RC, Brewer NS, Washington JA 2nd. Haemophilus aphrophilus : a microbiologic and clinical review and report of 42 cases. Medicine (Baltimore). 1978;57(4):345-55. Huang ST, Lee HC, Lee NY, Liu KH, Ko WC. Clinical characteristics of invasive Haemophilus aphrophilus infections. J Microbiol Immunol Infect. 2005;38(4):271-6. Clinical and Laboratory Standards Institute. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Guideline-3rd Edition. M45. CLSI, Wayne, PA, USA, 2016. Ratnayake L, Olver WJ, Fardon T. Aggregatibacter aphrophilus in a patient with recurrent empyema: a case report. Journal of Medical Case Reports. 2011;5:448; doi: 10.1186/1752-1947-5-448. Rodriguez-Segade S, Velasco D, Marcos PJ. Empyema due to Aggregatibacter aphrophilus and Parvimonas micra coinfection. Arch Bronconeumol. 2015;51(5):254-5; doi: 10.1016/j.arbres.2014.06.014. Capelli JP, Savacool JW, Randall EL. Haemophilus aphrophilus empyema. Ann Intern Med. 1965;62:771-7; doi: 10.7326/0003-4819-62-4-771. Frederiksen W, Tønning B. Possible misidentification of Haemophilus aphrophilus as Pasteurella gallinarum . Clin Infect Dis. 2001;32(6):987-9; doi: 10.1086/319358. Chien JT, Lin CH, Chen YC, Lay CJ, Wang CL, Tsai CC. Epidural abscess caused by Haemophilus aphrophilus misidentified as Pasteurella species. Intern Med. 2009;48(10):853-8; doi: 10.2169/internalmedicine.48.1930. Teranishi H, Ohzono N, Inamura N, Atsushi K, Wakabayashi T, Akaike H, et al. Detection of bacteria and fungi in blood of patients with febrile neutropenia by real-time PCR with universal primers and probes. J Infect Chemother. 2015;21(3):189-93; doi: 10.1016/j.jiac.2014.11.008. Choquet M, Pluquet E, Castelain S, Guihéneuf R, Decroix V. Bartholinitis due to Aggregatibacter aphrophilus: a case report. BMC Infect Dis. 2016;16(1):574; doi: 10.1186/s12879-016-1908-1. Table 1 Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table.doc Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 11 Mar, 2026 Reviewers agreed at journal 11 Mar, 2026 Reviews received at journal 05 Mar, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviewers invited by journal 26 Feb, 2026 Editor assigned by journal 20 Feb, 2026 Submission checks completed at journal 19 Feb, 2026 First submitted to journal 09 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-8831766","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":597694243,"identity":"11bf6750-180c-4e58-b2e1-d4a6131d1ec2","order_by":0,"name":"Deng-Wei Chou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAArElEQVRIiWNgGAWjYDACCSDmYbABkoyNB0jRkgbS0kCSlsNgNnFa+Gc3H5N423bebm37YaAtNTbRhC25cyxNcm7b7eRtZxKBWo6l5TYQ0mIgkWMmzbvtdrLZAaAWxobDRGs5l2x2/iFpWg7Ymd0g1haJG2nJlnP/JSeY3QDakkCMX/hnJB+88eaMnb3Z+fSHDz7U2BDWAgOJYJUJxCoHAXtSFI+CUTAKRsEIAwBzcEWW7gkVwgAAAABJRU5ErkJggg==","orcid":"","institution":"Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation)","correspondingAuthor":true,"prefix":"","firstName":"Deng-Wei","middleName":"","lastName":"Chou","suffix":""},{"id":597694244,"identity":"d18f232f-c03c-4a7b-ab8e-ea9464a980db","order_by":1,"name":"Chao-Tai Lee","email":"","orcid":"","institution":"Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation)","correspondingAuthor":false,"prefix":"","firstName":"Chao-Tai","middleName":"","lastName":"Lee","suffix":""},{"id":597694245,"identity":"c6cae581-2fe2-4409-87c1-0bcaef529dfd","order_by":2,"name":"Shu-Ling Wu","email":"","orcid":"","institution":"Chung Hwa University of Medical Technology","correspondingAuthor":false,"prefix":"","firstName":"Shu-Ling","middleName":"","lastName":"Wu","suffix":""}],"badges":[],"createdAt":"2026-02-09 14:55:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8831766/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8831766/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104403905,"identity":"9b6c361b-888b-45e3-9747-ec7cd123fcdd","added_by":"auto","created_at":"2026-03-11 