Treatment Of Gram-positive Bacterial Infections Research Articles

Total Syntheses and Antibacterial Studies of Natural Isoflavones: Scandenone, Osajin, and 6,8-Diprenylgenistein.

Isoflavones are a class of natural products that exhibit a wide range of interesting biological properties, including antioxidant, hepatoprotective, antimicrobial, and anti-inflammatory activities. Scandenone (1), osajin (2), and 6,8-diprenylgenistein (3) are natural prenylated isoflavones that share the same polyphenol framework. In this research, the key intermediate 15 was used for the synthesis of the natural isoflavones 1-3, establishing a stereoselective synthetic method for both linear and angular pyran isoflavones. The antibacterial activities of 1-3 were also evaluated, and all of them displayed good antibacterial activity against Gram-positive bacteria. Among them, 2 was the most potent one against MRSA, with a MIC value of 2 μg/mL, and the SEM assay indicated that the bacterial cell membranes of both MRSA and E. faecalis could be disrupted by 2. These findings suggest that this type of isoflavone could serve as a lead for the development of novel antibacterial agents for the treatment of Gram-positive bacterial infections.

Optimization of fermentation conditions and medium components for chrysomycin a production by Streptomyces sp. 891-B6

BackgroundChrysomycin A (CA) is a promising antibiotic for treatment of Gram-positive bacterial infections and cancers. In order to enhance CA yield, optimization of fermentation conditions and medium components was carried out on strain Streptomyces sp. 891-B6, an UV-induced mutant with improved CA titer compared with its wide-type marine strain 891.ResultsUsing one-way experiment, the optimal fermentation conditions for CA production in 1-L shake flask were obtained as follows: 12 days of fermentation time, 5 days of seed age, 5% of inoculum volume ratio, 200 mL of loading volume and 6.5 of initial pH. By response surface methodology, the optimal medium components determined as glucose (39.283 g/L), corn starch (20.662 g/L), soybean meal (15.480 g/L) and CaCO3 (2.000 g/L).ConclusionValidation tests showed that the maximum yield of CA reached 1601.9 ± 56.7 mg/L, which was a 60% increase compared to the initial yield (952.3 ± 53.2 mg/L). These results provided an important basis for scale-up production of CA by strain 891-B6.

Hit-to-Lead Identification and Validation of a Triaromatic Pleuromutilin Antibiotic Candidate.

Herein, we report the hit-to-lead identification of a drug-like pleuromutilin conjugate 16, based on a triaromatic hit reported in 2020. The lead arose as the clear candidate from a hit-optimization campaign in which Gram-positive antibacterial activity, solubility, and P-gp affinity were optimized. Conjugate 16 was extensively evaluated for its in vitro ADMET performance which, apart from solubility, was overall on par with lefamulin. This evaluation included Caco-2 cell permeability, plasma protein binding, hERG inhibition, cytotoxicity, metabolism in microsomes and CYP3A4, resistance induction, and time-kill kinetics. Intravenous pharmacokinetics of 16 proved satisfactory in both mice and pigs; however, oral bioavailability was limited likely due to insufficient solubility. The in vivo efficacy was evaluated in mice, systemically infected with Staphylococcus aureus, where 16 showed rapid reduction in blood bacteriaemia. Through our comprehensive studies, lead 16 has emerged as a highly promising and safe antibiotic candidate for the treatment of Gram-positive bacterial infections.

