Polymyxin resistance in klebsiella pneumoniae: Complexity at every level

The emergence and spread of carbapenemresistant Enterobacteriaceae (CRE) is an important threat to global health, and carbapenem-resistant Klebsiella pneumoniae is the most commonly encountered species of CRE. In the United States and many other countries, the CRE epidemic is largely driven by expansion of sequence type (ST) 258 or related clonal lineages of K. pneumoniae that produce carbapenemases in the K. pneumoniae carbapenemase (KPC) family

Outbreak of colistin-resistant, carbapenemase-producing klebsiella pneumoniae: Are we at the end of the road?

Carbapenem-resistant Klebsiella pneumoniae strains that produce K. pneumoniae carbapenemase (KPC) have spread globally in the last decade. Colistin is a key agent in treating infections caused by this pathogen. In this issue of the Journal of Clinical Microbiology, Giani et al. (T. Giani, F. Arena, G. Vaggelli, V. Conte, A Chiarell, L. H. De Angelis, R. Fornaini, M. Grazzini, F. Niccolini, P. Pecile, and G. M. Rossolini, J Clin Microbiol 53:3341–3344, 2015, http://dx.doi.org/10.1128/JCM.01017-15) describe a sustained outbreak of colistin-resistant KPC-producing K. pneumoniae

Multidrug-Resistant Pseudomonas aeruginosa Infection in a Child with Cystic Fibrosis

ABSTRACT We describe a pediatric cystic fibrosis patient who developed a pulmonary exacerbation due to two multidrug-resistant (MDR) Pseudomonas aeruginosa isolates. In addition to these MDR organisms, the case was further complicated by β-lactam allergy. Despite the MDR phenotype, both isolates were susceptible to an antimicrobial combination

Early appropriate diagnostics and treatment of MDR Gram-negative infections

The term difficult-to-treat resistance has been recently coined to identify Gram-negative bacteria exhibiting resistance to all fluoroquinolones and all β-lactam categories, including carbapenems. Such bacteria are posing serious challenges to clinicians trying to identify the best therapeutic option for any given patient. Delayed appropriate therapy has been associated with worse outcomes including increase in length of stay, increase in total in-hospital costs and ∼20% increase in the risk of in-hospital mortality. In addition, time to appropriate antibiotic therapy has been shown to be an independent predictor of 30 day mortality in patients with resistant organisms. Improving and anticipating aetiological diagnosis through optimizing not only the identification of phenotypic resistance to antibiotic classes/agents, but also the identification of specific resistance mechanisms, would have a major impact on reducing the frequency and duration of inappropriate early antibiotic therapy. In light of these considerations, the present paper reviews the increasing need for rapid diagnosis of bacterial infections and efficient laboratory workflows to confirm diagnoses and facilitate prompt de-escalation to targeted therapy, in line with antimicrobial stewardship principles. Rapid diagnostic tests currently available and future perspectives for their use are discussed. Early appropriate diagnostics and treatment of MDR Gram-negative infections require a multidisciplinary approach that includes multiple different diagnostic methods and further consensus of algorithms, protocols and guidelines to select the optimal antibiotic therapy

Clinical data from studies involving novel antibiotics to treat multidrug-resistant Gram-negative bacterial infections

Multidrug-resistant (MDR) Gram-negative bacteria (GNB) pose a critical threat to global healthcare, worsening outcomes and increasing mortality among infected patients. Carbapenemase- and extended-spectrum β-lactamase-producing Enterobacterales, as well as carbapenemase-producing Pseudomonas and Acinetobacter spp., are common MDR pathogens. New antibiotics and combinations have been developed to address this threat. Clinical trial findings support several combinations, notably ceftazidime–avibactam (CZA, a cephalosporin-β-lactamase inhibitor combination), which is effective in treating complicated urinary tract infections (cUTI), complicated intra-abdominal infections and hospital-acquired and ventilator-associated pneumonia caused by GNBs. Other clinically effective combinations include meropenem–vaborbactam (MVB), ceftolozane–tazobactam (C/T) and imipenem–relebactam (I–R). Cefiderocol is a recent siderophore β-lactam antibiotic that is useful against cUTIs caused by carbapenem-resistant Enterobacterales (CRE) and is stable against many β-lactamases. Carbapenem-resistant Enterobacterales are a genetically heterogeneous group that vary in different world regions and are a substantial cause of infections, among which Klebsiella pneumoniae are the most common. Susceptible CRE infections can be treated with fluoroquinolones, aminoglycosides or fosfomycin, but alternatives include CZA, MVB, I–R, cefiderocol, tigecycline and eravacycline. Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are increasingly common pathogens producing a range of different carbapenemases, and infections are challenging to treat, often requiring novel antibiotics or combinations. Currently, no single agent can treat all MDR-GNB infections, but new β-lactam–β-lactamase inhibitor combinations are often effective for different infection sites and, when used appropriately, have the potential to improve outcomes. This article reviews clinical studies investigating novel β-lactam approaches for treatment of MDR-GNB infections

Quantum magnetism in the stripe phase: bond- versus site order

It is argued that the spin dynamics in the charge-ordered stripe phase might be revealing with regards to the nature of the anomalous spin dynamics in cuprate superconductors. Specifically, if the stripes are bond ordered much of the spin fluctuation will originate in the spin sector itself, while site ordered stripes require the charge sector as the driving force for the strong quantum spin fluctuations.Comment: 4 pages, 3 figures, LaTe

Suppression of Antiferromagnetic Order by Light Hole Doping in La_2Cu_{1-x}Li_xO_4: A ^{139}La NQR Study

^{139}La nuclear quadrupole resonance measurements in lightly doped La_2Cu_{1-x}Li_xO_4 have been performed to reveal the dependence of the magnetic properties of the antiferromagnetic CuO_2 planes on the character of the doped holes and their interactions with the dopant. A detailed study shows that the magnetic properties are remarkably insensitive to the character of the dopant impurity. This indicates that the added holes form previously unrecognized collective structures.Comment: 4 pages, 3 figures. Slightly modified version, as accepted for publication in Physical Review Letter