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Aims: The aim of this study was to characterize Lactobacillus strains for their biological properties and amensalistic activities against genital and nongenital pathogens., Methods and Results: For the purpose, some special characteristics (H 2 O 2 , biofilm and antimicrobial substances production) as well as safety properties of 112 lactobacilli were evaluated. All the strains had good amensalistic characteristics, in particular cell-free supernatants of 10 strains showed antibacterial activity against bacteria, as well as Candida sp. Moreover, these 10 strains were excellent biofilm producers., Conclusions: These results provide evidence for the possible use as probiotics for vaginal co-therapy in case of dysbiosis., Significance and Impact of the Study: Recently, the problem of antibiotic resistance is constantly increasing, even though resources and energy are invested in order to increase knowledge on the mechanisms of action. Bacteriocins have a rapid mechanism of action, act at extremely low concentrations, are generally sensitive to proteases and they usually have a narrow killing spectrum; these characteristics reduce the possibility of the bacterium to develop resistance. This study is focused on the feasibility of a high production of antimicrobial substances and their characterization in order to be exploited as a therapeutic alterative or in co-therapy with antibiotics in case of vaginal dysbiosis., (© 2018 The Society for Applied Microbiology.)

Objective: Cakile maritima scop. (CKM) is a herbaceous plant (Brassicaceae) growing also in high salinity environment. It is an annual plant growing in clumps or mounds in the sand on beaches and bluffs., Materials and Methods: Stems, seeds, leaves and flowers of CKM were used to obtain 70% of ethanol extracts. The phenolic content of the different extracts was evaluated by the Folin-Ciocalteu method. The separation of phytochemical compounds was based on ultra-performance liquid chromatography coupled to mass spectrometry. Radical scavenging activity was determined by 1,1-diphenyl-2-picrylhydrazyl assay. The qualitative assay for the inhibition of α-glucosidase was quantified spectrophotometrically and the anti-inflammatory activity was determined in the U937 cell line by using gene expression of pro-inflammatory cytokines. Cell viability assay was done in U937, MM1S, and U266 cells by using the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The antimicrobial activity was investigated by MIC determination, "double-triple combinations assay", and growth inhibition curves analysis, using the extracts individually or in various combination. Statistical analysis was performed by the Student's t-test and ANOVA., Results: All parts of the plant exhibited a high antioxidant capacity as measured by DPPH assay. Furthermore, all extracts reduced (about 10 folds) the expression of inflammatory cytokines in macrophage following LPS treatment. As regards the antibacterial activity, only the seeds extract was able to inhibit both Gram-negative and Gram-positive bacteria when tested alone, whereas dual combinations of different extracts (leaves, flowers, stems and seeds) caused bacterial inhibition exhibiting a synergic action. Finally, we showed that the extracts did not exhibit cytotoxic effects in normal cells and that, surprisingly, it exhibited an anti-proliferative effect (inhibition ≈80%) in multiple myeloma U266 cells., Conclusions: Our study suggests that CKM possesses antioxidant, anti-inflammatory, antibacterial, anti-proliferative activities and such pleiotropic effects may be exploited under various pathological conditions.

Over the last twenty years there has been an alarming increase in isolation of Streptococcus pneumoniae strains with a reduced susceptibility not only to penicillin, but also to other betalactams and macrolides. This phenomenon justifies the great interest in new antibiotics. Cefditoren, a new aminothiazolyl oral cephalosporin, recently commercialized in Italy, is characterized by an extended activity against penicillin-resistant S. pneumoniae. The aim of this study is to evaluate the incidence of the resistance/susceptibility to various antibiotics in 1000 strains of S. pneumoniae (678 SPSS, 219 SPPI and 103 SPPR), clinically isolated during 2009. The data obtained by our in vitro study show that cefditoren is the most active agent against S. pneumoniae. In fact, the MIC90 values of 0.5 micrograms/ml obtained could be particularly significant in therms of therapeutic predictivity.

