Extensively Drug-Resistant Pseudomonas aeruginosa Outbreak associated with Artificial Tears.

BACKGROUND: Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) are extensively drug resistant bacteria. We investigated the source of a multistate CP-CRPA outbreak. METHODS: Cases were defined as a U.S. patient's first isolation of P. aeruginosa sequence type 1203 with the carbapenemase gene blaVIM-80 and cephalosporinase gene blaGES-9 from any specimen source collected and reported to CDC between January 1, 2022-May 15, 2023. We conducted a 1:1 matched case-control study at the post-acute care facility with the most cases, assessed exposures associated with case status for all case-patients, and tested products for bacterial contamination. RESULTS: We identified 81 case-patients from 18 states, 27 of whom were identified through surveillance cultures. Four (7%) of 54 case-patients with clinical cultures died within 30 days of culture collection, and four (22%) of 18 with eye infections underwent enucleation. In the case-control study, case-patients had increased odds of receiving artificial tears compared to controls (crude matched OR: 5.0, 95% CI: 1.1, 22.8). Overall, artificial tears use was reported by 61 (87%) of 70 case-patients with information; 43 (77%) of 56 case-patients with brand information reported use of Brand A, an imported, preservative-free, over-the-counter (OTC) product. Bacteria isolated from opened and unopened bottles of Brand A were genetically related to patient isolates. FDA inspection of the manufacturing plant identified likely sources of contamination. CONCLUSIONS: A manufactured medical product serving as the vehicle for carbapenemase-producing organisms is unprecedented in the U.S. The clinical impacts from this outbreak underscore the need for improved requirements for U.S. OTC product importers.

Transmission of Carbapenem-Resistant Klebsiella pneumoniae in US Hospitals.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKp) is the most prevalent carbapenem-resistant Enterobacterales in the United States. We evaluated CRKp clustering in patients in US hospitals. METHODS: From April 2016 to August 2017, 350 patients with clonal group 258 CRKp were enrolled in the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae, a prospective, multicenter, cohort study. A maximum likelihood tree was constructed using RAxML. Static clusters shared ≤21 single-nucleotide polymorphisms (SNP) and a most recent common ancestor. Dynamic clusters incorporated SNP distance, culture timing, and rates of SNP accumulation and transmission using the R program TransCluster. RESULTS: Most patients were admitted from home (n = 150, 43%) or long-term care facilities (n = 115, 33%). Urine (n = 149, 43%) was the most common isolation site. Overall, 55 static and 47 dynamics clusters were identified involving 210 of 350 (60%) and 194 of 350 (55%) patients, respectively. Approximately half of static clusters were identical to dynamic clusters. Static clusters consisted of 33 (60%) intrasystem and 22 (40%) intersystem clusters. Dynamic clusters consisted of 32 (68%) intrasystem and 15 (32%) intersystem clusters and had fewer SNP differences than static clusters (8 vs 9; P = .045; 95% confidence interval [CI]: -4 to 0). Dynamic intersystem clusters contained more patients than dynamic intrasystem clusters (median [interquartile range], 4 [2, 7] vs 2 [2, 2]; P = .007; 95% CI: -3 to 0). CONCLUSIONS: Widespread intrasystem and intersystem transmission of CRKp was identified in hospitalized US patients. Use of different methods for assessing genetic similarity resulted in only minor differences in interpretation.

Antifungal Resistance Trends of Candida auris Clinical Isolates in New York and New Jersey from 2016 to 2020.

About 55% of U.S. Candida auris clinical cases were reported from New York and New Jersey from 2016 through 2020. Nearly all New York-New Jersey clinical isolates (99.8%) were fluconazole resistant, and 50% were amphotericin B resistant. Echinocandin resistance increased from 0% to 4% and pan-resistance increased from 0 to <1% for New York C. auris clinical isolates but not for New Jersey, highlighting the regional differences.

Factors Associated With Candida auris Colonization and Transmission in Skilled Nursing Facilities With Ventilator Units, New York, 2016-2018.

