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 vancomycin resistance in Enterococcus faecium bloodstream infection on mortality: A retrospective analysis of nationwide surveillance data.

OBJECTIVES: It is unclear whether the poor outcome of patients with severe vancomycin-resistant enterococci (VRE) infection is attributable to vancomycin resistance or to Enterococcus faecium (Efm), which predominates among VRE. METHODS: Retrospective study of a prospectively identified cohort from nationwide surveillance. A cohort of consecutive, nonduplicate episodes of monomicrobial bloodstream infections (BSIs) caused by Efm in 2016 was selected. The primary outcome was all-cause, 30-day, in-hospital mortality. Inverse probability weighting was applied using the propensity score for vancomycin-resistant Efm (VREfm) BSI. RESULTS: A total of 241 Efm BSI episodes were included, of which 59 (24.5%) were VREfm. Patients with VREfm BSI were younger but had similar comorbidities to those with vancomycin-sensitive Efm (VSEfm) BSI. Multivariable logistic regression revealed that younger age, previous piperacillin-tazobactam use, and steroid use were significant risk factors for VREfm BSI, but 30-day in-hospital mortality did not differ significantly between groups (35.6% and 23.6% for VREfm and VSEfm, respectively; odds ratio, 1.79; 95% confidence interval, 0.95-3.37; P = 0.101). However, Cox regression with inverse probability weighting revealed that vancomycin resistance was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.18; 95% confidence interval, 1.03-4.62; P = 0.041). CONCLUSION: In patients with Efm BSI, vancomycin resistance was independently associated with mortality.

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.

WITHDRAWN: HM47118A, a novel insulinotropic GPR119 agonist and potential oral antidiabetic agent.

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Impact of high MIC of fluconazole on outcomes of Candida glabrata bloodstream infection: a retrospective multicenter cohort study.

To evaluate the impacts of fluconazole minimum inhibitory concentration (MIC) according to primary antifungal agents on Candida glabrata bloodstream infection (BSI), a multicenter retrospective cohort study was conducted in Korea, concerning the time period from January 2010 to February 2016. A total of 197 adult patients with C. glabrata BSI were included in the study, and neutropenia (P = 0.026), APACHE II score (P = 0.004), and fluconazole resistance (HR 3.960, 95% CI 1.395-11.246, P = 0.010) were associated with 30-day mortality in multivariate analysis. In subgroup analysis, fluconazole MIC = 32 µg/mL in the azole-treated group (HR 6.691, 95% CI 1.569-28.542, P = 0.010) and fluconazole MIC ≥ 64 µg/mL in the non-azole-treated group (HR 3.337, 95% CI 1.183-9.411, P = 0.023) showed the highest hazard ratio (HR) for 30-day mortality. Increased fluconazole MIC was associated with poor outcome both in azole- and non-azole-treated patients with C. glabrata BSI.

Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience.

BACKGROUND: The effects of convalescent plasma (CP) infusion, one of the treatment options for severe Middle East respiratory syndrome coronavirus (MERS-CoV) infections, have not yet been evaluated. METHODS: Serological responses of CP-infused MERS patients during the 2015 Korean MERS outbreak at a tertiary care centre were evaluated. Serological activity was evaluated with anti-MERS-CoV enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)G, ELISA IgA, immunofluorescence assay IgM and plaque reduction neutralization test (PRNT). Donor plasma and one or two recipient's serum samples per week of illness including one taken the day after each CP infusion were evaluated. For sensitivity and specificity analysis of ELISA IgG in predicting neutralization activity, a data set of 138 previously evaluated MERS-CoV-infected patients was used. RESULTS: Three of thirteen MERS patients with respiratory failure received four CP infusions from convalesced MERS-CoV-infected patients, and only two of them showed neutralizing activity. Donor plasma with a PRNT titre 1:80 demonstrated meaningful serological response after CP infusion, while that with a PRNT titre 1:40 did not. ELISA IgG predicted neutralization activity of a PRNT titre ≥1:80 with more than 95% specificity at a cutoff optical density (OD) ratio of 1.6, and with 100% specificity at an OD ratio of 1.9. CONCLUSIONS: For effective CP infusion in MERS, donor plasma with a neutralization activity of a PRNT titre ≥1:80 should be used. ELISA IgG could substitute for the neutralization test in resource-limited situations.

