Abstract Background Agr is a key regulator that controls expression of secreted exoproteins and surface protein in Staphylococcus aureus. It has been reported that mixed status of two different phenotypes including agr functional and nonfunctional subpopulations can coexist in vitro and in vivo. However, data on the natural course and clinical implication of the mixed agr status is limited. We thus investigated the frequency and characteristics of the mixed agr in clinical settings. Methods We evaluated isogenic paired MRSA isolates collected from patients with persistent S. aureus bacteremia (SAB) between October 2010 and April 2016, and then prospectively performed surveillance for the presence of mixed agr function in MRSA isolates from patients with SAB between May 2016 and December 2017. The mixed agr status was evaluated by single colony evaluation on sheep blood agar plate containing RN4220 supernatant (β-hemolysin) (Figure 1). Cross-streaking with RN4220 and RNAIII measurement were performed to confirm the agr functionality of each of hemolytic and non-hemolytic colonies, separately. The expression levels of RNAIII, hla, and saeS/saeR were measured by real-time reverse transcription polymerase chain reaction. Results A total of 161 first blood isolates were collected during study period, and 6 isolates (4%) displayed mixed phenotype by single colony test. The mixed hemolytic pattern was observed in 5 out of 52 ST72 isolates (10%) and 1 out of 82 ST5 isolates (1%) (Figure 1). No difference was found in the genotypes between hemolytic and non-hemolytic colonies from each isolate. Of the 6 isolates, three lost mixed hemolytic features in the follow-up blood cultures (Table 1). One ST72 and one ST5 isolate showed agr mixed pattern determined by different RNAIII levels, but remaining four ST72 isolates had mixed hemolytic pattern due to different expression of hla correlated with saeS/saeR expression (Figure 2). Conclusion The mixture of agr function status among the clinical blood isolates of MRSA was rarely observed and isolates displaying heterogeneous hemolytic phenotype were largely due to differential expression of α-hemolysin. Further investigation is needed to unveil the clinical significance of mixture of different hemolytic phenotypes. Disclosures All authors: No reported disclosures.
Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is an emerging clinical issue and shows high mortality rates. There are a few studies that have evaluated the microbiologic risk factors for mortality in CRAB bacteremia. Aim of this study is to identify the clinical and microbiologic risk factors for mortality in CRAB bacteremia. Methods Adult patients with monomicrobial CRAB bacteremia at a 2,700-bed tertiary hospital between December 2012 and December 2018 were retrospectively enrolled in the study. Risk factors for 30-day mortality were evaluated through a detailed clinical and microbiological analysis of study patients. All isolates collected on the first day of bacteremia were subjected to colistin susceptibility testing by broth microdilution and genotyping by multilocus sequence typing (MLST). Results A total of 164 patients were enrolled and 90 (55%) died within 30 days. Of the 164 patients, 111 (68%) were male and median age was 66.5 years. The most common MLST genotype was ST191 (80 isolates, 49%), followed by ST451 (14%) and ST784 (13%), and 12 (7%) isolates were resistant to colistin (MIC ≥4 mg/L). Deceased patients were more likely to have hematologic malignancy, neutropenia, pneumonia, and primary bacteremia; less likely to have solid tumor, catheter-related infection, and biliary tract infection; more likely to have a high Pitt bacteremia score; and less likely to receive appropriate antibiotic treatment, colistin, and combination therapy with colistin and tigecycline, compared with surviving patients (Table 1). Genotype, colistin MIC, and colistin resistance were not associated with mortality (Figure 1 and 2). In multivariable analysis, neutropenia (aOR, 3.25; 95% CI, 1.18–8.95), catheter-related infection (aOR, 0.33; 95% CI, 0.11–0.99), biliary tract infection (aOR, 0.20; 95% CI, 0.04–0.99), a high Pitt bacteremia score (aOR,1.42; 95% CI, 1.20–1.67), and combination therapy with colistin and tigecycline (aOR, 0.36; 95% CI, 0.14–0.92) were independent risk factors for mortality (Table 2). Conclusion Clinical factors such as the site of infection, severity of bacteremia, and specific combination therapy rather than microbiologic factors contributed to mortality in CRAB bacteremia. Appropriate combination therapy may help improving outcomes in CRAB bacteremia. Disclosures All authors: No reported disclosures.
