Single Antibiotic Treatment Research Articles

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)

Administering the maternal bovine appeasing substance improves overall productivity and health in high-risk cattle during a 60-d feedlot receiving period.

This experiment evaluated health, physiological, and performance responses of high-risk cattle administered the maternal bovine appeasing substance (mBAS) during feedlot receiving. Angus-influenced, newly weaned male calves (n = 120) were purchased from an auction facility. Calves arrived at the research feedyard on day -1 and body weight (BW) was recorded upon arrival (199 ± 1 kg). Calves were ranked by arrival BW and received 1 of 2 treatments prior to initial processing (day 0): (1) 10 mL of an mBAS (Ferappease; FERA Diagnostics and Biologicals; College Station, TX) or (2) 10 mL of mineral oil (CON; placebo). Treatments were applied topically to the nuchal skin area (5 mL) and above the muzzle (5 mL). Calves were vaccinated against Clostridium and respiratory pathogens, dewormed, implanted, band-castrated, and received metaphylaxis at initial processing, and then distributed into 10 drylot pens according to arrival BW and treatment (n = 12 calves/pen, 5 pens/treatment). Calves were reapplied treatments (mBAS or CON) concurrently with booster vaccination on d 14. Feed intake and incidence of bovine respiratory disease (BRD) were recorded daily. Blood and hair samples from the tail-switch were collected on days 0, 14, 28, 42, and 60 for analysis of physiological variables. Calves were sampled for nasal microbiota analysis via swab on days 0, 14, and 28. Final shrunk BW was recorded on day 61 after 16 h of feed and water restriction. Calf BW gain and final BW did not differ between treatments (P ≥ 0.40). Incidence of BRD was similar (P = 0.99) between mBAS and CON (56.7% for both treatments; SEM = 6.45). A greater (P = 0.04) proportion of mBAS calves diagnosed with BRD required a single antibiotic treatment to regain health (70.6 vs. 47.0%; SEM = 8.32), and mortality was greater (P = 0.03) in CON calves diagnosed with BRD (17.6 vs. 2.94%; SEM = 5.133). Relative abundance of Mycoplasma in nasal microbiota was reduced (P = 0.04) in mBAS calves compared with CON (34.7 vs. 27.4%; SEM = 2.35). Cortisol concentration in hair from the tail-switch was less (P = 0.01) on day 28 for mBAS calves compared with CON. Administering mBAS improved (P = 0.04) total pen-based liveweight change during the experiment (498 vs. 309 kg/pen; SEM = 65.2) and final pen-based total liveweight (2,676 vs. 2,484 kg/pen; SEM = 65.4). Administration of mBAS to high-risk cattle decreased physiological stress markers, reduced mortality, and increased pen-based productivity during a 60-d receiving period.

Additive Effects of Cyclic Peptide [R4W4] When Added Alongside Azithromycin and Rifampicin against Mycobacterium avium Infection.

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) counts were assessed after treating M. avium cultures with varying concentrations of cyclic [R4W4] alone or in conjunction with azithromycin or rifampicin 3 h and 4 days post-treatment. M. avium growth was significantly reduced 4 days after cyclic [R4W4] single treatment. Additionally, cyclic [R4W4]-azithromycin and cyclic [R4W4]-rifampicin combination treatments at specific concentrations significantly reduced M. avium survival 3 h and 4 days post-treatment compared with single antibiotic treatment alone. These findings demonstrate cyclic [R4W4] as a potent treatment method against M. avium and provide insight into novel therapeutic approaches against mycobacterium infections.

The impact of pharmacist behavioral intervention on antibiotics prescribing in pediatric wards

