Hospital-Acquired Pneumonia Caused by Multidrug-Resistant Streptococcus pneumoniae Serotype 15A

Hospital-Acquired Pneumonia Caused by Multidrug-Resistant Streptococcus pneumoniae Serotype 15A | 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 Hospital-Acquired Pneumonia Caused by Multidrug-Resistant Streptococcus pneumoniae Serotype 15A Hidemasa Akazawa, Shinnosuke Fukushima, Kenta Nakamoto, Kohei Oguni, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7185290/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Sep, 2025 Read the published version in Infection → Version 1 posted 7 You are reading this latest preprint version Abstract Background: Streptococcus pneumoniae remains a common cause of community-acquired pneumonia but is an infrequent pathogen in hospital-acquired pneumonia (HAP). Non-vaccine serotypes of multidrug-resistant (MDR) S. pneumoniae strains have been emerging globally, posing an increased risk of nosocomial infection. Case: A 71-year-old man developed pneumonia on postoperative day 4 following spinal fusion surgery. Despite initial treatment with ampicillin/sulbactam, his condition deteriorated, requiring ICU admission and mechanical ventilation. Microbiological testing confirmed S. pneumoniae as a causative pathogen, and ceftriaxone was empirically administered based on the local antibiogram. However, antimicrobial susceptibility testing revealed resistant profiles to penicillin (minimum inhibitory concentration [MIC], 8 µg/mL), ceftriaxone (MIC, 16 µg/mL), meropenem (MIC, 1 µg/mL), macrolides, and clindamycin, while demonstrating susceptibility to levofloxacin and vancomycin. The therapeutic regimen was subsequently adjusted to levofloxacin, resulting in clinical improvement. The isolate was later identified as serotype 15A, sequence type 63 (ST63). Conclusion: This case highlights that MDR S. pneumoniae can cause early-onset HAP and may not be covered by standard empiric therapies, emphasizing the need for careful evaluation of treatment response. Continued surveillance of infections caused by vaccine-escape clones like MDR serotype 15A is essential, given their increasing clinical relevance. antimicrobial resistance multidrug-resistant nosocomial infection sequence type 63 serotype 15A Streptococcus pneumoniae Figures Figure 1 Introduction Streptococcus pneumoniae is an encapsulated gram-positive diplococcus that commonly causes pneumonia, meningitis, and invasive pneumococcal disease [1]. S. pneumoniae accounts for approximately 20–50% of community-acquired bacterial pneumonia cases [2,3] and 5–9% of hospital-acquired pneumonia (HAP) cases [4,5]. According to recent surveillance studies, resistance rates based on non-meningeal breakpoints are relatively low, with penicillin G (PCG) resistance reported at 2–4% and ceftriaxone (CTRX) at 2–5%, meropenem (MEPM) at 2.7–33% [6–10]. The global incidence of pneumococcal infections has declined following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) [11]. However, an increasing number of infections caused by non-vaccine serotypes [12] and multidrug-resistant (MDR) strains, that is typically defined as resistance to three or more classes of antimicrobial agents [13], have been reported [14]. Among these, serotype 15A has attracted attention as a representative MDR strain not covered by currently-available vaccines [14,15]. Here, we report a case of hospital-acquired pneumonia caused by an MDR S. pneumoniae of serotype 15A. Case Report A 71-year-old man underwent simultaneous anterior and posterior spinal fusion surgery for cervical spondylotic myelopathy and was admitted to the intensive care unit (ICU) postoperatively as planned. On postoperative day (POD) 2, the patient was extubated and transferred to the general ward. On POD 4, the patient developed fever, purulent sputum, and decreased oxygen saturation, with the chest X-ray showing right lower lobe consolidation (Fig. 1 A). Chest computed tomography revealed consolidation in the dorsal segment of the right lower lobe and mucus accumulation within the bronchi (Fig. 1 B). Laboratory tests revealed the following results: white blood cell count, 6,730/µL; neutrophils: 86% (segmented neutrophils 78%, band forms 8%); and C-reactive protein, 22.17 mg/dL. Gram staining of a sputum sample classified as P1 by the Miller–Jones classification detected polymicrobial patterns, including encapsulated Gram-positive diplococci. Considering his advanced age, history of prolonged intubation, and recent cervical surgery, together with the radiographic and microbiological findings, he was diagnosed with aspiration pneumonia and was initially treated with ampicillin/sulbactam. Later that night, the patient’s respiratory condition deteriorated, accompanied by hypotension, necessitating readmission to the ICU and reintubation. Bronchoscopy revealed obstruction of the left upper and lower lobes with white secretions, and purulent sputum was obtained from the right lower lobe. Bronchial aspirate Gram stain demonstrated Gram-positive diplococci accompanied