BACKGROUND: Candida auris is an emerging, multidrug-resistant yeast that spreads in healthcare settings. People colonized with C. auris can transmit this pathogen and are at risk for invasive infections. New York State (NYS) has the largest US burden (>500 colonized and infected people); many colonized individuals are mechanically ventilated or have tracheostomy, and are residents of ventilator-capable skilled nursing facilities (vSNF). We evaluated the factors associated with C. auris colonization among vSNF residents to inform prevention interventions. METHODS: During 2016-2018, the NYS Department of Health conducted point prevalence surveys (PPS) to detect C. auris colonization among residents of vSNFs. In a case-control investigation, we defined a case as C. auris colonization in a resident, and identified up to 4 residents with negative swabs during the same PPS as controls. We abstracted data from medical records on patient facility transfers, antimicrobial use, and medical history. RESULTS: We included 60 cases and 218 controls identified from 6 vSNFs. After controlling for potential confounders, the following characteristics were associated with C. auris colonization: being on a ventilator (adjusted odds ratio [aOR], 5.9; 95% confidence interval [CI], 2.3-15.4), receiving carbapenem antibiotics in the prior 90 days (aOR, 3.5; 95% CI, 1.6-7.6), having ≥1 acute care hospital visit in the prior 6 months (aOR, 4.2; 95% CI, 1.9-9.6), and receiving systemic fluconazole in the prior 90 days (aOR, 6.0; 95% CI, 1.6-22.6). CONCLUSIONS: Targeted screening of patients in vSNFs with the above risk factors for C. auris can help identify colonized patients and facilitate the implementation of infection control measures. Antimicrobial stewardship may be an important factor in the prevention of C. auris colonization.

Laboratory Analysis of an Outbreak of Candida auris in New York from 2016 to 2018: Impact and Lessons Learned.

Candida auris is a multidrug-resistant yeast which has emerged in health care facilities worldwide; however, little is known about identification methods, patient colonization, environmental survival, spread, and drug resistance. Colonization on both biotic (patients) and abiotic (health care objects) surfaces, along with travel, appear to be the major factors for the spread of this pathogen across the globe. In this investigation, we present laboratory findings from an ongoing C. auris outbreak in New York (NY) from August 2016 through 2018. A total of 540 clinical isolates, 11,035 patient surveillance specimens, and 3,672 environmental surveillance samples were analyzed. Laboratory methods included matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for yeast isolate identification, real-time PCR for rapid surveillance sample screening, culture on selective/nonselective media for recovery of C. auris and other yeasts from surveillance samples, antifungal susceptibility testing to determine the C. auris resistance profile, and Sanger sequencing of the internal transcribed spacer (ITS) and D1/D2 regions of the ribosomal gene for C. auris genotyping. Results included (a) identification and confirmation of C. auris in 413 clinical isolates and 931 patient surveillance isolates as well as identification of 277 clinical cases and 350 colonized cases from 151 health care facilities, including 59 hospitals, 92 nursing homes, 1 long-term acute care hospital (LTACH), and 2 hospices, (b) successful utilization of an in-house developed C. auris real-time PCR assay for the rapid screening of patient and environmental surveillance samples, (c) demonstration of relatively heavier colonization of C. auris in nares than in the axilla/groin, and (d) predominance of the South Asia clade I with intrinsic resistance to fluconazole and elevated MIC to voriconazole (81%), amphotericin B (61%), flucytosine (5FC) (3%), and echinocandins (1%). These findings reflect greater regional prevalence and incidence of C. auris and the deployment of better detection tools in an unprecedented outbreak.

Brucella Exposure Risk Events in 10 Clinical Laboratories, New York City, USA, 2015 to 2017.

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.

Opportunities to Improve Antibiotic Appropriateness in U.S. ICUs: A Multicenter Evaluation.

