Altered Mitochondrial Function and Accelerated Aging Phenotype in Neural Stem Cells Derived from Dnm1l Knockout Embryonic Stem Cells.

Mitochondria are crucial for cellular energy metabolism and are involved in signaling, aging, and cell death. They undergo dynamic changes through fusion and fission to adapt to different cellular states. In this study, we investigated the effect of knocking out the dynamin 1-like protein (Dnm1l) gene, a key regulator of mitochondrial fission, in neural stem cells (NSCs) differentiated from Dnm1l knockout embryonic stem cells (Dnm1l-/- ESCs). Dnm1l-/- ESC-derived NSCs (Dnm1l-/- NSCs) exhibited similar morphology and NSC marker expression (Sox2, Nestin, and Pax6) to brain-derived NSCs, but lower Nestin and Pax6 expression than both wild-type ESC-derived NSCs (WT-NSCs) and brain-derived NSCs. In addition, compared with WT-NSCs, Dnm1l-/- NSCs exhibited distinct mitochondrial morphology and function, contained more elongated mitochondria, showed reduced mitochondrial respiratory capacity, and showed a metabolic shift toward glycolysis for ATP production. Notably, Dnm1l-/- NSCs exhibited impaired self-renewal ability and accelerated cellular aging during prolonged culture, resulting in decreased proliferation and cell death. Furthermore, Dnm1l-/- NSCs showed elevated levels of inflammation and cell stress markers, suggesting a connection between Dnm1l deficiency and premature aging in NSCs. Therefore, the compromised self-renewal ability and accelerated cellular aging of Dnm1l-/- NSCs may be attributed to mitochondrial fission defects.

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.

Co-introduction of plasmids harbouring the carbapenemase genes, blaNDM-1 and blaOXA-232, increases fitness and virulence of bacterial host.

BACKGROUND: Bacterial isolates with multiple plasmids harbouring different carbapenemase genes have emerged and been identified repeatedly, despite a general notion that plasmids confer fitness cost in bacterial host. In this study, we investigated the effects of plasmids with carbapenemase genes on the fitness and virulence of bacteria. METHODS: Different plasmids harbouring the carbapenemase genes, blaNDM-1 and blaOXA-232, were isolated from a carbapenem-resistant K. pneumoniae strain. Each plasmid was conjugated into the Escherichia coli strain DH5α, and a transconjugant with both plasmids was also obtained by transformation. Their in vitro competitive ability, biofilm formation, serum resistance, survival ability within macrophage and fruit fly, and fly killing ability were evaluated. RESULTS: The transconjugants with a single plasmid showed identical phenotypes to the plasmid-free strain, except that they decreased fly survival after infection. However, significantly increased fitness, virulence and biofilm production were observed consistently for the transconjugant with both plasmids, harbouring blaNDM-1 and blaOXA-232. CONCLUSIONS: Our data indicate that bacteria carrying multiple plasmids encoding different carbapenemases may have increased fitness and virulence, emphasizing the need for diverse strategies to combat antimicrobial resistance.

Evolution of Klebsiella pneumoniae with mucoid and non-mucoid type colonies within a single patient.

We obtained nine Klebsiella pneumoniae isolates successively isolated from a single patient. Four pairs (M1-M4 and NM1-NM4) obtained simultaneously from the same site showed different colony types, mucoid and non-mucoid, while the final isolate (M5) was isolated alone from the blood and showed a mucoid phenotype. The whole genome of isolate M5 was sequenced de novo using the PacBio RSII system, while the others were sequenced with an Illumina Hiseq4000 and mapped to the genome sequences of M5. To identify insertions or deletions in the cps locus, we amplified and sequenced cps locus genes. We identified insertion sequence (IS) elements in several genes of the cps locus or one amino acid substitution in WcaJ in all non-mucoid isolates. Five additional amino acid alterations in RpsJ, LolE, Lon-2, PpsE, and a hypothetical protein were detected in some mucoid and non-mucoid isolates. Based on the genome data and cps locus sequences, the mucoid phenotype may have been lost or converted into the non-mucoid phenotype because of the insertion of IS elements or amino acid alterations at this locus. We inferred a within-host evolutionary scenario, in which non-mucoid variants emerged repeatedly from mucoid isolates, but may be short-lived because of their low fitness.

Plasmid analysis of Escherichia coli isolates from South Korea co-producing NDM-5 and OXA-181 carbapenemases.