by phagocytosis, with no other organisms observed. The antimicrobial regimen was empirically switched to the combination of meropenem and vancomycin, considering his deteriorating condition. On POD 6, the causative pathogen was identified as S. pneumoniae . Given previous susceptibility data of our hospital indicating a 100% susceptibility rate of S. pneumoniae to ceftriaxone, the antimicrobial therapy was de-escalated to ceftriaxone before the susceptibility results became available. Next day, the testing results came out, showing resistance to penicillin G (PCG: MIC, 8 µg/mL), ceftriaxone (CTRX: MIC, ≥ 16 µg/mL), meropenem (MEPM: MIC, 1 µg/mL), azithromycin (AZM: MIC, ≥ 4 µg/mL), and clindamycin (CLDM: MIC, ≥ 8 µg/mL), while susceptibility to vancomycin (VCM: MIC, 0.5 µg/mL) and levofloxacin (LVFX: MIC, 2 µg/mL) (Table 1 ). The patient underwent definitive therapy with LVFX, and his subsequent clinical course was favorable. Table 1 Antimicrobial susceptibility of serotype 15A, sequence type 63 Streptococcus pneumoniae . Antimicrobials MIC (µg/ml) Susceptibility a Breakpoint reference Penicillin G (non-meningitis) 8 R S: ≤2 Ampicillin 4 - n.d. Ampicillin-Sulbactam 4 - n.d. Amoxicillin-Clavulanate 4 I S: ≤2/1 Cefotaxime (non-meningitis) ≥ 16 R S: ≤1 Cefditoren Pivoxil ≥ 16 - n.d. Meropenem 1 R S: ≤0.25 Tebipenem 0.12 - n.d. Erythromycin ≥ 8 R S: ≤0.25 Clarithromycin ≥ 16 R S: ≤0.25 Azithromycin ≥ 4 R S: ≤0.5 Clindamycin ≥ 8 R S: ≤0.25 Trimethoprim-Sulfamethoxazole 1/19 I S: ≤0.5/9.5 Levofloxacin 2 S S: ≤2 Vancomycin 0.5 S S: ≤1 ༊Abbreviations: MIC, minimum inhibitory concentration; R, resistant; I, intermediate; S, susceptible; n.d., Not defined. a MIC breakpoint reference: M100 (34th edition) by the Clinical and Laboratory Standards Institute. MICs were determined using the Eiken Dry Plate (Eiken Chemical Co., Ltd., Tokyo, Japan), a broth microdilution-based method. The pneumococcal isolate was transferred to the National Institute of Infectious Diseases (Tokyo, Japan), where it was serotyped by a capsule Quellung reaction with serotype-specific rabbit antiserum (Statens Serum Institute, Copenhagen, Denmark). Multilocus sequence typing was performed by sequencing seven housekeeping genes ( aroE, gdh, gki, recP, spi, xpt, ddl ) [16]. Consequently, it was determined to be serotype 15A and sequence type (ST) 63. Discussion We experienced a case of nosocomial pneumonia caused by serotype 15A-ST63 S. pneumoniae , which has an MDR phenotype. This serotype corresponds to the representative MDR clone in the Pneumococcal Molecular Epidemiology Network (PMEN), and its global prevalence has been increasing in recent years [17]. Before the introduction of PCV, only 6.5% of ST63 strains belonged to serotype 15A, whereas its proportion soared to 65.4% in the post-PCV era [18]. The serotype 15A-ST63 clone has attracted attention due to its resistance to β-lactam antibiotics commonly used in clinical settings [17,19,20]. The present isolate of S. pneumoniae demonstrated a broad spectrum of antimicrobial resistance, including PCG, CTX, MEPM, AZM, and CLDM. The acquisition of broad β-lactam resistance in S. pneumoniae is largely attributed to mutations and genetic recombination in penicillin-binding protein (PBP) genes. Although six PBPs (PBP1a, PBP1b, PBP2a, PBP2x, PBP2b, and PBP3) are encoded in the S. pneumoniae genome, resistance to β-lactam antibiotics is primarily associated with alterations in PBP1a, PBP2x, and PBP2b [13]. Nakano et al. performed whole-genome sequencing of serotype 15A-ST63 isolates with reduced susceptibility to MEPM, reporting that recombination events in the pbp1a and pbp2b regions were responsible for this phenotype [17]. The pbp1a gene identified in these isolates was identical to that of the serotype 19A-ST320 clone, another MDR strain with high-level MEPM resistance that emerged in the United States, and this recombination event has been shown to confer reduced susceptibility to carbapenems [21]. Furthermore, recombination in the pbp2x gene, which can be observed in the ST63 lineage, is known to play a critical role in cephalosporin resistance [19]. Macrolide resistance in S. pneumoniae is predominantly mediated by two mechanisms: ribosomal target modification via the erm(B) -encoded erythromycin ribosomal methylase, and active efflux pump by the major facilitator superfamily transporter encoded by mefA or mefE [13]. Taken together, the resistance phenotype observed in the present isolate—PCG-resistant, CTRX-resistant, and MEPM-resistant—suggests the presence of broad β-lactam resistance mediated by genetic alterations in pbp1a and pbp2x . In addition, the concurrent resistance to macrolides and lincosamides implies involvement of the erm(B) gene and associated methyltransferases in mediating ribosomal target modification. In general, typical pathogens of HAP include Pseudomonas aeruginosa, Acinetobacter baumanii complex, and Staphylococcus aureus , while S. pneumoniae is a relatively uncommon cause [5]. However, in early-onset HAP (defined as onset