OBJECTIVES: To use a standardized tool for a multicenter assessment of antibiotic appropriateness in ICUs and identify local antibiotic stewardship improvement opportunities. DESIGN: Pilot point prevalence conducted on October 5, 2016; point prevalence survey conducted on March 1, 2017. SETTING: ICUs in 12 U.S. acute care hospitals with median bed size 563. PATIENTS: Receiving antibiotics on participating units on March 1, 2017. INTERVENTIONS: The Centers for Disease Control and Prevention tool for the Assessment of Appropriateness of Inpatient Antibiotics was made actionable by an expert antibiotic stewardship panel and implemented across hospitals. Data were collected by antibiotic stewardship program personnel at each hospital, deidentified and submitted in aggregate for benchmarking. hospital personnel identified most salient reasons for inappropriate use by category and agent. MEASUREMENTS AND MAIN RESULTS: Forty-seven ICUs participated. Most hospitals (83%) identified as teaching with median licensed ICU beds of 70. On March 1, 2017, 362 (54%) of 667 ICU patients were on antibiotics (range, 8-81 patients); of these, 112 (31%) were identified as inappropriate and administered greater than 72 hours among all 12 hospitals (range, 9-82%). Prophylactic antibiotic regimens and PICU patients demonstrated a statistically significant risk ratio of 1.76 and 1.90 for inappropriate treatment, respectively. Reasons for inappropriate use included unnecessarily broad spectrum (29%), no infection or nonbacterial syndrome (22%), and duration longer than necessary (21%). Of patients on inappropriate antibiotic therapy in surgical ICUs, a statistically significant risk ratio of 2.59 was calculated for noninfectious or nonbacterial reasons for inappropriate therapy. CONCLUSIONS: In this multicenter point prevalence study, 31% of ICU antibiotic regimens were inappropriate; prophylactic regimens were often inappropriate across different ICU types, particularly in surgical ICUs. Engaging intensivists in antibiotic stewardship program efforts is crucial to sustain the efficacy of antibiotics and quality of infectious diseases care in critical care settings. This study underscores the value of standardized assessment tools and benchmarking to be shared with local leaders for targeted antibiotic stewardship program interventions.

Candida auris Isolates Resistant to Three Classes of Antifungal Medications - New York, 2019.

Candida auris is a globally emerging yeast that causes outbreaks in health care settings and is often resistant to one or more classes of antifungal medications (1). Cases of C. auris with resistance to all three classes of commonly prescribed antifungal drugs (pan-resistance) have been reported in multiple countries (1). C. auris has been identified in the United States since 2016; the largest number (427 of 911 [47%]) of confirmed clinical cases reported as of October 31, 2019, have been reported in New York, where C. auris was first detected in July 2016 (1,2). As of June 28, 2019, a total of 801 patients with C. auris were identified in New York, based on clinical cultures or swabs of skin or nares obtained to detect asymptomatic colonization (3). Among these patients, three were found to have pan-resistant C. auris that developed after receipt of antifungal medications, including echinocandins, a class of drugs that targets the fungal cell wall. All three patients had multiple comorbidities and no known recent domestic or foreign travel. Although extensive investigations failed to document transmission of pan-resistant isolates from the three patients to other patients or the environment, the emergence of pan-resistance is concerning. The occurrence of these cases underscores the public health importance of surveillance for C. auris, the need for prudent antifungal prescribing, and the importance of conducting susceptibility testing on all clinical isolates, including serial isolates from individual patients, especially those treated with echinocandin medications. This report summarizes investigations related to the three New York patients with pan-resistant infections and the subsequent actions conducted by the New York State Department of Health and hospital and long-term care facility partners.

Neonatal Conjunctivitis Caused by Neisseria meningitidis US Urethritis Clade, New York, USA, August 2017.

We characterized a case of neonatal conjunctivitis in New York, USA, caused by Neisseria meningitidis by using whole-genome sequencing. The case was a rare occurrence, and the isolate obtained belonged to an emerging clade (N. meningitidis US nongroupable urethritis) associated with an increase in cases of urethritis since 2015.

Artificial Differences in Clostridium difficile Infection Rates Associated with Disparity in Testing.

In 2015, Clostridium difficile testing rates among 30 US community, multispecialty, and cancer hospitals were 14.0, 16.3, and 33.9/1,000 patient-days, respectively. Pooled hospital onset rates were 0.56, 0.84, and 1.57/1,000 patient-days, respectively. Higher testing rates may artificially inflate reported rates of C. difficile infection. C. difficile surveillance should consider testing frequency.