Dried blood spot analysis for the quantification of vancomycin and creatinine using liquid chromatography – tandem mass spectrometry: Method development and validation

BackgroundVancomycin is a widely used antibiotic for the treatment of gram-positive bacterial infections, especially for methicillin-resistant Staphylococcus aureus (MRSA) infections. Due to a small therapeutic range and large inter-patient variability, therapeutic drug monitoring (TDM) of vancomycin is required to minimize toxicity and maximize treatment efficacy. Venous blood sampling is mostly applied for TDM of vancomycin, although this widely used sampling method is more invasive compared to less painful alternatives, such as the dried blood spot (DBS) method, which can be performed at home. MethodWe developed an UPLC-MS/MS method for the quantification of vancomycin and creatinine in DBS. A fast sample preparation and short analysis run time of 5.2 min were applied, which makes this method highly suitable for clinical settings. Validation was performed according to international (FDA and EMA) guidelines. ResultsThe validated concentration range was found linear for creatinine from 41.8 µmol/L to 722 µmol/L and for vancomycin from 3.8 mg/L to 76.6 mg/L (r2 > 0.990) and the inaccuracies, imprecisions, hematocrit effects, and recoveries were < 15 % for both compounds. No significant carryover effect was observed. ConclusionHence, we successfully validated a quantification method for the simultaneous determination of creatinine and vancomycin in DBS.

An electrochemical biosensor based on graphene intercalated functionalized black phosphorus/gold nanoparticles nanocomposites for the detection of bacterial enzyme

Sortase A (Srt A) is a key enzyme that catalyzes the covalent anchoring of surface proteins to the bacterial cell wall and plays a dominant role in the late stage of Gram-positive bacterial infections. Achieving activity detection of Srt A and inhibitors screening is important for the treatment of Gram-positive bacterial infections and novel antibacterial drugs research. Here, an electrochemical sensor pattern is proposed. Black phosphorus (BP) is a novel graphite-like two-dimensional material with excellent electrochemical properties. However, the extremely poor environmental stability limits its practical application. The surface modification of BP using graphene oxide (GO) significantly improves the stability, and obtained partially reduced graphite oxide functionalized BP composites combine both electrical conductivity and stability. In this paper, we develop an electrochemical biosensor based on partially reduced graphite oxide functionalized BP /gold nanoparticles (p-rGO-BP/AuNPs) nanocomposites for detecting Srt A activity. The assay utilizes two peptide chains, P1 (CLPETG) and P2 (GGGGG), which can be linked by the presence of Srt A. At the same time, the process is monitored by differential pulse voltammetry (DPV). The sensor showed good selectivity and stability with a linear dynamic range of 1 pM-100 nM and a detection limit (LOD) of 0.65 pM. In addition, the method was successfully used to detect Srt A in complex samples and estimate the half-inhibitory concentration (IC50) of Srt A inhibitors (curcumin, dihydromyricetin and rutin).

Separation and structural characterization of unknown impurity in vancomycin by two-dimensional preparative liquid chromatography, LC-MS and NMR

Vancomycin is an effective antibiotic used for the treatment of Gram-positive bacterial infections. During the analysis of vancomycin, an unknown impurity at the level of 0.5% was detected by high-performance liquid chromatography (HPLC). To characterize the structure of the impurity, a new two-dimensional preparative liquid chromatography (2D-Prep-LC) method was developed to separate the impurity from the vancomycin sample. After further analysis including liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy, the structure of the unknown impurity was identified as a vancomycin analog in which the N-Methyl-leucine residue on the side chain is replaced by an N-methylmethionine residue. In this study, we established a reliable and efficient method for separating and identifying vancomycin impurities, which will provide a valuable contribution to the field of pharmaceutical analysis and quality control.

Vancomycin-induced elevation of liver enzyme levels in a 3-year-old boy with bacterial meningitis: A pediatric case report

