Incidence of Clostridioides difficile Infections in Republic of Korea: A Prospective Study With Active Surveillance vs. National Data From Health Insurance Review & Assessment Service.

BACKGROUND: Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly. METHODS: To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020. RESULTS: In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patient-days was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25-12.05) and 4.18 per 1,000 admissions (range: 1.92-8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68-13.90) and 6.73 per 1,000 admissions (range: 3.18-15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively. CONCLUSION: The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.

Impact of Difficult-to-Treat Resistance in Gram-negative Bacteremia on Mortality: Retrospective Analysis of Nationwide Surveillance Data.

BACKGROUND: Clinically relevant categorization of antimicrobial resistance is critical to mitigating the threat it poses. Difficult-to-treat resistance (DTR) is a recently proposed category defined as nonsusceptibility to all first-line antibiotic agents. METHODS: A retrospective study was conducted with nonduplicate cases of gram-negative bloodstream infection (GNBSI) caused by 4 major taxa (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter species) identified from a nationwide surveillance database. DTR was defined as nonsusceptibility to all the ß-lactams and fluoroquinolones tested. Patient characteristics and mortality were compared between DTR GNBSI and GNBSI caused by carbapenem-resistant but not DTR and extended-spectrum cephalosporin-resistant but not DTR isolates using Centers for Disease Control and Prevention definitions. Adjusted odds ratios (aORs) for 30-day in-hospital mortality were examined for DTR in overall and in propensity score-matched cohorts. RESULTS: A total of 1167 episodes of monomicrobial GNBSI were identified, and 147 (12.6%) of the isolates were DTR. The majority of DTR isolates were Acinetobacter species (79.6%) and P. aeruginosa (17.7%). DTR infections were associated with previous antibiotic use, healthcare contact, ventilator use, and lower respiratory tract infection. Crude mortality for GNBSI caused by DTR was 50.3%. A multivariable model showed that only DTR, but not other categories, was significantly associated with mortality (adjusted odds ratio [aOR], 3.58 [95% confidence interval {CI}, 1.27-10.19]). DTR was also a significant predictor for mortality in the analysis of propensity score-matched cohorts (aOR, 3.48 [95% CI, 1.82-6.79]). CONCLUSIONS: In patients with GNBSI, DTR was associated with higher mortality than those in other resistance categories. Our findings suggest that DTR could be useful for surveillance and prognostication.

Clinical predictors of Stenotrophomonas maltophilia bacteremia in adult patients with hematologic malignancy.

Stenotrophomonas maltophilia (SM) has emerged as an important nosocomial pathogen with high morbidity and mortality. Because of its unique antimicrobial susceptibility pattern, appropriate antimicrobial therapy for SM bacteremia is still challenging, especially in immunocompromised patients. The present study was performed to assess clinical predictors of SM bacteremia in adult patients with hematologic malignancy. From 2006 through 2016, a case-control study was performed at a tertiary-care hospital. Case patients were defined as SM bacteremia in patients with hematologic malignancy. Date- and location-matched controls were selected from among patients with gram-negative bacteremia (GNB) other than SM. A total of 118 cases of SM bacteremia were identified and compared to 118 controls. While pneumonia was the most common source of SM bacteremia, centralline-associated infection was most common in the controls. The overall 30-day mortality rate of cases with SM bacteremia was significantly higher than that of the controls (61.0 and 32.2%, respectively; P < 0.001). A multivariable analysis showed that polymicrobial infection, previous SM isolation, the number of antibiotics previously used ≥ 3, and breakthrough bacteremia during carbapenem therapy were significantly associated with SM bacteremia (all P < 0.01). Previous use of trimethoprim/sulfamethoxazole (TMP/SMX) was negatively association with SM bacteremia (P = 0.002). Our data suggest that SM is becoming a significant pathogen in patients with hematologic malignancy. Several clinical predictors of SM bacteremia can be used for appropriate antimicrobial therapy in hematologic patients with suspected GNB.

Factors affecting the public awareness and behavior on antibiotic use.

