Prevalence of carbapenemase-producing organisms among hospitalized solid organ transplant recipients, five US hospitals, 2019-2020.

BACKGROUND: Passive reporting to the Centers for Disease Control and Prevention has identified carbapenemase-producing organisms (CPOs) among solid organ transplant (SOT) recipients, potentially representing an emerging source of spread. We analyzed CPO prevalence in wards where SOT recipients receive inpatient care to inform public health action to prevent transmission. METHODS: From September 2019 to June 2020, five US hospitals conducted consecutive point prevalence surveys (PPS) of all consenting patients admitted to transplant units, regardless of transplant status. We used the Cepheid Xpert Carba-R assay to identify carbapenemase genes (blaKPC , blaNDM , blaVIM , blaIMP , blaOXA-48 ) from rectal swabs. Laboratory-developed molecular tests were used to retrospectively test for a wider range of blaIMP and blaOXA variants. RESULTS: In total, 154 patients were screened and 92 (60%) were SOT recipients. CPOs were detected among 7 (8%) SOT recipients, from two of five screened hospitals: four blaKPC , one blaNDM , and two blaOXA-23 . CPOs were detected in two (3%) of 62 non-transplant patients. In three of five participating hospitals, CPOs were not identified among any patients admitted to transplant units. CONCLUSIONS: Longitudinal surveillance in transplant units, as well as PPS in areas with diverse CPO epidemiology, may inform the utility of routine screening in SOT units to prevent the spread of CPOs.

Performance Characteristics of BinaxNOW COVID-19 Antigen Card for Screening Asymptomatic Individuals in a University Setting.

We compared the performance of the Abbott BinaxNOW COVID-19 antigen card to that of a standard reverse transcription-PCR (RT-PCR) assay (Thermo Fisher TaqPath COVID-19 Combo kit) for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2,645 asymptomatic students presenting for screening at the University of Utah. SARS-CoV-2 RNA was detected in 1.7% of the study participants by RT-PCR. BinaxNOW identified 24 infections but missed 21 infections that were detected by RT-PCR. The analytical sensitivity (positive agreement) and analytical specificity (negative agreement) for the BinaxNOW were 53.3% and 100%, respectively, compared to the RT-PCR assay. The median cycle threshold (CT ) value in the specimens that had concordant positive BinaxNOW antigen results was significantly lower than that of specimens that were discordant (CT of 17.6 versus 29.6; P < 0.001). In individuals with presumably high viral loads (CT of <23.0), a 95.8% positive agreement was observed between the RT-PCR assay and BinaxNOW. Due to the possibility of false-negative results, caution must be taken when utilizing rapid antigen testing for screening asymptomatic individuals.

Antimicrobial Susceptibility Profiles To Predict the Presence of Carbapenemase Genes among Carbapenem-Resistant Pseudomonas aeruginosa Isolates.

Detection of carbapenem-resistant Pseudomonas aeruginosa (CRPA) with carbapenemase-producing (CP) genes is critical for preventing transmission. Our objective was to assess whether certain antimicrobial susceptibility testing (AST) profiles can efficiently identify CP-CRPA. We defined CRPA as P. aeruginosa with imipenem or meropenem MICs of ≥8 µg/ml; CP-CRPA was CRPA with CP genes (blaKPC/blaIMP/blaNDM/blaOXA-48/blaVIM). We assessed the sensitivity and specificity of AST profiles to detect CP-CRPA among CRPA isolates collected by CDC's Antibiotic Resistance Laboratory Network (AR Lab Network) and the Emerging Infections Program (EIP) during 2017 to 2019. Three percent (195/6,192) of AR Lab Network CRPA isolates were CP-CRPA. Among CRPA isolates, adding not susceptible (NS) to cefepime or ceftazidime to the definition had 91% sensitivity and 50% specificity for identifying CP-CRPA; adding NS to ceftolozane-tazobactam had 100% sensitivity and 86% specificity. Of 965 EIP CRPA isolates evaluated for CP genes, 7 were identified as CP-CRPA; 6 of the 7 were NS to cefepime and ceftazidime, and all 7 were NS to ceftolozane-tazobactam. Among 4,182 EIP isolates, clinical laboratory AST results were available for 96% of them for cefepime, 80% for ceftazidime, and 4% for ceftolozane-tazobactam. The number of CRPA isolates needed to test (NNT) to identify one CP-CRPA isolate decreased from 138 to 64 if the definition of NS to cefepime or ceftazidime was used and to 7 with NS to ceftolozane-tazobactam. Adding not susceptible to cefepime or ceftazidime to CRPA carbapenemase testing criteria would reduce the NNT by half and can be implemented in most clinical laboratories; adding not susceptible to ceftolozane-tazobactam could be even more predictive once AST for this drug is more widely available.