12:19:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":515517,"visible":true,"origin":"","legend":"\u003cp\u003eA chest radiograph (Fig. A) showed blunting of the right costophrenic sulcus and hazy increased opacity overlying the right lower lung (white arrow). In addition, branching tubular and nodular opacities (black arrow) were seen in the left lower lobe, which was suggestive of mucoid impaction in ectatic bronchi. Contrast-enhanced computed tomography (CT) of the chest (Fig. B) showed loculated fluid collection (white arrow) between the thickening parietal and visceral pleura, which was suggestive of empyema thoracis. A chest radiograph (Fig. C) showed a nearly total opacification of the right hemithorax with tracheal deviation to the left side. Non-contrast-enhanced CTof the chest (Fig. D) showed the right hemithorax was filled with thick multiloculated\u003cem\u003e \u003c/em\u003epleural effusion\u003cem\u003e \u003c/em\u003e(white arrows) with air bubbles, which was indicative of empyema thoracis.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8831766/v1/effaf73c73fa15e0693a1273.png"},{"id":104408483,"identity":"13e7738a-f4b3-4010-8f25-42f20902b8c4","added_by":"auto","created_at":"2026-03-11 12:42:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1110397,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8831766/v1/f038389e-e755-4afa-8585-bbdb3bdea7d3.pdf"},{"id":104170348,"identity":"f7c7c4dd-8016-4fad-a00f-90bb9cfc91ab","added_by":"auto","created_at":"2026-03-08 14:45:26","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":46080,"visible":true,"origin":"","legend":"","description":"","filename":"Table.doc","url":"https://assets-eu.researchsquare.com/files/rs-8831766/v1/4e00fcf0d29c402c4a7ffbfb.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"Empyema Thoracis caused by Aggregatibacter aphrophilus: two cases report","fulltext":[{"header":"Background","content":"\u003cp\u003e\u003cem\u003eAggregatibacter aphrophilus\u0026nbsp;\u003c/em\u003e(formerly named as \u003cem\u003eHaemophilus aphrophilus\u003c/em\u003e and \u003cem\u003eH. paraphrophilus\u003c/em\u003e) is a small, pleomorphic, nonmotile, nonsporting Gram-negative coccobacillus that\u0026nbsp;is a\u0026nbsp;normal commensal of the human\u0026nbsp;oropharynx\u0026nbsp;[1].\u0026nbsp;It is a member of the HACEK group of organisms (\u003cem\u003eHaemophilus\u003c/em\u003e species, \u003cem\u003eAggregatibacter\u003c/em\u003e species, \u003cem\u003eCardiobacterium hominis\u003c/em\u003e, \u003cem\u003eEikenella corrodens\u003c/em\u003e, and \u003cem\u003eKingella\u003c/em\u003e species)\u0026nbsp;[1].\u0026nbsp;This organism does not require X factor (hemin) and V factor (nicotinamide adenine dinucleotide) for growth and its growth is enhanced in a carbon dioxide (CO\u003csub\u003e2\u003c/sub\u003e)-enriched atmosphere [2]. Although \u003cem\u003eA. aphrophilus\u003c/em\u003e with a level of pathogenicity is a rare cause of human infection [3], this microorganism can cause a wide variety of infections [4]. Invasive\u0026nbsp;\u003cem\u003eA. aphrophilus\u0026nbsp;\u003c/em\u003einfections mainly cause\u0026nbsp;endocarditis and osteoarticular infections\u0026nbsp;[3, 4]. Other manifestations include pneumonitis, peritonitis, sinusitis, wound infection, ophthalamic infections, bacteremia, meningitis, brain abscess, cervical lymphadenitis, facial cellulitis, empyema, and pericarditis\u0026nbsp;[3, 4]. Among these infections, empyema thoracis caused by \u003cem\u003eA. aphrophilus\u003c/em\u003e is very rare. According to our review of relevant studies, only 6 cases of empyema thoracis caused by this microorganism have been reported from 1965 to 2025. The information about this rare disease is very limited. Herein, we report 2 cases having empyema thoracis due to \u003cem\u003eA. aphrophilus\u0026nbsp;\u003c/em\u003eand present a literature review to better understand this rare disease.