Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA).

Background: Data on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials. Methods: An international matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings: Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-ß-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation: The main risk factors for CRE infections in hospitals with high incidence included previous colonization, urinary catheter and exposure to broad spectrum antibiotics. Funding: The study was funded by the Innovative Medicines Initiative Joint Undertaking (https://www.imi.europa.eu/) under Grant Agreement No. 115620 (COMBACTE-CARE).

Spotlight on Early COVID-19 Research Productivity: A 1-Year Bibliometric Analysis.

Coronavirus disease 2019 (COVID-19), one of the most serious public health crises in over a century, has led to an unprecedented surge of publications across all areas of knowledge. This study assessed the early research productivity on COVID-19 in terms of vaccination, diagnosis, treatment, symptoms, risk factors, nutrition, and economy. The Scopus database was searched between January 1, 2020 and December 31, 2020 to initially examine the research productivity on COVID-19, as measured by total publications by the 20 highest-ranked countries according to gross domestic product. The literature search was then refined, and research productivity was assessed across seven major research domains related to COVID-19: vaccination, diagnosis, treatment, symptoms, risk factors, nutrition, and economy. The initial literature search yielded 53,348 publications. Among these, 27,801 publications involved authorship from a single country and 22,119 publications involved authorship from multiple countries. Overall, the United States was the most productive country (n = 13,491), with one and a half times or more publications than any other country, on COVID-19 and the selected domains related to it. However, following adjustment for population size, gross domestic product, and expenditure for research and development, countries of emerging economies such as India along countries of lower population density such as Switzerland, Indonesia, and Turkey exhibited higher research productivity. The surge of COVID-19 publications in such a short period of time underlines the capacity of the scientific community to respond against a global health emergency; however where future research priorities and resource distribution should be placed on the respective thematic fields at an international level, warrants further investigation.

Intravenous fosfomycin for the treatment of patients with bone and joint infections: a review.

INTRODUCTION: Fosfomycin is a wide spectrum bactericidal antibiotic with a unique mode of action, low toxicity, and good penetration in tissues with deep-seated infections, including bone and joint infections. AREAS COVERED: Data were extracted from 19 published articles. Three hundred and sixty-five patients, with broad age range, received intravenous fosfomycin for the treatment of bone and joint infections (including arthritis, acute and chronic osteomyelitis, discitis, periprosthetic joint infection). Fosfomycin was given as part of a combination antimicrobial therapy in the majority of patients (93.7%). The dosage of fosfomycin ranged from 4 g/day (in one case) to 24 g/day. The dosage of fosfomycin, in some cases, mostly pediatric, was calculated based on body weight, ranging from 50 mg/kg/day to 250 mg/kg/day. The duration of fosfomycin treatment ranged from a couple of days up to 3 months. The most common isolated pathogen was Staphylococcus aureus (38.9%). Three hundred patients (82.2%) were successfully treated. Fosfomycin was well tolerated, as few patients developed mild adverse events, mostly gastrointestinal discomfort, hypernatremia, skin rash, and neutropenia. EXPERT OPINION: The available data suggests that intravenous fosfomycin may be beneficial for the treatment of patients with bone and joint infections, especially when used as part of a combination antibiotic regimen.

Clinical use of intravenous polymyxin B for the treatment of patients with multidrug-resistant Gram-negative bacterial infections: An evaluation of the current evidence.