Rapid Identification of a Cooling Tower-Associated Legionnaires' Disease Outbreak Supported by Polymerase Chain Reaction Testing of Environmental Samples, New York City, 2014-2015.

We investigated an outbreak of eight Legionnaires' disease cases among persons living in an urban residential community of 60,000 people. Possible environmental sources included two active cooling towers (air-conditioning units for large buildings) <1 km from patient residences, a market misting system, a community-wide water system used for heating and cooling, and potable water. To support a timely public health response, we used real-time polymerase chain reaction (PCR) to identify Legionella DNA in environmental samples within hours of specimen collection. We detected L. pneumophila serogroup 1 DNA only at a power plant cooling tower, supporting the decision to order remediation before culture results were available. An isolate from a power plant cooling tower sample was indistinguishable from a patient isolate by pulsed-field gel electrophoresis, suggesting the cooling tower was the outbreak source. PCR results were available <1 day after sample collection, and culture results were available as early as 5 days after plating. PCR is a valuable tool for identifying Legionella DNA in environmental samples in outbreak settings.

White Paper: Developing Antimicrobial Drugs for Resistant Pathogens, Narrow-Spectrum Indications, and Unmet Needs.

Despite progress in antimicrobial drug development, a critical need persists for new, feasible pathways to develop antibacterial agents to treat people infected with drug-resistant bacteria. Infections due to resistant gram-negative bacilli continue to cause unacceptable morbidity and mortality rates. Antibacterial agents have been historically studied in noninferiority clinical trials that focus on a single site of infection (eg, complicated urinary tract infections, intra-abdominal infections), yet these designs may not be optimal, and often are not feasible, for study of infections caused by drug-resistant bacteria. Over the past several years, multiple stakeholders have worked to develop consensus regarding paths forward with a goal of facilitating timely conduct of antimicrobial development. Here we advocate for a novel and pragmatic approach and, toward this end, present feasible trial designs for antibacterial agents that could enable conduct of narrow-spectrum, organism-specific clinical trials and ultimately approval of critically needed new antibacterial agents.

Staphylococcus aureus bacteremia at 5 US academic medical centers, 2008-2011: significant geographic variation in community-onset infections.

BACKGROUND: The incidence of community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) bacteremia rose from the late 1990s through the 2000s. However, hospital-onset (HO) MRSA rates have recently declined in the United States and Europe. METHODS: Data were abstracted from infection prevention databases between 1 January 2008 and 31 December 2011 at 5 US academic medical centers to determine the number of single-patient blood cultures positive for MRSA and methicillin-susceptible S. aureus (MSSA) per calendar year, stratified into CO and HO infections. RESULTS: Across the 5 centers, 4171 episodes of bacteremia were identified. Center A (Los Angeles, California) experienced a significant decline in CO-MRSA bacteremia rates (from a peak in 2009 of 0.42 to 0.18 per 1000 patient-days in 2011 [P = .005]), whereas CO-MSSA rates remained stable. Centers B (San Francisco, California), D (Chicago, Illinois), and E (Raleigh-Durham, North Carolina) experienced a stable incidence of CO-MRSA and CO-MSSA bacteremia. In contrast, at center C (New York, New York), the incidence of CO-MRSA increased >3-fold (from 0.11 to 0.34 cases per 1000 patient-days [P < .001]). At most of the sites, HO-MRSA decreased and HO-MSSA rates were stable. USA300 accounted for 52% (104/202) of genotyped MRSA isolates overall, but this varied by center, ranging from 35% to 80%. CONCLUSIONS: CO-MRSA rates and the contribution of USA300 MRSA varied dramatically across diverse geographical areas in the United States. Enhanced infection control efforts are unlikely to account for such variation in CO infection rates. Bioecological and clinical explanations for geographical differences in CO-MRSA bacteremia rates merit further study.

Antimicrobial agents, drug adverse reactions and interactions, and cancer.

