Antibiotic Activity Research Articles

Evaluation of joint toxic action for antibiotics based on bacterial quorum sensing

Evaluation of joint toxic action for antibiotics based on bacterial quorum sensing

The Epiphyte Bacillus sp. G2112 Produces a Large Diversity of Nobilamide Peptides That Promote Biofilm Formation in Pseudomonads and Mycobacterium aurum.

Bacillus sp. G2112, an isolate from cucumber plants that inhibited plant pathogens, produces not only surfactins, iturins, and fengycins common to many Bacillus spp., but also a large variety of N-acyl-(depsi)peptides related to A-3302-B and nobilamides. Four known and fourteen previously unreported nobilamide peptides were characterized using high-resolution mass spectrometry, tandem mass spectrometry, and NMR. The stereochemistry of the amino acids of nobilamide peptides was determined using Marfey's method. The diversity of nobilamide peptides from Bacillus sp. G2112 resulted from the incorporation of different acyl groups and amino acids in the sequence. The peptides occur in linear or cyclic form. In addition, a truncated N-acetylpentapeptide was produced. Agar diffusion assays with selected nobilamide peptides against plant pathogens and human pathogens revealed that A-3302-B and its N-acyl homologs, A-3302-A and nobilamide J, exhibited powerful antibiotic activity (at 5 µg/hole) against Lysinibacillus sphaericus that can cause severe sepsis and bacteremia in patients. Moreover, nobilamide peptides from Bacillus sp. G2112 strongly promoted biofilm formation in the Gram-positive Mycobacterium aurum and Gram-negative pseudomonads. Structurally diverse nobilamides from Bacillus sp. G2112, whether linear or cyclic, penta and heptapeptides, induced biofilm formation, suggesting that the common N-acetyl-D-Phe-D-Leu-L-Phe-D-allo-Thr-L-Val amino acid sequence motif is important for the biofilm-inducing activity.

Teixobactin "Swapmers" with l Tail Stereochemistry Retain Antibiotic Activity.

The unusual d-l-l-d-d-l-l pattern of stereochemistry in residues 1-7 of the peptide antibiotic teixobactin is critical to its extraordinary antibiotic activity, creating an unusual amphiphilic β-sheetlike structure that is essential to its mechanism of action. The current study sought to replace the three d-amino acids in the tail with l-amino acids while maintaining amphiphilicity. We find that swapping residues d-Gln4 and d-allo-Ile5 in O-acyl isopeptide prodrugs of teixobactin permits the introduction of l-stereochemistry with retention of antibiotic activity. Nevertheless, modifying the N-terminal stereochemistry results in a loss of antibiotic activity.

Evaluation of the Disk Diffusion Test for Bacteroides fragilis Group Clinical Isolates.

Bacteroides fragilis group (BFG) isolates are the most frequently isolated gram-negative anaerobic bacteria and exhibit higher levels of antimicrobial resistance than other anaerobic bacteria. Reliable susceptibility testing is needed because of reports of resistance to the most active antibiotics. Recently, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) introduced disk zone diameter breakpoints. We evaluated the disk diffusion test (DDT) for susceptibility testing of BFG isolates compared with the agar dilution method. In total, 150 BFG isolates were collected from three institutes in Korea. The agar dilution method was conducted according to the CLSI guidelines. DDT was performed following the EUCAST guideline. Fastidious anaerobe agar supplemented with 5% defibrinated horse blood was used as the culture medium. Nine antimicrobials were evaluated: penicillin, cefoxitin, cefotetan, imipenem, meropenem, piperacillin-tazobactam, clindamycin, moxifloxacin, and metronidazole. The categorical agreement (CA) between the two methods was >90.0% for imipenem, meropenem, clindamycin, and metronidazole. However, the CA for piperacillintazobactam was low, at 83.2%. Major errors were found: 5.4% for imipenem, 7.4% for meropenem, and 12.8% for piperacillin-tazobactam. All minor errors were <10%. We propose using the area of technical uncertainty (ATU) zone-overlapping area for susceptible and resistant strains to reduce errors in the DDT. Outside the ATU, the CAs of cefoxitin, cefotetan, and piperacillin-tazobactam were >90.0%, whereas that of moxifloxacin was increased to 88.5%. The DDT can be a useful alternative antimicrobial susceptibility test for BFG isolates when using the ATU zone to reduce errors.

Itaconate induces tolerance of Staphylococcus aureus to aminoglycoside antibiotics.

