Proton pump inhibitors increase the risk of carbapenem-resistant Enterobacteriaceae colonization by facilitating the transfer of antibiotic resistance genes among bacteria in the gut microbiome.

Carbapenem-resistant Enterobacteriaceae (CRE) pose a global health threat; however, there is still limited understanding of the risk factors and underlying mechanisms of CRE colonization in the gut microbiome. We conducted a matched case-control study involving 282 intensive care unit patients to analyze influencing covariates on CRE colonization. Subsequently, their effects on the gut microbiome were analyzed in a subset of 98 patients (47 CRE carriers and 51 non-CRE carriers) using whole metagenome sequences. The concomitant use of proton pump inhibitors (PPIs) and antibiotics was a significant risk factor for CRE colonization. The gut microbiome differed according to PPI administration, even within the CRE and non-CRE groups. Moreover, the transfer of mobile genetic elements (MGEs) harboring carbapenem resistance genes (CRGs) between bacteria was higher in the PPI-treated group than in the PPI-not-treated group among CRE carriers. The concomitant use of PPIs and antibiotics significantly alters the gut microbiome and increases the risk of CRE colonization by facilitating the transfer of CRGs among bacteria of the gut microbiome. Based on these findings, improved stewardship of PPIs as well as antibiotics can provide strategies to reduce the risk of CRE colonization, thereby potentially improving patient prognosis.

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.

Effectiveness and Adverse Events of Nirmatrelvir/Ritonavir Versus Molnupiravir for COVID-19 in Outpatient Setting: Multicenter Prospective Observational Study.

BACKGROUND: In this study, we aimed to compare the effectiveness and adverse reactions of nirmatrelvir/ritonavir and molnupiravir in high-risk outpatients with coronavirus disease 2019 (COVID-19). METHODS: This multicenter prospective observational study evaluated the rate of hospitalization, death, and adverse events within 28 days of oral antiviral agent prescription (molnupiravir, n = 240; nirmatrelvir/ritonavir, n = 240) to 480 nonhospitalized adult patients with COVID-19 from August 2, 2022 to March 31, 2023. RESULTS: Patients receiving molnupiravir had a higher prevalence of comorbidities (85.8% vs. 70.4%; P < 0.001) and a higher Charlson comorbidity index (2.8 ± 1.4 vs. 2.5 ± 1.5; P = 0.009) than those receiving nirmatrelvir/ritonavir. Three patients required hospitalization (nirmatrelvir/ritonavir group, n = 1 [0.4%]; molnupiravir group, n = 2 [0.8%]; P = 1.000). Nirmatrelvir/ritonavir was associated with a higher risk of adverse events than molnupiravir (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.27-3.03), especially for patients aged 65 years and older (OR, 3.04; 95% CI, 1.71-5.39). The severity of adverse events in both groups was mild to moderate and improved after discontinuation of medication. In the molnupiravir group, age ≥ 65 years (OR, 0.43 95% CI, 0.22-0.86) and appropriate vaccination (OR, 0.37; 95% CI, 0.15-0.91) reduced the occurrence of adverse events. CONCLUSION: The rates of hospitalization and death were low and not significantly different between high-risk patients who received either nirmatrelvir/ritonavir or molnupiravir. Although adverse events were more frequent with nirmatrelvir/ritonavir than with molnupiravir, none were severe. Nirmatrelvir/ritonavir can be safely used to treat COVID-19, while molnupiravir could be considered as an alternative treatment option for high-risk groups.

Clinical and economic burden of bacteremia due to multidrug-resistant organisms in Korea: a prospective case control study.

