Intrapleural colistin for pleural empyema due to multi-drug resistant pathogen: a case report and review of the literature

Intrapleural colistin for pleural empyema due to multi-drug resistant pathogen: a case report and review of the literature | 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 Intrapleural colistin for pleural empyema due to multi-drug resistant pathogen: a case report and review of the literature Kobbai Alexandre, Fabio Silvio Taccone, Samuel Terrazzino, Charles-Hervé Vacheron This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7684980/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Pulmonary empyema caused by Pseudomonas aeruginosa producing Verona Integron-Encoded Metallo (VIM) β-lactamase represents a major therapeutic challenge due to the limited available therapeutic options. We reported the case of a 31-year-old patient admitted to intensive care unit (ICU) for drug intoxication, who subsequently developed aspiration pneumonia complicated by pleural empyema due to VIM-producing Pseudomonas aeruginosa . Due to clinical failure of intravenous therapy, intrapleural colistin was added, which resulted in significant clinical improvement and successful ICU discharge. This case highlights the potential role of intrapleural colistin administration in selected case of multidrug-resistant pleural infections to ensure adequate local antibiotic concentrations. Only two other similar cases with an intrapleural colistin administration have been previously reported, suggesting the need for evaluating this strategy in larger patients’ cohorts. Carbapenemase VIM Colistin Pulmonary empyema Figures Figure 1 Introduction The emergence of carbapenemase-producing Pseudomonas aeruginosa poses major therapeutic challenges due to extensive resistance to commonly used antibiotics and an increased risk of clinical and microbiological failure [ 1 ]. Consequently, there is a pressing need for innovative therapeutic strategies, including the optimization of existing drugs, the rational use of novel β-lactam–β-lactamase inhibitor combinations, and the development of combination regimens tailored to infection site and pathogen characteristics [ 2 ]. Alongside new-generation β-lactam agents, colistin remains an important therapeutic option against multidrug-resistant Gram-negative bacteria, despite limitations related to complex pharmacokinetics and potential toxicity [ 3 – 5 ]. However, data on non-intravenous routes of administration of colistin remain scarce. We reported a case of pleural empyema caused by a Verona Integron-Encoded Metallo (VIM) β-lactamase producing Pseudomonas aeruginosa successfully managed with combined intravenous and intrapleural colistin, highlighting the value of adaptive strategies to optimize local drug exposure in difficult-to-treat pulmonary infections. Case report A 31-year-old man with no prior medical history and no recent travel was admitted to the intensive care unit (ICU) with altered consciousness due to combined amphetamine and benzodiazepine intoxication, complicated by diabetic ketoacidosis. His condition rapidly deteriorated following aspiration pneumonia, leading to septic shock, anuric acute kidney injury and acute respiratory distress syndrome (ARDS), which necessitated veno-venous extracorporeal membrane oxygenation (V–V ECMO) for pulmonary support. Tracheal aspirate and blood cultures grew Klebsiella pneumoniae , susceptible to most standard antibiotics, while admission screening swabs revealed rectal colonization with a VIM-producing Pseudomonas aeruginosa . The patient’s condition progressively improved, allowing ECMO withdrawal on day 14. Three days later, he developed ventilator-associated pneumonia (VAP); bronchoalveolar lavage cultures yielded high bacterial loads of the same VIM-producing Pseudomonas aeruginosa . Targeted antimicrobial therapy was initiated with intravenous aztreonam (6 g/day by continuous infusion) and intravenous colistin (loading dose of 9 million IU followed by 3 million IU every 8 hours). Respiratory function showed partial improvement during the first treatment week; however, severe hypoxemia recurred, and chest computed tomography revealed a right-sided pleural empyema. Pleural fluid cultures confirmed infection by the same VIM-producing pathogen (Fig. 1 ). The patient underwent thoracoscopic pulmonary decortication with pleural drainage. Antimicrobial susceptibility testing demonstrated resistance to all conventional agents, with intermediate susceptibility to aztreonam (MIC: 8 mg/L) and sensitivity to colistin (MIC: 0.5 mg/L). Although the isolate was also susceptible in vitro to cefiderocol, this agent was not available. Considering the therapeutic failure and after multidisciplinary discussion with the Infectious Diseases specialist, intrapleural colistin therapy was initiated (0.5 million IU diluted in 50 mL of saline, instilled via pleural drains every 12 hours). Over the following two weeks, the patient’s clinical status improved, with progressive normalization of inflammatory markers, enhanced gas exchange, and radiological resolution of the pleural collection. Intrapleural colistin was discontinued after 14 days, while intravenous antibiotics were continued for six weeks. A tracheostomy was performed for ICU-acquired weakness and the patient was successfully weaned from mechanical ventilation on day 63. After completing rehabilitation, he was discharged home on day 124 after ICU admission. Discussion We reported a case of successful treatment