| Reference | [1]. Recent Pat Antiinfect Drug Discov. 2018;13(3):228-239. doi: 10.2174/1574891X13666181024154526.<br />
Levofloxacin Versus Ceftriaxone and Azithromycin Combination in the Treatment of Community Acquired Pneumonia in Hospitalized Patients.<br />
Izadi M(1), Dadsetan B(1), Najafi Z(2), Jafari S(2), Mazaheri E(2), Dadras O(3), Heidari H(2), SeyedAlinaghi S(2), Voltarelli F(4).<br />
Author information: (1)Infectious Diseases Department, Ghaem Hospital, Karaj, Alborz, Iran. (2)Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran. (3)Department of Global Health and Socioepidemiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. (4)Graduation Program of Health Sciences, Faculty of Medicine, Federal University of Mato Grosso, Cuiaba, Brazil.<br />
BACKGROUND: In Asia, an estimated one million deaths are caused by communityacquired pneumonia (CAP) each year. Despite the high mortality in elderly people, a large number of CAP patients have been treated and survived with optimal life expectancy. A few studies have been done on adult CAP therapeutic approaches in Asia. Moreover, differences have been noted between these studies and European data. We aimed to investigate the efficacy of oral Levofloxacin (TAVANEX), 750 mg, once daily for five days versus parenteral Ceftriaxone 1gr BD, plus oral Azithromycin (250 mg, once daily) for seven to ten days (standard regimen) in CAP treatment. MATERIALS AND METHODS: We conducted a prospective randomized trial among 150 patients with CAP in Qaem Hospital of Alborz city from December 2016 to June 2017. A group of CAP patients were randomized in two treatment groups. One group was treated with oral Levofloxacin (TAVANEX), 750 mg, once daily for five days and the other group with parenteral Ceftriaxone 1gr BD plus oral Azithromycin (250 mg, once daily) for seven to ten days (standard regimen). The efficacy and side effects of the assigned drugs were compared between two groups. The probability level for statistical significance was set at P ≤ 0.05. RESULTS: The body temperature (P value=0.09), WBC count (P value=0.15), respiratory sounds (P value=0.18) and admission duration (P value=0.15) showed no significant differences after treatment between two groups. There was no report of hospital mortality, clinical deterioration and antibiotic escalation during hospital admission in both groups of study. In standard regimen group, only two (2.7%) patients had skin rash while in Levofloxacin group one case (1.3%) had skin rash, two patients (2.7%) had gastrointestinal problems and three (4%) patients showed central nervous system (CNS) complications. In both groups, the reticulonodular pattern was more frequently observed in Chest X-ray. Although standard regimen group (n=27, 36%) showed more consolidation than patients in Levofloxacin group (n=22, 29.3%), and the ground glass pattern was observed more in Levofloxacin group. CONCLUSION: We concluded that monotherapy with oral Levofloxacin was as effective as treatment with Ceftriaxone plus Azithromycin combination in patients with CAP who required hospitalization.<br />
DOI: 10.2174/1574891X13666181024154526 PMID: 30360748 [Indexed for MEDLINE]<br />
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[2]. Arch Med Res. 2020 Oct;51(7):741-742. doi: 10.1016/j.arcmed.2020.06.004. Epub 2020 Jun 6.<br />
Could Respiratory Fluoroquinolones, Levofloxacin and Moxifloxacin, Prove to be Beneficial as an Adjunct Treatment in COVID-19?<br />
Karampela I(1), Dalamaga M(2).<br />
Author information: (1)Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Chaidari, Athens, Greece. (2)Department of Biological Chemistry, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: [email protected].<br />
Since the beginning of the COVID-19 pandemic, researchers have focused on repurposing of existing antibiotics, antivirals and anti-inflammatory drugs to find an effective therapy. Fluoroquinolones are broad spectrum synthetic antimicrobial agents, being chemical derivatives of quinoline, the prodrome of chloroquine. Interestingly, fluoroquinolones may exert antiviral actions against vaccinia virus, papovavirus, CMV, VZV, HSV-1, HSV-2, HCV and HIV. A recent in silico study has shown that the fluoroquinolones, ciprofloxacin and moxifloxacin, may inhibit SARS-CoV-2 replication by exhibiting stronger capacity for binding to its main protease than chloroquine and nelfinavir, a protease inhibitor antiretroviral drug. Remarkably, fluoroquinolones have shown multiple immunomodulatory actions leading to an attenuation of the inflammatory response through the inhibition of pro-inflammatory cytokines. Noteworthy, respiratory fluoroquinolones, levofloxacin and moxifloxacin, constitute fist line therapeutic agents for the management of severe community-acquired pneumonia. They are characterized by advantageous pharmacokinetic properties; higher concentrations in the lungs; and an excellent safety profile comparable to other antibiotics used to treat respiratory infections, such as macrolides and b-lactams. Based on their potential antiviral activity and immunomodulatory properties, the favorable pharmacokinetics and safety profile, we propose the use of respiratory fluoroquinolones as adjuncts in the treatment of SARS-CoV-2 associated pneumonia.<br />
