Antibacterial properties of photo-crosslinked chitosan/methacrylated hyaluronic acid nanoparticles loaded with bacitracin.

The current treatments for wounds often fail to induce adequate healing, leaving wounds vulnerable to persistent infections and development of drug-resistant microbial biofilms. New natural-derived nanoparticles were studied to impair bacteria colonization and hinder the formation of biofilms in wounds. The nanoparticles were fabricated through polyelectrolyte complexation of chitosan (CS, polycation) and hyaluronic acid (HA, polyanion). UV-induced photo-crosslinking was used to enhance the stability of the nanoparticles. To achieve this, HA was methacrylated (HAMA, degree of modification of 20 %). Photo-crosslinked nanoparticles obtained from HAMA and CS had a diameter of 478 nm and a more homogeneous size distribution than nanoparticles assembled solely through complexation (742 nm). The nanoparticles were loaded with the antimicrobial agent bacitracin (BC), resulting in nanoparticles with a diameter of 332 nm. The encapsulation of BC was highly efficient (97 %). The BC-loaded nanoparticles showed significant antibacterial activity against gram-positive bacteria Staphylococcus aureus, Methicillin-resistant S. aureus and S. epidermidis. Photo-crosslinked HAMA/CS nanoparticles loaded with BC demonstrated inhibition of biofilm formation and a positive effect on the proliferation of mammalian cells (L929). These crosslinked nanoparticles have potential for the long-term treatment of wounds and controlled antibiotic delivery at the location of a lesion.

A classic antibiotic reimagined: Rationally designed bacitracin variants exhibit potent activity against vancomycin-resistant pathogens.

Bacitracin is a macrocyclic peptide antibiotic that is widely used as a topical treatment for infections caused by gram-positive bacteria. Mechanistically, bacitracin targets bacteria by specifically binding to the phospholipid undecaprenyl pyrophosphate (C55PP), which plays a key role in the bacterial lipid II cycle. Recent crystallographic studies have shown that when bound to C55PP, bacitracin adopts a highly ordered amphipathic conformation. In doing so, all hydrophobic side chains align on one face of the bacitracin-C55PP complex, presumably interacting with the bacterial cell membrane. These insights led us to undertake structure-activity investigations into the individual contribution of the nonpolar amino acids found in bacitracin. To achieve this we designed, synthesized, and evaluated a series of bacitracin analogues, a number of which were found to exhibit significantly enhanced antibacterial activity against clinically relevant, drug-resistant pathogens. As for the natural product, these next-generation bacitracins were found to form stable complexes with C55PP. The structure-activity insights thus obtained serve to inform the design of C55PP-targeting antibiotics, a key and underexploited antibacterial strategy.

Optimal conditions for determination of bacitracin, bacitracin zinc and bacitracin methylene disalicylate in animal feed by ultra-performance liquid tandem mass spectrometry.

An integrated method combining solid-phase extraction (SPE) with ultra-performance liquid tandem mass spectrometry (UPLC-MS/MS) has been established for quantifying bacitracin (BTC), bacitracin zinc (BZ), and bacitracin methylene disalicylate (BMD) in animal feed. A pretreatment procedure that can effectively, quickly, and simultaneously extract and purify BTC, BZ, or BMD in feed was developed for the first time through the optimization of extraction and SPE conditions. After extraction with acetonitrile + methanol + 15 % ammonia solution (1:1:1, v:v:v) and dilution with EDTA solution (1.5 mmol/L, pH 7.0), a SPE procedure was carried out with C18 cartridge. Following LC-MS/MS analysis utilized a Waters Peptide BEH C18 column with a gradient elution of 0.1 % formic acid in water/acetonitrile with. This method demonstrated a strong linear correlation (R2 > 0.9980) across a 0.01-1.0 mg/L concentration span, based on a matrix-matched standard curve. Satisfactory recoveries of BTC (bacitracin A, B1, B2, and B3), BZ, and BMD in different feeds were obtained from 80.7 % to 108.4 %, with relative standard deviations below 15.7 %. Low limits of quantification ranging within 7.2-20 µg/kg were achieved for bacitracin A, B1, B2, and B3. This method provided an effective and reliable detection method to prevent the addition of BTC and different BTC formulations in feeds.

Bacitracin Methylene Disalicylate (BMD) Treatment Affects Spleen Proteome in Broiler Chicks Infected with Salmonella enteritidis.