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003e\u003cstrong\u003eCase 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn 88-year-old man with a history of bronchiectasis and periodontitis was admitted to our hospital with a 2-week history of right lower chest pain, a low-grade fever, and productive cough. On admission, his blood pressure was 150/62 mmHg, body temperature was 37.5 ℃, pulse rate was 80 beats/min, respiratory rate was 20 breaths/min, and oxygen saturation was 94% on room air. Chest auscultation revealed decreased breath sounds in the right lower lung field, and crackles in the left lower lung field. Laboratory examinations showed the following values: white blood cell count, 18,250/μL (with 80% neutrophils); hemoblobin 9.4 g/dL; and C-reactive protein, 24 mg/dL (reference range ＜ 0.3 mg/dL). A chest radiograph (Figure 1A) showed blunting of the right costophrenic sulcus and hazy increased opacity overlying the right lower lung (white arrow). In addition, branching tubular and nodular opacities were seen in the left lower lobe (black arrow), which was suggestive of mucoid impaction in ectatic bronchi. Contrast-enhanced computed tomography (CT) of the chest (Figure 1B) showed loculated fluid collection\u0026nbsp;(white arrow)\u0026nbsp;between the thickening parietal and visceral pleura, which was suggestive of empyema.\u0026nbsp;Thoracentesis was performed, and 10 mL of pus-like pleural effusion was obtained. Pleural effusion was turbid color and contained 0 mg/dL glucose (serum glucose: 120 mg/dL), 5.4 mg/dL total protein (serum total protein: 5.6 mg/dL), 984 U/L lactate dehydrogenase (serum lactate dehydrogenase: 304 U/L), 3,700/μL\u0026nbsp;red blood cells, and 12,000/μL white blood cells with 98 % neutrophils. Gram staining for pleural effusion showed Gram-negative coccobacilli. Ziehl-Neelsen staining showed negative.\u0026nbsp;Pleural effusion was cultured on blood agar, eosin-methylene blue agar and chocolate agar plates. After incubation in 5% CO\u003csub\u003e2\u003c/sub\u003e at 35ºC up to 48 hours, there was no growth on\u0026nbsp;eosin-methylene blue agar, but\u0026nbsp;the\u0026nbsp;blood agar and chocolate agar plates showed profuse growth of convex and opaque colonies which were identified as gram-negative coccobacilli. Biochemical tests showed the isolate was catalase-negative, oxidase-negative and indole-negative. The isolate was identified\u0026nbsp;\u003cem\u003eA. aphrophilus/A. paraphrophilus\u003c/em\u003e (code, 2777577770; confidence, 0.99993)by the\u0026nbsp;BBL Crystal NH Identification System (Becton Dickinson Microbiology System, Sparks, MD).\u0026nbsp;The\u0026nbsp;Haemophilus ID Quad agar plate (Becton Dickinson Microbiology System, Sparks, MD) revealed the isolate was\u0026nbsp;X factor and\u0026nbsp;V factor independent, indicating it was\u003cem\u003e\u0026nbsp;A. aphrophilus\u003c/em\u003e. The isolate was confirmed as\u0026nbsp;\u003cem\u003eA. aphrophilus\u0026nbsp;\u003c/em\u003e(score value, 1.919) by the matrix-assisted laser desorption ionization time-of-flight mass spectrometry\u0026nbsp;(MALDI-TOF MS)\u0026nbsp;using BioTyper 2.3 software package (Bruker Daltonics). Negative for\u0026nbsp;β-lactmase production\u0026nbsp;of this strain was detected by\u0026nbsp;the Cefinase paper disc\u0026nbsp;(Becton Dickinson Microbiology System, Sparks, MD). The antimicrobial susceptibility test was determined by applying\u0026nbsp;antimicrobial dilution and disk susceptibility testing used for HACEK group by\u0026nbsp;the\u0026nbsp;Clinical and Laboratory Standards Institute\u0026nbsp;[5]. The isolate was susceptible to\u0026nbsp;\u003cem\u003eco-trimoxazole, gentamicin, amikacin,\u0026nbsp;\u003c/em\u003ecefazolin, cefuroxime, flomoxef, ceftriaxone, ceftazidime, amoxicillin plus\u0026nbsp;\u003cem\u003esulbactam\u003c/em\u003e,\u0026nbsp;\u003cem\u003epiperacillin\u003c/em\u003e plus \u003cem\u003etazobactam, levofloxacin, and tigecycline.