Clinical Characteristics of and Risk Factors for Subsequent Carbapenemase-producing Enterobacterales (CPE) Bacteraemia in Rectal CPE Carriers.

BACKGROUND: Due to high mortality and limited treatment options, the rise in carbapenemase-producing Enterobacterales (CPE) has become a major concern. This study aimed to evaluate the incidence and characteristics of subsequent CPE bacteraemia in rectal CPE carriers and investigate the risk factors for CPE bacteraemia compared with non-carbapenemase-producing (non-CP) Enterobacterales bacteraemia. METHODS: A retrospective analysis was conducted on adult patients who were confirmed to have CPE colonisation by stool surveillance culture at a tertiary hospital from January 2018 to February 2022. All episodes of Enterobacterales bacteraemia up to 6 months after CPE colonisation were identified. RESULTS: Of 1174 patients identified as rectal CPE carriers, 69 (5.8%; 95% CI 4.6-7.3%) experienced subsequent CPE bacteraemia during the 6 months after the diagnosis of CPE colonisation. Colonisation by a Klebsiella pneumoniae carbapenemase (KPC) producer (or CP-K. pneumoniae), colonisation by multiple CPE species, chronic kidney disease and haematological malignancy were independently associated with CPE bacteraemia in CPE carriers. When CPE carriers developed Enterobacterales bacteraemia, the causative agent was more frequently non-CP Enterobacterales than CPE (63.6% vs. 36.4%). Among these patients, colonisation with a KPC producer, CPE colonisation at multiple sites, shorter duration from colonisation to bacteraemia (< 30 days) and recent intraabdominal surgery were independent risk factors for CPE bacteraemia rather than non-CP Enterobacterales bacteraemia. CONCLUSIONS: In CPE carriers, non-CP Enterobacterales were more often responsible for bacteraemia than CPE. Empirical antibiotic therapy for CPE should be considered when sepsis is suspected in a CPE carrier with risk factors for CPE bacteraemia.

Risk and Outcome of Infective Endocarditis in Streptococcal Bloodstream Infections according to Streptococcal Species.

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.

Clinical significance and outcomes of Clostridium tertium bacteremia: analysis of 62 cases in neutropenic and non-neutropenic patients.

The clinical significance of Clostridium tertium bacteremia is still uncertain. We evaluated the incidence, clinical characteristics, and outcomes of C. tertium bacteremia and identified differences between neutropenia and non-neutropenia. All adult patients with C. tertium bacteremia in a 2700-bed tertiary center between January 2004 and November 2021 were retrospectively enrolled. The first episode of C. tertium bacteremia in each patient was included in the analysis. Among 601 patients with Clostridium species bacteremia, 62 (10%) had C. tertium bacteremia, and of these 62 patients, 39 (63%) had had recent chemotherapy, and 31 (50%) had neutropenia or hematologic malignancy. C. tertium bacteremia originated frequently from a gastrointestinal tract infection such as enterocolitis (34%), primary bacteremia (29%), and secondary peritonitis (18%), and 34% of patients had polymicrobial bacteremia. Hematologic malignancy, prior antibiotic treatment, neutropenic enterocolitis, and primary bacteremia were significantly associated with C. tertium bacteremia in neutropenic patients, whereas solid tumor, hepatobiliary disease, secondary peritonitis, polymicrobial bacteremia, and a higher frequency of eradicable infection foci were significantly associated with C. tertium bacteremia in non-neutropenic patients. There was 15% 30-day mortality. APACHE II score (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.1-2.1) and secondary peritonitis (aOR, 25.9; 95% CI, 3.0-224.7) were independent risk factors for 30-day mortality. The prevalence of C. tertium bacteremia is low, and the characteristics of C. tertium bacteremia are significantly different between neutropenic and non-neutropenic patients. Appropriate investigation for gastrointestinal mucosal injury should be performed to improve treatment outcomes in this form of bacteremia.

Population Pharmacokinetics and Monte Carlo Simulation of Cefepime in Critically Ill Patients with Hospital-Acquired/Ventilator-Associated Pneumonia.

BACKGROUND: 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). MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Measles Virus Neutralizing Antibody Response and Durability Two Years after One or Two Doses of Measles-Mumps-Rubella Vaccine among Young Seronegative Healthcare Workers.