Bacitracin Methylene Disalicylate (BMD), as a feed additive to poultry diets, enhances digestion, prevents Salmonella enteritidis (SE) colonization, and treats current infections. The objective of this study was to utilize a quantitative proteomic approach to determine the effect of BMD feed additive on broiler chickens challenged with SE in the spleen proteome. At 1 d of age, chicks were randomly allocated into four groups: control with and without SE challenge (CON, n = 60; CON-SE, n = 60), BMD with and without SE challenge (BMD, n = 60; BMD-SE, n = 60). Birds in the CON-SE and BMD-SE treatment were administered SE inoculum by oral gavage. On day three and day seven post-gavage, the spleen was collected aseptically from birds in each treatment group (CON, n = 4/day; CON-SE, n = 4/day; BMD, n = 4/day; BMD-SE, n = 4/day). Proteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed an increased abundance of 115 proteins and decreased of 77 due to the BMD. Proteins that decreased in abundance were enriched for fibrinogen complex and extracellular space, whereas proteins that increased in abundance were enriched for proteasome-mediated ubiquitin-dependent protein catabolic process and mitochondrion. Analysis of the interaction between BMD and the Salmonella challenge found 230 differentially abundant proteins including proteins associated with RNA binding, spliceosome, protein transport, and cell adhesion among the upregulated proteins, and those associated with protein folding, carbon metabolism, biosynthesis of nucleotide sugars, response to oxidative stress, positive regulation of NIK/NF-kappaB signaling, and inflammatory response among the downregulated proteins. The impact of BMD treatment on spleen proteome indicates an anti-apoptotic effect. BMD also modified the response of the spleen to the SE challenge with a marked decrease in proteins that prompt cytokine synthesis and an increase in proteins involved in the selective removal of unfolded proteins.

Bacitracin-resistant Staphylococcus aureus induced in chicken gut and in vitro under bacitracin exposure.

It is common knowledge that prolonged and excessive use of antibiotics can lead to antimicrobial resistance. However, the characteristics and mechanism of resistant-bacteria induced by clinically recommended and prophylactic dose drugs remain largely unclear. This study aimed to observe the trends of drug resistance of the bacitracin-susceptible Staphylococcus aureus strain FS127 under exposure to bacitracin (BAC), which were induced in vitro and in chicken gut. Antimicrobial susceptibility testing was used to detect the susceptibility of S. aureus induced in vitro and in the chicken gut to gentamicin, chloramphenicol, tetracycline, doxycycline, penicillin and chloramphenicol. The research results showed that bacitracin could induce drug resistance in S. aureus both in vitro and in vivo. The bacitracin-resistance rate of S. aureus isolated from chicken gut was positively correlated with the dose and time of bacitracin administration. The findings revealed that bacitracin-resistant S. aureus induced in vivo had enhanced susceptibility to chloramphenicol but no such change in vitro. Meanwhile, RT-qPCR assay was used to detect the expression levels of vraD, braD, braR and bacA in typical strains with different bacitracin-resistance levels. It was found that BacA may play a key role in the bacitracin resistance of S. aureus. In conclusion, this work reveals the characteristics and mechanism of bacitracin-resistant S. aureus induced by bacitracin in vivo and in vitro respectively.

Assessing the Risk of Antimicrobial Resistant Enterococcal Infections in Humans Due to Bacitracin Usage in Poultry.

Bacitracin is an antimicrobial used in the feed or water of poultry in the U.S. for the prevention, treatment, and control of clostridial diseases such as necrotic enteritis. Concern has been raised that bacitracin can select for antimicrobial-resistant bacteria that can be transmitted to humans and subsequently cause disease that is more difficult to treat because of the resistance. The objective of the present study was to perform a quantitative risk assessment (QRA) to estimate the potential risk in the U.S. of human infection with antimicrobial-resistant Enterococcus faecalis and E. faecium derived from chicken and turkey products as a result of bacitracin usage in U.S. poultry. The modeling approach estimated the annual number of healthcare-associated enterococcal infections in the U.S. that would be resistant to antimicrobial therapy and that would be derived from poultry sources because of bacitracin use in poultry. Parameter estimates were developed to be "maximum risk" to overestimate the risk to humans. While approximately 60% of E. faecalis and E. faecium derived from poultry were predicted to possess bacitracin resistance based on the presence of the bcrABDR gene locus, very few human-derived isolates possessed this trait. Furthermore, no vancomycin or linezolid-resistant strains of E. faecalis or E. faecium were detected in poultry sources between the years 2002 and 2019. The model estimated the number of antimicrobial-resistant E. faecalis and E. faecium cases per year that might resist therapy due to bacitracin use in poultry as 0.86 and 0.14, respectively, which translates to an annual risk estimate for E. faecalis of less than 1 in 350 million and for E. faecium of less than 1 in 2 billion for members of the U.S. population. Even with the use of risk-maximizing assumptions, the results indicate that there is a high probability that the use of bacitracin according to label instructions in U.S. poultry presents a negligible risk to human health.

