Background: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales are antimicrobial resistant pathogens which cause difficult-to-treat infections. In April 2025, Hospital A notified the Indiana Department of Health about an outbreak of ESBL-Klebsiella pneumoniae. CDC assisted with identifying the sources of the outbreak and recommending control measures. Methods: We defined confirmed cases as ESBL-producing K. pneumoniae multi-locus sequence type (ST) 661 (or closely related ST) by whole genome sequencing (WGS). Suspect cases included 3rd- and 4th-generation cephalosporin-resistant K. pneumoniae without WGS data. All isolates originated from patient cultures collected on or after January 1, 2025, from Hospital A’s network of hospitals and outpatient clinics. An incident case was the first case identified from a patient. Among confirmed incident cases, we abstracted medical charts for 30 randomly selected patients. We assessed infection prevention and control (IPC) practices and sampled the hospital environment to identify potential reservoirs. Results: We identified 70 confirmed and 52 suspect incident cases between January and September. Median patient age was 70 years (range: 19–91 years); 67 (55%) were female. Within 90 days before incident case collection, 28 of the patients with charts abstracted (93%) received care at Hospital A; 27 (90%) received radiologic imaging, mostly CT scans (17/30; 57%) and transthoracic echocardiograms (16/30; 53%). We observed gaps in hand hygiene, personal protective equipment usage, and environmental cleaning. ESBL-K. pneumoniae was recovered from 23 environmental samples, including radiology equipment. WGS revealed that these isolates clustered with patient isolates, showing 0-26 pairwise high-quality single nucleotide variants across a 95.73% core genome. Following the implementation of IPC recommendations, the average number of monthly cases was 21% lower compared to the 9 months prior. Conclusions: Our investigation linked the outbreak to gaps in IPC practices and contamination of the healthcare environment, highlighting the often-overlooked role of the environment in the spread of ESBL-producing pathogens.

Stenotrophomonas maltophilia is an opportunistic bacterial pathogen found in healthcare settings. During May 2022-September 2023, an acute care hospital in northern California, USA, identified 13 S. maltophilia bloodstream infections among intensive care unit patients. Whole-genome sequencing showed the isolates were highly related. We identified risk factors for infection by conducting a matched case-control study, targeted assessment of infection prevention and control practices, and laboratory testing of suspected environmental reservoirs. Among 13 case-patients and 39 control-patients, patients exposed to iodinated contrast (odds ratio [OR] 12.0; 95% CI 2.1-∞), injectable propofol (OR 12.2; 95% CI 1.5-101.4), or fentanyl (OR 9.2; 95% CI 1.8-∞) had increased odds of S. maltophilia bloodstream infection. Although we did not have culture confirmation of a source, we suspect S. maltophilia was transmitted by exposure to nonsterile water from a common source. We recommended infection prevention and control practices to reduce risk for contamination from nonsterile water.

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 US patient's first isolation of P. aeruginosa sequence type 1203 with carbapenemase gene blaVIM-80 and cephalosporinase gene blaGES-9 from any specimen source collected and reported to the Centers for Disease Control and Prevention during 1 January 2022-15 May 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 4 (22%) of 18 with eye infections underwent enucleation. In the case-control study, case-patients had increased odds of receiving artificial tears versus 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. Food and Drug Administration 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 United States. The clinical impacts from this outbreak underscore the need for improved requirements for US OTC product importers. The source of an extensively drug-resistant Pseudomonas outbreak causing significant morbidity and mortality was a nationally distributed, over-the-counter product. This investigation highlights the potential for manufactured drugs to be sources of multidrug-resistant organisms and the need for increased manufacturer oversight. Graphical Abstract This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/a-multistate-outbreak-of-extensively-drug-resistant-pseudomonas-aeruginosa-associated-with-contaminated-artificial-tears-2022-2023

Background Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia.Methods A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates.Results Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year.Conclusions B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen. We describe 5 health care-associated neuroinvasive Bacillus cereus infections. No point source was identified, and isolates were unrelated. Enhancing environmental cleaning, laundry management, and the neutropenic diet, as well as modifying empiric treatment protocols for febrile neutropenia, aborted the cluster.