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.

Risk Factors for Community-Onset Pneumonia Caused by Levofloxacin-Nonsusceptible Streptococcus pneumoniae.

BACKGROUND: Fluoroquinolones are antibiotics commonly used in the treatment of infections caused by Streptococcus pneumoniae. However, rates of fluoroquinolone resistance are increasing with their frequent use. We designed this study to verify current fluoroquinolone resistance rates and risk factors for community-onset pneumococcal pneumonia. METHODS: A retrospective case-control study was conducted in a tertiary referral hospital. The study population comprised patients admitted for pneumococcal pneumonia between January 2011 and May 2017. The case group included community-onset pneumonia caused by levofloxacin-nonsusceptible S. pneumoniae. The control group consisted of two patients with levofloxacin-susceptible S. pneumoniae who were admitted around the same time as each case. RESULTS: A total of 198 pneumococcal pneumonia cases were identified during the study period. Twenty-five levofloxacin-resistant S. pneumoniae cases and 3 levofloxacin-intermediate S. pneumoniae cases were included in the case group (nonsusceptibility rate = 14.1%). Multivariate analysis showed that healthcare-associated factors (odds ratio [OR] 4.78, 95% confidence interval [CI] 1.39-16.43, p = 0.013), bronchopulmonary disease (OR 3.79, 95% CI 1.07-13.40, p = 0.039), cerebrovascular disease (OR 6.08, 95% CI 1.24-29.75, p = 0.026), and exposure to fluoroquinolones within the previous 3 months (OR 5.89, 95% CI 1.21-28.68, p = 0.028) were associated with nonsusceptibility to levofloxacin. CONCLUSION: Independent risk factors for levofloxacin-nonsusceptible pneumococcal pneumonia were recent hospitalization, bronchopulmonary disease, cerebrovascular disease, and prior antibiotic use within 3 months. Careful selection of empirical antibiotics is thus needed in at-risk patients. Similarly, efforts to prevent the interpersonal spread of drug-resistant pathogens in long-term care facilities and to restrict unnecessary fluoroquinolone prescriptions are important.

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.

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.

Failure of Ciprofloxacin Therapy in the Treatment of Community-Acquired Acute Pyelonephritis caused by In-Vitro Susceptible Escherichia coli Strain Producing CTX-Type Extended-Spectrum ß-Lactamase.

While carbapenems are the drug of choice to treat extended-spectrum-ß-lactamase (ESBL)-producing strains, some alternative carbapenem-sparing regimens are suggested for antibiotic stewardship. We experienced a case of ciprofloxacin treatment failure for acute pyelonephritis caused by an apparently susceptible Escherichia coli. A 71-year-old woman presented the emergency department with fever for 7 days and bilateral flank pain for 2 days. The laboratory results and abdominopelvic computed tomography finding were compatible with acute pyelonephritis. During 3-day ciprofloxacin therapy, the patient remained febrile with persistent bacteremia. After the change in antibiotics to ertapenem, the patient's clinical course started to improve. ESBL-producing E. coli isolates were identified in all three consecutive blood samples. Pulsed-field gel electrophoresis (PFGE) patterns, serotypes, and sequence types showed the three isolates were derived from the identical strain. The isolates produced CTX-M-14 type ESBL belonging to the ST69 clonal group. Despite in vitro susceptibility, the failure was attributed to a gyrA point mutation encoding Ser83Leu within quinolone resistance-determining regions. This case suggests that ciprofloxacin should be used cautiously in the treatment of serious infections caused by ciprofloxacin-susceptible, ESBL-producing E. coli, even in acute pyelonephritis because in-vitro susceptibility tests could fail to detect certain genetic mutations.