The Bacillus subtilis cell envelope stress-inducible ytpAB operon modulates membrane properties and contributes to bacitracin resistance.

Antibiotics that inhibit peptidoglycan synthesis trigger the activation of both specific and general protective responses. σM responds to diverse antibiotics that inhibit cell wall synthesis. Here, we demonstrate that cell wall-inhibiting drugs, such as bacitracin and cefuroxime, induce the σM-dependent ytpAB operon. YtpA is a predicted hydrolase previously proposed to generate the putative lysophospholipid antibiotic bacilysocin (lysophosphatidylglycerol), and YtpB is the branchpoint enzyme for the synthesis of membrane-localized C35 terpenoids. Using targeted lipidomics, we reveal that YtpA is not required for the production of lysophosphatidylglycerol. Nevertheless, ytpA was critical for growth in a mutant strain defective for homeoviscous adaptation due to a lack of genes for the synthesis of branched chain fatty acids and the Des phospholipid desaturase. Consistently, overexpression of ytpA increased membrane fluidity as monitored by fluorescence anisotropy. The ytpA gene contributes to bacitracin resistance in mutants additionally lacking the bceAB or bcrC genes, which directly mediate bacitracin resistance. These epistatic interactions support a model in which σM-dependent induction of the ytpAB operon helps cells tolerate bacitracin stress, either by facilitating the flipping of the undecaprenyl phosphate carrier lipid or by impacting the assembly or function of membrane-associated complexes involved in cell wall homeostasis.IMPORTANCEPeptidoglycan synthesis inhibitors include some of our most important antibiotics. In Bacillus subtilis, peptidoglycan synthesis inhibitors induce the σM regulon, which is critical for intrinsic antibiotic resistance. The σM-dependent ytpAB operon encodes a predicted hydrolase (YtpA) and the enzyme that initiates the synthesis of C35 terpenoids (YtpB). Our results suggest that YtpA is critical in cells defective in homeoviscous adaptation. Furthermore, we find that YtpA functions cooperatively with the BceAB and BcrC proteins in conferring intrinsic resistance to bacitracin, a peptide antibiotic that binds tightly to the undecaprenyl-pyrophosphate lipid carrier that sustains peptidoglycan synthesis.

Analysing polypeptide antibiotics residues in animal muscle tissues: The crucial role of HRMS.

A confirmatory method for the determination of polypeptide antibiotics (bacitracin, colistin, and polymyxin B) in muscle samples has been developed. Extraction is performed with acidified methanol, and a clean-up step by solid-phase extraction with polymeric cartridges is applied. Separation by ultra-high performance liquid chromatography (UHPLC) is carried out using a solid core C18 column and gradient elution with water/acetonitrile containing 0.2% formic acid. High-resolution mass spectrometry (HRMS) (Q-Orbitrap) detection using different working modes has proved to be highly advantageous in eliminating interfering signals from endogenous matrix components. The analytical method has been successfully validated according to Commission Regulation 2021/808/EU and is currently used in a public health laboratory involved in veterinary medicines residue surveillance activities.

Comparative impact of bacitracin and select feed additives in the feeding program of Lohmann LSL-Lite pullets at the onset of lay through to 31 weeks of age.