Background: Stenotrophomonas maltophilia is a gram-negative, biofilm-producing bacterium that is ubiquitous in water environments and often associated with healthcare-associated infections (HAIs). Outbreaks of S. maltophilia bloodstream infections are a rare event and raise the suspicion of a common source. We used whole-genome sequencing (WGS) for an investigation of a cluster of S. maltophilia HAIs at a single hospital. Methods: A patient was defined as an intensive care unit (ICU) patient with fever and S. maltophilia isolated from a culture and who was treated for an HAI from May to October 2022. The response to the cluster included an epidemiologic investigation, water infection control risk assessments (WICRA), and environmental sampling. We also conducted WGS to characterize and assess relatedness between clinical and environmental S. maltophilia isolates. Results: From May 5 to October 1, 2022, we identified 11 HAIs due to S. maltophilia : 9 bloodstream infections and 2 ventilator-associated pneumonia cases. The initial epidemiological investigation did not identify common medical products, procedures, or personnel as an exposure source. The WICRA identified several breaches that may have exposed patients to contaminated water from sink backsplashes in the ICU, computerized tomography (CT) rooms, and the emergency department. In the CT rooms, saline bags were sometimes used for multiple patients, as were single-use intravenous contrast solution bottles. No additional cases were identified once infection control breaches were mitigated by installing sink splashguards, disinfecting drains, dedicating sink use for handwashing, and adhering to single-patient use of pharmaceutical products in the CT rooms. Of 46 environmental water samples, 19 were culture-positive for S. maltophilia . Isolates available for WGS included 7 clinical isolates (6 blood and 1 respiratory) and 17 environmental isolates. Among the 24 isolates sequenced, 16 unique multilocus sequence types (MLSTs) were identified. The 6 blood isolates sequenced were highly related (ST239, 0–4 high-quality, single-nucleotide variants [hqSNV] over 98.99% core genome), suggesting a common source. Two clusters of related environmental isolates were identified; however, overall MLST and hqSNV analyses suggested no relatedness between clinical and environmental isolates. Conclusions: An ICU cluster of S. maltophilia bloodstream infections was likely associated with water contamination of room surfaces and use of single-use intravenous products for multiple patients in the setting of a national pharmaceutical product shortage. This investigation highlights the importance of strong surveillance and water infection control, including routine assessment of ancillary areas in which intravenous products are administered and interdisciplinary collaboration to properly mitigate nosocomial transmission. Disclosures: None

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.

Background: Carbapenem resistance in gram-negative organisms is an important public health problem. The CDC conducted Sentinel surveillance in 2018–2019 to characterize these organisms from 9 facilities in 9 different states. Methods: Carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter spp (CRA) obtained from clinical samples of patients in acute-care or long-term care facilities were submitted to the CDC. Identification was confirmed using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF), and antimicrobial susceptibility testing (AST) was performed via broth microdilution for 27 antibiotics. All confirmed CRE and CRPA were tested for carbapenemase production (CP) using the modified carbapenem inactivation method (mCIM). The isolates that were mCIM-positive were assessed by real-time PCR for presence of blaKPC, blaNDM, blaVIM, and blaIMP. CP-CRE were also assessed for blaOXA-48-like. All confirmed CRA were tested for the same genes as CRPA and blaOXA-23–like, blaOXA-24/40-like, blaOXA-58–like, and blaOXA-235–like genes. Difficult-to-treat resistance (DTR) was defined as resistance to all β-lactams (excluding newer β-lactam combination agents) and quinolones tested. Results: The CDC confirmed 208 CRE, 161 CRPA, and 94 CRA. Table 1 summarizes AST results for a selection of drugs. We identified 112 (53.8%) mCIM-positive CRE and 6 (3.7%) mCIM-positive CRPA. The PCR results are summarized in Table 2. One mCIM-positive and PCR-negative isolate was positive in a metallo-β-lactamase screen. Conclusions: Resistance among CRE and CRPA to newer β-lactam combination agents was detected. Options for treating CRA are limited. Of 112 CP-CRE, 85.7% harbored blaKPC; CP-CRPA were rare (3.7%); and most CRA harbored blaOXA-23-like (55.3%) or blaOXA-24/40-like (30.9%). Whole-genome sequencing is planned to better understand gene variants, sequence types, and additional resistance markers present among the isolates.Funding: NoneDisclosures: None