OBJECTIVES: The socioeconomic and clinical burden of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) have not yet been adequately addressed. METHODS: We prospectively searched for MDRO bacteremia cases with matched controls from 10 hospitals across Korea during a 6-month period in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had been selected according to predefined criteria. We collected clinical information and estimated the total additional medical cost due to MDRO infections using the multistate model. RESULTS: During the 6-month period, a total of 486 MDRO bacteremia cases (260, 87, 18, 20, and 101 cases of MRSA, MRAB, MRPA, CRE, and VRE, respectively) were identified. The 90-d mortality rates were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. The additional costs caused by bacteremia were $15 768, $35 682, $39 908, $72 051, and $33 662 per MDRO type, respectively. Based on these 6-month data, the estimated annual number of bacteremia cases due to these five MDRO in Korea were 7979 (4070, 1396, 218, 461, and 1834 cases, respectively). Overall, this caused an estimated 3280 (1237, 882, 36, 254, and 871, respectively) deaths and cost $294 505 002 ($84 707 359, $74 387 364, $10 344 370, $45 850 215, and $79 215 694, respectively) (range $170,627,020-$416,094,679) in socioeconomic loss. CONCLUSIONS: A tremendous clinical and economic burden is caused by MDRO bacteremia compared with antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed.

Socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in Korea.

We aimed to estimate the socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii (MRAB) and Pseudomonas aeruginosa (MRPA). We prospectively searched for MRAB and MRPA pneumonia cases and matched them with susceptible-organism pneumonia and non-infected patients from 10 hospitals. The matching criteria were: same principal diagnosis, same surgery or intervention during hospitalisation, age, sex, and admission date within 60 days. We calculated the economic burden by using the difference in hospital costs, the difference in caregiver costs, and the sum of productivity loss from an unexpected death. We identified 108 MRAB pneumonia [MRAB-P] and 28 MRPA pneumonia [MRPA-P] cases. The estimated number of annual MRAB-P and MRPA-P cases in South Korea were 1309-2483 and 339-644, with 485-920 and 133-253 deaths, respectively. The annual socioeconomic burden of MRAB-P and MRPA-P in South Korea was $64,549,723-122,533,585 and $15,241,883-28,994,008, respectively. The results revealed that MRAB-P and MRPA-P occurred in 1648-3127 patients, resulted in 618-1173 deaths, and caused a nationwide socioeconomic burden of $79,791,606-151,527,593. Multidrug-resistant organisms (MDRO) impose a great clinical and economic burden at a national level. Therefore, controlling the spread of MDRO will be an effective measure to reduce this burden.

Risk factors for early mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.

OBJECTIVES: Although many deaths due to carbapenem-resistant Acinetobacter baumannii (CRAB) bacteraemia occur within a few days after the onset of bacteraemia, risk factors for early mortality (EM) have not been deeply investigated. We aimed to determine the risk factors for EM and the difference between risk factors associated with EM and late mortality (LM) in CRAB bacteraemia. METHODS: Clinical information on all patients with CRAB bacteraemia in 10 hospitals during a 1-year period was collected. Among the cases with mortality within 30 days, EM and LM were defined as death within 3 and more than 5 calendar days from the first positive blood culture, respectively. RESULTS: In total, 212 CRAB bacteraemia cases were included in the analysis. Of 122 (57.5%) patients with 30-day mortality, EM was observed in 75 (61.5%) patients and LM in 39 (32.0%) patients. The proportion of severe sepsis or septic shock, Pitt score, and Sequential Organ Failure Assessment (SOFA) score was significantly higher in patients with EM than those with LM. Although urinary tract infection as the site of infection and the severity of illness were independent predictors of LM, only factors representing the severity of illness were independent risk factors for EM. CONCLUSION: Our results suggest that a large proportion of CRAB bacteraemia with high severity progresses to a rapidly fatal course, regardless of the underlying diseases or source of infection. Further studies might be needed to investigate the microbiological factors associated with CRAB and pathogen-host interaction in patients with EM.

Alteration of Gut Microbiota in Carbapenem-Resistant Enterobacteriaceae Carriers during Fecal Microbiota Transplantation According to Decolonization Periods.

