Louise Francois Watkins

Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene — Connecticut, 2016

The mcr-1 gene confers resistance to the polymyxins, including the antibiotic colistin, a medication of last resort for multidrug-resistant infections. The mcr-1 gene was first reported in 2015 in food, animal, and patient isolates from China (1) and is notable for being the first plasmid-mediated colistin resistance mechanism to be identified. Plasmids can be transferred between bacteria, potentially spreading the resistance gene to other bacterial species. Since its discovery, the mcr-1 gene has been reported from Africa, Asia, Europe, South America, and North America (2,3), including the United States, where it has been identified in Escherichia coli isolated from three patients and from two intestinal samples from pigs (2,4-6). In July 2016, the Pathogen Detection System at the National Center for Biotechnology Information (Bethesda, Maryland) identified mcr-1 in the whole genome sequence of an E. coli isolate from a Connecticut patient (7); this is the fourth isolate from a U.S. patient to contain the mcr-1 gene.

Epidemiology and Molecular Characteristics of Mycoplasma pneumoniae During an Outbreak of M. pneumoniae-Associated Stevens-Johnson Syndrome.

Background: An increase in Mycoplasma pneumoniae-associated Stevens-Johnson syndrome (SJS) cases at a Colorado pediatric hospital led to an outbreak investigation. We describe the epidemiologic and molecular characteristics of M. pneumoniae among SJS case-patients and surrounding community members during the outbreak. Methods: M. pneumoniae polymerase chain reaction-positive respiratory specimens from 5 Colorado hospitals and 4 referral laboratories underwent confirmatory polymerase chain reaction testing; positive specimens then underwent multilocus variable-number tandem-repeat analysis (MLVA) and macrolide resistance testing. Three SJS-M. pneumoniae case-patient households were surveyed using a standardized questionnaire, and nasopharyngeal/oropharyngeal swabs were obtained from all consenting/assenting household contacts. International Classification of Diseases, 9th revision codes were used to identify pneumonia cases among Colorado patients 5–21 years of age from January 2009 to March 2014. Results: Three different M. pneumoniae MLVA types were identified among the 5 SJS case-patients with confirmed infection; MLVA type 3-X-6-2 was seen more commonly in SJS case-patients (60%) than in 69 non-SJS community specimens (29%). Macrolide resistance was identified in 7% of community specimens but not among SJS case-patients. Of 15 household contacts, 5 (33%) were M. pneumoniae positive; all MLVA types were identical to those of the corresponding SJS case-patient, although the specimen from 1 contact was macrolide resistant. Overall pneumonia cases as well as those caused by M. pneumoniae specifically peaked in October 2013, coinciding with the SJS outbreak. Conclusions: The outbreak of M. pneumoniae-associated SJS may have been associated with a community outbreak of M. pneumoniae; clinicians should be aware of the M. pneumoniae–SJS relationship. Household transmission of M. pneumoniae was common within the households investigated.

Notes from the Field: Botulism Outbreak from Drinking Prison-Made Illicit Alcohol in a Federal Correctional Facility — Mississippi, June 2016

Botulism Outbreak from Drinking Prison-Made Illicit Alcohol in a Federal Correctional Facility — Mississippi, June 2016 Lindsey McCrickard, DVM1,2; Mariel Marlow, PhD1,2; Julie L. Self, PhD1,2; Louise Francois-Watkins, MD2; Kevin Chatham-Stephens, MD2; Jannifer Anderson3; Sheryl Hand3; Kathryn Taylor, MD3; Jennifer Hanson3; Keiundria Patrick3; Carolina Luquez, PhD2; Janet Dykes, MS2; Suzanne R. Kalb, PhD4; Kaitlin Hoyt4; John R. Barr, PhD4; Todd Crawford, MSN5; Anthony Chambers, MD5; Brian Douthit5; Robert Cox, MD6; Matt Craig, MD6; John Spurzem, MD6; Joseph Doherty, MD6; Michael Allswede, DO7; Paul Byers, MD3; Thomas Dobbs, MD3

Multistate Outbreak of Respiratory Infections Among Unaccompanied Children, June 2014–July 2014

