Cloxacillin

In Vitro Susceptibility Profiling of Cloxacillin against Bacterial Isolates

The in vitro susceptibility of bacterial isolates to this compound is a critical determinant in guiding therapeutic choices. Various laboratory methods are employed to assess the effectiveness of this compound against specific pathogens, providing essential data on its antimicrobial spectrum.

This compound, a penicillinase-stable penicillin, demonstrates significant activity primarily against Gram-positive bacteria, with a particular emphasis on Staphylococcus aureus. researchgate.net Its development was a direct response to the emergence of penicillinase-producing strains of S. aureus that rendered earlier penicillins ineffective. banglajol.info

Research has consistently shown that this compound is effective against penicillinase-producing staphylococci. researchgate.net However, the emergence of methicillin-resistant Staphylococcus aureus (MRSA) has presented a significant challenge, as these strains are also resistant to this compound. banglajol.inforesearchgate.net Studies have identified MRSA strains exhibiting high levels of resistance to this compound, with some showing 100% resistance. researchgate.net

Conversely, for methicillin-susceptible Staphylococcus aureus (MSSA), this compound remains a viable therapeutic agent. nih.gov Some studies have even explored the phenomenon of "tolerance," where certain S. aureus strains, while having a low minimum inhibitory concentration (MIC) to this compound, are not effectively killed by it. nih.gov The clinical significance of this tolerance, however, remains a subject of investigation. nih.gov

The table below summarizes the susceptibility of different Staphylococcus aureus strains to this compound based on various studies.

The minimum inhibitory concentration (MIC) is a fundamental measure in microbiology, representing the lowest concentration of an antimicrobial agent that prevents the visible growth of a microorganism. banglajol.info Several standardized methods are utilized to determine the MIC of this compound. researchgate.net

The agar dilution method is a well-established technique for determining the MIC of antimicrobial agents. researchgate.net In this method, varying concentrations of this compound are incorporated into an agar medium. researchgate.netbanglajol.info Each plate contains a different, specific concentration of the antibiotic. researchgate.net

The bacterial isolates to be tested are then inoculated onto the surface of these plates. nih.gov This can be done efficiently using an inoculum-replicating apparatus that transfers multiple inocula simultaneously. researchgate.net After incubation, the plates are examined for bacterial growth. The MIC is recorded as the lowest concentration of this compound that completely inhibits the visible growth of the organism. banglajol.info

For example, a study determining the MIC of this compound for MRSA strains used agar plates with concentrations of 128 μg/ml, 64 μg/ml, 32 μg/ml, 16 μg/ml, 8 μg/ml, 4 μg/ml, 2 μg/ml, and 1 μg/ml. banglajol.info The results from such studies can reveal high levels of resistance, with some MRSA strains growing even at concentrations of ≥128 μg/ml. banglajol.inforesearchgate.net

The disk diffusion assay, commonly known as the Kirby-Bauer method, is a widely used qualitative test for determining the susceptibility of bacteria to antibiotics. mymicrolab.comtmmedia.in This method is based on the principle of diffusion. An antibiotic-impregnated paper disk, containing a specific amount of this compound (e.g., 1 mcg or 5 mcg), is placed on an agar plate that has been uniformly inoculated with the test bacterium. mymicrolab.commicromasterlab.com

As the disk absorbs moisture from the agar, the this compound diffuses outward, creating a concentration gradient in the agar. tmmedia.in The concentration is highest near the disk and decreases with distance. mymicrolab.comtmmedia.in After an incubation period, typically 16-20 hours at 35 ± 2°C, a clear zone of inhibition will be visible around the disk if the bacteria are susceptible to this compound. mymicrolab.comhimedialabs.com The diameter of this zone is measured and compared to standardized charts to determine if the organism is susceptible, intermediate, or resistant. himedialabs.com

