Adjuvant Antibiotic Therapy Research Articles

Antimicrobial and antioxidant activities of Bromelin Propolis Spray

The indiscriminate use of antibiotics over the last 60 years has led to the development of resistant strains, leading an urgent need for new treatments, new molecules or combinations of products, safety and effective. In this regard, propolis has been used in traditional medicine due its therapeutic effects, such as antibacterial, antifungal and antiseptic, tested in vitro, in vivo and clinically. The aim of this study is to evaluate the antimicrobial and antioxidant activities of a commercial oral flavoring product against bacterial strains of clinical interest from the upper respiratory tract. Bacteria sensitivity against Bromelin Propolis Sprayâ (BPS) was evaluated using macrodilution in broth and no turbid tubes plated on TSA to confirm the results. Tested bacteria were Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa. BPS showed antimicrobial activity for all tested strains and the MBC was 2.5mg/mL. Moreover, the antioxidant activity was determined by the ability to scavenge the stable radical DPPH. 0.007% of BPS showed the maximum antioxidant effect, of 6.63mM, which demonstrate its high antioxidant effect. Therefore, these results indicate that the commercial product BPS at 0.7% can be a potential candidate as adjuvant in antibiotic therapy for upper respiratory tract disorders, due possible antimicrobial effect and its high antioxidant potential.

CLINICAL COMPLICATIONS OF MALIGNANT OTITIS EXTERNA AND SURGICAL TREATMENT

For clinical complications of malignant otitis externa and its surgical treatment, the introduction addresses a rare and serious condition, characterized by necrotizing infection of the external auditory canal, often associated with comorbidities such as decompensated diabetes mellitus. This condition requires rapid intervention due to the potential for spread to adjacent structures such as the skull and skull base, resulting in serious complications such as facial paralysis, osteomyelitis, and meningitis. Management includes broad-spectrum intravenous antibiotic therapy and, in many cases, surgical intervention to debride necrotic tissue and control infection. Objective: to synthesize recent evidence on the effectiveness of surgical treatments in malignant otitis externa, highlighting clinical outcomes and associated mortality. Methodology: it was structured according to the PRISMA checklist, using PubMed, Scielo and Web of Science databases to search for articles published in the last 10 years. Descriptors included "malignant otitis externa", "surgical treatment", "complications", "mortality" and "intervention". Inclusion criteria were clinical studies and systematic reviews that addressed surgical treatment and clinical outcomes. Exclusion criteria were studies focusing exclusively on non-surgical treatments, isolated case reports and studies with fewer than 10 participants. Results: highlighted the effectiveness of early surgical debridement in reducing mortality and serious neurological complications. The analysis revealed that adjuvant antibiotic therapy and intensive surveillance are crucial for successful management. Conclusion: the importance of a multidisciplinary approach and timely surgical intervention is emphasized to improve outcomes in patients with malignant otitis externa, highlighting the need for further studies to elucidate ideal therapeutic protocols and prevention strategies

Targeted elimination of Vancomycin resistance gene vanA by CRISPR-Cas9 system

ObjectiveThe purpose of this study is to reduce the spread of the vanA gene by curing the vanA-harboring plasmid of vancomycin-resistant using the CRISPR-Cas9 system.MethodsTwo specific spacer sequence (sgRNAs) specific was designed to target the vanA gene and cloned into plasmid CRISPR-Cas9. The role of the CRISPR-Cas system in the plasmid elimination of drug-resistance genes was verified by chemically transformation and conjugation delivery methods. Moreover, the elimination efficiency in strains was evaluated by plate counting, PCR, and quantitative real-time PCR (qPCR). Susceptibility testing was performed by broth microdilution assay and by Etest strips (bioMérieux, France) to detect changes in bacterial drug resistance phenotype after drug resistance plasmid clearance.ResultsIn the study, we constructed a specific prokaryotic CRISPR-Cas9 system plasmid targeting cleavage of the vanA gene. PCR and qPCR results indicated that recombinant pCas9-sgRNA plasmid can efficiently clear vanA-harboring plasmids. There was no significant correlation between sgRNA lengths and curing efficiency. In addition, the drug susceptibility test results showed that the bacterial resistance to vancomycin was significantly reduced after the vanA-containing drug-resistant plasmid was specifically cleaved by the CRISPR-Cas system. The CRISPR-Cas9 system can block the horizontal transfer of the conjugated plasmid pUC19-vanA.ConclusionIn conclusion, our study demonstrated that CRISPR-Cas9 achieved plasmid clearance and reduced antimicrobial resistance. The CRISPR-Cas9 system could block the horizontal transfer of plasmid carrying vanA. This strategy provided a great potential to counteract the ever-worsening spread of the vanA gene among bacterial pathogens and laid the foundation for subsequent research using the CRISPR-Cas9 system as adjuvant antibiotic therapy.