Staphylococcus aureus is one of the chief pathogens that cause chronic and recurrent infections. Failure of the antibiotics to curb the infections contributes to relapse and is an important reason for the high mortality rate. Treatment failure may also be due to antibiotic tolerance. Accumulating evidence suggests that t the host immune environment plays an important role in inducing antibiotic tolerance of S. aureus, but research in this area has been limited. In this study,the minimum inhibitory concentration (MIC) of the antibiotics against S. aureus was determined using the standard broth microdilution method.The study evaluated whether itaconate induces antibiotic tolerance in S. aureus through an antibiotic bactericidal activity assay.The effect of itaconate on the growth of S. aureus was evaluated by monitoring the growth of S. aureus in medium supplemented with itaconate. Additionally, RNA sequencing and metabolomics analyses were used to determine transcriptional and metabolic changes in S. aureus when exposed to itaconate. According to the study,we found that the immune metabolite itaconate can induce tolerance in both methicillin-resistant and -susceptible S. aureus to aminoglycosides. When S. aureus was exposed to itaconate, its growth slowed down and transcriptomic and metabolomic alterations associated with decreased energy metabolism, including the tricarboxylate cycle, glycolysis, pyruvate metabolism, and arginine biosynthesis, were observed. These changes are associated with aminoglycoside tolerance. This study highlights the role of immune signaling metabolites in bacterial antibiotic tolerance and suggests new strategies to improve antibiotic treatment by modulating the host immune response and stimulating the metabolism of bacteria.

Effect of The Temperature on The Size of Inhibition Zone of the Clindamycin, Levofloxacin, Tetracycline, and Trimethoprim Activity Against Staphylococcus aureus ATCC 25923

Antibiotic sensitivity should be tested. In the sensitivity test, there are technical factors that influence the formation of the inhibition zone diameter. Based on several research one of the technical factors that affect the diameter of the inhibition in the disc diffusion method is the temperature incubation of the media, this must be examined so that it can be controlled to ensure the validity of the sensitivity test results. This study aims to determine the mean, difference, and analyze the diameter of the inhibition zone of the antibiotics namely Clindamycin, Levofloxacin, Tetracycline, and Trimethoprim against Staphylococcus aureus on Mueller-Hinton agar media with incubation temperatures of 33°C, 34°C, 35°C, 36°C and 37°C for 18 hours. This research is observational, with a cross-sectional design. The data used are primary data with 100 data on the diameter of the antibiotic inhibition zone, obtained by measuring the diameter of the inhibition zone with different incubation temperatures. The selection of antibiotics is based on the mechanism of action of antibiotics inhibiting bacteria namely, the cell wall or membranes that surrounds the bacterial cell; the machineries that make the nucleic acids DNA and RNA and the machinery that produce proteins (the ribosome and associated proteins) with a range of inhibition zones based on Internal Quality Control CLSI. The data will be processed univariately and the Repeated Measure statistical test to determine the significance of the difference in the diameter of the formed inhibition zone using the ANOVA test. The results of the measurement of the inhibition zone diameter on the incubation temperature variation showed a significant difference with p-value 0.000 for Levofloxacin, Tetracycline and Trimethoprim, while for p-value Clindamycin is 0.010. Levofloxacin, Tetracycline, and Trimethoprim antibiotics, the higher the incubation temperature, the average diameter of the inhibition zone is smaller, while for Clindamycin the higher the incubation temperature, the higher the average diameter of the inhibition zone is the same. There is an effect of incubation temperature volume on the diameter of the antibiotic inhibition zone in the disc diffusion method antibiotic sensitivity test. The research indicates that incubation temperature affects the diameter of the antibiotic inhibition zone in disc diffusion tests, underscoring the need for standardized and precise testing conditions to ensure accurate and reliable antibiotic sensitivity results.

Synergistic Activity of Antibiotics and Bio Active Plant Extract: Astudy Against Mdr Gram Negative Bacteria in Kirkuk City

Increasing multidrug resistance (MDR) is becoming a problematic issue worldwide. Finding alternatives to cope with this rising problem is becoming crucial for community healthcare. The present study aimed to investigate the antibacterial activityCopper oxide nanoparticles (CuONPs) synthesised using hawthorn fruit extract against different MDR gram-negative bacteria isolates. CuoNPs were synthesized from Fresh hawthorn fruits (Crataegus). The biosynthesized copper oxide nanoparticles were Characterization of the synthesised nanoparticles was performed using UV-visible spectroscopy, Scanning Electron Microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD) to confirm CuONP production and assess their properties. Antibacterial activity was determined by disc diffusion and the healthy diffusion method. The considerable inhibitory action of hawthorn fruit extract was observed in gram-negative bacteria isolates. Also, the green synthesised CuoNPs demonstrated remarkable antibacterial activity against two human pathogenic bacteria when combined with commercially available antibiotics. The current study suggested that CuoNPs have become an essential approach for nanobiotechnology applications in the development of antibacterial treatments for different bacterial infections, particularly for non-treatable antibiotic resistance pathogen.

