Single Antibiotic Research Articles

Biochemical Characterization and Antibiotic Susceptibility Analysis of Escherichia coli and Salmonella typhi Isolated from Clinical Sample

Poor sensitivity of pathogenic bacteria to bacteria is a serious health issue worldwide specially in the developing and underdeveloped countries making greater concern to the scientists. This study followed the CLSI (Clinical and Laboratory Standards Institute) guidelines 30, Kirby-Bauer disc diffusion method to test sensitivity. We analyzed the antibiotic sensitivity pattern of Escherichia coli and Salmonella typhi isolated from clinical samples, collected from two hospitals of Dhaka, Bangladesh. The sensitivity of twelve different single antibiotics (cefepime, cefotaxime, chloramphenicol, ciprofloxacin, nitrofurantoin, meropenem, imipenem, amikacin, gentamicin, azithromycin, tetracycline, fosfomycin), and two combinations (piperacillin-tazobactam and amoxicillin-clavulanate) were evaluated against E. coli and S. typhi isolates. E. coli isolates showed significantly less susceptibility than S. typhi isolates to the antibiotics tested. Three antibiotics showed significant effectiveness against E. coli isolates, (chloramphenicol, nitrofurantoin, and fosfomycin). Ciprofloxacin was the least effective antibiotic to S. typhi isolates (only 20% isolates showed sensitivity). 85% E. coli isolates were MDR (Multi Drug Resistant), whereas only 5% S. typhi isolates were MDR. The highest MAR (Multiple Antibiotic Resistance) index value among E. coli isolates was 0.86, whereas highest value among S. typhi isolates was 0.21. The lowest MAR value among E. coli isolates was 0.21, whereas two S. typhi isolates had MAR value of zero (0). Almost all the single and combination antibiotics demonstrated poor sensitivity to the E. coli and S. typhi isolates. Thus, it makes infections much harder to treat and makes other medical procedures and treatment, such as surgery, caesarean sections and cancer therapy, much riskier. Bangladesh Pharmaceutical Journal 28(1): 94-104, 2025 (January)

Single Dose Prophylactic versus Multiple Dose Antibiotics for Reducing Surgical Site Infection in Elective Laparoscopic Cholecystectomy

Background: Surgical Site Infection (SSI) is a less commonly encountered condition in Laparoscopic Cholecystectomy (LC). Whether prophylactic use of antibiotics in elective LC can reduce the incidence of SSI remains inconclusive. Prophylactic multiple dose antibiotic therapy after surgery is a common practice in our country to combat SSI. The study aimed to compare the incidence of SSIs after elective LC with single dose antibiotic and conventional multi doses prophylaxis antibiotic regimen. Materials and methods: This prospective randomized study was conducted during the period September 2019 to August 2020. A total of 100 patients who were admitted for elective LC in the Department of Surgery, Chittagong Medical College Hospital were included in this study. Patients were randomly allocated into two equal groups based on antibiotic prophylaxis: Single Dose Group (SDG) and Multiple Dose Group (MDG). SD group was given Cefuroxime axetil (750 mg) intravenously at the time of induction of anaesthesia and MD group was given Cefuroxime axetil (750 mg) intravenously at the time of induction of anaesthesia, followed by Cefuroxime (500 mg) orally twice daily for 7 days. Patients were followed up till 30th post-operative day to assess postoperative outcome in terms of SSI and other complications. Results: Both the groups were similar in terms of their demographic characteristics. The mean duration of postoperative hospital stay was 1.44±0.57 and 1.5±0.61 days in SDG and MDG, respectively. Grade I (Normal healing with mild bruising or erythema according to Southampton Wound Grading System) was found 3(6.0%) and 5(10.0%) in SDG and MDG, respectively (p=0.461). Conclusion: As there is no statistical difference between use of single dose antibiotic before and use routine multi doses antibiotic before and after elective LC, it could be concluded that preoperative single dose antibiotic is comparable to conventional multi doses prophylaxis antibiotic regimen in elective LC. Chatt Maa Shi Hosp Med Coll J; Vol.23 (1); January 2024; Page 34-37

Comparison of the prophylactic effect of cefazolin injection versus oral levofloxacin as prophylactic antibiotic in TURP surgery: a randomized clinical trial