\u0026nbsp;\u003c/em\u003eSputum cultures were positive for \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e. Blood cultures did not grow any pathogen. The patient responded to a 2-week course of intravenous\u0026nbsp;piperacillin/tazobactam followed by a 2-week course of oral ceftibuten.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase 2\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 51-year-old man with a history of alcoholic liver cirrhosis (Child-Pugh C) and periodontitis visited our emergency department with complaint of right chest pain for one week. On arrival, his blood pressure was 90/48 mmHg, body temperature was 36.5 ℃, pulse rate was 105 beats/min, respiratory rate was 16 breaths/min, and oxygen saturation was 90% on room air. Chest auscultation revealed decreased breath sounds in the right lung. Laboratory examinations showed the following values: white blood cell count, 30,550/μL (with 91% neutrophils); ammonia 139 μg/dL (normal, 12-66 μg/dL); total bilirubin 5.1 mg/dL (normal, 0.2-1.0 mg/dL); direct bilirubin 4.1 mg/dL (normal, 0.1-0.5 mg/dL); albumin 1.6 gm/dL (normal, 3.5-5.0 gm/dL); and creatinine, 3.4 mg/dL. A chest radiograph (Figure 1C) showed a nearly total opacification of the right\u0026nbsp;hemithorax\u0026nbsp;(white arrow) with tracheal deviation to the left side. Non-contrast-enhanced CT\u0026nbsp;of the chest (Figure 1D) showed\u0026nbsp;the \u003cem\u003eright\u003c/em\u003e hemithorax\u0026nbsp;was filled with thick\u0026nbsp;multiloculated\u003cem\u003e\u0026nbsp;pleural effusion\u0026nbsp;\u003c/em\u003e(white arrows) \u003cem\u003ewith air bubbles\u003c/em\u003e, which was indicative of empyema.\u0026nbsp;The patient immediately underwent tube thoracotomy, and 1,500 mL of pus-like pleural effusion was obtained. Pleural effusion was milky color and contained 5 mg/dL glucose (serum glucose: 149 mg/dL), 3.8 mg/dL total protein (serum total protein: 4.8 mg/dL), 11,684 U/L lactate dehydrogenase (serum lactate dehydrogenase: 292 U/L), 5,000/μL\u0026nbsp;red blood cells, and 350,000/μL white blood cells with 100 % neutrophils. Ziehl-Neelsen staining for pleural effusion showed negative finding.\u0026nbsp;Empirical vancomycin and imipenem were initiated. Pleural effusion was\u0026nbsp;sent for further work-up. Methods of culture and identification for isolate from pleural effusion were the same as \u003cem\u003edescribed in the first case. The bacterial isolate was identified as\u0026nbsp;\u003c/em\u003e\u003cem\u003eA. aphrophilus\u003c/em\u003e\u003cem\u003e, and the r\u003c/em\u003eesults of antibiotic susceptibility testing indicated susceptibility to \u003cem\u003eco-trimoxazole,\u003c/em\u003e ampicillin, β-lactmase,\u0026nbsp;ampicillin\u0026nbsp;plus\u0026nbsp;\u003cem\u003esulbactam\u003c/em\u003e, cefuroxime, ceftriaxone, ceftazidime, imipenem, and levofloxacin. Sputum and blood cultures did not grow any pathogen. Due to shock and progressive deterioration of liver function, the patient expired on hospital Day 8.