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.

Clinical and microbiological characteristics of female patients with acute pyelonephritis who experienced urinary tract infections within the previous year.

BACKGROUND: This study aimed to examine the clinical and microbiological characteristics of female patients with recurrent acute pyelonephritis (APN). METHODS: A retrospective cohort study was conducted at a tertiary care hospital in South Korea from July 2019 to December 2021. All female patients aged ≥ 19 years who were diagnosed with community-acquired APN on admission were enrolled. The recurrent group included patients with APN who experienced urinary tract infections within the previous year. The clinical characteristics, types of causative organisms, major antibiotic resistance, and molecular characteristics of Escherichia coli strains were compared between the recurrent and non-recurrent groups. RESULTS: A total of 285 patients with APN were analyzed, including 41 (14.4%) in the recurrent group. Compared to the non-recurrent group, the recurrent group had a higher Charlson Comorbidity Index (1.8 ± 2.1 vs. 1.1 ± 1.5; P = 0.01) and a higher proportion of bladder abnormalities, such as neurogenic bladder (12.2% vs. 2.0%; P = 0.001) and urinary catheterization (12.2% vs. 1.6%; P < 0.001). Escherichia coli was the most common causative organism in both groups. The proportion of Klebsiella pneumoniae (17.1% vs. 4.7%; P = 0.007) and Pseudomonas aeruginosa (5.7% vs. 0.5%; P = 0.014) as a causative organism was higher in the recurrent group. Regarding the microbiological characteristics of Escherichia coli, there were no significant differences in the proportion of antibiotic resistance, phylogenetic groups, resistance genes, and virulence factors between the two groups. Multivariable analysis showed that neurogenic bladder and a history of admission or antibiotic use during 1 year prior to inclusion were significantly associated with recurrent APN. CONCLUSIONS: The proportion of causative organisms except Escherichia coli was higher in the recurrent group than in the non-recurrent group. Neurogenic bladder and a history of admission or antibiotic use during 1 year prior to inclusion were risk factors for recurrent APN.

Comparative analyses of the faecal resistome against ß-lactam and quinolone antibiotics in humans and livestock using metagenomic sequencing.

To assess the prevalence and abundance of antibiotic resistance genes in human and livestock gut microbiomes, 87 humans (healthy individuals and patients with Clostridioides difficile infection (CDI)) and 108 livestock (swine, cattle, and chickens) were enrolled. Gut microbiomes and fluoroquinolone-resistant Escherichia coli isolates were sequenced, and mobile genetic elements adjacent to the ß-lactamase (bla) and transferable quinolone resistance (qnr) genes were compared using metagenomic contigs. Each group of humans and livestock exhibited distinctive microbiota and resistome compositions in the gut. Concerning the resistome of bla and qnr, the prevalence rates between chickens and patients with CDI were the most similar (R2 = 0.46); blaTEM, blaOXA, blaCTX-M, and qnrS were highly prevalent in both groups. According to genomic and phylogenetic analyses, blaCTX-M and blaOXA expressed lineage specificity to either humans or livestock, while qnrS and blaTEM displayed a shared lineage between humans and livestock. A qnrS1 mobilome comprising five genes, including two recombinases, a transposase, and a plasmid gene, is commonly found in human and chicken gut microbiomes. Humans and chickens showed the most similar gut resistomes to ß-lactams and quinolones. QnrS and blaTEM displayed especially strong co-occurrence between the guts of humans and livestock.

Identification of Micrococcin P2-Derivatives as Antibiotic Candidates against Two Gram-Positive Pathogens.