IntroductionUse of antibiotic prophylaxis before transurethral resection of the prostate (TURP) is highly recommended. However, there is no agreement on the use of a single antibiotic for this purpose. This study aimed to compare the prophylactic effect of cefazolin injection with oral levofloxacin on postoperative complications in TURP surgery.Trial designBody temperature and urine culture results were obtained two and five days after surgery. Drugs’ side effects as well as surgery and catheterization time were also recorded.MethodsIn an analytical-comparative trial, the participants were randomly divided into two groups to receive cefazolin or levofloxacin before the surgery.ResultsThe duration of surgery (min) and catheterization (days) were 41.5 ± 11.7 and 4.7 ± 1.8 for levofloxacin-treated group and 43.9 ± 11.9 and 4.7 ± 1.8 for cefazolin-treated group, respectively. The number of positive urine cultures, 2 and 5 days post-surgery were 12 and 14 for levofloxacin-treated group and 9 and 12 for cefazolin-treated group, respectively. Furthermore, both groups reported one fever two days after surgery and had no fever after 5 days. In total, no significant difference was observed between the two groups. Additionally, no correlation was observed between the demographic data (i.e. age, BMI and prostate volume) and the postoperative complications (i.e. fever and urinary culture tests), except between age and urinary culture 2 days after the surgery.ConclusionConsidering the lack of significant differences between the two groups, the use of oral levofloxacin is suggested as an easy to take and cost-effective alternative to injection of cefazolin before TURP surgery.Trial registrationIranian registry of clinical trials, IRCT registration number IRCT20160514027893N4, available through www.irct.ir, Registration date: 2024-03-13 (Retrospectively registered).

Tetracycline but not sulfamethazine inhibits early root growth of wild grassland species, while seed germination is hardly affected by either antibiotic

Seed germination and early growth of grassland species might be influenced by veterinary antibiotics that are extensively released into agricultural habitats. Therefore, we tested impacts of the commonly used antibiotics tetracycline and sulfamethazine, single and in mixture, on seed germination and seedling root growth of six typical species of temperate European grasslands (Carum carvi, Centaurea jacea, Galium mollugo, Plantago lanceolata, Silene latifolia, Dactylis glomerata). In standardised germination experiments, we assessed three germination variables (germination percentage, mean germination time, synchrony of germination) and one post-germination variable (seedling root length) under different environmentally realistic antibiotic concentrations (0.1, 1, 10 mg l−1 and a water control). While the germination variables were only irregularly and weakly affected by both antibiotics, seedling root length was strongly reduced by tetracycline, but not by sulfamethazine. Among the test species, D. glomerata was most sensitive to tetracycline with the average root length reduced up to 81 % in the 10 mg l−1 treatment. Its germination behaviour, however, was almost insensitive to the two antibiotics. Mixture effects were only shown in relation to the germination of single species, where the binary mixture produced effects but not the two single antibiotics or, conversely, effects of single antibiotics were lost in the mixture. These findings highlight the potential threat of plant regeneration from seed by veterinary antibiotics, particularly affecting early root growth and potentially influencing plant population growth in natural habitats.

What is the risk of meningitis, utilising a single agent, single dose perioperative antibiotic following endonasal endoscopic repair of a CSF leak?

What is the risk of meningitis, utilising a single agent, single dose perioperative antibiotic following endonasal endoscopic repair of a CSF leak?

Predicting Bacterial Antibiotic Resistance using MALDI-TOF Mass Spectrometry Databases with ELM Applications.

Early detection of antibiotic resistance is a crucial task, especially for vulnerable patients under prolonged treatments with a single antibiotic. To solve this, machine learning approaches have been reported in the state of art. Researchers have used MALDI-TOF MS in order to predict antibiotic resistance and/or susceptibility in bacterial samples. Weis, et al. implemented LR, LightGBM and ANN to study the antibiotic resistance on bacterial strains of Escherichia Coli, Staphylococcus Aureus, and Klebsiella Pneumoniae. Despite promising results, the models have not achieved perfect accuracy, specifically when the classes are unbalanced. On the other hand, Extreme Learning Machine (ELM) is a training algorithm for forward propagation of single hidden layer neural networks, which converges much faster than traditional methods and offers promising performance along with less programmer intervention. In this way, this study introduced improved ELMs, including two weighted ELMs proposed by Zong, and the SMOTE technique in order to create new synthetic samples of the minority class. After heuristic optimization of ELM hiper-parameters, results demonstrated 85% in accuracy and 85% in geometric mean for the classification problem in the case of weighted ELM 1 subject to the SMOTE technique of oversampling.