Fecal microbiota transplantation (FMT) has been suggested as an alternative therapeutic option to decolonize carbapenem-resistant Enterobacteriaceae (CRE). However, the analysis of gut microbiota alteration in CRE carriers during FMT is still limited. Here, gut microbiota changes in CRE carriers were evaluated during FMT according to decolonization periods. The decolonization of 10 CRE carriers was evaluated after FMT, using serial consecutive rectal swab cultures. Alterations of gut microbiota before and after FMT (56 serial samples) were analyzed using high-throughput sequencing. The decolonization rates of CRE carriers were 40%, 50%, and 90% within 1, 3 and 5 months after initial FMT, respectively. Gut microbiota significantly changed after FMT (p = 0.003). Microbiota alteration was different between the early decolonization carriers (EDC) and late decolonization carriers (LDC). Microbiota convergence in carriers to donors was detected in EDC within 4 weeks, and keystone genera within the Bacteroidetes were found in the gut microbiota of EDC before FMT. The relative abundance of Klebsiella was lower in EDC than in LDC, before and after FMT. Our results indicate that FMT is a potential option for CRE decolonization. The gut microbiota of CRE carriers could be used to predict decolonization timing after FMT, and determine repeated FMT necessity.

Prolonged Carriage of Carbapenemase-Producing Enterobacteriaceae: Clinical Risk Factors and the Influence of Carbapenemase and Organism Types.

Prolonged carriage of carbapenemase-producing Enterobacteriaceae (CPE) constitutes a substantial epidemiologic threat. This study aimed to evaluate whether the types of carbapenemase and organism can affect the duration of carriage and to evaluate the clinical factors associated with prolonged carriage. We retrospectively reviewed data for patients admitted between May 2013 and August 2018 who were identified as CPE carriers. A total of 702 patients were identified; the major types of carbapenemase and organism were Oxacillinase (OXA)-48-like (n = 480, 68.4%) and Klebsiella pneumoniae (K. pneumoniae) (n = 584, 83.2%). The analyses of time to spontaneous decolonization using the Kaplan-Meier method showed that OXA-48-like and K. pneumoniae were significantly associated with prolonged carriage (log rank, p = 0.001 and p < 0.001). In multivariable logistic analysis to assess the risk factors for CPE prolonged carriage in the 188 patients with available follow-up culture data for 3 months, K. pneumoniae (adjusted odds ratio [aOR] 6.58; 95% confidence interval [CI], 1.05-41.27; p = 0.044), CPE positive clinical specimen (aOR 11.14; 95% CI, 4.73-26.25; p < 0.001), and concurrent Clostridioides difficile infection (CDI) (aOR 3.98, 95% CI 1.29-12.26; p = 0.016) were predictive of prolonged carriage. Our results suggest that CP-K. pneumoniae may have higher probability of prolonged carriage, while the effect of OXA-48-like CPE is inconclusive. Furthermore, patients with CP-K. pneumoniae who had positive clinical specimen or concurrent CDI can cause a vicious circle in prolonged carriage.

Prescription of Antibiotics for Adults with Acute Infectious Diarrhea in Korea: A Population-based Study.

BACKGROUND: Acute infectious diarrhea (AID) is a commonly observed condition globally. Several studies recommend against the use of empiric antibiotic therapy for AID, except in some cases of travelers' diarrhea. However, many physicians prescribe antimicrobial agents for AID. We aimed to determine the rate of antibiotic use and the associated prescription patterns among adults with AID. MATERIALS AND METHODS: This population-based, retrospective epidemiological study was performed using Korean National Health Insurance claims data from 2016 to 2017. The study population comprised adults (age ≥18 years) who had visited clinics with AID-related complaints. Exclusion criteria were the presence of Crohn's disease, ulcerative colitis, irritable bowel syndrome, and other non-infectious forms of colitis. Patients who underwent surgery during admission were also excluded. RESULTS: The study population comprised 1,613,057 adult patients with AID (767,606 [47.6%] men). Young patients (age 18 - 39 years) accounted for 870,239 (54.0%) of the study population. Overall, 752,536 (46.7%) cases received antibiotic prescriptions. The rate of antibiotic administration tended to be higher among elderly patients (age ≥65 years) than among younger patients (49.5% vs. 46.4%, P <0.001). The antibiotics most frequently prescribed in both monotherapy and combination regimens were fluoroquinolones (29.8%), rifaximin (26.8%), second-generation cephalosporins (9.2%), third-generation cephalosporins (7.3%), trimethoprim/sulfamethoxazole (5.5%), and ß-lactam/ß-lactamase inhibitors (5.3%). Patients who visited tertiary care hospitals had lower rates of antibiotic therapy (n = 14,131, 41.8%) than did those visiting private clinics (n = 532,951, 47.1%). In total, 56,275 (62.3%) admitted patients received antibiotic therapy, whereas outpatients had lower rates of antibiotic prescription (n = 694,204, 46.0%). CONCLUSION: This study revealed differences between the antibiotics used to treat AID in Korea and those recommended by the guidelines for AID treatment. Multifaceted efforts are necessary to strengthen physicians' adherence to published guidelines.