Discrepant susceptibility to gentamicin despite amikacin resistance in Klebsiella pneumoniae by VITEK 2 represents false susceptibility associated with the armA 16S rRNA methylase gene.

Because we experienced gentamicin failure in Klebsiella pneumoniae bacteraemia that was susceptible to gentamicin despite amikacin resistance, as determined by VITEK 2, we evaluated the true susceptibility and mechanism of resistance. We screened 2818 K. pneumoniae isolates during a 1-year period at a university hospital and reviewed anti-microbial susceptibility reports using the VITEK 2 system. The minimum inhibitory concentration was substantiated by broth microdilution (BMD), and the presence of 16S rRNA methylase genes and aminoglycoside-modifying enzymes was also investigated. A total of 131 amikacin-resistant isolates from 19 patients were gentamicin non-resistant according to the VITEK 2 system. Among these, we were able to collect isolates from 12 patients (63.2 %), and a single isolate from each patient was tested. Eleven of the gentamicin non-resistant isolates (91.7 %) showed high-level resistance to both amikacin and gentamicin by BMD in association with the armA gene. Gentamicin is not an adequate treatment option for amikacin-resistant K. pneumoniae, even if VITEK 2 reports susceptibility.

Serologic responses of 42 MERS-coronavirus-infected patients according to the disease severity.

We evaluated serologic response of 42 Middle East respiratory syndrome coronavirus (MERS-CoV)-infected patients according to 4 severity groups: asymptomatic infection (Group 0), symptomatic infection without pneumonia (Group 1), pneumonia without respiratory failure (Group 2), and pneumonia progressing to respiratory failure (Group 3). None of the Group 0 patients showed seroconversion, while the seroconversion rate gradually increased with increasing disease severity (0.0%, 60.0%, 93.8%, and 100% in Group 0, 1, 2, 3, respectively; P = 0.001). Group 3 patients showed delayed increment of antibody titers during the fourth week, while Group 2 patients showed robust increment of antibody titer during the third week. Among patients having pneumonia, 75% of deceased patients did not show seroconversion by the third week, while 100% of the survived patients were seroconverted (P = 0.003).

Bloodstream infections caused by Acinetobacter species with reduced susceptibility to tigecycline: clinical features and risk factors.

INTRODUCTION: During recent decades, the rates of multidrug resistance, including resistance to carbapenems, have increased dramatically among Acinetobacter species. Tigecycline has activity against multidrug-resistant Acinetobacter spp, including carbapenem-resistant isolates. However, reports of tigecycline-resistant Acinetobacter spp are emerging from different parts of the world. The purpose of this study was to evaluate potential risk factors associated with tigecycline non-susceptible Acinetobacter bacteremia. METHODS: The medical records of 152 patients with Acinetobacter bacteremia attending Samsung Medical Center between January 2010 and December 2014 were reviewed. Non-susceptibility to tigecycline was defined as a minimum inhibitory concentration (MIC) of tigecycline ≥4µg/ml. Cases were patients with tigecycline non-susceptible Acinetobacter bacteremia and controls were those with tigecycline-susceptible Acinetobacter bacteremia. RESULTS: Of the 152 patients included in the study, 61 (40.1%) had tigecycline non-susceptible Acinetobacter bacteremia (case group). These patients were compared to 91 patients with tigecycline-susceptible Acinetobacter bacteremia (control group). The case group showed high resistance to other antibiotics (>90%) except colistin (6.6%) and minocycline (9.8%) when compared to the control group, which exhibited relatively low resistance to other antibiotics (<50%). Multivariate analysis showed that recent exposure to corticosteroids (minimum 20mg per day for more than 5 days within 2 weeks) (adjusted odds ratio (OR) 2.887, 95% confidence interval (CI) 1.170-7.126) and carbapenems (within 2 weeks) (adjusted OR 4.437, 95% CI 1.970-9.991) were significantly associated with tigecycline non-susceptible Acinetobacter bacteremia. Although prior exposure to tigecycline was more common in the case group than in the control group (9.8%, 6/61 vs. 2.2%, 2/91; p=0.046), this variable was found not to be a significant factor associated with tigecycline non-susceptibility after adjustment for other variables (adjusted OR 1.884, 95% CI 0.298-11.920; p=0.501). CONCLUSIONS: These data suggest that tigecycline non-susceptible Acinetobacter spp have emerged and disseminated in the hospital in association with a recent exposure to carbapenems and an immunosuppressed state. This indicates that the rational use of antibiotics through a comprehensive antimicrobial stewardship program, especially in immunosuppressed patients, may be essential in limiting the emergence and spread of multidrug-resistant organisms such as tigecycline-resistant Acinetobacter spp, which are difficult to treat.

