Multispecies Outbreak of Verona Integron-Encoded Metallo-ß-Lactamase-Producing Multidrug Resistant Bacteria Driven by a Promiscuous Incompatibility Group A/C2 Plasmid.

BACKGROUND: Antibiotic resistance is often spread through bacterial populations via conjugative plasmids. However, plasmid transfer is not well recognized in clinical settings because of technical limitations, and health care-associated infections are usually caused by clonal transmission of a single pathogen. In 2015, multiple species of carbapenem-resistant Enterobacteriaceae (CRE), all producing a rare carbapenemase, were identified among patients in an intensive care unit. This observation suggested a large, previously unrecognized plasmid transmission chain and prompted our investigation. METHODS: Electronic medical record reviews, infection control observations, and environmental sampling completed the epidemiologic outbreak investigation. A laboratory analysis, conducted on patient and environmental isolates, included long-read whole-genome sequencing to fully elucidate plasmid DNA structures. Bioinformatics analyses were applied to infer plasmid transmission chains and results were subsequently confirmed using plasmid conjugation experiments. RESULTS: We identified 14 Verona integron-encoded metallo-ß-lactamase (VIM)-producing CRE in 12 patients, and 1 additional isolate was obtained from a patient room sink drain. Whole-genome sequencing identified the horizontal transfer of blaVIM-1, a rare carbapenem resistance mechanism in the United States, via a promiscuous incompatibility group A/C2 plasmid that spread among 5 bacterial species isolated from patients and the environment. CONCLUSIONS: This investigation represents the largest known outbreak of VIM-producing CRE in the United States to date, which comprises numerous bacterial species and strains. We present evidence of in-hospital plasmid transmission, as well as environmental contamination. Our findings demonstrate the potential for 2 types of hospital-acquired infection outbreaks: those due to clonal expansion and those due to the spread of conjugative plasmids encoding antibiotic resistance across species.

Epidemiologic Characteristics Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antigen-Based Test Results, Real-Time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) Cycle Threshold Values, Subgenomic RNA, and Viral Culture Results From University Testing.

BACKGROUND: Real-time reverse transcription polymerase chain reaction (rRT-PCR) and antigen tests are important diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sensitivity of antigen tests has been shown to be lower than that of rRT-PCR; however, data to evaluate epidemiologic characteristics that affect test performance are limited. METHODS: Paired mid-turbinate nasal swabs were collected from university students and staff and tested for SARS-CoV-2 using both Quidel Sofia SARS Antigen Fluorescent Immunoassay (FIA) and rRT-PCR assay. Specimens positive by either rRT-PCR or antigen FIA were placed in viral culture and tested for subgenomic RNA (sgRNA). Logistic regression models were used to evaluate characteristics associated with antigen results, rRT-PCR cycle threshold (Ct) values, sgRNA, and viral culture. RESULTS: Antigen FIA sensitivity was 78.9% and 43.8% among symptomatic and asymptomatic participants, respectively. Among rRT-PCR positive participants, negative antigen results were more likely among asymptomatic participants (odds ratio [OR] 4.6, 95% confidence interval [CI]: 1.3-15.4) and less likely among participants reporting nasal congestion (OR 0.1, 95% CI: .03-.8). rRT-PCR-positive specimens with higher Ct values (OR 0.5, 95% CI: .4-.8) were less likely, and specimens positive for sgRNA (OR 10.2, 95% CI: 1.6-65.0) more likely, to yield positive virus isolation. Antigen testing was >90% positive in specimens with Ct values < 29. Positive predictive value of antigen test for positive viral culture (57.7%) was similar to that of rRT-PCR (59.3%). CONCLUSIONS: SARS-CoV-2 antigen test advantages include low cost, wide availability and rapid turnaround time, making them important screening tests. The performance of antigen tests may vary with patient characteristics, so performance characteristics should be accounted for when designing testing strategies and interpreting results.