Comparison of Resistance Acquisition and Mechanisms in Erwinia amylovora against Agrochemicals Used for Fire Blight Control.

Agrochemicals containing antibiotics are authorized to manage fire blight that has been occurring in Korea since 2015. The minimum inhibitory concentration (MIC) of each antibiotic against Erwinia amylovora, the causal pathogen of fire blight, has increased over the years due to the pathogen's frequent exposure to antibiotics, indicating the necessity to prepare for the emergence of antibiotic resistance. In this study, E. amylovora was exposed to stepwise increasing concentrations of eight different agrochemicals, each containing single or mixed antibiotics, and gene mutation and changes in MIC were assessed. Streptomycin and oxolinic acid induced an amino acid substitution in RpsL and GyrA, respectively, resulting in a rapid increase in MIC. Oxytetracycline initially induced amino acid substitutions or frameshifts in AcrR, followed by substitutions of 30S small ribosomal protein subunit S10 or AcrB, further increasing MIC. E. amylovora acquired resistance in the order of oxolinic acid, streptomycin, and oxytetracycline at varying exposure frequencies. Resistance acquisition was slower against agrochemicals containing mixed antibiotics than those with single antibiotics. However, gene mutations conferring antibiotic resistance emerged sequentially to both antibiotics in the mixed formulations. Results suggested that frequent application of mixed antibiotics could lead to the emergence of multidrug-resistant E. amylovora isolates. This study provided essential insights into preventing the emergence of antibiotic-resistant E. amylovora and understanding the underlying mechanisms of resistance acquisition.

Antibiotic use in a co-infection of respiratory syncytial virus and pathogenic bacteria in children in a resource-limited setting in northeast Peninsular Malaysia.

To investigate co-infection of bacterial isolates associated with respiratory syncytial virus (RSV) in children aged less than two years who were admitted to hospital with confirmed lower respiratory tract infection (LRTI) in Kelantan, Malaysia. The demographic data, clinical history, case management, haematological as well as infectious parameters (white blood cell differential and count, plus C-reactive protein, CRP) of the patients were systematically recorded. Less than one-third of cases were RSV-positive (21.03% and 26.23% were diagnosed as acute bronchiolitis or pneumonia, respectively). Blood cultures from approximately 10% of patients demonstrated growth of Haemophilus influenzae, Staphylococcus aureus, coagulase-negative Staphylococcus, Pseudomonas stutzeri, haemolytic Streptococcus group A, and Bacillus subtilis. Further analysis indicated that children with positive bacterial growth had an insignificant predictive value of CRP (2.32-7.16 mg/dl). The total white cell counts were 2.97-7.33 x 109sup>/L despite increased lymphocyte values in the bacteria-positive blood culture. Platelet counts were also within normal limits except for a single case of H. influenzae infection (685.50 x 109sup>/L). Interestingly, 95.01% of patients were treated with antibiotics; 66.23% of RSV infection cases were administered with a combination of antibiotics and 33.77% with only a single antibiotic. The data indicate that the use of antibiotics, either singly or in combination, is not always effective in treating LRTI in infants. Alternative therapeutic regimens should be considered, especially in Asian countries that may have limited resources.

Antibiotic prophylaxis for the prevention of surgical site infections following colorectal surgery: protocol for network meta-analysis of randomized trials