Mueller-Hinton Agar is the recommended medium for this test due to its reproducibility and low levels of inhibitors. mymicrolab.comtmmedia.in It is important to note that for detecting methicillin-resistant strains of S. aureus, incubation at 35°C or below is crucial, as resistance may be missed at 37°C. nih.gov Interestingly, some research suggests that 1-μg this compound disks may not reliably differentiate between sensitive and resistant staphylococci. nih.gov

The microbroth dilution method is another quantitative technique for determining the MIC of this compound. This method involves using a series of wells in a microtiter plate, each containing a different concentration of the antibiotic in a liquid growth medium (broth). nih.govnih.gov

A standardized suspension of the test bacteria is added to each well. frontiersin.org The plates are then incubated, and the wells are observed for turbidity, which indicates bacterial growth. The MIC is the lowest concentration of this compound that shows no visible growth. idexx.dk

This method is amenable to automation and is considered a reference method by organizations like the Clinical and Laboratory Standards Institute (CLSI). researchgate.net In one study, the MIC of this compound against S. aureus was determined using a two-fold serial dilution in broth, with concentrations ranging from 256 to 0.007 μg/mL. frontiersin.org

The table below provides a comparative overview of the MIC determination methodologies.

Time-kill kinetic studies are performed to evaluate the bactericidal (killing) or bacteriostatic (inhibiting growth) activity of an antimicrobial agent over time. These studies provide a dynamic view of the interaction between the antibiotic and the bacteria.

In a typical time-kill assay, a standardized inoculum of bacteria is exposed to a specific concentration of this compound (often at multiples of the MIC) in a liquid culture medium. Samples are then taken at various time points (e.g., 0, 2, 4, 6, 8, 24 hours), diluted, and plated to determine the number of viable bacteria (colony-forming units per milliliter or CFU/mL). nih.gov

A bactericidal effect is generally defined as a ≥3-log10 (or 99.9%) reduction in the initial bacterial count. abjournals.org Research has shown that the bactericidal activity of this compound can be concentration-dependent. For instance, in a study on a tolerant S. aureus strain, a lower concentration of this compound (0.5 mg/L) resulted in a greater reduction in bacterial numbers after 6 and 24 hours compared to higher concentrations (2.5 and 25 mg/L), a phenomenon known as a paradoxical effect.

Time-kill curves graphically represent the change in bacterial viability over time. These curves can demonstrate the speed and extent of bacterial killing. For example, some studies have shown that the combination of this compound with other antibiotics, like daptomycin, can enhance the bactericidal effect against both MSSA and MRSA. nih.govasm.org

Comparative Antimicrobial Efficacy Studies in Preclinical Models and In Vitro Systems

This compound, a penicillinase-resistant beta-lactam, is frequently compared to other antibiotics to establish its relative efficacy, particularly against susceptible and resistant bacterial strains. In preclinical and in vitro settings, its performance varies depending on the comparator drug and the target organism.

Studies comparing this compound to other beta-lactams often focus on its activity against Staphylococcus aureus. In the treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia, retrospective cohort studies have found no significant difference in 90-day mortality between definitive treatment with this compound and the first-generation cephalosporin, cefazolin. researchgate.netnih.gov However, empirical treatment with this compound or cefazolin was associated with lower 30-day mortality compared to treatment with third-generation cephalosporins (ceftriaxone, cefotaxime) or beta-lactam/beta-lactamase inhibitor combinations. researchgate.net An in vitro study investigating coagulase-negative staphylococci found more strains were resistant to this compound and oxacillin than to dithis compound and fluthis compound. nih.gov A combination of amoxicillin-cloxacillin demonstrated synergy and proved effective against clinical isolates of S. aureus, including those resistant to a combination of ampicillin-cloxacillin. ajol.info

