Effects of sub-inhibitory concentrations of nafcillin, vancomycin, ciprofloxacin, and rifampin on biofilm formation of clinical methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are often difficult to treat because of their biofilm-forming ability and antimicrobial resistance. We investigated the effects of sub-minimal inhibitory concentrations (MICs) of antibiotics on MRSA biofilm formation. Clinical MRSA isolates were grown with sub-MICs (1/256-1/2 × MICs) of nafcillin, vancomycin, ciprofloxacin, and rifampin. The biofilm biomass was measured using crystal violet staining. Of the 107 MRSA isolates tested, 63 (58.9%) belonged to sequence type 5 (ST5), and 44 (41.1%) belonged to ST72. The MIC50/MIC90 values of nafcillin, vancomycin, ciprofloxacin, and rifampin were 256/512, 1/2, 64/512, and 0.008/0.03 mg/L, respectively. The sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin promoted biofilm formation in 75 (70.1%), 49 (45.8%), 89 (83.2%), and 89 (83.2%) isolates, respectively. At sub-MICs of nafcillin, the factors associated with strong biofilm induction were the ST5 strain (P = 0.001) and agr dysfunction (P = 0.005). For the sub-MICs of ciprofloxacin, the associated factors were the ST5 strain (P = 0.002), staphylococcal protein A type t002 strain (P < 0.001), and ciprofloxacin resistance (P < 0.001). Among the sub-MICs of rifampin, only ST5 was associated with strong biofilm induction (P = 0.006). Because the sub-MICs of rifampin were much lower than clinically relevant concentrations, we further tested the capability of biofilm induction in 0.03[Formula: see text]32 mg/L of rifampin. At these concentrations, rifampin-induced biofilm formation was rare in rifampin-susceptible MRSA [1.0% (1 of 100)] but common in rifampin-resistant MRSA [71.4% (5 of 7), P < 0.001]. Induction of biofilm biomass at sub-MICs of antibiotics is common in clinical MRSA isolates and is differentially affected by the MRSA strain and antibiotic class. IMPORTANCE: Bacteria can be exposed to sub-MICs of antibiotics at the beginning and end of a dosing regimen, between doses, or during low-dose therapies. Growing evidence suggests that sub-MICs of antimicrobials can stimulate MRSA biofilm formation and alter the composition of the biofilm matrix. Pevious studies have found that sub-MICs of oxacillin, methicillin, and amoxicillin promote biofilm formation in some community-acquired MRSA (CA-MRSA). We evaluated biofilm induction by sub-MICs of four different classes of antibiotics in 44 CA-MRSA and 63 healthcare-associated MRSA (HA-MRSA) strains. Our study indicated that sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin frequently promote biofilm induction in clinical MRSA isolates. Strong biofilm induction in sub-MICs of nafcillin, ciprofloxacin, and rifampin was more frequent in HA-MRSA than in CA-MRSA. Antibiotic-induced biofilm formation depends on the antibiotic class, MRSA strain, and antibiotic resistance. Our results emphasize the importance of maintaining effective bactericidal concentrations of antibiotics to treat biofilm-related infections.

Community-Acquired Pneumococcal Pneumonia in Highly Vaccinated Population: Analysis by Serotypes, Vaccination Status, and Underlying Medical Conditions.

BACKGROUND: Targeted risk population has been highly vaccinated against pneumococcal diseases in South Korea. Despite this, the pneumococcal serotype distribution is evolving, which impedes efficient roll-out of vaccines. METHODS: This prospective cohort study included patients aged ≥ 19 years with community-acquired pneumonia (CAP) from five university hospitals in South Korea between September 2018 and July 2021. The outcomes of interest were the demographic and clinical characteristics of patients with CAP, pneumococcal serotype distribution, and risk factors of 30-day mortality in patients with pneumococcal CAP (pCAP). Considering the high seroprevalence, we analyzed the clinical characteristics of serotype 3 pCAP. RESULTS: A total of 5,009 patients hospitalized with CAP was included (mean age ± standard deviation, 70.3 ± 16.0 years; 3,159 [63.1%] men). Streptococcus pneumoniae was the leading causative agent of CAP (11.8% overall, 17.7% in individuals aged < 65 years with chronic medical conditions). Among the 280 serotyped Streptococcus pneumococcus, serotype 3 was the most common (10.0%), followed by serotypes 19A (8.9%), 34 (8.9%), and 35B (8.9%). Non-vaccine serotypes (serotype 35B [13.9%] and 34 [12.0%]) were the most prevalent in 108 individuals vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23). Serotype 3 was prevalent, irrespective of PPSV23 vaccination status, and more common in individuals with chronic lung disease (P = 0.008). Advanced age (adjusted odds ratio [aOR], 1.040; 95% confidence interval [CI], 1.011-1.071), long-term care facility residence (aOR, 2.161; 95% CI, 1.071-4.357), and bacteremia (aOR, 4.193; 95% CI, 1.604-10.962) were independent risk factors for 30-day mortality in patients with pCAP. PPSV23 vaccination reduced the risk of mortality (aOR, 0.507; 95% CI, 0.267-0.961). CONCLUSION: Serotype 3 and 19A were still the most common serotypes of pCAP in South Korea despite the national immunization program of 13-valent pneumococcal conjugated vaccine in children and PPSV23 in old adults. PPSV23 vaccination might reduce the risk of mortality in patients with pCAP.

Fatal Primary Amebic Meningoencephalitis due to Naegleria fowleri: The First Imported Case in Korea.