of multidrug-resistant Pseudomonas aeruginosa pleural empyema using intrapleural colistin, which led to complete clinical recovery. Multidrug-resistant pathogens represent an increasing challenge in intensive care medicine, frequently limiting therapeutic options, as in this case, where colistin was the only viable agent. Colistin is often cited as having poor diffusion into the pleural space [ 3 , 6 ] and robust evidence supporting its effectiveness in treating pleural infections is limited. Based on a previous case report by Rana et al. [ 7 ], we administered colistin intrapleurally, achieving favorable outcomes. A review of the literature identified only two other reported cases of intrapleural colistin administration. The first case, described by Rana et al., involved a 92-year-old patient who developed VAP complicated by pleural empyema due to multidrug-resistant Acinetobacter baumannii and Escherichia coli [ 7 ]. Initial therapy with intravenous colistin and imipenem–cilastatin proved ineffective, leading clinicians to introduce combined intravenous and intrapleural colistin. This strategy was successful, with clinical improvement and eventual recovery. In this case, intrapleural colistin was administered as a 9-million IU loading dose, followed by 3 million IU every 8 hours after 24 hours. The second report described a 22-year-old lung transplant recipient with pleural empyema caused by multidrug-resistant Pseudomonas aeruginosa [ 8 ]. The same intrapleural colistin infusion protocol was applied, consistent with the regimen reported in our case. However, despite this aggressive therapeutic approach, the patient did not survive, underscoring the potential variability of clinical outcomes in this setting. Several reports in the literature describe the administration of antibiotics or antifungal agents directly into the pleural space [ 9 – 14 ]. This strategy represents a valuable adjunct in refractory infections caused by highly resistant pathogens, where systemic therapy alone may be insufficient to achieve adequate concentrations at the site of infection. The rationale is to maximize local bioavailability while potentially reducing systemic toxicity. However, concerns remain regarding possible side effects, including chemical pleuritis, pain, or systemic absorption leading to nephrotoxicity, particularly with agents such as colistin. Current evidence is limited to case reports and small series, precluding firm conclusions about safety, efficacy, or standardized dosing protocols. Larger clinical studies are therefore urgently needed to establish the therapeutic role, optimal regimens, and risk–benefit profile of intrapleural antimicrobial administration in critically ill patients. Conclusions This case underscores the importance of an individualized approach to managing pleural empyema caused by multidrug-resistant microorganisms and illustrates the potential role of intrapleural colistin as a therapeutic option. Such a strategy may represent a valuable alternative when conventional systemic antibiotics are limited or ineffective. Further studies are warranted to evaluate the efficacy and safety of combined systemic and localized administration protocols, with the goal of optimizing treatment outcomes in patients with highly resistant infections. Abbreviations ARDS acute respiratory distress syndrome ICU intensive care unit VAP ventilator-associated pneumonia VIM Verona Integron-Encoded Metallo V-V-ECMO veno-venous extracorporeal membrane oxygenation Declarations Consent for publication Oral consent of the patient Ethical Approval The written consent of the patient was granted regarding the publication of this case report Funding Not applicable Availability of data and materials Not applicable Competing interest None Author’s contributions AK: Investigation, Writing – review and editing FST: Review and editing CHV: Writing – review and editing ST: Editing Acknowledgements We would like to thank our entire medical team of intensive care physicians, as well as the infectious disease team, nurses, and physiotherapists involved in patient care. References Tenover FC, Nicolau DP, Gill CM. Carbapenemase-producing Pseudomonas aeruginosa -an emerging challenge. Emerg Microbes Infect. 2022;11:811–4. Grundmann H, Glasner C, Albiger B, et al. Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study. Lancet Infect Dis. 2017;17:153–63. Gurjar M. Colistin for lung infection: an update. J Intensive Care. 2015;3:3. Yahav D, Farbman L, Leibovici L, Paul M. Colistin: new lessons on an old antibiotic. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2012;18:18–29. Li J, Nation RL, Turnidge JD, et al. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis. 2006;6:589–601. Michalopoulos AS, Falagas ME. Colistin: recent data on pharmacodynamics properties and clinical efficacy in critically ill patients. Ann Intensive Care. 2011;1:30. Rana MA, Rahman BAE, Mady AF, et al. Intra-Pleural Colistin Methanesulfonate Therapy for Pleural Infection caused by Carbapenem-Resistant Acinetobacter Baumannii: A Successful Case Report. Infect Dis Rep. 2014;6:5413. Parra AP, Moral LD, Santed MR, Domingo DA, Gutiérrez JDR, Torner MG. 4CPS-038 Intrapleural colistin for pleural empyema caused by extensively drug-resistant Pseudomonas aeruginosa: a case report. Eur J Hosp Pharm. 