Combination Of Erythromycin Research Articles

Comparison of Topical Erythromycin with and without Zinc Acetate in the Treatment of Mild to Moderate Acne Vulgaris

Background and Objective: Considering the role of bacteria in causing some forms of acne, in recent years, the use of antibiotics along with other medications has had positive results in acne treatment; therefore, the present study aimed to compare the effect of the combination of topical erythromycin and zinc acetate with topical erythromycin alone in treating mild to moderate acne vulgaris. Materials and Methods: In this clinical trial, 76 patients with acne vulgaris who were referred to a specialized skin clinic were selected and randomly assigned into two treatment groups, namely, A (n=39) and B (n=37). Group A was treated with a local solution of erythromycin 4% without zinc acetate, and group B was treated with a combined local solution of erythromycin 4% and zinc acetate 1.2%. The treatment continued twice a day for three months. Results: In groups, A and B, respectively, the average lesion intensity score before treatment was 21.1 ± 6.5 and 21.9 ± 5.4 (P=0.555), the first month of treatment was 17.0 ± 6.4 and 15.7 ± 5.9 (P=0.578), the second month of treatment 9.1 ± 4.5 and 6.4 ± 3.3 (P=0.014), the third month of treatment 4.0 ± 3.0 and 2.0 ± 3.0 (P=0.001), and the frequency of complete recovery was 38.5 and 64.9%, respectively (P=0.021). In group B, the severity of papules in the second (P=0.002) and third (P=0.001) months of the treatment was significantly lower than in group A. Conclusion: Based on the obtained results, using a combination of erythromycin 4% with zinc acetate 1.2% as a topical solution is more effective than the topical solution of erythromycin 4% alone in treating acne lesions

Antimicrobial Drug-Drug Interactions in the Treatment of Infectious Keratitis.

Infectious keratitis is a serious disease requiring immediate, intensive, and broad-spectrum empiric treatment to prevent vision loss. Given the diversity of organisms that can cause serious corneal disease, current guidelines recommend treatment with several antimicrobial agents simultaneously to provide adequate coverage while awaiting results of microbiology cultures. However, it is currently unknown how the use of multiple ophthalmic antimicrobial agents in combination may affect the efficacy of individual drugs. Using a panel of 9 ophthalmic antibiotics, 3 antifungal agents, and 2 antiacanthamoeba therapeutics, fractional inhibitory concentration testing in the standard checkerboard format was used to study 36 antibiotic-antibiotic combinations, 27 antibiotic-antifungal combinations, and 18 antibiotic-antiacanthamoeba combinations against both Staphylococcus aureus and Pseudomonas aeruginosa for synergistic, additive, neutral, or antagonistic drug-drug interactions. We demonstrate that while most combinations resulted in no change in antimicrobial efficacy of individual components, the combination of erythromycin + polyhexamethylene biguanide was found to be antagonistic toward P. aeruginosa . Conversely, 18 combinations toward S. aureus and 15 combinations toward P. aeruginosa resulted in additive or synergistic activity, including 4 with improved activity toward both species. Understanding how drug-drug interactions may affect drug efficacy is critical to selecting the appropriate combination therapy and improving clinical outcomes of this blinding disease.

English

Currently, there is an upsurge of bacterial resistance in single-drug treatment regimens. This has stimulated a growing interest in research and development of new antibacterial agents containing several ingredients as one of the means to combat bacterial resistance. Herb-antibiotic combination therapy is one of the reported effective treatment regimens to combat antimicrobial resistance. This study was aimed to assess antibacterial effects of combined crude extracts of Synadenium glaucescens and Commiphora swynnertonii with antibiotics. In this study, three standard antibiotic drugs namely, ciprofloxacin, ampicillin and erythromycin in combination with crude extracts from S. glaucescens and C. swynnertonii were screened for antibacterial effects against two Gram-positive bacteria, Staphylococcus aureus and Enterococcus faecalis and three Gram-negative bacteria Escherichia coli,  Klebsiella pneumonia  and  Pseudomonas aeruginosa. Broth microdilution technique was used to determine the Minimum Inhibitory Concentration (MIC) while Fractional Inhibitory Concentration (FIC) indices were calculated from MIC values of combined extracts to determine the combination effects. Synergism was observed when ciprofloxacin was combined with all tested crude extracts against  E. coli (ΣFIC of 0.02), combination of ciprofloxacin with extract from root barks of  C. swynnertonii  (ΣFIC of 0.5) against  S. aureus, root barks of  Synadenium glaucescens (ΣFIC of 0.1) against  S. aureus  and combination of ampicillin with all tested crude extracts (ΣFIC of 0.03-0.1) against  E.  faecalis. Moreover, antagonism was observed between the combinations of ampicillin and erythromycin with all tested crude extracts against Gram-negative bacteria (ΣFIC of 4-8). Therefore, the combinations which demonstrated synergism may be promising alternatives for the treatment of infectious diseases caused by E. coli, S. aureus and E. faecalis. However, in the future, toxicity studies for combinations which demonstrated synergism are recommended. Key words: Antibacterial activity, antibiotic, crude extracts, herbs, synergism.