Although there have been several studies regarding the immunogenicity of one or two booster doses of the measles−mumps−rubella (MMR) vaccine in measles-seronegative young adults, limited data are available about how long the immune response is sustained compared with natural infection. This study included seronegative healthcare workers (HCWs) (aged 21−38 years) who received one or two doses of the measles−mumps−rubella (MMR) vaccine and HCWs with laboratory-confirmed measles infection during an outbreak in 2019. We compared neutralizing antibody titers measured using the plaque reduction neutralization (PRN) test and measles-specific immunoglobulin G (IgG) using chemiluminescent immunoassays 2 years after vaccination or infection. Among 107 HCWs with seronegative measles IgGs, the overall seroconversion rate of measles IgGs remained 82.2% (88/107), and 45.8% (49/107) of the participants had a medium (121−900) or high (>900) PRN titer after 2 years from one or two booster doses. The measles-neutralizing antibody titers of both PRN titer (ND50) and geometric mean concentration 2 years after natural infection were significantly higher than those of one or two booster doses of the MMR vaccine (p < 0.001 and p < 0.001, respectively). Our results suggest that serologic screening followed by appropriate postexposure prophylaxis can be beneficial for young HCWs without a history of natural infection especially in a measles outbreak setting, because of possible susceptibility to measles despite booster MMR vaccination 2 years ago. Long-term data about sustainable humoral immunity after one or two booster vaccination are needed based on the exact vaccination history.

Effect of Previous COVID-19 Vaccination on Humoral Immunity 3 Months after SARS-CoV-2 Omicron Infection and Booster Effect of a Fourth COVID-19 Vaccination 2 Months after SARS-CoV-2 Omicron Infection.

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.

Clinical impact of and microbiological risk factors for qacA/B positivity in ICU-acquired ST5-methicillin-resistant SCCmec type II Staphylococcus aureus bacteremia.

Concern about resistance to chlorhexidine has increased due to the wide use of the latter. The impact of the qacA/B and smr chlorhexidine tolerance genes on the outcome of methicillin-resistant Staphylococcus aureus (MRSA) infections is unclear. We evaluated the prevalence and clinical impact of, and microbiological risk factors for, qacA/B tolerance in MRSA bacteremia. MRSA bacteremia that occurred more than two days after intensive care unit admission between January 2009 and December 2018 was identified from a prospective cohort of S. aureus bacteremia in a tertiary-care hospital from South Korea. A total of 183 MRSA blood isolates was identified, and the major genotype found was ST5-MRSA-II (87.4%). The prevalences of qacA/B and smr were 67.2% and 3.8%, respectively. qacA/B-positive isolates were predominantly ST5-MRSA-II (96.7% [119/123]), the dominant hospital clone. In a homogenous ST5-MRSA-II background, qacA/B positivity was independently associated with septic shock (aOR, 4.85), gentamicin resistance (aOR, 74.43), and non-t002 spa type (aOR, 74.12). qacA/B positivity was found to have decreased significantly in ST5-MRSA-II in association with a decline in qacA/B-positive t2460, despite the increasing use of chlorhexidine since 2010 (P < 0.001 for trend). Continuous surveillance of the qac genes, and molecular characterization of their plasmids, are needed to understand their role in MRSA epidemiology.

Comparison of isolated respiratory and extrarespiratory mucormycosis: a 21-year observational study of 44 cases.

OBJECTIVES: This study aimed to compare the clinical characteristics and outcomes of patients with isolated respiratory and extrarespiratory mucormycosis. METHODS: Adult patients diagnosed with proven or probable invasive mucormycosis in a tertiary hospital in South Korea, between 1999 and 2020 were retrospectively reviewed. We compared the clinical, mycological characteristics, and outcomes of patients with isolated respiratory mucormycosis (IRM) and those with extrarespiratory mucormycosis (ERM). RESULTS: A total of 44 patients including 32 (72%) with IRM, and 12 (27%) with ERM were enrolled. Of these, 38 (86%) were classified as proven and 6 (14%) as probable invasive mucormycosis according to the EORTC/MSG criteria. Univariate analysis exhibited that old age, surgery, and intensive care unit were associated with ERM, and multivariable analysis revealed that variable associated with ERM was intensive care unit (aOR 9.80; 95% CI 2.07-46.35; P = 0.004). There were no significant differences in 90-day mortality between patients with IRM and ERM (38% vs 50%, P = 0.45). In multivariable analysis, neutropenia (aOR 6.88; 95% CI 1.67-28.27; P = 0.01) was an independent risk factor for 90-day mortality. CONCLUSIONS: More than a quarter of patients with mucormycosis had extrarespiratory manifestations, especially in patients who were admitted to intensive care unit. The mortality of the patients with ERM was comparable to that of the patients with IRM, although the patients with ERM received ICU care more frequently.