There are limited investigations on the role of feed additives in easing transition of pullets to egg production phase. We investigated the effects of supplementation of bacitracin methylene disalicylate (BMD) and select feed additives (myristic acid [MA], benzoic acid [BA], and Aspergillus niger probiotic [PRO]) in feeding program for pullets from the onset of lay through to 31 weeks of age (woa). Parameters measured included hen-day egg production (HDEP), feed intake (FI), feed conversion ratio (FCR), egg quality characteristics, ceca microbial activity, apparent retention of components, and plasma metabolites. A total of 1,200 Lohmann LSL Lite pullets were procured at 18 woa and placed in enriched cages (30 birds/cage) based on body weight (BW) and allocated to five diets. The diets were a basal diet formulated to meet specifications or basal mixed with either BMD, MA, BA, or PRO. Birds had free access to feed and water throughout the experiment. Between 18 and 20 woa, birds fed BMD ate a similar (P > 0.05) amount of feed to BA birds, but more (P = 0.0003) than birds fed basal, MA, or PRO diets. Basal birds had lower HDEP (P = 0.001) and lighter eggs (P < 0.0001) than birds fed any of the feed additives between 21 and 31 woa. The basal hens had a higher (P = 0.009) abundance of Escherichia coli than birds fed BMD, BA, and PRO diets. Consequently, BMD, BA, and PRO birds had a higher (P = 0.011) Lactobacilli: E. coli ratio (LER) than hens fed the basal diet. Specifically, relative to basal-fed hens, the LER of the BMD, MA, BA, and PRO hens was higher by 37%, 21%, 26%, and 45%, respectively. Moreover, birds fed PRO tended to have a higher concentration of ceca digesta acetic acid (P = 0.072) and a lower concentration of isobutyric acid (P = 0.096). In conclusion, supplementing pullet diets with broad-spectrum antibiotics or feed additives (MA, BA, and PRO) had a positive impact on FI, and egg production linked to modulation of indices of gut health. The results suggested supplementing feed additives in feeding programs for pullets at the onset of lay can bolster productivity outcomes.

Bacitracin agar vs. oleandomycin disk supplemented chocolate agar for the recovery of Haemophilus influenzae in diagnostic samples: A prospective comparison.

Haemophilus influenzae is an important pathogen able to cause various forms of respiratory and invasive disease. To provide high sensitivity for detection, culture media must inhibit growth of residential flora from the respiratory tract. This study aimed to identify and compare the diagnostic and economic advantages of using bacitracin containing selective agar (SEL) or oleandomycin disk supplemented chocolate agar (CHOC). Growth and semi-quantitative abundance of H. influenzae and growth suppression of residential flora was prospectively assessed in a 28-week period. H. influenzae was identified in 164 (5 %) of all included samples: CHOC and SEL, CHOC only, and SEL only were positive in 95, 24, and 45 cases. Diagnostic superiority of SEL was primarily attributable to the results of throat swabs. However, on average, € 200 had to be spent for the detection of each additional isolate that was recovered only because of additional incubation on SEL.

Bacitracin enhances ceftriaxone susceptibility of the high-level ceftriaxone-resistant gonococcal FC428 clone.

IMPORTANCE: Ceftriaxone-based antimicrobial therapies for gonorrhea are threatened by waning ceftriaxone susceptibility levels and the global dissemination of the high-level ceftriaxone-resistant gonococcal FC428 clone. Combination therapy can be an effective strategy to restrain the development of ceftriaxone resistance, and for that purpose, it is important to find an alternative antimicrobial to replace azithromycin, which has recently been removed in some countries from the recommended ceftriaxone plus azithromycin dual-antimicrobial therapy. Ideally, the second antimicrobial should display synergistic activity with ceftriaxone. We hypothesized that bacitracin might display synergistic activity with ceftriaxone because of their distinct mechanisms targeting bacterial cell wall synthesis. In this study, we showed that bacitracin indeed displays synergistic activity with ceftriaxone against Neisseria gonorrhoeae. Importantly, strains associated with the FC428 clone appeared to be particularly susceptible to the bacitracin plus ceftriaxone combination, which might therefore be an interesting dual therapy for further in vivo testing.

Impacts of a DUF2207 Family Protein on Streptococcus mutans Stress Tolerance Responses and Biofilm Formation.

