Multidrug-resistant Gram-positive Bacteria Research Articles

Antibacterial activity of Psidium guajava L. against certain multidrug resistant gram-negative and gram-positive bacteria

Antibacterial activity of Psidium guajava L. against certain multidrug resistant gram-negative and gram-positive bacteria

Tedizolid Activity Against Clinical Mycobacterium abscessus Complex Isolates-An in vitro Characterization Study.

Mycobacterium abscessus complex consist of three rapidly growing subspecies: M. abscessus, M. massiliense, and M. bolletii. They are clinically important human pathogens responsible for opportunistic pulmonary and skin and soft tissue infections. Treatment of M. abscessus infections is difficult due to in vitro resistance to most antimicrobial agents. Tedizolid (TZD) is a next-generation oxazolidinone antimicrobial with a wide spectrum of activity even against multidrug resistant Gram-positive bacteria. In this study, the in vitro activity of TZD against the M. abscessus complex (n = 130) was investigated. Susceptibility testing by broth microdilution showed lower TZD minimum inhibitory concentrations (MICs) when compared to linezolid. The MIC50 and MIC90 was 1 mg/L and 4 mg/L, respectively across all M. abscessus complex members, reflecting no difference in subspecies response to TZD. Pre-exposure of M. abscessus complex to subinhibitory concentrations of TZD did not trigger any inducible drug resistance. Single-drug time kill assays and bactericidal activity assays demonstrated bacteriostatic activity of TZD in all three M. abscessus subspecies, even at high drug concentrations of 4 to 8x MIC. Combination testing of TZD with clarithromycin, doxycycline and amikacin using the checkerboard approach showed no antagonistic interactions. TZD may be an effective therapeutic antimicrobial agent for the treatment of M. abscessus infections.

A3, a Scorpion Venom Derived Peptide Analogue with Potent Antimicrobial and Potential Antibiofilm Activity against Clinical Isolates of Multi-Drug Resistant Gram Positive Bacteria.

Current research in the field of antimicrobials is focused on developing novel antimicrobial agents to counteract the huge dilemma that the human population is mainly facing in regards to the rise of bacterial resistance and biofilm infections. Host defense peptides (HDPs) are a promising group of molecules for antimicrobial development as they display several attractive features suitable for antimicrobial activity, including their broad spectrum of activity and potency against bacteria. AamAP1 is a novel HDP that belongs to the venom of the North African scorpion Androctonus amoeruxi. In vitro antimicrobial assays revealed that the peptide displays moderate activity against Gram-positive and Gram-negative bacteria. Additionally, the peptide proved to be highly hemolytic and displayed significantly high toxicity against mammalian cells. In our study, a novel synthetic peptide analogue named A3 was synthetically modified from AamAP1 in order to enhance its activity and toxicity profile. The design strategy depended on modifying the amino acid sequence of AamAP1 in order to alter its net positive charge, percentage helicity and modify other parameters that are involved theoretically in HDPs activity. Accordingly, A3 was evaluated for its in vitro antimicrobial and anti-biofilm activity individually and in combination with four different types of conventional antibiotics against clinical isolates of multi-drug resistant (MDR) Gram-positive bacteria. A3 was also evaluated for its cytotoxicity against mammalian cells. A3 managed to selectively inhibit the growth of a wide range of resistant strains of Gram-positive bacteria. Our results also showed that combining A3 with conventional antibiotics caused a synergistic antimicrobial behavior that resulted in decreasing the MIC value for A3 peptide as low as 0.125 µM. At the concentrations needed to inhibit bacterial growth, A3 displayed minimal mammalian cell toxicity. In conclusion, A3 exhibits enhanced activity and selectivity when compared with the parent natural scorpion venom peptide. The combination of A3 with conventional antibiotics could provide researchers in the antimicrobial drug development field with a potential alternative for conventional antibiotics against MDR bacteria.

Synergy between conventional antibiotics and anti-biofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens.