To evaluate the effects of demographic and perceptive factors on the knowledge, perception, and behavior regarding antibiotic use in the general public, we conducted three serial telephone interview surveys in 2010, 2012, and 2015. Computer-aided telephone interview was conducted, with a predetermined quota stratified by sex, age, and geographic location. Respondents who answered correctly to four or more questions were categorized as having better knowledge. A total of 3013 respondents participated. Better knowledge was associated with age < 60 years (OR 1.37, 95% CI 1.04-1.82), college education (OR 1.57, 95% CI 1.26-1.97), healthcare-related occupation or education (OR 2.26, 95% CI 1.52-3.36), and media exposure (OR 1.25, 95% CI 1.02-1.54). In contrast, correct antibiotic use behavior was associated with male sex (OR 1.48, 95% CI 1.27-1.73), older age (OR 1.63, 95% CI 1.34-1.99), and being married (OR 1.26, 95% CI 1.04-1.52), along with better knowledge (OR 1.43, 95% CI 1.19-1.71). However, multifaceted analysis indicated that better knowledge was associated with correct behavior in all subgroups. Other demographic factors were associated only in respondents with poor knowledge. Various factors other than knowledge on antibiotics, many of them traditionally underappreciated, affect antibiotic use behavior.

Host susceptibility to MERS-CoV infection, a retrospective cohort study of the 2015 Korean MERS outbreak.

To evaluate host susceptibility factors to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we conducted a retrospective cohort study from the single largest exposure event of the 2015 Korean MERS outbreak. A total of 175 patients were closely exposed to a super-spreader, 26 of which were infected (14.9%). In a multivariate analysis, history of autologous stem cell transplantation (HR, 31.151; 95% CI, 5.447-178.145; P < 0.001) and tachypnea at ED (HR, 4.392; 95% CI, 1.402-13.761; P = 0.011) were significantly associated with MERS-CoV infection.

MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study.

BACKGROUND: In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital. METHODS: We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission. FINDINGS: 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% [23/117] vs 5% [3/58] in group B vs 1% [4/500] in group C; p<0·0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2-17, IQR 5-10). The median incubation period was significantly shorter in group A than in group C (5 days [IQR 4-8] vs 11 days [6-12]; p<0·0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure. INTERPRETATION: Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. FUNDING: None.

Impact of Targeted Interventions on Trends in Central Line-Associated Bloodstream Infection: A Single-Center Experience From the Republic of Korea.

OBJECTIVE: To assess the impact of targeted interventions on trends in central line-associated bloodstream infection. DESIGN: A before-and-after study between January 2013 and September 2014. SETTING: Tertiary hospital in the Republic of Korea. PATIENTS: All patients with central-line catheters in the hospital. INTERVENTIONS: In September 2013, interventions that targeted central line insertion practices were implemented in 10 ICUs, including compliance monitoring with a central line insertion practices bundle and use of an all-inclusive catheter kit. The impact of targeted interventions on trends in central line-associated bloodstream infection was evaluated by segmented autoregression analysis of an interrupted time series. MEASUREMENTS AND MAIN RESULTS: The average hospital-wide central line-associated bloodstream infection rates in the baseline and intervention periods were 1.84 and 1.56 per 1,000 catheter-days, respectively. During the baseline period, there was an increase of central line-associated bloodstream infection rate of 0.12 per 1,000 catheter-days per month. In the intervention period, there was a decrease of central line-associated bloodstream infection rate of 0.16 per 1,000 catheter-days per month (change in slope, -0.28; 95% CI, -0.37 to -0.19; p < 0.0001). In ICUs, the average central line-associated bloodstream infection rates in the baseline and intervention periods were 1.92 and 1.64 per 1,000 catheter-days, respectively. During the baseline period, there was an increase of central line-associated bloodstream infection rate of 0.18 per 1,000 catheter-days per month in ICUs. After sequential-targeted interventions, there was a decrease of central line-associated bloodstream infection rate of 0.16 per 1,000 catheter-days per month (change in slope, -0.34; 95% CI, -0.50 to -0.18; p = 0.0007). CONCLUSIONS: Targeted interventions were associated with significant changes in trends in the occurrence rate of central line-associated bloodstream infection in ICUs and the entire hospital.

Atypical presentations of MERS-CoV infection in immunocompromised hosts.