Evaluación de antibióticos y fungicidas, en la introducción in vitro de banano (Musa acuminata) en la Estación Experimental Sapecho

Decontamination of explants is a requirement for the efficiency of introduction and establishment of in vitro banana (Musa acuminata) explants. The work was carried out at the Plant Biotechnology Laboratory of the Sapecho Experimental Station, located in the municipality of Palos Blancos in the department of La Paz, with the objective of evaluating the efficiency of three antibiotics and three fungicides in the introduction and establishment of the banana (Musa acuminata) Grand Nain variety. The antibiotics used were Erythromycin, Tetracycline and Chloramphenicol, while the fungicides used were Benlate, Ridomil and Cuprocol in different doses. The three antibiotics were added to the introduction culture medium, while the fungicides were applied by submerging the explants before planting in the culture medium. For data analysis, a completely randomized design (CRD) was used, with nine treatments and three replicates. For the comparison of means, Fisher's test was applied at 5% probability. The variables evaluated were: total contamination and explant survival. After 45 days of in vitro culture, there were highly significant effects on fungal contamination (mean 33.3%) and bacterial contamination (48.1%). In the survival variable (mean 46%), there were significant differences in the fungicide x antibiotic interaction. The use of the antibiotic Erythromycin in combination with the fungicide Cuprocol in the introduction and establishment of banana allows the reduction of losses due to bacterial and fungal contamination. In addition, according to the results observed, treatments T1 and T4 presented the highest percentage of contamination (77.8%), and the treatment with the highest percentage of survival was T6 (100%).

Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens.

With the increasing bacterial resistance to traditional antibiotics, there is an urgent need for the development of alternative drugs or adjuvants of antibiotics to enhance antibacterial efficiency. The combination of antimicrobial peptides (AMPs) and traditional antibiotics is a potential alternative to enhance antibacterial efficiency. In this study, we investigated the synergistic bactericidal effect of AMPs, including chicken (CATH-1,−2,−3, and -B1), mice (CRAMP), and porcine (PMAP-36 and PR-39) in combination with conventional antibiotics containing ampicillin, tetracycline, gentamicin, and erythromycin against Staphylococcus aureus, Salmonella enteritidis, and Escherichia coli. The results showed that the minimum bactericidal concentration (MBC) of CATH-1,−3 and PMAP-36 was lower than 10 μM, indicating that these three AMPs had good bacterial activity against S. aureus, S. enteritidis, and E. coli. Then, the synergistic antibacterial activity of AMPs and antibiotics combination was determined by the fractional bactericidal concentration index (FBCI). The results showed that the FBCI of AMPs (CATH-1,−3 and PMAP-36) and erythromycin was lower than 0.5 against bacterial pathogens, demonstrating that they had a synergistic bactericidal effect. Furthermore, the time-killing kinetics of AMPs (CATH-1,−3 and PMAP-36) in combination with erythromycin showed that they had a continuous killing effect on bacteria within 3 h. Notably, the combination showed lower hemolytic activity and cytotoxicity to mammal cells compared to erythromycin and peptide alone treatment. In addition, the antibacterial mechanism of CATH-1 and erythromycin combination against E. coli was studied. The results of the scanning electron microscope showed that CATH-1 enhanced the antibacterial activity of erythromycin by increasing the permeability of bacterial cell membrane. Moreover, the results of bacterial migration movement showed that the combination of CATH-1 and erythromycin significantly inhibits the migration of E. coli. Finally, drug resistance analysis was performed and the results showed that CATH-1 delayed the emergence of E. coli resistance to erythromycin. In conclusion, the combination of CATH-1 and erythromycin has synergistic antibacterial activity and reduces the emergence of bacterial drug resistance. Our study provides valuable information to develop AMPs as potential substitutes or adjuvants for traditional antibiotics.