Background: Antibiotics may be prescribed irrationally, which can lead to significant consequences including the emergence of antimicrobial resistance. Pharmacists can play a key role in enhancing the rational antibiotic prescribing. This study aimed to evaluate the current clinical practice of prescribing antimicrobial agents in pediatric wards and to assess the clinical and economic impact of pharmacist interventions on antibiotic prescribing. Methodology: This study was conducted at the pediatric wards of a general hospital, Babel, Iraq. The study population included all pediatric inpatients aged ≤ 12 years and receiving antibiotic. The study consisted of three phases. The first was a pre-intervention phase where data about antibiotic prescription was collected retrospectively. The second phase involved pharmacist intervention where the researcher had provided an oral presentation to the healthcare workers. The third phase involved prospective data collection which was compared with the pre-intervention data. Independent T-test was used to compare the differences in the parameters between the pre-and post-intervention phases. Results: The study included 250 children in each of the pre- and post-intervention phases who received antibiotic treatment. The medical records were reviewed retrospectively. Four antibiotics (amoxicillin, cefotaxime, vancomycin and meropenem) were significantly less frequently used in the post-intervention phase. Single antibiotic treatment was significantly higher in the post-intervention phase (p-value<0.05). Length and days of therapy, and the total cost of the antibiotics used were significantly lower in the post-intervention phase. Culture and sensitivity tests were performed only in 28% of patients in the post-intervention phase where the isolated bacteria were found to be highly resistant to penicillin and cephalosporin. Conclusions: This study demonstrated that pharmacist intervention in general pediatric wards has resulted in favorable clinical and economic outcomes. This emphasizes the essential role pharmacists can play in rational antibiotic use, not only in the pediatric population but also in the adults.

Simultaneous removal of levofloxacin and sulfadiazine in water by dielectric barrier discharge (DBD) plasma: Enhanced performance and degradation mechanism

Antibiotics are abused and discharged into environmental water, posing a constant potential threat to ecosystem. It is still a challenge to treat the wastewater containing various antibiotics. While many studies have reported the plasma treatment of different antibiotics, how to treat multiple antibiotics simultaneously with high efficiency still remains an unsolved problem. In this work, we employed atmospheric-pressure dielectric barrier discharge (DBD) to treat levofloxacin and sulfadiazine as two typical antibiotics in water, and investigated the treatment efficiency and the involved mechanism. The experimental results indicated that under proper conditions, the total antibiotics removal efficiency could be enhanced compared to separate single antibiotic treatment. The contributions from the plasma-induced reactive oxygen/nitrogen species (RONS) were examined, showing that ·OH played a major role in levofloxacin degradation, while ozone and peroxynitrite also played a certain role in sulfadiazine degradation. The bio-toxicity evaluation for the plasma treatment of levofloxacin and sulfadiazine was also provided, showing that the DBD degradation products were harmless to the ecological environment. As such, this work may not only provide a practical solution to treatment of wastewater containing multiple antibiotics, but also give the insights into the mechanism for the efficient DBD treatment of mixed antibiotics in wastewater.

Clinical characteristics and treatment strategy of nocardiosis in lung transplant recipients: A single-center experience

Nocardia are infrequent pathogens that disproportionately afflict organ transplant recipients. The present study aimed to summarize the clinical manifestations, diagnostic approaches, and treatment strategies of nocardiosis in lung transplant recipients. This retrospective study reviewed the clinical data of adult lung transplant recipients who were complicated with nocardiosis between January 2018 and December 2021 at the largest lung transplant center in South China. The incidence of nocardiosis was 4.2% (13/316), including 9 cases of pulmonary nocardiosis and 4 disseminated nocardiosis (blood, pulmonary and intracranial). The accuracy in diagnosing nocardiosis was 77.8% by culture and 100% by metagenomic next-generation sequencing (mNGS). Nocardia farcinica was the most common causative pathogen. Trimethoprim-sulfamethoxazole-based combination therapy was administered initially, followed by a single antibiotic as the maintained therapy, lasting for 4-8 months. mNGS is more accurate than culture in diagnosing nocardiosis. Most patients responded well to the antibiotic therapy with combined antibiotics at the initial stage followed by a single antibiotic treatment.

The function of small RNA in Pseudomonas aeruginosa.

Pseudomonas aeruginosa, the main conditional pathogen causing nosocomial infection, is a gram-negative bacterium with the largest genome among the known bacteria. The main reasons why Pseudomonas aeruginosa is prone to drug-resistant strains in clinic are: the drug-resistant genes in its genome and the drug resistance easily induced by single antibiotic treatment. With the development of high-throughput sequencing technology and bioinformatics, the functions of various small RNAs (sRNA) in Pseudomonas aeruginosa are being revealed. Different sRNAs regulate gene expression by binding to protein or mRNA to play an important role in the complex regulatory network. In this article, first, the importance and biological functions of different sRNAs in Pseudomonas aeruginosa are explored, and then the evidence and possibilities that sRNAs served as drug therapeutic targets are discussed, which may introduce new directions to develop novel disease treatment strategies.