During the 2015 Korean MERS outbreak, we experienced atypical presentations of MERS-CoV infections in three immunocompromised hosts that warranted exceptional management. Case 1 showed delayed symptom development after a four-day asymptomatic period, Case 2 experienced a 20-day incubation period, and Case 3 exhibited persistent viral shedding without clinical deterioration. Recognizing these exceptions is extremely important in the management of MERS-CoV-exposed or -infected patients and for control of potential MERS outbreaks.

Control of an Outbreak of Middle East Respiratory Syndrome in a Tertiary Hospital in Korea.

BACKGROUND: In 2015, a large outbreak of Middle East respiratory syndrome (MERS) occurred in the Republic of Korea. Half of the cases were associated with a tertiary care university hospital. OBJECTIVE: To document the outbreak and successful control measures. DESIGN: Descriptive study. SETTING: A 1950-bed tertiary care university hospital. PATIENTS: 92 patients with laboratory-confirmed MERS and 9793 exposed persons. MEASUREMENTS: Description of the outbreak, including a timeline, and evaluation of the effectiveness of the control measures. RESULTS: During the outbreak, 92 laboratory-confirmed MERS cases were associated with a large tertiary care hospital, 82 of which originated from unprotected exposure to 1 secondary patient. Contact tracing and monitoring exposed patients and assigned health care workers were at the core of the control measures in the outbreak. Nontargeted screening measures, including body temperature screening among employees and visitors at hospital gates, monitoring patients for MERS-related symptoms, chest radiographic screening, and employee symptom monitoring, did not detect additional patients with MERS without existing transmission links. All in-hospital transmissions originated from 3 patients with MERS who also had pneumonia and productive cough. LIMITATIONS: This was a retrospective single-center study. Statistical analysis could not be done. Because this MERS outbreak originated from a superspreader, effective control measures could differ in endemic areas or in other settings. CONCLUSION: Control strategies for MERS outbreaks should focus on tracing contacts of persons with epidemiologic links. Adjusting levels of quarantine and personal protective equipment according to the assumed infectivity of each patient with MERS may be appropriate. PRIMARY FUNDING SOURCE: Samsung Biomedical Research Institute.

Differential Cell Count and CRP Level in Blood as Predictors for Middle East Respiratory Syndrome Coronavirus Infection in Acute Febrile Patients during Nosocomial Outbreak.

A case-control study was performed to identify clinical predictors for Middle East respiratory syndrome coronavirus (MERS-CoV) infection among patients with acute febrile illness during the nosocomial outbreak. Patients with MERS-CoV were more likely to have monocytosis with normal white blood cell (WBC) count and lower C-reactive protein (CRP) level. Simple laboratory data such as complete blood counts (CBC) with differential count could be a useful marker for the prediction of MERS and triage at the initial presentation of acute febrile patients in outbreak setting.

Clinical Features and Risk Factors for Development of Breakthrough Gram-Negative Bacteremia during Carbapenem Therapy.

With the increasing use of carbapenems, carbapenem-resistant Gram-negative bacteria have become a major concern in health care-associated infections. The present study was performed to evaluate the clinical and microbiological features of breakthrough Gram-negative bacteremia (GNB) during carbapenem therapy and to assess risk factors for development of breakthrough GNB. A case-control study was performed at a tertiary hospital from 2005 to 2014. Case patients were defined as individuals whose blood cultures grew Gram-negative bacteria while the patients were receiving carbapenems for at least 48 h before breakthrough GNB. Age-, sex-, and date-matched controls were selected from patients who received carbapenem for at least 48 h and did not develop breakthrough GNB during carbapenem treatment. A total of 101 cases of breakthrough GNB were identified and compared to 100 controls. The causative microorganisms for breakthrough GNB were Stenotrophomonas maltophilia (n = 33), Acinetobacter baumannii (n = 32), Pseudomonas aeruginosa (n = 21), and others (n = 15). Approximately 90% of S. maltophilia isolates were susceptible to levofloxacin and trimethoprim-sulfamethoxazole. The most common infection types were primary bacteremia (38.6%) and respiratory infections (35.6%). More than half of the patients died within a week after bacteremia, and the 30-day mortality rate was 70.3%. In a multivariate analysis, a longer hospital stay, hematologic malignancy, persistent neutropenia, immunosuppressant use, and previous colonization by causative microorganisms were significantly associated with breakthrough GNB. Our data suggest that S. maltophilia, A. baumannii, and P. aeruginosa are the major pathogens of breakthrough GNB during carbapenem therapy, in association with a longer hospital stay, hematologic malignancy, persistent neutropenia, immunosuppressant use, and previous colonization.