The aim of this study was to evaluate the in vitro antibiotic susceptibility of respiratory pathogens recently isolated in Italy to commonly used antibiotics including cefditoren. Six clinical microbiological laboratories collected, between January and September 2009, a total of 2,510 respiratory pathogens from subjects with community-acquired respiratory tract infections (CARTI). Ceftditoren, out of all the beta-lactams studied, had the lowest MIC(90 )against 965 strains of Streptococcus pneumoniae examined, followed by cefotaxime and ceftriaxone (2% resistance in penicillin-resistant S. pneumoniae (PRSP)). Against 470 Haemophilus influenzae , independently of their production of beta-lactamases or ampicillin resistance, cefditoren was the oral cephalosporin with the best in vitro activity, comparable to that of the injectable cephalosporins and levofloxacin. Higher MIC(90)s were found for the macrolides (4 - 16 mg/l) and cefaclor (4 - 32 mg/l). As was foreseeable, Streptococcus pyogenes (225 strains) was uniformly sensitive to all the beta-lactam antibiotics, but the elevated MIC(90 )values reduced (<75%) susceptibility of this pathogen to macrolides. Beta-lactamase-negative Moraxella catarrhalis (100 strains) had reduced susceptibility only to the macrolides, while the 250 beta-lactamase-producing strains also had reduced susceptibility to cefuroxime. Levofloxacin showed the lowest MIC(50)/MIC(90 )values in the producing strains, whereas cefditoren, cefotaxime and ceftriaxone in the non-producers. As regards the enterobacteriaceae, cefditoren and levofloxacin had the lowest MIC(90)s against Klebsiella pneumoniae. Cefditoren and the third-generation injectable cephalosporins had the lowest MIC(90)s against Escherichia coli (100% susceptibility) while levofloxacin was less active (86% susceptibility).In conclusion, cefditoren's wide spectrum and high intrinsic activity, as well as its capacity to overcome most of the resistance that has become consolidated in some classes of antibiotics widely used as empiric therapy for CARTI, allows us to suggest that cefditoren might be included in the european guidelines as one of the first-choice antibiotics in the treatment of CARTI.

The application of antimicrobial combinations may address the rising resistance to established classes of both systemic and topical agents and their clinical relevance is related to the presence of a significant postantibiotic effect (PAE). We investigated the effectiveness in vitro of the association between tobramycin and tea tree oil (TTO) against Gram-positive and Gram-negative bacteria. The minimal inhibitory concentrations, the bacterial killing and the PAE of tobramycin and TTO were determined both singly and in combination against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213. A synergistic interaction was observed against both strains tested: the mean PAEs were 1.3 and 1.7h for tobramycin against E. coli and S. aureus respectively, 10.8h for tobramycin and TTO (0.05%) against E. coli, 10.4h and 17.4h against S. aureus for tobramycin and TTO (0.25 and 0.50%, respectively). Longer PASMEs were observed with S. aureus after TTO/tobramycin exposure. In vitro interactions can improve the antimicrobial effectiveness of the antibiotic and may contribute for the development of novel topical agents for the treatment of skin lesions including conjunctiva and respiratory infections by inhalation., (Copyright 2009 Elsevier GmbH. All rights reserved.)

The aim of this study was to evaluate the in vivo effect of a repeated-dose regimen with prulifloxacin in comparison to amoxicillin/clavulanate on vaginal lactobacillus microflora. Thirty healthy female volunteers were treated with prulifloxacin or amoxicillin/clavulanate in this open, randomized, parallel-group, repeated-dose study. Vaginal signs and symptoms were assessed at the first doctor's Visit 0 (3 weeks prior to the start of the study), and subsequent examinations (1, 3, 5, 6, 7 and 8) (followup). Some volunteers treated with amoxicillin-clavulanate showed increased pH values and 73.3% of them had lower lactobacillus flora at Visit 3. this reduction was still present in 66.7% 3 days after the last dose and in 26.7% of subjects at the follow-up, about 7 - 13 days after the last dose. The situation was completely normalized at the second follow-up about one month after treatment stop. On the contrary, the repeated administration of prulifloxacin 600 mg tablets affected neither the pH nor the lactobacillus component of the vaginal flora in healthy fertile women. The oral administration of prulifloxacin may have advantages over some other antimicrobial agents because it preserves the normal vaginal microbiota in healthy women.

Eighty-one patients with clinical diagnosis of aerobic vaginitis (AV) were included in the study. The patients were randomized for treatment, 45 with kanamycin (100 mg vaginal ovules for 6 days, consecutively) and 36 with meclocycline (35 mg vaginal ovules for 6 days, consecutively). The patients were examined before starting the study, 1-2 days after treatment and 30 days after the end of the study. At the first follow-up the patients showed different levels of symptom reduction. Reduction in the presence of leukocytes, vaginal mucosa burning and itching were statistically significant in the group treated with kanamycin with respect to the group treated with meclocycline. Moreover, there was also reduced isolation of Enterobacteriaeae (97%) in the group treated with kanamycin versus those treated with meclocycline (76%). At the second follow-up, vaginal homeostasis (normalization of pH and presence of lactobacilli) was more evident in the kanamycin-treated group. In conclusion, our data suggest that the topical use of kanamycin could be considered a specific antibiotic for the therapy of this new pathology.