ST72-SCCmecIV, a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain in Korea, originated in the community and has been spreading in health care settings. Herein, we describe the clinical and microbiological characteristics of patients with hospital-acquired MRSA bacteremia (MRSAB) caused by community-associated strains.We analyzed hospital-acquired MRSAB cases caused by ST72-SCCmecIV using a prospective cohort of patients with SAB in a tertiary hospital in Korea from July 2008 to December 2018. We compared the clinical and microbiological characteristics of ST72-SCCmecIV with ST5-SCCmecII, a representative hospital-associated genotype strain.Of the 1782 S. aureus bacteremia (SAB) cases, 628 (35.2%) were hospital-acquired MRSAB. Of the 628 isolates, 431 (68.6%) were ST5-SCCmecII and 152 (24.2%) were ST72-SCCmecIV. Patients with ST72-SCCmecIV were younger than those with ST5-SCCmecII and less likely to have a history of recent surgery, antibiotic treatment, nasal MRSA colonization, and central venous catheter placement. Compared with ST5-SCCmecII, ST72-SCCmecIV isolates were more likely to have vancomycin MICs ≤1.0 mg/L (P < .001). Osteoarticular infection as the site of infection (7.2% [11/152] vs 1.4% [6/431]) was more common in patients with ST72-SCCmecIV. There were no significant differences in the rate of recurrence (≤90 days), persistent bacteremia (≥7 days), or 30- and 90-day mortality rates between the 2 groups.Osteoarticular infections were more prevalent in ST72-SCCmecIV MRSAB. Mortality rates between the ST72-SCCmecIV and ST5-SCCmecII groups were not significantly different.
There are limited long-term data on the trends in incidence and characteristics of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB) in intensive care units (ICUs) in which infection control measures have been adopted. We evaluated the trend of incidence and changes in characteristics of MRSA bacteremia in ICUs at a tertiary-care hospital over 10 years using prospective cohort data. ICU-acquired bacteremia was defined as S. aureus bacteremia (SAB) that occurred 48 h or more after ICU admission.
Abstract Glycopeptide antibiotics (vancomycin and teicoplanin) are usually used for the treatment of Staphylococcus epidermidis infections owing to their increased oxacillin resistance. However, S. epidermidis strains with decreased susceptibility to teicoplanin have become increasingly incident in recent years. We aimed to identify the characteristics of teicoplanin-non-susceptible (Teico-NS) S. epidermidis isolated at our hospital and analyze its relationship with teicoplanin usage. We retrospectively evaluated 328 S. epidermidis strains isolated from clinical isolates between January 2016 and December 2021. All strains were susceptible to vancomycin (minimal inhibitory concentration (MIC) ≤ 4 mg/L). The annual incidence for S. epidermidis strains with an elevated teicoplanin MIC of 8 mg/L ranged from 22.2 to 28.9%. In addition, in 2021, the number of S. epidermidis strains with teicoplanin MIC ≥ 16 mg/L rapidly increased (n = 13, 32.5%). Furthermore, teicoplanin use increased annually until 2019; however, in 2020, it decreased abruptly due to the COVID 19 pandemic. Thus, we could not confirm the existence of a clear correlation between teicoplanin usage and increased incidence of S. epidermidis with reduced teicoplanin-susceptibility. We showed the increased incidence of Teico-NS S. epidermidis in recent years. Further studies are needed to identify the mechanisms and risk factors for teicoplanin-resistance in S. epidermidis.
