Carbapenems are considered as last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. With the increasing use of carbapenems in clinical practice, the emergence of carbapenem-resistant pathogens now poses a great threat to human health. Currently, antibiotic options for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) are very limited, with polymyxins, tigecycline, fosfomycin, and aminoglycosides as the mainstays of therapy. The need for new and effective anti-CRE therapies is urgent. Here, we describe the current understanding of issues related to CRE and review combination therapeutic strategies for CRE infections, including high-dose tigecycline, high-dose prolonged-infusion of carbapenem, and double carbapenem therapy. We also review the newly available antibiotics which have potential in the future treatment of CRE infections: ceftazidime/avibactam, which is active against KPC and OXA-48 producers; meropenem/vaborbactam, which is active against KPC producers; plazomicin, which is a next-generation aminoglycoside with in vitro activity against CRE; and eravacycline, which is a tetracycline class antibacterial with in vitro activity against CRE. Although direct evidence for CRE treatment is still lacking and the development of resistance is a concern, these new antibiotics provide additional therapeutic options for CRE infections. Finally, we review other potential anti-CRE antibiotics in development: imipenem/relebactam and cefiderocol. Currently, high-dose and combination strategies that may include the new β-lactam/β-lactamase inhibitors should be considered in severe CRE infections to maximize treatment success. In the future, when more treatment options are available, therapy for CRE infections should be individualized and based on molecular phenotypes of resistance, susceptibility profiles, disease severity, and patient characteristics. More high-quality studies are needed to guide effective treatment for infections caused by CRE.
We develop a novel statistical approach for classifying generalists and specialists in two distinct habitats. Using a multinomial model based on estimated species relative abundance in two habitats, our method minimizes bias due to differences in sampling intensities between two habitat types as well as bias due to insufficient sampling within each habitat. The method permits a robust statistical classification of habitat specialists and generalists, without excluding rare species a priori. Based on a user-defined specialization threshold, the model classifies species into one of four groups: (1) generalist; (2) habitat A specialist; (3) habitat B specialist; and (4) too rare to classify with confidence. We illustrate our multinomial classification method using two contrasting data sets: (1) bird abundance in woodland and heath habitats in southeastern Australia and (2) tree abundance in second-growth (SG) and old-growth (OG) rain forests in the Caribbean lowlands of northeastern Costa Rica. We evaluate the multinomial model in detail for the tree data set. Our results for birds were highly concordant with a previous nonstatistical classification, but our method classified a higher fraction (57.7%) of bird species with statistical confidence. Based on a conservative specialization threshold and adjustment for multiple comparisons, 64.4% of tree species in the full sample were too rare to classify with confidence. Among the species classified, OG specialists constituted the largest class (40.6%), followed by generalist tree species (36.7%) and SG specialists (22.7%). The multinomial model was more sensitive than indicator value analysis or abundance-based phi coefficient indices in detecting habitat specialists and also detects generalists statistically. Classification of specialists and generalists based on rarefied subsamples was highly consistent with classification based on the full sample, even for sampling percentages as low as 20%. Major advantages of the new method are (1) its ability to distinguish habitat generalists (species with no significant habitat affinity) from species that are simply too rare to classify and (2) applicability to a single representative sample or a single pooled set of representative samples from each of two habitat types. The method as currently developed can be applied to no more than two habitats at a time.
BackgroundInfluenza B virus infection is generally considered to be mild and is rarely associated pulmonary cardiovascular involvement in adults. However fatal complications may occur.Case presentationA 43-year-old previously healthy Taiwanese male came to our emergency department due to high fever, chills, general malaise and myalgia for about 4 days. An influenza rapid test from a throat swab was negative. Chest radiography showed mild left lung infiltration and levofloxacin was prescribed. However, progressive shortness of breath and respiratory failure developed 48 h later after hospitalization. Emergent intubation was performed and he was transferred to the intensive care unit where oseltamivir (Tamiflu, Roche) 75 mg orally twice daily was given immediately. In the intensive care unit, cardiac catheterization revealed normal coronary arteries. However, a markedly elevated cardiac enzyme level (Troponin I level was up to 71.01 ng/ml), a positive cardiac magnetic resonance imaging findings and no coronary artery stenosis led to the diagnosis of acute myocarditis. Subsequent real-time polymerase chain reaction of endotracheal aspirates was positive for influenza B. His condition gradually improved and he was successfully weaned from the ventilator on day 22. He was discharged without prominent complications on day 35.ConclusionInfluenza B infection is not always a mild disease. Early detection, early administration of antiviral agents, appropriate antibiotics and best supportive care, is still the gold standard for patients such as the one reported.
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