DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20213685

Efficacy and safety of intravenous and/or oral levonadifloxacin in the management of secondary bacterial pulmonary infections in COVID-19 patients: findings of a retrospective, real-world, multi-center study

Sanjith Saseedharan, Pankaj Aneja, Aditya Chowti, Khokan Debnath, Kapil Dev Mehta, Pramit Sonone

Abstract


Background: Owing to dysregulated immune response, secondary bacterial pulmonary infections involving both gram-positive and gram-negative pathogens are common in COVID-19 patients and are often associated with higher mortality. This is a first ever report on the safety and efficacy of levonadifloxacin in the treatment of secondary bacterial pulmonary infections in patients with COVID-19 pneumonia.

Methods: This multi-center, retrospective, post-marketing and real-world study assessed the safety and efficacy of IV and/or oral levonadifloxacin in the treatment of bacterial infections encountered in COVID-19 patients. Data for 154 male/female patients above 18 years of age who received levonadifloxacin (injectable and/or oral) was collected from 44 participating sites. Study outcomes were the clinical and microbial success at the end of therapy. Safety was assessed based on clinical and laboratory adverse events.

Results: Among the 154 patients assessed, 121 (78.6%) were males and 142 (92.2%) were hospitalized. Majority of the patients (119) received all-IV therapy while 11 patients were prescribed with IV followed by oral regimen. All-oral therapy was received by 24 patients. The most common co-morbid conditions were diabetes (19.6%) and hypertension (19.2%). Post-treatment with levonadifloxacin, clinical and microbial success rates were 96.8% and 97.0% respectively.

Conclusions: Levonadifloxacin showed promising safety and efficacy when used as IV and/or oral therapy for the treatment of secondary bacterial pulmonary infections in COVID-19 patients. Clinically relevant features of levonadifloxacin such as availability of both IV and oral options, broad spectrum coverage and reassuring safety in patients with significant co-morbidities could help simplify the management.

Trial registration no. CTRI/2020/09/028152 [Registered on: 30/09/2020].


Keywords


COVID-19, Levonadifloxacin, Secondary bacterial infections, Real world study

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References


Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507-13.

Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA, 2020;323(13):1239-42.

Zahariadis G, Gooley TA, Ryall P, Hutchinson C, Latchford MI, Fearon MA et al. Risk of ruling out severe acute respiratory syndrome by ruling in another diagnosis: variable incidence of atypical bacteria coinfection based on diagnostic assays. Can Resp J. 2006;13(1):17-22.

Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, AL-Rabiah FA, Al-Hajjar S, Al-Barrak A et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis. 2013;13(9):752-61.

Chong WH, Saha BK, Ramani A, Chopra A. State-of-the-art review of secondary pulmonary infections in patients with COVID-19 pneumonia. Infection. 2021;11:1-15.

Khurana S, Singh P, Sharad N, Kiro VV, Rastogi N, Lathwal A et al. Profile of co-infections and secondary infections in COVID-19 patients at a dedicated COVID-19 facility of a tertiary care Indian hospital: Implication on antimicrobial resistance. Indian J Med Microbiol. 2020;39(2):147-53.

Joseph C, Togawa Y, Shindo N. Bacterial and viral infections associated with influenza. Influenza Other Respir Viruses. 2013;7(2):105-13.

Lai CC, Wang CY, Hsueh PR. Co-infections among patients with COVID-19: The need for combination therapy withnon-anti-SARS-CoV-2 agents? J Microbiol, Immunol Infect. 2020;53:505-12.

Chen, X, Liao, B, Cheng, L, Peng X, Xu X, Li Y et al. The microbial coinfection in COVID-19. Appl Microbiol Biotechnol. 2020;104:7777-85.

Indian Network for Surveillance of Antimicrobial Resistance (INSAR) group, India. Methicillin resistant Staphylococcus aureus (MRSA) in India: prevalence and susceptibility pattern. Indian J Med Res. 2013;137(2):363-369.

Gade ND, Qazi MS. Fluoroquinolone Therapy in Staphylococcus aureus Infections: Where Do We Stand? J Lab Physicians. 2013;5(2):109-12.

Selvabai AP, Abdul Sattar SB, Jayaraman P, Shanmugam P. Detection and Characterization of Heteroresistant Vancomycin Intermediate Staphylococcus aureus (hVISA) using Phenotypic and Genotypic Methods. J clin diagnostic res. 2019;13(5):DC01-5.

Bhatia A, Mastim M, Shah M, Gutte R, Joshi P, Kumbhar D et al. Efficacy and Safety of a Novel Broad-Spectrum Anti-MRSA Agent Levonadifloxacin Compared with Linezolid for Acute Bacterial Skin and Skin Structure Infections: A Phase 3, Openlabel, Randomized Study. J Assoc Physicians India. 2020;68(8):30-36.

Bakthavatchalam YD, Rao SV, Isaac B, Mahesh A, Nambi S, Swaminathan S et al. A comparative assessment of clinical, pharmacological and antimicrobial profile of novel anti-methicillin-resistant Staphylococcus aureus agent levonadifloxacin: Therapeutic role in nosocomial and community infections. Indian J Med Microbiol. 2019;37(4):478-87.

Bhagwat SS, Nandanwar M, Kansagara A, Patel A, Takalkar S, Chavan R et al. Levonadifloxacin, a Novel Broad-Spectrum Anti-MRSA Benzoquinolizine Quinolone Agent: Review of Current Evidence. Drug Design, Development Therapy. 2019;13:4351-65.

Feng Y, Ling Y, Bai T, Xie Y, Huang J, Li J et al. COVID-19 with different severities: a multicenter study of clinical features. Am J Respir Crit Care Med. 2020;201(11):1380-88.

Sharifipour E, Shams S, Esmkhani M, Khodadadi J, Fotouhi-Ardakani R, Koohpaei A, et al. Evaluation of bacterial co-infections of the respiratory tract in COVID-19 patients admitted to ICU. BMC Infect Dis. 2020;20(1):646.

Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect. 2020;81(2):266-75.

Dhesi Z, Enne VI, Brealey D, Livermpre DM, High J, Russell C et al. Organisms causing secondary pneumonias in COVID-19 patients at 5 UK ICUs as detected with the Film Array test. medRxiv. 2020.

Zhu X, Ge Y, Wu T, Zhao K, Chen Y, Wu B et al. Co-infection with respiratory pathogens among COVID-2019 cases. Virus Res. 2020;285:198005.

Bakthavatchalam YD, Shankar A, Muniyasamy R, Peter JV, Marcus Z, Triplicane Dwarakanathan H et al. Levonadifloxacin, a recently approved benzoquinolizine fluoroquinolone, exhibits potent in vitro activity against contemporary Staphylococcus aureus isolates and Bengal Bay clone isolates collected from a large Indian tertiary care hospital. J Antimicrobial Chemotherapy. 2020;75(8):2156-9.

Dubois J, Dubois M. Levonadifloxacin (WCK 771) exerts potent intracellular activity against Staphylococcus aureus in THP-1 monocytes at clinically relevant concentrations. J Med Microbiol. 2019;68(12):1716-22.

Patel A, Sangle GV, Trivedi J, Shengule SA, Thorve D, Patil M et al. Levonadifloxacin, a Novel Benzoquinolizine Fluoroquinolone, Modulates Lipopolysaccharide-Induced Inflammatory Responses in Human Whole-Blood Assay and Murine Acute Lung Injury Model. Antimicrob Agents Chemother. 2020;64(5):e00084-20.