OBJECTIVES: The epidemic dimensions of the emergence of multidrug-resistant (MDR) Gram-negative bacterial infections have led to the revival of old antibiotics, including the polymyxins. METHODS: We performed a review and meta-analysis to evaluate the current literature data regarding the effectiveness and safety of intravenous polymyxin B in patients with MDR Gram-negative bacterial infections and the overall mortality and nephrotoxicity in patients treated with intravenous polymyxin B either as monotherapy or combination therapy. RESULTS: A total of 5 prospective and 28 retrospective studies, 1 cross-sectional study, 2 retrospective case series and 7 case reports provided data regarding the effectiveness and/or toxicity of intravenous polymyxin B. All-cause mortality of 2910 patients (from 27 studies) who received intravenous polymyxin B was 41.2% (95% CI 35.5-47.0%). All-cause nephrotoxicity of 2994 patients (from 28 studies) treated with intravenous polymyxin B was 40.7% (95% CI 35.0-46.6%). Renal failure among 2111 patients (from 14 studies) was 11.2% (95% CI 8.7-13.9%). CONCLUSION: Mortality of patients treated with intravenous polymyxin B is similar to the literature-reported mortality of patients treated with intravenous colistin, while nephrotoxicity associated with polymyxin B use is possibly milder compared with colistin use based on literature data. Head-to-head prospective studies would help to clarify the benefit of polymyxin B over colistin. However, a critical evaluation of the existing worldwide literature data supports the need for availability of the intravenous formulation of polymyxin B as a potentially useful option for the treatment of patients with MDR and extensively drug-resistant (XDR) Gram-negative bacterial infections.

Benefits of prolonged infusion of beta-lactam antibiotics in patients with sepsis: personal perspectives.

INTRODUCTION: In the current era of relatively scarce antibiotic production and significant levels of antimicrobial resistance, optimization of pharmacokinetics and pharmacodynamics of antibiotic therapy is mandatory. Prolonged infusion of beta-lactam antibiotics in comparison to the intermittent infusion has the theoretical advantage of better patient outcomes. Apparently, conflicting data in the literature possibly underestimate the benefits of prolonged infusion of antibiotic treatment. AREAS COVERED: We provide our perspective on the subject based on our experience and by critically evaluating literature data. EXPERT OPINION COMMENTARY: In our opinion, the available data are suggestive of the beneficial role of prolonged infusion of beta-lactams in regard to piperacillin/tazobactam and carbapenems after administering a loading dose. While more data from randomized controlled trials are necessary to solidify or negate the evident benefits of prolonged infusion of the aforementioned antibiotics, clinicians should strongly consider this mode of administration of relevant antibiotics, especially in patients with severe infections.

Intravenous fosfomycin for the treatment of patients with central nervous system infections: evaluation of the published evidence.

INTRODUCTION: Central nervous system (CNS) infections have considerable morbidity and mortality. Fosfomycin is a broad spectrum bactericidal antibiotic with favorable pharmacokinetic properties and low toxicity, satisfactory penetration in the cerebrospinal fluid and is authorized for the treatment of bacterial meningitis. AREAS COVERED: The objective of this analysis was to evaluate the available data regarding the effectiveness and safety of intravenous fosfomycin for the treatment of CNS infections. Thirty-two relevant publications were identified. Data from 224 patients who received intravenous fosfomycin as treatment for CNS infections were evaluated. Overall, 93.8% of patients were cured from the infection. Staphylococcus was the most frequent pathogen; Streptococcus pneumoniae, Neisseria meningitidis, and several other microbial agents, including multi-drug resistant and extensively drug-resistant bacteria, were also implicated. Fosfomycin was given as part of a combination treatment in the vast majority of the patients. The dosage of fosfomycin ranged between 4 g and 24 g per day; a regimen with 14-16 g per day was used in the majority of the cases. Fosfomycin was generally well tolerated. EXPERT OPINION: The evaluation of the published evidence suggests that fosfomycin may be beneficial in the treatment of patients with CNS infections.

Tigecycline for the treatment of patients with Clostridium difficile infection: an update of the clinical evidence.

PURPOSE: Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea in adult patients and is associated with considerable morbidity and mortality. Apart from the standard treatment regimens, tigecycline has shown significant in vitro activity against C. difficile but data regarding its clinical impact remains controversial. The aim of this article is to update the evidence related to the clinical role of tigecycline against C. difficile. METHODS: PubMed and Scopus databases were searched for relevant literature published from January 2015 to July 2018. RESULTS: Six retrospective cohort studies, 1 prospective study, 1 case series, and 2 case reports provided data regarding the effectiveness of tigecycline against C. difficile and were included in our evaluation. Also, we performed a meta-analysis based on 186 patients (from 4 studies) that showed clinical cure 79% (95% CI 73.0-84.5%). CONCLUSION: Despite the heterogeneity of the included studies and the small number of patients, the available evidence suggests that tigecycline might be considered as a potential therapeutic option for patients with CDIs, especially in severe cases.