METHOD DEVELOPMENT AND VALIDATION OF ERYTHROMYCIN AND OLAPARIB IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY–TANDEM MASS SPECTROMETRY

The liquid chromatography–tandem mass spectrometry (LC-MS)/MS methodology was used to develop and validate a method for detecting erythromycin and olaparib in human plasma. Antibiotics such as erythromycin and olaparib fall into this category. Liquid chromatography is used to separate stationary and mobile phases based on differences in their affinities as well as to remove unwanted contaminants. It improves repeatability, sensitivity, resilience, and low-level protein detection. A C18 (C18, 5 m, 100×4.6 mm) column is utilized for high resolution and peak area. The calibration curve is created using linear regression. Internally, telmisartan is utilized as a benchmark. The flow rate of the mobile phase is 0.5 mL/min. Erythromycin and olaparib have mass-to-charge ratios of 735.43–115.97 and 435.08–102.04, respectively. Erythromycin in combination with olaparib resulted in a 98% recovery rate. The precision and accuracy of the results determined by interday QC samples are within acceptable limits. There was no evidence of instability.

Response of Group B Streptococcus to the Combination of Gold Nanoparticles-Erythromycin as a Nanoweapon

Background: Group B Streptococcus (GBS) causes a wide range of adverse effects in both mothers and infants during pregnancy and after delivery. Objectives: This study aimed to evaluate the effects of erythromycin either alone or in combination with gold nanoparticles (AuNPs) on the clinical GBS isolated from pregnant women. Methods: This descriptive cross-sectional study was performed on 106 women aged 16 - 48 years. After identification of GBS strains by phenotypic and genotypic methods (PCR), erythromycin-resistant isolates were identified using the Kirby-Bauer test and broth microdilution method according to CLSI-2015 guidelines. The antibacterial properties and minimum inhibitory concentration (MIC) of erythromycin (either alone or combined with AuNPs) were assessed by the agar well-diffusion and broth microdilution methods, respectively. Results: The frequency of GBS isolates was significantly high in the pregnant women aged less than 40 years (73.9%) (P = 0.0251), those with a history of abortion (60.9%) (P = 0.038), and residents of rural areas (60%) (P = 0.038). Moreover, 65.2% of the isolates were resistant to erythromycin. The MIC of AuNPs-erythromycin combination required to inhibit the growth of 50% of GBS isolates (MIC50 = 0.25 μg/mL) was significantly lower than the concentration of AuNP-erythromycin required to inhibit the growth of 90% of the isolates (MIC90 = 1 μg/mL) (P = 0.02), indicating a 16-fold lower dose than the values for erythromycin and AuNPs alone. In the agar well-diffusion method, the average diameter of the growth inhibition zone of AuNPs-erythromycin was 2.5-fold greater than that of free erythromycin (P = 0.037). Conclusions: The results showed that the combination of erythromycin with AuNPs increased the antibacterial effects of erythromycin against GBS isolates.

In vitro effects of quinine on the antibacterial activity of erythromycin against bacteria of clinical relevance

The study investigated the in vitro effects of quinine on the antibacterial activity of erythromycin for possible interactions. The antibacterial activities of each drug and their combinations were investigated by agar diffusion, agar and macrobroth dilution methods. While 100 µl of 1000 µg/ml of erythromycin produced inhibition zones ranging between 13 and 31 ± 1.0 mm in all the isolates except K. pneumoniae and P. aeruginosa ATCC 19582, combining the highest concentration of erythromycin with 35 µg/ml of quinine produced inhibition zones ranging between 14 and 34 ± 1.0 mm with the exception of S. flexneri KZN. Though quinine had no antibacterial effects on the isolates, erythromycin was effective at minimum inhibitory concentrations (MICs) ranging between 25 and 100 µg/ml while their combinations resulted in reduction of MICs of most of the isolates to 12.5 µg/ml except those against A. calcaoceuticus anitratus CSIR, Ps. aeruginosa ATCC 15442, P. shigelloides ATCC 51903, A. hydrophila ATCC 35654, Ps. aeruginosa ATCC 19582 and E. faecalis KZN that remained unchanged in agar dilution. While the MICs of erythromycin ranged between 25 and 50 µg/ml, the MICs of this antibiotic was reduced to concentrations ranging between 12.5 and 50 µg/ml indicating 50% to 75% in the presence of quinine. The combination of erythromycin and quinine, in vitro, resulted in synergistic (50%), additive/indifference (44.44%) and antagonistic (11.11%) interactions while quinine at concentrations lower than plasma quinine concentrations was inhibitory to the antibacterial activity of erythromycin. The synergistic effect may serve as remedy for bacterial infections in which the test bacteria have been implicated.