Locus SMU.243 in Streptococcus mutans was annotated as a member of the DUF2207 family proteins highly conserved in all bacteria but with unknown function. To investigate its role in S. mutans physiology, a SMU.243-deficient mutant was constructed using allelic exchange mutagenesis, and the impacts of SMU.243 deletion on bacterial growth, stress tolerance response, and biofilm formation were analyzed. Compared to the wild-type UA159, S. mutans lacking SMU.243 displayed a reduced growth rate and a reduced overnight culture density (p < 0.01) when grown at low pH and in the presence of methyl viologen. Relative to the parent strain, the deficient mutant also had a reduced survival rate following incubation in a buffer of pH 2.8 (p < 0.01) and in a buffer containing hydrogen peroxide at 58 mM after 60 min (p < 0.001) and had a reduced capacity in biofilm formation especially in the presence of sucrose (p < 0.01). To study any ensuing functional/phenotypical links between SMU.243 and uppP, which is located immediately downstream of SMU.243 and encodes an undecaprenyl pyrophosphate phosphatase involved in recycling of carrier lipid undecaprenyl phosphate, a uppP deficient mutant was generated using allelic exchange mutagenesis. Unlike the SMU.243 mutant, deletion of uppP affected cell envelope biogenesis and caused major increases in susceptibility to bacitracin. In addition, two variant morphological mutants, one forming rough colonies and the other forming mucoid, smooth colonies, also emerged following the deletion of uppP. The results suggest that the SMU.243-encoded protein of the DUF2207 family in S. mutans plays an important role in stress tolerance response and biofilm formation, but unlike the downstream uppP, does not seem to be involved in cell envelope biogenesis, although the exact roles in S. mutans' physiology awaits further investigation.

Probing the mechanism of reduced in vivo potency of insulin detemir.

BACKGROUND: Insulin detemir (IDet) is an insulin analog used to treat diabetes. IDet shows full efficacy but reduced potency compared to human insulin (HI) in both man and rat. In contrast, in pigs and dogs, IDet appears to have full in vivo potency. Non-receptor mediated degradation (NRMD) has previously been suggested as an explanation for the low potency of IDet, but this hypothesis has not been investigated further until now. Bacitracin is a nonspecific protease inhibitor which we hypothesized could inhibit NRMD of IDet in rats. RESEARCH DESIGN AND METHODS: Healthy male rats instrumented with permanent catheters underwent euglycemic clamp during constant infusion of either HI or IDet at effect-matched doses with co-infusion of vehicle or bacitracin. RESULTS: Plasma concentrations of IDet increased significantly (p < 0.005) during bacitracin compared to vehicle co-infusion and the concomitant increase in glucose infusion rate (GIR, p < 0.001) required to maintain euglycemic clamp indicates that the IDet rescued from NRMD indeed was active. No significant differences were detected with co-infusions of HI with either bacitracin or vehicle. CONCLUSIONS: A large proportion of NRMD of IDet which can be inhibited by bacitracin may partly explain the reduced potency of IDet observed in rats and likely also in man.

Microbial synthesis of bacitracin: Recent progress, challenges, and prospects.

Microorganisms are important sources of various natural products that have been commercialized for human medicine and animal healthcare. Bacitracin is an important antibacterial natural product predominantly produced by Bacillus licheniformis and Bacillus subtilis, and it is characterized by a broad antimicrobial spectrum, strong activity and low resistance, thus bacitracin is extensively applied in animal feed and veterinary medicine industries. In recent years, various strategies have been proposed to improve bacitracin production. Herein, we systematically describe the regulation of bacitracin biosynthesis in genus Bacillus and its associated mechanism, to provide a theoretical basis for bacitracin overproduction. The metabolic engineering strategies applied for bacitracin production are explored, including improving substrate utilization, using an enlarged precursor amino acid pool, increasing ATP supply and NADPH generation, and engineering transcription regulators. We also present several approaches of fermentation process optimization to facilitate the industrial large-scale production of bacitracin. Finally, the challenges and prospects associated with microbial bacitracin synthesis are discussed to facilitate the establishment of high-yield and low-cost biological factories.

Formulation and Characterization of Polymeric Cross-Linked Hydrogel Patches for Topical Delivery of Antibiotic for Healing Wound Infections.

