Antimicrobial resistance of genital mycoplasmas recovered from nonpregnant women in Greece: trends over the last 15 years.

Aim: To study antimicrobial susceptibilities of genital mycoplasmas recovered from endocervical samples of reproductive-age, nonpregnant women (n = 8,336). Materials & methods: For isolation and susceptibility testing, the Mycoplasma IST2 kit was used. Results: As many as 2093 samples were positive for mycoplasmas. The vast majority (>96%) of Ureaplasma urealyticum remained susceptible to tetracycline, doxycycline, josamycin and pristinamycin, whereas susceptibility rates to azithromycin and fluoroquinolones were significantly decreased. Mycoplasma hominis exhibited high susceptibility rates to doxycycline, pristinamycin and josamycin (98.1-100%), while susceptibilities to tetracycline and fluoroquinolones were considerably lower. Conclusion: Doxycycline remained highly potent for treating mycoplasmas; nevertheless, susceptibilities to other antimicrobials were significantly diminished.

Pharmacokinetic/Pharmacodynamic Determination of Systemic MIC Breakpoints for Intermittent, Extended, and Continuous Infusion Dosage Regimens of Mecillinam.

Intravenous mecillinam has been used for the treatment of urosepsis at several dosing regimens, including a dose of 1,000 mg three times a day (TID). In the current pharmacokinetic/pharmacodynamic (PK/PD) study, we analyzed intermittent, extended, and continuous infusion regimens of mecillinam to provide dosage recommendations to treat infections caused by Enterobacterales exhibiting relatively higher mecillinam MICs than the wild-type strains. Monte Carlo simulation studies indicated that regimens of 1,000 mg TID and 1,000 to 1,200 mg four times a day (QID) are efficacious against wild-type and extended-spectrum ß-lactamase-producing Enterobacterales, respectively. Prolonged infusion regimens (extended and continuous) could cover carbapenemase producers with a higher range of MICs (2 to 8 mg/L). IMPORTANCE Previous studies have shown that intravenous mecillinam might be suitable for treatment of urosepsis. Since multidrug-resistant Enterobacterales are common pathogens in such infections, an effort was made to delineate intermittent, extended, and continuous infusion regimens that could cover pathogens exhibiting relatively higher mecillinam MICs than the wild-type strains. Our PK/PD analysis has shown that mecillinam might be considered a valuable therapeutic option for the treatment of systemic infections caused by extended-spectrum ß-lactamase- and carbapenemase-producing Enterobacterales exhibiting mecillinam MICs up to 8 mg/L.

Microbiological findings in prepubertal and pubertal girls with vulvovaginitis.

Vulvovaginitis is a common and challenging gynaecological problem in prepubertal and pubertal girls. Such an infection, owing to a wide range of aetiologies, if not responding to hygienic measures, needs further investigation through vaginal cultures, since treatment should be tailored accordingly. This study aimed to investigate the pathogens isolated in prepubertal and pubertal girls with signs and symptoms of vulvovaginitis. A total of 2314 symptomatic girls, 1094 prepubertal and 1220 pubertal, aged 2 to 16 years, were included. Vaginal samples were inoculated on specific culture plates followed by incubation in aerobic, anaerobic or CO2 atmosphere at 37 °C for 24 or 48 h, as appropriate. The identification of the isolated pathogens was carried out using Gram stain, conventional methods and the automated system VITEK 2 (BioMerieux, Marcy l'Etoile, France). Positive cultures were obtained from 587 (53.7%) of prepubertal girls and 926 (75.9%) of pubertal girls. A total of 613 and 984 pathogens were detected in prepubertal and pubertal subjects, respectively. Isolated bacteria included 40.1% and 22.8% Gram-positive cocci, 35.6% and 24.8% Gram-negative rods in the prepubertal and pubertal groups, respectively, with faecal pathogens being the most prevalent. Bacterial vaginosis was diagnosed in 22.8% of prepubertal and 37.9% of pubertal girls. Candida species were isolated mostly in the pubertal girls (14.5%). CONCLUSION: Culture results should be evaluated with caution in children with vulvovaginitis. In the prepubertal girls, the most common isolated pathogens were opportunistic bacteria of faecal origin while girls in late puberty were more susceptible to bacterial vaginosis and vulvovaginal candidiasis. WHAT IS KNOWN: • Vulvovaginitis is the most frequent and challenging reason for referral to paediatric and adolescent gynaecology services. • Microbiological examination can prove to be a significant tool to help diagnosis although results should be evaluated with caution in children. WHAT IS NEW: • Significantly more positive vaginal cultures and pathogens were recorded in symptomatic pubertal girls compared to prepubertal children. • The prevalence of bacterial vaginosis was increased in both prepubertal and pubertal girls with vulvovaginitis although significantly more in girls at puberty.