Addressing clinical safety of antimicrobial resistance: personal perspectives.

Introduction: Antimicrobial resistance is an important challenge for patients, societies, practicing physicians and health care organizations worldwide. Predictions in regard to the morbidity and mortality of antimicrobial resistance are grave especially in the setting of an era where the pipeline of production of antimicrobial agents is relatively dry.Areas covered: Herein, a viewpoint will be provided regarding antimicrobial bacterial resistance as a clinical safety need based on personal experience and data from the literature.Expert opinion: A variety of antibiotics has been produced during the last decade but novelty regarding truly new antimicrobial agents is rather little, as these new antibiotics are mainly based on modifications of known pharmaceutical molecules. Therefore, as there is still a desperate need to address optimal clinical safety in regard to antimicrobial resistance, we believe that strong financial incentives and rewards to producers of antimicrobial agents (especially new in concept) are necessary. Furthermore, global surveillance of antimicrobial resistance as suggested by the World Health Organization, coordination of measures of justified and appropriate use of antibiotics and application of strict infection control principles are needed to lessen the negative clinical impact of antimicrobial resistance.

Trends of Mortality in Greece Prior to and During Its Current Financial Crisis (2009-2015).

OBJECTIVES: To study mortality changes in Greece prior to and during the financial crisis. STUDY DESIGN: Analysis of data by the Hellenic Statistical Authority (1955-2015). RESULTS: During the crisis, mortality increased from 9.76/1000 in 2009 to 10.52/1000 in 2012 and to 11.16/1000 in 2015, driven by an increase in the number of deaths and a decrease in the estimated population. The annual increase of the expected mortality accelerated during the crisis; in contrast, age-adjusted mortality continued to decrease up to 2014 and increased in 2015. The subpopulations that seemed to be affected more during the crisis were the elderly (especially those over 70 years), women, and citizens in southern Greece. The common denominator of all these subgroups was older age. Mortality due to heart diseases continued to decline at an accelerated pace; due to neoplasia continued to increase at an accelerated pace; and stroke mortality reversed (from decline to increment). CONCLUSIONS: The increment of crude mortality during the financial crisis in Greece should be attributed to the increase in deaths, only in part due to the aging population, the reduction in births, and the increase in emigration that contracted the population.

Developments on antibiotics for multidrug resistant bacterial Gram-negative infections.

Introduction: The constantly increasing spread of severe infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB) is a critical threat to the global medical community. After a long period of antibiotic pipeline pause, new antibiotic compounds are commercially available or are at late stages of clinical evaluation, promising to augment the therapeutic armamentarium of clinicians against deadly pathogens. Areas covered: This review summarizes available data regarding agents with potent activity against critical MDR Gram-negative pathogens, which urgently require new efficient antibiotics. Recently approved antibiotic formulations; and agents in advanced stages of development, including combinations of ß-lactam/ß-lactamase inhibitor, novel cephalosporins (cefiderocol), tetracyclines (eravacycline), aminoglycosides (plazomicin), quinolones (delafloxacin and finafloxacin) and pleuromutilins (lefamulin) are discussed in this review. Expert opinion: The recent introduction of new antibiotics into clinical practice is an encouraging step after a long period of pipeline stagnation. New formulations will be a useful option for clinicians to treat serious infections caused by several MDR Gram-negative pathogens. However, most of the new compounds are based on modifications of traditional antibiotic structures challenging their longevity as therapeutic options. More investment is needed for the discovery and clinical development of truly innovative and effective antibiotics without cross-resistance to currently used antibiotics.

Synergistic activity of colistin with azidothymidine against colistin-resistant Klebsiella pneumoniae clinical isolates collected from inpatients in Greek hospitals.

