Background Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. Methods At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case–control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. Results Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. Conclusions Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.

The aim of this study was to evaluate the impact of carbapenem-resistant K. pneumoniae bloodstream infections on mortality. During the study period 42, 68 and 120 patients were identified with carbapenem-resistant, extended-spectrum β-lactamase producers (ESBL) and susceptible K. pneumoniae bloodstream infections, respectively. Patients with carbapenem-resistant K. pneumoniae had higher rates of prior antimicrobial exposure, other nosocomial infections, and use of invasive devices. Infection-related mortality was 48% for carbapenem-resistant, 22% for ESBL producers and 17% for susceptible K. pneumoniae. Independent risk factors for infection-related mortality were Pitt bacteraemia score, Charlson score and carbapenem resistance.

The use of active surveillance and contact precautions, as part of a multifactorial intervention, may be an effective strategy to decrease rates of nosocomial transmission of carbapenem-resistant K. pneumoniae colonization or infection.

Carbapenem resistance among Enterobacteriaceae is an emerging problem worldwide. Klebsiella pneumoniae carbapenemase (bla KPC ) enzymes are among the most common ␤-lactamases described. In this study, we report the development and validation of a real-time PCR (q-PCR) assay for the detection of bla KPC genes using TaqMan chemistry. The q-PCR amplification of bla KPC DNA was linear over 7 log dilutions (r 2 ‫؍‬ 0.999; slope, 3.54), and the amplification efficiency was 91.6%. The q-PCR detection limit was 1 CFU, and there was no cross-reaction with DNA extracted from several multidrug-resistant bacteria. Perianal/rectal swabs (n ‫؍‬ 187) collected in duplicate from 128 patients admitted to Sheba Medical Center surgical intensive care units were evaluated for the presence of carbapenem-resistant bacteria by culturing on MacConkey agar-pluscarbapenem disks and for bla KPC genes by q-PCR. Carbapenem-resistant organisms, all K. pneumoniae, were isolated from 47 (25.1%) of the 187 samples collected, while bla KPC genes were detected in 54 (28.9%) of the patient samples extracted by the NucliSENS easyMAG system. Of these, seven samples were positive for bla KPC genes by q-PCR but negative for carbapenem resistance by culture, while all samples in which no carbapenemresistant bacteria were detected by culture also tested negative by q-PCR. Thus, the sensitivity and specificity of the q-PCR assay after extraction by the NucliSENS easyMAG system were 100% and 95%, respectively. Similar values were obtained after DNA extraction by the Roche MagNA Pure LC instrument: 97.9% sensitivity and 96.4% specificity. Overall, the bla KPC q-PCR assay appears to be highly sensitive and specific. The utilization of q-PCR will shorten the time to bla KPC detection from 24 h to 4 h and will help in rapidly isolating colonized or infected patients and assigning them to cohorts.