BackgroundSurgical site infections continue to be a significant challenge following colorectal surgery. These can result in extended hospital stays, hospital readmissions, increased treatment costs, and negative effects on patients’ quality of life. Antibiotic prophylaxis plays a crucial role in preventing infection during surgery, specifically in preventing surgical site infections after colorectal surgery in adult patients. However, the optimal antibiotic regimen is still unclear based on current evidence. Considering the limitations of existing reviews, our goal is to conduct a comprehensive systematic review and network meta-analysis of randomized controlled trials to evaluate the comparative benefits and harms of available antibiotic prophylaxis regimens for preventing surgical site infections following colorectal surgery in adult patients.MethodsWe will search the Medline, EMBASE, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials databases to identify relevant randomized controlled trials. We will include trials that (1) enrolled adults who underwent colorectal surgeries and (2) randomized them to any systemic administration of antibiotic (single or combined) prophylaxis before surgery compared to an alternative systemic antibiotic (single or combined antibiotic), placebo, control, or no prophylactic treatment. Pairs of reviewers will independently assess the risk of bias among eligible trials using a modified Cochrane risk of bias instrument for randomized trials. Our outcomes of interest include the rate of surgical site infection within 30 days of surgery, hospital length of stay, 30-day mortality, and treatment-related adverse effects. We will perform a contrast-based network meta-analysis using a frequentist random-effects model assuming a common heterogeneity parameter. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be utilized to assess the certainty of evidence for treatment effects.DiscussionBy synthesizing evidence from available RCTs, this study will provide valuable insight for clinicians, patients, and health policymakers on the most effective antibiotics for preventing surgical site infection.Systematic review registrationPROSPERO CRD42023434544.

A ruthenium single atom nanozyme-based antibiotic for the treatment of otitis media caused by Staphylococcus aureus.

Staphylococcus aureus (S. aureus) infection is a primary cause of otitis media (OM), the most common disease for which children are prescribed antibiotics. However, the abuse of antibiotics has led to a global increase in antimicrobial resistance (AMR). Nanozymes, as promising alternatives to traditional antibiotics, are being extensively utilized to combat AMR. Here, we synthesize a series of single-atom nanozymes (metal-C3N4 SANzymes) by loading four metals (Ag, Fe, Cu, Ru) with antibacterial properties onto a crystalline g-C3N4. These metal-C3N4 display a rob-like morphology and well-dispersed metal atoms. Among them, Ru-C3N4 demonstrates the optimal peroxidase-like activity (285.3 U mg-1), comparable to that of horseradish peroxidase (267.7 U mg-1). In vitro antibacterial assays reveal that Ru-C3N4 significantly inhibits S. aureus growth compared with other metal-C3N4 even at a low concentration (0.06mg mL-1). Notably, Ru-C3N4 acts as a narrow-spectrum nanoantibiotic with relative specificity against Gram-positive bacteria. Biofilms formed by S. aureus are easily degraded by Ru-C3N4 due to its high peroxidase-like activity. In vivo, Ru-C3N4 effectively eliminates S. aureus and relieves ear inflammation in OM mouse models. However, untreated OM mice eventually develop hearing impairment. Due to its low metal load, Ru-C3N4 does not exhibit significant toxicity to blood, liver, or kidney. In conclusion, this study presents a novel SANzyme-based antibiotic that can effectively eliminate S. aureus and treat S. aureus-induced OM.

Novel Nano Drug-Loaded Hydrogel Coatings for the Prevention and Treatment of CAUTI.

Catheter-associated urinary tract infection (CAUTI) is a prevalent type of hospital-acquired infection, affecting approximately 15% to 25% of patients with urinary catheters. Long-term use of the catheter can lead to colonization of microorganisms and biofilm formation, and may develop into bacterial CAUTI. However, the frequent replacement of catheters in clinical settings can result in tissue damage, inflammation, ulceration, and additional complications, causing discomfort and pain for patients. In light of these challenges, a novel nanodrug-supported hydrogel coating called NP-AM/FK@OMV-P/H has been developed in this study. Through in vitro experiments, it is confirmed that OMV nano-loaded liquid gel coating has an effective reaction against E.coli HAase and releases antibacterial drugs. This coating has also demonstrated strong inhibition of E.coli and has shown the ability to inhibit the formation of bacterial biofilm. These findings highlight the potential of the OMV nanoparticle gel coating in preventing and treating bacterial infections. Notably, NP-AM/FK@OMV-P/H has exhibited greater efficacy against multidrug-resistant E.coli associated with UTIs compared to coatings containing single antimicrobial peptides or antibiotics. Additionally, it has demonstrated good biosecurity. In conclusion, the NP-AM/FK@OMV-P/H coating holds great potential in providing benefits to patients with CAUTI.

Surveillance of antibiotics use in inpatients at Benjamin Mkapa Zonal Referral Hospital in Dodoma, Tanzania: a point prevalence survey

ObjectiveTo assess antibiotics prescribing and use patterns for inpatients at Benjamin Mkapa Zonal Referral Hospital (BMH) using the WHO-Point Prevalence Survey (WHO-PPS).DesignA cross-sectional survey.SettingThe Benjamin Mkapa Zonal Referral Hospital, Dodoma,...