Fluvoxamine Treatment of Patients with Symptomatic COVID-19 in a Community Treatment Center: A Preliminary Result of Randomized Controlled Trial.

BACKGROUND: This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC). MATERIALS AND METHODS: A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real time-polymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater. RESULTS: Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group (P >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration. CONCLUSION: In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863).

Comparison of the Clinical Outcomes of Patients With Positive Xpert Carba-R Tests for Carbapenemase-Producing Enterobacterales According to Culture Positivity.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Bedside risk prediction for positive follow-up blood culture in Gram-negative bacilli bacteremia: for whom is follow-up blood culture useful?

PURPOSE: The value of follow-up blood culture (FUBC) in Gram-negative bacteremia (GNB) management is controversial. We evaluated bedside risk predictors and their probabilities of yielding positive FUBCs in GNB. METHODS: All adult patients with GNB in a 2700-bed tertiary center were retrospectively enrolled between January 2019 and December 2019. Only one initial GNB episode was included per patient. Positive FUBC was defined as isolation of the same organism in blood culture 48-72 h after the initial blood culture. RESULTS: A total of 2216 patients with GNB were identified, of whom 34.4% underwent FUBC. Of the 645 patients with FUBCs analyzed in the study, 89 (13.8%) had positive FUBCs. In multivariate analysis, hemodialysis [adjusted odds ratio (aOR), 2.6], fever on the day of FUBCs (aOR 3.6), intravascular device (aOR 2.4), no use of in vitro active antibiotic within 24 h (aOR 2.5), non-fermenting bacteria (aOR 4.7), and multidrug resistance (aOR 5.4) were independent risk factors for positive FUBCs. If microbiological results were excluded in multivariate analysis, hemodialysis, immunosuppressive treatment, fever on the day of FUBCs, and intravascular device were independent bedside risk predictors for positive FUBCs. The yield of FUBCs increased from 3.0% (95% CI 1.0-7.0) to 63.6% (95% CI 25.6-100) as the number of bedside risk predictors increased from 0 to 4. In addition, positive FUBCs were significantly associated with 30 day mortality. CONCLUSIONS: FUBCs may not need to be routinely used for patients with GNB bacteremia, and bedside risk predictors could be helpful in identifying patients for whom FUBC is likely to be useful.

Radiologically Suspected Organizing Pneumonia in a Patient Recovering from COVID-19: A Case Report.

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.

Clinical features of patients with Legionnaires disease showing initial clinical improvement but radiological deterioration: A retrospective single-center analysis.

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.

Risk Factors for Mortality in Patients with Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae and Escherichia coli bacteremia.

BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales bacteremia is associated with significant mortality; however, no optimal antibiotic strategy is available. We aimed to evaluate the clinical outcomes according to the antibiotic regimens and identify risk factors for mortality in patients with KPC-producing K. pneumoniae and Escherichia coli bacteremia. MATERIALS AND METHODS: This retrospective cohort study included all adult patients with monomicrobial bacteremia (KPC-producing K. pneumoniae or E. coli) between January 2011 and March 2021 at a 2,700-bed tertiary center. RESULTS: Ninety-two patients were identified; 7 with E. coli bacteremia, and 85 with K. pneumoniae bacteremia. Thirty-day mortality was 38.0% (35/92). Non-survivors were more likely to have had nosocomial infection (88.6% vs. 63.2%, P = 0.01), high APACHE II scores (mean [interquartile range], 22.0 [14.0 - 28.0] vs. 14.0 [11.0 - 20.5], P <0.001), and septic shock (51.4% vs. 26.3%, P <0.001) and less likely to have been admitted to the surgical ward (5.7% vs. 22.8%, P = 0.04), undergone removal of eradicable foci (61.5% vs. 90.6%, P = 0.03), and received appropriate combination treatment (57.1% vs. 78.9%, P = 0.03) than survivors. No significant difference in mortality was observed according to combination regimens including colistin, aminoglycoside, and tigecycline. In multivariable analysis, high APACHE II scores (adjusted odds ratio [aOR], 1.14; 95% confidence interval [CI], 1.06 - 1.23, P <0.001), and appropriate definitive treatment (aOR, 0.25; CI, 0.08 - 0.74, P = 0.01) were independent risk factors for mortality. CONCLUSION: High APACHE II scores and not receiving appropriate definitive treatment were associated with 30-day mortality. Mortality did not significantly differ according to combination regimens with conventional drugs such as aminoglycoside and colistin.