Novel nanoconjugates of metal oxides and natural red pigment from the endophyte Monascus ruber using solid-state fermentation

BackgroundAntimicrobial resistance has emerged as a major global health threat, necessitating the urgent development of new antimicrobials through innovative methods to combat the rising prevalence of resistant microbes. With this view, we developed three novel nanoconjugates using microbial natural pigment for effective application against certain pathogenic microbes.ResultsA natural red pigment (RP) extracted from the endophyte Monascus ruber and gamma rays were applied to synthesize RP-ZnO, RP-CuO, and RP-MgO nanoconjugates. The synthesized nanoconjugates were characterized by different techniques to study their properties. The antimicrobial potential of these nanoconjugates was evaluated. Moreover, the antibiofilm, protein leakage, growth curve, and UV light irradiation effect of the synthesized nanoconjugates were also studied. Our results confirmed the nano-size, shape, and stability of the prepared conjugates. RP-ZnO, RP-CuO, and RP-MgO nanoconjugates showed broad antimicrobial potential against the tested bacterial and fungal pathogens. Furthermore, the RP-ZnO nanoconjugate possessed the highest activity, followed by the RP-CuO against the tested microbes. The highest % inhibition of biofilm formation by the RP-ZnO nanoconjugate. Membrane leakage of E. coli and S. aureus by RP-ZnO nanoconjugate was more effective than RP-MgO and RP-CuO nanoconjugates. Finally, UV light irradiation intensified the antibiotic action of the three nanoconjugates and RP-ZnO potential was greater than that of the RP-MgO, and RP-CuO nanoconjugates.ConclusionThese findings pave the way for exploiting the synthesized nanoconjugates as potential materials in biomedical applications, promoting natural, green, and eco-friendly approaches.

Mycobacteriophages and Their Applications.

Mycobacterial infections caused by tuberculous and non-tuberculous strains pose significant treatment challenges, especially among immunocompromised patients. Conventional antibiotic therapies often fail due to bacterial resistance, highlighting the need for alternative therapeutic strategies. Mycobacteriophages are emerging as promising candidates for the treatment of mycobacteria. This review comprehensively explores phage isolation, characterization, and clinical applications. Despite the need for more extensive in vitro and in vivo studies, existing evidence shows their efficacy against both sensitive and antibiotic-resistant mycobacterial strains, even under disease-mimicking conditions, particularly when used in cocktails to minimize resistance development. Mycobacteriophages can be engineered and evolved to overcome limitations associated with lysogeny and narrow host range. Furthermore, they exhibit activity in ex vivo and in vivo infection models, successfully targeting mycobacteria residing within macrophages. Delivery methods such as bacterial and liposomal vectors facilitate their entry into human cells. Considering the potential for phage-treatment-induced bacterial resistance, as described in this review, the combination of mycobacteriophages with antibiotics shows efficacy in countering mycobacterial growth, both in the laboratory setting and in animal models. Interestingly, phage-encoded products can potentiate the activity of relevant antibiotics. Finally, the application of phages in different compassionate cases is reported. The positive outcomes indicate that phage therapy represents a promising solution for the treatment of antibiotic-resistant mycobacteria.

A quantitative approach to measure and predict microbiome response to antibiotics.

Antibiotics are potent influencers of the human microbiome and can be a source for enduring dysbiosis and antibiotic resistance in healthcare. Existing microbiome data analysis methods can quantify perturbations of bacterial communities but cannot evaluate whether the differences are aligned with the expected activity of a specific antibiotic. Here, we present a novel method to quantify and predict antibiotic-specific microbiome changes, implemented in a ready-to-use software package. This has the potential to be a critical tool to broaden our understanding of the relationship between the microbiome and antibiotics.