When compared with non-beta-lactam antibiotics, this compound's efficacy is context-dependent. Against MSSA in a rabbit model of experimental endocarditis, the combination of daptomycin and this compound significantly reduced the bacterial load. researchgate.net In a separate foreign-body infection model using MSSA, this compound monotherapy was found to be less active than combination therapies, such as this compound-daptomycin or this compound-rifampin. asm.org While some research points to the superiority of beta-lactams over glycopeptides like vancomycin for MSSA infections, a mouse peritonitis model did not show evidence of a synergistic or additive effect when this compound was combined with vancomycin. researchgate.netresearchgate.net The discovery of non-β-lactam inhibitors, such as oxadiazoles, which target penicillin-binding proteins (PBPs), presents a novel comparison point, with these new compounds showing activity against MRSA. acs.org

The efficacy of this compound can be significantly altered when administered with other compounds. In vitro studies have identified both synergistic and antagonistic interactions with a range of other drugs.

Synergism, where the combined effect is greater than the sum of individual effects, has been observed with several antibiotics. A notable synergistic partner is the aminoglycoside netilmicin, which, in combination with this compound, showed a synergistic effect against a reference strain of S. aureus both in vitro and in vivo. nih.gov Combinations with daptomycin and fosfomycin have also demonstrated synergistic activity against methicillin-sensitive S. aureus (MSSA) in time-kill curve studies. researchgate.net A screen of FDA-approved drugs identified that this compound, along with other beta-lactamase-resistant penicillins, had the greatest synergy with the fifth-generation cephalosporin ceftobiprole against methicillin-resistant S. aureus (MRSA). asm.org Beyond conventional antibiotics, the essential oil of Melaleuca armillaris showed a clear synergistic effect when combined with this compound against S. aureus, significantly decreasing the concentration of the antibiotic needed to inhibit bacterial growth. frontiersin.org this compound can also inhibit AmpC β-lactamases, leading to a significant reduction in the minimum inhibitory concentrations (MICs) of carbapenems (imipenem, meropenem) and cephalosporins (ceftazidime, cefepime) against resistant Pseudomonas aeruginosa isolates. nih.gov

Conversely, antagonism has been documented, particularly with bacteriostatic antibiotics. Tetracyclines, such as doxycycline and tetracycline itself, may reduce the therapeutic effect of penicillins like this compound by inhibiting protein synthesis, which is necessary for the cell wall synthesis inhibition pathway of penicillins. drugbank.comdrugs.com Similarly, some in vitro data indicate that macrolide antibiotics, including clarithromycin and erythromycin, can act antagonistically with penicillins, although other data have shown synergism, leading to unpredictable therapeutic efficacy when combined. drugs.comdrugs.com

This compound's Impact on Bacterial Biofilm Formation and Eradication

This compound exhibits a complex, often concentration-dependent, relationship with bacterial biofilms. Research indicates it can both induce the formation of biofilms at low concentrations and inhibit or eradicate them at higher concentrations.

A significant body of evidence shows that sub-inhibitory concentrations of this compound can paradoxically promote biofilm formation in several bacterial species. plos.orgfrontiersin.org This effect has been documented in both Staphylococcus aureus and Staphylococcus epidermidis. plos.orgumh.es Studies suggest this antibiotic-induced biofilm formation may be a protective stress response by the bacteria. acs.org For instance, in methicillin-resistant S. epidermidis (MRSE), sub-MIC levels of this compound were found to significantly enhance biofilm production. plos.org Similarly, some beta-lactams, including this compound, have been shown to induce biofilm formation in S. aureus through a mechanism linked to the release of extracellular DNA (eDNA). frontiersin.org

Conversely, at sufficient concentrations, this compound can effectively inhibit the initial stages of biofilm formation and help eradicate mature biofilms. acs.orgdovepress.com In a study on S. epidermidis, this compound alone achieved a 95.28% reduction in biofilm. mdpi.com The efficacy of this compound against biofilms is often enhanced when used in combination with other agents. For example, combinations of cinnamic acid derivatives with this compound resulted in biofilm growth reductions of up to 95.51%. mdpi.com An in vivo model of a catheter-associated infection showed that this compound administered at a concentration equivalent to its biofilm MIC (bMIC) significantly reduced bacterial colonization on the catheter, whereas concentrations at the standard MIC had a limited effect. vivexia.frresearchgate.net However, other research has found this compound to be effective in eradicating planktonic cultures of S. aureus but not established biofilms. dovepress.com