Elimination of blaKPC−2-mediated carbapenem resistance in Escherichia coli by CRISPR-Cas9 system

ObjectiveThe purpose of this study is to re-sensitive bacteria to carbapenemases and reduce the transmission of the blaKPC−2 gene by curing the blaKPC−2-harboring plasmid of carbapenem-resistant using the CRISPR-Cas9 system.MethodsThe single guide RNA (sgRNA) specifically targeted to the blaKPC−2 gene was designed and cloned into plasmid pCas9. The recombinant plasmid pCas9-sgRNA(blaKPC−2) was transformed into Escherichia coli (E.coli) carrying pET24-blaKPC−2. The elimination efficiency in strains was evaluated by polymerase chain reaction (PCR) and quantitative real-time PCR (qPCR). Susceptibility testing was performed by broth microdilution assay and by E-test strips (bioMérieux, France) to detect changes in bacterial drug resistance phenotype after drug resistance plasmid clearance.ResultsIn the present study, we constructed a specific prokaryotic CRISPR-Cas9 system plasmid targeting cleavage of the blaKPC−2 gene. PCR and qPCR results indicated that prokaryotic CRISPR-Cas9 plasmid transforming drug-resistant bacteria can efficiently clear blaKPC−2-harboring plasmids. In addition, the drug susceptibility test results showed that the bacterial resistance to imipenem was significantly reduced and allowed the resistant model bacteria to restore susceptibility to antibiotics after the blaKPC−2-containing drug-resistant plasmid was specifically cleaved by the CRISPR-Cas system.ConclusionIn conclusion, our study demonstrated that the one plasmid-mediated CRISPR-Cas9 system can be used as a novel tool to remove resistance plasmids and re-sensitize the recipient bacteria to antibiotics. This strategy provided a great potential to counteract the ever-worsening spread of the blaKPC−2 gene among bacterial pathogens and laid the foundation for subsequent research using the CRISPR-Cas9 system as adjuvant antibiotic therapy.

Long-Term Follow-Up of Open Gustilo-Anderson IIIB Fractures Treated With an Adjuvant Local Antibiotic Hydroxyapatite Bio-Composite.

Background Open fractures associated with significant tissue loss are complex and present challenges in management; they are associated with poor outcomes such as infection, non-union or amputation. This study aimed to evaluate outcomes of using an adjuvant local antibiotic hydroxyapatite bio-composite in the management of open Gustilo-Anderson IIIB fractures with up to eight years of follow-up. Methods This was a retrospective study.A total of 81 patients with Gustilo-Anderson IIIB fractures treated with "fix and flap" limb reconstruction with adjuvant local antibiotic therapy using a bio-composite carrier were reviewed. Results The mean follow-up time for all the patients, at the time of data collection, was 55.8 months. Union was achieved in 96% with a limb salvage rate of 96.3% and a deep infection rate of 3.7%. Conclusion The use of local antibiotic therapy, together with a combined orthoplastic "fix and flap" approach for Gustilo-Anderson IIIB open fractures, was found to be associated with a very low rate of metalwork infection and high union and limb salvage rates. Future studies shouldinclude some functional and quality of life outcome measures to see the efficacy of this method.