BACKGROUND: New antibiotics are urgently needed to treat multi-drug resistant infections; however, production of novel antibiotics is diminishing. Synergistic combination drug therapy to enhance the activity of available antibiotics may improve management of patients with resistant infections. METHODS: Colistin-resistant Klebsiella pneumoniae isolates were collected from inpatients in 10 Greek hospitals and used to study combination activity of colistin plus azidothymidine. Combination activity was evaluated with the sum of fractional inhibitory concentrations (ΣFIC) using the mini checkerboard broth microdilution method. RESULTS: A hundred individual strains were tested. Synergistic activity was noted in 79% (79/100) of isolates and additive activity in the remaining 21% (21/100). ΣFIC50 and ΣFIC90 were 0.28 and 0.56, respectively. CONCLUSION: Colistin with azidothymidine exhibited promising synergistic activity against colistin-resistant Klebsiella pneumoniae isolates warranting further investigation of the combination.

Clinical relevance of in vitro synergistic activity of antibiotics for multidrug-resistant Gram-negative infections: A systematic review.

OBJECTIVES: The aim of this review was to investigate the outcomes of patients infected with multidrug-resistant (MDR) or extensively drug-resistant (XDR) Gram-negative bacteria following synergy-guided antibiotic combination therapy (SGACT). METHODS: A systematic review of PubMed and Scopus databases was performed. Published studies of any design reporting outcomes of patients with MDR Gram-negative bacteria treated with SGACT were included. Two reviewers independently assessed the relevancy and quality of the retrieved articles and extracted the available data. RESULTS: Nineteen reports (530 patients) were included. Eleven case reports/series described 26 cases of systemic infection due to MDR Gram-negative bacteria treated with SGACT. Five deaths were reported, two of which were attributed to the infection. Six studies (including one randomised controlled trial) provided comparative data for patients treated with SGACT and those treated with unguided combination therapy (UCT) or active monotherapy. In the pooled analysis of unadjusted data from these studies (504 patients), there was no difference between SGACT and UCT or monotherapy (OR=0.47, 95% CI 0.21-1.04; I2=52%). Analysis of adjusted data showed that SGACT was significantly associated with survival (OR=0.44, 95% CI 0.20-0.98; I2=54%). CONCLUSION: These limited but promising findings warrant further investigation of SGACT in the outcome of patients with MDR Gram-negative infections in well-designed trials.

Fluoroquinolone-based versus ß-lactam-based regimens for complicated intra-abdominal infections: a meta-analysis of randomised controlled trials.

Complicated intra-abdominal infections (cIAIs) are common and confer significant morbidity, mortality and costs. In this era of evolving antimicrobial resistance, selection of appropriate empirical antimicrobials is paramount. This systematic review and meta-analysis of randomised controlled trials compared the effectiveness and safety of fluoroquinolone (FQ)-based versus ß-lactam (BL)-based regimens for the treatment of patients with cIAIs. Primary outcomes were treatment success in the clinically evaluable (CE) population and all-cause mortality in the intention-to-treat (ITT) population. Subgroup analyses were performed based on specific antimicrobials, infection source and isolated pathogens. Seven trials (4125 patients) were included. FQ-based regimens included moxifloxacin (four studies) or ciprofloxacin/metronidazole (three studies); BL-based regimens were ceftriaxone/metronidazole (three studies), carbapenems (two studies) or piperacillin/tazobactam (two studies). There was no difference in effectiveness in the CE (2883 patients; RR = 1.00, 95% CI 0.95-1.04) or ITT populations (3055 patients; RR = 0.97, 95% CI 0.94-1.01). Mortality (3614 patients; RR = 1.04, 95% CI 0.75-1.43) and treatment-related adverse events (2801 patients; RR = 0.97, 95% CI 0.70-1.33) were also similar. On subset analysis, moxifloxacin was slightly less effective than BLs in the CE (1934 patients; RR = 0.96, 95% CI 0.93-0.99) and ITT populations (1743 patients; RR = 0.94, 95% CI 0.91-0.98). Although FQ- and BL-based regimens appear equally effective and safe for the treatment of cIAIs, limited data suggest slightly inferior results with moxifloxacin. Selection of empirical coverage should be based on local bacterial epidemiology and patterns of resistance as well as antimicrobial stewardship protocols.

Resistance to fosfomycin: Mechanisms, Frequency and Clinical Consequences.

