The impact of discontinuing single-room isolation of patients with vancomycin-resistant enterococci: a quasi-experimental single-centre study in South Korea.

OBJECTIVES: There is limited data on the effects of discontinuing single-room isolation while maintaining contact precautions, such as the use of gowns and gloves. In April 2021, our hospital ceased single-room isolation for patients with vancomycin-resistant enterococci (VRE) because of single-room unavailability. This study assessed the impact of this policy by examining the incidence of hospital-acquired VRE bloodstream infections (HA-VRE BSI). METHODS: This retrospective quasi-experimental study was conducted at a tertiary-care hospital in Seoul, South Korea. Time-series analysis was used to evaluate HA-VRE BSI incidence at the hospital level and in the haematology unit before (phase 1) and after (phase 2) the policy change. RESULTS: At the hospital level, HA-VRE BSI incidence level (VRE BSI per 1000 patient-days per month) and trend did not change significantly between phase 1 and phase 2 (coefficient -0.015, 95% confidence interval (CI): -0.053 to 0.023, P=0.45 and 0.000, 95% CI: -0.002 to 0.002, P=0.84, respectively). Similarly, HA-VRE BSI incidence level and trend in the haematology unit (-0.285, 95% CI: -0.618 to 0.048, P=0.09 and -0.018, 95% CI: -0.036 to 0.000, P = 0.054, respectively) did not change significantly across the two phases. CONCLUSIONS: Discontinuing single-room isolation of VRE-colonized or infected patients was not associated with an increase in the incidence of VRE BSI at the hospital level or among high-risk patients in the haematology unit. Horizontal intervention for multi-drug-resistant organisms, including measures such as enhanced hand hygiene and environmental cleaning, may be more effective at preventing VRE transmission.

Risk of transmission of COVID-19 from healthcare workers returning to work after a 5-day isolation, and kinetics of shedding of viable SARS-CoV-2 variant B.1.1.529 (Omicron).

BACKGROUND: There have been limited data on the risk of onward transmission from individuals with Omicron variant infections who return to work after a 5-day isolation. AIM: To evaluate the risk of transmission from healthcare workers (HCWs) with Omicron variant who returned to work after a 5-day isolation and the viable-virus shedding kinetics. METHODS: This investigation was performed in a tertiary care hospital, Seoul, South Korea. In a secondary transmission study, we retrospectively reviewed the data of HCWs confirmed as COVID-19 from March 14th to April 3rd, 2022 in units with five or more COVID-19-infected HCWs per week. In the viral shedding kinetics study, HCWs with Omicron variant infection who agreed with daily saliva sampling were enrolled between February and March, 2022. FINDINGS: Of the 248 HCWs who were diagnosed with COVID-19 within 5 days of the return of an infected HCW, 18 (7%) had contact with the returned HCW within 1-5 days after their return. Of these, nine (4%) had an epidemiologic link other than with the returning HCW, and nine (4%) had contact with the returning HCW, without any other epidemiologic link. In the study of the kinetics of virus shedding (N = 32), the median time from symptom onset to negative conversion of viable virus was four days (95% confidence interval: 3-5). CONCLUSION: Our data suggest that the residual risk of virus transmission after 5 days of isolation following diagnosis or symptom onset is low.