Guideline for the Antibiotic Use in Acute Gastroenteritis.

Acute gastroenteritis is common infectious disease in community in adults. This work represents an update of 'Clinical guideline for the diagnosis and treatment of gastrointestinal infections' that was developed domestically in 2010. The recommendation of this guideline was developed regarding the following; epidemiological factors, test for diagnosis, the indications of empirical antibiotics, and modification of antibiotics after confirming pathogen. Ultimately, it is expected to decrease antibiotic misuse and prevent antibiotic resistance.

In vitro activity of flomoxef against extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Korea.

To find an alternative regimen for the treatment of extended-spectrum ß-lactamase (EBSL)-producing Enterobacteriaceae infections, we examined the in vitro activity of flomoxef against Escherichia coli and Klebsiella pneumoniae having CTX-M-1 group and/or CTX-M-9 group ESBLs. Boronic acid disk methods and polymerase chain reaction amplification were used to detect for ESBL, and AmpC ß-lactamase and AmpC ß-lactamase co-producers were excluded. Minimum inhibitory concentrations (MICs) were determined for flomoxef by broth microdilution. One hundred seventy-six isolates (E. coli, n = 93 and K. pneumoniae, n = 83) were analyzed for susceptibility test. A total of 94.3% (166/176) of isolates were susceptible to flomoxef (MIC50/MIC90 were 0.5/8 µg/mL); 98.9% of the ESBL-producing E. coli (MIC50/MIC90 were 1/4 µg/mL) and 89.2% of the ESBL-producing K. pneumoniae (MIC50/MIC90 were 0.5/16 µg/mL) were susceptible to flomoxef. Flomoxef has good in vitro activity against ESBL-producing E. coli and K. pneumoniae and could be considered as an alternative for infections caused by these organisms.

Randomized controlled trial of piperacillin-tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli.

BACKGROUND: Due to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC). METHODS: This study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10-14 days with PTZ, cefepime, or ertapenem. RESULTS: A total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC. CONCLUSION: Results from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC. TRIAL REGISTRATION: The trial was registered with the Clinical Research Information Service of Korea Centers for Disease Control and Prevention. (KCT0001895).

Predictive risk factors for Listeria monocytogenes meningitis compared to pneumococcal meningitis: a multicenter case-control study.

PURPOSE: Various immunocompromised conditions increase the risk of meningitis caused by Listeria monocytogenes. However, the relative importance of these risk factors has not been well established. We determined the risk factors that predict meningitis due to L. monocytogenes compared to that caused by Streptococcus pneumoniae. METHODS: A nationwide multicenter case-control study was conducted in Korea. Cases of meningitis caused by L. monocytogenes between 1998 and 2013 were included. Patients with pneumococcal meningitis were included as controls. Multivariate logistic regression analysis was used to predict the risk factors of Listeria meningitis. RESULTS: A total of 36 cases and 113 controls were enrolled. The most significant predictive risk factor of Listeria meningitis was a prior history of receiving immunosuppressive therapy (odds ratio 8.12, 95 % CI 2.47-26.69). Chronic liver disease was the second most important predictive risk factor (OR 5.03, 95 % CI 1.56-16.22). Delaying appropriate antibiotic therapy by more than 6 h (hazard ratio 2.78) and fatal underlying disease (hazard ratio 2.88) were associated with increased mortality. CONCLUSIONS: Patients with a prior history of receiving immunosuppressive therapy within 1 month and chronic liver disease have 8.1-fold and 5-fold increased risk of meningitis by L. monocytogenes compared to S. pneumoniae, respectively.