With the antibiotic development pipeline running dry, many fear that we might soon run out of treatment options. High-density infections are particularly difficult to treat due to their adaptive multidrug-resistance and currently there are no therapies that adequately address this important issue. Here, a large-scale in vivo study was performed to enhance the activity of antibiotics to treat high-density infections caused by multidrug-resistant Gram-positive and Gram-negative bacteria. It was shown that synthetic peptides can be used in conjunction with the antibiotics ciprofloxacin, meropenem, erythromycin, gentamicin, and vancomycin to improve the treatment outcome of murine cutaneous abscesses caused by clinical hard-to-treat pathogens including all ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae) pathogens and Escherichia coli. Promisingly, combination treatment often showed synergistic effects that significantly reduced abscess sizes and/or improved clearance of bacterial isolates from the infection site, regardless of the antibiotic mode of action. In vitro data suggest that the mechanisms of peptide action in vivo include enhancement of antibiotic penetration and potential disruption of the stringent stress response.

Block Copolymer Nanoparticles Remove Biofilms of Drug-Resistant Gram-Positive Bacteria by Nanoscale Bacterial Debridement.

Biofilms and the rapid evolution of multidrug resistance complicate the treatment of bacterial infections. Antibiofilm agents such as metallic-inorganic nanoparticles or peptides act by exerting antibacterial effects and, hence, do not combat biofilms of antibiotics-resistant strains. In this Letter, we show that the block copolymer DA95B5, dextran- block-poly((3-acrylamidopropyl) trimethylammonium chloride (AMPTMA)- co-butyl methacrylate (BMA)), effectively removes preformed biofilms of various clinically relevant multidrug-resistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE V583), and Enteroccocus faecalis (OG1RF). DA95B5 self-assembles into core-shell nanoparticles with a nonfouling dextran shell and a cationic core. These nanoparticles diffuse into biofilms and attach to bacteria but do not kill them; instead, they promote the gradual dispersal of biofilm bacteria, probably because the solubility of the bacteria-nanoparticle complex is enhanced by the nanoparticle dextran shell. DA95B5, when applied as a solution to a hydrogel pad dressing, shows excellent in vivo MRSA biofilm removal efficacy of 3.6 log reduction in a murine excisional wound model, which is significantly superior to that for vancomycin. Furthermore, DA95B5 has very low in vitro hemolysis and negligible in vivo acute toxicity. This new strategy for biofilm removal (nanoscale bacterial debridement) is orthogonal to conventional rapidly developing resistance traits in bacteria so that it is as effective toward resistant strains as it is toward sensitive strains and may have widespread applications.

Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin.

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care.

Gold Nanoclusters for Targeting Methicillin-Resistant Staphylococcus aureus In Vivo.

Widespread multidrug resistance caused by the abuse of antibiotics calls for novel strategies and materials. Gold nanoclusters (AuNCs) are scarcely explored for combating multidrug-resistant (MDR) bacteria in vivo. We herein synthesized a novel class of AuNCs, namely quaternary ammonium (QA) capped AuNCs (QA-AuNCs) as potent antibiotics selectively targeting MDR Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), in vivo. QA-AuNCs kill bacteria through a combined physicochemical mechanism, and show excellent therapeutic effects in both a skin infection model and a bacteremia model induced by MRSA. In addition, owing to their intense fluorescence, QA-AuNCs can be used for the discrimination of live/dead bacteria and bacteria counting, suggesting their potential for clinical theranostics.

Septic shock from descending necrotizing mediastinitis \u2013 combined treatment with IgM-enriched immunoglobulin preparation and direct polymyxin B hemoperfusion: a case report

BackgroundDescending necrotizing mediastinitis is a common and progressive polymicrobial infection involving the neck and chest with a high death rate (10 to 40%). From a microbiological point of view, descending necrotizing mediastinitis is sustained by Gram-positive bacteria (43–62%), anaerobes (46–78%), and, rarely, Gram-negative bacteria. Data collected during the Antibiotic Resistance-Istituto Superiore di Sanità project confirmed that Italy is positioned among the countries with the highest levels of resistance in most pathogenic species under surveillance. In particular, 32.9% of Klebsiella pneumoniae isolates were resistant to carbapenem, 33.6% of Staphylococcus aureus to methicillin, and 28.7% and 43.9% of Escherichia coli isolates to third-generation cephalosporins and fluoroquinolones, respectively.Case presentationWe describe the case of a 38-year-old white man with septic shock due to descending necrotizing mediastinitis sustained by multidrug-resistant Gram-negative and Gram-positive bacteria treated after surgery with an IgM-enriched immunoglobulin preparation and polymyxin B hemoperfusion therapy.ConclusionDespite the contrasting data on the use of immunoglobulins and polymyxin B hemoperfusion in septic shock and the lack of literature in cases of acute mediastinitis caused by both Gram-negative and Gram-positive multidrug-resistant bacteria, we obtained an improvement in clinical conditions and the survival of our patient, against all odds.