Multiplex Real-Time Reverse Transcription PCR for Influenza A Virus, Influenza B Virus, and Severe Acute Respiratory Syndrome Coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, and the outbreak rapidly evolved into the current coronavirus disease pandemic. SARS-CoV-2 is a respiratory virus that causes symptoms similar to those caused by influenza A and B viruses. On July 2, 2020, the US Food and Drug Administration granted emergency use authorization for in vitro diagnostic use of the Influenza SARS-CoV-2 Multiplex Assay. This assay detects influenza A virus at 102.0, influenza B virus at 102.2, and SARS-CoV-2 at 100.3 50% tissue culture or egg infectious dose, or as few as 5 RNA copies/reaction. The simultaneous detection and differentiation of these 3 major pathogens increases overall testing capacity, conserves resources, identifies co-infections, and enables efficient surveillance of influenza viruses and SARS-CoV-2.

Evaluation of methods for detection of ß-lactamase production in MSSA.

OBJECTIVES: Correct determination of penicillin susceptibility is pivotal for using penicillin in the treatment of Staphylococcus aureus infections. This study examines the performance of MIC determination, disc diffusion and a range of confirmatory tests for detection of penicillin susceptibility in S. aureus. METHODS: A total of 286 consecutive penicillin-susceptible S. aureus blood culture isolates as well as a challenge set of 62 MSSA isolates were investigated for the presence of the blaZ gene by PCR and subjected to penicillin-susceptibility testing using broth microdilution MIC determination, disc diffusion including reading of the zone edge, two nitrocefin tests and the cloverleaf test. RESULTS: Using PCR-based detection of blaZ as the gold standard, both broth microdilution MIC testing and disc diffusion testing resulted in a relatively low accuracy (82%-93%) with a sensitivity ranging from 49%-93%. Among the confirmatory tests, the cloverleaf test performed with 100% accuracy, while zone edge interpretation and nitrocefin-based tests increased the sensitivity of ß-lactamase detection to 96%-98% and 82%-96% when using MIC determination or disc diffusion as primary test, respectively. CONCLUSIONS: This investigation showed that reliable and accurate detection of ß-lactamase production in S. aureus can be obtained by MIC determination or penicillin disc diffusion followed by interpretation of the zone edge as a confirmatory test for apparently penicillin-susceptible isolates. The more cumbersome cloverleaf test can also be used. Nitrocefin-based tests should not be used as the only test for confirmation of a presumptive ß-lactamase-negative isolate.

Genomic Surveillance for SARS-CoV-2 Variants Circulating in the United States, December 2020-May 2021.

SARS-CoV-2, the virus that causes COVID-19, is constantly mutating, leading to new variants (1). Variants have the potential to affect transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity. In November 2020, CDC established national surveillance for SARS-CoV-2 variants using genomic sequencing. As of May 6, 2021, sequences from 177,044 SARS-CoV-2-positive specimens collected during December 20, 2020-May 6, 2021, from 55 U.S. jurisdictions had been generated by or reported to CDC. These included 3,275 sequences for the 2-week period ending January 2, 2021, compared with 25,000 sequences for the 2-week period ending April 24, 2021 (0.1% and 3.1% of reported positive SARS-CoV-2 tests, respectively). Because sequences might be generated by multiple laboratories and sequence availability varies both geographically and over time, CDC developed statistical weighting and variance estimation methods to generate population-based estimates of the proportions of identified variants among SARS-CoV-2 infections circulating nationwide and in each of the 10 U.S. Department of Health and Human Services (HHS) geographic regions.* During the 2-week period ending April 24, 2021, the B.1.1.7 and P.1 variants represented an estimated 66.0% and 5.0% of U.S. SARS-CoV-2 infections, respectively, demonstrating the rise to predominance of the B.1.1.7 variant of concern† (VOC) and emergence of the P.1 VOC in the United States. Using SARS-CoV-2 genomic surveillance methods to analyze surveillance data produces timely population-based estimates of the proportions of variants circulating nationally and regionally. Surveillance findings demonstrate the potential for new variants to emerge and become predominant, and the importance of robust genomic surveillance. Along with efforts to characterize the clinical and public health impact of SARS-CoV-2 variants, surveillance can help guide interventions to control the COVID-19 pandemic in the United States.

Performance of an Antigen-Based Test for Asymptomatic and Symptomatic SARS-CoV-2 Testing at Two University Campuses - Wisconsin, September-October 2020.