DOI: 10.1016/j.arcmed.2020.06.004 PMCID: PMC7275144 PMID: 32546446 [Indexed for MEDLINE]<br />
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[3]. Expert Opin Drug Saf. 2015 Feb;14(2):295-303. doi: 10.1517/14740338.2015.989210. Epub 2014 Dec 10.<br />
Cardiac risks associated with antibiotics: azithromycin and levofloxacin.<br />
Lu ZK(1), Yuan J, Li M, Sutton SS, Rao GA, Jacob S, Bennett CL.<br />
Author information: (1)University of South Carolina, South Carolina College of Pharmacy, Clinical Pharmacy and Outcomes Sciences Department , 715 Sumter Street, CLS Building, Room 311G, Columbia, SC 29208 , USA +1 803 777 2653 ; +1 803 777 2820 ; [email protected].<br />
INTRODUCTION: Azithromycin and levofloxacin have been shown to be efficacious in treating infections. The adverse drug events associated with azithromycin and levofloxacin were considered rare. However, the US FDA released warnings regarding the possible risk of QT prolongation with azithromycin and levofloxacin. AREAS COVERED: Case reports/case series, observational studies and clinical trials assessing cardiovascular risks associated with azithromycin and levofloxacin were critically reviewed, including 15 case reports/series, 5 observational studies and 5 clinical trials that investigated the cardiac risks associated azithromycin and levofloxacin. EXPERT OPINION: Results are discordant. Two retrospective studies utilizing large databases demonstrated an increased risk of cardiovascular death with azithromycin, when azithromycin was compared with amoxicillin. Two other retrospective studies found no difference in cardiovascular death associated with azithromycin and other antibiotics. For levofloxacin, the increased risk of cardiovascular death was only found in one retrospective study. Therefore, the risks and benefits of antibacterial therapies should be considered when making prescription decisions. This study should not preclude clinicians from avoiding azithromycin and levofloxacin. If a patient has an indication to receive an antibiotic and if azithromycin or levofloxacin is needed, it may be used, but the potential risks must be understood.<br />
DOI: 10.1517/14740338.2015.989210 PMCID: PMC4404501 PMID: 25494485 [Indexed for MEDLINE]<br />
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[4]. Clin Microbiol Infect. 2017 Sep;23(9):653-658. doi: 10.1016/j.cmi.2017.02.030. Epub 2017 Mar 6.<br />
Levofloxacin versus azithromycin for treating legionella pneumonia: a propensity score analysis.<br />
Garcia-Vidal C(1), Sanchez-Rodriguez I(2), Simonetti AF(3), Burgos J(2), Viasus D(4), Martin MT(2), Falco V(2), Carratalà J(5).<br />
Author information: (1)Hospital Universitari de Bellvitge, IDIBELL (Institut D'investigació Biomèdica de Bellvitge), Universitat de Barcelona, Barcelona, Spain; REIPI (Spanish Network for the Research in Infectious Diseases), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: [email protected]. (2)Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. (3)Hospital Universitari de Bellvitge, IDIBELL (Institut D'investigació Biomèdica de Bellvitge), Universitat de Barcelona, Barcelona, Spain. (4)Hospital Universitari de Bellvitge, IDIBELL (Institut D'investigació Biomèdica de Bellvitge), Universitat de Barcelona, Barcelona, Spain; Health Science Division, Universidad del Norte and Hospital Universidad del Norte, Barranquilla, Colombia. (5)Hospital Universitari de Bellvitge, IDIBELL (Institut D'investigació Biomèdica de Bellvitge), Universitat de Barcelona, Barcelona, Spain; REIPI (Spanish Network for the Research in Infectious Diseases), Instituto de Salud Carlos III, Madrid, Spain.<br />