C8-Linked Pyrrolobenzodiazepine Monomers with Inverted Building Blocks Show Selective Activity against Multidrug Resistant Gram-Positive Bacteria.

Antimicrobial resistance has become a major global concern. Development of novel antimicrobial agents for the treatment of infections caused by multidrug resistant (MDR) pathogens is an urgent priority. Pyrrolobenzodiazepines (PBDs) are a promising class of antibacterial agents initially discovered and isolated from natural sources. Recently, C8-linked PBD biaryl conjugates have been shown to be active against some MDR Gram-positive strains. To explore the role of building block orientations on antibacterial activity and obtain structure activity relationship (SAR) information, four novel structures were synthesized in which the building blocks of previously reported compounds were inverted, and their antibacterial activity was studied. The compounds showed minimum inhibitory concentrations (MICs) in the range of 0.125-32 μg/mL against MDR Gram-positive strains with a bactericidal mode of action. The results showed that a single inversion of amide bonds reduces the activity while the double inversion restores the activity against MDR pathogens. All inverted compounds did not stabilize DNA and lacked eukaryotic toxicity. The compounds inhibit DNA gyrase in vitro, and the most potent compound was equally active against both wild-type and mutant DNA gyrase in a biochemical assay. The observed activity of the compounds against methicillin resistant S.aureus (MRSA) strains with equivalent gyrase mutations is consistent with gyrase inhibition being the mechanism of action in vivo, although this has not been definitively confirmed in whole cells. This conclusion is supported by a molecular modeling study showing interaction of the compounds with wild-type and mutant gyrases. This study provides important SAR information about this new class of antibacterial agents.

Eravacycline for the treatment of patients with bacterial infections.

Eravacycline is a novel, broad-spectrum, synthetic fluorocycline antibiotic for the treatment of complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) due to multidrug-resistant Gram-positive, Gram-negative and anaerobic bacteria that has demonstrated superior potency to that of currently marketed antibiotics. Tetraphase Pharmaceuticals has submitted a new drug application for eravacycline for the treatment of cIAI due to drug-resistant bacteria. In 2013, the U.S. Food and Drug Administration (FDA) granted eravacycline qualified infectious disease product designation for the treatment of cUTI and cIAI.

Antimicrobial Potential of Natural and Semi-Synthetic ent-Kaurane and ent-Pimarane Diterpenes against Clinically Isolated Gram-Positive Multidrug-Resistant Bacteria

In this work, a search for antimicrobial agents against multi-drug resistant (MDR) bacteria was undertaken. It involved two natural diterpenes of different basic skeletons, named ent-kaurenoic acid and ent-pimaradienoic acid, that were used as precursors to access 28 semi-synthetic derivatives that were also submitted to biological assays. All 30 substances were assayed against a set of seven clinically isolated MDR bacteria, including three Staphylococcus aureus strains. Results classified both natural compounds as promising bactericidal antimicrobial agents against these MDR bacteria, especially for their performance in time-kill curve assay, improving on the positive control vancomycin. Moreover, di-hydro ent-pimaradienoic acid, obtained as one of the derivatives, also displayed promising minimum inhibitory concentration (MIC) values against the microorganism set, proving optimum activity against S. aureus strains. Thereby, this work also yielded a promising semi-synthetic bacteriostatic antimicrobial agent against MDR S. aureus. Furthermore, the study was carried out with 30 structures in order to verify the veracity and scope of Urzua’s hypothesis about the structure-activity relationship between diterpenes and antimicrobial action. Our results are 93% in agreement with this hypothesis.