Prevalence and Molecular Characteristics of Carbapenemase-Producing Enterobacteriaceae From Five Hospitals in Korea.

BACKGROUND: The emergence of carbapenemase-producing Enterobacteriaceae (CPE) represents a major clinical problem because these bacteria are resistant to most antibiotics. CPE remain relatively uncommon in Korea. We report the prevalence, clinical characteristics, and molecular epidemiology of CPE isolates collected from five university hospitals in Korea. METHODS: Between January and December 2015, 393 non-duplicated isolates that were nonsusceptible to ertapenem were analyzed. Production of carbapenemase, extended-spectrum ß-lactamase, and AmpC ß-lactamase was determined by genotypic tests. Antimicrobial susceptibility profiles were determined by using an Etest. Clonality of Klebsiella pneumoniae carbapenemase (KPC)-2-producing and oxacillinase (OXA)-232-producing Klebsiella pneumoniae isolates was determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Of the 393 isolates tested, 79 (20.1%) were CPE. Of these 79 isolates, 47 (59.5%) harbored the bla(OXA-232) gene while the remaining isolates carried genes bla(KPC-2) (n=27), bla(IMP-1) (n=4), and bla(NDM-1) (n=1). Among the 24 KPC-2 K. pneumoniae isolates from hospital B, 100% were resistant to carbapenems, 8% to colistin, and 0% to tigecycline. Among the 45 OXA-232 K. pneumoniae at hospital C, 95% were resistant to ertapenem, 68% to imipenem, 95% to meropenem, 10% to colistin, and 24% to tigecycline. PFGE analysis revealed a unique pattern for KPC-2 K. pneumoniae and identified 30 isolates belonging to the dominant pulsotypes (PT)1 and PT2 among 41 OXA-232 K. pneumoniae isolates. CONCLUSIONS: CPE strains are present in Korea, with the majority of K. pneumoniae isolates producing OXA-232 and KPC-2. The prevalence and predominant genotypes of CPE show hospital-specific differences.

Effect of daily chlorhexidine bathing on the acquisition of methicillin-resistant Staphylococcus aureus in a medical intensive care unit with methicillin-resistant S aureus endemicity.

BACKGROUND: Universal decolonization is recommended in intensive care units (ICUs) that have unacceptably high rates of methicillin-resistant Staphylococcus aureus (MRSA) despite implementation of basic prevention strategies. METHODS: An interrupted time series study was performed to evaluate the effect of daily chlorhexidine bathing on the acquisition of MRSA in a medical ICU with MRSA endemicity. There was a 14-month control period and a 16-month chlorhexidine bathing period. Segmented Poisson regression analysis was performed to assess the impact of daily chlorhexidine bathing on the incidence density of MRSA. Also, chlorhexidine susceptibility testing with polymerase chain reaction for the qacA/B gene was performed on MRSA isolates collected during the chlorhexidine bathing period. RESULTS: There was a significant reduction in trend (-0.056; 95% confidence interval, -0.095 to -0.017; P = .005) of incidence density of MRSA despite a significant increase in both level and trend of MRSA prevalence rates during the chlorhexidine bathing period. However, there was no significant reduction in level of incidence density of MRSA during the interventional period. Minimum inhibitory concentration of chlorhexidine and the detection rates of the qacA/B gene for a total of 174 MRSA isolates did not increase during the chlorhexidine bathing period. CONCLUSIONS: Daily chlorhexidine bathing resulted in a significantly decreasing trend of MRSA acquisition rates irrespective of increased MRSA prevalence rates in the medical ICU. There was no shift of chlorhexidine-resistant MRSA strains.

Effects of inappropriate empirical antibiotic therapy on mortality in patients with healthcare-associated methicillin-resistant Staphylococcus aureus bacteremia: a propensity-matched analysis.