Fosfomycin has been used for the treatment of infections due to susceptible and multidrug-resistant (MDR) bacteria. It inhibits bacterial cell wall synthesis through a unique mechanism of action at a step prior to that inhibited by ß-lactams. Fosfomycin enters the bacterium through membrane channels/transporters and inhibits MurA, which initiates peptidoglycan (PG) biosynthesis of the bacterial cell wall. Several bacteria display inherent resistance to fosfomycin mainly through MurA mutations. Acquired resistance involves, in order of decreasing frequency, modifications of membrane transporters that prevent fosfomycin from entering the bacterial cell, acquisition of plasmid-encoded genes that inactivate fosfomycin, and MurA mutations. Fosfomycin resistance develops readily in vitro but less so in vivo. Mutation frequency is higher among Pseudomonas aeruginosa and Klebsiella spp. compared with Escherichia coli and is associated with fosfomycin concentration. Mutations in cAMP regulators, fosfomycin transporters and MurA seem to be associated with higher biological cost in Enterobacteriaceae but not in Pseudomonas spp. The contribution of fosfomycin inactivating enzymes in emergence and spread of fosfomycin resistance currently seems low-to-moderate, but their presence in transferable plasmids may potentially provide the best means for the spread of fosfomycin resistance in the future. Their co-existence with genes conferring resistance to other antibiotic classes may increase the emergence of MDR strains. Although susceptibility rates vary, rates seem to increase in settings with higher fosfomycin use and among multidrug-resistant pathogens.

Microablative fractional CO2 laser for the genitourinary syndrome of menopause: up to 12-month results.

OBJECTIVE: The aim of this study is to assess the efficacy of microablative fractional CO2 laser therapy for genitourinary syndrome of menopause (GSM) management, when three, four, or five laser therapies were applied in a follow-up period of 12 months. METHODS: Retrospective study evaluating GSM symptoms at baseline, and 1, 3, 6, and 12 months after last laser therapy. Visual analog scale, International Consultation on Incontinence Questionnaires- Female Urinary Tract Symptoms, International Consultation on Incontinence Questionnaires-Urinary Incontinence Short Form, Urogenital Distress Inventory-6, and Female Sexual Function Index were used for assessment of GSM symptoms' intensity or bothering and parameters of sexual function. RESULTS: Overall, 94 women were included (35, 35, and 24 received three, four, and five therapies, respectively). All GSM symptoms improved statistically significantly. Intensity of dyspareunia and dryness decreased from 9 (5-10) (median [minimum-maximum]) and 8 (0-10) at baseline to 0 (0-6) and 0 (0-8), 1 month after last laser therapy (all P < 0.001), respectively. FSFI and frequency of sexual intercourse increased from 10.8 (2-26.9) and 1 (0-8) at baseline to 27.8 (15.2-35.4) and 4 (2-8) 1 month after last laser therapy (all P < 0.001), respectively. The positive laser effect remained unchanged throughout the 12 months of follow-up. The same pattern was followed for symptom-free rates. Four or five laser therapies may be superior in lowering the intensity of GSM symptoms in comparison to three laser therapies, in short and long-term follow-up. Differences between four and five laser therapies were not found. CONCLUSIONS: Laser therapy may provide significant improvement and/or absence of GSM symptoms up to 12 months follow-up, irrespectively to the number of laser therapies applied. Symptoms intensity 1 month after last laser therapy may be indicative of GSM symptoms intensity at 12 months. One month after third laser therapy is the critical time to decide whether treatment extension should be offered.

Spotlight on inhaled ciprofloxacin and its potential in the treatment of non-cystic fibrosis bronchiectasis.

