Background. The spread of Klebsiella pneumoniae (Kp) strains that produce K. pneumoniae carbapenemases (KPCs) has become a significant problem, and treatment of infections caused by these pathogens ...is a major challenge for clinicians. Methods. In this multicenter retrospective cohort study, conducted in 3 large Italian teaching hospitals, we examined 125 patients with bloodstream infections (BSIs) caused by KPC-producing Kp isolates (KPC-Kp) diagnosed between 1 January 2010 and 30 June 2011. The outcome measured was death within 30 days of the first positive blood culture. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. Results. The overall 30-day mortality rate was 41.6%. A significantly higher rate was observed among patients treated with monotherapy (54.3% vs 34.1% in those who received combined drug therapy; P = .02). In logistic regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (odds ratio OR: 7.17; 95% confidence interval CI: 1.65–31.03; P = .008); inadequate initial antimicrobial therapy (OR: 4.17; 95% CI: 1.61–10.76; P = .003); and high APACHE III scores (OR: 1.04; 95% CI: 1.02–1.07; P < .001). Postantibiogram therapy with a combination of tigecycline, colistin, and meropenem was associated with lower mortality (OR: 0.11; 95% CI: .02–.69; P = .01). Conclusions. KPC-Kp BSIs are associated with high mortality. To improve survival, combined treatment with 2 or more drugs with in vitro activity against the isolate, especially those also including a carbapenem, may be more effective than active monotherapy.
Severe pulmonary infections are among the most common reasons for admission to intensive care units (ICU). Within the last decade, increasing reports of severe influenza pneumonia resulting in acute ...respiratory distress syndrome (ARDS) complicated by Aspergillus infection were published.
To provide a comprehensive review of management of influenza-associated pulmonary aspergillosis in patients with ARDS.
Review of the literature pertaining to severe influenza-associated pulmonary aspergillosis. PubMed database was searched for publications from the database inception to January 2019.
In patients with lower respiratory symptoms, development of respiratory insufficiency should trigger rapid and thorough clinical evaluation, in particular in cases of suspected ARDS, including electrocardiography and echocardiography to exclude cardiac dysfunction, arrhythmias and ischaemia. Bronchoalveolar lavage should obtain lower respiratory tract samples for galactomannan assay, direct microscopy, culture, and bacterial, fungal and viral PCR. In case of positive Aspergillus testing, chest CT is the imaging modality of choice. If influenza pneumonia is diagnosed, neuraminidase inhibitors are the preferred approved drugs. When invasive aspergillosis is confirmed, first-line therapy consists of isavuconazole or voriconazole. Isavuconazole is an alternative in case of intolerance to voriconazole, drug–drug interactions, renal impairment, or if a spectrum of activity including the majority of Mucorales is desired. Primary anti-mould prophylaxis with posaconazole is recommended in haematology patients at high-risk. It may be considered in newly diagnosed influenza and ARDS, but ideally in clinical trials.
The rising reports of influenza-associated pulmonary aspergillosis in patients with ARDS, who are otherwise not considered at risk for fungal pneumonia demands heightened clinical awareness. Tracheobronchitis and Aspergillus in respiratory tract samples should prompt suspicion of invasive fungal infection and further work-up. The management algorithm should comprise bronchoalveolar lavage, CT imaging, sophisticated ventilator-management, rescue extracorporeal membrane oxygenation, and antifungal and antiviral therapy. To decrease the burden of influenza-related illness, vaccination is of utmost importance, specifically in patients with co-morbidities.
The timing, routing, and processes of sediment transfer from the continents to the oceans at millennial time-scale are still largely unknown. The potential of turbidite systems (dominantly deposited ...during sea-level lowstands) to record global or regional environmental fluctuations is usually under-exploited because of the difficulty to obtain robust chronostratigraphic constraints in turbiditic deposits, and therefore to tie changes in sedimentary processes to environmental fluctuations. We were able to obtain a millennial-scale chronostratigraphy based on oxygen isotopes of the scarce foraminifera preserved in turbiditic deposits of the Rhone Turbidite System within the Western Mediterranean. Our results show that 1) objective criteria can be defined for the selection of foraminifera preserved within the pelagic intervals between the turbiditic sequences, in order to obtain a reliable isotope stratigraphy; 2) turbidites triggered by hyperpycnal currents are described for the first time within the Rhone Turbidite System. They are related to the periods of direct fluvial connection with the canyon head (during the sea-level lowstand and early rise), and to a period of high sediment flux in relation to the massive recession of the Rhone glaciers in the Alps; 3) the lithofacies change passing from hyperpycnal to “Bouma-type” is dated at ca 19cal.ka BP, which might correspond to an acceleration of sea-level rise (19-ka Meltwater Pulse).
Treating severe infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) is one of the most important challenges for clinicians worldwide, partly because resistance may remain ...unrecognized until identification of the causative agent and/or antimicrobial susceptibility testing (AST). Recently, some novel rapid test for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with bloodstream infections (BSIs) have become available.
The objective of this narrative review is to discuss the advantages and limitations of different rapid tests for identification and/or AST of MDR-GNB from positive blood cultures or the blood of patients with BSI, as well as the available evidence on their possible role to improve therapeutic decisions and antimicrobial stewardship.
Inductive PubMed search for publications relevant to the topic.
The present review is structured in the following way: (a) rapid tests on positive blood cultures; (b) rapid tests directly on whole blood; (c) therapeutic implications.
