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

2020 ◽  
Author(s):  
Yamuna Devi Bakthavatchalam ◽  
Abirami Shankar ◽  
Rajeshwari Muniyasamy ◽  
John Victor Peter ◽  
Zervos Marcus ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Vitro Activity ◽  
Care Hospital ◽  
In Vitro Activity ◽  
College Hospital ◽  
Diabetic Foot Infections ◽  
Broth Microdilution Method

Abstract Objectives Levonadifloxacin (WCK 771; IV) and its prodrug alalevonadifloxacin (WCK 2349; oral) are benzoquinolizine fluoroquinolones, recently approved in India for the treatment of acute bacterial skin and skin structure infections with concurrent bacteraemia and diabetic foot infections. Ahead of its market launch, the present study aimed to assess the in vitro activity of levonadifloxacin against contemporary Staphylococcus aureus isolates collected from a large tertiary care hospital in India. Additionally, levonadifloxacin activity was tested against hVISA and Bengal Bay clone MRSA isolates. Methods Non-duplicate S. aureus (n = 793) isolates collected at Christian Medical College hospital, Vellore, India during 2013–19 were included in the study. MRSA isolates were identified using a cefoxitin disc diffusion assay. MICs of levonadifloxacin and comparator antibiotics were determined using the broth microdilution method. Mutations in QRDRs were identified for selected levofloxacin-non-susceptible isolates. MLST profiling was undertaken to detect the Bengal Bay clone. Results Among the 793 isolates, 441 (55.6%) were MRSA and 626 (78.9%) were non-susceptible to levofloxacin. Levonadifloxacin showed MIC50 and MIC90 values of 0.25 and 0.5 mg/L, respectively, for all S. aureus, which included hVISA and Bengal Bay clone MRSA. The potency of levonadifloxacin was 16 times superior compared with levofloxacin. Conclusions The present study demonstrated potent activity of levonadifloxacin against contemporary S. aureus isolates, which included MRSA isolates, hVISA isolates, Bengal Bay clone isolates and a high proportion of quinolone-non-susceptible isolates. The potent activity of levonadifloxacin observed in this study supports its clinical use for the treatment of S. aureus infections.

scholarly journals 522. In Vitro Antimicrobial Activity of Ceftazidime/Avibactam Compared with Ceftolozane/Tazobactam Against Real-world Clinical Isolates of Pseudomonas aeruginosa at a Large Academic Tertiary Care Hospital

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S251-S252
Author(s):  
Twisha S Patel ◽  
Keith S Kaye ◽  
Vince Marshall ◽  
Jay Krishnan ◽  
John Mills ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Real World ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Care Hospital ◽  
In Vitro Activity ◽  
Routine Testing

Abstract Background Ceftazidime/avibactam (CZA) and ceftolozane-tazobactam (CT) are new additions to the antibiotic armamentarium with activity against gram-negative pathogens, most notably drug-resistant Pseudomonas aeruginosa (PSA). The purpose of this study was to compare the in vitro activity of CZA and CT against a large real-world sample of clinical isolates of PSA displaying different phenotypes of resistance to conventional β-lactams at an institution where both CZA and CT are routinely tested on all isolates. Methods All cultures from patient infections with PSA from May 2018 to February 2019 at Michigan Medicine were included. Minimum inhibitory concentrations (MICs) for all β-lactams were determined using TREK broth microdilution panels and isolates were considered susceptible to CZA if the MIC was ≤8 mg/L and CT if the MIC was ≤4 mg/L. Results A total of 2,972 isolates of PSA from clinical specimens were included. Table 1 compares CZA and CT susceptibility, MIC50, MIC90, and MIC range for all isolates including those displaying resistance to various β-lactams. Among all isolates of PSA, CZA (96.2% susceptible) was slightly more active than CT (94.2%) and both agents were ~10% more active than the closest comparator (ceftazidime, 86.6%). In vitro activity of cefepime, piperacillin/tazobactam, and meropenem were 84.8%, 78%, and 80.3%, respectively. The activity of both CZA and CT dropped significantly among isolates with pan-β-lactam resistance (i.e., resistance to all conventional anti-pseudomonal β lactams, PBR) but CZA remained more active than CT (59.4% vs. 41.5%, P < 0.001). Of isolates displaying resistance to CT, 84 (48.6%) were susceptible to CZA. However, of those with resistance to CZA, only 24 (21.2%) were susceptible to CT (Table 2). Conclusion CZA was the most active β-lactam against PSA isolates at Michigan Medicine. Among PSA with PBR, CZA demonstrated superior activity compared with CT. Additionally, a significant number of isolates with resistance to CT were susceptible to CZA. Our findings are unique compared with other published reports where CT has consistently demonstrated greater activity than CZA against resistant P. aeruginosa and suggest routine testing of both CT and CZA should occur. Disclosures All authors: No reported disclosures.

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

2020 ◽  
Vol 12 (03) ◽  
pp. 230-232
Author(s):  
Dhruv Mamtora ◽  
Sanjith Saseedharan ◽  
Ritika Rampal ◽  
Prashant Joshi ◽  
Pallavi Bhalekar ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Blood Stream ◽  
Tolerability Profile ◽  
Care Hospital ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Methicillin Resistant

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 MIC50/90 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.