Abstract This study evaluated the determinants of mortality and the T cell immune response in patients with persistent Staphylococcus aureus bacteremia (SAB). This was a prospective cohort study and patients with confirmed SAB were enrolled from 2008 to 2020. We compared clinical, microbiological, and genotypic features between surviving and deceased patients with persistent SAB. The concentrations of cytokines and the proportions of IFN-γ secreting CD4 + T cells were measured serially during the bacteremia period. Of the 1760 patients, 242 had persistent bacteremia (PB), and 49 PB patients died within 30 days. In the multivariate analysis, the APACHE II score and female sex were independently associated with 30 days mortality. The level of IL-10 was significantly increased in the plasma of patients with a high Pitt bacteremia score and those who died within 12 weeks from the index day. The proportion of IFN-γ-secreting CD4 + T cells were the highest just before the positive-to-negative conversion of blood cultures in patients with a low Pitt bacteremia score and those who survived for 12 weeks. The level of IL-10 is correlated with clinical outcomes in PB patients. IFN-γ secreting CD4 + T cells might play a pivotal role in SAB PB.
Abstract Background There is a concern that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concomitant colistin administered against multidrug-resistant gram-negative pathogen. Methods We confirmed the molecular genotypes of MRSA blood isolates collected in a tertiary hospital in Seoul, South Korea, and selected representative strains from the community-associated MRSA strains (CA-MRSA, ST72-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA, ST5-SCCmec II). USA CA-MRSA (USA300, ST8-SCCmec IV) and MRSA standard strain (ATCC 43300, ST39-SCCmec II) were also used for comparison with representative. We identified changes of the vancomycin MIC in MRSA by colistin exposure in a checkerboard assay and performed a time-kill assay to evaluate the combined effect of vancomycin and colistin on MRSA. In addition, we administered vancomycin, colistin, and combination of two antibiotics, respectively, to a neutropenic murine thigh infection model to evaluate the in vivo antagonistic effect of colistin on vancomycin treatment. Results In the checkerboard assay, all 4 MRSA strains showed a tendency for the vancomycin MIC to increase along with increasing concentrations of colistin. However, the time-kill assay showed the antagonism of vancomycin and colistin only against ST5-MRSA, when vancomycin concentration was 2 times the vancomycin MIC (Figure 1). No antagonism was observed in other strains. In the murine thigh infection model of ST5-MRSA, vancomycin monotherapy showed a significant log CFU reduction compared with a combination of vancomycin and colistin at 24 hours, demonstrating the antagonistic effect of vancomycin and colistin combination (Figure 2). Conclusion This study showed that exposure of colistin to certain MRSA strains may reduce the susceptibility to vancomycin. Combination therapy with vancomycin and colistin for MDR pathogens infections might result in treatment failure for concurrent MRSA infection. Disclosures All authors: No reported disclosures.
Abstract Patients with Legionnaires disease occasionally experience initial clinical improvement but radiological progression. However, data on this issue are so far limited. The aim of this study was to investigate changes in chest radiograph findings in patients with Legionnaires disease who showed initial clinical improvement and to identify risk factors and outcomes in these patients. All patients diagnosed with Legionnaires disease at a tertiary hospital in South Korea between March 2011 and May 2020 were retrospectively enrolled. Legionnaires disease was defined as abnormal chest radiographs accompanied by a positive finding on at least one of the following tests: urinary antigen test, sputum Legionella polymerase chain reaction, and sputum Legionella culture. Clinical improvement was defined as defervescence and decreased C-reactive protein level. Clinical and radiological records were reviewed on treatment days 7 and 14 and at discharge. We describe the characteristics of patients with clinical improvement but radiological deterioration on treatment for Legionnaires disease and compared them with patients with initial clinical improvement and stable or resolving chest radiograph findings. Of 140 patients with Legionnaires disease, 33 (24%) showed initial clinical deterioration, while the remaining 107 (76%) showed initial clinical improvement on day 7. The latter 107 patients were analyzed in this study; 22 (21%) showed radiological progression despite the clinical improvement. Risk factors for these patients were a high pneumonia severity index score and the use of mechanical ventilation. Mortality did not significantly differ between those with initial clinical improvement but radiological deterioration and those with both initial clinical and radiological improvement (28% vs 12%, P = .49). About one-fifth of patients with Legionnaires disease, especially those who had a high pneumonia severity index score and underwent mechanical ventilation, showed radiological deterioration despite of clinical improvement 1 week after appropriate treatment, while outcomes were not significantly worse in these patients. Therefore, our findings support that close monitoring without modification of antibiotics use is warranted in those who have clinical improvement regardless of radiologic findings.
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