Optimal dose and duration of enteral erythromycin as a prokinetic: A surgical intensive care experience.

Background: Enteral feeding has various advantages over parenteral feeding in critically ill patients. Acutely ill patients are at risk of developing enteral feeding intolerance. Prokinetic medications improve gastrointestinal mobility and enteral feed migration and absorption. Among the available prokinetic agents, erythromycin is the most potent. Erythromycin is used in different dosages and durations with variable efficacy. Intravenous erythromycin has an early and high rate of tachyphylaxis; hence, enteral route is preferred. Recently, the combination of prokinetic medications has been increasingly used because they accelerate the prokinetic action and decrease the adverse effects.Aim: This study aimed to determine the optimal effective prokinetic dose and duration of administering enteral erythromycin in combination with metoclopramide in critically ill patients.Patients and methods: This study has a prospective observation design. After obtaining permission from the medical research center of the institution, all patients in the surgical and trauma intensive care unit having enteral feed intolerance and those who were already on metoclopramide for 24 hour (h) were enrolled in the study. Patients’ demographic data, diagnosis, surgical intervention, disease severity scores, erythromycin dose, duration of administration, any adverse effects, factors affecting erythromycin response, and outcome were recorded. All patients received 125 mg syrup erythromycin twice daily through a nasogastric tube (NGT). The NGT was clamped for 2 h, and half amount of previous enteral feeds was resumed. If the patient did not tolerate the feeds, the erythromycin dose was increased every 24 h in the increment of 250, 500, and 1000 mg (Figure 1). Statistical significance was considered at P < 0.05. A total of 313 patients were enrolled in the study. Majority of the patients were male, and the mean age was 45 years.Results: Majority (48.2%) of the patients (96) with feed intolerance were post laparotomy. Ninety percent (284) of the patients responded to prokinetic erythromycin therapy, and 54% received lower dose (125 mg twice daily). In addition, 14% had diarrhea, and none of these patients tested positive for Clostridium difficile toxin or multidrug resistance bacteria. The mean duration of erythromycin therapy was 4.98 days. The most effective prokinetic dose of erythromycin was 125 mg twice daily (P = 0.001). Erythromycin was significantly effective in patients with multiple organ dysfunction and shock (P = 0.001). Patients with high disease severity index and multiple organ dysfunction had significantly higher mortality (p < 0.05). Patients not responding to erythromycin therapy also had a significant higher mortality (p = 0.001).Conclusion: Post-laparotomy patients had high enteral feed intolerance. Enteral erythromycin in combination with metoclopramide was effective in low dose and was required for short duration. Patients who did not tolerate feeds despite increasing dose of erythromycin had higher mortality.

Spectrum and resistance determinants of oral streptococci clinical isolates.

The profiles of oral streptococci sensitivity to antibacterial drugs may reflect information about the presence of macroorganism resistance determinants. The aim of the work was to isolate the spectrum of oral streptococci from the microbiota of the oral cavity of patients and to determine their sensitivity to a wide range of antibiotics. A total of 342 microbial streptococcal isolates were isolated from saliva samples and a periodontal pocket and tested for antibiotic sensitivity. Species identification of streptococci was carried out using biochemical API test systems. Evaluation of antibiotic resistance was performed using E-tests. Real-time PCR was used to identify the presence of tetracycline and macrolide resistance genes. The study identified six types of oral streptococci: S. oralis, S. salivarius, S. mitis, S. sanguinis, S. anginosus and S. mutans. All streptococci were sensitive to linezolid and meropenem. The proportion of penicillin-resistant streptococci in the subgroup S. oralis / mitis / mutans was 47,8% versus 23,5% in the subgroup S. salivarius / sanguinis / anginosus (p = 0.020). Significant levels of resistance were revealed to macrolides (erythromycin) - 47,9%, tetracyclines (tetracycline) - 44,4% and quinolones (ofloxacin) - 41%. Multiple drug resistance (MDR) was detected in 31,9% of oral streptococcal isolates, a combination of erythromycin, tetracycline and ofloxacin resistance was prevalent in 79 isolates (23,1%). The most common genotypes of macrolides and tetracycline resistant oral streptococci (in 127 streptococcal isolates with combined resistance) were ermB-mefE + and tetM + tetQ-, respectively. Thus, S. oralis / mitis / mutans group streptococci predominated in the structure of antibiotic-resistant oral streptococci, including MDR. So, being in one of the most densely populated biotopes of a macroorganism, oral streptococci can mediate the transfer of resistance determinants to more pathogenic and clinically significant microorganisms, which requires careful monitoring of their level of susceptibility to antimicrobial agents.