In vitro activity of a novel antibacterial agent, levonadifloxacin, against clinical isolates collected in a prospective, multicentre surveillance study in India during 2016–18

2019 ◽  
Vol 75 (3) ◽  
pp. 600-608 ◽  
Author(s):  
Boppe Appalaraju ◽  
Sujata Baveja ◽  
Shrikala Baliga ◽  
Suchitra Shenoy ◽  
Renu Bhardwaj ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Tertiary Care ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Surveillance Study ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
In Vitro Activity ◽  
Broth Microdilution Method

Abstract Background Levonadifloxacin is a novel antibiotic belonging to the benzoquinolizine subclass of fluoroquinolones with potent activity against MRSA and quinolone-resistant Staphylococcus aureus. IV levonadifloxacin and its oral prodrug alalevonadifloxacin have recently been approved in India for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) including diabetic foot infections. Objectives To investigate the in vitro activity of levonadifloxacin against contemporary clinical isolates collected from multiple tertiary care hospitals across India in the Antimicrobial Susceptibility Profiling of Indian Resistotypes (ASPIRE) surveillance study. Methods A total of 1376 clinical isolates, consisting of staphylococci (n = 677), streptococci (n = 178), Enterobacterales (n = 320), Pseudomonas aeruginosa (n = 140) and Acinetobacter baumannii (n = 61), collected (2016–18) from 16 tertiary hospitals located across 12 states in India, were included in the study. The MICs of levonadifloxacin and comparator antibiotics were determined using the reference agar dilution method and broth microdilution method. Results Levonadifloxacin exhibited potent activity against MSSA (MIC50/90: 0.5/1 mg/L), MRSA (MIC50/90: 0.5/1 mg/L) and levofloxacin-resistant S. aureus (MIC50/90: 1/1 mg/L) isolates. Similarly, potent activity of levonadifloxacin was also observed against CoNS including MDR isolates (MIC50/90: 1/2 mg/L). Against Streptococcus pneumoniae, levonadifloxacin (MIC50/90: 0.5/0.5 mg/L) showed superior activity compared with levofloxacin (MIC50/90: 1/2 mg/L). Among levofloxacin-susceptible Enterobacterales, 80.6% of isolates were inhibited at ≤2 mg/L levonadifloxacin. Conclusions Levonadifloxacin displayed potent activity against contemporary MRSA and fluoroquinolone-resistant staphylococcal isolates, thus offering a valuable IV as well as an oral therapeutic option for the treatment of ABSSSIs. Furthermore, levonadifloxacin exhibited a broad-spectrum activity profile as evident from its activity against streptococci and levofloxacin-susceptible Gram-negative isolates.

scholarly journals In vitro activity of the trinem sanfetrinem (GV104326) against gram-positive organisms.

1996 ◽  
Vol 40 (9) ◽  
pp. 2142-2146 ◽  
Author(s):  
K V Singh ◽  
T M Coque ◽  
B E Murray
Keyword(s):  
Staphylococcus Aureus ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Gentamicin Resistance ◽  
High Level

The in vitro activity of the trinem sanfetrinem (formerly GV104326) (GV) was compared with that of vancomycin, ampicillin, and/or nafcillin against 287 gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and multiresistant enterococci, by the agar and microbroth dilution methods. GV demonstrated 2 to 16 times more activity than ampicillin and nafcillin against the majority of these organisms. The MIC range of GV was 16 to 64 micrograms/ml for 19 Enterococcus faecium strains that were highly resistant to ampicillin (ampicillin MIC range, 64 to 512 micrograms/ml) and vancomycin resistant and 0.25 to 32 micrograms/ml for resistant Rhodococcus spp. Similar activities (+/-1 dilution) were observed by either the agar or the broth microdilution method. GV demonstrated bactericidal activity against a beta-lactamase-producing Enterococcus faecalis strain and against two methicillin-susceptible Staphylococcus aureus strains in 10(5)-CFU/ml inocula. Synergy between GV and gentamicin was observed against an E. faecalis strain that lacked high-level gentamicin resistance. The activity of GV suggests this compound warrants further study.

scholarly journals Detection of Oxacillin (Methicillin)-resistant Staphylococcus aureus Isolated from a Tertiary-care Hospital, Georgetown, Guyana

2020 ◽  
pp. 1-7
Author(s):  
Paul Cheddie ◽  
Drovashti Seepersaud ◽  
Tereasia Ramlochan
Keyword(s):  
Staphylococcus Aureus ◽  
Tertiary Care Hospital ◽  
Methicillin Resistance ◽  
Tertiary Care ◽  
Hospital Setting ◽  
Tertiary Hospital ◽  
Care Hospital ◽  
Prevalence Survey ◽  
Methicillin Resistant ◽  
Broth Microdilution Method

Background and Aim: Methicillin-resistant Staphylocccus aureus (MRSA) continues to be a major problem globally. Previous data had suggested that the prevalence of MRSA infections in the tertiary hospital setting was 51%. The aim of this study was to conduct a point prevalence survey of MRSA infections occurring at a tertiary-care hospital in Georgetown, Guyana, and to determine to what extent methicillin-resistance was occurring among Staphylococcus aureus isolates utilising the minimum inhibitory concentration (MIC) data. Study Design: This study was based on a prospective, analytical design. Place and Duration of Study: Microbiology department, Georgetown Public Hospital Corporation (GPHC), and Department of Medical Technology, University of Guyana, between May 2019 and July 2019. Methodology: A total of 101 consecutive, non-repetitive, laboratory-identified MRSA and methicillin-susceptible Staphylococcus aureus (MSSA) isolates were tested using an oxacillin broth microdilution method. Results: We found that 65.4% of Staphylococcus aureus were oxacillin (methicillin) resistant with a majority of the isolates being high level oxacillin resistant strains (i.e., MICs > 256 μg/ml) (84.85%). Most of the resistant isolates were collected from patients admitted to medical and surgical wards. Conclusion: Methicillin-resistance continues to be a major problem in the hospital setting and conventional techniques are unlikely to identify all of the potentially resistant isolates.

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