Source elimination of antibiotic resistance risk in aquaculture water by VUV/sulfite pretreatment

Antibiotic resistance risk in the aquaculture industry is increasing with the excessive consumption of antibiotics. Although various efficient technologies for the degradation of antibiotics are available, the potential risk from antibiotic resistance in treated waters is often overlooked. This study compared the risks of antibiotic resistance in anaerobic sludge fed with pretreated florfenicol (FLO) containing wastewater after four UV or vacuum UV (VUV)-driven ((V)UV-driven) pretreatments, and established the VUV/sulfite recirculating water system to validate the effect of controlling the antibiotic resistance risk in the actual aquaculture water. Metagenomics sequencing revealed that a remarkable decrease in the abundance of antibiotic resistance genes (ARGs) was observed in four different pretreated groups, and results among the four pretreated groups were sorted in descending order based on ARG abundance: UV > VUV > UV/sulfite > VUV/sulfite. The low abundance of ARGs from VUV/sulfite group was close to that in the CK group (wastewater without FLO and without any pretreatments), which was 0.41 copies/cell. From the perspective of the temporal changes in the relative abundance of floR, the abundance in VUV/sulfite group remained lower than 11.67 ± 0.73 during the cultivation time. Additionally, microbial diversity analysis found that Proteobacteria and Firmicutes were major carriers of ARGs. Two species from Burkholderiaceae and Rhodocyclales were identified as potential co-hosts to spread by the correlation analysis of the abundances between floR or intI1 and the top 50 genera. Finally, the abundances of ARGs and MGEs in the VUV/sulfite recirculating water system with actual aquaculture water were reduced by 39.15% and 46.04%, respectively, compared to that in the blank group without any pretreatment. This study verified that VUV/sulfite pretreatment system could effectively control the antibiotic resistance risk of ARGs proliferation and transfer in aquaculture water. Furthermore, the study demonstrated that the reduction of antibiotic antibacterial activity plays an important role in the source control of resistance risk.

Model-based translation of results from in vitro to in vivo experiments for afabicin activity against Staphylococcus aureus.

Translation of experimental data on antibiotic activity typically relies on pharmacokinetic/pharmacodynamic (PK/PD) indices. Model-based approaches, considering the full antibiotic killing time course, could be an alternative. To develop a mechanism-based modelling framework to assess the in vitro and in vivo activity of the FabI inhibitor antibiotic afabicin, and explore the ability of a model built on in vitro data to predict in vivo outcome. A PK/PD model was built to describe bacterial counts from 162 static in vitro time-kill curves evaluating the effect of afabicin desphosphono, the active moiety of the prodrug afabicin, against 21 Staphylococcus aureus strains. Combined with a mouse PK model, outcomes of afabicin doses of 0.011-190 mg/kg q6h against nine S. aureus strains in a murine thigh infection model were predicted, and thereafter refined by estimating PD parameters. A sigmoid Emax model, with EC50 scaled by the MIC described the afabicin desphosphono killing in vitro. This model predicted, without parameter re-estimation, the in vivo bacterial counts at 24 h within a ±1 log margin for most dosing groups. When parameters were allowed to be estimated, EC50 was 38%-45% lower in vivo, compared with in vitro, within the studied MIC range. The developed PK/PD model described the time course of afabicin activity across experimental conditions and bacterial strains. This model showed translational capacity as parameters estimated on in vitro time-kill data could well predict the in vivo outcome for a wide variety of doses in a mouse thigh infection model.

Computational Study of Aminoglycoside and Fluoroquinolone Antibiotics

Molecular Docking has become an important component of the drug discovery process. Since first being developed in the 1980s, advancements in the power of computer hardware and the increasing number of and ease of access to small molecule and protein structures have contributed to the development of improved methods, making docking more popular in both industrial and academic settings. In this research Molecular Docking performed on Ciprofloxacin and Streptomycin by using Auto dock and Discovery Studio Software. QSAR study revealed that substitution of different electron donating or withdrawing group at different position on Ciprofloxacin and Streptomycin. Lead nucleus elaborate change in pharmacological activity. Molecular docking done by substituting or replacing different group at different position affected the potency of drug. On addition of methyl and nitro group decreases the activity of Ciprofloxacin while replacement of Guanidino groups from streptidine ringincreases its antibiotic activity.