The intent of this chapter is to review the types of adverse drug reactions and interactions associated with antimicrobial agents, specifically in the setting of patients with malignancies. The initial sections will discuss categorizing and describing the mechanisms of adverse reactions and interactions. The later sections include a detailed discussion about adverse reactions and drug interactions associated with commonly used antibacterial, antiviral, and antifungal agents in this subpopulation. Where relevant, the clinical use and indication for the drugs will be reviewed. The antibacterial section will specifically address the emergence of antimicrobial resistance and drugs of last resort (newer agents, such as linezolid and daptomycin and novel uses of older previously retired agents, such as polymyxin B). The antifungal section will address the ramification of pharmacokinetic interactions and the need to measure drug levels. The chapter is not meant to be exhaustive and as such will not extensively address all antimicrobials or all interactions for each of these agents.

Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry to resolve complex clinical cases of patients with recurrent bacteremias.

Matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) is a rapid and accurate method of identifying microorganisms. Throughout Europe, it is already in routine use but has not yet been widely implemented in the United States, pending FDA approval. Here, we describe two medically complex patients at a large tertiary-care academic medical center with recurring bacteremias caused by distinct but related species. Bacterial identifications were initially obtained using the Vitek-2 system with the GPI card for Enterococcus and the API system for staphylococci. Initial results misled clinicians as to the source and proper management of these patients. Retrospective investigation with MALDI-TOF MS clarified the diagnosis by identifying a single microorganism as the pathogen in each case. To our knowledge, this is one of the first reports in the United States demonstrating the use of MALDI-TOF MS to facilitate the clinical diagnosis in patients with recurrent bacteremias of unclear source.

Candida auris admission screening pilot in select units of New York City health care facilities, 2017-2019.

BACKGROUND: This pilot project implemented admission screening for Candida auris (C. auris) using real-time polymerase chain reaction (rt-PCR) in select high-risk units within health care facilities in New York City. METHODS: An admission screening encounter consisted of collecting 2 swabs, to be tested by rt-PCR, and a data collection form for individuals admitted to ventilator units at 2 nursing homes (NHA and NHB), and the ventilator/pulmonary unit, intensive care unit, and cardiac care unit at a hospital (Hospital C) located in New York City from November 2017 to November 2019. RESULTS: C. auris colonization was identified in 6.9% (n = 188/2,726) of admissions to participating units. Rates were higher among admissions to NHA and NHB (20.7% and 22.0%, respectively) than Hospital C (3.6%). Within Hospital C, the ventilator/pulmonary unit had a higher rate (5.7%) than the intensive care unit (3.8%) or cardiac care unit (2.5%). DISCUSSION: Consistent with prior research, we found that individuals admitted to ventilator units were at higher risk of C. auris colonization. CONCLUSIONS: This project demonstrates the utility of admission screening using rt-PCR testing to rapidly identify C. auris colonization among admissions to health care facilities so that appropriate transmission-based precautions and control measures can be implemented rapidly to help decrease transmission.

Low pathogenic avian influenza A (H7N2) virus infection in immunocompromised adult, New York, USA, 2003.

In 2003, infection with low pathogenic avian influenza A (H7N2) virus was identified in an immunocompromised man with fever and community-acquired pneumonia in New York, USA. The patient recovered. Although the source of the virus was not identified, this case indicates the usefulness of virus culture for detecting novel influenza A viruses.

A description of the first Candida auris-colonized individuals in New York State, 2016-2017.

Candida auris (C. auris) is a globally emerging multidrug-resistant yeast. New York State (NYS) first detected C. auris in July 2016 and is the state most affected. This brief report describes characteristics of the first 114 individuals colonized with C. auris identified through active surveillance/screening by NYS Department of Health. "Colonized/screened" individuals were old (median age, 74 year), had extensive health care exposures and underlying conditions (multiple health care facility admissions in the 90 days prior with more than 80% requiring mechanical ventilation), and had 30- and 90-day mortality rates of 17.5% and 37.7%, respectively (with approximately 60% expired in the 2-year follow-up period). This description is helpful to inform additional prevention measures and add to the collective understanding of C. auris in the United States.