Characterization of Salmonella phages isolated from poultry coops and its effect with nisin on food bio-control.

Salmonella is a bacterium associated with food contaminated by various animals, primarily poultry. Interest and research on bacteriophages are increasing because they can be used as an alternative against increasing antibiotic resistance. In our study, eight Salmonella-specific lytic bacteriophages were isolated from chicken feces. Two of the isolated phages (AUFM_Sc1 and AUFM_Sc3) were chosen for their characterization due to their broader host range. Based on morphological and genomic analysis, AUFM_Sc1 was identified to be close to similar Enterobacteria spp. CC31 (Myoviridae) and AUFM_Sc3 was identified to be close to Salmonella phage vB_Sen_I1 (Demerecviridae (formerly Siphoviridae)). Although these phages have shown promise for use in phage therapy applications for chickens, further studies are needed on their suitability. When a cocktail of these phages (AUFM_Sc1 + AUFM_Sc3) and nisin combination was applied on chicken breast meat, it was determined that it was effective against Salmonella contamination and while a good inhibitory effect was observed on the food, especially during the first 48 h, the effect decreased later, but the bacterial concentration was still low compared to the control group. Therefore, it is considered that the combination of AUFM_Sc1 + AUFM_Sc3 + nisin can be used as a food preservative against Salmonella.

Characterization of two bacteriophages specific to Acinetobacter baumannii and their effects on catheters biofilm.

Multidrug-resistant strains of Acinetobacter baumannii cause major nosocomial infections. Bacteriophages that are specific to the bacterial species and destroy bacteria can be effectively used for treatment. In this study, we characterized lytic bacteriophages specific to A. baumannii strains. We isolated lytic bacteriophages from environmental water samples and then investigated their morphology, host range, growth characteristics, stability, genome analysis, and biofilm destruction on the catheter surface. Our results showed that the efficacy of the phages varied between 32% and 78%, tested on 78 isolates of A. baumannii; 80 phages were isolated, and two lytic bacteriophages, vB_AbaP_HB01 (henceforth called C2 phage) and vB_AbaM_HB02 (henceforth called K3 phage), were selected for characterization. Electron microscopy scans revealed that the C2 and K3 phages were members of the Podoviridae and Myoviridae families, respectively. Whole-genome sequencing revealed that the sequence of the C2 phage is available in the NCBI database (accession number: OP917929.1), and it was found sequence identity with Acinetobacter phage AB1 18%, the K3 phage DNA sequence is closely related to Acinetobacter phage vB_AbaM_phiAbaA1 (94% similarity). The cocktail of C2 and K3 phages demonstrated a promising decrease in the bacterial cell counts of the biofilm after 4 h. Under a scanning electron microscope, the cocktail treatment destructed the biofilm on the catheter. We propose that the phage cocktail could be a strong alternative to antibiotics to control the A. baumannii biofilm in catheter infections.

The effect of phage-antibiotic combination strategy on multidrug-resistant Acinetobacter baumannii biofilms.

Acinetobacter baumannii (A. baumannii) is considered a critical human pathogen due to multi-drug resistance and increased infections. As a result of the resistance of A. baumannii biofilms to antimicrobial agents, it is necessary to develop new biofilm control strategies. In the present study, we evaluated the efficacy of two previously isolated bacteriophage C2 phage, K3 phage and phage cocktail (C2 + K3 phage) as a therapeutic agent in combination with antibiotic (colistin) against biofilm of multidrug-resistant A. baumannii strains (n = 24). The effects of phage and antibiotics on mature biofilm were investigated simultaneously and sequentially in 24 and 48 h. The combination protocol was more effective than antibiotics alone in 54.16% of the strains in 24 h. The sequential application was more effective than the simultaneous protocol compared with the 24 h single applications. When the application of antibiotics and phages alone was compared with their combined administration in 48 h. The sequential and simultaneous applications were more effective than single applications in all strains except two. We observed that combination of phage and antibiotics could increase biofilm eradication and provides new insights into the use of bacteriophages and antibiotics in the treatment of biofilm-associated infections caused by antibiotic-resistant bacteria.

Pregnancy outcomes following maternal macrolide use: A systematic review and meta-analysis.