\u003c/p\u003e"},{"header":"Review of the literature","content":"\u003cp\u003eWe searched PubMed for papers published in English from 1965 to December 2025 using the following terms: (\"\u003cem\u003eAggregatibacter aphrophilus\u003c/em\u003e\" OR \"\u003cem\u003eHaemophilus aphrophilus\u003c/em\u003e\" AND (\"empyema\"). Four cases with empyema were reported\u0026nbsp;[4, 6, 7, 8]. In addition, we used search terms of \"\u003cem\u003eAggregatibacter aphrophilus\u003c/em\u003e OR \u003cem\u003eHaemophilus aphrophilus\u003c/em\u003e\" with limitation in review article. One article with 2 cases was relevant [3]. According to our review of relevant studies, only a total of 8 cases (Table 1), including our 2 patients had been diagnosed in the English literature. There were 5 men (63%) and 3 women (37%) with a mean age of 55 years, ranging from 26 to 88 years. Six cases (75%) were less than 65 years old. The majority of cases had underlying diseases (5 cases, 63%) including malignancies (2 cases, 25%), excessive alcoholic consumption (2 cases, 25%), and bronchiectasis (1 case, 13%).\u0026nbsp;Cough, dyspnea, fever and pleuritic chest pain were the common symptoms at initial presentation. All patients underwent thoracentesis or tube thoracostomy therapy. All pleural effusion cultures grew\u003cem\u003e\u0026nbsp;A. aphrophilus\u003c/em\u003e. Sputum and blood cultures from all patients were negative for \u003cem\u003eA. aphrophilus\u003c/em\u003e. Three cases (patients 1-3) reported before 1978 were treated with penicillin. Three cases (patients 4-6) reported after 2005 were treated with amoxicillin-clavulanate or amoxicillin. One case (patient 7) reported after 2005 were treated with piperacillin/tazobactam. Although appropriate antibiotic therapy, 2 cases (25%) with intractable underlying diseases including lung cancer and alcoholic cirrhosis of liver died during hospitalization.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cem\u003eA. aphrophilus\u003c/em\u003e bundles together two previously separate species, \u003cem\u003eH. aphrophilus\u003c/em\u003e and \u003cem\u003eH. paraphrophilus\u003c/em\u003e [1]. This micro-organism requires 5% CO\u003csub\u003e2\u003c/sub\u003e for primary isolation and grows best on the\u0026nbsp;chocolate blood agar. \u003cem\u003eA. aphrophilus\u003c/em\u003e is oxidase-negative, catalase-negative and X and V independent, in contrast to the common isolated \u003cem\u003eH. influenzae\u003c/em\u003e and \u003cem\u003eH. para influenzae\u003c/em\u003e, which are both oxidase-positive and catalase-positive [2]. Because\u003cem\u003e\u0026nbsp;A. aphrophilus\u003c/em\u003e has been misidentified as \u003cem\u003ePasteurella\u003c/em\u003e species\u0026nbsp;using \u003cem\u003ecommercial identification kits\u003c/em\u003e [9, 10], diagnostic laboratories may have difficulty identifying this microorganism correctly. Therefore, the combination of \u003cem\u003ecommercial identification kits\u003c/em\u003e with a real-time PCR assay\u0026nbsp;[11] or\u0026nbsp;MALDI-TOF\u0026nbsp;[12] could improve microbiological documentation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;Clinical and Laboratory Standards Institute has published consensus guidelines for antimicrobial susceptibility testing for infrequently isolated or fastidious bacteria\u0026nbsp;[5]\u0026nbsp;including\u0026nbsp;\u003cem\u003eA. aphrophilus\u003c/em\u003e.\u0026nbsp;In a case series study, antimicrobial therapy for\u0026nbsp;\u003cem\u003eA. aphrophilus\u003c/em\u003e including amoxicillin or ampicillin with a\u0026nbsp;β-lactmase inhibitor, the third-generation cephalosporins, or the fluoroquinolones can lead to a favorable outcome [4]. Despite\u0026nbsp;this microorganism is susceptible to doxycycline, which was ineffective for the treatment of empyema in a case report [6].\u003c/p\u003e\n\u003cp\u003eThe initial presentation, radiological pattern and clinical course of patients with\u0026nbsp;\u003cem\u003eA. aphrophilus\u003c/em\u003e empyema thoracis\u0026nbsp;are indistinguishable from infections caused by other microorganisms. C\u003cem\u003eommercial identification kits\u003c/em\u003e may have difficulty identifying \u003cem\u003eA. aphrophilus\u0026nbsp;\u003c/em\u003ecorrectly.