Thiopeptides exhibit potent antimicrobial activity against Gram-positive pathogens by inhibiting bacterial protein synthesis. Micrococcins are among the structurally simpler thiopeptides, but they have not been exploited in detail. This research involved a computational simulation of micrococcin P2 (MP2) docking in parallel with the structure-activity relationship (SAR) studied. The incorporation of particular nitrogen heterocycles in the side chain of MP2 enhances the antimicrobial activity. Micrococcin analogues 6c and 6d thus proved to be more effective against impetigo and C. difficile infection (CDI), respectively, as compared to current first-line treatments. Compound 6c also showed a shorter treatment period than that of a first-line treatment for impetigo. This may be attributed to its ability to downregulate pro-inflammatory cytokines. Compound 6d had no observed recurrence for C. difficile and exerted a minimal impact on the beneficial gut microbiome. Their pharmacokinetic properties and low toxicity profile make these compounds ideal candidates for the treatment of impetigo and CDI and validate their involvement in preclinical development.

Diversity of binary toxin positive Clostridioides difficile in Korea.

The objective of this study is to determine the trend and diversity of binary toxin-positive Clostridioides difficile over 10 years in Korea. Binary toxin-positive strains were selected from a tertiary hospital in Korea in 2009-2018. The multi-locus sequence typing and antibiotic susceptibility test were performed. Among the 3278 isolates in 2009-2018, 58 possessed binary toxin genes (1.7%). The proportion of CDT- positive isolates was 0.51-4.82% in 2009-2018, which increased over the 10-year period (P = 0.023). Thirteen sequence types (STs) were identified; ST5 (14 [24%]), ST11 (11 [19%]), ST221 (10 [17%]), ST201 (7 [12%]) and ST1 (5 [9%]) were popular. All 58 isolates were susceptible to vancomycin and piperacillin/tazobactam, and clindamycin and moxifloxacin were active in 69.0% and 62% of isolates, respectively. ST1 strains were resistant to several antibiotics, including moxifloxacin (80%), clindamycin (60%) and rifaximin (60%). Moreover, four of five ST1 presented a metronidazole minimum inhibitory concentration of 4 µg/mL. Moxifloxacin resistance was highest (72.3%) for ST11. In conclusion, binary toxin-positive strains are non-prevalent in Korea and involve diverse STs. ST1 strains were resistant to several antibiotics.

Different maturation of gut microbiome in Korean children.

Introduction: Gut microbiome plays a crucial role in maintaining human health and is influenced by food intake, age, and other factors. Methods: In this study based in Korea, we examined the bacterial taxonomic composition of the gut microbiota in infants (≤ 1 year), toddlers (1-<4 years), and school-aged children (4-13 years) and compared them with those of healthy adults to investigate the microbiota changes in early life and their association with the resistome. We used whole metagenome sequences obtained by Illumina HiSeq sequencing and clinical information of 53 healthy children, and sequence data of 61 adults from our previous study. Results: Our results indicate that the bacterial proportion of the gut in the population ranging from infants to adults forms three clusters: the Ruminococcus-Eubacterium (G1), Bifidobacterium-Escherichia (G2), and Bacteroides-Faecalibacterium (G3) groups. The gut microbiota of infants and toddlers (100% of infants and 85% of toddlers) constituted mostly of G2 and G3 groups, whereas 90% of adults showed G1-type gut microbiota. School-aged children showed a transitional gut microbiota composition of both infants and adults (31%, 38%, and 31% in G1, G2, and G3, respectively). Notably, the three clusters of microbiota showed significantly different patterns of bacterial diversity (p < 0.001): G2 showed the lowest Shannon index, followed by G3 and G1 (1.41, 2.08, and 2.48, respectively; median Shannon index). When combined with the adult group, alpha diversity showed a positive correlation with age (R2 = 0.3). Furthermore, clustering the composition of antibiotic resistance genes (ARG) identified two clusters (A1 and A2), and most of G1 (95%) and G3 (80%) belonged to A1. However, G2 showed the least diversity and the highest abundance of ARGs. Nine ARG families showed a significant difference among age groups; three tetracycline resistance genes, tet32, tetO, and tetW, showed a positive correlation, and six other genes, ampC, TEM, ileS, bacA, pmr transferase, and cepA, showed a negative correlation with age. Discussion: In conclusion, our results highlighted that a delayed persistence of the Bifidobacterium-dominant enterotype with a lower bacterial diversity was observed in Korean children up to 13 years of age, which suggests a different maturation process with a delayed maturation time.

