Key Points Question Do patients with cancer develop adequate antibody responses to messenger RNA SARS-CoV-2 vaccines? Findings In this cohort study that included 102 patients with cancer who were receiving active treatment and 78 healthy controls, 92 patients with cancer (90%) and 100% of the controls were seropositive after the second messenger RNA BNT162b2 vaccine dose.. Meaning The findings of this study suggest that patients with cancer who are receiving active treatment and are at higher risk for severe COVID-19 disease respond well to messenger RNA SARS-CoV-2 vaccines and that vaccination of these patients should be seriously considered.

SUMMARY The limited armamentarium against drug-resistant Gram-negative bacilli has led to the development of several novel β-lactam–β-lactamase inhibitor combinations (BLBLIs). In this review, we summarize their spectrum of in vitro activities, mechanisms of resistance, and pharmacokinetic-pharmacodynamic (PK-PD) characteristics. A summary of available clinical data is provided per drug. Four approved BLBLIs are discussed in detail. All are options for treating multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa. Ceftazidime-avibactam is a potential drug for treating Enterobacterales producing extended-spectrum β-lactamase (ESBL), Klebsiella pneumoniae carbapenemase (KPC), AmpC, and some class D β-lactamases (OXA-48) in addition to carbapenem-resistant Pseudomonas aeruginosa. Ceftolozane-tazobactam is a treatment option mainly for carbapenem-resistant P. aeruginosa (non-carbapenemase producing), with some activity against ESBL-producing Enterobacterales. Meropenem-vaborbactam has emerged as treatment option for Enterobacterales producing ESBL, KPC, or AmpC, with similar activity as meropenem against P. aeruginosa. Imipenem-relebactam has documented activity against Enterobacterales producing ESBL, KPC, and AmpC, with the combination having some additional activity against P. aeruginosa relative to imipenem. None of these drugs present in vitro activity against Enterobacterales or P. aeruginosa producing metallo-β-lactamase (MBL) or against carbapenemase-producing Acinetobacter baumannii. Clinical data regarding the use of these drugs to treat MDR bacteria are limited and rely mostly on nonrandomized studies. An overview on eight BLBLIs in development is also provided. These drugs provide various levels of in vitro coverage of carbapenem-resistant Enterobacterales, with several drugs presenting in vitro activity against MBLs (cefepime-zidebactam, aztreonam-avibactam, meropenem-nacubactam, and cefepime-taniborbactam). Among these drugs, some also present in vitro activity against carbapenem-resistant P. aeruginosa (cefepime-zidebactam and cefepime-taniborbactam) and A. baumannii (cefepime-zidebactam and sulbactam-durlobactam).

Objectives We aimed to evaluate rates of antibody response to mRNA SARS-CoV-2 vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity. Methods A prospective cohort study including consecutive kidney transplant recipients in a single referral transplant center. Participants were tested for anti-spike (anti-S) antibodies 2-4 weeks following second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity. Results Of 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2-4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titer was 15.5 AU/mL (interquartile range [IQR] 3.5-163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio [OR] 1.025 per ml/min/1.73m 2 , 95% confidence interval [CI] 1.014 - 1.037, p<0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95% CI 1.782 - 3.089, p<0.001), younger age (OR 1.032 per year decrease, 95% CI 1.015 - 1.05, p<0.001) and lower calcineurin inhibitors (CNI) blood level (OR 1.987, 95% CI 1.146 - 3.443, p=0.014). No serious adverse events to the vaccine were reported. Conclusions Kidney transplant recipients demonstrated inadequate antibody response to mRNA SARS-CoV-2 vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.