Streptogramins represent a unique class of antibiotics remarkable for their antibacterial activity and their unique mechanism of action. These antibiotics are produced naturally as secondary metabolites by a number of Streptomyces species and have been classified into two main groups. They consist of at least two structurally unrelated compounds, group A or M (macrolactones) and group B or S (cyclic hexadepsipeptides). Both groups bind bacterial ribosomes and inhibit protein synthesis at the elongation step and they act synergistically in vitro against many microorganisms. Streptogramins A and B act synergistically in vivo; the mixture of the two compounds is more powerful than the individual components and their combined action is irreversible. The pharmacokinetic parameters of group A and B streptogramins in blood are similar. The major gap, limiting the therapeutic use of the natural compounds, was represented by the lack dissolution in water. The synthesis of water-soluble derivatives of pristinamycin I(A) and II(B) has allowed the development of injectable, first represented by quinupristin/dalfopristin (Synercid) and oral formulations, represented by RPR-106972, streptogramins with fixed compositions. Streptogramins have demonstrated activity against Gram-positive microorganisms in vitro and in vivo, including those with multi-drug resistance. Moreover, the absence of cross-resistance to macrolides in many of these microorganisms and the rarity of cross-resistance between the two groups of antibiotics associated with the rapid bacterial killing are the principal features of the streptogramins, offering the possibility for treating the rising number of infections that are caused by multi-resistant Gram-positive bacteria.

The levels of flurithromycin in gynecological tissue in 20 female patients were studied after preoperative administration. The tissue flurithromycin levels obtained were comparable to those obtained in serum at 3 and 4 h but were frequently higher than those in serum at 6 and 12 h. Flurithromycin reached the highest concentrations in ovary at 4 h and in endometrium at 6 h.

The object of study was the evaluation of both the in-vitro and in-vivo activity of roxithromycin against Chlamydia trachomatis. In-vitro activity against C. trachomatis was achieved by means of minimum inhibitory concentration (MIC) determinations and was recorded as 0.05 mg/l. In vivo activity was tested in 15 of 60 women, attending the Planning Clinic, who were positive for C. trachomatis. Microbiological diagnosis of chlamydial infection was achieved by using a monoclonal direct smear test (Biomerieux-C trachomatis direct IF). All the patients and their partners were treated with 150 mg of roxithromycin twice a day for 15 days. All the patients were requested to avoid unprotected sexual intercourse up to the end of the therapy. The criterion for clinical efficacy was defined as disappearance of clinical signs and the criterion for microbiological efficacy was evidence of eradication of C. trachomatis at the follow-up (mean time: 30 days). A clinical cure and chlamydial eradication was recorded for all the patients at the end of the treatment and at follow-up. Clinical safety was also satisfactory.

Macrolides belong to a large family of drugs called macrocyclic antibiotics, that can be divided into four groups: macrolactamas or ansamycins, polyene macrolides, macrolide-like compounds and macrolide antibiotics. Macrolide antibiotics comprise a large group of drugs, which are very much alike, characterized by large lactonic cycle with 12, 14, 15 or 16 atoms, to which are bound sugar and/or aminosugar. Although there are very large structural differences, macrolides represent a homogeneous group of drugs for which both a spectrum and a mode of action are similar. Macrolide antibiotics bind to the large subunit of prokaryotic ribosomes and perturb protein synthesis. The antimicrobial activity of macrolides is broad spectrum, being exhibited against gram-positive and gram-negative bacteria, including actinomyces and mycobacteria, as well as against treponemes, mycoplasmas, chlamydiae, rickettsias and also against some protozoa. Depending on the drug concentrations, bacterial species and phase of growth, macrolides may be bacteriostatic or bactericidal. Macrolides show high tissue/serum rations and greater concentrations of antibiotics are though to be achieved at the presumed site of infection. Such findings are in agreement with the apparent volumes of distribution for all the macrolide drugs, which are generally large. The worldwide resurgence of interest in macrolide antibiotics has yielded several semisynthetic derivatives of 14- and 16-membered macrolides which have progressed to clinical trials.

A new macrolide, roxithromycin, appears to have some interesting pharmacokinetic characteristics dissimilar to those of erythromycin, e.g. it has the unusual property of a long serum half-life and the possibility of once daily dosing. Moreover tissue levels are higher than those obtained with other macrolides, and the drug is still present in the tissues up to 24 h. after dosing. The pharmacokinetics of roxithromycin were studied in 36 women undergoing gynecological surgery, and divided by means of the time of sampling into six different groups. Each group received an initial 300 mg dose followed by 8 successive doses of 150 mg at 12 h intervals. Blood and tissues samples were taken during surgery at 2, 6, 9, 12, 18 and 24 h after the last dose of roxithromycin and the patients were then allocated to one of the six groups by means of the sampling time. Tissue fragments were obtained from ovary, fallopian tubes, endometrium, myometrium, cervix and vagina immediately after the surgical resection of the organs. Tissue and serum concentrations were determined by the microbiological method using Sarcina lutea ATCC 9341; the lowest limit of detection was 0.01 microg/ml or 0.01 microg/g. Roxithromycin reached the highest concentration at the 9th hour after last administration and its tissue levels would encourage a wide use of this drug as a satisfactory alternative to tetracyclines for the therapy of some gynecological infections.