Recently, Escherichia coli isolates co-producing New Delhi metallo-ß-lactamase (NDM)-5 and oxacillinase (OXA)-181 were identified in a tertiary-care hospital of South Korea. Isolate CC1702-1 was collected from urine in January 2017 and isolate CC1706-1 was recovered from a transtracheal aspirate of a hospitalized patient in May 2017. Carbapenemase genes were identified by multiplex PCR and sequencing, and whole genome sequencing was performed subsequently using the PacBio RSII system. Both E. coli isolates belonged to the same clone (ST410) and were resistant to all ß-lactams including carbapenems. We obtained whole plasmid sequences of the isolates: pCC1702-NDM-5 from CC1702-1 and pCC1706-NDM-5 and pCC1706-OXA-181 from CC1706-1. The two E. coli isolates belonged to the same clone (ST410) and they were completely resistant to all ß-lactams, as well as carbapenems. Two blaNDM-5-harboring plasmids belonged to the same incompatibility group, IncFIA/B, and consisted of 79,613 bp and 111,890 bp with 87 and 130 coding sequences, respectively. The genetic structures of the two blaNDM-5-bearing plasmids, which were distinct from the blaNDM-5-bearing plasmids from the Klebsiella pneumoniae isolates previously transmitted from the United Arab Emirates (UAE) to South Korea, differed from each other. While pCC1702-NDM-5 showed high degree of identity with the plasmid from a multidrug-resistant isolate of Citrobacter fruendii P5571 found in China, pCC1706-NDM-5 was very similar to the plasmid from a multidrug-resistant isolate of E. coli AMA1176 found in Denmark. pCC1706-OXA-181, which was a 51 kb, self-transmissible IncX3 plasmid, was identical to the E. coli plasmids pAMA1167-OXA-181 from Denmark and pOXA-181-WCHEC14828 from China. Plasmids harboring blaNDM-5 in E. coli isolates might not be transferred from K. pneumoniae isolates co-producing NDM-5 and OXA-181. They probably originated from multiple sources.

Genome characterization of an extensively drug-resistant Streptococcus pneumoniae serotype 11A strain.

In this study, the whole genome sequences of two Streptococcus pneumoniae clinical isolates from South Korea were determined and compared. They were found to be the same serotype (11 A) and multilocus sequence typing analysis showed that they are single-locus variants (SLVs; ST8279 and ST166) of each other, differing at one allele (aroE). However, the ST8279 strain is extensively drug-resistant (XDR) whereas the ST166 strain is not. The genome of the XDR strain is very similar in structure to that of two previously reported genomes, AP200 (11 A:ST62) and 70585 (5:ST5803); however, some regions were inverted and there were some exogenous regions in the ST8279 strain. It was found that 6,502 single nucleotide polymorphisms are dispersed across the genome between the two serotype 11 A ST8279 and ST166 strains. Many of them are located in genes associated with antibiotic resistance. In addition, many amino acid differences were also identified in genes involved in DNA repair (mutL, uvrA and uvrC) and recombination (recU, recR and recA). On the basis of these results, it was inferred that the XDR strain did not evolve from its SLV via a single recombination event involving a large portion of the genome including the aroE gene. Rather, the strain likely evolved through many point mutations and recombination events involving small portions of the genome.

Evaluation of a Carbapenem-Saving Strategy Using Empirical Combination Regimen of Piperacillin-Tazobactam and Amikacin in Hemato-Oncology Patients.

We implemented a carbapenem-saving strategy in hemato-oncology patients from 2013, using an empirical combination of piperacillin-tazobactam and amikacin for high-risk hemato-oncology patients with febrile neutropenia, who remain hemodynamically unstable > 72 hours despite initial cefepime treatment. All-cause mortality was not different between the two periods (6.54 and 6.57 deaths per 1,000 person-day, P = 0.926). Group 2 carbapenem use significantly decreased after strategy implementation (78.43 vs. 67.43 monthly days of therapy, P = 0.018), while carbapenem-resistant gram-negative bacilli did not show meaningful changes during the study period. Our carbapenem-saving strategy could effectively suppress carbapenem use without an increase of overall mortality.

Activity of Ceftolozane-Tazobactam against Carbapenem-Resistant, Non-Carbapenemase-Producing Pseudomonas aeruginosa and Associated Resistance Mechanisms.