BackgroundVancomycin as a glycopeptide antibiotic agent plays a vital role in the treatment of gram-positive bacterial infections, especially methicillin-resistant Staphylococcus aureus. Vancomycin-induced liver disease is rarely reported previously; isolated cases have been reported only in adults and none in children except in a 3-month-old girl published in a Chinese journal. Case SummaryA 3-year-old boy received vancomycin for the treatment of bacterial meningitis for more than 3 weeks. The baseline liver enzyme levels of alanine aminotransferase (ALT) (12 U/L), aspartate aminotransferase (AST) (18 U/L), and gamma-glutamyl transferase (GGT) (26 U/L) were obtained after administering vancomycin for 2 days. Liver enzyme levels of ALT (191 U/L), AST (175 U/L), and GGT (92 U/L) were obviously elevated after administering vancomycin for 22 days; this elevation was reversed after vancomycin discontinuation. This case suggested that regular examination of liver function is necessary for all individuals who initiated vancomycin. Practice ImplicationsThis is a rarely known case of vancomycin-induced elevation of ALT and AST and the first reported case of vancomycin causing GGT elevation in children, which suggested that regular examination of liver function is required during the use of vancomycin in children and could help avoid progressive liver injury. This case adds to the limited number of reports on vancomycin-induced liver disease.

Dose adjustment not required for contezolid in patients with moderate hepatic impairment based on pharmacokinetic/pharmacodynamic analysis.

Objective: Contezolid is an oxazolidinone antimicrobial agent newly approved for treatment of Gram-positive bacterial infections. It is primarily metabolized by the liver. This study aimed to assess whether it is required to adjust the dose of contezolid in patients with moderate hepatic impairment for clinicians to use the drug more rationally. Methods: A single-center, open-label, parallel-group study was conducted to compare the pharmacokinetic (PK) parameters of contezolid and its metabolite M2 between the patients with moderate hepatic impairment and healthy controls with normal liver function after oral administration of 800mg contezolid tablets. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) of contezolid based on the PK and pharmacodynamic data. Results: Oral treatment with 800mg contezolid tablets was safe and well tolerated in both the patients with moderate hepatic impairment and healthy controls. Moderate hepatic impairment did not result in substantial difference in the area under the concentration-time curve from 0 to 24h (AUC0-24h, 106.79 vs. 97.07hμg/mL) of contezolid even though lower maximum concentration (Cmax, 19.03 vs. 34.49μg/mL) compared with healthy controls. The mean cumulative amount excreted in urine from 0 to 48h (Ae0-48h) and renal clearance (CLR) of contezolid did not show significant difference between the two groups. Moderate hepatic impairment was associated with lower Cmax, slightly lower AUC and Ae0-48h of M2 compared to the healthy controls. fAUC/MIC was the best PK/PD index to predict the clinical efficacy of contezolid. Monte Carlo simulation results indicated that at the proposed fAUC/MIC target value of 2.3, the dosing regimen of oral contezolid 800mg q12h could achieve satisfactory PTA and CFR (both >90%) for the target pathogen (methicillin-resistant S. aureus, MIC ≤4mg/L) in patients with moderate hepatic impairment. Conclusion: Our preliminary data suggest that dose adjustment is not required for contezolid in patients with moderate hepatic impairment. Clinical Trial Registration: https://chinadrugtrials.org.cn, identifier: CTR20171377.

Synthesis of an amphiphilic vancomycin aglycone derivative inspired by polymyxins: overcoming glycopeptide resistance in Gram-positive and Gram-negative bacteria in synergy with teicoplanin in vitro

Gram-negative bacteria possess intrinsic resistance to glycopeptide antibiotics so these important antibacterial medications are only suitable for the treatment of Gram-positive bacterial infections. At the same time, polymyxins are peptide antibiotics, structurally related to glycopeptides, with remarkable activity against Gram-negative bacteria. With the aim of breaking the intrinsic resistance of Gram-negative bacteria against glycopeptides, a polycationic vancomycin aglycone derivative carrying an n-decanoyl side chain and five aminoethyl groups, which resembles the structure of polymyxins, was prepared. Although the compound by itself was not active against the Gram-negative bacteria tested, it synergized with teicoplanin against Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii, and it was able to potentiate vancomycin against these Gram-negative strains. Moreover, it proved to be active against vancomycin- and teicoplanin-resistant Gram-positive bacteria.

Targeting Peptide-Based Quorum Sensing Systems for the Treatment of Gram-Positive Bacterial Infections.