\u0026nbsp;The combination of \u003cem\u003ecommercial identification kits\u003c/em\u003e with\u0026nbsp;MALDI-TOF\u0026nbsp;MS\u0026nbsp;could improve microbiological documentation. The leading underlying diseases of death are malignancies and excessive alcoholic consumption\u003cem\u003e.\u003c/em\u003e The first-choice\u0026nbsp;antibiotics\u0026nbsp;for treating\u0026nbsp;\u003cem\u003eA. aphrophilus\u003c/em\u003e empyema\u0026nbsp;thoracis are\u0026nbsp;penicillin/β-lactam inhibitor combinations and the third-generation cephalosporins. Other effective options, according to antimicrobial sensitivity, include fluoroquinolones and meropenem.\u0026nbsp;\u003cem\u003eA. aphrophilus\u003c/em\u003e empyema\u0026nbsp;thoracis\u0026nbsp;can be a life-threatening opportunistic infection in immunocompromised patients.\u0026nbsp;The empirical antimicrobial therapy for \u003cem\u003eA. aphrophilus\u003c/em\u003e empyema thoracis should cover potential infections according to the patients’ underlying diseases\u0026nbsp;especially malignancy and alcoholism. \u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe effective treatment of\u0026nbsp;\u003cem\u003eA. aphrophilus\u003c/em\u003e empyema\u0026nbsp;thoracis should comprise (i) accurate causative pathogen identification by\u003cem\u003e\u0026nbsp;conforming with a\u003c/em\u003e combination of a \u003cem\u003ecommercial identification system\u003c/em\u003eand\u0026nbsp;MALDI-TOF MS\u003cem\u003e,\u003c/em\u003e\u003cem\u003e\u0026nbsp;(ii)\u0026nbsp;\u003c/em\u003eadequate empyema drainage, (iii) appropriate antimicrobial therapy with\u0026nbsp;penicillin/β-lactam inhibitor combinations or the third-generation cephalosporins, and (iv) underlying diseases management especially malignancy and alcoholism.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eCO\u003csub\u003e2\u003c/sub\u003e:\u003c/strong\u003eCarbon dioxide\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCT:\u003c/strong\u003e Computed tomography\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMALDI-TOF MS:\u0026nbsp;\u003c/strong\u003eMatrix-assisted laser desorption ionization time-of-flight mass spectrometry\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThis study follows the ethical principles of the \u003cstrong\u003eDeclaration of Helsinki\u003c/strong\u003e and has been\u0026nbsp;approved by the Institutional Review Board of Tainan Municipal Hospital (No. 1141201).\u0026nbsp;Written informed consent for publication was obtained from the next of kin of all patients.\u003c/p\u003e\n\u003col start=\"2\"\u003e\n \u003cli\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eConsent for publication\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ewas obtained from the next of kin of all patients. Written consent is available upon request.\u003c/p\u003e\n\u003col start=\"3\"\u003e\n \u003cli\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003col start=\"4\"\u003e\n \u003cli\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003col start=\"5\"\u003e\n \u003cli\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThere is no source of funding in submission of this report.\u003c/p\u003e\n\u003col start=\"6\"\u003e\n \u003cli\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eDW C was responsible for diagnosing and managing the patients. He also participated in the editing and writing of the manuscript. CT L participated in laboratory examinations. SL W participated in the data organization. All authors have reviewed the manuscript.