Intestinal epithelial barrier dysfunction plays an important role in the development of multiple organ failure during systemic inflammation. The opening of the epithelial barrier leads to increased leukocyte infiltration into the lamina propria, the event therefore promotes microbial translocation and augments intestinal inflammation that contribute to the severity of trauma-associated complications. The aim of the study was to explore the roles of protein kinase 6 (PTK6) and focal adhesion kinase (FAK) in the intestinal epithelial barrier dysfunction following the treatment of TNFα/IFNγ. Epithelial barrier function was analyzed by measuring transcellular electrical resistance (TER) in cultured mouse intestinal epithelial cells. Our data revealed that stimulation of the epithelial cells with TNFα/IFNγ caused a decrease in transcellular electric resistance coupled with decrease expression of cell junctional proteins. The responses were prevented by the inhibitions of either PTK6 or FAK. Western blot analysis showed that elevated levels of active PTK6 and decreased detection of the tight junction protein claudin-3 upon TNFα stimulation. In addition, the downregulation of PTK6 in cells with siRNA attenuates TNFα/IFNγ induced FAK activation via diminished detection of FAK phosphorylation at Y397. Transfection of PTK6-deficient cells with active PTK6 rescued the FAK activation resulting in epithelial barrier dysfunction in response to TNFα/IFNγ. The results suggest that PTK6 mediated FAK activation plays a critical role in gut epithelial barrier dysfunction during inflammatory injury.

Background: The CDC has performed surveillance for invasive Staphylococcus aureus (iSA) infections through the Emerging Infections Program (EIP) since 2004. SCCmec and spa typing for clonal complex (CC) assignment and genomic markers have been used to characterize isolates. In 2019, whole-genome sequencing (WGS) of isolates began, allowing for high-resolution assessment of genomic diversity. Here, we evaluate the reliability of SCCmec typing, spa typing, and CC assignment using WGS data compared to traditional methods to ensure that backwards compatibility is maintained. Methods:S. aureus isolates were obtained from a convenience sample of iSA cases reported through the EIP surveillance system. Overall, 78 iSA isolates with diverse spa repeat patterns, CCs, SCCmec types, and antimicrobial susceptibility profiles were sequenced (MiSeq, Illumina). Real-time PCR and Sanger sequencing were used as the SCCmec and spa typing reference methods, respectively. spa-MLST mapping (Ridom SpaServer) served as the reference method for CC assignment. WGS assembly and multilocus sequence typing (MLST) were performed using the CDC QuAISAR-H pipeline. WGS-based MLST CCs were assigned using eBURST and SCCmec types using SCCmecFinder. spa types were assigned from WGS assemblies using BioNumerics. For isolate subtyping, previously published and validated canonical single-nucleotide polymorphisms (canSNPs) as well as the presence of the Panton-Valentine leukocidin (PVL) toxin and arginine catabolic mobile element (ACME) virulence factor were assessed for all genome assemblies. Results: All isolates were assigned WGS-based spa types, which were 100% concordant (78 of 78) with Sanger-based spa typing. SCCmecFinder assigned 91% of isolates (71 of 78) SCCmec types, which were 100% concordant with reference method results. Also, 7 isolates had multiple cassettes predicted or an incomplete SCCmec region assembly. Using WGS data, 96% (75 of 78) of isolates were assigned CCs; 3 isolates had unknown sequence types that were single-locus variants of established sequence types. Overall, 70 isolates had CCs assigned by the reference method; 100% (70 of 70) concordance was observed with WGS-based CCs. Analysis of canSNPs placed 42% (33 of 78) of isolates into CC8, with 17 (52%) of these isolates classified as USA300. PVL and ACME were not accurate markers for inferring the USA300 subtype as 24% (4 of 17) of isolates did not contain these markers. Conclusions:S. aureus CCs, SCCmec, and spa types can be reliably determined using WGS. Incorporation of canSNP analysis represents a more efficient method for CC8 assignment than the use of genomic markers alone. WGS allows for the replacement of multiple typing methods for increased laboratory efficiency, while maintaining backward compatibility with historical typing nomenclature.Funding: NoneDisclosures: None

Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociacion Latinoamericana del Torax. Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions. Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.

Report for the Years 1916–1917 from the Ear and Throat Department, Royal Infirmary, Edinburgh Part I Antro-Nasal Or Choanal Polypus: A Clinical And Pathological Report Of Thirty-Five Cases - Volume 33 Issue 8