Enhanced removal of antibiotics and antibiotic resistance genes in a soil microbial fuel cell via in situ remediation of agricultural soils with multiple antibiotics

Soil microbial fuel cells (MFCs) have been applied for the in situ remediation of soils polluted by single antibiotics. However, the investigation of only single antibiotic pollution has hindered MFC application in real-world soil remediation, where the effects of multiple antibiotics with similar chemical structures on the fate of antibiotics and their corresponding antibiotic resistance genes (ARGs) remain unknown. In this study, antibiotic removal rates, microbial community compositions, metabolite compositions, and ARG abundances were investigated in soil MFCs by adding two commonly used antibiotics (sulfadiazine, SDZ, and sulfamethoxazole, SMX), and comparing them with the addition of only a single antibiotic (SDZ). The antibiotic removal rate was higher in the soil MFC with addition of mixed antibiotics compared to the single antibiotic due to enhanced biodegradation efficiency in both the upper (57.24% of the initial antibiotic concentration) and lower layers (57.07% of the initial concentration) of the antibiotic-polluted soils. Bacterial community diversity in the mixed antibiotic conditions increased, and this likely resulted from the decreased toxicity of intermediates produced during antibiotic biodegradation. Moreover, the addition of mixed antibiotics led to lower risks of ARG release into soil environments, as reflected by higher abundances of host bacteria in the single antibiotic treatment. These results encourage the further development of soil MFC technology for in situ remediation of antibiotic-polluted soils.

Association Between Aortic Aneurysm and Aortic Dissection With Fluoroquinolones Use in Patients With Urinary Tract Infections: A Population-Based Cohort Study.

BackgroundFluoroquinolones are first‐line antibiotics recommended for the treatment of complicated urinary tract infections (UTIs), with frequent reports of adverse effects of aortic aneurysm (AA) and aortic dissection (AD). We examined whether fluoroquinolones can increase the risk of AA and AD in patients with UTIs in the Taiwanese population.Methods and ResultsWe used the National Health Insurance Research Database to identify patients diagnosed with UTIs under single antibiotic treatment of fluoroquinolones and first‐, second‐, or third‐generation cephalosporins. An AA and AD diagnosis within a year constituted the study event. Multivariable analysis with a multiple Cox regression model was applied for comparing the hazard risk of AA and AD between fluoroquinolones and first‐ or second‐generation cephalosporins. Propensity score matching was performed to reduce the potential for bias caused by measured confounding variables. Among 1 249 944 selected patients with UTIs, 28 568 patients were assigned to each antibiotic group after propensity score matching. The incidence of AA and AD was not significantly different between the fluoroquinolones and first‐ or second‐generation cephalosporins (adjusted HR [aHR], 0.86 [95% CI, 0.59–1.27]). However, the mortality increased in the fluoroquinolones group (aHR, 1.10 [95% CI, 1.04–1.16]).ConclusionsCompared with first‐ or second‐generation cephalosporins, fluoroquinolones were not associated with increased risk of AA and AD in patients with UTI. However, a significant risk of mortality was still found in patients treated with fluoroquinolones. The priority is to control infections with adequate antibiotics rather than exclude fluoroquinolones considering the risk of AA and AD for patients with UTI.

Presepsin as a biomarker for risk stratification for acute cholangitis in emergency department: A single-center study