Expanding the amplitude of propolis uses

Propolis is an apiculture product containing beeswax, bee saliva and resins that bees collect from selected plants. Among the various uses of propolis by the hive, protection against natural enemies, chiefly of microbial origin, stands out, contributing to enhance the hive immunity and resistance against infection. Most known types of propolis have phenolic substances as main resin constituents. Several phenolic compounds from propolis including flavonoids, are active against bacteria. Experiments and clinical practice have shown that propolis is helpful in several areas, the antibacterial activity of propolis constituents being the driving force of the performance. Propolis extracts have been used as preservative of several kind of animal and plant derived foods, food packages, as well as in veterinary, dentistry and therapies for human care against infectious diseases. Propolis extracts have been used experimentally as adjuvant in antibiotic therapy against infectious diseases, with positive results regarding reduction of effective doses of the antibiotic, and is expected as well to reduce the risk of development of bacteria resistance against antibiotics. Hospital therapies have benefited of the association of propolis extract as adjuvant with drugs used in the treatment of COVID-19. Fostering the uses of propolis in therapies require the development of active fractions of propolis, containing a limited number of constituents and exact qualitative and quantitative constitution.

Personalised azithromycin+metronidazole (PAZAZ), in combination with standard induction therapy, to achieve a faecal microbiome community structure and metagenome changes associated with sustained remission in paediatric Crohn’s disease (CD): protocol of a pilot study

IntroductionEarly relapse in Crohn’s disease (CD) is associated with a more severe disease course. The microbiome plays a crucial role, yet strategies targeting the microbiome are underrepresented in current guidelines....

Response to Adjuvant Therapy of Granulomatous Lymphadenitis: Evidence from High Burden Country

Introduction: A granulomatous lymphadenitis is a form of inflammation of the lymph nodes that are often found. Until now, effective treatment of granulomatous lymphadenitis is still inconsistent, namely between surgical intervention, antibiotics, or adjuvant therapy. Objective: This study aims to determine the response to adjuvant therapy in patients with granulomatous lymphadenitis at RSUD Prof. Dr. Margono Soekarjo in 2019 – 2020. Methods: The research was a descriptive observational study with a retrospective approach that used secondary data from the medical records of the polyclinic and inpatient ward of RSUD Prof. Dr. Margono Soekarjo Purwokerto. Results: A total of 5 patients with tuberculous granulomatous lymphadenitis (66,7%) experienced a complete response to therapy after surgical excision followed by administration of anti-tuberculosis adjuvants an average of 6,5 ± 3,6 times and a mean duration of administration of 22,5 ± 14,7 weeks. A total of 14 patients with non-tuberculous granulomatous lymphadenitis (73,7%) experienced a complete response to therapy after surgical excision, incision drainage followed by adjuvant antibiotic therapy alone or in combination with 1-3 times and the median duration of administration was 3,5 weeks. Conclusion: Surgical excision followed by adjuvant therapy in tuberculous and non-tuberculous granulomatous lymphadenitis has good cure rates.

Development and optimization of RofA-PAMAM dendrimer complex materials for sustained drug delivery

The current indagation is observed on anatomization of drug release dynamics aiming at preceding the anti-inflammation activity of roflumilast analogue (RofA), post assemblage with dendrimer. The study pondered the development and optimization of RofA-Dendrimer complexes for sustained delivery. Many physiological and physicochemical factors, like encapsulation potency, drug loading, drug release, dissolvability, stability, and anti-inflammation activity were determined. The study results in the observation of encapsulation potency of 72.64 ± 0.189%, loading capability of 63.41 ± 0.166%, and in vitro release of RofA-4.0 G PAMAM complex was found to increase making it an appropriate candidate for sustained drug release progressively . It has been found by constructing drug release kinetics, that the release followed was a non- fickian diffusion ( n<0.89). The phase solubility diagram indicated an increment of solubility of RofA with varied dendrimer generation as well as pH. The study was initiated to prepare a suited candidate fit to scale back site-specific inflammation. Further concluding the contemplation for its sustained delivery, enhanced solubility, and potentially augmented anti-inflammation activity. • The aims of this study were to assess the potentially augmented effect of roflumilast analogue post assemblage with different generations of polyamidoamine dendrimer. • In this study, RofA-Dendrimer complexes, with RofA as the model drug, the encapsulation potency, loading capacity, in vitro drug release behavior, and stability were studied. • The effect of the concentration of varied generations of PAMAM dendrimer on the solubility of RofA has been discussed in detail. • We also examined the anti-inflammatory activity and sought to determine the inhibitory effect on protein denaturation. • The results were affirmed by the determination of n value i.e. hill coefficient with respect to the substrate concentration and rate of inhibition. • The impact of adjuvant antibiotic therapy was also explored by the means of a cytotoxicity assay.