within 4 to 7 days of hospitalization), S. pneumoniae may also be a causative organism, accounting for approximately 9% of cases [4]. A nosocomial cluster caused by MDR serotype 15A S. pneumoniae was reported in the Netherlands [22], highlighting the potential risk of nosocomial transmission of MDR S. pneumoniae . We presented an early-onset HAP case of serotype 15A-ST63 S. pneumoniae. This case underscores the importance of considering S. pneumoniae infection even under broad-spectrum antimicrobial therapy and highlights the need for careful evaluation of treatment response. Furthermore, it suggests a potential risk of nosocomial transmission of MDR S. pneumoniae , emphasizing its relevance from both clinical and infection control perspectives. Declarations Authorship statement : H.A. drafted the manuscript; S.F and H.H. revised the manuscript; H.A, S.F, H.H, K.N, K.O, S.M. contributed to the clinical management of the patient; B.C. and Y.A. contributed to the microbiological testing. All the authors interpreted the results and approved the submission of the manuscript. Funding No authors have any funding in this case. Informed Consent Informed consent was obtained from the patient for the publication of our information and images. Ethics approval and consent to participate This case report is the author’s original work and has not been previously published elsewhere. Competing interests No authors have any competing interests in this case. References Mitchell AM, Mitchell TJ. Streptococcus pneumoniae: virulence factors and variation. Clin Microbiol Infect. 2010;16:411–8. Fujikura Y, Somekawa K, Manabe T, Horita N, Takahashi H, Higa F, et al. Aetiological agents of adult community-acquired pneumonia in Japan: systematic review and meta-analysis of published data. BMJ Open Respir Res. 2023;10:e001800. Shoar S, Musher DM. Etiology of community-acquired pneumonia in adults: a systematic review. Pneumonia (Nathan). 2020;12:11. Koulenti D, Tsigou E, Rello J. Nosocomial pneumonia in 27 ICUs in Europe: perspectives from the EU-VAP/CAP study. Eur J Clin Microbiol Infect Dis. 2017;36:1999–2006. Ibn Saied W, Mourvillier B, Cohen Y, Ruckly S, Reignier J, Marcotte G, et al. A comparison of the mortality risk associated with ventilator-acquired bacterial pneumonia and nonventilator ICU-acquired bacterial pneumonia. Crit Care Med. 2019;47:345–52. Yanagihara K, Kosai K, Mikamo H, Mukae H, Takesue Y, Abe M, et al. Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae associated with invasive pneumococcal disease among adults in Japan. Int J Infect Dis. 2021;102:260–8. Atıcı S, Güneşer D, Kepenekli E, Söyletir G, Soysal A. Serotypes distribution and antibiotic susceptibility of Streptococcus pneumoniae strains: five-year surveillance results of post-PCV-13. BMC Pediatr. 2025;25:244. Zhou M, Wang Z, Zhang L, Kudinha T, An H, Qian C, et al. Serotype distribution, antimicrobial susceptibility, multilocus sequencing type and virulence of invasive Streptococcus pneumoniae in China: A six-year multicenter study. Front Microbiol. 2021;12:798750. Tsai Y-T, Lee Y-L, Lu M-C, Shao P-L, Lu P-L, Cheng S-H, et al. Nationwide surveillance of antimicrobial resistance in invasive isolates of Streptococcus pneumoniae in Taiwan from 2017 to 2019. J Microbiol Immunol Infect. 2022;55:215–24. Kulkarni N, Routray A, Taur S. A multicenter evaluation of overall susceptibility and antimicrobial resistance among Streptococcus pneumoniae isolates. Cureus. 2023;15:e41984. Ouldali N, Varon E, Levy C, Angoulvant F, Georges S, Ploy M-C, et al. Invasive pneumococcal disease incidence in children and adults in France during the pneumococcal conjugate vaccine era: an interrupted time-series analysis of data from a 17-year national prospective surveillance study. Lancet Infect Dis. 2021;21:137–47. Redin A, Ciruela P, de Sevilla MF, Gomez-Bertomeu F, Gonzalez-Peris S, Benitez MA, et al. Serotypes and clonal composition of Streptococcus pneumoniae isolates causing IPD in children and adults in Catalonia before 2013 to 2015 and after 2017 to 2019 systematic introduction of PCV13. Microbiol Spectr. 2021;9:e0115021. Li L, Ma J, Yu Z, Li M, Zhang W, Sun H. Epidemiological characteristics and antibiotic resistance mechanisms of Streptococcus pneumoniae: An updated review. Microbiol Res. 2023;266:127221. Siira L, Vestrheim DF, Winje BA, Caugant DA, Steens A. Antimicrobial susceptibility and clonality of Streptococcus pneumoniae isolates recovered from invasive disease cases during a period with changes in pneumococcal childhood vaccination, Norway, 2004-2016. Vaccine. 2020;38:5454–63. Savinova T, Brzhozovskaya E, Shagin D, Mikhaylova Y, Shelenkov A, Yanushevich Y, et al. A multiple drug-resistant Streptococcus pneumoniae of serotype 15A occurring from serotype 19A by capsular switching. Vaccine. 