BACKGROUNDAcute cholangitis is caused by bacterial infection and has high morbidity and mortality risk. The grade of cholangitis can guide clinical treatment from single antibiotic treatment to biliary drainage. With the introduction of white blood cell (WBC) count, C-reactive protein (CRP), and total bilirubin (T-Bil) into the diagnostic criteria and severity grading for acute cholangitis, the diagnosis rate and grading have significantly improved. However, early risk stratification assessments are challenging in the emergency department. Therefore, we hope to find an ideal predictive biomarker for cholangitis grade. Presepsin is a promising biomarker for the early diagnosis, severity, and prognosis of acute bacterial infections.AIMTo assess the grading value of presepsin in patients with acute cholangitis.METHODSThis clinical study was conducted at the Beijing Friendship Hospital, a 2000-bed teaching hospital with approximately 200000 emergency admissions per year. In this prospective observational study, 336 patients with acute cholangitis meeting the Tokyo Guidelines 2018 diagnostic criteria in the emergency department from May 2019 to December 2020 were analyzed. WBC count, CRP, procalcitonin (PCT), presepsin, T-Bil, and blood culture results were collected. The values were compared using the Pearson χ2 test, Fisher’s exact test, or Mann-Whitney U test. The area under the receiver operating characteristic curve (AUC) of the value was examined using the Delong test. The correlations among the key research indicators were determined using Pearson correlation.RESULTSIn total, 336 patients were examined, which included 107, 106, and 123 patients classified as having mild, moderate, and severe cholangitis, respectively. WBC count, CRP, PCT, presepsin, T-Bil, direct bilirubin, and sequential organ failure assessment scores of moderate and severe cholangitis patients were higher than those of mild cholangitis patients (P = 0.000). The AUC of presepsin in predicting moderate acute cholangitis was 0.728, which was higher than that of CRP (0.631, P = 0.043) and PCT (0.585, P = 0.002), and same as that of WBC count (0.746, P = 0.713) and T-Bil (0.686, P = 0.361). The AUC of presepsin in predicting severe acute cholangitis was 0.715, which was higher than that of WBC count (0.571, P = 0.008), CRP (0.590, P = 0.009), PCT (0.618, P = 0.024), and T-Bil (0.559, P = 0.006). The presepsin levels in the positive blood culture group were higher (2830.8pg/mLvs1987.8pg/mL, P = 0.000), and the AUC of presepsin (0.688) proved that it was a good biomarker for predicting positive bacterial culture.CONCLUSIONPresepsin can predict positive blood culture in patients with acute cholangitis. It is superior to WBC count, CRP, PCT, and T-Bil for the risk stratification of acute cholangitis.

Is combined rather than single antibiotic therapy actually reasonable in patients with acute calculous cholecystitis?

Acute calculous cholecystitis (AC) is a frequently encountered emergency surgery disease and its standard treatment is cholecystectomy. In patients with high risk in surgery, antibiotic treatment (AT) is important. In routine clinical practices, antibiotics are frequently used either as single or in combination in the treatment of AC. This study examined whether or not combined antibiotic treatment (CAT) had superiority over single antibiotic treatment (SAT) in AC. Patients with cholecystitis who received treatment in the period of 2016-2019 were retrospectively examined. The treatment procedures applied, patient findings, and laboratory data were analyzed using relevant statistical software. The patients were categorized into groups based on the treatment approaches applied, and the effects of SAT and CAT on infection parameters were analyzed. In all, 184 patients received treatment for AC, with a mean age of 57.7, and the female-to-male ratio was 77:107. Of these, 139 patients received SAT and 45 received CAT. No significant difference was found in terms of effectiveness between the SAT and CAT in the patients who received early cholecystectomy treatment and those who received medical treatment with noninvasive intervention. In patients with AC, antibiotics are commonly used either as single or in combination for prophylaxis and therapeutic purposes. As no significant difference was observed between single and combined use in terms of treatment effectiveness and hospitalization duration, CAT is not recommended due to its possibility of allergic side effects, toxicity, and cost-increasing effects.

Amikacin and bacteriophage treatment modulates outer membrane proteins composition in Proteus mirabilis biofilm

Modification of outer membrane proteins (OMPs) is the first line of Gram-negative bacteria defence against antimicrobials. Here we point to Proteus mirabilis OMPs and their role in antibiotic and phage resistance. Protein profiles of amikacin (AMKrsv), phage (Brsv) and amikacin/phage (AMK/Brsv) resistant variants of P. mirabilis were compared to that obtained for a wild strain. In resistant variants there were identified 14, 1, 5 overexpressed and 13, 5, 1 downregulated proteins for AMKrsv, Brsv and AMK/Brsv, respectively. Application of phages with amikacin led to reducing the number of up- and downregulated proteins compared to single antibiotic treatment. Proteins isolated in AMKrsv are involved in protein biosynthesis, transcription and signal transduction, which correspond to well-known mechanisms of bacteria resistance to aminoglycosides. In isolated OMPs several cytoplasmic proteins, important in antibiotic resistance, were identified, probably as a result of environmental stress, e.g. elongation factor Tu, asparaginyl-tRNA and aspartyl-tRNA synthetases. In Brsv there were identified: NusA and dynamin superfamily protein which could play a role in bacteriophage resistance. In the resistant variants proteins associated with resistance mechanisms occurring in biofilm, e.g. polyphosphate kinase, flagella basal body rod protein were detected. These results indicate proteins important in the development of P. mirabilis antibiofilm therapies.

Elucidation of Gut Microbiota-Associated Lipids Using LC-MS/MS and 16S rRNA Sequence Analyses.