Antimicrobial activity of cyclic dipeptides produced by Lactobacillus plantarum LBP-K10 against multidrug-resistant bacteria, pathogenic fungi, and influenza A virus

The antimicrobial activity of lactic acid bacteria (LAB) is well recognized, particularly because they can produce antimicrobial cyclic dipeptides (CDPs). CDPs serve as attractive scaffolds for drug design owing to the structural variety of their chiral side chains. Using filtrates from fermented kimchi produced using Leuconostoc mesenteroides LBP-K06 starter cultures, we previously demonstrated a combined chromatographic fractionation and gas chromatography-mass spectroscopy method for screening bioactive CDPs. However, the entire pool of CDPs from a given lactic acid bacterial culture is not fully understood. The present study identified the CDP produced by Lactobacillus plantarum LBP-K10, which was the most potent antimicrobial isolated from Korean kimchi. In total, 15 CDPs containing proline and a single CDP without proline were identified in the culture filtrates (CFs) using gas chromatography-mass spectroscopy (GC-MS). These CDPs were also commonly found in the CFs from other isolated LAB. We developed a new method for purifying a massive amount of complete sets of CDPs from CFs using the anion exchange resins Amberlite IRA-67, Purolite A420S, or both. Compared with the activities of the individual CDPs, the entire set showed remarkable potency including bioactivities against multidrug-resistant Gram-positive and Gram-negative bacteria, human and plant pathogenic fungi, and the influenza A virus (H3N2). We demonstrated that the combination of 16 CDPs naturally produced by one organism exhibited strong antimicrobial activity. This novel strategy for profiling metabolites would enable more effective assessments of fermented foods and LAB.

Phytochemical characterisation and bioprospection for antibacterial and antioxidant activities of Lippia alba Brown ex Britton & Wilson (Verbenaceae)

Ethanol extract and fractions obtained from fresh and dry aerial parts of Lippia alba were examined in order to determine their phytochemical composition, antioxidant capacity and antibacterial activities. The ethanol extracts and fractions exhibited an antioxidant effect by the DPPH assay, especially samples of fresh plant. HPLC analysis of the ethyl acetate fractions identified the presence of phenolic acids and flavonoids. The ethanol extract and fractions showed activity against reference and multidrug-resistant strains of Staphylococcus aureus and Enterococcus faecalis (MIC range 2000–250 μg/mL). The hexane and dichloromethane fractions of fresh plant showed better activity against reference strains of Escherichia coli (MIC of 250 and 125 μg/mL, respectively), but all extracts and fractions were less active against multidrug-resistant strains of all the Gram-negative species evaluated. The results showed that the extract and fractions of L alba aerial parts showed antibacterial activity, even against multidrug-resistant Gram-positive bacteria, and antioxidant effect (DPPH assay).

Antimicrobial AApeptides.

Antibiotic resistance is one of the biggest public concerns in the 21st century. Host-defense peptides (HDPs) can potentially mitigate the problem through bacterial membrane disruption; however, they suffer from moderate activity and low stability. We recently developed a new class of peptidomimetics termed "AApeptides". This class of peptidomimetics can mimic the mechanism of action of HDPs, and effectively arrest the growth of multidrug resistant Gram-positive and Gram-negative bacteria. As they are built on unnatural backbone, they are resistant to proteolytic degradation. In this review, we summarize the development of this class of antimicrobial peptidomimetics, and discuss the future perspective on how they can move forward on combating antibiotic resistance.

Recent Developments in Accelerated Antibacterial Inactivation on 2D Cu-Titania Surfaces under Indoor Visible Light

This review focuses on Cu/TiO2 sequentially sputtered and Cu-TiO2 co-sputtered catalytic/photocatalytic surfaces that lead to bacterial inactivation, discussing their stability, synthesis, adhesion, and antibacterial kinetics. The intervention of TiO2, Cu, and the synergic effect of Cu and TiO2 on films prepared by a colloidal sol-gel method leading to bacterial inactivation is reviewed. Processes in aerobic and anaerobic media leading to bacterial loss of viability in multidrug resistant (MDR) pathogens, Gram-negative, and Gram-positive bacteria are described. Insight is provided for the interfacial charge transfer mechanism under solar irradiation occurring between TiO2 and Cu. Surface properties of 2D TiO2/Cu and TiO2-Cu films are correlated with the bacterial inactivation kinetics in dark and under light conditions. The intervention of these antibacterial sputtered surfaces in health-care facilities, leading to Methicillin-resistant Staphylococcus Aureus (MRSA)-isolates inactivation, is described in dark and under actinic light conditions. The synergic intervention of the Cu and TiO2 films leading to bacterial inactivation prepared by direct current magnetron sputtering (DCMS), pulsed direct current magnetron sputtering (DCMSP), and high power impulse magnetron sputtering (HIPIMS) is reported in a detailed manner.