Change in the Perception of Oral Antibiotics Among Medical Students After Participating in a Parenteral-to-Oral Conversion Program for Highly Bioavailable Antibiotics.

Background: Appropriate conversion of antibiotics from a parenteral to the oral route can lower the risk of catheter-associated infections, reduce medical costs, and shorten hospitalization. This study investigated the effect of a parenteral-to-oral conversion program for highly bioavailable antibiotics on the perceptions of medical students regarding oral antibiotics. Methods: In 2021, the parenteral-to-oral conversion program was implemented as one of the activities of an antimicrobial stewardship program at a tertiary-care hospital in South Korea. This program was also implemented for fifth-year medical students in the hospital's infectious diseases department as a core clinical practice course. Medical students reviewed the medical records of patients taking antibiotics with a high oral bioavailability and wrote a recommendation for oral conversion after confirmation by an infectious disease specialist. A survey on the perception of oral antibiotics was administered to medical students before and after clinical practice to evaluate the educational effect of the program. Results: A total of 923 cases were reviewed, and more than one-fifth of the antibiotics with a high oral bioavailability were administered parenterally despite their oral conversion (20.6%, 190/923). Of these, 24.2% (46/190) accepted the written proposal within 48 hours, and 43.7% (83/190) declined the proposal. Through this program, students gained a proper perception of oral antibiotics. Conclusions: The parenteral-to-oral conversion program demonstrated an acceptance rate of oral antibiotic conversion in the hospital of 24.2% and had significant educational benefits for medical students, giving them the ability to construct an appropriate perception of oral antibiotics.

Quantitative Evaluation of the Economic Impact of Antimicrobial Resistance on the Treatment of Community-Acquired Acute Pyelonephritis in Korea.

BACKGROUND: The proportion of antimicrobial-resistant Enterobacteriales as a causative pathogen of community-acquired acute pyelonephritis (APN) has been increasing. The aim of this study was to quantitatively evaluate the impact of antimicrobial resistance on medical costs and length of hospital stay for the treatment of APN. MATERIALS AND METHODS: A single-center retrospective cohort study was conducted between January 2018 and December 2019. All hospitalized patients aged ≥19 years who were diagnosed with community-acquired APN were recruited, and those diagnosed with Enterobacteriales as a causative pathogen were included. Log-linear regression analysis was performed to determine the risk factors for medical costs and length of hospital stay. RESULTS: A total of 241 patients participated in this study. Of these, 75 (31.1%) and 87 (36.1%) had extended-spectrum beta-lactamase (ESBL)-producing pathogens and ciprofloxacin-resistant pathogens as the causative pathogen, respectively. Based on the log-linear regression model, ESBL-producing Enterobacteriales is a causative pathogen that is, on average, 27.0%, or United States Dollar (USD) 1,211 (P = 0.026) more expensive than non-ESBL-producing Enterobacteriales. A patient who is a year older would incur USD 23 (P = 0.040) more, those having any structural problems in the urinary tract would incur USD 1,231 (P = 0.015) more, and those with a unit increase in the Pitt bacteremia score would incur USD 767 (P <0.001) more, with all other variables constant. Having a case in which ESBL-producing Enterobacteriales is a causative pathogen would explain staying 22.0% longer or 2 more days (P = 0.050) in the hospital than non-ESBL-producing Enterobacteriales. A patient who is 10 years older would, on average, would have to stay for half a day longer (P = 0.045). Any structural problems in the urinary tract explain a longer stay (2.4 days longer; P = 0.032), and moving from 0 to 5 on the Pitt bacteremia score would explain four more days (P = 0.038) in the hospital. CONCLUSION: Patients with community-acquired APN with ESBL-producing Enterobacteriale as the causative pathogen would incur, on average, 27.0% higher medical costs and 22.0% longer hospitalization days than patients detected with non-ESBL-producing pathogens.