Infections following rattlesnake envenomation and use of antibiotics.

There are 7000-8000 venomous snake bites annually in the USA. Antibiotics are commonly administered to bite victims because infection is difficult to differentiate from local tissue injury following envenomation. The Arizona Poison and Drug Information Center (APDIC) in Tucson oversees antivenom administration for 14 Arizona counties. Records (1999-2021) were searched for antibiotic use and confirmed infections after a rattlesnake bite. There were 4160 calls to APDIC regarding rattlesnakes. After excluding bites to animals, 'dry bites', prisoners and records with missing data, 2059 records were evaluated. Systemic antibiotics were administered to 206 patients (10% of bite victims). Twenty patients (0.97%) had confirmed infections, including cellulitis (n=10), fasciitis (n=4), abscess (n=3) and osteomyelitis (n=3). Five of the victims had positive blood cultures. The presence of tissue necrosis, leukocytosis, fever and elevated fibrinogen levels did not discriminate between toxic effects of venom and infection. Confirmed infections following a rattlesnake bite are uncommon (0.97% of bites). Physicians should refrain from prescribing antibiotics, as they are not justified for most rattlesnake bite victims and the variety of pathogens encountered precludes use of any single effective antibiotic.

Synergistic Effect of Combination Antibiotics against Multidrug-Resistant Salmonella enterica serovar Typhi

Background: Infection caused by multidrug-resistant (MDR) Salmonella enterica serovar Typhi (S. Typhi) is a major health problem in low- and middle-income countries (LMICs). S. Typhi has been reported to be resistant to fluoroquinolones and cephalosporins. Objective: To find out the anti-microbial activity of combination antibiotics against resistant S. typhi. Materials and Methods: First, single antibiotic disks of ciprofloxacin, imipenem and vancomycin with the concentrations of 20, 40, 60 and 80 μg/ml were prepared and applied against sensitive S. typhi to confirm its susceptibility. Later, a resistant strain of Shigella flexneri was treated with single antibiotic (ciprofloxacin, vancomycin and imipenem) at the highest concentration (80 μg/ml) to determinets resistant behavior by measuring the zones of inhibition obtained from the disc diffusion assay. Co-culture was performed between the sensitive and resistant strains to develop the resistant strain of S. typhi. Combinations of antibiotics were used for susceptibility testing against the newly resistant strain of S. typhi by using Kirby–Bauer disk diffusion method. Experiments were carried out in triplicates and the average reading was recorded. Results: The study showed that different concentrations of the combination of vancomycin and imipenem (20, 40, 60, 80 μg/ml) exhibited 18, 20, 24- and 29-mm respective zone of inhibition (ZOI) against S. typhi. A combination of ciprofloxacin and imipenem also exhibited optimum ZOI. It was observed in this study that a single antibiotic treatment did not show any activity against newly resistant strains of S. typhi. Conclusions: The combination therapy can be used as a beneficial treatment approach in multi-drug resistant S. typhi infections. Dhaka Univ. J. Pharm. Sci. 23(1): 37-42, 2024 (June)

Toxic effects of a single sulfonamide antibiotic on two indicator organisms

The widespread use of antibiotics leads to more and more serious pollution of antibiotics in the environment, which has become a global ecological environment problem. Antibiotic pollution will affect the normal life activities of organisms and threaten human health through the food chain. In order to investigate the toxic effects of antibiotic pollution on different indicator organisms, Scenedesmus obliquus and Vibrio qinghaiensis sp-Q67 were used as indicator organisms. Eight widely used sulfonamides antibiotics (SAs), namely, sulfapyridine (SPY), sulfamethazine (SMR), sulfadimethazine (SM2), sulfamethoxazine (SMP), sulfamethoxazole (SMZ), sulfaquinoxaline (SQ), sulfamethoxine (SMM), sulfamethoxine (SMM), and sulfamethoxine (SMM), were studied by microplate toxicity test. The growth inhibition toxicity of sulfamide chloropyrazine sodium (2-SPZ) and its binary mixture to Cyanobacteria obliqua (96h) and Vibrio Qingqingensis Q67 (15min acute and 1h chronic); Based on the actual environmental concentration of SAs in Huixian wetland of Guilin, two groups of six-element mixtures were designed to study their combined toxicity to two different indicator organisms.

