{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:17:38Z","timestamp":1787840258828,"version":"build-2784847793"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1]]},"abstract":"\n Objective:<\/jats:title>\n Ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a major intensive care unit challenge, particularly in Iran, due to limited antibiotic options. This study compared the efficacy of adding levofloxacin and colistin inhalation form to the baseline regimen of colistin and meropenem in treating VAP caused by MDR-GNB.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n Patients with VAP were randomly assigned to the colistin group (\n n<\/jats:italic>\n = 24), receiving 2 million international unit (MIU) every 8 h, and the levofloxacin group (\n n<\/jats:italic>\n = 22), receiving 250 mg every 12 h, alongside intravenous colistin (4.5 MIU every 12 h) and meropenem (1 g every 8 h). Clinical improvement using the Clinical Pulmonary Infection Score (CPIS) on days 1, 5, and 7, the clinical response on day 7, and inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) on days 1, 3, 5, and 7 were evaluated.\n <\/jats:p>\n <\/jats:sec>\n \n Findings:<\/jats:title>\n \n CPIS scores significantly decreased in both groups: Colistin (\u22123.67 \u00b1 2.14,\n P<\/jats:italic>\n < 0.001) and levofloxacin (\u22124.41 \u00b1 1.71,\n P<\/jats:italic>\n < 0.001), with no intergroup difference (\n P<\/jats:italic>\n = 0.200). The clinical response analysis indicated that levofloxacin was associated with fewer treatment failures and more partial responses, whereas colistin demonstrated higher rates of complete response; however, these differences were not statistically significant (\n P<\/jats:italic>\n > 0.05). Acute kidney injury occurred only in the colistin group (\n n<\/jats:italic>\n = 8; 33.3%). Bronchospasm and cough occurred in one levofloxacin patient (4.54%), showing a significant difference in adverse effects (\n P<\/jats:italic>\n = 0.004). Mortality rates were higher in the colistin group (\n n<\/jats:italic>\n = 17; 70.8%) compared to the levofloxacin group (\n n<\/jats:italic>\n = 10; 45.5%), though this difference was not statistically significant (\n P<\/jats:italic>\n = 0.08).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Levofloxacin inhalation may be considered an effective alternative to colistin inhalation for treating VAP caused by MDR-GNB. It offers similar efficacy and lower nephrotoxicity.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/jrpp.jrpp_12_25","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T04:00:10Z","timestamp":1749787210000},"page":"9-17","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of the Efficacy of Adding Inhaled Levofloxacin and Colistin to a Basic Regimen of Colistin and Meropenem in the Treatment of Ventilator-associated Pneumonia Caused by Multidrug-resistant Gram-negative Bacteria: A Randomized Open-label Clinical Trial"],"prefix":"10.4103","volume":"14","author":[{"given":"Masoumeh","family":"Sohrabi","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahram","family":"Ala","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Gholipour-Baradari","sequence":"additional","affiliation":[{"name":"Professor of Anesthesiology and Critical Care, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Heydari","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza Nikzad","family":"Jamnani","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Mousazadeh","sequence":"additional","affiliation":[{"name":"Gastrointestitional Cancer Research Center, Non-Communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamidreza","family":"Namvar","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"R1-20260422","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1007\/s00134-020-05980-0","article-title":"Ventilator-associated pneumonia in adults: A narrative review","volume":"46","author":"Papazian","year":"2020","journal-title":"Intensive Care Med"},{"key":"R2-20260422","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.ajic.2019.08.023","article-title":"International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2012-2017: Device-associated module","volume":"48","author":"Rosenthal","year":"2020","journal-title":"Am J Infect Control"},{"key":"R3-20260422","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jgar.2016.12.016","article-title":"Epidemiology of multidrug-resistant gram-negative pathogens isolated from ventilator-associated pneumonia in ICU patients","volume":"9","author":"Gupta","year":"2017","journal-title":"J Glob Antimicrob Resist"},{"key":"R4-20260422","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0140-6736(24)02081-6","article-title":"Multidrug-resistant gram-negative bacterial infections","volume":"405","author":"Macesic","year":"2025","journal-title":"Lancet"},{"key":"R5-20260422","doi-asserted-by":"crossref","first-page":"1154.","DOI":"10.3390\/microorganisms9061154","article-title":"Nebulized