Extensive severe fever with thrombocytopenia syndrome virus contamination in surrounding environment in patient rooms.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease in Korea and China. Although there is previous evidence of person-to-person transmission via direct contact with body fluids, the role of environmental contamination by SFTS virus (SFTSV) in healthcare settings has not been established. We therefore investigated the contamination of the healthcare environment by SFTSV. METHODS: We investigated the possible contamination of hospital air and surfaces with SFTSV transmission by collecting air and swabbing environmental surface samples in two hospitals treating six SFTS patients between March and September 2017. The samples were tested using real-time RT-PCR for SFTS M and S segments. RESULTS: Of the six SFTS patients, four received mechanical ventilation and three died. Five rooms were occupied by those using mechanical ventilation or total plasma exchange therapy in isolation rooms without negative pressure and one room was occupied by a patient bedridden due to SFTS. SFTSV was detected in 14 (21%) of 67 swab samples. Five of 24 swab samples were obtained from fomites including stethoscopes, and 9 of 43 were obtained from fixed structures including doorknobs and bed guardrails. Some samples from fixed structures such as television monitors and sink tables were obtained in areas remote from the patients. SFTSV RNA was not detected in five air samples from three patients' rooms. CONCLUSIONS: Our data suggest that SFTSV contamination was extensive in surrounding environments in SFTS patients' rooms. Therefore, more strict isolation methods and disinfecting procedures should be considered when managing SFTS patients.

Severe fever with thrombocytopenia syndrome-associated encephalopathy/encephalitis.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) virus has a variety of central nervous system (CNS) manifestations. However, there are limited data regarding SFTS-associated encephalopathy/encephalitis (SFTSAE) and its mechanism. METHODS: All patients with confirmed SFTS who underwent cerebrospinal fluid (CSF) examination due to suspected acute encephalopathy were enrolled in three referral hospitals between January 2013 and October 2016. Real-time RT-PCR for SFTS virus and chemokine/cytokines levels from blood and CSF were analysed. RESULTS: Of 41 patients with confirmed SFTS by RT-PCR for SFTS virus using blood samples, 14 (34%) underwent CSF examination due to suspected SFTSAE. All 14 patients with SFTSE revealed normal protein and glucose levels in CSF, and CSF pleocytosis was uncommon (29%, 4/14). Of the eight patients whose CSF was available for further analysis, six (75%) yielded positive results for SFTS virus. Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) level in CSF were significantly higher than those in serum (geometric mean 1889 pg/mL in CSF versus 264 pg/mL in serum for MCP-1, p = 0.01, and geometric mean 340 pg/mL in CSF versus 71 pg/mL in serum for IL-8, p = 0.004). CONCLUSIONS: The CNS manifestation of SFTS as acute encephalopathy/encephalitis is a common complication of SFTS. Although meningeal inflammation was infrequent in patients with SFTSAE, SFTS virus was frequently detected in CSF with elevated MCP-1 and IL-8. These findings indicate that possible direct invasion of the CNS by SFTS virus with the associated elevated cytokine levels in CSF may play an important role in the pathogenesis of SFTSAE.

Molecular epidemiology and environmental contamination during an outbreak of parainfluenza virus 3 in a haematology ward.

BACKGROUND: Although fomites or contaminated surfaces have been considered as transmission routes, the role of environmental contamination by human parainfluenza virus type 3 (hPIV-3) in healthcare settings is not established. AIM: To describe an hPIV-3 nosocomial outbreak and the results of environmental sampling to elucidate the source of nosocomial transmission and the role of environmental contamination. METHODS: During an hPIV-3 outbreak between May and June 2016, environmental surfaces in contact with clustered patients were swabbed and respiratory specimens used from infected patients and epidemiologically unlinked controls. The epidemiologic relatedness of hPIV-3 strains was investigated by sequencing of the haemagglutinin-neuraminidase and fusion protein genes. FINDINGS: Of 19 hPIV-3-infected patients, eight were haematopoietic stem cell recipients and one was a healthcare worker. In addition, four had upper and 12 had lower respiratory tract infections. Of the 19 patients, six (32%) were community-onset infections (symptom onset within <7 days of hospitalization) and 13 (68%) were hospital-onset infections (≥7 days of hospitalization). Phylogenetic analysis identified two major clusters: five patients, and three patients plus one healthcare worker. Therefore, seven (37%) were classified as nosocomial transmissions. hPIV-3 was detected in 21 (43%) of 49 environmental swabs up to 12 days after negative respiratory polymerase chain reaction conversion. CONCLUSION: At least one-third of a peak season nosocomial hPIV-3 outbreak originated from nosocomial transmission, with multiple importations of hPIV-3 from the community, providing experimental evidence for extensive environmental hPIV-3 contamination. Direct contact with the contaminated surfaces and fomites or indirect transmission from infected healthcare workers could be responsible for nosocomial transmission.

