The marked increase in the incidence of infections due to antibiotic-resistant gram-negative bacilli in recent years is of great concern, as patients infected by those isolates might initially receive antibiotics that are inactive against the responsible pathogens. To evaluate the effect of inappropriate initial antimicrobial therapy on survival, a total of 286 patients with antibiotic-resistant gram-negative bacteremia, 61 patients with Escherichia coli bacteremia, 65 with Klebsiella pneumoniae bacteremia, 74 with Pseudomonas aeruginosa bacteremia, and 86 with Enterobacter bacteremia, were analyzed retrospectively. If a patient received at least one antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture collection, the initial antimicrobial therapy was considered to have been appropriate. High-risk sources of bacteremia were defined as the lung, peritoneum, or an unknown source. The main outcome measure was 30-day mortality. Of the 286 patients, 135 (47.2%) received appropriate initial empirical antimicrobial therapy, and the remaining 151 (52.8%) patients received inappropriate therapy. The adequately treated group had a 27.4% mortality rate, whereas the inadequately treated group had a 38.4% mortality rate (P ‫؍‬ 0.049). Multivariate analysis showed that the significant independent risk factors of mortality were presentation with septic shock, a high-risk source of bacteremia, P. aeruginosa infection, and an increasing APACHE II score. In the subgroup of patients (n ‫؍‬ 132) with a high-risk source of bacteremia, inappropriate initial antimicrobial therapy was independently associated with increased mortality (odds ratio, 3.64; 95% confidence interval, 1.13 to 11.72; P ‫؍‬ 0.030). Our data suggest that inappropriate initial antimicrobial therapy is associated with adverse outcome in antibiotic-resistant gram-negative bacteremia, particularly in patients with a high-risk source of bacteremia.Gram-negative bacilli such as Enterobacteriaceae and Pseudomonas aeruginosa are the leading causes of nosocomial bloodstream infections. Antibiotic-resistant strains have emerged among the gram-negative bacilli and are being increasingly recognized (8,20). This marked increase in the incidence of infections due to antibiotic-resistant gram-negative bacilli in recent years is of great concern. It is presumed that infections caused by antibiotic-resistant bacteria result in greater mortality, longer hospitalization, and higher costs than infections caused by antibiotic-susceptible bacteria, although little data are available to support this intuitive concept (2, 3, 12). The assumption that infections caused by antibiotic-resistant bacteria are associated with a higher mortality rate is based on the possibility that appropriate antimicrobial therapy for such infections might be initiated later than for infections caused by antibiotic-susceptible bacteria (14).Appropriate antimicrobial therapy has been shown to reduce mortality among patients with gram-negative bacteremia (10, 1...

NCT00890708.

We investigated the kinetics of the Middle East respiratory syndrome coronavirus (MERS-CoV) neutralizing and spike protein antibody titers over the course of 1 year in 11 patients who were confirmed by reverse transcription PCR to have been infected during the outbreak in South Korea in 2015. Robust antibody responses were detected in all survivors who had severe disease; responses remained detectable, albeit with some waning, for <1 year. The duration of viral RNA detection (but not viral load) in sputum significantly correlated with the antibody response magnitude. The MERS S1 ELISA antibody titers correlated well with the neutralizing antibody response. Antibody titers in 4 of 6 patients who had mild illness were undetectable even though most had evidence of pneumonia. This finding implies that MERS-CoV seroepidemiologic studies markedly underestimate the extent of mild and asymptomatic infection. Obtaining convalescent-phase plasma with high antibody titers to treat MERS will be challenging.

Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.

No potential conflict of interest relevant to this letter was reported. The authors reply: Campochiaro and Caruso are correct that mention of cardiovascular associations with ankylosing spondylitis and axial spondyloarthritis, including specific conductionsystem lesions and aortic-root lesions, was largely absent from our review of spondyloarthritis. These specific lesions are uncommon and tend to occur late in the disease course, as does the other more common but less specific cardiovascular illness mentioned in their letter. The focus of our article was on early diagnosis and clinical management of the axial disease, and this priority, along with space and citation limitations, precluded our describing specific cardiovascular manifestations. Rudwaleit M, van derRudwaleit and colleagues make the important point that diagnosis in clinical practice cannot be based solely on fulfillment of classification criteria. We tried to make this point in the article, but perhaps our wording conveyed some unintended ambiguity. In order to introduce the new concept of axial spondyloarthritis, we described the classification criteria for this entity proposed by the ASAS in 2009. In discussing this concept, including the critical role of MRI, we referred to this entity as a diagnosis, in the sense of its being a defined medical condition. We did not intend by this to imply that one can rely strictly on these criteria to establish a diagnosis in clinical practice. In fact, we stated explicitly, "These classification criteria have limited use outside the arena of clinical research," to introduce the algorithm (in Fig. 2 of our article) for use in clinical practice.The algorithm itself is a modification of one published by the correspondents and their colleagues, 1 but it was modified specifically to further emphasize the importance of weighing clinical data and post-test probabilities 2 and of applying clinical judgment to the diagnostic process. Moreover, the discussion of MRI findings includes mention of lesions that are not part of the classification criteria but that can be helpful in supporting a diagnosis in clinical practice. Finally, the Summary section in our article reemphasizes the potential difficulty in accurately establishing or ruling out a diagnosis of axial spondyloarthritis, with no mention of criteria. Viral Load Kinetics of MERS Coronavirus InfectionTo the Editor: The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in South Korea involved 186 patients and resulted in 38 deaths, with four large hospital outbreaks accounting for 82% of the total cases. 1,2 Here, we report changes in viral load over time in patients with MERS.We included all patients who were admitted to three Seoul National University-affiliated hospitals; the institutional review boards of these hospitals approved this study and waived the need for written informed consent on public health grounds. The patients were categorized into a group with severe disease (severe group) or a group with mild disease (mild grou...