Comparison of subsequent infection in methicillin-resistant Staphylococcus aureus nasal carriers between ST72 community-genotype and hospital genotypes: a retrospective cohort study.

BACKGROUND: Carriage of methicillin-resistant Staphylococcus aureus (MRSA) is an important risk factor of subsequent infection. The purpose of our study was to compare the rates of subsequent infection among newly-admitted patients carrying MRSA between community-genotype and hospital-genotypes. METHODS: In this retrospective cohort study, we compared the rates of subsequent MRSA infection, time to subsequent infection and mortality in the following 6 months between the community-genotype ST72 MRSA cohort and the hospital-genotypes ST5 / ST239 MRSA cohort. RESULTS: We identified 198 patients carrying ST72 and 156 patients carrying ST5 or ST239. There was no difference in the rates of subsequent infection between ST72 cohort and ST5 / ST239 cohort (13.1% vs. 12.8%; P = 0.931). The median time to development of subsequent infection was not significantly different (27 days vs. 88 days; P = 0.0877). The Kaplan-Meier method showed no difference in the cumulative rate of being free of subsequent infection between the cohorts (P = 0.9209). Overall mortality rates at 6 months did not differ (1.5% vs. 1.9%; P = 1.000). CONCLUSIONS: We found no evidence that rates of subsequent MRSA infection were different between newly-admitted patients carrying community-genotype ST72 MRSA and those whom carrying hospital-genotypes ST5 or ST239 MRSA.

Emergence of Community-Genotype Methicillin-Resistant Staphylococcus aureus in Korean Hospitals: Clinical Characteristics of Nosocomial Infections by Community-Genotype Strain.

BACKGROUND: As community-genotype methicillin-resistant Staphylococcus aureus (MRSA) strains spread into hospitals, the genotypes of the MRSA strains causing hospital-acquired (HA) infections have become more diverse. We describe clinical characteristics of nosocomial MRSA infections by a community-genotype of sequence type (ST) 72. MATERIALS AND METHODS: A case-control study was designed among patients with HA-MRSA infections. Forty patients with infections caused by ST72-MRSA SCCmec type IV were selected as cases. Cases were matched to the controls with 106 patients infected with ST5/ST239 MRSA, which are representative hospital genotypes in Korea. RESULTS: Patients infected with ST72 isolates were younger than those with ST5/ST239 isolates. Female gender predominated among ST72 MRSA group compared to ST5/ST239 MRSA group. Solid tumor was a more frequent underlying disease in MRSA infections by ST72 isolates, whereas underlying renal, lung, heart, and neurologic diseases were more frequently found in those by ST5/ST239 isolates. The most common type of infection was pneumonia in both ST72 and ST5/ST239 groups (45.0% vs. 51.9%), followed by skin and soft tissue infection (SSTI). Female gender and underlying solid tumor were identified to be independent predictors for MRSA infections by ST72 isolates. All-cause mortality rates (20.0% vs. 30.2%) were not different between the groups. CONCLUSION: A community-genotype MRSA, ST72 isolate has emerged as a nosocomial pathogen presenting as hospital-acquired pneumonia and SSTI. Although differences in underlying disorders were found, the distribution of infection type and mortality rate did not differ between the groups.

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.

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.