BACKGROUND: The purported value of empirical therapy to cover methicillin-resistant Staphylococcus aureus (MRSA) has been debated for decades. The purpose of this study was to evaluate the effects of inappropriate empirical antibiotic therapy on clinical outcomes in patients with healthcare-associated MRSA bacteremia (HA-MRSAB). METHODS: A prospective, multicenter, observational study was conducted in 15 teaching hospitals in the Republic of Korea from February 2010 to July 2011. The study subjects included adult patients with HA-MRSAB. Covariate adjustment using the propensity score was performed to control for bias in treatment assignment. The predictors of in-hospital mortality were determined by multivariate logistic regression analyses. RESULTS: In total, 345 patients with HA-MRSAB were analyzed. The overall in-hospital mortality rate was 33.0 %. Appropriate empirical antibiotic therapy was given to 154 (44.6 %) patients. The vancomycin minimum inhibitory concentrations of the MRSA isolates ranged from 0.5 to 2 mg/L by E-test. There was no significant difference in mortality between propensity-matched patient pairs receiving inappropriate or appropriate empirical antibiotics (odds ratio [OR] = 1.20; 95 % confidence interval [CI] = 0.71-2.03). Among patients with severe sepsis or septic shock, there was no significant difference in mortality between the treatment groups. In multivariate analyses, severe sepsis or septic shock (OR = 5.45; 95 % CI = 2.14-13.87), Charlson's comorbidity index (per 1-point increment; OR = 1.52; 95 % CI = 1.27-1.83), and prior receipt of glycopeptides (OR = 3.24; 95 % CI = 1.08-9.67) were independent risk factors for mortality. CONCLUSION: Inappropriate empirical antibiotic therapy was not associated with clinical outcome in patients with HA-MRSAB. Prudent use of empirical glycopeptide therapy should be justified even in hospitals with high MRSA prevalence.

Effect of daily chlorhexidine bathing on acquisition of carbapenem-resistant Acinetobacter baumannii (CRAB) in the medical intensive care unit with CRAB endemicity.

BACKGROUND: There is insufficient evidence for daily chlorhexidine bathing to reduce nosocomial spread of carbapenem-resistant Acinetobacter baumannii (CRAB) in endemic situations. METHODS: An interrupted time series study was performed to evaluate the effect of daily chlorhexidine bathing on the acquisition of CRAB in a medical intensive care unit (ICU) with CRAB endemicity. There was a 14-month control period and 12-month chlorhexidine bathing period. Segmented Poisson regression analysis was performed to assess the impact of chlorhexidine bathing on the level and trend of the series of prevalence rates and incidence density. Also, chlorhexidine susceptibility testing was performed on CRAB isolates collected during the chlorhexidine bathing period. RESULTS: There was a 51.8% reduction of CRAB acquisition rates after an introduction of daily chlorhexidine bathing (44.0 vs 21.2 cases/1,000 at-risk patient days, P < .001). There was a significant reduction in the level (-0.604; 95% CI, -0.904 to -0.305; P < .001) of incidence density of CRAB, whereas there was no significant change in both level and trend of CRAB prevalence rates. Minimum inhibitory concentration of chlorhexidine against a total of 98 CRAB isolates ranged from 8-64 µg/mL. CONCLUSION: Daily chlorhexidine bathing significantly reduces the acquisition of CRAB in a medical ICU with CRAB endemicity.

Drug utilization review of mupirocin ointment in a Korean university-affiliated hospital.