Clinical presentation and risk factors for cytomegalovirus colitis in immunocompetent adult patients.

BACKGROUND: Cytomegalovirus (CMV) colitis is a common manifestation of CMV end-organ disease, which has typically been described in immunocompromised hosts. Recently, it has been noted that this also occurs in immunocompetent patients. To gather relevant data about clinical presentation, prognosis, and risk factors for development of CMV colitis in immunocompetent hosts, we analyzed all cases that occurred during a 19-year period at our institution. METHODS: A case-control study was performed to identify risk factors for CMV colitis in immunocompetent hosts. Electronic medical records of individuals who were admitted and diagnosed with CMV colitis between January 1995 and February 2014 at a tertiary care university hospital were reviewed. Two non-CMV colitis patients who were age- and sex-matched were selected as controls for each case. RESULTS: A total of 51 patients with CMV colitis were included in this study along with 102 control patients. Certain conditions including renal disease on hemodialysis, neurologic disease, rheumatologic disease, intensive care unit admission, and exposure to antibiotics, antacids, steroids, or red blood cell (RBC) transfusions within 1 month of diagnosis of colitis were associated with CMV colitis on univariate analysis. Among these, steroid use and RBC transfusion within 1 month were identified as independent risk factors for developing CMV colitis on multivariate analysis. The 30-day mortality rate was 7.8% without any attributable mortality. CONCLUSIONS: Steroid use and RBC transfusion within 1 month of the diagnosis of colitis were independent risk factors for development of CMV colitis in immunocompetent hosts.

In vitro activities of 21 antimicrobial agents alone and in combination with aminoglycosides or fluoroquinolones against extended-spectrum-ß-lactamase-producing Escherichia coli isolates causing bacteremia.

We evaluated the in vitro activity of various antimicrobials alone and in combination against 291 extended-spectrum-ß-lactamase-producing Escherichia coli (ESBL-EC) isolates causing bacteremia in South Korean hospitals. Ceftazidime, cefepime, and piperacillin-tazobactam in combination with amikacin showed greater activity than found in combination with ciprofloxacin. In settings with a high prevalence of ESBL-producing pathogens, combination aminoglycoside antimicrobial therapy, especially with amikacin, may be considered for empirical therapy against suspected Gram-negative sepsis as a carbapenem-saving strategy.

Case-control study of the risk factors for acquisition of Pseudomonas and Proteus species during tigecycline therapy.

Tigecycline is an important agent in clinical practice because of its broad-spectrum activity. However, it has no activity against Pseudomonas or Proteus species. We conducted a case-control study to analyze risk factors for the acquisition of Pseudomonas or Proteus spp. during tigecycline therapy. Placement of suction drainage at infected wound sites, ICU stay, and neurologic disease were identified as independent risk factors for the acquisition of Pseudomonas and Proteus spp.

Clinical features and risk factors for development of Bacillus bacteremia among adult patients with cancer: a case-control study.

PURPOSE: Bacillus species have been frequently reported in recent decades as true pathogens among cancer patients. The purpose of this study was to evaluate the clinical features and risk factors of Bacillus bacteremia among adult patients with cancer. METHODS: A case-control study was performed to identify the risk factors of Bacillus bacteremia among adult patients with cancer at a 1,950-bed tertiary care university hospital. Electronic medical records were reviewed for individuals who were diagnosed with Bacillus bacteremia during the period of January 1995 through December 2012. Each case was matched to two controls with cancer and non-Bacillus bacteremia. Logistic regression model was used to identify independent risk factors for Bacillus bacteremia development. RESULTS: A total of 86 patients with Bacillus bacteremia were included and compared with 172 control patients. The presence of a central venous catheter and use of extended-spectrum cephalosporin within 1 month were identified to be independent risk factors for the development of Bacillus bacteremia. Hospital stays longer than 14 days, a history of hematopoietic stem cell transplantation, and prior use of glycopeptides had a negative association. CONCLUSIONS: The presence of a central venous catheter and prior use of extended-spectrum cephalosporin within 1 month were independent risk factors for the development of Bacillus bacteremia in adult cancer patients.