To determine whether gestational use of all or specific macrolides (azithromycin, clarithromycin, roxithromycin or erythromycin) lead to an increase in rates of overall major congenital malformations, organ-specific malformations, and other adverse pregnancy outcomes in infants. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and Reprotox® databases were searched. Dichotomous outcomes or calculated log odds ratios and standard errors from observational studies are combined using the random-effects method in Review Manager 5.3. No significant increased risks for major congenital malformation (OR 1.06 [95% CI 0.99, 1.13]) and congenital heart defect (OR 1.05 [95% CI 0.92, 1.19]) following all macrolides use during the first trimester were detected. Prenatal azithromycin use was associated with a significantly increased risk of major congenital malformations in the analysis of cohort studies (OR 1.21 [95% CI 1.08-1.36]). This significance was also present in the sensitivity analysis. There were no statistically significant associations between the risk of organ specific malformations and all or specific macrolide exposures except for the decreased risk in hypospadias following erythromycin use in the meta-analysis of case-control studies (OR 0.38 [95% CI 0.18, 0.81]. Also, a significant 1.5-fold increased risk for spontaneous abortion following macrolide use was detected. A slight yet significantly increased rate of major congenital malformation with azithromycin exposure during pregnancy may be associated with maternal confounders. Nevertheless, level II ultrasound can be suggested following maternal azithromycin use during the first trimester. Future studies should take into account the inclusion of a disease-matched control group and accurate classification of the malformations.

Molecular mechanisms involved in pre-eclampsia through expressional regulation of endothelin-1.

INTRODUCTION: Preeclampsia (PE) is a condition affecting 2-8% of all pregnancies and is a leading cause of perinatal morbidity and mortality. In our study; we aim to investigate the differences in endothelin-1 (ET-1) at both tissue and blood level in the placenta, umbilical cord, and maternal blood obtained from different experimental groups and the changes in the contraction response of umbilical arteries in order to explain how PE affects mother and fetus. METHODS: Umbilical cord and placenta samples were obtained from normotensive controls (n = 10) and patients with preeclampsia (n = 10), aged 20-39 years, who delivered by cesarean section at term (between 37 and 39 weeks). All samples were investigated with isolated tissue bath, histopathological, immunohistochemical and real-time PCR methods. RESULTS: ET-1 messenger RNA expression levels and immunoreactivity were found significantly higher in the PE group while microRNA-1 and microRNA-125b (miR-125b) levels were significantly decreased in placenta compared to control. miR-125b levels were found significantly higher in maternal and umbilical cord blood samples of the PE group. The enlargement in intervillous space, decrease in villous branching, increase in syncytial knots and smaller lumen areas in umblicard cord vessels were also observed. In tissue bath experiments, there were no significant differences in ET-1 responses between groups. DISCUSSION: We tried to evaluate molecular mechanisms of PE pathogenesis through expressional regulation and contraction response of ET-1. Although quite abundant work in this field has previously highlighted the importance of ET-1 system, further work is needed to determine the molecular mechanisms underlying expressional regulation of ET-1 in PE.

Pregnancy outcomes following maternal exposure to statins: A systematic review and meta-analysis.

AIMS: The objective of this meta-analysis was to determine whether maternal exposure to statins is associated with increased rates of major congenital malformations and other adverse pregnancy outcomes. METHODS: PubMed/Medline, Web of Science and Reprotox® databases were searched. Cohort and case control studies with prenatal exposure to statins were included. RESULTS: Analysis of five cohort studies and one case-control study showed no significant increase in rate of major congenital malformations when the exposed group was compared with the control ([OR 1.27; 95% CI 0.80-2.04], [aOR 1.05; 95% CI 0.84-1.31]). A significant increase in heart defect risk was detected in the statin-exposed group when unadjusted ORs were combined (OR 2.47; 95% CI 1.36-4.49). Further analysis of the same outcome by using adjusted ORs showed no significant increase in heart defect risk in the statin-exposed group compared with the controls (aOR 1.24; 95% CI 0.93-1.66). A significantly lower live birth rate (OR 0.60, 95% CI 0.49-0.75) and a higher spontaneous abortion rate (OR 1.36; 95% Cl 1.06-1.75) were detected in the statin-exposed group. CONCLUSIONS: Gestational statin exposure was not associated with a significant increase in risk of major congenital malformations, heart defects and other adverse pregnancy outcomes, except spontaneous abortion and live birth rate, which may be associated with maternal comorbidity and other unadjusted risk factors. Further research focusing on particular statins is needed to draw more definitive conclusions.

The comparison of lytic activity of isolated phage and commercial Intesti bacteriophage on ESBL producer E. coli and determination of Ec_P6 phage efficacy with in vivo Galleria mellonella larvae model.