ATP synthase of E. coli: F1-ATPase activity is functionally decoupled from the proton-transporting complex (FO) by tributyltin

The F-type ATP synthase/ATPase (FOF1) is important for cellular bioenergetics in eukaryotes and bacteria. We recently showed that venturicidins, a class of macrolides that inhibit the proton transporting complex (FO), can also induce time-dependent functional decoupling of F1-ATPase from FO on membranes from Escherichia coli and Pseudomonas aeruginosa. This dysregulated ATPase activity could deplete bacterial ATP levels and contribute to venturicidin's capacity to enhance the bactericidal action of aminoglycosides antibiotics. We now show that a distinct type of FO inhibitor, tributyltin, also can decouple FOF1-ATPase activity of E. coli membranes. In contrast to the action of venturicidins, decoupling by tributyltin is not dependent on ATP, indicating mechanistic differences. Tributyltin disrupts the coupling role of the ε subunit of F1 but does not induce dissociation of the F1-ATPase complex from membrane-embedded FO. Understanding such decoupling mechanisms could support development of novel antibacterial compounds that target dysregulation of FOF1 functions.

Novel antimicrobial peptides based on Protegrin-1: In silico and in vitro assessments

The development of antibiotic resistance has caused significant health problems. Antimicrobial peptides (AMPs) are considered next-generation antibiotics. Protegrin-1 (PG-1) is a β-hairpin AMP with a membrane-binding capacity. This study used twelve PG-1 analogs with different amino acid substitutions. Coarse-grained molecular dynamics (MD) simulations were used to assess these analogs, and their physicochemical properties were computed using the Antimicrobial Peptide Database. Three AMPs, PEP-D, PEP-C, and PEP-H, were chosen and synthesized for antibacterial testing. The microbroth dilution technique and hemolytic assays evaluated the antimicrobial efficacy and cellular toxicity. The checkerboard method was used to test the combined activity of AMP and standard antibiotics. Cell membrane permeability and electron microscopy were used to evaluate the mode of action. The chemical stability of the selective AMP, PEP-D, was assessed by a validated HPLC method. PEP-D consists of 16–18 amino acid residues and has a charge of +7 and a hydrophobicity of 44 %, similar to PG-1. It can efficiently inactivate bacteria by disrupting cell membranes and significantly reducing hemolytic activity. Chemical stability studies indicated that AMP was stable at 40 °C for six months under autoclave conditions. This study could introduce the potential therapeutic application of selective AMP as an anti-infective agent.

Facile synthesis and antifungal evaluation of hypervalent organoantimony(III) and organobismuth(III) thioates with tridentate C,N,C-coordinating ligands.

In the present work, a series of organometallic thioates bearing a 5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine or -azabismocine framework were synthesized through the cross-coupling reactions of the corresponding halide precursors with thiols and disulfides at room temperature. The former transformation can be achieved under additive-free conditions, and mild dithiothreitol (DTT) is the only additive in the latter. Both methods feature simple operation, a broad substrate scope, and good reaction yields. Antifungal assays showed that the synthesized organobismuth(III) thioates possess significantly higher antibiotic activity against Candida albicans than clinical fluconazole, while the inhibitory effects of Sb-sulfenylated products are low to negligible. Furthermore, the antibiofilm potential of such Bi-S bond-containing compounds was discovered as well.

In vitro Tolerance of Staphylococcus haemolyticus and Candida albicans Biofilms to Dalbavancin and Anidulafungin

Background: Concerns about infections resulting from bacterial biofilm formation in invasive devices such as catheters and prostheses are becoming widespread in the public health domain. Staphylococcus haemolyticus, a coagulase-negative bacterium, and Candida albicans, a yeast, have become recurrent pathogens of these diseases because their presence in these devices enhances the likelihood of infection. It is believed that these microorganisms produce biofilms, which complicate treatment and slow the patient´s recuperation. Dalba-vancin is a semisynthetic, lipoglycopeptide-class antibiotic utilized as an anti-infective agent to break down gram-positive bacteria biofilms. Anidulafungin is an echinocandin class anti-fungal medication that works very well against resistant yeast strains and removes biofilms. Objective: This study aims to examine the anti-infective agents´ tolerance to the biofilms of Staphylococcus haemolyticus and Candida albicans. Methods: Polymicrobial biofilms were grown in a CDC Biofilm Reactor (CBR) for use in in vitro experiments. Results: When dalbavancin maintained its antibiotic activities against Staphylococcus hae-molyticus in comparison with their activity against the sessile forms, the antifungal anidula-fungin lost efficacy in eliminating Candida albicans. Conclusion: The planktonic forms of microbes are examined in relation to the tolerance to these anti-infective drugs.

Small molecule produced by Photorhabdus interferes with ubiquinone biosynthesis in Gram-negative bacteria.