2020;38:5114–8. Public databases for molecular typing and microbial genome diversity. Streptococcus pneumoniae [Internet]. PubMLST. [cited 2025 Jul 16]. Available from: https://pubmlst.org/organisms/streptococcus-pneumoniae. Nakano S, Fujisawa T, Ito Y, Chang B, Matsumura Y, Yamamoto M, et al. Spread of meropenem-resistant streptococcus pneumoniae serotype 15A-ST63 clone in Japan, 2012-2014. Emerg Infect Dis. 2018;24:275–83. Hawkins PA, Chochua S, Lo SW, Belman S, Antonio M, Kwambana-Adams B, et al. A global genomic perspective on the multidrug-resistant Streptococcus pneumoniae 15A-CC63 sub-lineage following pneumococcal conjugate vaccine introduction. Microb Genom [Internet]. 2023 [cited 2025 Jul 7];9. Available from: http://dx.doi.org/10.1099/mgen.0.000998 Nakano S, Fujisawa T, Ito Y, Chang B, Matsumura Y, Yamamoto M, et al. Whole-genome sequencing analysis of multidrug-resistant serotype 15A streptococcus pneumoniae in Japan and the emergence of a highly resistant serotype 15A-ST9084 clone. Antimicrob Agents Chemother [Internet]. 2019 [cited 2025 Jul 7];63. Available from: http://dx.doi.org/10.1128/AAC.02579-18 Ardanuy C, de la Campa AG, García E, Fenoll A, Calatayud L, Cercenado E, et al. Spread of Streptococcus pneumoniae serotype 8-ST63 multidrug-resistant recombinant Clone, Spain. Emerg Infect Dis. 2014;20:1848–56. Metcalf BJ, Gertz RE Jr, Gladstone RA, Walker H, Sherwood LK, Jackson D, et al. Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA. Clin Microbiol Infect. 2016;22:60.e9-60.e29. Bastiaens GJH, Cremers AJH, Coolen JPM, Nillesen MT, Boeree MJ, Hopman J, et al. Nosocomial outbreak of multi-resistant Streptococcus pneumoniae serotype 15A in a centre for chronic pulmonary diseases. Antimicrob Resist Infect Control. 2018;7:158. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 23 Sep, 2025 Read the published version in Infection → Version 1 posted Editorial decision: Revision requested 03 Sep, 2025 Reviews received at journal 01 Sep, 2025 Reviewers agreed at journal 17 Aug, 2025 Reviewers invited by journal 24 Jul, 2025 Editor assigned by journal 23 Jul, 2025 Submission checks completed at journal 23 Jul, 2025 First submitted to journal 22 Jul, 2025 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-7185290","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":490872350,"identity":"eba5b9b1-08da-4062-aa1a-7e31fdb13dd9","order_by":0,"name":"Hidemasa Akazawa","email":"","orcid":"","institution":"Okayama University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hidemasa","middleName":"","lastName":"Akazawa","suffix":""},{"id":490872351,"identity":"9cf6fe70-af1e-426a-a7ec-bf7191ce2d33","order_by":1,"name":"Shinnosuke Fukushima","email":"","orcid":"","institution":"Okayama University 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16:07:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":776446,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7185290/v1/2d9cfcd4-c8fc-4994-a8d0-3cc6f8785704.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Hospital-Acquired Pneumonia Caused by Multidrug-Resistant Streptococcus pneumoniae Serotype 15A","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e is an encapsulated gram-positive diplococcus that commonly causes pneumonia, meningitis, and invasive pneumococcal disease [1]. \u003cem\u003eS. pneumoniae\u003c/em\u003e accounts for approximately 20–50% of community-acquired bacterial pneumonia cases [2,3] and 5–9% of hospital-acquired pneumonia (HAP) cases [4,5]. According to recent surveillance studies, resistance rates based on non-meningeal breakpoints are relatively low, with penicillin G (PCG) resistance reported at 2–4% and ceftriaxone (CTRX) at 2–5%, meropenem (MEPM) at 2.7–33% [6–10].\u003c/p\u003e\u003cp\u003eThe global incidence of pneumococcal infections has declined following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) [11]. However, an increasing number of infections caused by non-vaccine serotypes [12] and multidrug-resistant (MDR) strains, that is typically defined as resistance to three or more classes of antimicrobial agents [13], have been reported [14]. Among these, serotype 15A has attracted attention as a representative MDR strain not covered by currently-available vaccines [14,15]. Here, we report a case of hospital-acquired pneumonia caused by an MDR \u003cem\u003eS. pneumoniae\u003c/em\u003e of serotype 15A.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 71-year-old man underwent simultaneous anterior and posterior spinal fusion surgery for cervical spondylotic myelopathy and was admitted to the intensive care unit (ICU) postoperatively as planned. On postoperative day (POD) 2, the patient was extubated and transferred to the general ward. On POD 4, the patient developed fever, purulent sputum, and decreased oxygen saturation, with the chest X-ray showing right lower lobe consolidation (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Chest computed tomography revealed consolidation in the dorsal segment of the right lower lobe and mucus accumulation within the bronchi (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Laboratory tests revealed the following results: white blood cell count, 6,730/µL; neutrophils: 86% (segmented neutrophils 78%, band forms 8%); and C-reactive protein, 22.17 mg/dL. Gram staining of a sputum sample classified as P1 by the Miller–Jones classification detected polymicrobial patterns, including encapsulated Gram-positive diplococci. Considering his advanced age, history of prolonged intubation, and recent cervical surgery, together with the radiographic and microbiological findings, he was diagnosed with aspiration pneumonia and was initially treated with ampicillin/sulbactam.