Seminal plasma visfatin levels negatively correlate with sperm concentration.

INTRODUCTION: Visfatin is involved in nicotinamide adenine dinucleotide biosynthesis, with a possible role in spermatogenesis. We investigated seminal plasma visfatin levels and its possible correlations with sperm parameters (concentration, motility, morphology) and BMI.

Baseline Values and Kinetics of IL-6, Procalcitonin, and TNF-α in Landrace-Large White Swine Anesthetized with Propofol-Based Total Intravenous Anesthesia.

The baseline levels of various inflammatory mediators and their changes during anesthesia in swine are not known. The aim of this animal study was to measure the baseline values and kinetics of interleukin-6, procalcitonin, and tumor necrosis factor-alpha in healthy Landrace-Large White swine anesthetized with propofol-based total intravenous anesthesia. We included 8 healthy male pigs with an average weight of 19 ± 2 kg (aged 10-15 weeks) that were subjected to propofol-based total intravenous anesthesia for 8 hours. Complete blood count, serum chemistry, and serum levels of interleukin-6, procalcitonin, and tumor necrosis factor-alpha were analyzed, and serum levels were quantified hourly. Blood was also collected for bacterial culturing. Baseline values of interleukin-6 and procalcitonin were 18 pg/ml and 21 ng/ml, respectively, while tumor necrosis factor-alpha was not detectable during collection of baseline samples. A statistically significant difference was observed in interleukin-6 levels between time points (p < 0.0001). Procalcitonin increased with time, but there were no significant differences between time points (p = 0.152). Tumor necrosis factor-alpha increased until the 3rd hour of propofol-based total intravenous anesthesia, while after the 4th hour, it gradually decreased, reaching its baseline undetectable values by the 7th hour (p < 0.001). Our results can serve as the basis for further translational research.

Initial Immune Response in Escherichia coli, Staphylococcus aureus, and Candida albicans Bacteremia.

Sepsis remains a leading cause of mortality worldwide and is characterized by sustained inflammatory responses, reflected as changes in the expression profile of cytokines with time. The aim of the present study was to investigate the dynamic changes in complete blood count, serum chemistry, procalcitonin (PCT), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in Escherichia coli, Staphylococcus aureus, and Candida albicans bacteremia. Study subjects were 32 healthy male Landrace-Large White pigs, aged 10-15 weeks and of average weight 19 ± 2 kg. Bacteremia was induced by continuous intravenous infusion of microbial suspensions during a period of 8 h. E. coli and S. aureus bacteremia were associated with a significant gradual decrease in white blood cells and platelets, respectively (p = 0.002 and p = 0.004), while candidemia was characterized by a significant gradual decrease in lymphocytes (p = 0.009). Serum PCT levels were either undetectable or very low, with no significant changes with time in all groups. E. coli bacteremia elicited a strong pro-inflammatory response, characterized by a significant increase in TNF-α expression from the onset of bacteremia (p = 0.042). C. albicans exhibited a different profile with an early, moderate increase in TNF-α followed by a subsequent marked increase in IL-6 levels (p = 0.03). The differential regulation of inflammatory and hematological responses depending on the pathogenic agent can reveal differences in the underlying inflammatory mechanisms, which may assist in the ongoing quest for the identification of a panel of circulating biomarkers during bacteremia.

Correction to: Initial Immune Response in Escherichia coli, Staphylococcus aureus, and Candida albicans Bacteremia.

The original version of this article contained mistakes, and the authors would like to correct them.

Genital tract infection and associated factors affect the reproductive outcome in fertile females and females undergoing in vitro fertilization.