Antibiotic resistance is one of the crucial public health challenges. As a result of rising resistance, as an alternative to antimicrobials, demands for bacteriophage therapy have increased significantly over the years. The objective of this study was to isolate and characterize potentially therapeutic phages active against Escherichia coli (E. coli) and compare the efficacy with commercial Intesti bacteriophage on the extended-spectrum beta-lactamase (ESBL) positive E. coli (ESBL-EC) and performed the effectiveness of bacteriophage using the Galleria mellonella (G. mellonella) larvae model. Intesti bacteriophage is a polyvalent bacteriophage-based drug. The isolated bacteriophages were obtained from the river and clinical isolates of E. coli were used for the enrichment of bacteriophage isolation. The phages were first screened based on plaque morphology and host ranges determined on clinical strains. The susceptibility of phages was determined against 50 clinical isolates of E. coli and eight different laboratory isolates using the spot test technique. E. coli lytic phage Ec_P6 was used to determine the therapeutic and preventive effects on the G. mellonella larvae model. The slides were prepared by G. mellonella hemolymph for cytologic examination, stained with May Grünwald Giemsa (MGG), and evaluated by light microscopy. The results of the activities revealed lytic spectra ranging from 24% to 97%. Overall strains were susceptible to one or more phages from the panel. It was proved that Intesti bacteriophage is very effective in a wide variety of strains of E. coli including test strains, also showed that isolated Ec_P6 phage is as effective as commercial phage. The best MOI of this phage was 0.01, and infectivity decreased above 60 °C. The results suggest that phage is stable at pH values ranging between 5.0 and 9.0. In vivo study was found that in E. coli infection to achieve a survival high rate the infected larvae should be after 2 h treated with 0.01 MOI phage (10 µL, 106 PFU/mL) and colistin doses (10 µL, 2.5 mg/kg). It also prevented infection, increasing the survival of the larvae compared to the untreated control group. Ec_P6 phage was found to have a potential for the treatment of E. coli infections.

Paroxetine overdose during pregnancy.

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of depression and anxiety disorders. In some epidemiological studies, slightly increased risks of major malformations and cardiac malformations have been reported following paroxetine exposure in the first trimester of pregnancy. However, such findings have been inconsistent. There is only one report of any overdose of an SSRI during pregnancy, and that involved escitalopram. The aim of this case report was to describe the impact of a paroxetine overdose in the first trimester of pregnancy on the health of the foetus. A 21-year-old mother of one child who was pregnant with a second child was prescribed 20 mg/day paroxetine hydrochloride for the treatment of anxiety/depression. The patient ingested 15 or 16 20-mg tablets of paroxetine hydrochloride (300-320 mg) during the 5th week of pregnancy as a suicide attempt. Within 15 min of ingestion, she was admitted to hospital and treated for intoxication. No evidence of maternal SSRI intoxication was observed after treatment. The patient consulted our teratology information service for further risk assessment regarding possible major congenital malformations following the paroxetine overdose. We were unable to find previous reports of paroxetine overdose during pregnancy in the literature. The timely administration of the overdose treatment and the lack of maternal intoxication symptoms were considered positive for the foetal well-being, and the patient was referred for perinatology and psychiatry follow-ups. A healthy, 3 500-g male infant was born at 38 weeks' gestation, and his development at the age of 2 years was normal. This is the first reported case of paroxetine overdose during pregnancy. Comprehensive studies are needed to evaluate pregnancy outcomes after SSRI overdose.Key PointsThere are no reported data on paroxetine overdose during pregnancy.The aim of this case report was to describe the impact of a maternal paroxetine overdose in the first trimester of pregnancy on the health of the foetus. No evidence of maternal SSRI intoxication was observed.No congenital malformations or developmental disorders were observed in the child at 2 years of age.Comprehensive studies are needed to evaluate pregnancy outcomes following SSRI overdose.

The evaluation of five commercial bacteriophage cocktails against methicillin-resistant Staphylococcus aureus isolated from nasal swab samples.

Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are a growing concern for public health resulting in increase in morbidity, length of hospital stay, and cost of treatment. MRSA nasal swab screening may give clinicians additional information for decision of empiric antimicrobial agents. While increasing antibiotic resistance leads to new treatment approaches, bacteriophages are one of the most promising methods for these alternatives. It was aimed to determine the effectiveness of bacteriophages against MRSA isolates. Nasal swab samples were collected from outpatients without any evidence of infection who applied to Hatay, Mersin and Gaziantep family and immigration health centers. A series (35) were isolated from Turkish patients, and G series (64) were isolated from Syrian immigrants. Methicillin resistance was determined phenotypically and genotypically. Also, antibiotic susceptibilities of all isolates were determined against erythromycin, clindamycin, gentamicin, linezolid, rifampicin, and mupirocin. The total antimicrobial resistance rates of isolates were found to be 11%, 28%, 8%, 5%, 16%, 19%, and 29% respectively. The high susceptibility rate against ciprofloxacin (88.8%) was remarkable. The overall susceptibility of MRSA strains to ENKO, INTESTI, PYO, SES, and staphylococcal bacteriophages was 67.7%, 55.5%, 53.5%, 61.6% and 44.4%, respectively. The antibiotic susceptibility rates (except erythromycin) and efficacy of bacteriophages were higher in group A. Considering that high efficacy rates were not achieved in the study and the sensitivity rates of Turkish isolates to all phages were found to be higher than those of Syrian isolates, searching for phages in the geographic regions where the pathogen is common may be helpful to obtain suitable phages for treatment.