One-pot synthesis of multifunctional nanoscale metal-organic frameworks as an effective antibacterial agent against multidrug-resistant Staphylococcus aureus

Drug-resistant bacteria are an increasingly serious threat to global public health. In particular, infections from multidrug-resistant (MDR) Gram-positive bacteria (i.e. Staphylococcus aureus) are growing global health concerns. In this work, we report the first use of nanoscale metal-organic frameworks (NMOFs) coencapsulating an antibiotic (vancomycin) and targeting ligand (folic acid) in one pot to enhance therapeutic efficacy against MDR S. aureus. Zeolitic imidazolate framework (ZIF-8) NMOFs, which have globular morphologies coencapsulating vancomycin and folic acid, are characterized by transmission electron microscopy, field-emission scanning electron microscopy, powder x-ray diffraction, ulltraviolet–visible spectroscopy, and dynamic light-scattering techniques. We determined that the presence of folic acid on the surface of the NMOFs is significant in the sense of effective uptake by MDR S. aureus through endocytosis. The functionalized NMOFs transport vancomycin across the cell wall of MDR S. aureus and enhance antibacterial activity, which has been confirmed from studies of the minimum inhibitory concentration, minimum bactericidal concentration, cytotoxicity of bacterial cells, and generation of reactive oxygen species. This work shows that functionalized NMOFs hold great promise for effective treatment of MDR S. aureus.

Antibacterial activity of Limonium brasiliense (Baicuru) against multidrug-resistant bacteria using a statistical mixture design

Ethnopharmacological relevanceLimonium brasiliense (Boiss.) Kuntze (Plumbaginaceae) is commonly known as “baicuru” or “guaicuru” and preparations of its dried rhizomes have been popularly used in the treatment of premenstrual syndrome and menstrual disorder, and as an antiseptic in genito-urinary infections. This study evaluated the potential antibacterial activity of rhizome extracts against multidrug–resistant bacterial strains using statistical mixture design. Materials and methodsThe statistical design of four components (water, methanol, acetone, and ethanol) produced 15 different extracts and also a confirmatory experiment, which was performed using water:acetone (3:7, v/v). The crude extracts and their ethyl-acetate fractions were tested against vancomycin–resistant Enterococcus faecium (VREfm), methicillin–resistant Staphylococcus aureus (MRSA) and Klebsiella pneumoniae carbapenemase (KPC)–producing K. pneumoniae, all of which have been implicated in hospital and community–acquired infections. The dry residue, total polyphenol, gallocatechin and epigallocatechin contents of the extracts were also tested and statistical analysis was applied in order to define the fit models to predict the result of each parameter for any mixture of components. The principal component and hierarchical clustering analyses (PCA and HCA) of chromatographic data, as well as mass spectrometry (MS) analysis were performanced to determine the main compounds present in the extracts. ResultsThe Gram-positive bacteria were susceptible to inhibition of bacterial growth, in special the ethyl-acetate fraction of ternary extracts from water:acetone:ethanol and methanol:acetone:ethanol against, respectively, VREfm (MIC=19µg/mL) and MRSA (MIC=39µg/mL). On the other hand, moderate activity of the ethyl-acetate fractions from primary (except water), secondary and ternary extracts (MIC=625µg/mL) was noted against KPC. The quadratic and special cubic models were significant for polyphenols and gallocatechin contents, respectively. Fit models to dry residue and epigallocatechin contents were not possible. PCA and HCA of the chromatographic fingerprints were disturbed by displacement retention time of some peaks, but the ultraviolet spectra indicated the homogeneous presence of flavan-3-ols characteristic of tannins. The MS confirmed the presence of gallic acid, gallocatechin, and epigallocatechin in extracts, and suggested the presence of monomers and dimers of B- and A-type prodelphinidins gallate, as well as a methyl gallate. ConclusionOur results showed the antibacterial potential of L. brasiliense extracts against multidrug–resistant Gram-positive bacteria, such as VREfm and MRSA. The statistical design was a important tool to evaluate the biological activity by optimized form. The presence of some phenolic compounds was also demonstrated in extracts.