2022;29:A39–40. Ader A, Reimer P, Kam R, et al. Feasibility of irrigation and instillation of antimicrobial or antibiotic solutions in patients with parapneumonic empyema — A prospective randomized study. Indian J Thorac Cardiovasc Surg. 2008;24:184–90. Baquero-Artigao F, García-Miguel MJ, Hernández F, Hernández N, del Castillo F. Combined systemic and intrapleural treatment of Aspergillus pulmonary empyema after invasive aspergillosis. Pediatr Infect Dis J. 2003;22:471–3. Chen T-T, Chen S-M, Liu H-Y. Ceftazidime-avibactam and intrapleural amikacin therapy for extensively drug-resistant Pseudomonas aeruginosa thoracic empyema: A case report. Med (Baltim). 2022;101:e29467. Cui N, Wang L, Zhao J. A Case Report of Histoplasma-Associated Empyema Treated With Intravenous Injection and Local Thoracic Irrigation of Amphotericin B Plus Medical Thoracoscopy. Front Public Health. 2022;10:914529. Long R, Barrie J, Stewart K, Peloquin CA. Treatment of a tuberculous empyema with simultaneous oral and intrapleural antituberculosis drugs. Can Respir J. 2008;15:241–3. Sarot IA, Littman ML, Cerruti MM. Intrathoracic injection of amphotericin B in the treatment of monilial empyema. Sea View Hosp Bull. 1959;17:95–100. Additional Declarations No competing interests reported. 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1","display":"","copyAsset":false,"role":"figure","size":721252,"visible":true,"origin":"","legend":"\u003cp\u003eChest CT-scan showing right pleural empyema and residual pneumonia.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7684980/v1/db63d1dd3c85be2bbc645532.png"},{"id":100368029,"identity":"ee75f05e-6738-4506-825a-023e09b27e90","added_by":"auto","created_at":"2026-01-16 07:57:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1059072,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7684980/v1/a97b9cd2-da95-40d2-b888-de7ccadf6692.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Intrapleural colistin for pleural empyema due to multi-drug resistant pathogen: a case report and review of the literature","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe emergence of carbapenemase-producing \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e poses major therapeutic challenges due to extensive resistance to commonly used antibiotics and an increased risk of clinical and microbiological failure [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Consequently, there is a pressing need for innovative therapeutic strategies, including the optimization of existing drugs, the rational use of novel β-lactam\u0026ndash;β-lactamase inhibitor combinations, and the development of combination regimens tailored to infection site and pathogen characteristics [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Alongside new-generation β-lactam agents, colistin remains an important therapeutic option against multidrug-resistant Gram-negative bacteria, despite limitations related to complex pharmacokinetics and potential toxicity [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, data on non-intravenous routes of administration of colistin remain scarce. We reported a case of pleural empyema caused by a Verona Integron-Encoded Metallo (VIM) β-lactamase producing \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e successfully managed with combined intravenous and intrapleural colistin, highlighting the value of adaptive strategies to optimize local drug exposure in difficult-to-treat pulmonary infections.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 31-year-old man with no prior medical history and no recent travel was admitted to the intensive care unit (ICU) with altered consciousness due to combined amphetamine and benzodiazepine intoxication, complicated by diabetic ketoacidosis. His condition rapidly deteriorated following aspiration pneumonia, leading to septic shock, anuric acute kidney injury and acute respiratory distress syndrome (ARDS), which necessitated veno-venous extracorporeal membrane oxygenation (V\u0026ndash;V ECMO) for pulmonary support. Tracheal aspirate and blood cultures grew \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e, susceptible to most standard antibiotics, while admission screening swabs revealed rectal colonization with a VIM-producing \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e. The patient\u0026rsquo;s condition progressively improved, allowing ECMO withdrawal on day 14. Three days later, he developed ventilator-associated pneumonia (VAP); bronchoalveolar lavage cultures yielded high bacterial loads of the same VIM-producing \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e. Targeted antimicrobial therapy was initiated with intravenous aztreonam (6 g/day by continuous infusion) and intravenous colistin (loading dose of 9\u0026nbsp;million IU followed by 3\u0026nbsp;million IU every 8 hours). Respiratory function showed partial improvement during the first treatment week; however, severe hypoxemia recurred, and chest computed tomography revealed a right-sided pleural empyema. Pleural fluid cultures confirmed infection by the same VIM-producing pathogen (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe patient underwent thoracoscopic pulmonary decortication with pleural drainage. Antimicrobial susceptibility testing demonstrated resistance to all conventional agents, with intermediate susceptibility to aztreonam (MIC: 8 mg/L) and sensitivity to colistin (MIC: 0.5 mg/L). Although the isolate was also susceptible \u003cem\u003ein vitro\u003c/em\u003e to cefiderocol, this agent was not available. Considering the therapeutic failure and after multidisciplinary discussion with the Infectious Diseases specialist, intrapleural colistin therapy was initiated (0.5\u0026nbsp;million IU diluted in 50 mL of saline, instilled via pleural drains every 12 hours). Over the following two weeks, the patient\u0026rsquo;s clinical status improved, with progressive normalization of inflammatory markers, enhanced gas exchange, and radiological resolution of the pleural collection. Intrapleural colistin was discontinued after 14 days, while intravenous antibiotics were continued for six weeks. A tracheostomy was performed for ICU-acquired weakness and the patient was successfully weaned from mechanical ventilation on day 63. After completing rehabilitation, he was discharged home on day 124 after ICU admission.