Wound healing faces significant challenges in clinical settings. It often contains a series of dynamic and complex physiological healing processes. Instead of creams, ointments and solutions, alternative treatment approaches are needed. The main objective of the study was to formulate bacitracin zinc-loaded topical patches as a new therapeutic agent for potential wound healing. A free radical polymerization technique was optimized for synthesis. Polyethylene glycol-8000 (PEG-8000) was chemically cross-linked with acrylic acid in aqueous medium, using Carbopol 934 as a permeation enhancer and tween 80 as surfactant. Ammonium persulfate and N,N'-Methylenebisacrylamide (MBA) were utilized as initiator and cross-linker. FTIR, DSC, TGA, and SEM were performed, and patches were evaluated for swelling dynamics, sol-gel analysis, in vitro drug release in various media. A Franz diffusion cell was used for the permeation study. Irritation and wound healing with the drug-loaded patches were also studied. The characterization studies confirmed the formation of a cross-linked hydrogel network. The highest swelling and drug release were observed in formulations containing highest Polyethylene glycol-8000 and lowest N,N'-Methylenebisacrylamide concentrations. The pH-sensitive behavior of patches was also confirmed as more swelling, drug release and drug permeation across skin were observed at pH 7.4. Fabricated patches showed no sign of irritation or erythema as evaluated by the Draize scale. Faster wound healing was also observed with fabricated patches compared to marketed formulations. Therefore, such a polymeric network can be a promising technology for speeding up wound healing and minor skin injuries through enhanced drug deposition.

Effects of partial or complete replacement of soybean meal with commercial black soldier fly larvae (Hermetia illucens) meal on growth performance, cecal short chain fatty acids, and excreta metabolome of broiler chickens.

Black soldier fly larvae meal (BSFLM) is receiving great attention as a rich source of protein and antimicrobials for poultry. Therefore, we evaluated the effects of partially or completely replacing soybean meal (SBM) with commercial BSFLM on growth performance, tibia traits, cecal short chain fatty acid (SCFA) concentrations, and excreta metabolomes in broiler chickens (Gallus gallus domesticus). A total of 480 day-old male Ross × Ross 708 chicks were assigned to 6 diets (8 replicates/diet): a basal corn-SBM diet with in-feed bacitracin methylene disalicylate (BMD), a corn-SBM diet without BMD (0% BSFLM), and four diets in which the SBM was substituted with 12.5, 25, 50, and 100% BSFLM. Body weight (BW), feed intake (FI) and cumulative feed conversion ratio (cFCR) were monitored on days 14, 28, and 35. Cecal SCFA levels were determined on days 14, 28, and 35. Tibia traits and excreta metabolomes were determined on day (d) 35. On d14, birds fed 12.5 and 25% BSFLM had a similar BW, FI, and cFCR as birds fed BMD (P > 0.05). On d 35, birds fed 12.5% BSFLM had a similar BW, FI and cFCR as birds fed BMD or 0% BSFLM (P > 0.05). For each phase, birds fed 100% BSFLM had a lower BW, FI and higher cFCR than birds fed BMD or 0% BSFLM (P < 0.05). On d 35, BW decreased linearly, quadratically, and cubically with increasing levels of BSFLM (P < 0.01). Overall (d 0-35), BSFLM linearly, quadratically, and cubically decreased FI and quadratically and cubically increased cFCR (P < 0.01). Quadratic responses were observed for tibia fresh weight (P = 0.049) and ash content (P = 0.022). BSFLM did not impact cecal SCFAs levels. The excreta metabolome of birds fed 100% BSFLM clustered independently from all other groups and exhibited greater levels of putatively identified methionine, lysine, valine, glutamine, histidine and lower levels of arginine as compared to all diets. Taken together, substitution of SBM with ≤25% of BSFLM in the starter phase may be used as an alternative to BMD.

Did the National Ban on Bacitracin Irrigation Affect Infection Rates in Implant-Based Breast Reconstruction? An Analysis of a National Database.