Bacteremic meningitis caused by Parvimonas micra in an immunocompetent host.

A 61-year-old man with chronic hepatitis B and dyslipidemia visited the emergency department with a fever and severe headache. He was diagnosed with bacterial meningitis after a lumbar puncture, and blood culture revealed Parvimonas micra bacteremia. Although he had a history of extraction of a molar two weeks before symptom onset, there was no evidence of abscess formation on physical examination or imaging studies. He was successfully treated with oral metronidazole for 12 days after 9 days of treatment with IV ceftriaxone and vancomcycin. This is the first report of primary bacterial meningitis caused by this organism, which indicates that this organism is capable of being a bacterial meningitis pathogen.

Mycobacterium chelonae infections associated with bee venom acupuncture.

We report 3 cases of Mycobacterium chelonae infections after bee venom acupuncture. All were treated with antibiotics and surgery. Mycobacterium chelonae infections should be included in the differential diagnosis of chronic skin and soft tissue infections following bee venom acupuncture.

Extensively drug-resistant Streptococcus pneumoniae, South Korea, 2011-2012.

To better understand extensively drug resistant Streptococcus pneumoniae, we assessed clinical and microbiological characteristics of 5 extensively drug-resistant pneumococcal isolates. We concluded that long-term care facility residents who had undergone tracheostomy might be reservoirs of these pneumococci; 13- and 23-valent pneumococcal vaccines should be considered for high-risk persons; and antimicrobial drugs should be used judiciously.

Can levofloxacin be a useful alternative to trimethoprim-sulfamethoxazole for treating Stenotrophomonas maltophilia bacteremia?

A retrospective study was conducted to evaluate the efficacy of levofloxacin in the treatment of Stenotrophomonas maltophilia bacteremia. The 30-day mortality rates were similar between the trimerthoprim-sulfamethoxazole (TMP-SMX) and levofloxacin treatment groups. Adverse events related to antibiotics occurred more frequently in patients receiving TMP-SMX, and recurrent bacteremia due to levofloxacin-resistant S. maltophilia strains developed in patients treated with levofloxacin. Our data suggest that levofloxacin can be a useful alternative option for treating S. maltophilia infections.

Risk factor of community-onset spontaneous bacterial peritonitis caused by fluoroquinolone-resistant Escherichia coli in patients with cirrhosis.

BACKGROUND & AIMS: Despite the high prevalence of antimicrobial-resistant Escherichia coli in hospital-acquired infections, the clinical epidemiology of fluoroquinolone (FQ) resistance in community-onset spontaneous bacterial peritonitis (SBP) in patients with cirrhosis is not well understood. This study was performed to evaluate clinical features and risk factors for community-onset SBP caused by FQ-resistant E. coli. METHODS: A case-control control study was performed using cases of community-onset SBP from June 2000 to August 2011 at Samsung Medical Center (Seoul, Korea). Patients with FQ-resistant E. coli were designated as case patients. A control group I (CG I) patient was defined as a person whose clinical sample yielded FQ-susceptible E. coli, and a control group II (CG II) patient was defined as a person with a negative culture result. RESULTS: A total of 82 subjects with community-onset SBP caused by E. coli were identified, of which 26 (31.7%) were FQ-resistant E. coli infection. Fifty-seven matched subjects were randomly selected for CG II. Compared with CG I, previous SBP episodes (OR, 4.91; 95% CI, 1.50-16.53; P = 0.010), prior use of FQ within 30 days (OR, 7.05; 95% CI, 1.17-42.38; P = 0.033), and third-generation cephalosporin resistance (OR, 17.68; 95% CI, 1.67-187.26; P = 0.017) were significantly associated with FQ-resistant E. coli. Compared with CG II, a previous SBP episode was significantly associated with FQ-resistant E. coli (OR, 4.20; 95% CI, 1.50-11.80; P = 0.006). CONCLUSION: FQ-resistant E. coli is a significant cause of community-onset SBP, with relation to previous SBP episodes, recent FQ use and third-generation cephalosporin resistance.