Deciphering Resistome in Patients With Chronic Obstructive Pulmonary Diseases and Clostridioides difficile Infections.

Antibiotics alter the gut microbiome and cause dysbiosis leading to antibiotic-resistant organisms. Different patterns of antibiotic administration cause a difference in bacterial composition and resistome in the human gut. We comprehensively investigated the association between the distribution of antibiotic resistance genes (ARGs), bacterial composition, and antibiotic treatments in patients with chronic obstructive pulmonary diseases (COPD) and Clostridioides difficile infections (CDI) who had chronic or acute intermittent use of antibiotics and compared them with healthy individuals. We analyzed the gut microbiomes of 61 healthy individuals, 16 patients with COPD, and 26 patients with CDI. The COPD patients were antibiotic-free before stool collection for a median of 40 days (Q1: 9.5; Q3: 60 days), while the CDI patients were antibiotic-free for 0 days (Q1: 0; Q3: 0.3). The intra-group beta diversity measured by the median Bray-Curtis index was the lowest for the healthy individuals (0.55), followed by the COPD (0.69) and CDI groups (0.72). The inter-group beta diversity was the highest among the healthy and CDI groups (median index = 0.89). The abundance of ARGs measured by the number of reads per kilobase per million reads (RPKM) was 684.2; 1,215.2; and 2,025.1 for the healthy, COPD, and CDI groups. It was negatively correlated with the alpha diversity of bacterial composition. For the prevalent ARG classes, healthy individuals had the lowest diversity and abundance of aminoglycoside, ß-lactam, and macrolide-lincosamide-streptogramin (MLS) resistance genes, followed by the COPD and CDI groups. The abundances of Enterococcus and Escherichia species were positively correlated with ARG abundance and the days of antibiotic treatment, while Bifidobacterium and Ruminococcus showed negative correlations for the same. In addition, we analyzed the mobilome patterns of aminoglycoside and ß-lactam resistance gene carriers using metagenomic sequencing data. In conclusion, the ARGs were significantly enhanced in the CDI and COPD groups than in healthy individuals. In particular, aminoglycoside and ß-lactam resistance genes were more abundant in the CDI and COPD groups, but the dominant mobile genetic elements that enable the transfer of such genes showed similar prevalence patterns among the groups.

Micrococcin P2 Targets Clostridioides difficile.

Clostridioides difficile infection is a global public health threat. Extensive in vitro assays using clinical isolates have identified micrococcin P2 (MP2, 1) as a particularly effective anti-C. difficile agent. MP2 possesses a mode of action that differs from other antibiotics and pharmacokinetic properties that render it especially promising. Its time-kill studies have been investigated using hypervirulent C. difficile ribotype 027. DSS (dextran sulfate sodium)-induced in vivo mouse studies with that strain indicate that 1 is better than vancomycin and fidaxomicin. Thus, micrococcin P2 is a valuable platform to be exploited for the development of new anti-C. difficile antibiotics.

Which is the Preferred Regimen for Non-Severe Clostridioides difficile Infection in Korea, Vancomycin or Metronidazole?

The emergence of hypervirulent Clostridioides difficile strains has decreased the efficacy of metronidazole in the treatment of C. difficile infection (CDI). Therefore, revised guidelines no longer recommend the use of metronidazole as a first-line regimen for CDI and restrict its use for non-severe CDI, only when vancomycin and fidaxomicin are unavailable. In Korea, an epidemic caused by a hypervirulent C. difficile strain or the emergence of metronidazole resistant C. difficile strains have not been reported. This review article aims to compare the treatment outcomes and adverse effects of vancomycin and metronidazole and discuss the validity of the guidelines of various agencies, which restrict the use of metronidazole, for Korean patients. There are no substantial adverse effects of metronidazole, and its clinical outcomes against non-severe CDI are similar to those of vancomycin. Based on these findings, we recommend that the use of metronidazole for the treatment of non-severe CDI is still an appropriate option in Korea.