Although carbapenems are effective for treating serious multidrug-resistant Pseudomonas aeruginosa infections, carbapenem-resistant P. aeruginosa (CRPA) is now being reported worldwide. Ceftolozane-tazobactam (C/T) demonstrates activity against many multidrug-resistant isolates. We evaluated the activity of C/T and compared its activity to that of ceftazidime-avibactam (C/A) using a well-characterized collection of non-carbapenemase-producing CRPA isolates. Forty-two non-carbapenemase-producing CRPA isolates from a previous study (J. Y. Lee and K. S. Ko, Int J Antimicrob Agents 40:168-172, 2012, https://doi.org/10.1016/j.ijantimicag.2012.04.004) were included. All had been previously shown to be negative for blaIMP, blaVIM, blaSPM, blaGIM, blaSIM, and blaKPC by PCR. In the prior study, expression of oprD, ampC, and several efflux pump genes had been defined by quantitative reverse transcription-PCR. Here, antimicrobial susceptibility was determined by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Time-kill curve assays were performed using three C/T- and C/A-susceptible CRPA isolates. Among 42 non-carbapenemase-producing CRPA isolates, overall susceptibility to C/T was 95.2%, compared to 71.4%, 42.9%, 23.8%, 21.4%, and 2.4% for C/A, ceftazidime, piperacillin-tazobactam, cefepime, and meropenem, respectively. The C/T resistance rate was significantly lower than that of C/A among isolates showing decreased oprD and increased mexB expression (5.1% versus 25.6%, P = 0.025, and 4.3% versus 34.8%, P = 0.022, respectively). In time-kill curve studies, C/T was less bactericidal than C/A against an isolate with decreased oprD and increased ampC expression. C/T was active against 95.2% of non-carbapenemase-producing CRPA clinical isolates. No apparent correlation of C/T MIC values with specific mutation-driven resistance mechanisms was noted.

Emergence of an extensively drug-resistant (XDR) Streptococcus pneumoniae serotype 15A by capsular switching.

Recently, we have identified an extensively drug-resistant (XDR) Streptococcus pneumoniae serotype 15A isolate from a patient with bacterial meningitis. It belonged to sequence type 8279 (ST8279), a clone identified as XDR serotype 11A isolated in South Korea. We obtained and compared the genome sequences of an XDR 15A and an XDR 11A isolate. The genomes of two XDR isolates were highly identical, except for the capsular polysaccharide (cps) locus and another small region. Capsular switching from 11A to 15A may have occurred via recombination of the cps locus. The emergence of a new XDR clone via capsular switching would be a great concern for public health and in clinical settings.

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

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

Factors affecting the public awareness and behavior on antibiotic use.

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

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

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

Antimicrobial Effects of ß-Lactams on Imipenem-Resistant Ceftazidime-Susceptible Pseudomonas aeruginosa.

We studied the resistance mechanism and antimicrobial effects of ß-lactams on imipenem-resistant Pseudomonas aeruginosa isolates that were susceptible to ceftazidime as detected by time-kill curve methods. Among 215 P. aeruginosa isolates from hospitalized patients in eight hospitals in the Republic of Korea, 18 isolates (23.4% of 77 imipenem-resistant isolates) were imipenem resistant and ceftazidime susceptible. Multilocus sequence typing revealed diverse genotypes, which indicated independent emergence. These 18 isolates were negative for carbapenemase genes. All 18 imipenem-resistant ceftazidime-susceptible isolates showed decreased mRNA expression of oprD, and overexpression of mexB was observed in 13 isolates. In contrast, overexpression of ampC, mexD, mexF, or mexY was rarely found. Time-kill curve methods were applied to three selected imipenem-resistant ceftazidime-susceptible isolates at a standard inoculum (5 × 105 CFU/ml) or at a high inoculum (5 × 107 CFU/ml) to evaluate the antimicrobial effects of ß-lactams. Inoculum effects were detected for all three ß-lactam antibiotics, ceftazidime, cefepime, and piperacillin-tazobactam, against all three isolates. The antibiotics had significant killing effects in the standard inoculum, but no effects in the high inoculum were observed. Our results suggest that ß-lactam antibiotics should be used with caution in patients with imipenem-resistant ceftazidime-susceptible P. aeruginosa infection, especially in high-inoculum infections such as endocarditis and osteomyelitis.

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

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

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

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

Genetic alterations responsible for reduced susceptibility to vancomycin in community-associated MRSA strains of ST72.

Objectives: We previously reported the first case of vancomycin treatment failure due to development of vancomycin-intermediate resistance in a patient with an MRSA of ST72, a community genotype in Korea. We investigated two isogenic MRSA strains from this patient, who experienced treatment failure with vancomycin and rifampicin. Methods: We tracked the genetic alterations that confer reduced susceptibility to vancomycin on those two isogenic MRSA strains by WGS. Results: Five non-synonymous mutations were identified, including rpoB (H481Y), dprA (G196C), femA (F92C), vraR (E127K) and agrC (E391stop). We further studied the role of a mutation of vraR in reduced susceptibility to vancomycin. Introduction of the mutated vraR (E127K) into a vancomycin-susceptible Staphylococcus aureus strain resulted in an increase in vraSR mRNA expression and vancomycin MIC and development of the hetero-VISA phenotype, which was confirmed by the population analysis profile (PAP)/AUC. Electron microscopy showed increased cell wall thickness in the strains with mutated vraR. Conclusions: Based on the genomic data, molecular experiments and PAP and cell wall analyses, we propose that a single mutation of vraR is associated with the reduced susceptibility to vancomycin in MRSA and further treatment failure.

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.

Atypical presentations of MERS-CoV infection in immunocompromised hosts.

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

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

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