Bacteria utilize a cell density-dependent communication system called quorum sensing (QS) to coordinate group behaviors. In Gram-positive bacteria, QS involves the production of and response to auto-inducing peptide (AIP) signaling molecules to modulate group phenotypes, including pathogenicity. As such, this bacterial communication system has been identified as a potential therapeutic target against bacterial infections. More specifically, developing synthetic modulators derived from the native peptide signal paves a new way to selectively block the pathogenic behaviors associated with this signaling system. Moreover, rational design and development of potent synthetic peptide modulators allows in depth understanding of the molecular mechanisms that drive QS circuits in diverse bacterial species. Overall, studies aimed at understanding the role of QS in microbial social behavior could result in the accumulation of significant knowledge of microbial interactions, and consequently lead to the development of alternative therapeutic agents to treat bacterial infectivity. In this review, we discuss recent advances in the development of peptide-based modulators to target QS systems in Gram-positive pathogens, with a focus on evaluating the therapeutic potential associated with these bacterial signaling pathways.

Florfenicol and oxazolidone resistance status in livestock farms revealed by short- and long-read metagenomic sequencing.

Antibiotic resistance genes (ARGs) as a novel type of environmental pollutant pose a health risk to humans. Oxazolidinones are one of the most important antibiotics for the treatment of Gram-positive bacterial infections in humans. Although oxazolidinones are not utilized in the livestock industry, florfenicol is commonly used on farms to treat bacterial infections, which may contribute to the spread of the cfr, optrA, and poxtA genes on farms. Using metagenomics sequencing, we looked into the antibiotic resistome context of florfenicol and oxazolidinone in 10 large-scale commercial farms in China. We identified 490 different resistance genes and 1,515 bacterial genera in the fecal samples obtained from 10 farms. Florfenicol-resistant Kurthia, Escherichia, and Proteus were widely present in these samples. The situation of florfenicol and oxazolidone resistance in pig farms is even more severe. The total number of genes and the abundance of drug resistance genes were higher in pigs than in chickens, including optrA and poxtA. All the samples we collected had a high abundance of fexA and floR. Through nanopore metagenomic analysis of the genetic environment, we found that plasmids, integrative and conjugative element (ICE), and transposons (Tn7-like and Tn558) may play an important role in the spread of floR, cfr, and optrA. Our findings suggest that florfenicol and oxazolidinone resistance genes have diverse genetic environments and are at risk of co-transmission with, for example, tetracycline and aminoglycoside resistance genes. The spread of florfenicol- and oxazolidinone-resistant bacteria on animal farms should be continuously monitored.

Design and Synthesis of Phenyl Sulfide-Based Cationic Amphiphiles as Membrane-Targeting Antimicrobial Agents against Gram-Positive Pathogens.

Due to the emergence of antimicrobial resistance and the lack of new antibacterial agents, it has become urgent to discover and develop new antibacterial agents against multidrug-resistant pathogens. Antimicrobial peptides (AMPs) serve as the first line of defense for the host. In this work, we have designed, synthesized, and biologically evaluated a series of phenyl sulfide derivatives by biomimicking the structural features and biological functions of AMPs. Among these derivatives, the most promising compound 17 exhibited potent antibacterial activity against Gram-positive bacteria (minimum inhibitory concentrations = 0.39-1.56 μg/mL), low hemolytic activity (HC50 > 200 μg/mL), and high membrane selectivity. In addition, 17 can rapidly kill Gram-positive bacteria within 0.5 h through membrane-targeting action and avoid antibiotic resistance. More importantly, 17 showed high in vivo efficacy against Staphylococcus aureus in a murine corneal infection model. Therefore, 17 has great potential as a lead compound for the treatment of Gram-positive bacterial infections.