Assisted reproductive techniques including in vitro fertilization (IVF) are being used increasingly worldwide and screening for genital tract infections (GTIs) is recommended prior to treatment as their presence may affect the success rate of IVF. The current study aimed to assess the possible associations between GTI-associated factors and reproductive outcome in a group of reproductive age fertile females and infertile females receiving IVF. A total of 111 infertile women enrolled in an IVF programme (Group A) and 104 fertile women (mothers of at least one child; Group B) underwent microbiological screening of vaginal and cervical samples. All samples were cultured using different protocols for aerobic pathogens, bacterial vaginosis (BV), Ureaplasma urealyticum, Mycoplasma hominis, Chlamydia trachomatis and human papilloma virus (HPV). Although each group were comparable in age, more infertile women were >30 years (P=0.0064), had a higher education level (P=0.0001) and were smokers (P=0.007). Only BV (P=0.0013) was more prevalent in Group A. Of the 111 infertile females who were scheduled for IVF, 32 females had a successful pregnancy (Group C) and 79 females exhibited IVF failure (Group D). Tubal factor (P=0.012), estradiol-2 (E2) levels <2,500 pg/ml (P=0.0009) and Mycoplasma infection (P=0.003) were identified to be the strongest predictors of IVF failure. The current study determined certain GTI-associated factors that may contribute to infertility in Greek females of reproductive age as well as other risk factors associated with failure in patients undergoing IVF. Further studies are required to confirm this conclusion.

Serum and follicular fluid irisin levels in women with polycystic ovaries undergoing ovarian stimulation: correlation with insulin resistance and lipoprotein lipid profiles.

Irisin, a novel exercise-induced myokine, has been implicated in different aspects of human metabolism and could be connected to polycystic ovary syndrome (PCOS). This study aimed to investigate serum and follicular fluid (FF) irisin levels in PCOS and normal women undergoing controlled ovarian stimulation and correlate them to the lipid and lipoprotein levels as well as with other metabolic parameters. Serum and FF irisin, together with serum lipid and lipoprotein levels were assessed in 70 women with diagnosed PCOS and 70 non-PCOS controls, under in vitro fertilization (IVF) treatment. Regardless of BMI, PCOS women had a significantly increased number of oocytes retrieved, fertilized oocytes and transferred embryos, although the number of women achieving pregnancies did not differ between groups. No correlation between FF irisin levels and pregnancy could be established. Serum and FF irisin levels were significantly higher in PCOS and overweight women and were positively associated with BMI and dyslipidemia. FF irisin levels correlated positively to and were lower than serum irisin levels. Further research would be helpful to analyze irisin's role in female reproduction, if any, as well as in human metabolism and the pathophysiology of PCOS.

Adropin levels in women with polycystic ovaries undergoing ovarian stimulation: correlation with lipoprotein lipid profiles.

This study aimed to investigate serum and follicular fluid (FF) adropin levels in polycystic ovary syndrome (PCOS) and normal women undergoing controlled ovarian stimulation and correlate them with the lipid and lipoprotein levels. We included 60 women (30 lean and 30 overweight) with diagnosed PCOS, and 60 age and weight-matched non-PCOS controls (30 lean and 30 overweight), under in vitro fertilization (IVF) treatment. Serum lipid and lipoprotein levels were assessed by the Abbott Architect c8000 autoanalyzer while adropin levels were determined by enzyme immunoassay. Serum and FF adropin levels were significantly lower in PCOS women compared with controls and FF adropin levels were lower than serum levels. Significantly higher serum levels of total cholesterol, LDL-C, triglycerides, apolipoprotein B, lipoprotein(a) and homocysteine were encountered in PCOS subjects, while HDL-C and apolipoprotein A1 were significantly lower compared with controls. According to univariate and multivariate analysis, serum and FF adropin levels were positively correlated with BMI and HDL-C levels and negatively correlated with LDL-C levels. Women with polycystic ovaries exhibit lipid lipoprotein alterations increasing the risk of cardiovascular diseases later in life. Our findings suggest a probable involvement of adropin both in human metabolism and in the pathophysiology of PCOS.

Antenatal group B streptococcus detection in pregnant women: culture or PCR?

INTRODUCTION: Group B streptococcus (GBS) is an important cause of neonatal infections. Maternal GBS colonization screening and intrapartum antimicrobial prophylaxis of colonized women can prevent neonatal diseases. The aim of this study was to assess the prevalence of GBS colonization in pregnant and non-pregnant women and to compare the performance of a polymerase chain reaction (PCR) assay with the established as gold standard technique, culture method, used for the detection of this microorganism. METHODOLOGY: Vaginal and rectal samples collected from 857 pregnant and 370 non-pregnant women were examined through cultures, while the samples collected from 452 pregnant women between 35 and 37 weeks of gestation were assayed by culture and PCR method targeting the cfb gene. RESULTS: GBS colonization was present in both pregnant and non-pregnant women. The colonization rate was similar in non-pregnant and first trimester pregnant women and then increased from first to the third trimester of pregnancy. GBS cultures for vaginal and rectal samples were positive in 13.2% and 14.3% in non-pregnant women, while in pregnant women 13.2% and 13.7% in the first trimester, and 15.0% and 16.5% in the second trimester, respectively. In third trimester pregnant women, compared to culture method, PCR identified a significantly increased number of GBS positive vaginal (18.4% vs 22.6%, p = 0.0006) and rectal (18.1% vs 21.2%, p = 0.01) samples. CONCLUSIONS: GBS colonization rate was higher in the third trimester. PCR proved to be a rapid and useful GBS screening method allowing a shorter detection time, while identifying more colonized women than culture.