Phenotypic changes of methicillin-resistant Staphylococcus aureus during vancomycin therapy for persistent bacteraemia and related clinical outcome.

Persistent bacteraemia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) that fails to respond to glycopeptide therapy is a well-documented clinical problem. There are limited data on changes in agr functionality, vancomycin susceptibility and heteroresistance during MRSA PB. Thus, the frequency of these changes and their clinical significance remain unclear. Only patients with MRSA PB (≥7 days) from a prospective cohort of S. aureus bacteraemia were included. We collected isogenic paired strains and compared vancomycin MIC, vancomycin heteroresistance, and agr functionality between initial and final blood isolates. We also assessed the clinical outcome. A total of 49 patients had MRSA PB over 22 months. Bacteraemia persisted for a median of 13 days and most patients (98%) received glycopeptide as initial therapy. Among 49 isogenic pairs, only one pair showed a vancomycin MIC increase ≥2-fold by broth microdilution method, and only seven (14%) by E-test. Significant portions of initial isolates had vancomycin heteroresistance (49%) and agr dysfunction (76%). Development of vancomycin heteroresistance during PB occurred in four (16%) among 25 initial vancomycin-susceptible isolates, and acquisition of agr dysfunction occurred in two (16%) among 12 initial agr-functional isolates. Changes in the opposite direction occasionally occurred. These phenotypic changes during PB were not associated with mortality, whereas agr dysfunction of the initial isolates was significantly associated with mortality. During MRSA PB, phenotypic changes of MRSA isolates occurred occasionally under prolonged vancomycin exposure but were not significantly associated with clinical outcome. In contrast, initial agr dysfunction could be a predictor for mortality in MRSA PB.

Emergence of Panton-Valentine leucocidin-positive ST8-methicillin-resistant Staphylococcus aureus (USA300 clone) in Korea causing healthcare-associated and hospital-acquired bacteraemia.

Panton-Valentine leucocidin (PVL)-positive sequence type (ST)8-MRSA-SCCmec IVa (USA300) is the epidemic strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in North America. USA300 is extremely rare in South Korea, and PVL-negative ST72 SCCmec type IVc is the predominant CA-MRSA clone. In a multicentre, prospective cohort study of S. aureus bacteraemia, we identified PVL-positive ST8-MRSA isolates by performing multilocus sequence typing and PCR for PVL. We analyzed the clinical characteristics of patients with PVL-positive ST8-MRSA bacteraemia, and performed SCCmec, spa, and agr typing, PCR for arginine catabolic mobile element (ACME), virulence gene profiling, and pulsed-field gel electrophoresis (PFGE). Among a total of 818 MRSA isolates, we identified ten isolates of PVL-positive ST8-MRSA (USA300) (3 from Hospital D, 4 from Hospital G, and 3 from Hospital A), all of which involved exclusively healthcare-associated (5 isolates) and hospital-acquired bacteraemia (5 isolates). This strain accounted for 8~10 % of the hospital-acquired MRSA bacteraemia in Hospitals D and G. Bacteraemia of unknown origin was the most common type of infection followed by pneumonia. All the isolates were SCCmec type IVa, spa type t008, and agr group I. Eight of the isolates harboured ACME. In a PFGE analysis, four isolates were identical to the USA300 control strain, five differed by a single band, and the remaining one differed by two bands. All the isolates were pulsed-field type USA300. This is the first report of healthcare-associated and hospital-acquired bacteraemia caused by USA300 in South Korea. USA300 seems to be an emerging hospital clone in this country.

Late paradoxical lymph node enlargement during and after anti-tuberculosis treatment in non-HIV-infected patients.