Enhancing the Antibacterial Activity of Erythromycin with Titanium Dioxide Nanoparticles against MRSA.

Staphylococcus aureus (S. aureus) is the most common infectious agent in the community and hospitals. Infections with S. aureus are now becoming difficult to be treated by using conventional antibiotics due to its emerging methicillin-resistant S. aureus (MRSA) strain. In the present study, MRSA was isolated from clinical samples and evaluated for resistance against different antibiotics, TiO2 nanoparticles, and their combinations. Clinical samples were collected from Ayub Medical Complex (AMC), Abbottabad, Pakistan, and identified by different biochemical tests and polymerase chain reactions (PCR). Kirby-Bauer disk diffusion method was performed to evaluate antimicrobial susceptibility. Minimum Inhibitory Concentration (MIC) of ampicillin, ciprofloxacin, erythromycin, and vancomycin was found out by agar dilution method while the broth dilution method was used for the MIC of TiO2 nanoparticles and their combinations with erythromycin. All 13/100 (13%) MRSA were successfully identified. All isolates were susceptible to quinupristin/ dalfopristin, teicoplanin, and vancomycin, while the highest resistance was seen with erythromycin, penicillin, and tetracycline. MIC showed high resistance against ampicillin (0.25-512 mg/L) and erythromycin (0.25-1024 mg/L). The MIC value of 2 mM TiO2 nanoparticles was found to be the most effective concentration after 12 h of incubation, while the combination of erythromycin with 3 mM TiO2 nanoparticles was found to be more potent which significantly lowered down the MIC of erythromycin to 2-16 mg/L.

Virulence, antimicrobial resistance and phylogenetic analysis of zoonotic walking pneumonia Mycoplasma arginini in the one-humped camel (Camelus dromedarius)

In the scientific literature, a small amount of information is found concerning mycoplasmosis in camel species. A variety of pathogens could be causative agents for pneumonia, but walking pneumonia is mostly caused by Mycoplasma with slow development and mild symptoms. The aim of this study was to identify mycoplasmas from camels (Camelus dromedarius) and extending the arsenal of factors implicated in pathogenicity of M. arginini to shed light on the current knowledge gap. 460 lung samples (pneumonic; n=210 and apparently healthy; n=250) were randomly collected from the one-humped camels (C. domedarius) that have been imported from Sudan and slaughtered at Cairo Slaughterhouse. 48 out of 210 isolates (22.9%) recovered from the pneumonic lungs were recorded as M. arginini. Positive PCR results were obtained for all 48 isolates. On the other hand, infection with the organism was not detected in the apparently healthy lungs. Hemolysis and hydrogen sulphide (H2S) production, a compound that has previously not been identified as a virulence factor in M. arginini, was evident in 100% of the isolates. The 48 M. arginini isolates were weak in their ability to form biofilm on polystyrene surfaces. All isolates were 100% susceptible to florfenicol and streptomycin and 100% resistant to ciprofloxacin. Resistance to lincomycin, spiromycin, tylosin, doxacyclin and erythromycin was observed at different frequencies. 13 different combinations of antibiotics representing one to four classes were evident with the Macrolide erythromycin being the most represented. It also should be noted that the ciprofloxacin, doxacyclin, lincomycin, erythromycin combination was the most noted in 21/48 isolates. Surprisingly, none of the virulence genes (vsp, uvrC and gapA) and quinolone resistance genes (parC and gyrA) were detected by PCR.