Evaluation of ellagic acid and gallic acid as efflux pump inhibitors in strains of Staphylococcus aureus.

ABSTRACTThe Gram-positive bacterium Staphylococcus aureus is responsible for a number of infections and has been described to exhibit resistance to antibacterial drugs through different resistance mechanisms. Among these, active efflux has been shown to be one of the main mechanisms of bacterial resistance associated with S. aureus. In this sense, the aim of the present study was to evaluate the ability of ellagic acid and gallic acid to reverse resistance by inhibiting the efflux pumps present in S. aureus strains IS-58 and K2068, which express the TetK and MepA flux pumps, respectively. In addition, the toxicity of both compounds was verified in Drosophila melanogaster. Broth microdilution assays were performed to obtain the minimum inhibitory concentration (MIC) values of ellagic acid and gallic acid, whereas efflux pump inhibition was tested using a subinhibitory concentration of standard efflux pump inhibitors, gallic acid and ellagic acid (MIC/8), where the ability of these compounds to decrease the MIC of ethidium bromide (EtBr) and antibiotics was verified. Toxicity was evaluated by mortality and negative geotaxis assays in D. melanogaster. Ellagic acid and gallic acid showed no direct antibacterial activity on S. aureus strains carrying the efflux pumps TetK and MepA. However, when we looked at the results for the TetK pump, we saw that when the two acids were associated with the antibiotic tetracycline, a potentiation of the antibacterial effect occurred; this behavior was also observed for the antibiotic ciprofloxacin in the MepA strain. For the efflux pump inhibition results, only the compound gallic acid showed potentiating effect on antibacterial activity when associated with the substrate EtBr for the IS-58 strain carrying the TetK efflux pump. Ellagic acid and gallic acid showed no toxicity on the model arthropod D. melanogaster. These results indicate the possible use of gallic acid as an adjuvant in antibiotic therapy against multidrug-resistant bacteria.

Drug therapy for COVID-19 inpatients in West Nusa Tenggara hospital

Background: COVID-19 represents an unprecedented challenge to the world. Various attempts have been made to overcome COVID-19, including employing multiple drug therapies. Objective: This study was conducted to describe the drug therapy of COVID-19 inpatients at the West Nusa Tenggara Hospital in 2020. Methods: Observation of 102 patients was conducted retrospectively. Data collection was performed by analysing medical records. Results: A total of 62 out of the 102 patients (60.8%) were hospitalised more than four weeks. 57 patients (55.9%) received antivirus therapy with Oseltamivir and 47 patients (46.1%) recieved azithromycin as adjuvant antibiotic therapy. Most of the patients (63.7%) received vitamin C as an immunomodulator. A small number of patients received other supportive therapies recommended to decrease the symptoms of COVID-19. The most frequent administered therapies for COVID-19 patients hospitalised at the West Nusa Tenggara Hospital are antivirals, antibiotics, and immunomodulatory. Conclusion: The findings provide an overview of therapy use for COVID-19 inpatients in West Nusa Tenggara Hospital. There is a need to assess the effectiveness of the therapy to promote safe and effective use of drugs for COVID-19 patients in the future.

Brain Abscess of Dental Origin: A Case Report and Literature Review

Introduction: Brain abscess (BA)of dental origin is a rare but potentially life-threatening complication of odontogenic infection that requires immediate neurosurgical attention. It is defined as an encapsulated collection of pus in various areas of the brain. The infectious process spreads from the dental site and occurs in 2 ways: haematogenous route or by contiguity. Treatment should ideally be based on the etiological factor excision, combined with drainage and adjuvant antibiotic therapy. The aim of this article was to report a case of frontal brain abscess of dental origin and to review the literature. Case report: We present the case of a 36-year-old man diagnosed with a brain abscess located in the frontal lobe and caused by a periodontal lesion of the right upper first molar. The final diagnosis was established due to the availability of computed tomography and magnetic resonance imaging. Drainage of the pus combined with extraction of the tooth and antibiotic therapy was followed by an excellent recovery. Clinical and radiological features, treatment and follow-up data were documented. A review of the literature using the PubMed database was performed Conclusion: Oral infections can lead to life-threatening infections, such as brain abscesses. Early detection of this condition through correct diagnosis is essential to give the patient the best treatment; in addition, improving of the oral environment and treating oral infections is highly recommended to limit this serious condition.