Bacterial etiology of bloodstream infections and antimicrobial resistance in Dhaka, Bangladesh, 2005\u20132014

BackgroundBloodstream infections due to bacterial pathogens are a major cause of morbidity and mortality in Bangladesh and other developing countries. In these countries, most patients are treated empirically based on their clinical symptoms. Therefore, up to date etiological data for major pathogens causing bloodstream infections may play a positive role in better healthcare management. The aim of this study was to identify the bacterial pathogens causing major bloodstream infections in Dhaka, Bangladesh and determine their antibiotic susceptibility pattern.MethodsFrom January 2005 to December 2014, a total of 103,679 single bottle blood samples were collected from both hospitalized and domiciliary patients attending Dhaka hospital, icddrb, Bangladesh All the blood samples were processed for culture using a BACT/Alert blood culture machine. Further identification of bacterial pathogens and their antimicrobial susceptibility test were performed using standard microbiological procedures.ResultsOverall, 13.6% of the cultured blood samples were positive and Gram-negative (72.1%) bacteria were predominant throughout the study period. Salmonella Typhi was the most frequently isolated organism (36.9% of samples) in this study and a high percentage of those strains were multidrug-resistant (MDR). However, a decreasing trend in the S. Typhi isolation rate was observed and, noticeably, the percentage of MDR S. Typhi isolated declined sharply over the study period. An overall increase in the presence of Gram-positive bacteria was observed, but most significantly we observed the percentage of MDR Gram-positive bacteria to double over the study period. Overall, Gram positive bacteria were more resistant to most of the commonly used antibiotics than Gram-negative bacteria, but the MDR level was high in both groups.ConclusionsThis study identified the major bacterial pathogens involved with BSI in Dhaka, Bangladesh and also revealed their antibiotic susceptibility patterns. We expect our findings to help healthcare professionals to make informed decisions and provide better care for their patients. Also, we hope this study will assist researchers and policy makers to prioritize their research options to face the future challenges of infectious diseases.

Chemical Composition and Bactericidal Activities of the Leaf Essential Oil of Eucalyptus maculata Hook

This study examined the phytochemicals and medicinal potentials of the leaf essential oil of E. maculata from Nigeria. The essential oil was extracted by hydro-distillation technique and was analysed for various chemical composition using GC-MS. The essential oil was also screened for its antimicrobial activities against multi-drug resistant gram-positive and gram-negative bacteria using the agar well diffusion method. The GC-MS analysis revealed that s-citronellol (18.5%), s-pinene (9.4%), 2,6-dimethyl-2,6-octadiene (8.3%), a-pinene (7.1%), 2,6-dimethyl-1,3,5,7- octatetraene (6.7%), and citronellyl acetate (6.0%) were the major compounds in the leaf essential oil. The essential oil exhibited strong antibacterial activities against most of the tested bacteria, with diameters of inhibition zones ranging from 15.0-30.0 mm. The leaf essential oil of E. maculata is a possible alternative antibiotic drug for treatment of disease caused by multi-drug resistant bacteria.

A novel combination approach of human polyclonal IVIG and antibiotics against multidrug-resistant Gram-positive bacteria.

BackgroundGram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) and enterococci, have shown a remarkable ability to develop resistance to antimicrobial agents.ObjectiveWe aimed to assess possible enhancement of the antimicrobial activity of vancomycin, amoxicillin, clarithromycin, and azithromycin by human polyclonal intravenous immunoglobulin G (IVIG) against 34 multidrug-resistant (MDR) bacterial isolates, including MRSA, Enterococcus faecium, and Enterococcus faecalis.Materials and methodsDouble combinations of the antibiotics with the IVIG were assessed by checkerboard assay, where the interaction was evaluated with respect to the minimum inhibitory concentration (MIC) of the antibiotics. The results of the checkerboard assay were verified in vitro using time-kill assay and in vivo using an invasive sepsis murine model.ResultsThe checkerboard assay showed that IVIG enhanced the antimicrobial activity of amoxicillin and clarithromycin against isolates from the three groups of bacteria, which were resistant to the same antibiotics when tested in the absence of IVIG. The efficacy of vancomycin against 15% of the tested isolates was enhanced when it was combined with the antibodies. Antagonism was demonstrated in 47% of the E. faecalis isolates when clarithromycin was combined with the IVIG. Synergism was proved in the time-kill assay when amoxicillin was combined with the antibodies; meanwhile, antagonism was not demonstrated in all tested combinations, even in combinations that showed such response in checkerboard assay.ConclusionThe suggested approach is promising and could be helpful to enhance the antimicrobial activity of not only effective antibiotics but also antibiotics that have been proven to be ineffective against MDR bacteria. To our knowledge, this combinatorial approach against MDR bacteria, such as MRSA and enterococci, has not been investigated before.