Semi-Synthetic Production Pathways of Cloxacillin

This compound is classified as a semi-synthetic penicillin, meaning it is derived from a naturally occurring penicillin nucleus that is subsequently modified through chemical reactions. The fundamental building block for this compound and other semi-synthetic penicillins is 6-aminopenicillanic acid (6-APA) bocsci.comnih.gov. 6-APA is the core bicyclic structure common to all penicillins, comprising a β-lactam ring fused to a thiazolidine ring [Search Result 19 from previous turn].

The semi-synthetic nature allows for the introduction of various side chains at the 6-amino position of 6-APA, thereby tailoring the antimicrobial properties of the resulting antibiotic [Search Result 4 from previous turn]. This approach has been instrumental in developing penicillins with improved stability against enzymatic degradation and altered spectrums of activity.

Structure-Activity Relationship (SAR) Studies of this compound and its Analogs

Structure-Activity Relationship (SAR) studies are crucial in medicinal chemistry for understanding how modifications to a molecule's structure influence its biological activity. For this compound, SAR investigations have focused on its resistance to β-lactamase enzymes and the impact of its stereochemistry on potency.

Design and Synthesis of Novel this compound Derivatives with Modified Antimicrobial Properties

The ongoing challenge of antimicrobial resistance necessitates the continuous design and synthesis of novel derivatives with improved or altered antimicrobial properties. While direct modifications to the core this compound structure are explored, research also extends to synthesizing compounds with similar structural motifs, particularly the isoxazole ring, to achieve enhanced activity.

For instance, studies have focused on synthesizing novel isoxazole derivatives that share structural characteristics with the side chain of this compound. These efforts aim to identify compounds with superior antibacterial activity against both Gram-negative and Gram-positive bacteria, including resistant strains.

An example of such research involves the synthesis and antibacterial screening of N3, N5-di(substituted)isoxazole-3,5-diamine derivatives. These compounds, while not direct this compound derivatives, incorporate the isoxazole moiety central to this compound's side chain. Research findings indicate that certain modifications to these isoxazole structures can lead to enhanced antimicrobial properties. For example, the presence of electron-withdrawing groups, such as fluorine and chlorine, at the para position of the phenyl rings generally increased antibacterial activity.

The following table illustrates the comparative minimum inhibitory concentrations (MICs) of some novel isoxazole derivatives against common bacterial strains, demonstrating their modified antimicrobial properties relative to this compound:

Table 1: Comparative MIC Values of Novel Isoxazole Derivatives vs. This compound

Note: Lower MIC values indicate higher antibacterial potency.

This data suggests that strategic modifications to the isoxazole scaffold can yield compounds with improved antibacterial efficacy, surpassing that of this compound against certain strains. Such findings contribute to the broader understanding of SAR within the β-lactam class and guide the rational design of future antimicrobial agents.

Pharmacodynamic Principles Governing Cloxacillin's Efficacy in Research Models

This compound is a semisynthetic penicillin antibiotic that exerts its bactericidal activity by interfering with the synthesis of the bacterial cell wall. This mechanism involves the binding of this compound to specific penicillin-binding proteins (PBPs) located within the bacterial cell wall, thereby inhibiting the final transpeptidation step of peptidoglycan synthesis. nih.govwikipedia.orgwikipedia.orgwikipedia.orgwikipedia.orgmims.com The integrity of the β-lactam ring is crucial for its antibacterial activity, and this compound is particularly effective against penicillinase-producing Staphylococcus aureus strains due to the steric hindrance provided by its acyl side chain, which prevents bacterial penicillinase from attacking and opening the β-lactam ring. wikipedia.orgnih.gov