\u003c/p\u003e\n\u003col start=\"7\"\u003e\n \u003cli\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003col start=\"8\"\u003e\n \u003cli\u003e\u003cstrong\u003eAuthors and Affiliations\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(optional)\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eN\u0026oslash;rskov-Lauritsen N, Kilian M. Reclassification of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis as Aggregatibacter actinomycetemcomitans gen. nov., comb. nov., Aggregatibacter aphrophilus comb. nov. and Aggregatibacter segnis comb. nov., and emended description of Aggregatibacter aphrophilus to include V factor-dependent and V factor-independent isolates. Int J Syst Evol Microbiol. 2006;56(Pt 9):2135-46; doi: 10.1099/ijs.0.64207-0.\u003c/li\u003e\n \u003cli\u003eMurphy TF. \u003cem\u003eHaemophilus\u003c/em\u003e species (including \u003cem\u003eH. influenzae\u003c/em\u003e and chancroid). In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett\u0026rsquo;s principles and practice of infectious diseases.\u0026nbsp;Philadelphia, Pennsylvania: Churchill Livingstone Elsevier; 2010. p. 2917-18.\u003c/li\u003e\n \u003cli\u003eBieger RC, Brewer NS, Washington JA 2nd. \u003cem\u003eHaemophilus aphrophilus\u003c/em\u003e: a microbiologic and clinical review and report of 42 cases.\u0026nbsp;Medicine (Baltimore). 1978;57(4):345-55.\u003c/li\u003e\n \u003cli\u003eHuang ST, Lee HC, Lee NY, Liu KH, Ko WC. Clinical characteristics of invasive \u003cem\u003eHaemophilus aphrophilus\u003c/em\u003e infections. J Microbiol Immunol Infect. 2005;38(4):271-6.\u003c/li\u003e\n \u003cli\u003eClinical and Laboratory Standards Institute. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Guideline-3rd Edition. M45. CLSI, Wayne, PA, USA, 2016.\u003c/li\u003e\n \u003cli\u003eRatnayake L, Olver WJ, Fardon T.\u003cem\u003e\u0026nbsp;Aggregatibacter aphrophilus\u003c/em\u003e in a patient with recurrent empyema: a case report.\u0026nbsp;Journal of Medical Case Reports. 2011;5:448;\u0026nbsp;doi: 10.1186/1752-1947-5-448.\u003c/li\u003e\n \u003cli\u003eRodriguez-Segade S, Velasco D, Marcos PJ.\u0026nbsp;Empyema due to \u003cem\u003eAggregatibacter aphrophilus\u003c/em\u003e and \u003cem\u003eParvimonas micra\u003c/em\u003e coinfection.\u0026nbsp;Arch Bronconeumol. 2015;51(5):254-5;\u0026nbsp;doi: 10.1016/j.arbres.2014.06.014.\u003c/li\u003e\n \u003cli\u003eCapelli JP, Savacool JW, Randall EL.\u0026nbsp;\u003cem\u003eHaemophilus aphrophilus\u003c/em\u003e empyema.\u0026nbsp;Ann Intern Med. 1965;62:771-7;\u0026nbsp;doi: 10.7326/0003-4819-62-4-771.\u003c/li\u003e\n \u003cli\u003eFrederiksen W, T\u0026oslash;nning B.\u0026nbsp;Possible misidentification of \u003cem\u003eHaemophilus aphrophilus\u003c/em\u003e as \u003cem\u003ePasteurella gallinarum\u003c/em\u003e.\u0026nbsp;Clin Infect Dis. 2001;32(6):987-9;\u0026nbsp;doi: 10.1086/319358.\u003c/li\u003e\n \u003cli\u003eChien JT, Lin CH, Chen YC, Lay CJ, Wang CL, Tsai CC. Epidural abscess caused by \u003cem\u003eHaemophilus aphrophilus\u003c/em\u003e misidentified as \u003cem\u003ePasteurella\u003c/em\u003e species.\u0026nbsp;Intern Med. 2009;48(10):853-8;\u0026nbsp;doi: 10.2169/internalmedicine.48.1930.\u003c/li\u003e\n \u003cli\u003eTeranishi H, Ohzono N, Inamura N, Atsushi K,\u0026nbsp;Wakabayashi T, Akaike H, et al.\u0026nbsp;Detection of bacteria and fungi in blood of patients with febrile neutropenia by real-time PCR with universal primers and probes.\u0026nbsp;J Infect Chemother. 2015;21(3):189-93;\u0026nbsp;doi: 10.1016/j.jiac.2014.11.008.\u003c/li\u003e\n \u003cli\u003eChoquet M, Pluquet E, Castelain S, Guih\u0026eacute;neuf R, Decroix V. Bartholinitis due to Aggregatibacter aphrophilus: a case report. BMC Infect Dis. 2016;16(1):574; doi: 10.1186/s12879-016-1908-1.