colistin in ventilator-associated pneumonia and tracheobronchitis: Historical background, pharmacokinetics and perspectives","volume":"9","author":"Zhu","year":"2021","journal-title":"Microorganisms"},{"key":"R6-20260422","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2478\/jccm-2018-0011","article-title":"Endotracheal tube biofilm and its impact on the pathogenesis of ventilator-associated pneumonia","volume":"4","author":"Diaconu","year":"2018","journal-title":"J Crit Care Med (Targu Mures)"},{"key":"R7-20260422","doi-asserted-by":"crossref","first-page":"338.","DOI":"10.3390\/antibiotics10030338","article-title":"Cystic fibrosis: Recent insights into inhaled antibiotic treatment and future perspectives","volume":"10","author":"Taccetti","year":"2021","journal-title":"Antibiotics (Basel)"},{"key":"R8-20260422","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1586\/14787210.2015.1041925","article-title":"Novel inhaled combined antibiotic formulations in the treatment of Pseudomonas aeruginosa airways infections in cystic fibrosis","volume":"13","author":"Antoniu","year":"2015","journal-title":"Expert Rev Anti Infect Ther"},{"key":"R9-20260422","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.jmii.2015.10.010","article-title":"Activity of levofloxacin in combination with colistin against Acinetobacter baumannii: In vitro and in a Galleria mellonella model","volume":"50","author":"Wei","year":"2017","journal-title":"J Microbiol Immunol Infect"},{"key":"R10-20260422","doi-asserted-by":"crossref","first-page":"962","DOI":"10.4187\/respcare.07024","article-title":"Aerosolized antibiotics for treatment of pneumonia in mechanically ventilated subjects","volume":"64","author":"Wong","year":"2019","journal-title":"Respir Care"},{"key":"R11-20260422","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1007\/s40265-017-0787-0","article-title":"Inhaled antimicrobials for ventilator-associated pneumonia: Practical aspects","volume":"77","author":"Poulakou","year":"2017","journal-title":"Drugs"},{"key":"R12-20260422","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1089\/jamp.2021.0023","article-title":"The unfulfilled promise of inhaled therapy in ventilator-associated infections: Where do we go from here?","volume":"35","author":"Palmer","year":"2022","journal-title":"J Aerosol Med Pulm Drug Deliv"},{"key":"R13-20260422","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.1128\/AAC.00268-09","article-title":"Efficacy of aerosol MP-376, a levofloxacin inhalation solution, in models of mouse lung infection due to Pseudomonas aeruginosa","volume":"53","author":"Sabet","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"R14-20260422","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s10096-014-2231-7","article-title":"Time-kill effect of levofloxacin on multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: Synergism with imipenem and colistin","volume":"34","author":"Safarika","year":"2015","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"R15-20260422","doi-asserted-by":"crossref","first-page":"129","DOI":"10.2147\/IDR.S182585","article-title":"In vitro activity of colistin in combination with various antimicrobials against Acinetobacter baumannii species, a report from South Iran","volume":"12","author":"Kheshti","year":"2019","journal-title":"Infect Drug Resist"},{"key":"R16-20260422","doi-asserted-by":"crossref","first-page":"35.","DOI":"10.1186\/s13613-016-0140-x","article-title":"Characteristics of an ideal nebulized antibiotic for the treatment of pneumonia in the intubated patient","volume":"6","author":"Bassetti","year":"2016","journal-title":"Ann Intensive Care"},{"key":"R17-20260422","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1093\/cid\/ciw353","article-title":"Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the infectious diseases society of America and the American Thoracic Society","volume":"63","author":"Kalil","year":"2016","journal-title":"Clin Infect Dis"},{"key":"R18-20260422","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1128\/AAC.00248-09","article-title":"In vitro pharmacodynamics of levofloxacin and other aerosolized antibiotics under multiple conditions relevant to chronic pulmonary infection in cystic fibrosis","volume":"54","author":"King","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"R19-20260422","doi-asserted-by":"crossref","first-page":"9597.","DOI":"10.3390\/ijms23179597","article-title":"Differential performance and lung deposition of levofloxacin with different nebulisers used in cystic fibrosis","volume":"23","author":"Schwarz","year":"2022","journal-title":"Int J Mol Sci"},{"key":"R20-20260422","doi-asserted-by":"crossref","first-page":"6128.","DOI":"10.1038\/s41598-019-42599-8","article-title":"Size distributions of droplets produced by ultrasonic nebulizers","volume":"9","author":"Kooij","year":"2019","journal-title":"Sci