The First Case of Multisystem Inflammatory Syndrome in Adult after COVID-19 in Korea.

Multisystem inflammatory disease in children is a Kawasaki disease like illness occurring after severe acute respiratory syndrome coronavirus 2 infection in children. As the pandemic progresses, similar syndromes were also reported in adult with a decreased incidence. Multisystem inflammatory syndrome in adults (MIS-A) can be characterized with shock, heart failure, and gastrointestinal symptoms with elevated inflammatory markers after coronavirus disease 2019 (COVID-19) infection. Herein, we describe the first case of MIS-A in South Korea. A 38-year-old man presented to our hospital with a 5-day history of abdominal pain and fever. He had been treated with antibiotics for 5 days at the previous hospital, but symptoms had worsened and he had developed orthopnea on the day of presentation. He suffered COVID-19 six weeks ago. Laboratory data revealed elevated white blood cell counts with neutrophil dominance, C-reactive protein, and B-type natriuretic peptide. Chest X-ray showed normal lung parenchyme and echocardiography showed severe biventricular failure with normal chamber size. We diagnosed him as MIS-A and treated with intravenous immunoglobulin and steroid.

Diagnostic performance of real-time polymerase chain reaction assay on blood for invasive aspergillosis and mucormycosis.

OBJECTIVES: This study aimed to evaluate the diagnostic usefulness of real-time (RT) polymerase chain reaction (PCR) on blood samples for diagnosis of invasive aspergillosis and mucormycosis in patients with suspected invasive mould infection. METHODS: Adult patients with suspected invasive mould infection were prospectively enrolled at a tertiary referral hospital in Seoul, South Korea between 2017 and 2020. Standard tests for diagnosis of invasive mould infection and RT-PCR for Aspergillus, Mucor and Rhizopus using blood samples were performed. We evaluated the diagnostic performance of RT-PCR tests in patients diagnosed with proven and probable invasive aspergillosis or mucormycosis infection, according to the modified definitions of the EORTC/MSG 2019. RESULTS: A total of 102 patients with suspected invasive mould infection were enrolled. Of these patients, 46 (45%) were classified as having proven (n = 13) or probable (n = 33) invasive aspergillosis, 21 (21%) as proven (n = 17) or probable (n = 4) invasive mucormycosis and 18 (18%) as possible invasive mould infection. The remaining 13 (13%) were classified as not having invasive mould infection. Patients with possible invasive mould infection (n = 18) and coinfection of aspergillosis and mucormycosis (n = 4) were excluded from the final analysis. The sensitivity and specificity of the Aspergillus PCR were 54.3% ([25/46], 95% confidence interval [CI]: 40.2-67.9%) and 94.1% ([32/34], 95% CI: 80.9-98.4%), respectively. The sensitivity and specificity of the Mucor or Rhizopus PCR were 57.1% ([12/21], 95% CI: 36.6-75.5%) and 76.3% ([45/59], 95% CI: 64.0-85.3), respectively. CONCLUSIONS: Our study suggests that blood PCR can be a useful adjunct test for diagnosing patients with suspected invasive mould infection.

Comparison of clinical outcomes of patients infected with KPC- and NDM-producing Enterobacterales: a retrospective cohort study.