Prevalence of vaginitis in different age groups among females in Greece.

Patients with vaginitis were classified into four groups: Group A (prepubertal under-aged females); Group B (pubertal under-aged females); Group C (reproductive age adult females); Group D (postmenopausal adult females). All vaginal specimens underwent microscopy, amine testing, Gram staining and culturing. Overall, 163 patients were included (33, 14, 81 and 35 patients, respectively). The most common infection was bacterial vaginosis (BV), followed by Ureaplasma infection, aerobic vaginitis (AV) and candidiasis. The most common AV-associated organism was Escherichia coli and the most common BV-associated organism was Gardnerella vaginalis. AV was more frequent in Group A, BV in Group C and Ureaplasma infections in Groups C/D. Decreased lactobacilli concentrations were associated with BV in fertile patients (Groups B-C). Although presentation of vaginitis is similar among females of different age in Greece, type and prevalence of pathogens differ. Normal vaginal flora changes are associated with higher risk of vaginitis in specific age groups. Impact Statement The worldwide incidence of reproductive tract infections has been increasing, with specific pathogens being associated with significant risk of morbidity and complications. However, literature data on the distribution of such infections in different age groups is limited. Therefore, the aim of this study was to provide data on the prevalence and causes of vaginitis in adult and non-adult females of all ages. This study has shown that although presentation of vaginitis is similar among females of different age groups and menstrual status in Greece, type and prevalence of responsible pathogens are different among groups. Changes in normal vaginal flora seem to be associated with higher risk of vaginitis in specific age-groups as well. These findings could contribute in adjusting diagnostic and therapeutic strategies for each age group according to the prevailing pathogens. Further research on antibiotic resistance and treatment outcomes for each age group should be conducted.

Cord blood copeptin concentrations in fetal macrosomia.

BACKGROUND/AIM: Excessive fetal growth is associated with increased adiposity and reduced insulin sensitivity at birth. Copeptin, a surrogate marker of arginine vasopressin (AVP) secretion, is upregulated in states of hyperinsulinemia and is considered one of the mediators of insulin resistance. We aimed to investigate cord blood concentrations of copeptin (C-terminal fragment of AVP pro-hormone) in healthy large-for-gestational-age (LGA) infants at term. METHODS: This prospective study was conducted on 30 LGA (n=30) and 20 appropriate-for-gestational-age (AGA, n=20) singleton full-term healthy infants. Cord blood copeptin and insulin concentrations were determined by ELISA and IRMA, respectively. Infants were classified as LGA or AGA, based on customized birth-weight standards adjusted for significant determinants of fetal growth. RESULTS: Cord blood copeptin concentrations were similar in LGA cases, compared to AGA controls, after adjusting for delivery mode. However, in the LGA group, cord blood copeptin concentrations positively correlated with birth-weight (r=0.422, p=0.020). In the AGA group, cord blood copeptin concentrations were elevated in cases of vaginal delivery vs elective cesarean section (p=0.003). Cord blood insulin concentrations were higher in LGA cases, compared to AGA controls (p=0.036). No association was recorded between cord blood copeptin concentrations and maternal age, parity, gestational age or fetal gender in both groups. CONCLUSIONS: Cord blood copeptin concentrations may not be up-regulated in non-distressed LGA infants. However, the positive correlation between cord blood copeptin concentrations and birth-weight in the LGA group may point to the documented association between AVP release and increased fat deposition. Vaginal delivery vs elective cesarean section is accompanied by a marked stress-related increase of cord blood copeptin concentrations.

Adropin concentrations in term pregnancies with normal, restricted and increased fetal growth.