SETTINGS: A tertiary referral centre in South Korea. OBJECTIVE: To investigate the incidence, clinical characteristics and outcomes of late paradoxical response (>4 months after the initiation of anti-tuberculosis treatment) during and after anti-tuberculosis treatment in non-human immunodeficiency virus (HIV) infected patients with lymph node tuberculosis (TB). DESIGN: We retrospectively reviewed the medical records of non-HIV-infected patients with lymph node TB between 1997 and 2007, and prospectively enrolled patients with newly diagnosed lymph node TB between 2008 and 2013. RESULTS: Of 467 patients with confirmed and probable lymph node TB, 83 (18%) displayed a paradoxical response: 57 of these (69%) were classified as early and 26 (31%) as late paradoxical response. Patients with late paradoxical response (median 12 months) received more prolonged anti-tuberculosis treatment than those with early (median 9 months, P < 0.001) or no paradoxical response (median 9 months, P < 0.001). The frequency of post-treatment lymph node enlargement increased progressively from those without any paradoxical response (6%), through those with an early response (12%) to those with a late response (23%). CONCLUSIONS: Paradoxical response presents late in about one third of non-HIV-infected patients with lymph node TB who experience a response. Although anti-tuberculosis treatment is commonly prolonged in patients with late paradoxical response, post-treatment lymph node enlargement is more frequent in these patients.

Comparison of the clinical characteristics of Mycobacterium tuberculosis and nontuberculous mycobacteria patients with joint involvement.

Nontuberculous mycobacteria (NTM) joint involvement is rare. However, the incidence of NTM disease is increasing and it is difficult to distinguish NTM from Mycobacterium tuberculosis (MTB). Here, the clinical characteristics of NTM joint involvement were compared with those of MTB. Distal joint involvement and precipitating factors were significantly more frequent for NTM joint infections. Because pathologic findings of NTM and MTB were similar, microbiological investigations are needed.

Prevalence of blaZ gene types and the cefazolin inoculum effect among methicillin-susceptible Staphylococcus aureus blood isolates and their association with multilocus sequence types and clinical outcome.

Cefazolin treatment failures have been described for bacteraemia caused by methicillin-susceptible Staphylococcus aureus (MSSA) with type A ß-lactamase and inoculum effect (InE). We investigated the prevalence of blaZ (ß-lactamase) gene types and a cefazolin InE among MSSA blood isolates in South Korea and evaluated their association with specific genotypes. The clinical impact of the cefazolin InE was also evaluated. A total of 220 MSSA isolates were collected from a prospective cohort study of S. aureus bacteraemia. A pronounced InE with cefazolin was defined as a ≥4-fold increase in the minimum inhibitory concentration (MIC) between a standard and high inoculum, resulting in a non-susceptible MIC. Sequencing of blaZ and multilocus sequence typing (MLST) were performed. Clinical outcomes were assessed in 77 patients treated with cefazolin. The blaZ gene was detected in 92 % of the 220 MSSA isolates. Type C ß-lactamase was the most common (53 %), followed by type B (20 %) and type A (17 %). Certain genotypes were significantly associated with specific ß-lactamase types (notably, ST30 and type A ß-lactamase). A pronounced cefazolin InE was observed in 13 % of isolates. Most of these (79 %) expressed type A ß-lactamase and ST30 was the predominant (55 %) clone amongst them. Cefazolin treatment failure was not observed in patients infected with strains exhibiting a pronounced InE. These strains had no impact on other clinical outcomes. In conclusion, the prevalence of a pronounced InE with cefazolin could be dependent upon distributions of MSSA genotypes. Cefazolin can likely be used for the treatment of MSSA bacteraemia (except endocarditis), without consideration of an InE.

Exploration of optimal dosing regimens of vancomycin in patients infected with methicillin-resistant Staphylococcus aureus by modeling and simulation.