Antigen-based tests for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), are inexpensive and can return results within 15 minutes (1). Antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in asymptomatic and symptomatic persons within the first 5-12 days after symptom onset (2). These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3-5). However, test performance data from symptomatic and asymptomatic persons are limited. This investigation evaluated performance of the Sofia SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin. During September 28-October 9, a total of 1,098 paired nasal swabs were tested using the Sofia SARS Antigen FIA and real-time RT-PCR. Virus culture was attempted on all antigen-positive or real-time RT-PCR-positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, the antigen test sensitivity was 41.2%, specificity was 98.4%, and in this population the estimated positive predictive value (PPV) was 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). Virus was isolated from 34 (46.6%) of 73 antigen-positive or real-time RT-PCR-positive nasal swab specimens, including two of 18 that were antigen-negative and real-time RT-PCR-positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. However, these advantages need to be balanced against lower sensitivity and lower PPV, especially among asymptomatic persons. Confirmatory testing with an FDA-authorized nucleic acid amplification test (NAAT), such as RT-PCR, should be considered after negative antigen test results in symptomatic persons, and after positive antigen test results in asymptomatic persons (1).

Qualitative Variation among Commercial Immunoassays for Detection of Measles-Specific IgG.

Measurement of measles virus-specific IgG is used to assess presumptive evidence of immunity among immunocompetent individuals with uncertain immune or vaccination status. False-negative test results may lead to unnecessary quarantine and exclusion from activities such as employment, education, and travel or result in unnecessary revaccination. In contrast, false-positive results may fail to identify susceptible individuals and promote spread of disease by those who are exposed and unprotected. To better understand the performance characteristics of tests to detect measles IgG, we compared five widely used, commercially available measles IgG test platforms using a set of 223 well-characterized serum samples. Measles virus neutralizing antibodies were also measured by in vitro plaque reduction neutralization, the gold standard method, and compared to IgG test results. Discrepant results were observed for samples in the low-positive ranges of the most sensitive tests, but there was good agreement across platforms for IgG-negative sera and for samples with intermediate to high levels of IgG. False-negative test results occurred in approximately 11% of sera, which had low levels of neutralizing antibody.

Carbapenemase-Producing Organisms: A Global Scourge.

The dramatic increase in the prevalence and clinical impact of infections caused by bacteria producing carbapenemases is a global health concern. Carbapenemase production is especially problematic when encountered in members of the family Enterobacteriaceae. Due to their ability to readily spread and colonize patients in healthcare environments, preventing the transmission of these organisms is a major public health initiative and coordinated international effort are needed. Central to the treatment and control of carbapenemase-producing organisms (CPOs) are phenotypic (growth-/biochemical-dependent) and nucleic acid-based carbapenemase detection tests that identify carbapenemase activity directly or their associated molecular determinants. Importantly, bacterial isolates harboring carbapenemases are often resistant to multiple antibiotic classes, resulting in limited therapy options. Emerging agents, novel antibiotic combinations and treatment regimens offer promise for management of these infections. This review highlights our current understanding of CPOs with emphasis on their epidemiology, detection, treatment, and control.

Phenotypic and Genotypic Characterization of Enterobacteriaceae Producing Oxacillinase-48-Like Carbapenemases, United States.

Oxacillinase (OXA)-48-like carbapenemases remain relatively uncommon in the United States. We performed phenotypic and genotypic characterization of 30 Enterobacteriaceae producing OXA-48-like carbapenemases that were recovered from patients during 2010-2014. Isolates were collected from 12 states and not associated with outbreaks, although we could not exclude limited local transmission. The alleles ß-lactamase OXA-181 (blaOXA-181) (43%), blaOXA-232 (33%), and blaOXA-48 (23%) were found. All isolates were resistant to ertapenem and showed positive results for the ertapenem and meropenem modified Hodge test and the modified carbapenem inactivation method; 73% showed a positive result for the Carba Nordmann-Poirel test. Whole-genome sequencing identified extended-spectrum ß-lactamase genes in 93% of isolates. In all blaOXA-232 isolates, the gene was on a ColKP3 plasmid. A total of 12 of 13 isolates harboring blaOXA-181 contained the insertion sequence ΔISEcp1. In all isolates with blaOXA-48, the gene was located on a TN1999 transposon; these isolates also carried IncL/M plasmids.

Burden of Clostridium difficile infection in the United States.