BACKGROUND/AIMS: Intranasal mupirocin and chlorhexidine bathing are candidate strategies to prevent healthcare-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). In Korea, intranasal mupirocin is not available, and mupirocin ointment, an over-the-counter drug, has been used indiscriminately. Furthermore, because it is covered by health insurance, mupirocin is easy to prescribe within hospitals. METHODS: We performed a mupirocin drug utilization review (DUR) within Hallym University Sacred Heart Hospital. Annual use of mupirocin was investigated between 2003 and 2013, and monthly consumption of mupirocin was assessed during the final 2-year period. The DUR focused on August 2012, the period of highest use of mupirocin. Also, we investigated trends in mupirocin resistance in MRSA between 2011 and 2013. RESULTS: Annual consumption of mupirocin increased from 3,529 tubes in 2003 to 6,475 tubes in 2013. During August 2012, 817 tubes were prescribed to 598 patients; of these, 84.9% were prescribed to outpatients, and 77.6% at the dermatology department. The most common indication was prevention of skin infections (84.9%), and the ointment was combined with systemic antibiotics in 62.9% of cases. The average duration of systemic antibiotic administration was about 7.8 days. The rate of low-level mupirocin resistance in MRSA increased from 8.0% to 22.0%, and that of high-level mupirocin resistance increased from about 4.0% to about 7.5%. CONCLUSIONS: Inappropriate use of mupirocin is prevalent. Considering the increase in resistance and the future application of intranasal mupirocin, prophylactic use of mupirocin in dermatology departments should be reconsidered.

Anti-anaerobic coverage is not necessary for Klebsiella pneumoniae liver abscess: a propensity score-matched cohort study.

Although most Klebsiella pneumoniae liver abscesses have been reported to be monomicrobial, clinical outcomes have not been compared between antimicrobial therapy with and without anti-anaerobic coverage. A propensity score-matched cohort study was conducted using the 731 cases of K. pneumoniae liver abscess. Clinical outcomes were compared between a group discontinuing anti-anaerobic agents after K. pneumoniae identification and a group continuing. A total of 170 cases were matched at a 1:1 ratio using their propensity to discontinue anti-anaerobic agents. The McNemar's test showed no difference in mortality rates (1.8% for discontinuation versus 2.3% for continuation; P = 1.00) or relapse (1.8% versus 2.9%; P = 0.73) between groups. Early discontinuation of anti-anaerobic agents had no association with treatment failure by means of the generalized estimating equation model (odds ratio 0.48; P = 0.14) and the Kaplan-Meier method (P = 0.85) in matched groups. Early discontinuation of anti-anaerobic agents does not affect the clinical outcomes of patients with K. pneumoniae liver abscess.

Improved Hand Hygiene Compliance is Associated with the Change of Perception toward Hand Hygiene among Medical Personnel.

BACKGROUND: Hand hygiene compliance has improved significantly through hand hygiene promotion programs that have included poster campaign, monitoring and performance feedback, and education with special attentions to perceived subjective norms. We investigated factors associated with improved hand hygiene compliance, focusing on whether the improvement of hand hygiene compliance is associated with changed perception toward hand hygiene among medical personnel. MATERIALS AND METHODS: Hand hygiene compliance and perceptions toward hand hygiene among medical personnel were compared between the second quarter of 2009 (before the start of a hand hygiene promotion program) and the second quarter of 2012. We assessed adherence to hand hygiene among medical personnel quarterly according to the WHO recommended method for direct observation. Also, we used a modified self-report questionnaire to collect perception data. RESULTS: Hand hygiene compliance among physicians and nurses improved significantly from 19.0% in 2009 to 74.5% in 2012 (P < 0001), and from 52.3% to 91.2% (P < 0.001), respectively. These improvements were observed in all professional status or all medical specialties that were compared between two periods, regardless of the level of the risk for cross-transmission. Hand hygiene compliance among the medical personnel continued to improve, with a slight decline in 2013. Perceptions toward hand hygiene improved significantly between 2009 and 2012. Specifically, improvements were evident in intention to adhere to hand hygiene, knowledge about hand hygiene methods, knowledge about hand hygiene indications including care of a dirty and a clean body site on the same patient, perceived behavioral and subjective norms, positive attitude toward hand hygiene promotion campaign, perception of difficulty in adhering to hand hygiene, and motivation to improve adherence to hand hygiene. CONCLUSIONS: The examined hand hygiene promotion program resulted in improved hand hygiene compliance and perception toward hand hygiene among medical personnel. The improved perception increased hand hygiene compliance. Especially, the perception of being a role model for other colleagues is very important to improve hand hygiene compliance among clinicians.