SummaryHost-microbiota interactions create a unique metabolic milieu that modulates intestinal environments. Integration of 16S ribosomal RNA (rRNA) sequences and mass spectrometry (MS)-based lipidomics has a great potential to reveal the relationship between bacterial composition and the complex metabolic network in the gut. In this study, we conducted untargeted lipidomics followed by a feature-based molecular MS/MS spectral networking to characterize gut bacteria-dependent lipid subclasses in mice. An estimated 24.8% of lipid molecules in feces were microbiota-dependent, as judged by > 10-fold decrease in antibiotic-treated mice. Among these, there was a series of unique and microbiota-related lipid structures, including acyl alpha-hydroxyl fatty acid (AAHFA) that was newly identified in this study. Based on the integrated analysis of 985 lipid profiles and 16S rRNA sequence data providing 2,494 operational taxonomic units, we could successfully predict the bacterial species responsible for the biosynthesis of these unique lipids, including AAHFA.

Effect of Macrolides and β-lactams on Clearance of Bordetella pertussis in the Nasopharynx in Children With Whooping Cough.

The purpose of the current study is to investigate the bactericidal effect of macrolides and β-lactams on Bordetella pertussis (B. pertussis) in the nasopharynx and provide guidance for treating macrolides-resistant B. pertussis infections. Patients with whooping cough was diagnosed by culture of nasopharynx swabs between January 2016 to December 2018. B. pertussis was identified using specific antisera against pertussis and parapertussis. Drug susceptibility test was carried out using the E-test method. The clearance of B. pertussis in nasopharynx at 7 and 14 days into and posttreatment with macrolides, and β-lactams was compared. A total of 125 B. pertussis samples were collected from patients who received single antibiotic treatment. Among those isolates, 62.4% (78/125) had high resistance with minimum inhibitory concentrations greater than 256 mg/L for erythromycin and azithromycin. The MIC90 of piperacillin, cefoperazone-sulbactam, meropenem, ampicillin, ceftriaxone, ceftazidime and trimethoprim-sulfamethoxazole for these isolates was <0.016, 0.094, 0.094, 0.19, 0.19, 0.25 and 0.75 mg/L, respectively. The clearance rate with β-lactams treatment (68.8%, 44/64) was significantly higher than that with macrolides treatment at 14 days posttreatment (50.8%, 31/61) (χ2 = 4.18, P = 0.04). Macrolides had a better clearance rate at 7 days posttreatment than β-lactams (χ2 = 4.49, P = 0.03) for macrolides-sensitive isolates and a worse clearance rate for macrolides-resistant isolates. B. pertussis isolates had a high-resistant rate for macrolides in our study. Macrolides are the first choice for treating pertussis caused by macrolides-sensitive strains, and some β-lactams such as piperacillin should be considered as alternative antibiotics for treatment of macrolides-resistant B. pertussis infection.

Comparative effects of different antibiotics on antibiotic resistance during swine manure composting

This study explored commonly-used antibiotics (lincomycin, chlorotetracycline, sulfamethoxazole, and ciprofloxacin) and their collective effects on antibiotic resistance during composting. In the first 7 days, ciprofloxacin showed the greatest influence on the physicochemical factors among the studied antibiotics; the removal of antibiotic resistance genes (ARGs) in the multiple-antibiotic treatment was significantly less than single-antibiotic treatments; especially, the largest removal of ribosomal protection genes (tetW and tetO) occurred in single ciprofloxacin treatment. In the end of composting, similar removal ratio (29.71–99.79%) of ARGs was achieved in different treatments (p greater than 0.05); Chloroflexi became the main phylum and it was closely associated with ARGs removal based on the network analysis. Potential host bacteria of ARGs varied with different antibiotics; in particular, the presence of multiple antibiotics increased potential host bacteria of ermA, sul1 and tetO. Above all, collective effects of different antibiotics led to the enrichment of antibiotic resistance in the composting.

Distinct Commensal Bacterial Signature in the Gut Is Associated With Acute and Long-Term Protection From Ischemic Stroke.