Pharmacodynamic models have been extensively utilized to establish the in vitro efficacy of this compound against various bacterial strains, notably Staphylococcus aureus. These models aim to quantify the relationship between antibiotic concentration and the resulting bacterial killing rate over time. Research has demonstrated that the killing rate of this compound is dependent on both concentration and time. fishersci.fiwikidata.org Studies determining the 50% effective concentration (EC50) for this compound against two Staphylococcus aureus strains reported values of 0.105 mg/liter and 0.121 mg/liter, respectively. fishersci.fiwikidata.org These parameters derived from in vitro pharmacodynamic models have shown satisfactory predictive capabilities for bacterial colony-forming unit (CFU) counts under exponentially decreasing concentrations in vitro (R² between 0.862 and 0.894). fishersci.fiwikidata.org

Mechanistic Investigations of this compound's Interactions with Other Compounds (Non-Clinical)

Mechanistic investigations in non-clinical settings have shed light on this compound's interactions with other antimicrobial agents and compounds. This compound has been identified as an inhibitor of AmpC β-lactamases. wikipedia.orgwikipedia.org This inhibitory activity is particularly significant in the context of antibiotic resistance. For instance, in vitro studies have demonstrated that this compound can significantly reduce the minimum inhibitory concentrations (MICs) of carbapenems (such as imipenem and meropenem) and cephalosporins (such as ceftazidime and cefepime) when combined against carbapenem-resistant Pseudomonas aeruginosa isolates. wikipedia.org The MICs of these antibiotics, which ranged from 1-256 µg/mL for carbapenems and 4-1024 µg/mL for cephalosporins when used alone, were reduced to 1-32 µg/mL and 1-512 µg/mL, respectively, in combination with this compound, indicating a potential synergistic effect attributed to this compound's AmpC β-lactamase inhibition. wikipedia.org

However, not all interactions are beneficial. Penicillinase-resistant penicillins, including this compound, have been shown to be physically and/or chemically incompatible with aminoglycosides in vitro, leading to the inactivation of aminoglycoside drugs. wikipedia.orgwikipedia.org This inactivation can also occur in serum samples obtained from patients receiving concomitant therapy, which could adversely affect the results of serum aminoglycoside assays. wikipedia.org Furthermore, bacteriostatic drugs, such as chloramphenicol, erythromycin, sulfonamides, and tetracyclines, may interfere with the bactericidal effect of this compound. wikipedia.orgmims.com This antagonism highlights the importance of understanding drug-drug interactions at a mechanistic level in preclinical research. In another instance of non-clinical interaction, quinine has been observed to decrease the antimicrobial activity of this compound in vitro, resulting in a five- to sevenfold increase in the MIC of this compound. fishersci.ca

Table 3: Effect of this compound on MICs of Other Antibiotics Against Carbapenem-Resistant Pseudomonas aeruginosa Isolates (In Vitro) wikipedia.org

Development and Validation of Chromatographic Techniques for Cloxacillin Quantification

Chromatographic techniques are the cornerstone for the analysis of this compound in bulk drug substances, pharmaceutical formulations, and biological matrices. thepharmajournal.comafricaresearchconnects.comnih.gov These methods offer high selectivity and sensitivity, allowing for the separation and quantification of this compound from related substances and degradation products. nih.govchromatographyonline.com

Advanced Sample Preparation Techniques for this compound Analysis in Complex Matrices

Effective sample preparation is a critical step to remove interfering substances and concentrate the analyte, especially when analyzing this compound in complex matrices like biological fluids, food, and environmental samples. tandfonline.commdpi.comresearchgate.net

Impurity Profiling and Degradation Product Characterization

Impurity profiling is a comprehensive process that involves the detection, identification, and quantification of impurities in a drug substance. rroij.com For this compound, this process is crucial due to its propensity to form degradation and polymerized impurities that can impact its quality and potentially lead to adverse effects. nih.gov

Recent studies have utilized advanced analytical techniques to identify and characterize impurities in this compound. A study employing reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with ion trap/time-of-flight mass spectrometry (MS) successfully elucidated the structures of 10 previously unknown impurities in this compound. nih.gov Among these, three were identified as polymerized impurities. nih.gov

Commonly identified degradation products of penicillins like this compound include penicilloic acids, which result from the hydrolysis of the β-lactam ring. Specifically for this compound, key impurities include:

This compound Penicilloic Acid (Impurity A): Formed through the hydrolysis of the β-lactam ring, which renders the molecule pharmacologically inactive.

