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      In Vitro activity of a Novel Benzoquinolizine Antibiotic, Levonadifloxacin (WCK 771) against Blood Stream Gram-Positive Isolates from a Tertiary Care Hospital

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          Abstract

          Background  Blood stream infections (BSIs) due to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are associated with high mortality ranging from 10 to 60%. The current anti-MRSA agents have limitations with regards to safety and tolerability profile which limits their prolonged usage. Levonadifloxacin and its oral prodrug alalevonadifloxacin, a novel benzoquinolizine antibiotic, have recently been approved for acute bacterial skin and skin structure infections including diabetic foot infections and concurrent bacteremia in India.

          Methods  The present study assessed the potency of levonadifloxacin, a novel benzoquinolizine antibiotic, against Gram-positive blood stream clinical isolates ( n = 31) collected from January to June 2019 at a tertiary care hospital in Mumbai, India. The susceptibility of isolates to antibacterial agents was defined following the Clinical and Laboratory Standard Institute interpretive criteria (M100 E29).

          Results  High prevalence of MRSA (62.5%), quinolone-resistant Staphylococcus aureus (QRSA) (87.5%), and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) (82.35%) were observed among bacteremic isolates. Levonadifloxacin demonstrated potent activity against MRSA, QRSA, and MR-CoNS strains with significantly lower minimum inhibitory concentration MIC 50/90 values of 0.5/1 mg/L as compared with levofloxacin (8/32 mg/L) and moxifloxacin (2/8 mg/L).

          Conclusion  Potent bactericidal activity coupled with low MICs support usage of levonadifloxacin for the management of BSIs caused by multidrug resistant Gram-positive bacteria.

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          Most cited references14

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          Correlation between Reduced Daptomycin Susceptibility and Vancomycin Resistance in Vancomycin-Intermediate Staphylococcus aureus.

          We present here findings of a strong positive correlation between reduced daptomycin susceptibility and vancomycin resistance in vancomycin-intermediate Staphylococcus aureus (VISA). This correlation is related to cell wall thickening, suggesting that, similar to the case with vancomycin resistance in VISA, the physical barrier of a thickened cell wall may contribute to daptomycin resistance in S. aureus.
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            Acquired bloodstream infection in the intensive care unit: incidence and attributable mortality

            Introduction To estimate the incidence of intensive care unit (ICU)-acquired bloodstream infection (BSI) and its independent effect on hospital mortality. Methods We retrospectively studied acquisition of BSI during admissions of >72 hours to adult ICUs from two university-affiliated hospitals. We obtained demographics, illness severity and co-morbidity data from ICU databases and microbiological diagnoses from departmental electronic records. We assessed survival at hospital discharge or at 90 days if still hospitalized. Results We identified 6339 ICU admissions, 330 of which were complicated by BSI (5.2%). Median time to first positive culture was 7 days (IQR 5-12). Overall mortality was 23.5%, 41.2% in patients with BSI and 22.5% in those without. Patients who developed BSI had higher illness severity at ICU admission (median APACHE III score: 79 vs. 68, P < 0.001). After controlling for illness severity and baseline demographics by Cox proportional-hazard model, BSI remained independently associated with risk of death (hazard ratio from diagnosis 2.89; 95% confidence interval 2.41-3.46; P < 0.001). However, only 5% of the deaths in this model could be attributed to acquired-BSI, equivalent to an absolute decrease in survival of 1% of the total population. When analyzed by microbiological classification, Candida, Staphylococcus aureus and gram-negative bacilli infections were independently associated with increased risk of death. In a sub-group analysis intravascular catheter associated BSI remained associated with significant risk of death (hazard ratio 2.64; 95% confidence interval 1.44-4.83; P = 0.002). Conclusions ICU-acquired BSI is associated with greater in-hospital mortality, but complicates only 5% of ICU admissions and its absolute effect on population mortality is limited. These findings have implications for the design and interpretation of clinical trials.
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              Methicillin resistant Staphylococcus aureus (MRSA) in India: Prevalence & susceptibility pattern

              Background & objectives: Methicillin resistant Staphylococcus aureus (MRSA) is endemic in India and is a dangerous pathogen for hospital acquired infections. This study was conducted in 15 Indian tertiary care centres during a two year period from January 2008 to December 2009 to determine the prevalence of MRSA and susceptibility pattern of S. aureus isolates in India. Methods: All S. aureus isolates obtained during the study period in the participating centres were included in the study. Each centre compiled their data in a predefined template which included data of the antimicrobial susceptibility pattern, location of the patient and specimen type. The data in the submitted templates were collated and analysed. Results: A total of 26310 isolates were included in the study. The overall prevalence of methicillin resistance during the study period was 41 per cent. Isolation rates for MRSA from outpatients, ward inpatients and ICU were 28, 42 and 43 per cent, respectively in 2008 and 27, 49 and 47 per cent, respectively in 2009. The majority of S. aureus isolates was obtained from patients with skin and soft tissue infections followed by those suffering from blood stream infections and respiratory infections. Susceptibility to ciprofloxacin was low in both MSSA (53%) and MRSA (21%). MSSA isolates showed a higher susceptibility to gentamicin, co-trimoxazole, erythromycin and clindamycin as compared to MRSA isolates. No isolate was found resistant to vancomycin or linezolid. Interpretation & conclusions: The study showed a high level of MRSA in our country. There is a need to study epidemiology of such infections. Robust antimicrobial stewardship and strengthened infection control measures are required to prevent spread and reduce emergence of resistance.
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                Author and article information

                Journal
                J Lab Physicians
                J Lab Physicians
                10.1055/s-00044881
                Journal of Laboratory Physicians
                Thieme Medical and Scientific Publishers Pvt. Ltd. (A-12, Second Floor, Sector -2, NOIDA -201301, India )
                0974-2727
                0974-7826
                December 2020
                23 November 2020
                : 12
                : 3
                : 230-232
                Affiliations
                [1 ]Department of Microbiology, S.L. Raheja Hospital, Mumbai, Maharashtra, India
                [2 ]Department of Critical Care Medicine, S.L. Raheja Hospital, Mumbai, Maharashtra, India
                [3 ]Department of Medical Affairs, Wockhardt Ltd., Mumbai, Maharashtra, India
                [4 ]Drug Discovery Research, Wockhardt Research Center, Aurangabad, Maharashtra, India
                Author notes
                Address for correspondence Dhruv Mamtora, MD Department of Microbiology, S.L. Raheja Hospital Raheja Rugnalaya Marg, Mahim West, Mahim, Mumbai, Maharashtra 400016India dhruv_mamtora@ 123456yahoo.com
                Article
                JLP2020057
                10.1055/s-0040-1720944
                7684988
                33268943
                53b6eebe-9a82-4514-8fa9-4af52a5dc9f1
                The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited.

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                Clinical chemistry
                blood stream infections, methicillin-resistant s. aureus,levonadifloxacin, quinolone-resistant s. aureus

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