OBJECTIVE: To determine levels of adropin (implicated in insulin resistance and endothelial dysfunction) in intrauterine growth restricted (IUGR), large (LGA) and appropriate for gestational age (AGA) pregnancies. METHODS: Cord-blood (UC) adropin and insulin concentrations were measured in 30 IUGR, 30 LGA and 20 AGA full-term infants and their mothers (MS). RESULTS: No significant differences in adropin concentrations were observed between the three groups. In the IUGR group MS adropin was significantly decreased when neonates had higher birth weights [b = -0.003, 95% CI -0.006 to 0.0, p = 0.043]. In all groups, MS adropin levels were positively correlated with UC ones (r = 0.282, p = 0.011) and were significantly increased in female neonates [b = 0.977, 95% CI 0.122-1.832, p = 0.026]. In the LGA group, MS insulin was negatively correlated with UC adropin (r = -0.362 p = 0.049). CONCLUSIONS: Increased maternal adropin levels in severe IUGR cases might represent a regulatory feedback mechanism against endothelial placental dysfunction. The positive correlation between maternal and umbilical cord adropin levels implies its transplacental transfer. Increased maternal adropin levels in female neonates could be attributed to interaction of adropin with fetal estrogens through vascular endothelial growth factor (VEGF). The negative correlation between maternal insulin and fetal adropin levels in the LGA group is probably attributed to their respective insulin resistance.

Cord blood irisin at the extremes of fetal growth.

BACKGROUND/AIMS: Irisin, a novel myokine with antiobesity properties, drives brown-fat-like conversion of white adipose tissue, thus increasing energy expenditure and improving glucose tolerance. We aimed to investigate circulating irisin concentrations in large-for-gestational-age (LGA) and intrauterine-growth-restricted (IUGR) fetuses, both associated with metabolic dysregulation and long-term susceptibility to obesity and metabolic syndrome development. METHODS: Plasma irisin and insulin concentrations were determined by ELISA and IRMA, respectively, in 80 mixed arteriovenous cord blood samples from LGA (n=30), IUGR (n=30) and appropriate-for-gestational-age (AGA, n=20) singleton full-term pregnancies. Fetuses were classified as LGA, IUGR or AGA, based on customized birth-weight standards adjusted for significant determinants of fetal growth. RESULTS: Fetal irisin concentrations were lower in IUGR cases than AGA controls (p=0.031). Cord blood irisin concentrations were similar in LGA and AGA groups and positively correlated with birth-weight, as well as customized centiles (r=0.245, p=0.029 and r=0.247, p=0.027, respectively). Insulin concentrations were higher in LGA, compared to AGA fetuses (p=0.036). In the LGA group, fetal irisin concentrations positively correlated with fetal insulin concentrations (r=0.374, p=0.042). CONCLUSIONS: Impaired skeletal muscle metabolism in IUGR fetuses may account for their irisin deficiency, which may be part of the fetal programming process, leading to increased susceptibility to later metabolic syndrome development. Furthermore, irisin down-regulation may predispose IUGR infants to hypothermia at birth, by inducing less "browning" of their adipose tissue and consequently less non-shivering thermogenesis. Irisin upregulation with increasing birth-weight may contribute to a slower fat gain during early infancy ("catch-down"), by promoting higher total energy expenditure. The positive correlation between irisin and insulin in the LGA group may reflect a counterbalance of the documented hyperinsulinemia, which is partly responsible for the excessive fat deposition in the LGA fetus.

The role of microRNAs in the pathogenesis of endometrial cancer: a systematic review.

INTRODUCTION: Epigenetics seem to play a primary role in the current research on the pathogenesis of different types of endometrial cancer. Data so far indicate that microRNAs regulate different pathways that could lead to carcinogenesis when not functioning properly. The aim of this review is to summarize current knowledge on microRNAs that have been associated with endometrial cancer development. MATERIAL AND METHODS: From July 2014 to August 2014, we conducted a comprehensive research utilizing major online search engines (Pubmed, Crossref, Google Scholar). The main keywords used in our search were endometrial cancer/carcinoma; microRNA; epigenetics; novel biomarkers; pathogenesis. RESULTS: Overall, we identified 155 studies, although only 77 were eligible for this review. Different miRNAs were identified to contribute either promoting the carcinogenesis in the endometrium or inhibiting different steps of endometrial cancer development. Tumour growth, cell proliferation, apoptosis and invasion metastasis have been identified as the main processes where miRNAs seem to be implicated. CONCLUSIONS: microRNAs are effective regulators of gene expression that has a significant role in the pathogenesis of endometrial cancer. Research concerning possible therapeutic implications has been promising, although there is still a significant distance to be covered between research observations and clinical results. Extensive preclinical and translational research is still required to improve the efficacy and minimize unwanted effects of miRNAs-based therapy.