\u003c/p\u003e\u003cp\u003eLater that night, the patient’s respiratory condition deteriorated, accompanied by hypotension, necessitating readmission to the ICU and reintubation. Bronchoscopy revealed obstruction of the left upper and lower lobes with white secretions, and purulent sputum was obtained from the right lower lobe. Bronchial aspirate Gram stain demonstrated Gram-positive diplococci accompanied by phagocytosis, with no other organisms observed. The antimicrobial regimen was empirically switched to the combination of meropenem and vancomycin, considering his deteriorating condition.\u003c/p\u003e\u003cp\u003eOn POD 6, the causative pathogen was identified as \u003cem\u003eS. pneumoniae\u003c/em\u003e. Given previous susceptibility data of our hospital indicating a 100% susceptibility rate of \u003cem\u003eS. pneumoniae\u003c/em\u003e to ceftriaxone, the antimicrobial therapy was de-escalated to ceftriaxone before the susceptibility results became available. Next day, the testing results came out, showing resistance to penicillin G (PCG: MIC, 8 µg/mL), ceftriaxone (CTRX: MIC, ≥ 16 µg/mL), meropenem (MEPM: MIC, 1 µg/mL), azithromycin (AZM: MIC, ≥ 4 µg/mL), and clindamycin (CLDM: MIC, ≥ 8 µg/mL), while susceptibility to vancomycin (VCM: MIC, 0.5 µg/mL) and levofloxacin (LVFX: MIC, 2 µg/mL) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The patient underwent definitive therapy with LVFX, and his subsequent clinical course was favorable.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAntimicrobial susceptibility of serotype 15A, sequence type 63 \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntimicrobials\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMIC (µg/ml)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSusceptibility\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Breakpoint reference\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePenicillin G (non-meningitis)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS: ≤2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAmpicillin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003en.d.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAmpicillin-Sulbactam\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003en.d.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAmoxicillin-Clavulanate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS: ≤2/1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCefotaxime (non-meningitis)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e≥ 16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS: ≤1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCefditoren Pivoxil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e≥ 16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003en.d.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMeropenem\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS: ≤0.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTebipenem\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003en.d.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eErythromycin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e≥ 8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS: ≤0.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClarithromycin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e≥ 16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS: ≤0.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAzithromycin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e≥ 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS: ≤0.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClindamycin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e≥ 8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS: ≤0.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTrimethoprim-Sulfamethoxazole\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1/19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS: ≤0.5/9.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLevofloxacin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS: ≤2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVancomycin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS: ≤1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e༊Abbreviations: MIC, minimum inhibitory concentration; R, resistant; I, intermediate; S, susceptible; n.d., Not defined.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e MIC breakpoint reference: M100 (34th edition) by the Clinical and Laboratory Standards Institute.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eMICs were determined using the Eiken Dry Plate (Eiken Chemical Co., Ltd., Tokyo, Japan), a broth microdilution-based method.