OBJECTIVES: Concerns have arisen regarding the equivalence of levofloxacin and some macrolides for treating community-acquired legionella pneumonia (LP). We aimed to compare the outcomes of current patients with LP treated with levofloxacin, azithromycin and clarithromycin. METHODS: Observational retrospective multicentre study of consecutive patients with LP requiring hospitalization (2000-2014) conducted in two hospitals. The primary outcome assessed was 30-day mortality. To control for confounding, therapy was assessed by multivariate analysis. RESULTS: We documented 446 patients with LP, of which 175 were treated with levofloxacin, 177 with azithromycin and 58 with clarithromycin. No significant differences in time to defervescence (2 (interquartile range (IQR) 1-4) versus 2 (IQR 1-3) days; p 0.453), time to achieve clinical stability (3 (2-5) versus 3 (2-5) days; p 0.486), length of intravenous therapy (3 (2-5.25) versus 4 (3-6) days; p 0.058) and length of hospital stay (7 (5-10) versus 6 (5-9) days; p 0.088) were found between patients treated with levofloxacin and those treated with azithromycin. Patients treated with clarithromycin had longer intravenous antibiotic treatment (3 (2-5.25) versus 5 (3-6.25) days; p 0.002) and longer hospital stay (7 (5-10) versus 9 (7-14) days; p 0.043) compared with those treated with levofloxacin. The overall mortality was 4.3% (19 patients). Neither univariate nor multivariate analysis showed a significant association of levofloxacin versus azithromycin on mortality (4 (2.3%) versus 9 (5.1%) deaths; p 0.164). The results did not change after incorporation of the propensity score into the models. CONCLUSIONS: In our study, no significant differences in most outcomes were found between patients treated with levofloxacin and those treated with azithromycin. Due to the small number of deaths, results regarding mortality should be interpreted with caution.<br />
DOI: 10.1016/j.cmi.2017.02.030 PMID: 28267637 [Indexed for MEDLINE]<br />
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[5]. Clin Infect Dis. 2018 Nov 28;67(suppl_3):S293-S302. doi: 10.1093/cid/ciy611.<br />
Levofloxacin Pharmacokinetics/Pharmacodynamics, Dosing, Susceptibility Breakpoints, and Artificial Intelligence in the Treatment of Multidrug-resistant Tuberculosis.<br />
Deshpande D(1), Pasipanodya JG(1), Mpagama SG(2), Bendet P(1), Srivastava S(1), Koeuth T(1), Lee PS(1), Bhavnani SM(3), Ambrose PG(3), Thwaites G(4)(5), Heysell SK(6), Gumbo T(1).<br />
Author information: (1)Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas. (2)Kibong'oto Infectious Diseases Hospital, Sanya Juu, Tanzania. (3)Institute for Clinical Pharmacodynamics, Schenectady, New York. (4)Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, Churchill Hospital, Oxford, United Kingdom. (5)Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. (6)Division of Infectious Diseases and International Health, University of Virginia, Charlottesville.<br />
BACKGROUND: Levofloxacin is used for the treatment of multidrug-resistant tuberculosis; however the optimal dose is unknown. METHODS: We used the hollow fiber system model of tuberculosis (HFS-TB) to identify 0-24 hour area under the concentration-time curve (AUC0-24) to minimum inhibitory concentration (MIC) ratios associated with maximal microbial kill and suppression of acquired drug resistance (ADR) of Mycobacterium tuberculosis (Mtb). Levofloxacin-resistant isolates underwent whole-genome sequencing. Ten thousands patient Monte Carlo experiments (MCEs) were used to identify doses best able to achieve the HFS-TB-derived target exposures in cavitary tuberculosis and tuberculous meningitis. Next, we used an ensemble of artificial intelligence (AI) algorithms to identify the most important predictors of sputum conversion, ADR, and death in Tanzanian patients with pulmonary multidrug-resistant tuberculosis treated with a levofloxacin-containing regimen. We also performed probit regression to identify optimal levofloxacin doses in Vietnamese tuberculous meningitis patients. RESULTS: In the HFS-TB, the AUC0-24/MIC associated with maximal Mtb kill was 146, while that associated with suppression of resistance was 360. The most common gyrA mutations in resistant Mtb were Asp94Gly, Asp94Asn, and Asp94Tyr. The minimum dose to achieve target exposures in MCEs was 1500 mg/day. AI algorithms identified an AUC0-24/MIC of 160 as predictive of microbiologic cure, followed by levofloxacin 2-hour peak concentration and body weight. Probit regression identified an optimal dose of 25 mg/kg as associated with >90% favorable response in adults with pulmonary tuberculosis. CONCLUSIONS: The levofloxacin dose of 25 mg/kg or 1500 mg/day was adequate for replacement of high-dose moxifloxacin in treatment of multidrug-resistant tuberculosis.<br />
DOI: 10.1093/cid/ciy611 PMCID: PMC6260169 PMID: 30496461 [Indexed for MEDLINE]
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