Telavancin, a new lipoglycopeptide antimicrobial, in complicated skin and soft tissue infections

Saraf, Lida Jafari; Wilson, Samuel E.

doi:10.2147/idr.s5327

Cited by 4 publications

(2 citation statements)

References 43 publications

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“…However, the LAMP method exhibits significant advantages in the detection of fastidious bacteria, such as Haemophilus influenzae and Streptococcus pneumoniae , and can avoid such disadvantages [24]. Methicillin-resistant Staphylococcus aureus infection causes severe illness and is associated with increased mortality; patients with MRSA usually require hospitalization and mechanical ventilation [25]. It has been reported that the positive rate of MRSA culture in the clinic is not high [26].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of loop-mediated isothermal amplification in detecting lower respiratory pathogens

Yuan¹,

Huang²,

Du³

et al. 2023

J Infect Dev Ctries

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Introduction: To investigate the diagnostic value of loop-mediated thermostatic amplification (LAMP) in detecting pathogenic bacteria from bronchoalveolar lavage fluid (BALF) of patients with pulmonary disorders combined with lower respiratory tract infections (LRTI). Methodology: This cross-sectional study included patients with pulmonary disorders combined with LRTI, including chronic obstructive pulmonary disease (COPD), bronchiectasis, or lung cancer, hospitalized in Meizhou People’s Hospital between January 2020 and October 2021. BALF was collected using local bronchoalveolar lavage and electronic bronchoscopy. The presence of the pathogens was confirmed using the LAMP method and the bacterial culture method. Results: In total, 249 patients were included (135 with COPD, 73 with bronchiectasis, and 41 with lung cancer). The proportions of Methicillin-resistant Staphylococcus aureus (4.8% vs 0.4%, p = 0.02) and Haemophilus influenzae (6.8% vs 0.4%, p < 0.001) detected by the LAMP method was higher, while the proportion of Pseudomonas aeruginosa was lower compared with that of the culture method (6.8% vs 12.4%, p = 0.034). The bacterial species with the highest agreement coefficient was Stenotrophomonas maltophilia (Kappa = 0.798, p < 0.001). Furthermore, 9 COPD patients exhibited mixed infections as determined by the LAMP method, whereas the culture method detected only 2 of these cases (1.48%) (p < 0.05). Conclusions: LAMP can detect more pathogenic bacteria, notably Haemophilus influenza, Methicillin-resistant Staphylococcus aureus, and atypical pathogens in patients with clinically common pulmonary disorders combined with LRTI. LAMP may provide etiological evidence to guide the clinical use of antibiotics in primary hospitals.

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Section: Discussionmentioning

confidence: 99%

Diagnostic value of loop-mediated isothermal amplification in detecting lower respiratory pathogens

Yuan¹,

Huang²,

Du³

et al. 2023

J Infect Dev Ctries

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“…Cell wall biosynthesis is one of the prime targets for drug discovery, because it is an essential process in the bacterial life cycle. Enzymes involved in the later stage of bacterial cell wall biosynthesis have been the targets of successfully marketed antibacterial drugs such as β-lactams including pencillins, carbapenems and cephalosporins, and vancomycin as well as several promising agents in advanced clinical study such as telavancin and capuramycin [ 5 ]. In contrast, except for fosfomycin no successful antibacterial agents targeting the first cytoplasmic steps of murein biosynthesis have appeared on the market.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antibacterial Evaluation of a New Series of N-Alkyl-2-alkynyl/(E)-alkenyl-4-(1H)-quinolones

et al. 2012

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To gain further insight into the structural requirements of the aliphatic group at position 2 for their antimycobacterial activity, some N-alkyl-4-(1H)-quinolones bearing position 2 alkynyls with various chain length and triple bond positions were prepared and tested for in vitro antibacterial activity against rapidly-growing strains of mycobacteria, the vaccine strain Mycobacterium bovis BCG, and methicillin-resistant Staphylococcus aureus strains, EMRSA-15 and -16. The compounds were also evaluated for inhibition of ATP-dependent MurE ligase of Mycobacterium tuberculosis. The lowest MIC value of 0.5 mg/L (1.2–1.5 µM) was found against M. fortuitum and M. smegmatis. These compounds displayed no or only weak toxicity to the human lung fibroblast cell line MRC-5 at 100 µM concentration. The quinolone derivatives exhibited pronounced activity against the epidemic MRSA strains (EMRSA-15 and -16) with MIC values of 2–128 mg/L (5.3–364.7 µM), and M. bovis BCG with an MIC value of 25 mg/L (66.0–77.4 µM). In addition, the compounds inhibited the MurE ligase of M. tuberculosis with moderate to weak activity showing IC50 values of 200–774 µM. The increased selectivity towards mycobacterial bacilli with reference to MRC-5 cells observed for 2-alkynyl quinolones compared to their corresponding 2-alkenyl analogues serves to highlight the mycobacterial specific effect of the triple bond. Exploration of a terminal bromine atom at the side chain of N-alkyl-2-(E)-alkenyl-4-(1H)-quinolones showed improved antimycobacterial activity whereas a cyclopropyl residue at N-1 was suggested to be detrimental to antibacterial activity.