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003eThe pneumococcal isolate was transferred to the National Institute of Infectious Diseases (Tokyo, Japan), where it was serotyped by a capsule Quellung reaction with serotype-specific rabbit antiserum (Statens Serum Institute, Copenhagen, Denmark). Multilocus sequence typing was performed by sequencing seven housekeeping genes (\u003cem\u003earoE, gdh, gki, recP, spi, xpt, ddl\u003c/em\u003e) [16]. Consequently, it was determined to be serotype 15A and sequence type (ST) 63.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe experienced a case of nosocomial pneumonia caused by serotype 15A-ST63 \u003cem\u003eS. pneumoniae\u003c/em\u003e, which has an MDR phenotype. This serotype corresponds to the representative MDR clone in the Pneumococcal Molecular Epidemiology Network (PMEN), and its global prevalence has been increasing in recent years [17]. Before the introduction of PCV, only 6.5% of ST63 strains belonged to serotype 15A, whereas its proportion soared to 65.4% in the post-PCV era [18]. The serotype 15A-ST63 clone has attracted attention due to its resistance to β-lactam antibiotics commonly used in clinical settings [17,19,20].\u003c/p\u003e\u003cp\u003eThe present isolate of \u003cem\u003eS. pneumoniae\u003c/em\u003e demonstrated a broad spectrum of antimicrobial resistance, including PCG, CTX, MEPM, AZM, and CLDM. The acquisition of broad β-lactam resistance in \u003cem\u003eS. pneumoniae\u003c/em\u003e is largely attributed to mutations and genetic recombination in penicillin-binding protein (PBP) genes. Although six PBPs (PBP1a, PBP1b, PBP2a, PBP2x, PBP2b, and PBP3) are encoded in the \u003cem\u003eS. pneumoniae\u003c/em\u003e genome, resistance to β-lactam antibiotics is primarily associated with alterations in PBP1a, PBP2x, and PBP2b [13]. Nakano \u003cem\u003eet al.\u003c/em\u003e performed whole-genome sequencing of serotype 15A-ST63 isolates with reduced susceptibility to MEPM, reporting that recombination events in the \u003cem\u003epbp1a\u003c/em\u003e and \u003cem\u003epbp2b\u003c/em\u003e regions were responsible for this phenotype [17]. The \u003cem\u003epbp1a\u003c/em\u003e gene identified in these isolates was identical to that of the serotype 19A-ST320 clone, another MDR strain with high-level MEPM resistance that emerged in the United States, and this recombination event has been shown to confer reduced susceptibility to carbapenems [21]. Furthermore, recombination in the \u003cem\u003epbp2x\u003c/em\u003e gene, which can be observed in the ST63 lineage, is known to play a critical role in cephalosporin resistance [19]. Macrolide resistance in \u003cem\u003eS. pneumoniae\u003c/em\u003e is predominantly mediated by two mechanisms: ribosomal target modification via the \u003cem\u003eerm(B)\u003c/em\u003e-encoded erythromycin ribosomal methylase, and active efflux pump by the major facilitator superfamily transporter encoded by \u003cem\u003emefA\u003c/em\u003e or \u003cem\u003emefE\u003c/em\u003e [13]. Taken together, the resistance phenotype observed in the present isolate\u0026mdash;PCG-resistant, CTRX-resistant, and MEPM-resistant\u0026mdash;suggests the presence of broad β-lactam resistance mediated by genetic alterations in \u003cem\u003epbp1a\u003c/em\u003e and \u003cem\u003epbp2x\u003c/em\u003e. In addition, the concurrent resistance to macrolides and lincosamides implies involvement of the \u003cem\u003eerm(B)\u003c/em\u003e gene and associated methyltransferases in mediating ribosomal target modification.\u003c/p\u003e\u003cp\u003eIn general, typical pathogens of HAP include \u003cem\u003ePseudomonas aeruginosa, Acinetobacter baumanii\u003c/em\u003e complex, and \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, while \u003cem\u003eS. pneumoniae\u003c/em\u003e is a relatively uncommon cause [5]. However, in early-onset HAP (defined as onset within 4 to 7 days of hospitalization), \u003cem\u003eS. pneumoniae\u003c/em\u003e may also be a causative organism, accounting for approximately 9% of cases [4]. A nosocomial cluster caused by MDR serotype 15A \u003cem\u003eS. pneumoniae\u003c/em\u003e was reported in the Netherlands [22], highlighting the potential risk of nosocomial transmission of MDR \u003cem\u003eS. pneumoniae\u003c/em\u003e.\u003c/p\u003e\u003cp\u003eWe presented an early-onset HAP case of serotype 15A-ST63 \u003cem\u003eS. pneumoniae.\u003c/em\u003e This case underscores the importance of considering \u003cem\u003eS. pneumoniae\u003c/em\u003e infection even under broad-spectrum antimicrobial therapy and highlights the need for careful evaluation of treatment response. Furthermore, it suggests a potential risk of nosocomial transmission of MDR \u003cem\u003eS. pneumoniae\u003c/em\u003e, emphasizing its relevance from both clinical and infection control perspectives.