Quantifying the clinical virulence of Klebsiella pneumoniae producing carbapenemase Klebsiella pneumoniae with a Galleria mellonella model and a pilot study to translate to patient outcomes.

BACKGROUND: Previous studies may have overestimated morbidity and mortality due to Klebsiella pneumoniae producing carbapenemase (KPC) Klebsiella pneumoniae infections because of difficulties in modeling patient comorbidities. This pilot study sought to evaluate KPC virulence by combining clinical and Galleria mellonella models in patients with K. pneumoniae blood stream infections (BSIs). METHODS: G. mellonella were inoculated using KPC(+) and KPC(-) isolates from these patients. Extent and rapidity of insect mortality was analyzed. Patients were stratified by KPC BSI status. Clinical outcomes of mortality and length of stay post-infection for survivors (LOS) were analyzed. Median virulence scores calculated from the insect studies were imputed in the clinical model. RESULTS: The in-vivo model revealed greater mortality in KPC(-) isolates (p < 0.001). Fifteen patients with KPC(+) BSI were matched with 60 patients with KPC(-) BSI. Hospital mortality was greater in the KPC(+) group versus the KPC(-) group (OR 3.79, 95% CI 1.00 - 14.34). LOS was longer in the KPC(+) group (p < 0.01). Conversely the virulence score attenuated the association between KPC(+) status and mortality and LOS in the final translational models. CONCLUSIONS: KPC(+) status was associated with decreased virulence in GM. Opposite findings were observed in patients. This pilot study demonstrates that measured virulence from GM may differ from human estimates of virulence.

COVID-19 outbreak and genomic investigation in an inpatient behavioral health unit.

Background: Inpatient behavioral health units (BHUs) had unique challenges in implementing interventions to mitigate coronavirus disease 2019 (COVID-19) transmission, in part due to socialization in BHU settings. The objective of this study was to identify the transmission routes and the efficacy of the mitigation strategies employed during a COVID-19 outbreak in an inpatient BHU during the Omicron surge from December 2021 to January 2022. Methods: An outbreak investigation was performed after identifying 2 COVID-19-positive BHU inpatients on December 16 and 20, 2021. Mitigation measures involved weekly point prevalence testing for all inpatients, healthcare workers (HCWs), and staff, followed by infection prevention mitigation measures and molecular surveillance. Whole-genome sequencing on a subset of COVID-19-positive individuals was performed to identify the outbreak source. Finally, an outbreak control sustainability plan was formulated for future BHU outbreak resurgences. Results: We identified 35 HCWs and 8 inpatients who tested positive in the BHU between December 16, 2021, and January 17, 2022. We generated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomes from 15 HCWs and all inpatients. Phylogenetic analyses revealed 3 distinct but genetically related clusters: (1) an HCW and inpatient outbreak likely initiated by staff, (2) an HCW and inpatient outbreak likely initiated by an inpatient visitor, and (3) an HCW-only cluster initiated by staff. Conclusions: Distinct transmission clusters are consistent with multiple, independent SARS-CoV-2 introductions with further inpatient transmission occurring in communal settings. The implemented outbreak control plan comprised of enhanced personal protective equipment requirements, limited socialization, and molecular surveillance likely minimized disruptions to patient care as a model for future pandemics.

Virulence of vancomycin-resistant Enterococcus faecium according to linezolid resistance and clinical outbreak status.