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe reported a case of successful treatment of multidrug-resistant \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e pleural empyema using intrapleural colistin, which led to complete clinical recovery. Multidrug-resistant pathogens represent an increasing challenge in intensive care medicine, frequently limiting therapeutic options, as in this case, where colistin was the only viable agent. Colistin is often cited as having poor diffusion into the pleural space [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and robust evidence supporting its effectiveness in treating pleural infections is limited. Based on a previous case report by Rana et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], we administered colistin intrapleurally, achieving favorable outcomes. A review of the literature identified only two other reported cases of intrapleural colistin administration.\u003c/p\u003e\u003cp\u003eThe first case, described by Rana et al., involved a 92-year-old patient who developed VAP complicated by pleural empyema due to multidrug-resistant \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e and \u003cem\u003eEscherichia coli\u003c/em\u003e [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Initial therapy with intravenous colistin and imipenem\u0026ndash;cilastatin proved ineffective, leading clinicians to introduce combined intravenous and intrapleural colistin. This strategy was successful, with clinical improvement and eventual recovery. In this case, intrapleural colistin was administered as a 9-million IU loading dose, followed by 3\u0026nbsp;million IU every 8 hours after 24 hours. The second report described a 22-year-old lung transplant recipient with pleural empyema caused by multidrug-resistant \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The same intrapleural colistin infusion protocol was applied, consistent with the regimen reported in our case. However, despite this aggressive therapeutic approach, the patient did not survive, underscoring the potential variability of clinical outcomes in this setting.\u003c/p\u003e\u003cp\u003eSeveral reports in the literature describe the administration of antibiotics or antifungal agents directly into the pleural space [\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This strategy represents a valuable adjunct in refractory infections caused by highly resistant pathogens, where systemic therapy alone may be insufficient to achieve adequate concentrations at the site of infection. The rationale is to maximize local bioavailability while potentially reducing systemic toxicity. However, concerns remain regarding possible side effects, including chemical pleuritis, pain, or systemic absorption leading to nephrotoxicity, particularly with agents such as colistin. Current evidence is limited to case reports and small series, precluding firm conclusions about safety, efficacy, or standardized dosing protocols. Larger clinical studies are therefore urgently needed to establish the therapeutic role, optimal regimens, and risk\u0026ndash;benefit profile of intrapleural antimicrobial administration in critically ill patients.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis case underscores the importance of an individualized approach to managing pleural empyema caused by multidrug-resistant microorganisms and illustrates the potential role of intrapleural colistin as a therapeutic option. Such a strategy may represent a valuable alternative when conventional systemic antibiotics are limited or ineffective. Further studies are warranted to evaluate the efficacy and safety of combined systemic and localized administration protocols, with the goal of optimizing treatment outcomes in patients with highly resistant infections.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eARDS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eacute respiratory distress syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eintensive care unit\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVAP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eventilator-associated pneumonia\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVIM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eVerona Integron-Encoded Metallo\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eV-V-ECMO\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eveno-venous extracorporeal membrane oxygenation\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Oral consent of the patient\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe written consent of the patient was granted regarding the publication of this case report\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAK: Investigation, Writing \u0026ndash; review and editing\u003c/p\u003e\n\u003cp\u003eFST: Review and editing\u003c/p\u003e\n\u003cp\u003eCHV: Writing \u0026ndash; review and editing\u003c/p\u003e\n\u003cp\u003eST: Editing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank our entire medical team of intensive care physicians, as well as the infectious disease team, nurses, and physiotherapists involved in patient care.