3-(2-Chlorophenyl)-5-methylisoxazole-4-carboxylic Acid (Impurity D): This impurity arises from the cleavage of the amide bond connecting the side chain to the β-lactam core.

This compound Penicillamide (Impurity E): A degradation product resulting from the breakdown of the thiazolidine ring.

The presence of polymerized impurities is a significant concern for penicillins, including this compound, as they have been associated with allergic reactions. nih.govresearchgate.net Techniques like high-performance size exclusion chromatography (HPSEC) and two-dimensional liquid chromatography (2D-LC) have been employed to separate and characterize these high-molecular-weight impurities. researchgate.netmdpi.com

Identified this compound Impurities

The formation of impurities in this compound primarily occurs through hydrolysis and polymerization reactions. nih.gov

Hydrolysis: The β-lactam ring, a core structural feature of penicillins, is susceptible to hydrolysis, leading to the formation of the corresponding penicilloic acid. This reaction is a major degradation pathway for this compound, resulting in the inactive this compound Penicilloic Acid. The hydrolysis of the amide linkage is another degradation route, yielding the side-chain derivative, 3-(2-chlorophenyl)-5-methylisoxazole-4-carboxylic acid.

Polymerization: this compound can undergo polymerization, especially under conditions of high humidity and temperature. nih.govresearchgate.net These reactions can lead to the formation of dimers and higher-order polymers. nih.govresearchgate.net The mechanisms of polymerization are complex and can involve the opening of the β-lactam ring and subsequent reactions between this compound molecules. The presence of these polymerized impurities is a critical quality attribute to monitor due to their potential to trigger allergic responses. nih.govresearchgate.netmdpi.com

The structural elucidation of this compound impurities relies heavily on a combination of spectroscopic techniques. rroij.comijpacr.com

Nuclear Magnetic Resonance (NMR) Spectroscopy: Both ¹H and ¹³C NMR are powerful tools for determining the precise molecular structure of isolated impurities. researchgate.net Two-dimensional NMR techniques can provide further detailed information about the connectivity of atoms within the molecule.

Fourier-Transform Infrared (FT-IR) Spectroscopy: FT-IR spectroscopy is instrumental in identifying the functional groups present in the impurity molecules. ijpacr.comresearchgate.net The presence or absence of characteristic absorption bands, such as the β-lactam carbonyl stretch, can confirm degradation pathways like hydrolysis. researchgate.net

Mass Spectrometry (MS): Often coupled with liquid chromatography (LC-MS), mass spectrometry provides crucial information about the molecular weight of the impurities. nih.govnih.gov High-resolution mass spectrometry (HRMS) can help determine the elemental composition, further aiding in structure elucidation. nih.gov

These spectroscopic methods, often used in conjunction, provide the necessary data to definitively identify and characterize the structure of unknown impurities. rroij.comnih.gov

Stability Studies and Degradation Kinetics in Controlled Environments

Stability studies are essential to understand how the quality of this compound varies with time under the influence of environmental factors such as temperature, humidity, and pH. mdpi.com These studies are crucial for determining appropriate storage conditions and shelf-life.