Antibiotic usage patterns in COVID-19 patients in five tertiary hospitals from Bangladesh: A countrywide picture

ObjectivesIrrational and injudicious use of antibiotics in COVID-19 patients could be detrimental in a tropical country with a weak antibiotic stewardship policy such as Bangladesh. This study aimed to focus on the antibiotic usage patterns in COVID-19 patients in Bangladesh. MethodsThis prospective observational study was performed from July 2020 to June 2021 in five tertiary hospitals in Bangladesh. Data on demographic profile, disease severity, and antibiotic usage were collected directly from the patients’ hospital documents. ResultsA total of 3486 (94.4%) patients were treated with at least one antibiotic; 3261 (93.6%) patients received a single antibiotic, and 225 (6.5%) received multiple antibiotics. The most used antibiotics were ceftriaxone (37.3%), co-amoxiclav (26.3%), azithromycin (10.6%), and meropenem (10.3%). According to the World Health Organization AWaRe categorization, most (2260; 69.6%) of the antibiotics prescribed in this study belonged to the “Watch” group. Culture and sensitivity reports were available in 111 cases from one center. Only 18.9% of the patients were found to be co-infected with multi-drug-resistant bacteria (52.4% yield from sputum, 28.6% from urine, and 14.3% from blood). ConclusionsStrict antibiotic prescribing policy and antibiotic stewardship should be implemented immediately to limit the future threat of antimicrobial resistance in countries such as Bangladesh.

Pseudo-Siamese network combined with label-free Raman spectroscopy for the quantification of mixed trace amounts of antibiotics in human milk: A feasibility study

The utilization of antibiotics is prevalent among lactating mothers. Hence, the rapid determination of trace amounts of antibiotics in human milk is crucial for ensuring the healthy development of infants. In this study, we constructed a human milk system containing residual doxycycline (DXC) and/or tetracycline (TC). Machine learning models and clustering algorithms were applied to classify and predict deficient concentrations of single and mixed antibiotics via label-free SERS spectra. The experimental results demonstrate that the CNN model has a recognition accuracy of 98.85% across optimal hyperparameter combinations. Furthermore, we employed Independent Component Analysis (ICA) and the pseudo-Siamese Convolutional Neural Network (pSCNN) to quantify the ratios of individual antibiotics in mixed human milk samples. Integrating the SERS technique with machine learning algorithms shows significant potential for rapid discrimination and precise quantification of single and mixed antibiotics at deficient concentrations in human milk.

Triple-Antibiotic Combination Exerts Effective Activity against Mycobacterium avium subsp. hominissuis Biofilm and Airway Infection in an In Vivo Murine Model.

Slow-growing nontuberculous mycobacteria (NTMs) are highly prevalent and routinely cause opportunistic intracellular infectious disease in immunocompromised hosts. The activity of the triple combination of antibiotics, clarithromycin (CLR), rifabutin (RFB), and clofazimine (CFZ), was evaluated and compared with the activity of single antibiotics as well as with double combinations in an in vitro biofilm assay and an in vivo murine model of Mycobacterium avium subsp. hominissuis (M. avium) lung infection. Treatment of 1-week-old biofilms with the triple combination exerted the strongest effect of all (0.12 ± 0.5 × 107 CFU/mL) in reducing bacterial growth as compared to the untreated (5.20 ± 0.5 × 107/mL) or any other combination (≥0.75 ± 0.6 × 107/mL) by 7 days. The treatment of mice intranasally infected with M. avium with either CLR and CFZ or the triple combination provided the greatest reduction in CLR-sensitive M. avium bacterial counts in both the lung and spleen compared to any single antibiotic or remaining double combination by 4 weeks posttreatment. After 4 weeks of treatment with the triple combination, there were no resistant colonies detected in mice infected with a CLR-resistant strain. No clear relationships between treatment and spleen or lung organ weights were apparent after triple combination treatment. The biofilm assay data and mouse disease model efficacy results support the further investigation of the triple-antibiotic combination.

Bacteroidales-Specific Antimicrobial Genes Can Influence the Selection of the Dominant Fecal Strain of Bacteroides vulgatus and Bacteroides uniformis from the Gastrointestinal Tract Microbial Community.

