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.

The Relation between Caffeine Consumption and Endometriosis: An Updated Systematic Review and Meta-Analysis.

While the contributing factors leading to endometriosis remain unclear, its clinical heterogeneity suggests a multifactorial causal background. Amongst others, caffeine has been studied extensively during the last decade as a putative contributing factor. In this systematic review and meta-analysis, we provide an overview/critical appraisal of studies that report on the association between caffeine consumption and the presence of endometriosis. In our search strategy, we screened PubMed and Scopus for human studies examining the above association. The main outcome was the relative risk of endometriosis in caffeine users versus women consuming little or no caffeine (<100 mg/day). Subgroup analyses were conducted for different levels of caffeine intake: high (>300 mg/day) or moderate (100-300 mg/day). Ten studies were included in the meta-analysis (five cohort and five case-control studies). No statistically significant association was observed between overall caffeine consumption and risk for endometriosis (RR 1.12, 95% confidence interval (CI) 0.97-1.28, I2 = 70%) when compared to little or no (<100 mg/day) caffeine intake. When stratified according to level of consumption, high intake was associated with increased risk of endometriosis (RR 1.30, 95%CI 1.04-1.63, I2 = 56%), whereas moderate intake did not reach nominal statistical significance (RR 1.18, 95%CI 0.99-1.40, I2 = 37%). In conclusion, caffeine consumption does not appear to be associated with increased risk for endometriosis. However, further research is needed to elucidate the potential dose-dependent link between caffeine and endometriosis or the probable role of caffeine intake as a measurement of other unidentified biases.

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.

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.

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.

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.

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.

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.

Temporal Trends (1999-2015) in the Impact Factor of Biomedical Journals Published by US and EU Scientific Societies.

OBJECTIVE: The impact factor has emerged as the most popular index of scientific journals' resonance. In this study we aimed to examine the impact factor trends of journals published by scientific bodies in the United States of America (USA) and Europe (EU). METHODS: We randomly chose 11 categories of Journal of Citation Reports and created three research classes: clinical medicine, laboratory medicine, and basic science. The impact factor values for the years 1999-2015 were abstracted, and the impact factor of US and EU journals was studied through the years. RESULTS: A total of 265 journals were included in the final analysis. The impact factor of US journals was higher than that of EU journals throughout the study period. In addition, for both US and EU journals the median impact factor increased throughout the study period. The rate of annual change in the impact factor throughout the study period was lower for US than EU journals (1.85% versus 3.55%, P=0.019). A higher median annual increase was seen in the impact factor during the period 1999-2008 compared to the period 2009-2015 for both US (P<0.001) and EU (P=0.001) journals. In fact, during the second period the US median impact factor value did not show significant changes (P=0.31), while the EU median impact factor continued to increase (P<0.001). CONCLUSION: The impact factor of EU journals increased at a significantly higher rate than and approached that of the US journals during the last 16 years.

In vitro susceptibility and resistance phenotypes in contemporary Citrobacter isolates in a University Hospital in Crete, Greece.

BACKGROUND: Data on Citrobacter spp. susceptibility are scarce. We sought to study the evolution in the susceptibility of 385 Citrobacter spp. at the University Hospital of Heraklion, Crete, Greece during a six-year period (2010-2015). METHODS: Non-duplicate strains isolated from inpatients (intensive care unit, oncology, surgery, internal medicine, paediatrics) and outpatients were studied using Vitek 2. Phenotypic confirmatory tests were applied for detection of ß-lactamases and aminoglycoside modifying enzymes. RESULTS: C. freundii (172, 44.7%) and C. koseri (166, 43.1%) were the most commonly isolated species. C. braakii (34), C. amalonaticus (6), C. youngae (6) and C. sedlakii (1) were the remaining isolates. Colistin and fosfomycin were the most active antibiotics (both 99.2%) followed by carbapenems (99%) aminoglycosides (96.6-98.4%), tigecycline (96.1%), cefepime (94.8%), ciprofloxacin (94.3%), tetracycline (92.7%), trimethoprim/sulphamethoxazole (91.4%), chloramphenicol (88.1%), piperacillin/tazobactam (86.5%) and 3rd generation cephalosporins (85.7%). C. freundii were more resistant than C. koseri. Antibiotic resistance did not increase during the study period for most antibiotics. Lower susceptibility to all antibiotics was observed among multi-drug resistant (MDR) strains. AmpC was the most common resistant mechanism (10.9%); carbapenemases (1.3%) and aminoglycoside modifying enzymes (2.9%) were also detected. All AmpC producers were resistant to cephalosporins but not to carbapenems. In all but one isolates aminoglycoside resistance was accompanied by acquired ß-lactamases. CONCLUSIONS: Although Citrobacter species in general were susceptible, antibiotic susceptibility testing is required for the detection of resistant isolates.