Changes in the characteristics of community-onset fluoroquinolone-resistant Escherichia coli isolates causing community-acquired acute pyelonephritis in South Korea.

PURPOSE: This study aimed to examine the changes in the characteristics of community-onset fluoroquinolone-resistant (FQ-R) Escherichia coli isolates causing community-acquired acute pyelonephritis (APN) in South Korea. METHODS: Blood or urine samples were prospectively collected from patients aged ≥15 years with community-acquired APN who were admitted to one of the eight Korean hospitals included in this study between September 2017 and August 2018. Phylogenetic typing, multilocus sequence typing, and molecular characterization of ß-lactamase resistance and plasmid-mediated quinolone resistance (PMQR) determinants were performed. The data were compared with those from a previous study with the same design conducted in 2010-2011. RESULTS: A total of 300 and 346 isolates were identified in 2010-2011 and 2017-2018, respectively. Among them, 76 (22.0%) and 77 (25.7%) FQ-R isolates were identified in 2010-2011 and 2017-2018, respectively. A significantly higher antimicrobial resistance against third-to fourth-generation cephalosporins, including cefotaxime (23.9% vs. 77.9%, P < 0.001), were observed among FQ-R isolates in 2017-2018 than among those in 2010-2011. A higher proportion of ST131 isolates (27.6% vs. 66.2%, P < 0.001), as well as isolates that had extended-spectrum ß-lactamase (ESBL)/plasmid-mediated AmpC ß-lactamase (PABL) (23.7% vs. 79.2%, P < 0.001), was observed in 2017-2018 than in 2010-2011. Further, more PMQR determinants (11.8% vs. 40.8%, P < 0.001) were observed in 2017-2018 than in 2010-2011. CONCLUSIONS: Among uropathogenic FQ-R E. coli isolates in South Korea, the prevalence of ST131 and the proportion of isolates containing ESBL and/or PMQR determinants have increased.

Relationship between the appropriateness of antibiotic treatment and clinical outcomes/medical costs of patients with community-acquired acute pyelonephritis: a multicenter prospective cohort study.

BACKGROUND: Inappropriate use of antibiotics not only increases antibiotic resistance as collateral damage but also increases clinical failure rates and medical costs. The purpose of this study was to determine the relationship between the appropriateness of antibiotic prescription and outcomes of community-acquired acute pyelonephritis (CA-APN). METHODS: A multicenter prospective cohort study was conducted at eight hospitals in Korea between September 2017 and August 2018. All hospitalized patients aged ≥ 19 years who were diagnosed with CA-APN on admission were recruited. The appropriateness of empirical and definitive antibiotics, as well as the appropriateness of antibiotic treatment duration and route of administration, was evaluated in accordance with the guideline and expert opinions. Clinical outcomes and medical costs were compared between patients who were administered antibiotics 'appropriately' and 'inappropriately.' RESULTS: A total of 397 and 318 patients were eligible for the analysis of the appropriateness of empirical and definitive antibiotics, respectively. Of them, 10 (2.5%) and 18 (5.7%) were administered 'inappropriately' empirical and definitive antibiotics, respectively. Of the 119 patients whose use of both empirical and definitive antibiotics was classified as 'optimal,' 57 (47.9%) received antibiotics over a longer duration than that recommended; 67 (56.3%) did not change to oral antibiotics on day 7 of hospitalization, even after stabilization of the clinical symptoms. Patients who were administered empirical antibiotics 'appropriately' had shorter hospitalization days (8 vs. 10 days, P = 0.001) and lower medical costs (2381.9 vs. 3235.9 USD, P = 0.002) than those who were administered them 'inappropriately.' Similar findings were observed for patients administered both empirical and definitive antibiotics 'appropriately' and those administered either empirical or definitive antibiotics 'inappropriately'. CONCLUSIONS: Appropriate use of antibiotics leads to better outcomes, including reduced hospitalization duration and medical costs.