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Telavancin in Therapy of Experimental Aortic Valve Endocarditis in Rabbits Due to Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus

Xiong

Hady

Bayer

et al. 2012

Antimicrob Agents Chemother

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A number of cases of both methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains that have developed daptomycin resistance (DAP-R) have been reported. Telavancin (TLV) is a lipoglycopeptide agent with a dual mechanism of activity (cell wall synthesis inhibition plus depolarization of the bacterial cell membrane). Five recent daptomycin-susceptible (DAP-S)/DAP-R MRSA isogenic strain pairs were evaluated for in vitro TLV susceptibility. All five DAP-R strains (DAP MICs ranging from 2 to 4 g/ml) were susceptible to TLV (MICs of <0.38 g/ml). In vitro time-kill analyses also revealed that several TLV concentrations (1-, 2-, and 4-fold MICs) caused rapid killing against the DAP-R strains. Moreover, for 3 of 5 DAP-R strains (REF2145, A215, and B 2.0 ), supra-MICs of TLV were effective at preventing regrowth at 24 h of incubation. Further, the combination of TLV plus oxacillin (at 0.25؋ or 0.50؋ MIC for each agent) increased killing of DAP-R MRSA strains REF2145 and A215 at 24 h (ϳ2-log and 5-log reductions versus TLV and oxacillin alone, respectively). Finally, using a rabbit model of aortic valve endocarditis caused by DAP-R strain REF2145, TLV therapy produced a mean reduction of >4.5 log 10 CFU/g in vegetations, kidneys, and spleen compared to untreated or DAP-treated rabbits. Moreover, TLV-treated rabbits had a significantly higher percentage of sterile tissue cultures (87% in vegetations and 100% in kidney and spleen) than all other treatment groups (P < 0.0001). Together, these results demonstrate that TLV has potent bactericidal activity in vitro and in vivo against DAP-R MRSA isolates. (1,2,6,24,29). (Although the currently accepted term for reduced in vitro susceptibility to daptomycin is "nonsusceptible," we will use the terms "daptomycin resistant [DAP-R]" and "daptomycin susceptible [DAP-S]" in this paper for a more facile presentation.) Potential alternative regimens for such infections are limited to the bacteriostatic agent linezolid and the clinically cumbersome agent quinupristin-dalfopristin (Synercid) (17).Telavancin (TLV) is a novel lipoglycopeptide with bactericidal activity against Gram-positive pathogens, including S. aureus (4,9,18,19). The bactericidal action of TLV results from a dual mechanism that includes both cell wall synthesis inhibition and disruption of the target bacterial membrane (7,18). In the current investigation, we evaluated (i) in vitro efficacy of TLV against several recent clinical DAP-R MRSA strains, (ii) whether combinations of TLV and oxacillin (OXA) would enhance in vitro efficacy of these single agents against DAP-R MRSA strains, taking advantage of the so-called DAP-OXA "see-saw" phenomenon (38), and (iii) the in vivo efficacy of TLV in a prototypic rabbit IE model of invasive systemic infection caused by a DAP-R MRSA strain. MATERIALS AND METHODSBacterial strains and growth conditions. The S. aureus strains employed in this study are listed in Table 1. We used five recent clinically derived DAP-S/DAP-R MRSA strain pair...

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Telavancin, a new lipoglycopeptide antimicrobial, in complicated skin and soft tissue infections

Cited by 4 publications

References 43 publications

Diagnostic value of loop-mediated isothermal amplification in detecting lower respiratory pathogens

Diagnostic value of loop-mediated isothermal amplification in detecting lower respiratory pathogens

Synthesis and Antibacterial Evaluation of a New Series of N-Alkyl-2-alkynyl/(E)-alkenyl-4-(1H)-quinolones

Telavancin in Therapy of Experimental Aortic Valve Endocarditis in Rabbits Due to Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus

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