We aimed to compare the clinical outcomes of patients with positive Xpert Carba-R assay results for carbapenemase-producing Enterobacterales (CPE) according to CPE culture positivity.We retrospectively collected data for patients with positive CPE (positive Xpert Carba-R or culture) who underwent both tests from August 2018 to March 2021 in a 2700-bed tertiary referral hospital in Seoul, South Korea. We compared the clinical outcomes of patients positive for Xpert Carba-R according to whether they were positive (XPCP) or negative (XPCN) for CPE culture.Of 322 patients with CPE who underwent both Xpert Carba-R and culture, 313 (97%) were positive for Xpert Carba-R for CPE. Of these, 87 (28%) were XPCN, and 226 (72%) were XPCP. XPCN patients were less likely to have a history of previous antibiotic use (75.9% vs 90.3%; P = .001) and to have Klebsiella pneumoniae carbapenemase (21.8% vs 48.9%; P < .001). None of the XPCN patients developed infection from colonization within 6 months, whereas 13.4% (29/216) of the XPCP patients did (P < .001). XPCN patients had lower transmission rates than XPCP patients (3.0% [9/305] vs 6.3% [37/592]; P = .03). There was no significant difference in CPE clearance from positive culture results between XPCN and XPCP patients (40.0% [8/20] vs 26.7% [55/206]; P = .21).Our study suggests that XPCN patients had lower rates of both infection and transmission than XPCP patients. The Xpert Carba-R assay is clinically useful not only for rapid identification of CPE but also for predicting risks of infection and transmission when performed along with culture.
We report a case of coronavirus disease 2019 (COVID-19)-associated radiologically suspected organizing pneumonia with repeated negative Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) results from nasopharyngeal swab and sputum samples, but positive result from bronchoalveolar lavage fluid. Performing SARS-CoV-2 RT-PCR in upper respiratory tract samples only could fail to detect COVID-19-associated pneumonia, and SARS-CoV-2 could be an etiology of radiologically suspected organizing pneumonia.
This study aimed to identify which streptococcal species are closely associated with infective endocarditis (IE) and to evaluate risk factors for mortality in patients with streptococcal IE. We performed a retrospective cohort study of all patients with streptococcal bloodstream infection (BSI) from January 2010 to June 2020 in a tertiary hospital in South Korea. We compared clinical and microbiological characteristics of streptococcal BSIs according to the diagnosis of IE. We performed multivariate analysis to evaluate the risk of IE according to streptococcal species and risk factors for mortality in streptococcal IE. A total of 2,737 patients were identified during the study period, and 174 (6.4%) were diagnosed with IE. The highest IE prevalence was in patients with Streptococcus mutans BSI (33% [9/27]) followed by S. sanguinis (31% [20/64]), S. gordonii (23% [5/22]), S. gallolyticus (16% [12/77]), and S. oralis (12% [14/115]). In multivariate analysis, previous IE, high-grade BSI, native valve disease, prosthetic valve, congenital heart disease, and community-onset BSI were independent risk factors for IE. After adjusting for these factors, S. sanguinis (adjusted OR [aOR], 7.75), S. mutans (aOR, 5.50), and S. gallolyticus (aOR, 2.57) were significantly associated with higher risk of IE, whereas S. pneumoniae (aOR, 0.23) and S. constellatus (aOR, 0.37) were associated with lower risk of IE. Age, hospital-acquired BSI, ischemic heart disease, and chronic kidney disease were independent risk factors for mortality in streptococcal IE. Our study points to significant differences in the prevalence of IE in streptococcal BSI according to species. IMPORTANCE Our study of risk of infective endocarditis in patients with streptococcal bloodstream infection demonstrated that Streptococcus sanguinis, S. mutans, and S. gallolyticus were significantly associated with higher risk of infective endocarditis. However, when we evaluated the performance of echocardiography in patients with streptococcal bloodstream infection, patients with S. mutans and S. gordonii bloodstream infection had a tendency of low performance in echocardiography. There are significant differences in the prevalence of infective endocarditis in streptococcal bloodstream infection according to species. Therefore, performing echocardiography in streptococcal bloodstream infection with a high prevalence of, and significant association with, infective endocarditis is desirable.
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.
This study aimed to investigate the population pharmacokinetics (PK) profile and determine the optimal dosage regimen of cefepime in critically ill adult patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP).Population-PK models for cefepime were developed using a nonlinear mixed-effect modeling approach. The percentage of time within 24 h in which the free concentration exceeded the minimum inhibitory concentration (MIC) at a steady state (50%fT>MIC, 100%fT>MIC, and 100%fT>4×MIC) for various combinations of dosage regimens and renal function was explored using Monte Carlo simulation.Twenty-one patients were prospectively enrolled in this study. Cefepime PK was best described using a two-compartment model in which creatinine clearance (CLCR) through Cockcroft-Gault (CG) was a significant covariate for the total clearance of cefepime. The simulation results to determine the optimal cefepime dosing regimen for 50%fT>MIC as treatment target with Cmin <20 mg/L as safety target showed that a dosage regimen of 2 g through intravenous (IV) infusion every 12 h administered over 4 h was optimal at an MIC of 4 mg/L, rather than the currently recommended dosage regimen of 2 g administered through IV infusion every 8 h, in patients with normal renal function (CLCR = 90 - 130 mL/min). For a treatment target of 100%fT>MIC with Cmin <35 mg/L as a safety target, a dosage regimen of 0.75 g administered through continuous infusion over 24 h would be sufficient at an MIC equal to or less than 8 mg/L in patients with renal dysfunction (CLCR = 10 - 30 mL/min).Our results suggest that clinicians should consider renal function and potential neurotoxicity when deciding the dosing regimen of cefepime in critically ill patients with HAP or VAP. Therapeutic drug monitoring (TDM) to adjust cefepime trough levels may be useful to improve clinical outcomes and reduce cefepime neurotoxicity.
In this study, we aimed to determine the effect of COVID-19 vaccination on 3-month immune response and durability after natural infection by the Omicron variant and to assess the immune response to a fourth dose of COVID-19 vaccination in patients with prior natural infection with the Omicron variant. Overall, 86 patients aged ≥60 years with different vaccination histories and 39 health care workers (HCWs) vaccinated thrice before Omicron infection were enrolled. The sVNT50 titer was significantly lower in patients with incomplete vaccination before SARS-CoV-2 infection with the S clade (p < 0.001), Delta variant (p < 0.001), or Omicron variant (p = 0.003) than in those vaccinated thrice. The sVNT results against the Omicron variant did not differ significantly in patients aged ≥60 years (p = 0.49) and HCWs (p = 0.17), regardless of the recipient receiving the fourth dose 2 months after COVID-19. Incomplete COVID-19 vaccination before Omicron infection for individuals aged ≥60 years conferred limited protection against homologous and heterologous virus strains, whereas two or three doses of the vaccine provided cross-variant humoral immunity against Omicron infection for at least 3 months. However, a fourth dose 2 months after Omicron infection did not enhance immunity against the homologous strain. A future strategy using the bivalent Omicron-containing booster vaccine with appropriate timing will be crucial.
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