The degradation kinetics of this compound have been investigated under various conditions. In aqueous solutions, the degradation of penicillins like amoxicillin has been shown to follow pseudo-first-order kinetics. nih.gov The degradation rate is significantly influenced by pH, with both specific-acid and specific-base catalysis observed. nih.gov

A study on the degradation kinetics of this compound sodium revealed that the degradation process is dependent on the solvent system. researchgate.net In methanol, the degradation followed zero-order kinetics, while the addition of butyl acetate shifted the kinetics to first-order and accelerated the degradation. researchgate.net The pH of the system also played a critical role in the degradation rate. researchgate.net The apparent activation energy for the degradation of this compound in an aqueous solution was determined to be 80.34 ± 5.88 kJ mol⁻¹. researchgate.net

Forced degradation studies, where the drug substance is exposed to stress conditions such as acid, base, oxidation, heat, and light, are performed to identify potential degradation products and establish the degradation pathways. mdpi.comneliti.com For instance, a study on amoxicillin and this compound in a combined dosage form utilized RP-HPLC to assess their stability under various stress conditions, demonstrating the method's specificity for the drugs in the presence of their degradation products. neliti.com

The stability of this compound formulations can also be influenced by excipients. In a study on fluthis compound, a closely related isoxazolyl penicillin, it was found that the choice and amount of excipient significantly impacted the stability of the drug in a high-humidity environment. innovareacademics.in

Kinetic Parameters of this compound Degradation

Exploration of Novel Therapeutic Strategies to Counter Antimicrobial Resistance

Antimicrobial resistance (AMR) is a significant global health threat, driven by various bacterial mechanisms including enzymatic degradation (e.g., beta-lactamases), modifications to drug targets (such as PBPs), altered cell membrane permeability, and the overexpression of efflux pumps mims.commims.comoup.commims.comnih.gov. While cloxacillin is effective against beta-lactamase-producing Staphylococcus species, it is generally not effective against methicillin-resistant Staphylococcus aureus (MRSA), which remains a major clinical challenge wikipedia.orgwikipedia.orgflybase.orgwikidata.org.

Future research directions aim to circumvent these resistance mechanisms by exploring novel therapeutic strategies. This includes the investigation of compounds that can potentiate this compound's activity against resistant strains. For instance, studies have shown that certain dihydropyridine derivatives can enhance the antibacterial effect of this compound against this compound-resistant MRSA strains. One such compound, 6g, demonstrated a 329% potentiation of this compound's activity against MRSA1 at a concentration of 1000 µ g/disc flybase.orgontosight.ai. This suggests a promising avenue for developing adjunctive therapies that restore or augment this compound's effectiveness. Other emerging approaches to combat AMR include the development of biofilm-disrupting agents, quorum-sensing inhibitors, and advanced nanoparticle-based drug delivery systems, all of which could potentially be combined with or enhance the action of this compound mims.com.

Application of Advanced Computational and Bioinformatic Tools in this compound Research

Advanced computational and bioinformatic tools are increasingly indispensable in modern drug discovery and antimicrobial resistance research, offering efficient ways to understand drug mechanisms, predict interactions, and design new compounds. In this compound research, molecular docking studies have been extensively utilized to analyze its binding characteristics with bacterial proteins. These studies have investigated this compound's interaction with targets such as the AmpC beta-lactamase receptor (1FCM) and various penicillin-binding proteins (PBPs) fishersci.fimims.comwikipedia.orgfishersci.ca.

Computational methods can predict the binding affinities of this compound and its derivatives, as well as identify key amino acid residues involved in these interactions. For example, in silico studies have revealed that this compound exhibits strong binding affinities for the PBPs of Neisseria sicca and Escherichia coli mims.com. Tools like AutoDock Vina facilitate these docking simulations, allowing researchers to explore numerous structural modifications to this compound and predict their potential impact on binding affinity and efficacy fishersci.fi.

Beyond molecular docking, broader bioinformatics approaches are applied for the in silico detection and characterization of antimicrobial resistance phenotypes and genes. These tools process high-throughput sequencing data from clinical and environmental samples, employing methods such as alignment-based analysis, k-mer based genomic signatures, and machine learning algorithms nih.govnih.govnih.gov. The integration of structural biology databases (e.g., Protein Data Bank (PDB), Structural Classification of Proteins (SCOP), InterPro, AlphaFold DB) with computational modeling techniques enables a deeper understanding of protein structures and their interactions with this compound, aiding in the rational design of new antibacterial agents nih.gov.

