A multicenter, retrospective study of patients infected with carbapenem-resistant Pseudomonas aeruginosa who were treated with ceftolozane/tazobactam was performed. Among 35 patients, pneumonia was the most common indication and treatment was successful in 26 (74%). Treatment failure was observed in all cases where isolates demonstrated ceftolozane-tazobactam minimum inhibitory concentrations ≥8 μg/mL.

Key Points Question Does COVID-19 convalescent plasma (CCP), compared with placebo, improve the clinical status of hospitalized patients with COVID-19 requiring noninvasive supplemental oxygen? Findings In this randomized clinical trial including 941 patients, based on the World Health Organization 11-point Ordinal Scale for Clinical Improvement, CCP did not benefit 468 participants randomized to CCP compared with 473 randomized to placebo from April 2020 to March 2021. However, in exploratory analyses, CCP appeared to benefit those enrolled from April to June 2020, the period when most participants received high-titer CCP and were not receiving remdesivir and corticosteroids at randomization. Meaning In this trial, CCP did not meet prespecified outcomes for efficacy, but high-titer CCP may have benefited hospitalized patients with COVID-19 early in the pandemic when other treatments were not in use, suggesting a heterogenous treatment effect over time.

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fWe have shown previously that changes in LiaFSR, a three-component regulatory system predicted to orchestrate the cell membrane stress response, are important mediators of daptomycin (DAP) resistance in enterococci. Indeed, deletion of the gene encoding the response regulator LiaR in a clinical strain of Enterococcus faecalis reversed DAP resistance (DAP-R) and produced a strain hypersusceptible to antimicrobial peptides. Since LiaFSR is conserved in Enterococcus faecium, we investigated the role of LiaR in a variety of clinical E. faecium strains representing the most common DAP-R genetic backgrounds. Deletion of liaR in DAP-R E. faecium R446F (DAP MIC of 16 g/ml) and R497F (MIC of 24 g/ml; harboring changes in LiaRS) strains fully reversed resistance (DAP MICs decreasing to 0.25 and 0.094 g/ml, respectively). Moreover, DAP at concentrations of 13 g/ml (achieved with human doses of 12 mg/kg body weight) retained bactericidal activity against the mutants. Furthermore, the liaR deletion derivatives of these two DAP-R strains exhibited increased binding of boron-dipyrromethene difluoride (BODIPY)-daptomycin, suggesting that high-level DAP-R mediated by LiaR in E. faecium involves repulsion of the calcium-DAP complex from the cell surface. In DAP-tolerant strains HOU503F and HOU515F (DAP MICs within the susceptible range but bacteria not killed by DAP concentrations of 5؋ the MIC), deletion of liaR not only markedly decreased the DAP MICs (0.064 and 0.047 g/ ml, respectively) but also restored the bactericidal activity of DAP at concentrations as low as 4 g/ml (achieved with human doses of 4 mg/kg). Our results suggest that LiaR plays a relevant role in the enterococcal cell membrane adaptive response to antimicrobial peptides independent of the genetic background and emerges as an attractive target to restore the activity of DAP against multidrug-resistant strains.

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Enterococcus spp. are among the common pathogens causing infective endocarditis (IE). Despite major medical advances and new potent antimicrobial agents, the mortality has not significantly improved for several decades. The usual lack of bactericidal activity of penicillin or ampicillin, the toxicity from the combination of penicillin plus aminoglycosides, and the increased reports of high-level resistance to aminoglycosides have led to the exploration of other regimens for treatment of Enterococcus faecalis IE. As an example, ampicillin plus ceftriaxone is now a well-recognized regimen for this organism. However, the emerging of new drug resistances in Enterococcus faecium dramatically reduces the therapeutic alternatives for this organism in IE which continues to be an immense challenge for clinicians even with the availability of newer antimicrobial agents. This article summarizes the current treatment options for enterococcal endocarditis and reviews of recent publications on the topic.

Delayed cerebral injury occurred in 4.1% of adults with bacterial meningitis, and it was associated with the use of adjunctive steroids. Future studies should explore the etiology and prevention of this devastating complication.

This journal section presents a real, challenging case involving a multidrugresistant organism. The case authors present the rationale for their therapeutic strategy and discuss the impact of mechanisms of resistance on clinical outcome. An expert clinician then provides a commentary on the case. ABSTRACT We report a case of infective endocarditis (IE) caused by ceftarolineresistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillinresistant S. aureus (MRSA). Resistance to ceftaroline emerged in the absence of drug exposure, and the E447K substitution in the active site of PBP2a previously associated with ceftaroline resistance was identified. Additionally, we present evidence of patient-to-patient transmission of the strain within the same unit. This case illustrates the difficulties in treating MRSA IE in the setting of a multidrug-resistant phenotype.