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthorship statement\u003c/strong\u003e:\u0026nbsp;H.A. drafted the manuscript; S.F and H.H. revised the manuscript; H.A, S.F, H.H, K.N, K.O, S.M. contributed to the clinical management of the patient; B.C. and Y.A. contributed to the microbiological testing. All the authors interpreted the results and approved the submission of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo authors have any funding in this case.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from the patient for the publication of our information and images.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report is the author\u0026rsquo;s original work and has not been previously published elsewhere.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo authors have any competing interests in this case.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMitchell AM, Mitchell TJ. Streptococcus pneumoniae: virulence factors and variation. Clin Microbiol Infect. 2010;16:411\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eFujikura Y, Somekawa K, Manabe T, Horita N, Takahashi H, Higa F, et al. Aetiological agents of adult community-acquired pneumonia in Japan: systematic review and meta-analysis of published data. BMJ Open Respir Res. 2023;10:e001800.\u003c/li\u003e\n\u003cli\u003eShoar S, Musher DM. Etiology of community-acquired pneumonia in adults: a systematic review. Pneumonia (Nathan). 2020;12:11.\u003c/li\u003e\n\u003cli\u003eKoulenti D, Tsigou E, Rello J. Nosocomial pneumonia in 27 ICUs in Europe: perspectives from the EU-VAP/CAP study. Eur J Clin Microbiol Infect Dis. 2017;36:1999\u0026ndash;2006.\u003c/li\u003e\n\u003cli\u003eIbn Saied W, Mourvillier B, Cohen Y, Ruckly S, Reignier J, Marcotte G, et al. A comparison of the mortality risk associated with ventilator-acquired bacterial pneumonia and nonventilator ICU-acquired bacterial pneumonia. Crit Care Med. 2019;47:345\u0026ndash;52.\u003c/li\u003e\n\u003cli\u003eYanagihara K, Kosai K, Mikamo H, Mukae H, Takesue Y, Abe M, et al. Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae associated with invasive pneumococcal disease among adults in Japan. Int J Infect Dis. 2021;102:260\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eAtıcı S, G\u0026uuml;neşer D, Kepenekli E, S\u0026ouml;yletir G, Soysal A. Serotypes distribution and antibiotic susceptibility of Streptococcus pneumoniae strains: five-year surveillance results of post-PCV-13. BMC Pediatr. 2025;25:244.\u003c/li\u003e\n\u003cli\u003eZhou M, Wang Z, Zhang L, Kudinha T, An H, Qian C, et al. Serotype distribution, antimicrobial susceptibility, multilocus sequencing type and virulence of invasive Streptococcus pneumoniae in China: A six-year multicenter study. Front Microbiol. 2021;12:798750.\u003c/li\u003e\n\u003cli\u003eTsai Y-T, Lee Y-L, Lu M-C, Shao P-L, Lu P-L, Cheng S-H, et al. 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Serotypes and clonal composition of Streptococcus pneumoniae isolates causing IPD in children and adults in Catalonia before 2013 to 2015 and after 2017 to 2019 systematic introduction of PCV13. Microbiol Spectr. 2021;9:e0115021.\u003c/li\u003e\n\u003cli\u003eLi L, Ma J, Yu Z, Li M, Zhang W, Sun H. Epidemiological characteristics and antibiotic resistance mechanisms of Streptococcus pneumoniae: An updated review. Microbiol Res. 2023;266:127221.\u003c/li\u003e\n\u003cli\u003eSiira L, Vestrheim DF, Winje BA, Caugant DA, Steens A. Antimicrobial susceptibility and clonality of Streptococcus pneumoniae isolates recovered from invasive disease cases during a period with changes in pneumococcal childhood vaccination, Norway, 2004-2016. Vaccine. 2020;38:5454\u0026ndash;63.\u003c/li\u003e\n\u003cli\u003eSavinova T, Brzhozovskaya E, Shagin D, Mikhaylova Y, Shelenkov A, Yanushevich Y, et al. A multiple drug-resistant Streptococcus pneumoniae of serotype 15A occurring from serotype 19A by capsular switching. Vaccine. 2020;38:5114\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003ePublic databases for molecular typing and microbial genome diversity. Streptococcus pneumoniae [Internet]. PubMLST. [cited 2025 Jul 16]. Available from: https://pubmlst.org/organisms/streptococcus-pneumoniae.\u003c/li\u003e\n\u003cli\u003eNakano S, Fujisawa T, Ito Y, Chang B, Matsumura Y, Yamamoto M, et al. Spread of meropenem-resistant streptococcus pneumoniae serotype 15A-ST63 clone in Japan, 2012-2014. Emerg Infect Dis. 2018;24:275\u0026ndash;83.\u003c/li\u003e\n\u003cli\u003eHawkins PA, Chochua S, Lo SW, Belman S, Antonio M, Kwambana-Adams B, et al. A global genomic perspective on the multidrug-resistant Streptococcus pneumoniae 15A-CC63 sub-lineage following pneumococcal conjugate vaccine introduction. Microb Genom [Internet]. 2023 [cited 2025 Jul 7];9. Available from: http://dx.doi.org/10.1099/mgen.0.000998\u003c/li\u003e\n\u003cli\u003eNakano S, Fujisawa T, Ito Y, Chang B, Matsumura Y, Yamamoto M, et al. Whole-genome sequencing analysis of multidrug-resistant serotype 15A streptococcus pneumoniae in Japan and the emergence of a highly resistant serotype 15A-ST9084 clone. Antimicrob Agents Chemother [Internet]. 