BACKGROUND: The magnitude and scope of Clostridium difficile infection in the United States continue to evolve. METHODS: In 2011, we performed active population- and laboratory-based surveillance across 10 geographic areas in the United States to identify cases of C. difficile infection (stool specimens positive for C. difficile on either toxin or molecular assay in residents ≥ 1 year of age). Cases were classified as community-associated or health care-associated. In a sample of cases of C. difficile infection, specimens were cultured and isolates underwent molecular typing. We used regression models to calculate estimates of national incidence and total number of infections, first recurrences, and deaths within 30 days after the diagnosis of C. difficile infection. RESULTS: A total of 15,461 cases of C. difficile infection were identified in the 10 geographic areas; 65.8% were health care-associated, but only 24.2% had onset during hospitalization. After adjustment for predictors of disease incidence, the estimated number of incident C. difficile infections in the United States was 453,000 (95% confidence interval [CI], 397,100 to 508,500). The incidence was estimated to be higher among females (rate ratio, 1.26; 95% CI, 1.25 to 1.27), whites (rate ratio, 1.72; 95% CI, 1.56 to 2.0), and persons 65 years of age or older (rate ratio, 8.65; 95% CI, 8.16 to 9.31). The estimated number of first recurrences of C. difficile infection was 83,000 (95% CI, 57,000 to 108,900), and the estimated number of deaths was 29,300 (95% CI, 16,500 to 42,100). The North American pulsed-field gel electrophoresis type 1 (NAP1) strain was more prevalent among health care-associated infections than among community-associated infections (30.7% vs. 18.8%, P<0.001). CONCLUSIONS: C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011. (Funded by the Centers for Disease Control and Prevention.).

Multicenter Evaluation of the Modified Carbapenem Inactivation Method and the Carba NP for Detection of Carbapenemase-Producing Pseudomonas aeruginosa and Acinetobacter baumannii.

The purpose of this study was to develop the modified carbapenem inactivation method (mCIM) for the detection of carbapenemase-producing Pseudomonas aeruginosa (CP-PA) and carbapenemase-producing Acinetobacter baumannii (CP-AB) and perform a multicenter evaluation of the mCIM and Carba NP tests for these nonfermenters. Thirty P. aeruginosa and 30 A. baumannii isolates previously characterized by whole-genome sequencing from the CDC-FDA Antibiotic Resistance Isolate Bank were evaluated, including CP isolates (Ambler class A, B, and D), non-carbapenemase-producing (non-CP) carbapenem-resistant isolates, and carbapenem-susceptible isolates. Initial comparison of a 1-µl versus 10-µl loop inoculum for the mCIM was performed by two testing sites and showed that 10 µl was required for reliable detection of carbapenemase production among P. aeruginosa and A. baumannii Ten testing sites then evaluated the mCIM using a 10-µl loop inoculum. Overall, the mean sensitivity and specificity of the mCIM for detection of CP-PA across all 10 sites were 98.0% (95% confidence interval [CI], 94.3 to 99.6; range, 86.7 to 100) and 95% (95% CI, 89.8 to 97.7; range, 93.3 to 100), whereas the mean sensitivity and specificity among CP-AB were 79.8% (95% CI, 74.0 to 84.9; range, 36.3 to 95.7) and 52.9% (95% CI, 40.6 to 64.9; range, 28.6 to 100), respectively. At three sites that evaluated the performance of the Carba NP test using the same set of isolates, the mean sensitivity and specificity of the Carba NP test were 97.8% (95% CI, 88.2 to 99.9; range, 93.3 to 100) and 97.8% (95% CI, 88.2 to 99.9; range, 93.3 to 100) for P. aeruginosa and 18.8% (95% CI, 10.4 to 30.1; range, 8.7 to 26.1) and 100% (95% CI, 83.9 to 100; range, 100) for A. baumannii Overall, we found both the mCIM and the Carba NP test to be accurate for detection of carbapenemase production among P. aeruginosa isolates and less reliable for use with A. baumannii isolates.

Modified Carbapenem Inactivation Method for Phenotypic Detection of Carbapenemase Production among Enterobacteriaceae.

