Intravenous fosfomycin-back to the future. Systematic review and meta-analysis of the clinical literature

Objectives: We conducted a systematic review and meta-analysis to summarize the clinical evidence and usage patterns of intravenous fosfomycin from its development to the present time. Methods: PubMed, the Cochrane Library and local journals were searched for relevant studies reporting aggregated data of intravenous fosfomycin use in adults and children, with no restrictions regarding study design. Single case reports were excluded. Data were systematically abstracted for all included studies. Clinical and microbiological efficacy from randomized controlled and comparative observational studies were synthesized using meta-analysis to calculate pooled effect sizes. Results: In all, 128 studies on intravenous fosfomycin in 5527 patients were evaluated. Fosfomycin was predominantly used for sepsis/bacteraemia, urinary tract, respiratory tract, bone and joint, and central nervous system infections. No difference in clinical (OR 1.44, 95% CI 0.96-2.15) or microbiological (OR 1.28, 95% CI 0.82-2.01) efficacy between fosfomycin and other antibiotics was observed in comparative trials. The pooled estimate for resistance development during fosfomycin monotherapy was 3.4% (95% CI 1.8%-5.1%). Fosfomycin showed a favourable safety profile, with generally mild adverse events not requiring discontinuation of treatment. Included studies explored intravenous fosfomycin as an antistaphylococcal agent in monotherapy and combination therapy, whereas studies from 1990 focused on combination therapy (fosfoymcin + beta-lactams or aminoglycosides) for challenging infections frequently caused by multidrug-resistant organisms. Conclusion: Intravenous fosfomycin can play a vital role in the antibiotic armamentarium, given its long history of effective and safe use. However, well-designed randomized controlled trials are still desired. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases

Eradication of Acinetobacter baumannii/Enterobacter cloacae complex in an open proximal tibial fracture and closed drop foot correction with a multidisciplinary approach using the Taylor Spatial Frame®

Background Multi-drug-resistant bacteria (e.g. Carbapenem-resistant Acinetobacter baumannii, extended-spectrum betalactamase or carbapenemase-producing enterobacteriaceae) are emerging in early-onset infections. So far, there is no report describing the eradication of these bacteria in a osseous infection of an open proximal tibial fracture in combination with the hexapod technology to address both osseous consolidation and closed drop foot correction. Case presentation After sustaining a proximal tibial fracture (Gustilo 3B), a 41-year-old man was primarily treated with open reduction and internal fixation by a locking plate and split-thickness skin graft in the home country. At the time of admission to our hospital there was a significant anterolateral soft tissue defect covered with an already-necrotic split-thickness graft and suspicious secretion. CAT and MRI scans revealed no signs of osseous healing, intramedullary distinctive osteomyelitis, as well as a large abscess zone in the dorsal compartment. Multiple wound smears showed multi-drug-resistant bacteria: Acinetobacter baumannii (Carbapenem resistant) as well as Enterobacter cloacae complex (AmpC overexpression). After implant removal, excessive osseous and intramedullary debridements using the Reamer Irrigator Aspirator (RIA®) as well as initial negative pressure wound therapy were performed. Colistin hand-modelled chains and sticks were applied topically as well as an adjusted systemic antibiotic scheme was applied. After repetitive surgical interventions, the smears showed bacterial eradication and the patient underwent soft tissue reconstruction with a free vascularized latissimus dorsi muscle flap. External fixation was converted to a hexapod fixator (TSF®) to correct primary varus displacement, axial assignment and secure osseous healing. A second ring was mounted to address the fixed drop foot in a closed fashion without further intervention. At final follow-up, 12 months after trauma, the patient showed good functional recovery with osseous healing, intact soft tissue with satisfactory cosmetics and no signs of reinfection. Conclusions A multidisciplinary approach with orthopaedic surgeons for debridement, planning and establishing osseous and joint correction and consolidation, plastic surgeons for microvascular muscle flaps for soft tissue defect coverage as well as clinical microbiologists for the optimized anti-infective treatment is essential in these challenging rare cases

In-depth profiling of COVID-19 risk factors and preventive measures in healthcare workers

Purpose To determine risk factors for coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs), characterize symptoms, and evaluate preventive measures against SARS-CoV-2 spread in hospitals. Methods In a cross-sectional study conducted between May 27 and August 12, 2020, after the first wave of the COVID-19 pandemic, we obtained serological, epidemiological, occupational as well as COVID-19-related data at a quaternary care, multicenter hospital in Munich, Germany. Results 7554 HCWs participated, 2.2% of whom tested positive for anti-SARS-CoV-2 antibodies. Multivariate analysis revealed increased COVID-19 risk for nurses (3.1% seropositivity, 95% CI 2.5-3.9%, p = 0.012), staff working on COVID-19 units (4.6% seropositivity, 95% CI 3.2-6.5%, p = 0.032), males (2.4% seropositivity, 95% CI 1.8-3.2%, p = 0.019), and HCWs reporting high-risk exposures to infected patients (5.5% seropositivity, 95% CI 4.0-7.5%, p = 0.0022) or outside of work (12.0% seropositivity, 95% CI 8.0-17.4%, p < 0.0001). Smoking was a protective factor (1.1% seropositivity, 95% CI 0.7-1.8% p = 0.00018) and the symptom taste disorder was strongly associated with COVID-19 (29.8% seropositivity, 95% CI 24.3-35.8%, p < 0.0001). An unbiased decision tree identified subgroups with different risk profiles. Working from home as a preventive measure did not protect against SARS-CoV-2 infection. A PCR-testing strategy focused on symptoms and high-risk exposures detected all larger COVID-19 outbreaks. Conclusion Awareness of the identified COVID-19 risk factors and successful surveillance strategies are key to protecting HCWs against SARS-CoV-2, especially in settings with limited vaccination capacities or reduced vaccine efficacy