Background and Purpose- Commensal gut bacteria have a profound impact on stroke pathophysiology. Here, we investigated whether modification of the microbiota influences acute and long-term outcome in mice subjected to stroke. Methods- C57BL/6 male mice received a cocktail of antibiotics or single antibiotic. After 4 weeks, fecal bacterial density of the 16S rRNA gene was quantitated by qPCR, and phylogenetic classification was obtained by 16S rRNA gene sequencing. Infarct volume and hemispheric volume loss were measured 3 days and 5 weeks after middle cerebral artery occlusion, respectively. Neurological deficits were tested by the Tape Test and the open field test. Results- Mice treated with a cocktail of antibiotics displayed a significant reduction of the infarct volume in the acute phase of stroke. The neuroprotective effect was abolished in mice recolonized with a wild-type microbiota. Single antibiotic treatment with either ampicillin or vancomycin, but not neomycin, was sufficient to reduce the infarct volume and improved motorsensory function 3 days after stroke. This neuroprotective effect was correlated with a specific microbial population rather than the total bacterial density. In particular, random forest analysis trained for the severity of the brain damage revealed that Bacteroidetes S24.7 and the enzymatic pathway for aromatic metabolism discriminate between large versus small infarct size. Additionally, the microbiota signature in the ampicillin-treated mice was associated with a reduced gut inflammation, long-term favorable outcome shown by an amelioration of the stereotypic behavior, and a reduction of brain tissue loss in comparison to control and was predictive of a regulation of short-chain fatty acids and tryptophan pathways. Conclusions- The findings highlight the importance of the intestinal microbiota in short- and long-term outcomes of ischemic stroke and raises the possibility that targeted modification of the microbiome associated with specific microbial enzymatic pathways may provide a preventive strategy in patients at high risk for stroke. Visual Overview- An online visual overview is available for this article.

Development of de novo resistance in Salmonella Typhimurium treated with antibiotic combinations.

This study was designed to evaluate the evolution of antibiotic resistance in Salmonella enterica serovar Typhimurium treated with the combination of antibiotics. The experimental evolution of antibiotic resistance of S. Typhimurium was evaluated either under single antibiotic (kanamycin, KAN; penicillin, PEN; erythromycin, ERY) or in combination of two antibiotics (KAN+PEN or KAN+ERY) as measured by fractional inhibitory concentrations (FICs), stepwise resistance selection, cross-resistance evaluation, resistance fitness and relative gene expression. KAN+PEN and KAN+ERY showed the synergistic effect against S. Typhimurium (FIC index < 0.5). KAN+ERY delayed the induction of de novo mutations in S. Typhimurium. The cross-resistance of S. Typhimurium to all antibiotics except ERY and tetracycline was observed in KAN and PEN alone. The fitness cost was lower in single antibiotic treatments than combinations. The highest relative fitness was 0.91 in PEN, followed by KAN (0.84) and ERY (0.78), indicating the low fitness costs in single antibiotic treatments. The overexpression of efflux pump-related genes (acrA and acrB), outer membrane-related gene (ompC) and adherence-related gene (csgD) were observed in the single antibiotic treatments. Our results suggest that KAN+PEN and KAN+ERY could be used as a potential therapeutic treatment by decreasing the evolution of antibiotic resistance in S. Typhimurium and reusing conventional antibiotics.

Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces.

ABSTRACTDue to the spread of resistance, antibiotic exposure receives increasing attention. Ecological consequences for the different niches of individual microbiomes are, however, largely ignored. Here, we report the effects of widely used antibiotics (clindamycin, ciprofloxacin, amoxicillin, and minocycline) with different modes of action on the ecology of both the gut and the oral microbiomes in 66 healthy adults from the United Kingdom and Sweden in a two-center randomized placebo-controlled clinical trial. Feces and saliva were collected at baseline, immediately after exposure, and 1, 2, 4, and 12 months after administration of antibiotics or placebo. Sequences of 16S rRNA gene amplicons from all samples and metagenomic shotgun sequences from selected baseline and post-antibiotic-treatment sample pairs were analyzed. Additionally, metagenomic predictions based on 16S rRNA gene amplicon data were performed using PICRUSt. The salivary microbiome was found to be significantly more robust, whereas the antibiotics negatively affected the fecal microbiome: in particular, health-associated butyrate-producing species became strongly underrepresented. Additionally, exposure to different antibiotics enriched genes associated with antibiotic resistance. In conclusion, healthy individuals, exposed to a single antibiotic treatment, undergo considerable microbial shifts and enrichment in antibiotic resistance in their feces, while their salivary microbiome composition remains unexpectedly stable. The health-related consequences for the gut microbiome should increase the awareness of the individual risks involved with antibiotic use, especially in a (diseased) population with an already dysregulated microbiome. On the other hand, understanding the mechanisms behind the resilience of the oral microbiome toward ecological collapse might prove useful in combating microbial dysbiosis elsewhere in the body.