ANTIBIOTIC SENSITIVITY ISOLATION EVALUATION OF MAJOR MICROORGANISMS IN PERIODONTAL TISSUE PATHOLOGY

Relevance of research The loss of effectiveness and activity of antibiotics is caused by their irrational and inappropriate use (especially in self-medication). The risk of antibiotic-resistant mikrobiom potentially be associated not only with time proceeding systemic antibacterial component in the protocol complex treatment of periodontitis but with specific combinations of different used drugs duration, efficiency previously performed mechanical treatment by open or closed curettage, especially the dosing of selected antibiotics middlemen. In – depth study and development of or personalized approaches to treatment is relevant periodontitis by individualizing the choice of appropriate antibiotics for incorporation into the algorithm of complex therapy, or universal approaches, the possibility of implementation of which depends on arguing the effectiveness of a particular combination of antibacterial agents for the vast majority of patients according to studies with sufficient samples. Study Goal is to assess the levels of antibiotic resistance and antibiotic sensitivity of isolates of major microorganisms in periodontal tissue pathology. Materials and methods of research. The research was conducted on the basis of the University Dental Clinic and private dental clinics in Uzhhorod. Determination of levels antibiotic sensitivity was carried out using a disco-diffusion method with the advice and algorithm identified by order MOH Ukraine 05.04.2007 № 167 "On Approval of guidelines" Determination of the sensitivity of microorganisms to antibiotics and in accordance with the recommendations EUCAST (Eurepean Committee on Antimicrobial Susceptibility Testing). During the testing, standard sets of discs with antibiotics and appropriate test cultures were used, which were seeded with microorganisms obtained from patients with generalized periodontitis of varying severity. Research results and their discussion. During the microbiological analysis of smears obtained from periodontal pockets of whole patients study group, microorganisms were identified, which were characterized by relatively high levels of prevalence, among them: P. gingivalis, T. forsythia, F. nucleatum, P. intermedia, A. actinomycetemcomitans, K. pneumoniae, E. coli, E. cloaceae, S. aureus, S. haemolyticus, S. viridans, S. pyogenes. A detailed analysis of the distribution of mean levels of prevalence of antibiotic sensitivity and antibiotic resistance among the analyzed isolates was performed. The results of antibioticograms differ depending on the qualitative and quantitative composition of the isolated microorganisms, their levels of antibiotic sensitivity and antibiotic resistance. This distribution of results indicates the feasibility of a patient-centered approach to treatment, based on the preliminary identification of microorganisms isolated from periodontal pockets of patients, as well as determining the levels of their antibiotic sensitivity and antibiotic resistance. Conclusion. The application of the approach with preliminary determination of antibiotic sensitivity to microorganisms cultured from the oral cavity is characterized by the relevant biological principles of conducting. Prospects for further research. The analysis of the effectiveness of adjuvant antibiotic therapy in the process of complex treatment of periodontal patients and the development of personalized approaches to the treatment of periodontitis are promising.

Pseudoaneurysm of the ascending aorta: case report of a donor-derived Pseudomonas infection in a heart transplant recipient

BackgroundMycotic aortic pseudoaneurysm is a rare complication after heart transplantation (HTX) with remarkable mortality. Intrathoracic infection is a well-documented predisposing factor for this disease. Staphylococcus aureus, Pseudomonas aeruginosa or Candida species are commonly isolated from resected specimens of the pseudoaneurysms. We demonstrate a unique case of mycotic pseudoaneurysm caused by presumably donor-derived Pseudomonas infection in a heart transplant recipient.Case presentationOur 67-year-old male patient treated with diabetes mellitus underwent HTX. The donor suffered from epiglottic abscess and pneumonia with known microorganisms including Pseudomonas, therefore both the donor and recipient received targeted antimicrobial therapy and prophylaxis. Five months after the uneventful HTX, lab test of the asymptomatic patient showed moderate, increasing C-reactive protein level without obviuos source of infection. Chest computed tomography showed a large (90 mm) saccular dilatation of the tubular portion of ascending aorta. Urgent surgical intervention identified a pseudoaneurysm, histological examinations and cultures of the resected aorta verified Pseudomonas aeruginosa aortitis, while all blood cultures remained negative. Retrospective interrogation of other transplanted organs of the donor supported donor-derived infection as the transport fluid of the right kidney grew Pseudomonas. The patient received 3 weeks of ceftazidime followed by 7 months of oral ciprofloxacin therapy. One year after the operation the patient was asymptomatic with normal inflammatory markers.ConclusionsDonor-derived infection is a rare but potential cause of aortitis. Early diagnosis, surgical intervention and adjuvant antibiotic therapy seem to be the keys to successful management of mycotic pseudoaneurysms after HTX.