Non-cystic fibrosis bronchiectasis (NCFB) is a severe chronic illness characterized by irreversible dilation of airways and thickening of bronchial walls, chronic inflammation, repeated infections, and progressive obstruction of the airways. In contrast to cystic fibrosis bronchiectasis (CFB), which is a well-defined genetic disorder, NCFB is a heterogeneous disease caused by many different medical entities. Inhaled antibiotics are effective for patients with CFB, but their efficacy in NCFB has not been proven. The main pathogens involved in the colonization of patients with bronchiectasis are Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa. The latter is associated with increased morbidity and mortality. In addition, in NCFB, P. aeruginosa strains are frequently more resistant than those in CFB. At present, there are no approved inhaled antibiotic therapies for NCFB patients. Inhaled ciprofloxacin has been under investigation in the last few years. In two phase II randomized, double-blind, placebo-controlled trials, the use of inhaled ciprofloxacin was significantly associated with reduction in sputum bacterial density and greater eradication rates. In four phase III randomized, double-blind, placebo-controlled trials, the results regarding the time of the first exacerbation and the rate of exacerbations were inconsistent. Specifically, ORBIT-4 and RESPIRE-1 trials showed clinical benefit (prolongation of the time of the first exacerbation and reduced rate of exacerbations in the treatment group compared to the placebo group), whereas the ORBIT-3 and RESPIRE-2 failed to achieve their primary endpoints. The RESPIRE-1 was the first trial that examined the 14-days on/off course separate from the standard 28-days on/off regimen, which is based on CFB protocol treatments. The current data on the efficacy of inhaled ciprofloxacin are encouraging, but further evaluation is needed to determine the appropriate target group and the ideal duration of treatment.

A Model for Out-of-Hospital Multispecialty Emergency Medicine: Accomplishments and Challenges.

Home care has been traditionally considered as an important type of medical service. "SOS Doctors" is a Greek organization providing out-of-hospital multispecialty emergency medicine services the past 25 years. Its services mainly meet the demands of the elderly and the nonambulatory patients. The decreased number of hospitalizations, hospital-related infections, and need for patient transportation are the main advantages of a model for out-of-hospital multispecialty emergency medicine. However, the time consumed by the doctor related to transportation is a drawback of medical house calls. Despite the challenges, medical house calls are a useful part of health services in the modern health care system.

Efficacy of vaginal therapies alternative to vaginal estrogens on sexual function and orgasm of menopausal women: A systematic review and meta-analysis of randomized controlled trials.

Genitourinary syndrome of menopause (GSM) increases the probability of female sexual dysfunction (FSD). The aim of the current study is to systematically assess data regarding sexual function and use of vaginal therapies, alternative to vaginal estrogens (VE), in menopausal women with GSM. PubMed, Scopus and Cochrane Library were searched (May-September 2017) using combination keywords: "dyspareunia and vaginal therapy", "sexual function and vaginal therapy", "orgasm and vaginal therapy", "vaginal atrophy" and "genitourinary syndrome of menopause". Eligible studies were RCTs focusing on the use of vaginal therapies, alternative to VE, in menopausal women. These studies were written in English language and published in peer-reviewed journals with impact factor. Assessment of risk of bias was performed using the Cochrane Risk of Bias Tool. Outcomes involved dyspareunia, vaginal dryness, orgasm and all parameters of sexual function. Twenty-nine RCTs including 3689 menopausal women, were included. Vaginal therapies, alternative to VE included non-hormonal (vaginal laser, lubricants/moisturizers, phytoestrogens and lidocaine) and hormonal ones (Dehyadroapiandrosterone (DHEA), testosterone and oxytocin). Dyspareunia and/or vaginal dryness were assessed in 72% of the articles, while the FSD and orgasm in 45% and 28% of articles, respectively. Dyspareunia and vaginal dryness improved in all relevant studies. Sexuality scores of lubricants were inferior to estrogens [3 studies, n = 138, standardized mean difference (smd) -0.64, (95%CI -1.1, -0.2)]. Orgasm domain was the same for the DHEA 0.5% and placebo (2 studies, n = 663, smd 1.29 (95% -0.47, 3.05), I2:90%). Sexual satisfaction and sexuality score were the same when testosterone was compared or added to estrogen therapy (2 studies, n = 99, smd 0.16 (95%CI-0.23,0.56), I2:12% and 2 studies (n = 87), smd 0.20 (95%CI-0.23,0.62), I2:0%, respectively. Available data are not adequate to provide counseling by the physicians in menopausal women regarding the efficacy of vaginal therapies as an alternative to estrogens, on all parameters of sexual function.