WHAT IS KNOWN AND OBJECTIVE: Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus (MRSA) infection and shows time-dependent bacterial killing. The current study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of vancomycin and explored its optimal dosing regimens by modeling and simulation. METHODS: Pharmacokinetics study was performed for 20 patients who were treated with vancomycin intravenously, 1000 mg, every 12 h, and blood for PK was randomly drawn within prespecified time windows. PD study was in vitro time-kill experiment for vancomycin against 20 MRSA strains independent of the PK study, where bacterial titre was measured at 0, 2, 4, 8, 24 h after the beginning of vancomycin exposure at 0, 1, 2, 4, 8, 16, 32× minimum inhibitory concentrations. PK and PD models were built from each data set, and simulation for MRSA titre changes over time in human body was performed for various vancomycin dosing regimens using NONMEM(®) . RESULTS: Vancomycin followed a two-compartment PK model, and creatinine clearance was the significant covariate affecting the clearance of vancomycin. PD model described the in vitro time-kill data well. The PK/PD model predicted clear dose-response relationships of vancomycin. The therapeutic dosing regimens of vancomycin, suggested by the simulation studies, showed good agreement with the current clinical practice guidance, which indicates that this PK/PD modeling and simulation approach could prove useful for identifying optimal dosing regimens of other antibiotics and expediting novel antibiotic development. Using PD model from in vitro time-kill study and human PK model from phase 1 study, we could predict whether the drug is going to be efficacious or obtain insight into the optimal dosing regimens for a novel antibiotic agent in the early phases of drug development process.

agr Dysfunction and persistent methicillin-resistant Staphylococcus aureus bacteremia in patients with removed eradicable foci.

PURPOSE: Persistent Staphylococcus aureus bacteremia (SAB) has been observed in patients with eradicated foci, but there are few studies of the risk factors and clinical outcomes of persistent bacteremia. This study determined the risk factors for persistent methicillin-resistant S. aureus (MRSA) bacteremia in patients without retained eradicable foci, including genotypic characteristics. METHODS: All adult SAB patients were investigated between 2008 and 2010. Persistent bacteremia was defined as bacteremia lasting >7 days after treatment and patients were monitored prospectively. The study included patients without retained eradicable foci, e.g., removed prosthetic devices and intravenous catheters removed after diagnosis, and those without metastatic infections. RESULTS: Persistent bacteremia occurred in 36 % (31/87) SAB patients with eradicated foci. There were no significant differences in successful defervescence (2.0 vs. 2.0 days, P = 0.55) and total length of hospital stay after bacteremia in the persistent bacteremia group and resolved bacteremia group (P = 0.32). The difference in MRSA bacteremia-related 30-day mortality with persistent bacteremia and resolved bacteremia was not significant (P = 0.12). However, agr dysfunction was higher in persistent bacteremia patients (94 %) than those with resolved bacteremia (75 %, P = 0.03). Multivariate analysis using a logistic regression model found that only agr dysfunction [odds ratio (OR) 4.83, 95 % confidence interval (CI) 1.02-22.89, P = 0.04] was an independent risk factor for persistent bacteremia. CONCLUSIONS: This study suggests that persistent bacteremia with eradicated foci might not adversely affect the outcome for MRSA bacteremia patients. agr dysfunction in S. aureus was significantly associated with persistent bacteremia.

Clinical significance of Staphylococcus aureus bacteremia in patients with liver cirrhosis.