BACKGROUND From January 2014-July 2014, more than 46 000 unaccompanied children (UC) from Central America crossed the US-Mexico border. In June-July, UC aged 9-17 years in 4 shelters and 1 processing center in 4 states were hospitalized with acute respiratory illness. We conducted a multistate investigation to interrupt disease transmission. METHODS Medical charts were abstracted for hospitalized UC. Nonhospitalized UC with influenza-like illness were interviewed, and nasopharyngeal and oropharyngeal swabs were collected to detect respiratory pathogens. Nasopharyngeal swabs were used to assess pneumococcal colonization in symptomatic and asymptomatic UC. Pneumococcal blood isolates from hospitalized UC and nasopharyngeal isolates were characterized by serotyping and whole-genome sequencing. RESULTS Among 15 hospitalized UC, 4 (44%) of 9 tested positive for influenza viruses, and 6 (43%) of 14 with blood cultures grew pneumococcus, all serotype 5. Among 48 nonhospitalized children with influenza-like illness, 1 or more respiratory pathogens were identified in 46 (96%). Among 774 nonhospitalized UC, 185 (24%) yielded pneumococcus, and 70 (38%) were serotype 5. UC transferring through the processing center were more likely to be colonized with serotype 5 (odds ratio, 3.8; 95% confidence interval, 2.1-6.9). Analysis of core pneumococcal genomes detected 2 related, yet independent, clusters. No pneumococcus cases were reported after pneumococcal and influenza immunization campaigns. CONCLUSIONS This respiratory disease outbreak was due to multiple pathogens, including Streptococcus pneumoniae serotype 5 and influenza viruses. Pneumococcal and influenza vaccinations prevented further transmission. Future efforts to prevent similar outbreaks will benefit from use of both vaccines.

Lessons From an Outbreak of Legionnaires' Disease on a Hematology-Oncology Unit.

OBJECTIVES To define the scope of an outbreak of Legionnaires’ disease (LD), to identify the source, and to stop transmission. DESIGN AND SETTING Epidemiologic investigation of an LD outbreak among patients and a visitor exposed to a newly constructed hematology-oncology unit. METHODS An LD case was defined as radiographically confirmed pneumonia in a person with positive urinary antigen testing and/or respiratory culture for Legionella and exposure to the hematology-oncology unit after February 20, 2014. Cases were classified as definitely or probably healthcare-associated based on whether they were exposed to the unit for all or part of the incubation period (2–10 days). We conducted an environmental assessment and collected water samples for culture. Clinical and environmental isolates were compared by monoclonal antibody (MAb) and sequence-based typing. RESULTS Over a 12-week period, 10 cases were identified, including 6 definite and 4 probable cases. Environmental sampling revealed Legionella pneumophila serogroup 1 (Lp1) in the potable water at 9 of 10 unit sites (90%), including all patient rooms tested. The 3 clinical isolates were identical to environmental isolates from the unit (MAb2-positive, sequence type ST36). No cases occurred with exposure after the implementation of water restrictions followed by point-of-use filters. CONCLUSIONS Contamination of the unit’s potable water system with Lp1 strain ST36 was the likely source of this outbreak. Healthcare providers should routinely test patients who develop pneumonia at least 2 days after hospital admission for LD. A single case of LD that is definitely healthcare associated should prompt a full investigation.

Novel trimethoprim resistance gene dfrA34 identified in Salmonella Heidelberg in the USA

Background Trimethoprim/sulfamethoxazole is a synthetic antibiotic combination recommended for the treatment of complicated non-typhoidal Salmonella infections in humans. Resistance to trimethoprim/sulfamethoxazole is mediated by the acquisition of mobile genes, requiring both a dfr gene (trimethoprim resistance) and a sul gene (sulfamethoxazole resistance) for a clinical resistance phenotype (MIC ≥4/76 mg/L). In 2017, the CDC investigated a multistate outbreak caused by a Salmonella enterica serotype Heidelberg strain with trimethoprim/sulfamethoxazole resistance, in which sul genes but no known dfr genes were detected. Objectives To characterize and describe the molecular mechanism of trimethoprim resistance in a Salmonella Heidelberg outbreak isolate. Methods Illumina sequencing data for one outbreak isolate revealed a 588 bp ORF encoding a putative dfr gene. This gene was cloned into Escherichia coli and resistance to trimethoprim was measured by broth dilution and Etest. Phylogenetic analysis of previously reported dfrA genes was performed using MEGA. Long-read sequencing was conducted to determine the context of the novel dfr gene. Results and conclusions The novel dfr gene, named dfrA34, conferred trimethoprim resistance (MIC ≥32 mg/L) when cloned into E. coli. Based on predicted amino acid sequences, dfrA34 shares less than 50% identity with other known dfrA genes. The dfrA34 gene is located in a class 1 integron in a multiresistance region of an IncC plasmid, adjacent to a sul gene, thus conferring clinical trimethoprim/sulfamethoxazole resistance. Additionally, dfrA34 is associated with ISCR1, enabling easy transmission between other plasmids and bacterial strains.