Fabrication and characterization of tretinoin-loaded nanofiber for topical skin delivery

BackgroundTretinoin or all-trans retinoic acid is used in the treatment of acne vulgaris and photo-aging. This work aims to develop tretinoin-loaded nanofibers as a potential anti-acne patch and to investigate its physicochemical characteristics.MethodNanofibers were produced via electrospinning method and surface topography was evaluated by Field Emission Scanning Electron Microscopy (FESEM). The functional groups of polymer and the drug molecule and the possible interactions were studied by Fourier Transform Infrared Spectroscopy (FTIR). Drug release studies were carried out by total immersion method at 25 °C and 32 °C. Tretinoin stability was evaluated at room temperature and fridge for 45 days. The possibility of synergistic antibacterial activity of tretinoin and erythromycin combination was investigated on Staphylococcus aureus (ATCC® 25923™) and (ATCC® 29213™) by Kirby Bauer disc diffusion method.ResultsUniform fibers without drug crystals were fabricated via electrospinning. Drug-loaded nanofibers show inherent stability under various storage conditions. Electrospun nanofibers showed a prolonged release of tretinoin. The stability of formulations in FT was higher than RT. Disc diffusion tests did not show any synergism in the antibacterial activity of erythromycin when used in combination with tretinoin.ConclusionIt can be anticipated that the easy fabrication, low costs and dosing frequency of the construct reported here provide a platform that can be adapted for on-demand delivery of tretinoin.Graphical abstract

In vitro synergistic activity of erythromycin and nisin against clinical Group B Streptococcus isolates.

This study investigated the potential synergy between erythromycin and nisin against clinical Group B Streptococcus (GBS) strains. The combination of erythromycin and nisin was examined for synergistic activity using checkerboard and time-kill assays against invasive and colonizing GBS strains. Additionally, the immunological effect of the antibiotic combination was investigated in vitro using human U937 cells and ELISA analysis. Checkerboard assays confirmed an additive effect when the antimicrobials were combined, while time-kill assays demonstrated a synergistic effect when antimicrobials were combined for invasive GBS isolates. Furthermore, a significantly lower TNF-alpha response (P<0·05) was observed in U937 cells challenged with GBS when erythromycin and nisin were used in combination. The results suggest that erythromycin and nisin can act synergistically to inhibit the growth of GBS. Group B Streptococcus is the leading cause of invasive neonatal disease worldwide and is becoming increasingly more prevalent in adults. Resistance to some conventionally used antibiotics, such as erythromycin and clindamycin, continue to rise among GBS, indicating a need for alternative treatments. This study demonstrates the potential of an erythromycin-nisin combination for treatment of GBS infections and encourages further investigation of this treatment option.

Combination Treatment of Erythromycin and Furamidine Provides Additive and Synergistic Rescue of Mis-Splicing in Myotonic Dystrophy Type 1 Models.

Myotonic dystrophy type 1 (DM1) is a multi-systemic disease that presents with clinical symptoms including myotonia, cardiac dysfunction and cognitive impairment. DM1 is caused by a CTG expansion in the 3' UTR of the DMPK gene. The transcribed expanded CUG repeat RNA sequester the muscleblind-like (MBNL) and up-regulate the CUG-BP Elav-like (CELF) families of RNA-binding proteins leading to global mis-regulation of RNA processing and altered gene expression. Currently, there are no disease-targeting treatments for DM1. Given the multi-step pathogenic mechanism, combination therapies targeting different aspects of the disease mechanism may be a viable therapeutic approach. Here, as proof-of-concept, we studied a combination of two previously characterized small molecules, erythromycin and furamidine, in two DM1 models. In DM1 patient-derived myotubes, rescue of mis-splicing was observed with little to no cell toxicity. In a DM1 mouse model, a combination of erythromycin and the prodrug of furamidine (pafuramidine), administered orally, displayed both additive and synergistic mis-splicing rescue. Gene expression was only modestly affected and over 40 % of the genes showing significant expression changes were rescued back toward WT expression levels. Further, the combination treatment partially rescued the myotonia phenotype in the DM1 mouse. This combination treatment showed a high degree of mis-splicing rescue coupled with low off-target gene expression changes. These results indicate that combination therapies are a promising therapeutic approach for DM1.

Analysis of screening strategy of group B streptococcus in the third trimester and its influence on pregnancy outcome