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-bronchology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Bronchology](https://ejb.springeropen.com/)","snPcode":"43168","submissionUrl":"https://submission.nature.com/new-submission/43168/3","title":"The Egyptian Journal of Bronchology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Aggregatibacter aphrophilus, HACEK, Empyema Thoracis, Matrix-assisted laser desorption ionization time-of-flight mass spectrometry","lastPublishedDoi":"10.21203/rs.3.rs-8831766/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8831766/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e \u003cem\u003eAggregatibacter aphrophilus\u003c/em\u003e is a normal commensal of the human oropharynx and a member of the HACEK group of organisms. This microorganism can cause a wide variety of infections mainly including endocarditis and osteoarticular infections. However, empyema thoracis caused by \u003cem\u003eA. aphrophilus\u003c/em\u003e is very rare. The information about this rare disease is very limited. We herein report 2 rare cases having empyema thoracis due to \u003cem\u003eA. aphrophilus\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e An 88-year-old man with a history of bronchiectasis and periodontitis was admitted for a 2-week history of right lower chest pain, a low-grade fever, and productive cough. Another 51-year-old man with a history of alcoholic liver cirrhosis was admitted with complaint of right chest pain for one week. The cultures of the pleural effusion in both cases were positive for\u003cem\u003e A. aphrophilus \u003c/em\u003ewhich was confirmed by the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The former case responded to a 2-week course of intravenous piperacillin/tazobactam. The latter case died from shock and progressive deterioration of liver function.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e The effective treatment of \u003cem\u003eA. aphrophilus\u003c/em\u003e empyema thoracis should comprise (i) accurate causative pathogen identification by\u003cem\u003e conforming with \u003c/em\u003eMALDI-TOF MS\u003cem\u003e, \u003c/em\u003e(ii)\u003cem\u003e \u003c/em\u003eadequate empyema drainage, (iii) appropriate antimicrobial therapy with penicillin/β-lactam inhibitor combinations or the third-generation cephalosporins, and (iv) underlying diseases management especially malignancy and alcoholism.\u003c/p\u003e","manuscriptTitle":"Empyema Thoracis caused by Aggregatibacter aphrophilus: two cases report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 14:45:21","doi":"10.21203/rs.3.rs-8831766/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-11T12:13:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"327851287031320462844838536219897156893","date":"2026-03-11T11:30:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-06T01:44:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"4807329734809197713530466552054419194","date":"2026-02-26T16:42:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-26T09:40:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-20T21:43:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-19T15:35:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Egyptian Journal of Bronchology","date":"2026-02-09T14:24:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-bronchology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Bronchology](https://ejb.springeropen.com/)","snPcode":"43168","submissionUrl":"https://submission.nature.com/new-submission/43168/3","title":"The Egyptian Journal of Bronchology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c3e13ebb-fd30-42ba-aef5-36d9a989a2cb","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-25T14:56:41+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 14:45:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8831766","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8831766","identity":"rs-8831766","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}