Novel molecular and phenotypic rapid tests for identification and AST show the potential for favourably influencing patients' outcomes and results of antimicrobial stewardship interventions by reducing both the time to effective treatment and the misuse of antibiotics, although the interpretation about their impact on actual therapeutic decisions and patients' outcomes is still complex. Factors such as feasibility and personnel availability, as well as the detailed knowledge of the local microbiological epidemiology, need to be considered very carefully when implementing novel rapid tests in laboratory workflows and algorithms. Providing high-level, comparable evidence on the clinical impact of rapid identification and AST is becoming of paramount importance for MDR-GNB infections, since in the near future rapid identification of specific resistance mechanisms could be crucial for guiding rapid, effective, and targeted therapy against specific resistance mechanisms.
Dead benthic foraminiferal faunas (>150μm) from the Rhône prodelta (Gulf of Lions, NW Mediterranean) were analysed at 41 stations (15–100m water depth) sampled in June 2005 and September 2006, and ...compared to the living faunas investigated during previous studies at the same stations. The comparison between dead and living assemblages enhances the understanding of taphonomic processes that may modify the composition of the dead faunas in this area. We observed a loss of individuals from living to dead assemblages of species characterised by a fairly fragile test and therefore more prone to fragmentation or dissolution (e.g., Bolivina alata, Quinqueloculina tenuicollis). Allochthonous dead and/or live specimens may be transported to some parts of the prodelta, particularly the shallowest sites where hydrodynamic processes (i.e., river flood, storm swells, longshore currents) are more intense. These specimens may originate from relict deltaic structures (e.g., Elphidium spp. from the lobe of Bras de Fer) or from surrounding areas (e.g., Ammonia beccarii forma beccarii from the river). Opportunistic species (e.g., Bulimina marginata, Cassidulina carinata) characterised by high reproductive rates have much higher relative abundances in the dead than in the living fauna. Cluster analyses based on dead foraminiferal assemblages divide our study area into four main thanatofacies directly related to distinct local environmental conditions prevailing in the prodelta. Close to the river mouth, Ammonia beccarii forma beccarii and Ammonia tepida are found in sediments subject to a high riverine influence (i.e., bottom currents, high organic and inorganic material input of continental origin). Elphidium species are abundant in the silty-sandy relict deltaic lobe west of the river mouth which is characterised by strong longshore currents that disturb the benthic environment. Nonion fabum, Rectuvigerina phlegeri and Valvulineria bradyana are found along the coast west of the Rhône River mouth, in the area defined as the “river plume” thanatofacies. In the more stable and deeper prodeltaic area, species known to feed on fresh phytodetritus (e.g., Bulimina aculeata/marginata, C. carinata, Hyalinea balthica) dominate the faunas. Since only minor variations in species relative abundances and spatial distributional patterns are observed between the living and the dead faunas, we consider that our thanatofacies have not been influenced by substantial transport of dead tests. This suggests that fossil benthic foraminifera can provide a reliable tool for investigating the development of the palaeo-Rhône prodelta.
•Dead faunas were compared with living ones at 41 stations in the Rhône prodelta.•Minor compositional and spatial variations exist between living and dead faunas.•Four thanatofacies reflect distinct local environmental conditions in the prodelta.•Fossil benthic foraminifera are reliable tools to study the palaeo-Rhône prodelta.
Abstract
Introduction
This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the ...MERINO trial.
Methods
Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations.
Results
In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval CI 2.8–87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%–15%) and 8% (95% CI 2%–15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI −1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum β-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%–28%).
Conclusions
After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.
Piperacillin/tazobactam should be avoided for ceftriaxone nonsusceptible Escherichia coli and Klebsiella spp. bloodstream infections, especially when minimum inhibitory concentrations are > 16 mg/L. Further assessment of current testing is warranted given disparity between commonly used methods and broth microdilution.
Clin Microbiol Infect 2012; 18 (Suppl. 7): 19–37
This part of the EFISG guidelines focuses on non‐neutropenic adult patients. Only a few of the numerous recommendations can be summarized in the . ...Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastrointestinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconazole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of 14 days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treatment after 10 days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of indwelling catheters is strongly recommended. If catheters cannot be removed, lipid‐based amphotericin B or echinocandins should be preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifungal regimen of choice is liposomal amphotericin B +/− flucytosine. In ocular candidiasis, liposomal amphotericin B +/− flucytosine is recommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives. Amphotericin B deoxycholate is not recommended for any indication due to severe side effects.
Complicated skin and soft tissue infections (cSSTIs) are a diverse group of infections, with a range of presentations and microbiological causes. Hospitalization is common for patients with a cSSTI, ...which is treated by drainage of the affected area and with antibiotics. Host factors such as co-morbidities, and microbial factors, in particular drug resistance, complicate the management of these infections. Methicillin-resistant Staphylococcus aureus (MRSA) is an important cSSTI pathogen in Europe, and its involvement can be associated with poor patient outcomes. European guidelines recommend vancomycin, teicoplanin, linezolid, daptomycin, tigecycline or ceftaroline for treatment of MRSA cSSTIs. Of primary importance when treating cSSTIs is the agent’s clinical efficacy against the causative pathogens, as well as its bioavailability in the skin and associated structures. Linezolid is well-suited for the treatment of MRSA cSSTIs; it achieves high penetration into skin and soft tissues with 100% oral bioavailability, and therefore enables an intravenous to oral switch and outpatient treatment. When eligible patients are offered oral therapy the associated length of hospital stay and overall costs can be reduced. Linezolid has demonstrated clinical efficacy and favourable outcomes in patients for the treatment of MRSA cSSTIs including the treatment of lower extremity infections. Furthermore, efficacy has been documented in key defined populations, such as individuals with renal impairment and the obese. The safety profile of linezolid is well-documented, making this antibacterial a viable choice for the treatment of MRSA cSSTIs.
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