Assessing clinical virulence differences between vancomycin-resistant Enterococcus faecium (VREF) strains resistant to linezolid (LRVRE) and linezolid-susceptible VRE (LSVRE) strains is difficult due to confounding patient variables. Galleria mellonella is a validated host interaction model allowing straightforward organism virulence assessment. The objective of this study was to assess the virulence of VREF in G. mellonella according to linezolid resistance and clinical outbreak status. A genetically related pair of VREF strains with and without genotypically confirmed linezolid resistance was selected for analysis. Additionally, six strains of LSVRE and two strains of LRVRE were selected according to epidemiologic outbreak status. Mortality of G. mellonella was assessed daily over a 5-day period and analyzed using Kaplan-Meier survival curves and log rank tests. Linezolid resistance did not have a significant effect on G. mellonella mortality in the genetically related pair (P = 0.93). There was no significant difference in mortality over time between strains (non-outbreak [i.e., no patient transmissions were recorded] [n = 2] versus outbreak [i.e., transmission occurred between 3 or more patients in a period of 30 days] [n = 6], P = 0.84; extensive transmission [i.e., the isolate was transmitted between at least 80 patients] [n = 2] versus limited transmission [i.e., the isolate was transmitted between fewer than 10 patients] [n = 4], P = 0.78). These results suggest that patients infected with LRVRE or outbreak strains of VREF are at no greater risk of poor outcomes mediated by organism virulence than those infected with LSVRE or non-outbreak strains.

Characterization of ciprofloxacin resistant Escherichia coli isolates among men undergoing evaluation for transrectal ultrasound guided prostate biopsy.

PURPOSE: We determine the prevalence of ciprofloxacin resistant gram-negative bacilli in patients scheduled for transrectal ultrasound guided prostate biopsy, characterize the Escherichia coli strains recovered from this patient population, and characterize the mechanisms responsible for ß-lactam and ciprofloxacin resistance. MATERIALS AND METHODS: Rectal swabs from 991 patients were cultured for ciprofloxacin resistant gram-negative bacilli with a selective medium. Recovered E. coli isolates were further analyzed with susceptibility testing, pulsed field gel electrophoresis, plasmid isolation and sequencing. RESULTS: A total of 193 ciprofloxacin resistant gram-negative bacilli were recovered and of these isolates 167 (87%) were E. coli. The prevalence of ciprofloxacin resistant E. coli in the study population was 17%. Only 38 (26%) of the 149 E. coli isolates that received susceptibility testing were susceptible to ampicillin and ampicillin-sulbactam. In select isolates transferrable plasmids carrying ß-lactamase were responsible for the resistance to the ß-lactam agents and other nonß-lactam antimicrobials. Diverse combinations of gyrA and parC mutations associated with fluoroquinolone resistance were identified. Strain typing and plasmid typing indicated that the E. coli isolates did not share a common origin. CONCLUSIONS: Of the patients in our study 17% carried ciprofloxacin resistant E. coli. Analysis of resistance mechanisms and plasmid analysis along with strain typing demonstrated that this patient population harbored organisms with heterogeneous phenotypic susceptibility, indicating that universal prophylaxis would not provide optimal coverage for patients undergoing transrectal ultrasound guided prostate biopsy.

A systemwide approach to validation of electronic device denominator data.

A multidisciplinary team collaborated to develop and validate a process to electronically capture patient and device denominator data at 6 hospitals in the same healthcare system. Validation was completed within 4-16 months. Manual count errors were identified as the main driver of electronic versus manual discrepancies.

Healthcare system strategy for seasonal influenza implementation plan.

Healthcare systems are expanding, no longer bound by county, state or country, thus necessitating the importance of consistent and standardized guidelines for the management and control of communicable diseases, including influenza. As a healthcare system consisting of diverse facilities with a focus not only on safe patient care but also patient satisfaction, there was a clear need for a multifaceted approach to manage influenza across the system. This resulted in the development of a strategic plan for decision-making, depiction of data and dissemination of information at both a system- and local facility-level.

Triage documentation-based decision support to improve infectious disease risk screening and mitigate exposure.

Multidisciplinary focus group review of current triage practice identified gaps in identification of potentially infectious diseases. Modifications were made to triage and nursing assessment forms that were easy to maneuver, rapidly modifiable, and provided documentation-based decision support to expedite infection prevention measures. Development of a decision support infectious disease risk screening tool enhances outbreak preparedness, occupational safety, and response.