Genetic Relatedness of 5-Year Isolates of Clostridioides difficile Polymerase Chain Reaction Ribotype 017 Strains in a Hospital.

The objective of this study was to analyse the genetic relatedness of Clostridioides difficile polymerase chain reaction ribotype 017 (RT017) strains from patients with hospital-acquired C. difficile infection (HA-CDI) in a hospital with a high RT017 prevalence. From 2009 to 2013, 200 RT017 strains (26.8%) were collected from 745 HA-CDI patient isolates. They comprised 64 MLVA types, and 197 (98.5%) strains were genetically related to 5 clonal complexes (CCs). The largest cluster, CC-A, included 163 isolates of 40 MLVA types. CC-A accounted for 20% of RT017 strains in 2009 and sharply increased to 94.9% in 2010, 94% in 2011, 86.2% in 2012, and 73.5% in 2013. The other 4 CCs included 20 isolates with 7 MLVA types. The resistance rates of antimicrobials were as follows: clindamycin 100%, moxifloxacin 99%, rifaximin 88.5%, and vancomycin 1%. All isolates were susceptible to metronidazole and piperacillin/tazobactam. Comparing antibiotic resistance among CCs, the geometric mean of the minimum inhibitory concentrations of moxifloxacin, vancomycin, and piperacillin/tazobactam were significantly higher for CC-A isolates than for the other CCs. RT017 clones constantly evolved over the 5 years studied with regard to genetic relatedness. The levels of antibiotic resistance may contribute to the persistence of organisms in the institution.

Clinical Characteristics of Patients with Adrenal Insufficiency and Fever.

BACKGROUND: Because persistent fever often occurs in adrenal insufficiency, it might be confused with infectious diseases. This study aimed to identify clinical characteristics and risk factors of patients with adrenal insufficiency and fever. METHODS: All adult patients (n = 150) admitted to a tertiary care hospital in South Korea and diagnosed with adrenal insufficiency between 1 March 2018, and 30 June 2019, were recruited. Patients were excluded if they had: 1) proven structural problems in the adrenal or pituitary gland; 2) a history of chemotherapy within 6 months prior to the diagnosis of adrenal insufficiency; and 3) other medical conditions that may cause fever. RESULTS: Among the included patients, 45 (30.0%) had fever at the time of the diagnosis of adrenal insufficiency. The mean C-reactive protein level was higher (11.25 ± 8.54 vs. 4.36 ± 7.13 mg/dL) in patients with fever than in those without fever. A higher proportion of patients with fever changed antibiotics (33.3% vs. 1.0%). On multivariate logistic regression analysis, female sex (odds ratio [OR], 0.32) lowered the risk of adrenal insufficiency with fever, while a history of surgery within 6 months (OR, 4.35), general weakness (OR, 7.21), and cough (OR, 17.29) were significantly associated with that. CONCLUSION: The possibility of adrenal insufficiency should be considered in patients with fever of unknown origin, especially those with risk factors.

Comparison of the clinical characteristics of community-acquired acute pyelonephritis between male and female patients.

BACKGROUND: Community-acquired acute pyelonephritis (CA-APN) is relatively rare in men. This study aimed to compare the clinical characteristics of CA-APN between male and female patients. METHODS: We prospectively collected the clinical and microbiological data of hospitalized CA-APN patients aged ≥19 years in South Korea from March 2010 to February 2011 in 11 hospitals and from September 2017 to August 2018 in 8 hospitals. Only the first episodes of APN of each patient during the study period were included. RESULTS: From 2010 to 2011, 573 patients from 11 hospitals were recruited, and from 2017 to 2018, 340 patients were recruited from 8 hospitals. Among them, 5.9% (54/913) were male. Male patients were older (66.0 ± 15.2 vs. 55.3 ± 19.0 years, P < 0.001), had a higher Charlson comorbidity index (1.3 ± 1.5 vs. 0.7 ± 1.2, P = 0.027), and had a higher proportion of structural problems in the urinary tract (40.7% vs. 6.1%, P < 0.001) than female patients. Moreover, the total duration of antibiotic treatment was longer (21.8 ± 17.8 d vs. 17.3 ± 9.4 d, P = 0.001) and the proportion of carbapenem usage was higher (24.1% vs. 9.5%, P = 0.001) in men than in women. Male patients were hospitalized for longer durations than female patients (median, 10 d vs. 7 d, P < 0.001). CONCLUSIONS: Male CA-APN patients were older and had more comorbidities than female CA-APN patients. In addition, male patients received antibiotic treatment for a longer duration than female patients.