Antibiotic therapy in the treatment of skin abscess meta-analysis.

Skin abscess is one of the most common infections of skin and soft tissues. Incision and drainage under local anesthesia is the mainstay of treatment. Although previous small-scale studies failed to show abenefit of antibiotics in patients with simple abscesses, the use of antibiotic therapy is still encountered in the treatment of uncomplicated skin abscesses in our practice. The purpose of our study was to evaluate existing data assessing the effect of adjuvant antibiotic therapy on abscess management. Although as indicated by two recent multicenter studies, antibiotics may provide apositive effect in the management, it is important to consider the risk of resistance associated with antibiotic overuse and to approach each case individually.

Evaluation effectiveness analysis of adjuvant antibiotic therapy in the process of complex periodontal patients treatment

Annotation. Received the large set of factors influencing the success of the results and duration of patients treatment with periodontal disease, as well as different levels of correlation of these factors it is advisable to study the use of adjuvant antibiotic therapy in the patients treatment with periodontal disease, which became the purpose of our work. To test the effectiveness of adjuvant antibiotic therapy in the complex treatment of periodontal pathology from the primary study category of patients, four groups were formed a total numbering of 240 people: the group of antibiotics without determining antibiotic sensitivity, the group of antibiotics according to rapid diagnosis, the group of antibiotics according to detailed analysis group of amoxiclav and ciprofloxacin. Mathematical and statistical data processing was performed using the application software STATISTICA 6.0. According to a meta-analysis of the effectiveness of antimicrobial and subantimicrobial antibiotic therapy as an adjuvant approach to the treatment of periodontal disease, it was found that the use of broad-spectrum agents and targeted antianaerobic drugs contributed to a more pronounced improvement in clinical attachment and reduced depth levels. Thus, antibacterial support of the active phase of the periodontal therapy protocol contributes to the clinically significant reduction of the main symptoms associated with the influence of relevant associations of periodontal pathogens, reducing the actual number of such and imbalance of their quantitative ratios in the biofilm structure as a specific factor. Reducing the volume of repeated iatrogenic surgical and conservative interventions due to the early use of antibacterial agents also contributes to the increase in cost-effectiveness, as fewer total manipulations contribute to achieving the appropriate target effect.

Structural, Vibrational and Electrochemical Analysis and Antibacterial Potential of Isomeric Chalcones Derived from Natural Acetophenone

Background: Chalcones are part of a family of small phenolic compounds that are being extensively studied for presenting a diversity of molecular structures and biological activities. In this paper, two chalcones, (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(3-nitrophenyl)prop-2-en-1-one (1), (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(4-nitrophenyl)prop-2-en-1-one (2), were synthesized by Claisen–Schmidt condensation. Methods: The molecular structures of these chalcones were determined by Nuclear Magnetic Resonance and characterized by infrared, Raman spectroscopy, and electrochemical analysis at room temperature. Vibrational wavenumbers were predicted using Functional Density Theory (DFT) calculations, and their normal modes were analyzed in terms of potential energy distribution (PED). Besides this, DFT calculations were performed to obtain the molecular orbitals and their quantum descriptors. The UV-Vis absorption spectrum of the synthesized chalcones was measured and compared with each other. In addition, analyses of antimicrobial activity and modulation of antibiotic resistance were carried out to assess the antibacterial potential of these chalcones. Results: The vibrational spectra of polycrystalline chalcones obtained by ATR-FTIR, FT-Raman and DFT calculations allowed a complete assignment of the vibrational modes, and revealed the quantum chemical parameters. Both chalcones did not show good responses when associated with the antibiotics Ciprofloxacin and Cephalexin against S. aureus 10 and E. coli 06 strains. However, a significant potentiating of the Gentamicin activity against S. aureus 10 and E. col 06 strains was observed for chalcone 2. On the other hand, when associated with Norfloxacin, an antagonistic effect was observed. The results found for EtBr suggest that, although the tested chalcones behave as efflux pump inhibitors, probably inhibiting other efflux pumps, they were not able to inhibit NorA. Thus, these synthetic chalcones are not recommended for use in association with Norfloxacin against strains of S. aureus 1199-B that overexpress the NorA gene. Conclusions: Spectroscopic data confirmed the structure of the chalcones, and chalcone 2 showed potential as an adjuvant in antibiotic therapy.