2019 [cited 2025 Jul 7];63. Available from: http://dx.doi.org/10.1128/AAC.02579-18\u003c/li\u003e\n\u003cli\u003eArdanuy C, de la Campa AG, Garc\u0026iacute;a E, Fenoll A, Calatayud L, Cercenado E, et al. Spread of Streptococcus pneumoniae serotype 8-ST63 multidrug-resistant recombinant Clone, Spain. Emerg Infect Dis. 2014;20:1848\u0026ndash;56.\u003c/li\u003e\n\u003cli\u003eMetcalf BJ, Gertz RE Jr, Gladstone RA, Walker H, Sherwood LK, Jackson D, et al. Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA. Clin Microbiol Infect. 2016;22:60.e9-60.e29.\u003c/li\u003e\n\u003cli\u003eBastiaens GJH, Cremers AJH, Coolen JPM, Nillesen MT, Boeree MJ, Hopman J, et al. Nosocomial outbreak of multi-resistant Streptococcus pneumoniae serotype 15A in a centre for chronic pulmonary diseases. Antimicrob Resist Infect Control. 2018;7:158.\u003c/li\u003e\n\u003c/ol\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":"infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infe","sideBox":"Learn more about [Infection](http://link.springer.com/journal/15010)","snPcode":"15010","submissionUrl":"https://submission.nature.com/new-submission/15010/3","title":"Infection","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"antimicrobial resistance, multidrug-resistant, nosocomial infection, sequence type 63, serotype 15A, Streptococcus pneumoniae","lastPublishedDoi":"10.21203/rs.3.rs-7185290/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7185290/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003e\u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e remains a common cause of community-acquired pneumonia but is an infrequent pathogen in hospital-acquired pneumonia (HAP). Non-vaccine serotypes of multidrug-resistant (MDR) \u003cem\u003eS. pneumoniae\u003c/em\u003e strains have been emerging globally, posing an increased risk of nosocomial infection.\u003c/p\u003e\u003ch2\u003eCase:\u003c/h2\u003e\u003cp\u003eA 71-year-old man developed pneumonia on postoperative day 4 following spinal fusion surgery. Despite initial treatment with ampicillin/sulbactam, his condition deteriorated, requiring ICU admission and mechanical ventilation. Microbiological testing confirmed \u003cem\u003eS. pneumoniae\u003c/em\u003e as a causative pathogen, and ceftriaxone was empirically administered based on the local antibiogram. However, antimicrobial susceptibility testing revealed resistant profiles to penicillin (minimum inhibitory concentration [MIC], 8 \u0026micro;g/mL), ceftriaxone (MIC, 16 \u0026micro;g/mL), meropenem (MIC, 1 \u0026micro;g/mL), macrolides, and clindamycin, while demonstrating susceptibility to levofloxacin and vancomycin. The therapeutic regimen was subsequently adjusted to levofloxacin, resulting in clinical improvement. The isolate was later identified as serotype 15A, sequence type 63 (ST63).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eThis case highlights that MDR \u003cem\u003eS. pneumoniae\u003c/em\u003e can cause early-onset HAP and may not be covered by standard empiric therapies, emphasizing the need for careful evaluation of treatment response. Continued surveillance of infections caused by vaccine-escape clones like MDR serotype 15A is essential, given their increasing clinical relevance.\u003c/p\u003e","manuscriptTitle":"Hospital-Acquired Pneumonia Caused by Multidrug-Resistant Streptococcus pneumoniae Serotype 15A","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-28 11:49:00","doi":"10.21203/rs.3.rs-7185290/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-03T12:44:04+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-01T19:38:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"69652388968726976844935478267468422568","date":"2025-08-17T18:49:51+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-24T07:49:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-23T11:40:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-23T08:24:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"Infection","date":"2025-07-22T09:23:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infe","sideBox":"Learn more about [Infection](http://link.springer.com/journal/15010)","snPcode":"15010","submissionUrl":"https://submission.nature.com/new-submission/15010/3","title":"Infection","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"65e1ae1e-f86a-4d5a-aa1d-aeec4f14d601","owner":[],"postedDate":"July 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-29T16:04:02+00:00","versionOfRecord":{"articleIdentity":"rs-7185290","link":"https://doi.org/10.1007/s15010-025-02652-3","journal":{"identity":"infection","isVorOnly":false,"title":"Infection"},"publishedOn":"2025-09-23 15:57:58","publishedOnDateReadable":"September 23rd, 2025"},"versionCreatedAt":"2025-07-28 11:49:00","video":"","vorDoi":"10.1007/s15010-025-02652-3","vorDoiUrl":"https://doi.org/10.1007/s15010-025-02652-3","workflowStages":[]},"version":"v1","identity":"rs-7185290","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7185290","identity":"rs-7185290","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}