Objective: To investigate the screening strategy of group B streptococcus (GBS) in the reproductive tract of women in the third trimester and analyze its impact on pregnancy outcome. Methods: A total of 85 461 pregnant women in 35-37 weeks of gestation from Bao'an Maternity and Child Health Hospital, Jinan University from January 2011 to June 2018 were enrolled. They were divided into 3 periods according to different GBS screening strategies, the unscreened period included 31 384 cases (36.72%), 33 267 cases (38.93%) were included in partial screening period, 20 810 cases (24.35%) were included in screening period. All GBS screening positive pregnant women were given intrapartum antibiotic prophylaxis (IAP). The impact on pregnancy outcomes, and the impact of different GBS collection transport and culture methods on the positive rate of GBS screening were analyzed. Results: (1) The incidence of neonatal early onset GBS disease (EOGBSD) in unscreened period was 0.03% (11/31 773), in partial screening period was 0.02%(6/33 887), and in screening period, the incidence of neonatal EOGBSD decreased to 0, the difference was statistically significant (χ(2)=7.86, P=0.02).(2) The incidence of hematogenous infection of GBS in pregnant women was 0.02%(6/33 887) in partial screening period, and there was none in screening period, there was no significant difference (adjusted χ(2)=3.75, P=0.05). (3) In the screening period, the positive rate of GBS was 14.08%(2 719/19 306), which was significantly higher than the positive rate of GBS in the partial screening period (11.48%, 2 058/17 920; χ(2)=56.12, P=0.00). (4) Antibiotic sensitivity tests of 4 777 GBS strains showed that the antibiotics with higher resistance rate were tetracycline (81.52%, 3 896/4 777), erythromycin (66.59%, 3 181/4 777), and clindamycin (64.31%, 3 072/4 777). The combination of erythromycin, clindamycin and tetracycline was the most common resistant pattern, accounting for 48.80% (2 331/4 777). No penicillin, ceftriaxone or vancomycin resistant strains was found. Conclusions: GBS screening strategy in different regions could combine the local neonatal EOGBSD incidence rate, maternal GBS colonization rate, and the socioeconomic factors to determine whether universal GBS screening or screening for high-risk maternal women. GBS screening positive rate is related to the population, scope of the investigation, the sample collection, delivery and culture methods. The multi-drug resistance rate of GBS is high.

Methanolic Extracts of the Rhizome of &lt;i&gt;R. emodi&lt;/i&gt; Act as Bioenhancer of Antibiotics against Bacteria and Fungi and Antioxidant Potential

Rheum emodi (Himalayan rhubarb) is used as a medicinal herb in the greater Himalayas. The present study investigated the antimicrobial and antioxidant properties of methanolic extracts of rhizome of R. emodi . The methanolic extract showed the presence of phenolics, tannins, flavonoids, carbohydrates, glycosides and phytosteroids. Methanolic extract showed higher total phenolic content (258±6.87 mg/gm GAE) as compared to flavonoid content (50±2.6 mg/gm RE) and inhibited the growth of Gram positive ( Bacillus subtilis , Staphylococcus aureus ), and Gram negative ( Escherichia coli , Klebsiella pneumonia ) bacteria. Minimum inhibitory concentration was comparatively less for Gram-negative (0.2-0.39 µg/ml) as compared to Gram-positive bacteria (0.78-1.56 µg/ml). When tested against yeast, R. emodi extract also showed comparatively more growth inhibition to Candida albicans (MTCC277) and C. albicans (ATCC90028) as compared to Saccharomyces cerevisiae (H1086). DPPH radical scavenging and FRAP assays of the methanolic extracts of R. emodi (IC 50 value 60.89 μg/ml with DPPH assay and 13.022 µM Fe (II) equivalents) were comparable to ascorbic acid (IC 50 value 43.84 μg/ml with DPPH assay and 2.682 µM Fe (II) equivalents). Methanolic extract of R. emodi showed synergistic antifungal activity when combined with fluconazole ( S. cerevisiae and C. albicans ) and amphotericin B ( S. cerevisiae ) and converting the extract from fungistatic to fungicidal. Combination of erythromycin and tetracycline with R. emodi extract showed synergistic antibacterial activity against E. coli and K . pneumonia and a combination of R. emodi extract with tetracycline demonstrated antibacterial activity against K . pneumonia . Moreover, extract alone showed fungistatic activity but specific fungicidal activity when combined with amphotericin B or fluconazole.

Combination of Erythromycin and Curcumin Alleviates Staphylococcus aureus Induced Osteomyelitis in Rats.