Bacteroides vulgatus and Bacteroides uniformis are known to be abundant in the human fecal microbial community. Although these strains typically remain stable over time in humans, disruption of this microbial community following antibiotics resulted in the transient change to new strains suggesting that a complex, dynamic strain community exists in humans. To further study the selection of dominant fecal microbial strains from the gastrointestinal tract (GIT) community, we analyzed three longitudinal metagenomic sequencing data sets using BLAST+ to identify genes encoding Bacteroidales-specific antimicrobial proteins (BSAP) that have known functions to restrict species-specific replication of B. uniformis (BSAP-2) or B. vulgatus (BSAP-3) and have been postulated to provide a competitive advantage in microbial communities. In the HMP (Human Microbiome Project) data set, we found fecal samples from individuals had B. vulgatus or B. uniformis with either complete or deleted BSAP genes that did not change over time. We also examined fecal samples from two separate longitudinal data sets of individuals who had been given either single or multiple antibiotics. The BSAP gene pattern from most individuals given either single or multiple antibiotics recovered to be the same as the pre-antibiotic strain. However, in a few individuals, we found incomplete BSAP-3 genes at early times during the recovery that were replaced by B. vulgatus with the complete BSAP-3 gene, consistent with the function of the BSAP to specifically restrict Bacteroides spp. The results of these studies provide insights into the fluxes that occur in the Bacteroides spp. GIT community following perturbation and the dynamics of the selection of a dominant fecal strain of Bacteroides spp.

Triterpenoid saponin from Panax ginseng increases the sensitivity of methicillin-resistant Staphylococcus aureus to β-lactam and aminoglycoside antibiotics.

The triterpenoid saponins, ginsenosides, are the major bioactive compound of red ginseng and can exert various physiological activities. In the present study, we examined whether red ginseng extract (RGE) exerts antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). RGE had no bactericidal activity, at least in the range of dissolvable concentration. However, RGE reduced 0.03-0.25-fold the minimum inhibitory concentration (MIC) values of β-lactam antibiotics (oxacillin, ampicillin, carbenicillin, and cefazolin) and aminoglycoside antibiotics (kanamycin and gentamicin) against the two laboratory strains of MRSA. Moreover, the fractional inhibitory concentration index indicated the synergistic activity of RGE with each of the antibiotics. RGE also increased the kanamycin sensitivity of 15 MRSA strains isolated from human volunteers and increased the ampicillin sensitivity of five MRSA strains isolated from dairy cows diagnosed with bovine mastitis. In contrast, RGE did not alter the MIC values of fosfomycin, tetracycline, and erythromycin, suggesting that RGE acts selectively. In contrast, Triton X-100, which was reported to reduce the MIC value of β-lactam antibiotics to MRSA by increasing membrane permeability, reduced the MIC values of fosfomycin and tetracycline. These results indicate that RGE increases the bactericidal effect of antibiotics via a mechanism different from that used by Triton X-100. We found that ginsenoside Rg3 (Rg3), a component of RGE, was an essential compound that exhibits synergy activity with antibiotics. Furthermore, the non-natural compound K, which contains a common protopanaxadiol aglycon moiety with Rg3, also showed synergistic activity with antibiotics. Thus, Rg3 and compound K are potentially new antibiotic adjuvants against MRSA.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant organism that is prevalent worldwide. Therefore, the research and development of new agents against MRSA are required. We first found that ginsenoside Rg3 (Rg3) in red ginseng, made from the roots of Panax ginseng C. A. Meyer, increased the sensitivity of β-lactam antibiotics and aminoglycoside antibiotics to MRSA. Furthermore, we identified that compound K, an unnatural ginsenoside analog, also increased the sensitivity of antibiotics to MRSA, similar to Rg3. By contrast, neither Rg3 nor compound K increased the sensitivity of fosfomycin, tetracycline, and erythromycin to MRSA, suggesting that these act selectively. In the present study, the natural compound Rg3 and its structural isomer, compound K, are potentially new antibiotic adjuvants against MRSA. Currently, multiple antibiotics are used to treat MRSA, but the use of these adjuvants is expected to enable the treatment of MRSA with a single antibiotic and low concentrations of antibiotics.