Beef cow prepartum supplement level and age at weaning: II. Effects of developmental programming on performance and carcass composition of steer progeny.

Objectives were to determine the interaction of prepartum dam supplement level and age at weaning on growth performance, glucose and insulin concentrations, and carcass characteristics of steers (134 steers in yr 1; 147 steers in yr 2). Mature, multiparous Angus × Simmental cows were used in a split-plot design that included 3 supplement levels (no supplement [NS], 2.16 kg·cow·d [LS], and 8.61 kg·cow·d [HS]) and 2 ages at weaning (78 ± 11 d of age [early weaned; EW] or 186 ± 11 d of age [normal weaned; NW]). Cows grazed endophyte-infected tall fescue/red clover pastures and were bunk fed supplement (70% dried distiller's grains plus solubles and 30% soybean hulls) 103 ± 11 d prepartum to 2 ± 11 d postpartum. Dam prepartum supplement level did not affect ( ≥ 0.29) finishing phase growth performance or morbidity. The percentage of steers grading Average Choice or greater was increased ( = 0.04) for steers from cows fed HS compared to the percentage of steers from cows fed NS. Early weaning increased ( < 0.01) finishing phase initial BW and final BW and reduced ( < 0.01) G:F compared to normal weaning. A year × wean interaction ( = 0.04) occurred for ADG; EW resulted in reduced ( < 0.01) ADG compared to NW in yr 2. At slaughter, EW steers had greater ( < 0.01) HCW, yield grade, and back fat than NW steers. A year × wean interaction ( ≤ 0.05) occurred for quality grade distribution; in yr 2, EW steers had a greater ( < 0.01) proportion of carcasses that graded Low Choice or greater and Average Choice or greater than carcasses from NW steers. The EW steers had greater ( ≤ 0.05) occurrence of single antibiotic treatments in yr 2 and mortality due to respiratory disease than NW steers. A trend for a year × wean interaction ( ≤ 0.07) occurred for plasma insulin concentration and insulin:glucose; EW steers had numerically greater plasma insulin concentrations and insulin:glucose than NW steers in yr 1. In conclusion, these data suggest that there is no interaction between maternal level of supplement during late gestation and age at weaning on steer finishing phase performance, glucose and insulin concentrations, and carcass yield and quality characteristics. Overfeeding supplement to the dam did not affect finishing phase growth performance but did improve quality grades of steers. Early weaning increased HCW and improved carcass quality. Both dam supplement level and age at weaning are effective strategies in increasing beef quality and are independent of each other.

Identification and Antibiotic Susceptibility of the Bacteria from Non-odontogenic Infectious Lesions

The purpose of this study was to isolate and identify bacteria from the 4 patients with non-odontogenic infectious lesions (mucormycosis, chronic inflammation from wound infection, and two actinomycosis) and determine their antimicrobial susceptibility against eight antibiotics. Bacterial culture was performed under three culture conditions (anaerobic, CO2, and aerobic incubator). The bacterial strains were identified by 16S rRNA gene (16S rDNA) sequence comparison analysis method. For investigating the antimicrobial susceptibility of the bacteria against eight antibiotics, penicillin G, amoxicillin, tetracycline, cefuroxime, erythromycin, clindamycin, vancomycin, and Augmentin® (amoxicillin + clavulanic acid), minimum inhibitory concentration (MIC) measurement was performed using broth microdilution assay. Nosocomial pathogens such as Enterococcus faecalis, Klebsiella pneumoniae, Bacillus subtilis, and Neisseria flavescens were isolated from mucormycosis. Veillonella parvula, Enterobacter hormaechei, and Acinetobacter calcoaceticus were isolated from chronic inflammatory lesion. Actinomyces massiliensis was isolated from actinomycosis in parotid gland. Capnocytophaga ochracea was isolated from actinomycosis in buccal region in anaerobic condition. There was no susceptible antibiotic to all bacteria in mucormycosis. Tetracycline was susceptible to all bacteria in chronic inflammation. C. ochracea was resistant to vancomycin and penicillin G; and other antibiotics showed susceptibility to all bacteria in actinomycosis. The results indicated that the combined treatment of two or more antibiotics is better than single antibiotic treatment in mucormycosis, and penicillin is the first recommended antibiotic to treat actinomycosis.