Report of erm(B)+ Campylobacter jejuni in the United States

Campylobacter is a leading cause of foodborne illness in the United States, causing an estimated 1.3 million illnesses annually (1).….

Isolates from Patients with Noninvasive Listeria monocytogenes : Are They Important?

Abstract Background From 2004–2015, CDC received 82 reports of patients with Listeria monocytogenes (Lm) cultured from non-sterile sites. Whereas invasive listeriosis (Lm isolated from typically sterile sites) is nationally notifiable and well described, information about patients with “noninvasive” Lm (isolated from other sites) is limited to a small number of case reports. We summarize the demographic and clinical characteristics of a convenience sample of patients with noninvasive Lm and compare to patients with invasive Lm reported through routine surveillance. Methods The Listeria Initiative (LI) is a national surveillance system that collects demographic, clinical, laboratory, and food exposure information on laboratory-confirmed listeriosis cases in the United States. While not nationally notifiable, public health agencies can also submit similar information to LI for patients with noninvasive Lm. We reviewed all reports to LI from 2004–2015 and used a standardized approach to characterize isolate sources as invasive or noninvasive. We then compared demographic and clinical factors between patients with invasive and noninvasive Lm using Fisher’s exact and Wilcoxon rank-sum tests. Results The most common sources of noninvasive isolates (n = 82) were skin or soft tissue (n = 35, 43%), urine (n = 19, 23%), and stool (n = 17, 21%). Compared with patients with noninvasive Lm, patients with invasive Lm (n = 4599) were more likely to be older than 65 years (66% vs. 54% P = 0.03), to be associated with an outbreak (17% vs. 7%, P = 0.02), to be hospitalized (92% vs. 54%, P < 0.01), and to die (20% vs. 4%, P < 0.01). Conclusion This is the first review of patients with noninvasive Lm using US LI surveillance data. Patients with invasive Lm were older and more likely to be associated with an outbreak, hospitalization, or death when compared with patients with noninvasive Lm. The reasons that patients with noninvasive Lm have a less severe clinical course are not well understood; however, the frequency of hospitalizations and deaths in patients with noninvasive isolates indicates their clinical relevance and public health significance. Disclosures All authors: No reported disclosures.

Emergence of mcr-1 among Nontyphoidal Salmonella Isolates in the United States

Abstract Background Colistin is considered a critically important antimicrobial for its role in the treatment of severe multidrug-resistant infections. Colistin resistance conferred by the plasmid-mediated gene mcr-1 has been reported in enteric pathogens globally since 2015, but remains rare in the United States. We describe the search for mcr-1 among nontyphoidal Salmonella (NTS) and the identification of the first human cases in the United States. Methods Whole genome sequencing (WGS) was performed on NTS isolates from humans by state health departments, from retail meat by the US Food and Drug Administration, and from food animals by the US Department of Agriculture. Sequences were uploaded to the National Center for Biotechnology Information and screened through their pathogen detection pipeline for the presence of resistance determinants (including mcr-1) beginning in late 2015; screening included some retrospective sequences. Isolates with the suspected mcr-1 gene were submitted to CDC for confirmatory PCR. Epidemiological information on human cases was collected from state health departments. Results Over 70,000 Salmonella isolates from humans, retail meat, and food animals were screened for mcr-1. No NTS with mcr-1 were identified in retail meat or food animals. Four human cases of NTS with mcr-1 were identified by WGS and three were confirmed by PCR (1 pending testing): Salmonella Corvallis in an 18-year-old man from Tennessee (isolation July 2014), Salmonella Enteritidis in a 55 year-old woman from Connecticut (isolation May 2016), Salmonella Typhimurium in a 57-year-old woman from Virginia (isolation November 2016), and Salmonella Enteritidis in a 47-year-old man from Minnesota (isolation April 2017). All patients traveled internationally in the 10 days prior to illness onset. Conclusion NTS rarely contain mcr-1 in the United States. To date, all human cases have been linked to international travel, reflecting the higher prevalence of mcr-1 reported from other parts of the world. The absence of mcr-1 in NTS from US food animals and retail meat is likely because colistin has not been used in food animal agriculture in the United States, underscoring the importance of a One Health approach to combat antimicrobial resistance. Disclosures All authors: No reported disclosures.

A Cluster of Group A Streptococcal Infections in a Skilled Nursing Facility—the Potential Role of Healthcare Worker Presenteeism

To determine the extent of a group A streptococcus (GAS) cluster (2 residents with invasive GAS (invasive case‐patients), 2 carriers) caused by a single strain (T antigen type 2 and M protein gene subtype 2.0 (T2, emm 2.0)), evaluate factors contributing to transmission, and provide recommendations for disease control.