Osteomyelitis is commonly caused by Staphylococcus aureus. Both erythromycin and curcumin can suppress S. aureus growth, but their roles in osteomyelitis are barely studied. We aim to explore the activities of erythromycin and curcumin against chronical osteomyelitis induced by methicillin-resistant S. aureus (MRSA). Chronicle implant-induced osteomyelitis was established by MRSA infection in male Wistar rats. Four weeks after bacterial inoculation, rats received no treatment, erythromycin monotherapy, curcumin monotherapy, or erythromycin plus curcumin twice daily for 2 weeks. Bacterial levels, bone infection status, inflammatory signals and side effects were evaluated. Rats tolerated all treatments well, with no death or side effects such as, diarrhea and weight loss. Two days after treatment completion, erythromycin monotherapy did not suppress bacterial growth and had no effect in bone infection, although it reduced serum pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6. Curcumin monotherapy slightly suppressed bacterial growth, alleviated bone infection and reduced TNF-α and IL-6. Erythromycin and curcumin combined treatment markedly suppressed bacterial growth, substantially alleviated bone infection and reduced TNF-α and IL-6. Combination of erythromycin and curcumin lead a much stronger efficiency against MRSA induced osteomyelitis in rats than monotherapy. Our study suggests that erythromycin and curcumin could be a new combination for treating MRSA induced osteomyelitis.

Effect of sodium houttuyfonate in combination with erythromycin on luxS, agr/RNAⅢ of Staphylococus epidermidis

Quorum sensing of bacteria and its specific gene expression regulation have a very important role in bacterial biofilm formation. LuxS and agr are the key regulatory genes in quorum sensing of Staphylococcus epidermidis, and RNA Ⅲ is the effector molecule of agr system. In order to evaluate the effects of sodium houttuyfonate in combination with erythromycin on the transcription level of S. epidermidis, serial dilution method was used to determine the MIC of sodium houttuyfonate, erythromycin and vancomycin on S. epidermidis, and fluorescent quantitative PCR method was used to detect the transcription levels of luxS, agr/RNAⅢ in different time periods after treatment on S. epidermidis by sodium houttuyfonate in combination with erythromycin, vancomycin, and erythromycin alone. Our results showed that in treatment by 1/2MIC, 1/4MIC sodium houttuyfonate, 1/2MIC sodium houttuyfonate +1/2MIC erythromycin, 1/4MIC sodium houttuyfonate+1/4MIC erythromycin, and 1/8MIC sodium houttuyfonate+1/8MIC erythromycin for ATCC 35984, they could rapidly up-regulate the expression of luxS of S. epidermidis from the beginning as compared with negative control, with significant differences (P<0.05); furthermore, sodium houttuyfonate can still up-regulate the expression of luxS even after treatment for 6, 12 and 48 h. Sodium houttuyfonate in MIC and 1/2MIC concentration can significantly down-regulate the expression of agr (P<0.05); 1/2MIC sodium houttuyfonate+1/2MIC erythromycin, 1/4MIC sodium houttuyfonate+1/4MIC erythromycin, can also significantly down-regulate the expression of agr in 6 h, 12 h and 24 h(P<0.05). Sodium houttuyfonate in MIC, can significantly down-regulate the expression of RNA Ⅲ (P<0.05), and 1/2MIC sodium houttuyfonate+1/2MIC erythromycin can also significantly down-regulate the expression of RNAⅢ(P<0.05). Therefore, our presented results showed that sodium houttuyfonate in combination with erythromycin can rapidly up-regulate the transcription of luxS of S. epidermidis, and can down-regulate the expression of agr/RNA Ⅲ in certain concentrations, and suggested that sodium houttuyfonate in combination of erythromycin could inhibit mutual aggregation between S. epidermidis and biofilm bacteria, inhibit membrane nutrition and formation of water transport channels, prevent separation of bacterial cells in biofilm, and inhibit the formation of bacterial exotoxin of S. epidermidis.

Combination of erythromycin and propranolol for treatment of childhood cyclic vomiting syndrome: a novel regimen.

This study aimed to evaluate the erythromycin efficacy in childhood cyclic vomiting syndrome. Cyclic vomiting syndrome (CVS) is an unusual cause of episodic emesis in children and erythromycin is an effective treatment. In this prospective study, 301 patients with a final diagnosis of CVS enrolled in two separated groups. The first group received erythromycin for 7 days and propranolol for at least 9 months (n=155). The second group was treated with propranolol alone for at least 9 months (n=146). These two groups were compared for response to the treatment and the recurrence of symptoms after treatment completion. Relationship of response, recurrence, and characteristics of the disease was assessed. Both groups showed a significant difference in terms of response to treatment (P=0.002), however the recurrence after treatment completion had no considerable difference (P=0.563). There was no relationship between CVS characteristics and these two items (response and recurrence). In our point of view, the addition of erythromycin to standard propranolol treatment can improve the response to treatment, although it has no significant effect on recurrence of CVS symptoms. We suggest the use of erythromycin for 7 days in addition to CVS standard therapy.