The ability of clinical microbiology laboratories to reliably detect carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) is an important element of the effort to prevent and contain the spread of these pathogens and an integral part of antimicrobial stewardship. All existing methods have limitations. A new, straightforward, inexpensive, and specific phenotypic method for the detection of carbapenemase production, the carbapenem inactivation method (CIM), was recently described. Here we describe a two-stage evaluation of a modified carbapenem inactivation method (mCIM), in which tryptic soy broth was substituted for water during the inactivation step and the length of this incubation was extended. A validation study was performed in a single clinical laboratory to determine the accuracy of the mCIM, followed by a nine-laboratory study to verify the reproducibility of these results and define the zone size cutoff that best discriminated between CP-CRE and members of the family Enterobacteriaceae that do not produce carbapenemases. Bacterial isolates previously characterized through whole-genome sequencing or targeted PCR as to the presence or absence of carbapenemase genes were tested for carbapenemase production using the mCIM; isolates with Ambler class A, B, and D carbapenemases, non-CP-CRE isolates, and carbapenem-susceptible isolates were included. The sensitivity of the mCIM observed in the validation study was 99% (95% confidence interval [95% CI], 93% to 100%), and the specificity was 100% (95% CI, 82% to 100%). In the second stage of the study, the range of sensitivities observed across nine laboratories was 93% to 100%, with a mean of 97%; the range of specificities was 97% to 100%, with a mean of 99%. The mCIM was easy to perform and interpret for Enterobacteriaceae, with results in less than 24 h and excellent reproducibility across laboratories.

Multicenter Performance Assessment of Carba NP Test.

Eighty Gram-negative bacilli (54 Enterobacteriaceae and 26 nonfermenting Gram-negative bacilli) obtained from multiple institutions in the United States were distributed in a blinded manner to seven testing laboratories to compare their performance of a test for detection of carbapenemase production, the Carba NP test. The Carba NP test was performed by all laboratories, following the Clinical and Laboratory Standards Institute (CLSI) procedure. Site-versus-site comparisons demonstrated a high level of consistency for the Carba NP assay, with just 3/21 site comparisons yielding a difference in sensitivity (P < 0.05). Previously described limitations with blaOXA-48-like carbapenemases and blaOXA carbapenemases associated with Acinetobacter baumannii were noted. Based on these data, we demonstrate that the Carba NP test, when implemented with the standardized CLSI methodology, provides reproducible results across multiple sites for detection of carbapenemases.

What's in a Name? The Impact of Accurate Staphylococcus pseudintermedius Identification on Appropriate Antimicrobial Susceptibility Testing.

Bacteria in the Staphylococcus intermedius group, including Staphylococcus pseudintermedius, often encode mecA-mediated methicillin resistance. Reliable detection of this phenotype for proper treatment and infection control decisions requires that these coagulase-positive staphylococci are accurately identified and specifically that they are not misidentified as S. aureus. As correct species level bacterial identification becomes more commonplace in clinical laboratories, one can expect to see changes in guidance for antimicrobial susceptibility testing and interpretation. The study by Wu et al. in this issue (M. T. Wu, C.-A. D. Burnham, L. F. Westblade, J. Dien Bard, S. D. Lawhon, M. A. Wallace, T. Stanley, E. Burd, J. Hindler, R. M. Humphries, J Clin Microbiol 54:535-542, 2016, http://dx.doi.org/10.1128/JCM.02864-15) highlights the impact of robust identification of S. intermedius group organisms on the selection of appropriate antimicrobial susceptibility testing methods and interpretation.

The Problem of Carbapenemase-Producing-Carbapenem-Resistant-Enterobacteriaceae Detection.

The emergence and spread of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are a significant clinical and public health concern. Reliable detection of CP-CRE is the first step in combating this problem. There are both phenotypic and molecular methods available for CP-CRE detection. There is no single detection method that is ideal for all situations.

Improved Phenotype-Based Definition for Identifying Carbapenemase Producers among Carbapenem-Resistant Enterobacteriaceae.

Preventing transmission of carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) is a public health priority. A phenotype-based definition that reliably identifies CP-CRE while minimizing misclassification of non-CP-CRE could help prevention efforts. To assess possible definitions, we evaluated enterobacterial isolates that had been tested and deemed nonsusceptible to >1 carbapenem at US Emerging Infections Program sites. We determined the number of non-CP isolates that met (false positives) and CP isolates that did not meet (false negatives) the Centers for Disease Control and Prevention CRE definition in use during our study: 30% (94/312) of CRE had carbapenemase genes, and 21% (14/67) of Klebsiella pneumoniae carbapenemase-producing Klebsiella isolates had been misclassified as non-CP. A new definition requiring resistance to 1 carbapenem rarely missed CP strains, but 55% of results were false positive; adding the modified Hodge test to the definition decreased false positives to 12%. This definition should be considered for use in carbapenemase-producing CRE surveillance and prevention.