Development of this compound-Based Combination Therapies for Enhanced Efficacy

Studies have demonstrated that combining this compound with daptomycin can lead to enhanced efficacy against MRSA bacteremia and foreign-body infections. This combination has been shown to improve the bactericidal activity of daptomycin, especially against bacteria in the log phase of growth wikipedia.orgwikipedia.orgfishersci.cafishersci.ca. While the exact mechanism is not fully elucidated, it is hypothesized that daptomycin's action on the Gram-positive cell membrane may improve the activity of beta-lactams like this compound against MRSA wikipedia.org.

In another experimental model of Staphylococcus aureus endocarditis, the addition of fosfomycin or this compound to daptomycin significantly improved the efficacy of daptomycin in sterilizing vegetations, outperforming this compound monotherapy or this compound combined with gentamicin rcsb.org. Furthermore, this compound has been shown to reduce the minimum inhibitory concentrations (MICs) of carbapenems (like imipenem and meropenem) and cephalosporins (like ceftazidime and cefepime) in carbapenem-resistant Pseudomonas aeruginosa isolates, particularly when AmpC beta-lactamase overexpression is a contributing resistance mechanism fishersci.ca.

Beyond traditional antibiotics, multi-drug combinations involving this compound are being investigated. For example, a three-drug combination of this compound, thioridazine, and tetracycline demonstrated synergistic anti-Staphylococcal activity in vitro by inhibiting bacterial efflux pumps and autolysins rcsb.org. The strategic use of beta-lactamase inhibitors, such as clavulanic acid and avibactam, in combination with beta-lactam antibiotics is a well-established approach to restore antibiotic efficacy by neutralizing the enzymes that degrade them mims.commims.comsynhet.com. While this compound itself is beta-lactamase resistant, its inclusion in broader combination regimens can contribute to a more robust and effective therapeutic approach against complex resistant infections.

Innovations in this compound Synthesis and Formulation Technologies

Innovations in synthesis and formulation technologies are critical for improving the therapeutic profile of this compound, addressing challenges such as bioavailability, stability, and targeted delivery.

Research has focused on developing novel drug delivery systems for this compound. For instance, this compound-loaded Poly(D,L-Lactide-Co-Glycolide) Acid (PLGA) nanoparticles have been synthesized using methods like single emulsion solvent evaporation wikidata.org. These nanoparticles aim to enhance the antimicrobial efficiency of this compound, particularly against intracellular bacteria and under acidic pH conditions, by potentially co-localizing the drug with the bacteria within intracellular compartments wikidata.org.

In the realm of oral formulations, efforts have been made to develop tasteless dispersible tablets containing this compound, often in combination with other antibiotics like ampicillin. Techniques such as incorporating microspheres for taste masking and utilizing wet granulation methods are employed to achieve patient acceptability and rapid disintegration researchgate.netuni.lu.

To address issues of low bioavailability and short plasma half-life, the development of gastroretentive microspheres of this compound has been explored. Polymers like Eudragit RS 100 and Kollicoat MAE 100P are used to create these microspheres, aiming for a controlled release of the drug over an extended period, thereby improving its pharmacokinetic profile dsmz.de.

Furthermore, novel synthetic approaches are being investigated to produce this compound sodium with higher purity, reduced impurity content, enhanced stability, and shorter production times mims.com. In addition to traditional synthesis, polymerizable cholinium-based antibiotics have been designed to act as polymer carriers for this compound, leading to the creation of single and dual-drug delivery systems that can ionically bond the drug anion to the polymer matrix wikipedia.org. The synthesis of molecularly imprinted polymers (MIPs) for the selective solid-phase extraction of this compound also highlights advancements in purification and analytical technologies relevant to its production and quality control nih.gov.