Oral pharmacokinetic profile and withdrawal time estimation for tylosin tartrate in the cultured olive flounder Paralichthys olivaceus

The Korean government regulates pharmaceutical parameters and withdrawal times for antimicrobials in aquaculture. Tylosin tartrate (TT) is a bacteriostatic antibacterial agent mainly used in veterinary medicine for the prevention and treatment of gram-positive bacterial infections. However, pharmacokinetic (PK) and drug withdrawal reports in aquatic animals, including olive flounder (Paralichthys olivaceus), are limited. This study aimed to determine the PK profile and drug withdrawal time following oral TT administration (10 or 20 mg/kg) in olive flounder. The concentrations of tylosin in the serum and muscle plus skin were analyzed using liquid chromatography and tandem mass spectrometry. PK parameters were calculated for serum samples using the PKSolver software based on a non-compartmental model. The PK parameters after a single oral dose of 10 (or 20) mg/kg were as follows: Cmax, 0.7 (1.49) μg/mL; Tmax, 12 h; t1/2, 22.83 (19.44) h; area under the concentration curve, 10.58 (33.17) μg/mL h; and mean residence time, 20.53 (25.62) h. Oral administration of TT at a dose of 10 mg/kg at 24–48 h intervals may help achieve efficacy comparable to that obtained with antimicrobials at minimum inhibitory concentration values of ≤ 1 μg/mL. After a 5-day oral administration of TT in olive flounder (water temperature, 22 ℃), a withdrawal time of 17.8 (rounded up to 18 days) days was required to achieve muscle plus skin TT residue levels below 100 μg/kg, which is the European limit; the corresponding value at a lower water temperature (13 ℃) was 20 days. Overall, this study not only serves as a reference for authorizing the clinical use of TT in olive flounder but also provides valuable data for evaluating the safety of food derived from aquatic animals.

Recent advances in oxazolidinones as antituberculosis agents.

Tuberculosis (TB) is an infectious and fatal disease caused by Mycobacterium tuberculosis (Mtb) and remains a serious public health threat; therefore, the development of new antitubercular agents is a priority for the World Health Organization's End TB strategy and the United Nations' Sustainable Development Goals to eradicate TB. Oxazolidinones are a class of synthetic antibacterial agents with a distinct mode of action developed for the treatment of Gram-positive bacterial infections. Many oxazolidinones exhibit good activity against Mtb, and some are currently in clinical trials for multidrug-resistant TBand extensively drug-resistant TBtherapy. In this review, the mechanism of action, activityand toxicity of oxazolidinonesand recent progress in the research and development of oxazolidinones as anti-TB agentsare summarized.

Clinical efficacy and safety of linezolid in intensive care unit patients

BackgroundTo characterize the population of critically ill patients and infections treated with linezolid in the intensive care unit (ICU), and to evaluate the clinical efficacy and safety of linezolid therapy. MethodsThis multi-center, observational, real-world study was conducted across 52 hospitals between June 9, 2018, and December 28, 2019. Patients who met the following inclusion criteria were included: (1) admitted to the ICU, (2) of any age group, and (3) having a clinical or laboratory diagnosis of a Gram-positive bacterial infection. Clinical efficacy was categorized as success (cured or improved), failed, or non-evaluable. Adverse events and serious adverse events were recorded during treatment. ResultsA total of 366 ICU patients who met the inclusion criteria were evaluated. Linezolid was used as second- and first-line treatment in 232 (63.4%) and 134 (36.6%) patients, respectively. The most common isolated strain was Staphylococcus aureus (methicillin-resistant Staphylococcus aureus: n=37/119, 31.1%; methicillin-susceptible Staphylococcus aureus: n=15/119, 12.6%); this was followed by Enterococci (vancomycin-resistant Enterococci: n=8/119, 6.7%; vancomycin-susceptible Enterococci: n=11/119, 9.2%) and Streptococcus pneumoniae (multidrug-resistant: n=4/119, 3.4%; non-multidrug resistant: n=2/119, 1.7%). The main infection sites where pathogens were detected included the lung (n=216/366, 59.6%), skin and soft tissue (n=104/366, 28.4%), and blood (n=50/366, 13.7%). Clinical success was achieved in 301 (82.2%) patients; 34 (9.3%) were cured and 267 (73.0%) improved; treatment failure and non-evaluable outcomes were observed in 29 (7.9%) in 36 (9.8%) patients, respectively. Linezolid-related adverse events were reported in 8 (2.2%) patients. No treatment-related serious adverse events were reported. ConclusionsBased on real-world results, linezolid was found to be effective and safe in the treatment of Gram-positive bacterial infections in critically ill patients.