INTRODUCTION: The current standard of practice in implant-based breast reconstruction is irrigation of the mastectomy pocket with antimicrobial solution before implant placement. Prior to being banned and formally recalled in January 2020, bacitracin was a very commonly utilized antibiotic. This study characterizes the effects of the national bacitracin ban on implant-based breast reconstruction infection rates by using a nationwide database to compare complication rates before and after bacitracin was banned. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) database was queried retrospectively for all patients who underwent implant-based breast reconstruction before the bacitracin ban (2012-2019) and afterwards (2020). Demographics, comorbidities, and complications were collected. Univariate analysis and multivariate analysis were conducted to determine if there were significant changes in wound complications, local wound infections, and systemic infections between the 2 case-control matched cohorts. RESULTS: A total of 37,126 patients were in the pre-ban cohort and 6333 patients were in the post-ban cohort. Before matching, there were significant differences in race distribution, BMI, ASA class, inpatient vs. outpatient status, preoperative smoking, and preoperative diabetes mellitus (all P < .05). After case-control matching, there were 6313 patients in each cohort. Univariate analysis revealed differences in postoperative superficial and organ space surgical site infection, wound complications/infections, all cause complications, and reoperations (all P < .05). Multivariate analysis showed that patients who underwent breast reconstruction before the ban had decreased odds of having wound infections, related infections, all cause complications, and reoperations (all P < .05). CONCLUSION: This study provides a macroscopic view into the effects of the formal injectable bacitracin ban on breast reconstruction outcomes. Patients who underwent implant-based breast reconstruction after the ban of injectable bacitracin had higher odds of developing wound infections, related infections, and reoperations. More study into suitable alternatives to injectable bacitracin for surgical site antimicrobial irrigation is warranted.

Synthetic Studies with Bacitracin A and Preparation of Analogues Containing Alternative Zinc Binding Groups.

The growing threat of drug-resistant bacteria is a global concern, highlighting the urgent need for new antibiotics and antibacterial strategies. In this light, practical synthetic access to natural product antibiotics can provide important structure-activity insights while also opening avenues for the development of novel analogues with improved properties. To this end, we report an optimised synthetic route for the preparation of the clinically used macrocyclic peptide antibiotic bacitracin. Our combined solid- and solution-phase approach addresses the problematic, and previously unreported, formation of undesired epimers associated with the stereochemically fragile N-terminal thiazoline moiety. A number of bacitracin analogues were also prepared wherein the thiazoline motif was replaced by other known zinc-binding moieties and their antibacterial activities evaluated.

Formulation, In Vitro Characterization and Antibacterial Activity of Chitosan-Decorated Cream Containing Bacitracin for Topical Delivery.

(1) Background: Bacitracin is a broad spectrum antibiotic that is used against various microorganisms. Chitosan is a natural polymer that has been widely investigated as an antimicrobial agent for preventing and treating infections owing to its intrinsic antimicrobial properties, as well as its ability to effectively deliver extrinsic antimicrobial compounds to infected areas. Topical drug delivery offers important benefits for improving the therapeutic effect and reducing systemic side effects of administered compounds/drugs. The topical use of chitosan-decorated bacitracin-loaded cream improves the permeation of the drug across the skin and enhances the drug bioavailability by prolonging the residence time of the drug when applied topically, as well as producing synergistic effects and reducing the side effects of the drug. Topical chitosan-decorated cream can be a promising approach to administer the drug more efficiently and enhance the efficacy of treatment in wound healing and antibacterial activity. (2) Methods: This study was conducted to prepare, assess and investigate the synergistic antibacterial activity of a chitosan-coated bacitracin cream. The results were compared to the antibacterial activity of simple bacitracin-loaded cream. The prepared cream was evaluated for various in vitro characteristics such as rheology, pH, viscosity, drug content and antibacterial activity studies. (3) Result: The formulations were found to be stable regarding color, liquefaction and phase separation at all accelerated conditions. It was observed that with time, substantial variations in the pH of the preparations were found. The introduction of chitosan results in controlled release of the drug from the formulations. The antibacterial activity of the formulated creams was assessed with the disc diffusion method against Staphylococcus aureus(ATCC),Escherichiacoli (STCC),Pseudomonas aeruginosa(ATCC) and Bacillus cereus(ATCC). The strains, E. coli, S. aureus, P. aeruginosa and B. cereus were susceptible to 50 µg chitosan-decorated bacitracin cream, showing inhibition zones of 10 ± 0.6, 34 ± 1.5, 31 ± 0.76 and 21 ± 2.02 mm, respectively. The zones of inhibition for simple bacitracin-loaded cream were significantly smaller than chitosan-decorated cream, at 2 ± 0.2, 28 ± 0.92, 15 ± 0.5 and 11 ± 1.25 mm (ANOVA; p < 0.05), respectively. (4) Conclusion: It was observed that the zones of inhibition of simple bacitracin-loaded cream were significantly smaller than those of chitosan-decorated bacitracin-loaded cream. Chitosan synergistically improves the antimicrobial activity of bacitracin. Hence, the developed formulation was effective and should be considered as a suitable candidate for topical management of skin infections and wound healing.