Staphylococcus aureus Colonization and Strain Type at Various Body Sites among Patients with a Closed Abscess and Uninfected Controls at U.S. Emergency Departments.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a prevalent cause of skin and soft tissue infections (SSTI), but the association between CA-MRSA colonization and infection remains uncertain. We studied the carriage frequency at several body sites and the diversity of S. aureus strains from patients with and without SSTI. Specimens from the nares, throat, rectum, and groin of case subjects with a closed skin abscess (i.e., without drainage) and matched control subjects without a skin infection (n = 147 each) presenting to 10 U.S. emergency departments were cultured using broth enrichment; wound specimens were cultured from abscess cases. Methicillin resistance testing and spa typing were performed for all S. aureus isolates. S. aureus was found in 85/147 (57.8%) of abscesses; 49 isolates were MRSA, and 36 were methicillin-susceptible S. aureus (MSSA). MRSA colonization was more common among cases (59/147; 40.1%) than among controls (27/147; 18.4%) overall (P < 0.001) and at each body site; no differences were observed for MSSA. S. aureus-infected subjects were usually (75/85) colonized with the infecting strain; among MRSA-infected subjects, this was most common in the groin. The CC8 lineage accounted for most of both infecting and colonizing isolates, although more than 16 distinct strains were identified. Nearly all MRSA infections were inferred to be USA300. There was more diversity among colonizing than infecting isolates and among those isolated from controls versus cases. CC8 S. aureus is a common colonizer of persons with and without skin infections. Detection of S. aureus colonization, and especially MRSA, may be enhanced by extranasal site culture.

Notes from the Field: Carbapenem-resistant Enterobacteriaceae Producing OXA-48-like Carbapenemases--United States, 2010-2015.

Carbapenem-resistant Enterobacteriaceae (CRE) are bacteria that are often resistant to most classes of antibiotics and cause health care-associated infections with high mortality rates. Among CRE, strains that carry plasmid-encoded carbapenemase enzymes that inactivate carbapenem antibiotics are of greatest public health concern because of their potential for rapid global dissemination, as evidenced by the increasing distribution of CRE that produce the Klebsiella pneumoniae carbapenemase and the New Delhi metallo-ß-lactamase. Newly described resistance in Enterobacteriaceae, such as plasmid-mediated resistance to the last-line antimicrobial colistin, recently detected in China, and resistance to the newly approved antimicrobial, ceftazidime-avibactam, identified from a U.S. K. pneumoniae carbapenemase-producing isolate, highlight the continued urgency to delay spread of CRE. Monitoring the emergence of carbapenemases is crucial to limiting their spread; identification of patients carrying carbapenemase-producing CRE should result in the institution of transmission-based precautions and enhanced environmental cleaning to prevent transmission.* The OXA-48 carbapenemase was first identified in Enterobacteriaceae in Turkey in 2001, and OXA-48-like variants have subsequently been reported around the world. The first U.S. reports of OXA-48-like carbapenemases were published in 2013 and included retrospectively identified isolates from 2009 and two isolates collected in 2012 from patients in Virginia who had recently been hospitalized outside the United States. Although there are limited additional published reports from the United States, CDC continues to receive reprots of these organisms. This report describes patients identified as carrying CRE producing OXA-48-like carbapenemases in the United States during June 2010-August 2015.

Vancomycin-Resistant Staphylococcus aureus - Delaware, 2015.

Vancomycin-resistant Staphylococcus aureus (VRSA) is a rare, multidrug-resistant bacterium of public health concern that emerged in the United States in 2002. VRSA (S. aureus with vancomycin minimum inhibitory concentration [MIC] ≥16 µg/mL) arises when vancomycin resistance genes (e.g., the vanA operon, which codes for enzymes that result in modification or elimination of the vancomycin binding site) from vancomycin-resistant enterococci (VRE) are transferred to S. aureus (1). To date, all VRSA strains have arisen from methicillin-resistant S. aureus (MRSA). The fourteenth VRSA isolate (VRSA 14) identified in the United States was reported to CDC in February 2015.