Synergistic Antibacterial Activity Between 1,4-Naphthoquinone and β-Lactam Antibiotics Against Methicillin-Resistant Staphylococcus aureus.

Aims: Currently, limited antibiotics are available to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. One approach is the use of adjuvants in antibiotic therapy. 1,4-Naphthoquinones are naturally occurring alkaloids shown to have antibacterial properties. The objective of this study is to investigate the synergy between 1,4-naphthoquinone and selected β-lactam antibiotics and to evaluate the potential use of 1,4-naphthoquinone as an adjuvant in antibiotic treatment against MRSA infections. Methods: The antibacterial activity of 1,4-naphthoquinone and plumbagin was tested against nine pathogenic bacterial strains using the microdilution broth method. The interactions between 1,4-naphthoquinone and three antibiotics (cefuroxime, cefotaxime, and imipenem) were estimated by calculating the fractional inhibitory concentration of the combination. Results: The compounds 1,4-naphthoquinone and plumbagin exhibited a broad range of bacteriostatic and bactericidal effects against both Gram-positive and Gram-negative bacteria. The interaction between 1,4-naphthoquinone and imipenem, cefuroxime, and cefotaxime was synergistic against methicillin-sensitive Staphylococcus aureus and MRSA clinical strains. Against ATCC-cultured MRSA, a synergistic effect was observed between 1,4-naphthoquinone and cefotaxime. However, combination with imipenem only produced an additive effect, and an antagonistic action was observed between 1,4-naphthoquinone and cefuroxime. Conclusions: Although individually less potent than common antibiotics, 1,4-naphthoquinone acts synergistically with imipenem, cefuroxime, and cefotaxime against MRSA clinical strains and could potentially be used in adjuvant-antibiotic therapy against multidrug resistant bacteria.

Adjuvant Antibiotic Therapy After Incision and Drainage of Cutaneous Abscesses.

Annually more than 3 million patients present to U.S. emergency departments (EDs) with cutaneous abscess, a number that has been increasing.1 Standard treatment involves incision and drainage (I&D), while routine use of systemic antibiotics after incision and drainage is controversial. Recently, two large studies found increased cure rates with systemic antibiotics after I&D compared to placebo.

AcrAB–TolC Inhibition by Peptide-Conjugated Phosphorodiamidate Morpholino Oligomers Restores Antibiotic Activity in Vitro and in Vivo

Overexpression of bacterial efflux pumps is a driver of increasing antibiotic resistance in Gram-negative pathogens. The AcrAB-TolC efflux pump has been implicated in resistance to a number of important antibiotic classes including fluoroquinolones, macrolides, and β-lactams. Antisense technology, such as peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs), can be utilized to inhibit expression of efflux pumps and restore susceptibility to antibiotics. Targeting of the AcrAB-TolC components with PPMOs revealed a sequence for acrA, which was the most effective at reducing antibiotic efflux. This acrA-PPMO enhances the antimicrobial effects of the levofloxacin and azithromycin in a panel of clinical Enterobacteriaceae strains. Additionally, acrA-PPMO enhanced azithromycin in vivo in a K.pneumoniae septicemia model. PPMOs targeting the homologous resistance-nodulation-division (RND)-efflux system in P.aeruginosa, MexAB-OprM, also enhanced potency to several classes of antibiotics in a panel of strains and in a cell culture infection model. These data suggest that PPMOs can be used as an adjuvant in antibiotic therapy to increase the efficacy or extend the spectrum of useful antibiotics against a variety of Gram-negative infections.