Fusidic Acid/Tea-Tree Oil Nanoemulsions: A Potentially Safe and Effective Anti MRSA/MSSA Topical Agent for Chronic Wound Healing

Fusidic acid (FA) is clinically used as an antibacterial agent for the treatment of Gram-positive bacterial infections. It interferes with bacterial protein synthesis, specifically by preventing the translocation of the elongation factor G on the ribosome. In the present work, oil-in-water nanoemulsion (NE) was developed as a carrier for the transdermal delivery of FA. Different oils, surfactants and co-surfactants were screened. The solubility of FA, the emulsifying capacity of the surfactants and phase diagrams for each oil and surfactant mix were constructed. From the analysis, eight stable NE formulations were chosen, and their physicochemical properties were further evaluated. The antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) were also evaluated, and cytotoxicity was conducted on HS-27 cell line to determine the safety of the formula. It was found that the NE produced from tea tree oil has the most optimal stability with promising antibacterial activity against MRSA as compared to a commercially available product. The safety profile of the NE was also comparable to the commercial product; thus, the formulated FA-NE is promising for clinical use.

In Vitro Antibacterial Effect of Essential Oil and Two Extracts of Myrtus Communis Leaves

Our study aims at evaluating the efficacy of extracts and essential oil of Myrtus communis leaves from the Syrian coast against several bacterial strains. The leaves were collected and dried, extracted for essential oil and ethanolic and hexan extracts were prepared. The yield of essential oil was measured and the chemical composition of the essential oil was determined using Gas Chromatography. The yield of essential oil was 1.3 ml/100 g, and the richest component was alpha-pinene. Our results showed that the ethanolic and hexan extracts of Myrtus communis had higher antibacterial activity against Gram positive bacteria (Staphylococcus aureus and Streptococcus pyogenes) than Gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa). The ethanolic extract showed the greatest inhibitory effect against Staphylococcus aureus. These results demonstrate that Myrtus communis leaves extract has high antibacterial activity, making it a source of compounds to be used for the treatment of Gram-positive bacterial infections.

Neurodegenerative Disease Treatment Drug PBT2 Breaks Intrinsic Polymyxin Resistance in Gram-Positive Bacteria.

Gram-positive bacteria do not produce lipopolysaccharide as a cell wall component. As such, the polymyxin class of antibiotics, which exert bactericidal activity against Gram-negative pathogens, are ineffective against Gram-positive bacteria. The safe-for-human-use hydroxyquinoline analog ionophore PBT2 has been previously shown to break polymyxin resistance in Gram-negative bacteria, independent of the lipopolysaccharide modification pathways that confer polymyxin resistance. Here, in combination with zinc, PBT2 was shown to break intrinsic polymyxin resistance in Streptococcus pyogenes (Group A Streptococcus; GAS), Staphylococcus aureus (including methicillin-resistant S. aureus), and vancomycin-resistant Enterococcus faecium. Using the globally disseminated M1T1 GAS strain 5448 as a proof of principle model, colistin in the presence of PBT2 + zinc was shown to be bactericidal in activity. Any resistance that did arise imposed a substantial fitness cost. PBT2 + zinc dysregulated GAS metal ion homeostasis, notably decreasing the cellular manganese content. Using a murine model of wound infection, PBT2 in combination with zinc and colistin proved an efficacious treatment against streptococcal skin infection. These findings provide a foundation from which to investigate the utility of PBT2 and next-generation polymyxin antibiotics for the treatment of Gram-positive bacterial infections.