The spread of resistant pathogens has led to the antimicrobial resistance crisis, and the need for new compounds acting against Gram-negative pathogens is especially acute. From a screen of Photorhabdus symbionts of nematodes, we identified 3,6-dihydroxy-1,2-benzisoxazole (DHB) that acts against a range of Gram-negative bacteria, including Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Acinetobacter baumannii. DHB had previously been isolated from other bacterial species, but its mechanism of action remained unknown. We show that DHB is unique among antimicrobials, with dual action as an inhibitor of an important enzyme, UbiA, in the biosynthesis pathway of ubiquinone and as a prodrug. DHB is a mimic of the natural substrate, and UbiA modifies it into a toxic product, contributing to the antimicrobial action of this unusual antibiotic. We also uncover the mechanism of DHB selectivity, which depends on a particular fold of the UbiA enzyme.

Efflux pumps mediate changes to fundamental bacterial physiology via membrane potential.

Efflux pumps are well known to be an important mechanism for removing noxious substances such as antibiotics from bacteria. Given that many antibiotics function by accumulating inside bacteria, efflux pumps contribute to resistance. Efflux pump inactivation is a potential strategy to combat antimicrobial resistance, as bacteria would not be able to pump out antibiotics. We recently discovered that the impact of loss of efflux function is only apparent in actively growing cells. We demonstrated that the global transcriptome of Salmonella Typhimurium is drastically altered during slower growth leading to stationary-phase cells having a remodeled, less permeable envelope that prevents antibiotics entering the cell. Here, we investigated the effects of deleting the major efflux pump of Salmonella Typhimurium, AcrB, on global gene transcription across growth. We revealed that an acrB knockout entered stationary phase later than the wild-type strain SL1344 and displayed increased and prolonged expression of genes responsible for anaerobic energy metabolism. We devised a model linking efflux and membrane potential, whereby deactivation of AcrB prevents influx of protons across the inner membrane and thereby hyperpolarization. Knockout or deactivation of AcrB was demonstrated to increase membrane potential. We propose that the global transcription regulator ArcBA senses changes to the redox state of the quinol pool (linked to the membrane potential of the bacterium) and coordinates the shift from exponential to stationary phase via the key master regulators RpoS, Rsd, and Rmf. Inactivation of efflux pumps therefore influences the fundamental physiology of Salmonella, with likely impacts on multiple phenotypes.IMPORTANCEWe demonstrate for the first time that deactivation of efflux pumps brings about changes to gross bacterial physiology and metabolism. Rather than simply being a response to noxious substances, efflux pumps appear to play a key role in maintenance of membrane potential and thereby energy metabolism. This discovery suggests that efflux pump inhibition or inactivation might have unforeseen positive consequences on antibiotic activity. Given that stationary-phase bacteria are more resistant to antibiotic uptake, late entry into stationary phase would prolong antibiotic accumulation by bacteria. Furthermore, membrane hyperpolarization could result in increased generation of reactive species proposed to be important for the activity of some antibiotics. Finally, changes in gross physiology could also explain the decreased virulence of efflux mutants.

Improving Antibiotic Use in Pediatric Preseptal Cellulitis Using a Clinical Practice Guideline.

The purpose of this study was to evaluate the impact of a clinical practice guideline (CPG) on antibiotic use and resource utilization for pediatric preseptal cellulitis. This retrospective quasiexperimental study included patients between the age of 2 months and 17 years admitted for preseptal cellulitis between January 2013 and December 2023. The preseptal cellulitis CPG was implemented in December 2020 using a multifaceted strategy that included buy-in from key stakeholders, education of frontline providers, the official CPG launch, and stakeholder check-ins. The primary outcome was the use of broad-spectrum antibiotics, including dual/triple therapy and methicillin-resistant Staphylococcus aureus (MRSA) active antibiotics. The secondary outcome was resource utilization including blood testing and imaging. Outcomes were compared pre- and post-CPG implementation using the Fisher exact test and logistic regressions. Of 236 patients meeting inclusion criteria, 175 and 61 patients composed the pre- and post-CPG cohorts, respectively. Median age (interquartile range) was 4.0 (1.8-8.3) years and 46% of the population were female. Post-CPG implementation changes in empirical antibiotic use included decreases in broad-spectrum use from 100% to 66% (P < .001), dual/triple therapy from 47% to 16% (P < .001), and MRSA active agents from 86% to 26% (P < .001). There was a decrease in complete blood count and blood culture orders from 75% to 57% (P = .014) and 32% to 18% (P = .047), respectively. Use of broad-spectrum antibiotics, including dual/triple therapy and MRSA active antibiotics for the treatment of pediatric preseptal cellulitis, decreased after CPG implementation.