Whole-Genome Sequencing Reveals the High Nosocomial Transmission and Antimicrobial Resistance of Clostridioides difficile in a Single Center in China, a Four-Year Retrospective Study

Clostridioides difficile infections (CDI) are the leading cause of healthcare-associated diarrhea and are known to be resistant to multiple antibiotics. In the past decade, C. difficile has emerged rapidly and has spread globally, causing great concern among American and European countries.

Colistin Dependency among Colistin-Heteroresistant Acinetobacter baumannii Isolates

Colistin dependent (CD) isolates are dependent on colistin for optimal growth. Here we aimed to systematically determine the emergence of CD among colistin-heteroresistant carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. We also examined the phenotypic characteristics of CD and the evolution of CD strains to overt resistance. Additionally, we examined whether detection of growth in blood cultures was impaired by CD. Heteroresistant isolates, as determined by population analysis profiling, were exposed to colistin; when the colony count with colistin was significantly higher than without, isolates were suspected to be CD. CD was confirmed by Etest and growth curves. CD strains with colistin minimum inhibitory concentrations > 2 mg/L after growth in colistin-free media were considered colistin-resistant. Of the 65 heteroresistant strains tested, eight became CD after colistin exposure. These strains attained higher colony counts and growth rates with colistin vs. without, and grew adjacent to the colistin Etest strip. CD strains exhibited increased susceptibilities to multiple antibiotics compared to their parent heteroresistant strains. All CD strains tested became colistin-resistant following growth without colistin. CD strains were detected in blood culture bottles, but time to detection was significantly prolonged compared with parent strains, suggesting that CD may lead to delay in detection of CRAB bacteremia.

Case Report: Adult Onset Still’s Disease after vaccination against Covid-19

Vaccination against the virus responsible for COVID-19 has become a key in preventing mortality and morbidity related to the infection. Studies have shown that the benefits of vaccination outweigh the risks. However, there are concerns regarding serious adverse events of some vaccines, although they are fortunately rare. Here, we report a case of a 47-year-old female from Kathmandu who presented with high grade fever, dry cough and erythematous rash a week after exposure to the Oxford-AstraZeneca vaccine. She had hepatosplenomegaly, persistent leucocytosis, anaemia and thrombocytosis along with markedly raised inflammatory markers. Her tests for infectious causes and haematological malignancies was negative and she showed no response to multiple antibiotics. Finally, she had a dramatic response to steroids with disappearance of fever and normalization of other laboratory parameters. Hence, she was diagnosed with Adult-onset Still’s Disease (AOSD). She was under methotrexate and prednisolone tapering dose and doing well as at time of writing. The trigger for the disease was hypothesized to be the vaccine because of the strong temporal association.

Function and Inhibitory Mechanisms of Multidrug Efflux Pumps

Multidrug efflux pumps are inner membrane transporters that export multiple antibiotics from the inside to the outside of bacterial cells, contributing to bacterial multidrug resistance (MDR). Postgenomic analysis has demonstrated that numerous multidrug efflux pumps exist in bacteria. Also, the co-crystal structural analysis of multidrug efflux pumps revealed the drug recognition and export mechanisms, and the inhibitory mechanisms of the pumps. A single multidrug efflux pump can export multiple antibiotics; hence, developing efflux pump inhibitors is crucial in overcoming infectious diseases caused by multidrug-resistant bacteria. This review article describes the role of multidrug efflux pumps in MDR, and their physiological functions and inhibitory mechanisms.

Membrane Transporters of the Major Facilitator Superfamily Are Essential for Long-Term Maintenance of Phenotypic Tolerance to Multiple Antibiotics in E. coli

We recently showed that the antibiotic-tolerant subpopulation of bacteria or persisters actively maintain the transmembrane proton motive force (PMF) to survive starvation stress for a prolonged period. This work further shows that the reason why antibiotic persisters need to maintain PMF is that PMF is required to support a range of efflux or transportation functions.

287. Characteristics and Outcomes of COVID-19 Patients with Candidemia at a Community Hospital in Chicago

Background 1,416 patients with acute COVID-19 infection were admitted to our hospital in 2020. During that year we noticed an alarming increase in cases of nosocomial Candidemia: 26 versus an average of 2.8 cases per year over the previous 5 years. 19 of the 26 episodes (73%) of Candidemia occurred in patients who were admitted with acute COVID-19 infection. Recent reports suggest that hospitalized patients with COVID-19 are at increased risk for developing Candidemia, however their clinical characteristics, risk factors and outcomes have not been well described. We evaluated the risk factors and mortality of hospitalized COVID-19 patients with Candidemia. Methods We performed a retrospective chart review of 19 patients with Candidemia and confirmed COVID-19 infection at a 292-bed community teaching hospital in Chicago, Illinois from January through December 2020. We report a descriptive analysis of the demographic characteristics, comorbidities, complications, and outcomes of these patients. Results The average age of our study population was 65 years; 68% were male. The average hospital length of stay (LOS) was 34 days. The mean time from admission to the development of Candidemia was 16 days. Associated co-morbidities included cardiovascular diseases (CVD) in 79%, diabetes mellitus (DM), in 68%, and obesity in 50%. Underlying kidney disease was present in 10%. Treatments for COVID-19 included convalescent plasma (53%), remdesivir (53%), steroids (52%) and tocilizumab (19%). All patients were managed in the intensive care unit (ICU) and 95% required multiple central line (CL) placements. Most of the patients (58%) required hemodialysis (HD); all patients were treated with multiple antibiotics. The average LOS in the ICU was 25 days. Despite anti-fungal treatment, 68% expired. The 28-day mortality was 50%. Conclusion The occurrence of Candidemia in our hospitalized patients with acute COVID-19 infection was associated with a history of CVD, DM, obesity, prolonged hospital LOS, requirement for multiple CL, HD, treatment with multiple antibiotics and a long stay in the ICU. The mortality of COVID-19 patients with Candidemia is high. The development of strategies to mitigate the occurrence of nosocomial Candidemia in this population of patients is urgently needed. Disclosures All Authors: No reported disclosures