OBJECTIVES: We aimed to compare clinical outcomes of patients with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales and those with New Delhi metallo-ß-lactamase (NDM)-producing Enterobacterales. METHODS: We performed a retrospective cohort study of all adult patients with KPC- or NDM-producing Enterobacterales isolates in a 2700-bed tertiary referral hospital in Seoul, South Korea, between 2010 and 2019. The primary outcome was 30-day mortality after first isolation of KPC- or NDM-producing Enterobacterales. The secondary outcome was the development of infection within 30 days by the colonizing isolates, among colonized patients. We performed Cox regression analysis for 30-day mortality and competing risk analysis for development of infection. RESULTS: A total of 859 patients were identified during the study period; 475 (55%) had KPC and 384 (45%) had NDM. Thirty-day mortality was significantly higher in the KPC group than in the NDM group (17% (81/475) vs 9% (33/384); p < 0.001). The KPC group developed infection within 30 days from the initial colonization after first isolation more frequently than the NDM group (8% (27/353) vs. 3% (10/295); p 0.02). Multivariable analysis revealed that independent risk factors for 30-day mortality were solid cancer (adjusted hazard ratio (aHR) 2.51; 95% confidence interval (CI) 1.66-3.79; p < 0.001), solid organ transplant (aHR 0.32; 95% CI 0.17-0.61; p < 0.001), a high APACHE II score (aHR 1.11; 95% CI 1.08-1.13; p < 0.001), KPC-producing Enterobacterales (aHR 1.69; 95% CI 1.02-2.79; p 0.04), previous carbapenem use within 3 months (aHR 1.86; 95% CI 1.26-2.75; p < 0.001) and site of KPC- or NDM-producing Enterobacterales infection at the time of the first culture (p < 0.001). DISCUSSION: Our study suggests that KPC-producing Enterobacterales is significantly associated with poorer outcomes than NDM-producing Enterobacterales.

Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bacteremia.

OBJECTIVES: The aims of this study were to identify whether the site of acquisition or the underlying carbapenem-resistant Enterobacteriaceae (CRE) resistance mechanism was associated with clinical outcomes, and to evaluate risk factors for 14-day mortality in patients with CRE bacteremia. MATERIALS AND METHODS: A retrospective cohort study was conducted at a 2700-bed tertiary center. All adult patients with monomicrobial carbapenem-resistant Escherichia coli or Klebsiella pneumoniae bacteremia from 2011 to 2018 were included. All blood isolates collected were tested with a modified carbapenem inactivation method for phenotypic detection of carbapenemase. RESULTS: Of 133 patients with monomicrobial CRE bacteremia, 63 (47.4%) were infected with carbapenemase-producing CRE (CP-CRE), and 70 (52.6%) with non-CP-CRE. Patients with community-onset infection (COI) were more likely to present with biliary or urinary tract infections, less likely to have ineradicable or non-eradicated foci and to receive appropriate empirical therapy, and marginally more likely to have CP-CRE compared with those with hospital-acquired infection (HAI). However, 14-day mortality was significantly lower in COI than HAI (7% vs 29%, P = 0.01). Patients who died were more likely to have had a higher APACHE II score, ineradicable or non-eradicated foci, and a lower chance of having received appropriate antibiotic treatment. Multivariate analysis revealed that HAI, high APACHE II score, and inappropriate antibiotic treatment were independent risk factors for mortality. Carbapenemase production did not affect mortality. CONCLUSIONS: The results of this study indicate that timely, appropriate treatment is essential for managing CRE bacteremia, regardless of carbapenemase production, particularly in critically ill patients with hospital-acquired bacteremia.

Clinical characteristics and outcomes of Staphylococcus aureus bacteremia from a biliary source.

Staphylococcus aureus is a virulent gram-positive organism, which rarely involves the biliary tract. This study aimed to analyze the clinical characteristics and outcomes of S. aureus bacteremia (SAB) originating from the biliary tract by comparing them with those of catheter-related SAB and biliary Klebsiella pneumoniae bacteremia. A matched case-control study within a prospective observational cohort of patients with SAB was conducted. Biliary SAB was defined as the isolation of S. aureus from blood cultures with symptoms and signs of biliary infection. Biliary SAB patients were matched (1:3) with the control groups: patients with catheter-related SAB and biliary Klebsiella pneumoniae bacteremia. Out of 1818 patients with SAB enrolled in the cohort, 42 (2%) had biliary SAB. Majority of these patients had solid tumors involving the pancreaticobiliary tract or liver, biliary drainage stent, and/or recent broad-spectrum antibiotic exposure. Patients with biliary SAB were more likely to have community-onset SAB, solid tumors, and lower APACHE II score than those with catheter-related SAB. They were less likely to have community-acquired infection and solid tumors and more likely to have lower Charlson comorbidity index and higher APACHE II score as compared with biliary K. pneumoniae bacteremia. The 12-week mortality in the biliary SAB group was higher than those in other control groups (60% vs. 20% and 14%). After adjusting for confounding factors, biliary SAB was independently associated with higher mortality. Biliary SAB is relatively rare. When it is clinically suspected, early aggressive treatment should be considered due to high mortality.