Donor-derived transmission through lung transplantation of carbapenem-resistant Acinetobacter baumannii producing the OXA-23 carbapenemase during an ongoing healthcare facility outbreak.

We describe a rare instance of donor-derived OXA-23-producing carbapenem-resistant Acinetobacter baumannii transmission during lung transplantation and the subsequent public health response. This investigation highlights how transplantation can introduce rare multidrug-resistant organisms into different healthcare facilities and regions.

Fever, Rash, and Cough in a 7-Year-Old Boy.

A 7-year-old boy presented to the emergency department with fever, cough, congestion, abdominal pain, myalgias, and morbilliform rash. Several aspects of the patient's history, including recent travel, living on a farm, exposure to sick contacts, and new medications, resulted in a wide differential diagnosis. Initial laboratory testing revealed leukocytosis with neutrophilia and elevated atypical lymphocytes, but did not reveal any infectious causes of illness. He was discharged from the hospital, but then represented to the emergency department a day later with worsening rash, continued fever, abdominal pain, and poor intake. He was then admitted. A more comprehensive laboratory evaluation was initiated. During this hospital course, the patient's physical examination changed when he developed head and neck edema, and certain laboratory trends became clearer. With the assistance of several specialists, the team was able to reach a more definitive diagnosis and initiate treatment to appropriately manage his condition.

Nanopore MinION Sequencing Reveals Possible Transfer of bla KPC-2 Plasmid Across Bacterial Species in Two Healthcare Facilities.

Carbapenemase-producing Enterobacteriaceae are a major threat to global public health. Klebsiella pneumoniae carbapenemase (KPC) is the most commonly identified carbapenemase in the United States and is frequently found on mobile genetic elements including plasmids, which can be horizontally transmitted between bacteria of the same or different species. Here we describe the results of an epidemiological investigation of KPC-producing bacteria at two healthcare facilities. Using a combination of short-read and long-read whole-genome sequencing, we identified an identical 44 kilobase plasmid carrying the bla KPC-2 gene in four bacterial isolates belonging to three different species (Citrobacter freundii, Klebsiella pneumoniae, and Escherichia coli). The isolates in this investigation were collected from patients who were epidemiologically linked in a region in which KPC was uncommon, suggesting that the antibiotic resistance plasmid was transmitted between these bacterial species. This investigation highlights the importance of long-read sequencing in investigating the relatedness of bacterial plasmids, and in elucidating potential plasmid-mediated outbreaks caused by antibiotic resistant bacteria.

Reassessing the role of the secreted protease CPAF in Chlamydia trachomatis infection through genetic approaches.

The secreted Chlamydia protease CPAF cleaves a defined set of mammalian and Chlamydia proteins in vitro. As a result, this protease has been proposed to modulate a range of bacterial and host cellular functions. However, it has recently come into question the extent to which many of its identified substrates constitute bona fide targets of proteolysis in infected host cell rather than artifacts of postlysis degradation. Here, we clarify the role played by CPAF in cellular models of infection by analyzing Chlamydia trachomatis mutants deficient for CPAF activity. Using reverse genetic approaches, we identified two C. trachomatis strains possessing nonsense, loss-of-function mutations in cpa (CT858) and a third strain containing a mutation in type II secretion (T2S) machinery that inhibited CPAF activity by blocking zymogen secretion and subsequent proteolytic maturation into the active hydrolase. HeLa cells infected with T2S(-) or CPAF(-) C. trachomatis mutants lacked detectable in vitro CPAF proteolytic activity and were not defective for cellular traits that have been previously attributed to CPAF activity, including resistance to staurosporine-induced apoptosis, Golgi fragmentation, altered NFκB-dependent gene expression, and resistance to reinfection. However, CPAF-deficient mutants did display impaired generation of infectious elementary bodies (EBs), indicating an important role for this protease in the full replicative potential of C. trachomatis. In addition, we provide compelling evidence in live cells that CPAF-mediated protein processing of at least two host protein targets, vimentin filaments and the nuclear envelope protein lamin-associated protein-1 (LAP1), occurs rapidly after the loss of the inclusion membrane integrity, but before loss of plasma membrane permeability and cell lysis. CPAF-dependent processing of host proteins correlates with a loss of inclusion membrane integrity, and so we propose that CPAF plays a role late in infection, possibly during the stages leading to the dismantling of the infected cell prior to the release of EBs during cell lysis.