High fecal carriage of blaCTX-M, blaCMY-2, and plasmid-mediated quinolone resistance genes among healthy Korean people in a metagenomic analysis.

To characterize the carriage of antibiotic resistance genes (ARGs) in the gut microbiome of healthy individuals. Fecal carriage of ARGs was investigated in 61 healthy individuals aged 30 to 59 years through whole metagenome sequencing of the gut microbiome and a targeted metagenomic approach. The number of ARGs in the gut microbiome was counted and normalized per million predicted genes (GPM). In the Korean population, the resistome ranged from 49.7 to 292.5 GPM (median 89.7). Based on the abundance of ARGs, the subjects were categorised into high (> 120 GPM), middle (60‒120 GPM), and low (< 60 GPM) ARG groups. Individuals in the high ARG group tended to visit hospitals more often (P = 0.065), particularly for upper respiratory tract infections (P = 0.066), and carried more blaCTX-M (P = 0.008). The targeted metagenome approach for bla and plasmid-mediated quinolone resistance (PMQR) genes revealed a high fecal carriage rate; 23% or 13.1% of the subjects carried blaCTX-M or blaCMY-2, respectively. Regarding PMQR genes, 59% of the subjects carried PMQR, and 83% of them harboured 2‒4 PMQR genes (qnrB 44.3%, qnrS 47.5% etc.). The presence of blaCTX-M correlated with ARG abundance in the gut resistome, whereas PMQR genes were irrelevant to other ARGs (P = 0.176). Fecal carriage of blaCTX-M and PMQR genes was broad and multiplexed among healthy individuals.

What is the optimal antibiotic treatment strategy for carbapenem-resistant Acinetobacter baumannii (CRAB)? A multicentre study in Korea.

OBJECTIVES: The optimal treatment option for carbapenem-resistant Acinetobacter baumannii (CRAB) is still limited. This study investigated the efficacy of three or more antibiotic types and regimens for treatment of CRAB infection in high CRAB endemic areas. METHODS: A multicentre retrospective study was conducted to evaluate the efficacy of treatment types and regimens of CRAB infections in 10 tertiary hospitals in the Republic of Korea. The outcomes comprised 7-day and 28-day mortality, and clinical and microbiological responses at 7 days, 28 days, and the end of treatment. Nephrotoxicity and hepatotoxicity were evaluated as drug adverse reactions. RESULTS: A total of 282 patients were included in the study. Among the CRAB strains, the two most susceptible antibiotics were colistin (99.6%) and minocycline (80.4%). A combination of colistin and carbapenem significantly reduced 7-day mortality, and a sulbactam-containing regimen significantly reduced 28-day mortality. Colistin monotherapy was significantly associated with increased 7-day and 28-day mortality. A minocycline-containing regimen showed the best microbiological responses at 7 days, 28 days, and the end of treatment. Colistin and tigecycline were associated with increased nephrotoxicity and hepatotoxicity, respectively. Subgroup analysis of patients with pneumonia showed similar results to the overall CRAB infection. CONCLUSIONS: A combination of colistin and carbapenem and sulbactam-containing regimen may contribute improved mortality in CRAB infections. Colistin monotherapy should be considered cautiously in severe CRAB infections or CRAB pneumonia. A minocycline-containing regimen showed the best microbiological responses, and further studies may be needed to evaluate improved mortality.