Efficacy and safety of novel glycopeptides versus vancomycin for the treatment of gram-positive bacterial infections including methicillin resistant Staphylococcus aureus: A systematic review and meta-analysis.

ObjectiveTo compare between current evidence of novel glycopeptides against vancomycin for the treatment of gram-positive bacterial infections.MethodologyA systematic review and meta-analysis was done. Major databases were searched for eligible randomized control trials that assessed clinical success, microbiological success and safety profile of novel glycopeptides versus vancomycin for infections caused by gram-positive bacteria.ResultsThis meta-analysis included eleven trials (7289 participants) comparing telavancin, dalbavancin and oritavancin with vancomycin. No differences were detected between novel glycopeptides and vancomycin for the treatment of skin and soft tissue infections (SSTIs) among modified intent-to-treat patients (OR: 1.04, CI: 0.92–1.17) as well as within the clinically evaluable patients (OR: 1.09, CI: 0.91–1.30). Data analysed from SSTIs, HAP and bacteremia studies on telavancin showed insignificant high clinical response in microbiologically evaluable patients infected with methicillin resistant Staphylococcus aureus (MRSA) (OR: 1.57, CI: 0.94–2.62, p: 0.08) and in the eradication of MRSA (OR: 1.39, CI: 0.99–1.96, P:0.06). Dalbavancin was non-inferior to vancomycin for the treatment of osteomyelitis in a phase II trial, while it was superior to vancomycin for the treatment of bacteremia in a phase II trial. Data analysed from all trials showed similar rates of all-cause mortality between compared antibiotics groups (OR: 0.67, CI: 0.11–4.03). Telavancin was significantly related with higher adverse events (OR: 1.24, CI: 1.07–1.44, P: <0.01) while dalbavancin and oritavancin were associated with significant fewer adverse events (OR: 0.73, CI: 0.57–0.94, p: 0.01; OR: 0.72, CI: 0.59–0.89, p: <0.01 respectively).ConclusionEfficacy and safety profiles of both dalbavancin and oritavancin were the same as vancomycin in the treatment of gram-positive bacterial infections in different clinical settings, while telavancin might be an effective alternative to vancomycin in MRSA infections, but caution is required during its clinical use due to the high risk of adverse events, especially nephrotoxicity.

1172 Maggot Debridement Therapy (MDT) In Treating Group A Streptococcus Necrotizing Fasciitis of The Lower Limb as A Part of Multimodal Therapy

Abstract Background Medical-grade maggots have been commercially available recently and today there is a resurge interest in MDT. They are approved for debridement of wounds with necrotic tissue, including pressure ulcers, venous ulcers. However, for necrotising fasciitis, it has been used with precaution due to the complexity of the disease. In our practice, Maggot debridement therapy (MDT) has been proven to be very effective in the treatment of gram-positive bacterial infections. Worldwide, Case reports on the results of 15 patients with necrotizing fasciitis treated with MDT have been reported. However, in current practice, Maggot Debridement therapy has not been widely applied. Case presentation A 63-year-old lady admitted to a general surgery ward with uncomplicated cellulitis of the right leg. After 2 days, the patient then was diagnosed with Necrotising fasciitis which was treated with wound debridement. Postoperative histopathology specimen confirmed necrotizing fasciitis V.A.C. VERAFLO™ Therapy was used postoperatively followed by two more debridement sessions. To reduce the need for further surgical debridement Maggot Debridement Therapy was started. Over the next 3 weeks, six sessions of Maggot Debridement therapy were applied to the infected area. Skin grafting then was performed 3 months later. The patient then discharged home with regular surgical fellow up. Conclusions NF is a complex disease, associated with high morbidity and mortality. Multimodal therapies are essential to achieve aggressive yet conservative wound debridement with preservation of viable tissue. This case report showed that MDT is a feasible, safe, cost-effective option that to be added to the other treatment modalities