Rep"},{"key":"R21-20260422","doi-asserted-by":"crossref","first-page":"e110254.","DOI":"10.5812\/archcid.111084","article-title":"Comparison of inhaled colistin with inhaled Amikacin-Fosfomycin in the treatment of ventilator-associated pneumonia caused by extensively drug-resistant (XDR) Acinetobacter: A clinical trial","volume":"16","author":"Hakamifard","year":"2021","journal-title":"Arch Clin Infect Dis"},{"key":"R23-20260422","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin Microbiol Infect"},{"key":"R24-20260422","doi-asserted-by":"crossref","first-page":"901","DOI":"10.2217\/cer-2018-0037","article-title":"Meropenem\/colistin versus meropenem\/ampicillin-sulbactam in the treatment of carbapenem-resistant pneumonia","volume":"7","author":"Khalili","year":"2018","journal-title":"J Comp Eff Res"},{"key":"R25-20260422","doi-asserted-by":"crossref","first-page":"39","DOI":"10.4103\/1735-5362.363594","article-title":"The effectiveness of colistin\/levofloxacin compared to colistin\/meropenem in the treatment of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii: A randomized controlled clinical trial","volume":"18","author":"Momenzadeh","year":"2023","journal-title":"Res Pharm Sci"},{"key":"R26-20260422","doi-asserted-by":"crossref","first-page":"207.","DOI":"10.1186\/s13054-022-04083-0","article-title":"Comparison of diagnostic criteria for acute kidney injury in critically ill children: A multicenter cohort study","volume":"26","author":"Kuai","year":"2022","journal-title":"Crit Care"},{"key":"R27-20260422","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.ejcdt.2013.07.015","article-title":"Clinical pulmonary infection score and C-reactive protein in the prediction of early ventilator associated pneumonia","volume":"62","author":"Mohamed","year":"2013","journal-title":"Egypt J Chest Dis Tuberc"},{"key":"R28-20260422","doi-asserted-by":"crossref","first-page":"26.","DOI":"10.1186\/s13613-016-0127-7","article-title":"Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia: A prospective, randomised trial","volume":"6","author":"Abdellatif","year":"2016","journal-title":"Ann Intensive Care"},{"key":"R29-20260422","doi-asserted-by":"crossref","first-page":"e0207588.","DOI":"10.1371\/journal.pone.0207588","article-title":"Risk factors of colistin safety according to administration routes: Intravenous and aerosolized colistin","volume":"13","author":"Min","year":"2018","journal-title":"PLoS One"},{"key":"R30-20260422","first-page":"206","article-title":"Interim study: Comparison of safety and efficacy of levofloxacin plus colistin regimen with levofloxacin plus high dose ampicillin\/sulbactam infusion in treatment of ventilator-associated pneumonia due to multi drug resistant Acinetobacter","volume":"17","author":"Mosaed","year":"2018","journal-title":"Iran J Pharm Res"},{"key":"R31-20260422","doi-asserted-by":"crossref","first-page":"1.","DOI":"10.1186\/s13613-022-01088-4","article-title":"Role of nebulized colistin as a substitutive strategy against nosocomial pneumonia caused by CR-GNB in intensive care units: A retrospective cohort study","volume":"13","author":"Feng","year":"2023","journal-title":"Ann Intensive Care"},{"key":"R32-20260422","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1177\/0897190020958246","article-title":"Safety of nebulized colistin solution as adjunctive treatment of lower respiratory tract infections","volume":"35","author":"Nadeem","year":"2022","journal-title":"J Pharm Pract"},{"key":"R33-20260422","doi-asserted-by":"crossref","first-page":"555","DOI":"10.21037\/jtd.2017.02.61","article-title":"Efficacy of nebulized colistin-based therapy without concurrent intravenous colistin for ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii","volume":"9","author":"Kim","year":"2017","journal-title":"J Thorac Dis"},{"key":"R34-20260422","doi-asserted-by":"crossref","first-page":"479","DOI":"10.2165\/00002018-200022060-00006","article-title":"Fluoroquinolone-induced renal failure","volume":"22","author":"Lomaestro","year":"2000","journal-title":"Drug Saf"},{"key":"R35-20260422","doi-asserted-by":"crossref","first-page":"E475","DOI":"10.1503\/cmaj.121730","article-title":"Risk of acute kidney injury associated with the use of fluoroquinolones","volume":"185","author":"Bird","year":"2013","journal-title":"CMAJ"}],"container-title":["Journal of Research in Pharmacy Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/jrpp.jrpp_12_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:18:37Z","timestamp":1787836717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/jrpp.jrpp_12_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.4103\/jrpp.jrpp_12_25","relation":{},"ISSN":["2319-9644","2279-042X"],"issn-type":[{"value":"2319-9644","type":"print"},{"value":"2279-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-08-25","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-04","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}