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTenover FC, Nicolau DP, Gill CM. Carbapenemase-producing Pseudomonas aeruginosa -an emerging challenge. Emerg Microbes Infect. 2022;11:811\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGrundmann H, Glasner C, Albiger B, et al. Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study. Lancet Infect Dis. 2017;17:153\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGurjar M. Colistin for lung infection: an update. J Intensive Care. 2015;3:3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYahav D, Farbman L, Leibovici L, Paul M. Colistin: new lessons on an old antibiotic. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2012;18:18\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi J, Nation RL, Turnidge JD, et al. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis. 2006;6:589\u0026ndash;601.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMichalopoulos AS, Falagas ME. Colistin: recent data on pharmacodynamics properties and clinical efficacy in critically ill patients. Ann Intensive Care. 2011;1:30.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRana MA, Rahman BAE, Mady AF, et al. Intra-Pleural Colistin Methanesulfonate Therapy for Pleural Infection caused by Carbapenem-Resistant Acinetobacter Baumannii: A Successful Case Report. Infect Dis Rep. 2014;6:5413.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eParra AP, Moral LD, Santed MR, Domingo DA, Guti\u0026eacute;rrez JDR, Torner MG. 4CPS-038 Intrapleural colistin for pleural empyema caused by extensively drug-resistant Pseudomonas aeruginosa: a case report. Eur J Hosp Pharm. 2022;29:A39\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAder A, Reimer P, Kam R, et al. Feasibility of irrigation and instillation of antimicrobial or antibiotic solutions in patients with parapneumonic empyema \u0026mdash; A prospective randomized study. Indian J Thorac Cardiovasc Surg. 2008;24:184\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaquero-Artigao F, Garc\u0026iacute;a-Miguel MJ, Hern\u0026aacute;ndez F, Hern\u0026aacute;ndez N, del Castillo F. Combined systemic and intrapleural treatment of Aspergillus pulmonary empyema after invasive aspergillosis. Pediatr Infect Dis J. 2003;22:471\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen T-T, Chen S-M, Liu H-Y. Ceftazidime-avibactam and intrapleural amikacin therapy for extensively drug-resistant Pseudomonas aeruginosa thoracic empyema: A case report. Med (Baltim). 2022;101:e29467.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCui N, Wang L, Zhao J. A Case Report of Histoplasma-Associated Empyema Treated With Intravenous Injection and Local Thoracic Irrigation of Amphotericin B Plus Medical Thoracoscopy. Front Public Health. 2022;10:914529.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLong R, Barrie J, Stewart K, Peloquin CA. Treatment of a tuberculous empyema with simultaneous oral and intrapleural antituberculosis drugs. Can Respir J. 2008;15:241\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSarot IA, Littman ML, Cerruti MM. Intrathoracic injection of amphotericin B in the treatment of monilial empyema. Sea View Hosp Bull. 1959;17:95\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Carbapenemase, VIM, Colistin, Pulmonary empyema","lastPublishedDoi":"10.21203/rs.3.rs-7684980/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7684980/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePulmonary empyema caused by \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e producing Verona Integron-Encoded Metallo (VIM) β-lactamase represents a major therapeutic challenge due to the limited available therapeutic options. We reported the case of a 31-year-old patient admitted to intensive care unit (ICU) for drug intoxication, who subsequently developed aspiration pneumonia complicated by pleural empyema due to VIM-producing \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e. Due to clinical failure of intravenous therapy, intrapleural colistin was added, which resulted in significant clinical improvement and successful ICU discharge. This case highlights the potential role of intrapleural colistin administration in selected case of multidrug-resistant pleural infections to ensure adequate local antibiotic concentrations. Only two other similar cases with an intrapleural colistin administration have been previously reported, suggesting the need for evaluating this strategy in larger patients\u0026rsquo; cohorts.\u003c/p\u003e","manuscriptTitle":"Intrapleural colistin for pleural empyema due to multi-drug resistant pathogen: a case report and review of the literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-21 23:24:46","doi":"10.21203/rs.3.rs-7684980/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"eebc3fe4-55ca-4652-9391-6a4ab8542ed4","owner":[],"postedDate":"October 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-13T16:39:03+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-21 23:24:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7684980","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7684980","identity":"rs-7684980","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}