Patients with liver cirrhosis (LC) have impaired immunity and thus are predisposed to infections. Few studies have attempted to evaluate Staphylococcus aureus bacteremia (SAB) in LC patients. Therefore, this study prospectively evaluated the clinical characteristics and outcomes of 642 episodes of SAB from August 1, 2008 to September 31, 2010. Of 642 patients with SAB, 109 (17.0 %) were classified as LC patients whereas the remaining 533 (83.0 %) were classified as non-LC patients. The 30-day mortality rate of LC patients was significantly higher than that of patients with other diseases (32 % vs. 22 %, respectively; P = 0.047). The 30-day mortality rates of patients with MSSA bacteremia and MRSA bacteremia were not significantly different among LC patients (35.1 % with MSSA vs. 26.9 % with MRSA; P = 0.41). A univariate analysis of the 30-day mortality rate of LC patients with SAB for survivors and non-survivors showed that rapidly fatal or ultimately fatal according to the criteria of McCabe and Jackson (OR 5.0; 95 % CI 1.60-15.65), septic shock at initial presentation (OR 3.5; 95 % CI 1.18-10.39) and Child-Pugh class C (OR 2.8; 95 % CI 1.20-6.59) were associated with increased mortality. In contrast, the removal of the eradicable focus was associated with decreased mortality (OR 0.14; 95 % CI 0.04-0.52). Disease severity and liver dysfunction may be useful for predicting the prognosis of SAB in LC patients.

Enterococcus avium bacteremia: a 12-year clinical experience with 53 patients.

Because Enterococcus avium is rarely isolated from blood cultures, little is known about the clinical features and outcomes of bacteremia caused by this organism, formerly called "group Q streptococcus". We retrospectively evaluated the clinical features and outcomes of patients with clinically significant bacteremia caused by E. avium presenting at a tertiary-care hospital in Korea between February 1997 and February 2009. We identified 53 patients over the 12-year period; of these, 27 (50.9%) had biliary and 13 (24.5%) had intra-abdominal E. avium infections. Thirty-six (67.9%) of the episodes were polymicrobial. Thirty-three (62.3%) episodes were nosocomial bloodstream infections and resistance to vancomycin was not observed. The crude mortality rate was 24.5% (13/53), and the E. avium bacteremia-related mortality rate was 11.3% (6/53). Multivariate analysis showed that underlying rapidly fatal or ultimately fatal disease (adjusted odds ratio [AOR], 6.92; 95% confidence interval [CI], 1.56-30.65; P = 0.011) and inadequate antimicrobial therapy (AOR, 7.29; CI, 1.27-41.93; P = 0.026) were independent risk factors for mortality. In summary, bacteremia due to E. avium was commonly of biliary or intraabdominal origin and was often associated with polymicrobial bacteremia. The crude mortality rate was considerable. Severe underlying conditions and inadequate antimicrobial therapy were significant and independent risk factors for crude patient mortality.

Development of bacteraemia or fungaemia after removal of colonized central venous catheters in patients with negative concomitant blood cultures.

There are limited data on the clinical significance of positive central venous catheter (CVC) tip cultures associated with concomitant negative blood cultures performed at the time of CVC removal. A retrospective cohort study of all patients who yielded isolated positive CVC tip cultures was conducted in a tertiary-care hospital with 2200 beds during a 10-year period. All patients with isolated positive CVC tip cultures were observed for the development of subsequent bacteraemia or fungaemia between 2 and 28 days after CVC removal. An isolated positive CVC tip culture was defined as a case in which (i) a CVC tip culture yielded > or = 15 colonies using a semiquantitative culture method and (ii) at least two sets of blood samples revealed no organism at, or close to, the time of CVC removal (48 h before to 48 h after CVC removal). During the study period, 312 patients with isolated positive CVC cultures were enrolled. Eight (2.6%; 95% CI 1.2-5.1) of the 312 patients yielding isolated bacterial or fungal CVC tip cultures developed subsequent bloodstream infection (BSI) caused by the same species as that isolated from the tip culture (Staphylococcus aureus, 1: Enterococcus spp.; 2: Pseudomonas aeruginosa; and 3: Candida spp.). Among 125 patients from whose CVC tips the above four organisms were grown, seven (12.3%) of 57 patients who did not receive appropriate antibiotic therapy within 48 h after CVC removal subsequently developed BSI, but only one (1.5%) of 68 patients who did receive appropriate therapy developed BSI (OR 0.11, p 0.02).