Primary amebic meningoencephalitis (PAM) is a rare, but almost always fatal, central nervous system infection caused by Naegleria fowleri, which are thermophilic free-living amoeba. Here, we report the first case of PAM detected in South Korea, probably imported from Thailand. Despite antimicrobial treatment for N. fowleri infection with a combination of intravenous liposomal amphotericin B, fluconazole, azithromycin, and oral rifampin, the patient died 13 days after the onset of symptoms. Clinicians in South Korea treating severe meningoencephalitis, especially in individuals returning from tropical areas, are encouraged to include PAM in the differential diagnoses, given the accelerated global warming and increased overseas trips.

Persistent Pneumonic Consolidations due to Secondary Organizing Pneumonia in a Patient Recovering from COVID-19 Pneumonia: A Case Report and Literature Review.

In patients recovering from coronavirus disease 2019 (COVID-19) pneumonia, respiratory symptoms and radiographic pneumonic infiltrate occasionally persist for many weeks even after viral clearance; thereby, making it difficult to decide on an appropriate treatment. Here, we describe a 46-year-old woman with COVID-19 pneumonia who had persistent radiographic pneumonic infiltration and respiratory symptoms for almost 4 weeks after illness onset, despite viral clearance, and was subsequently diagnosed with secondary organizing pneumonia (SOP) using video-assisted thoracoscopic (VATS) wedge lung biopsy. Intravenous methylprednisolone was administered at an initial dose of 50 mg/day (1 mg/kg) for 7 days and was tapered to a dose of prednisolone 30 mg/day following improvement in the patient's respiratory symptoms and chest radiographic findings. The patient was discharged from the hospital 14 days after the initiation of corticosteroid treatment. The dose of prednisolone was tapered monthly to 20, 15, 10, and 5 mg/day, respectively, at the outpatient clinic for a total duration of 6 months; nearly resolved pneumonic infiltrations were observed in a follow-up computed tomography scan approximately 2 months after she was admitted. To the best of our knowledge, this is the first case report of a COVID-19 associated SOP that was pathologically confirmed through VATS wedge lung biopsy in Korea. SOP should be considered in the differential diagnosis of patients with COVID-19 pneumonia with persistent respiratory symptoms and radiographic pneumonic infiltrations during the recovery phase to avoid the redundant use of antimicrobial or antiviral agents. Furthermore, histological confirmation is essential for the definitive diagnosis of SOP to avoid unnecessarily prolonged corticosteroid treatment.

Real World Experience with Regdanvimab Treatment of Mild-to-Moderate Coronavirus Disease-19 in a COVID-19 Designated Hospital of Korea.

BACKGROUND: Real-world clinical data concerning regdanvimab, a monoclonal antibody treatment for patients with mild-to-moderate coronavirus disease 2019 (COVID-19), are urgently needed. Here, we describe our experience with regdanvimab. MATERIALS AND METHODS: This retrospective cohort study enrolled high-risk adults with mild-to-moderate COVID-19 who were admitted to a dedicated COVID-19 hospital in Korea from March to September 2021. We used multiple logistic regression and propensity score-matching to compare the outcomes of patients who did or did not receive regdanvimab. The primary outcome was in-hospital progression to severe or critical status, or death. RESULTS: Of 586 patients eligible for regdanvimab, 256 patients who received regdanvimab and 251 untreated patients were included. The median age was 66 years and 47.5% were men. The most common underlying illnesses were hypertension (53.8%) and diabetes (36.9%). Patients were admitted to the hospital at a median of 2 days after symptom onset; regdanvimab was administered at a median of 3 days after symptom onset. Multivariate analysis indicated that regdanvimab significantly reduced the risk of disease progression during hospitalization [odds ratio (OR): 0.285; 95% confidence interval (CI): 0.144 - 0.564]. In a 1:1 propensity score-matched cohort (172 patients in either group), regdanvimab also decreased the risk of progression (OR: 0.162; 95% CI: 0.068 - 0.386). CONCLUSION: In high-risk patients with mild-to-moderate COVID-19, regdanvimab decreased the risk of progression to severe COVID-19.

Persistent serotype 3 and 19A invasive pneumococcal diseases in adults in vaccine era: Serotype-dependent difference in ceftriaxone susceptibility.

BACKGROUND: Invasive pneumococcal disease (IPD) is associated with substantial morbidity and mortality in children and elderly populations. Serotype distribution and antibiotic susceptibility of IPD isolates are changing with the implementation of pneumococcal vaccination and increasing antibiotic use worldwide. We aimed to determine serotype distribution, antibiogram, and molecular epidemiology of pneumococci in the late stage of PCV13 era. METHODS: Prospective multicenter IPD surveillance study was conducted for adults aged ≥ 19 years from July 2019 to June 2021. Clinical and epidemiologic data were collected. In addition, antibiotic susceptibility test, serotype identification and multi-locus sequence typing (MLST) was taken for pneumococcal isolates. RESULTS: A total of 160 IPD cases were collected with mean age of 65.1 years (male, 72.5%). Serotyping was taken for 116 available pneumococcal isolates. PCV13 and PPSV23 serotypes were 32.8% (n = 38) and 56.0% (n = 65), respectively. Serotype 3 (13.8%) and 19A (9.5%) were the most common causative agents of IPD, followed by serogroup 11 (6.9%), 23A (6.9%), 10A (4.3%), and 15B (4.3%). Notably, 32.5% of invasive pneumococcal isolates were non-susceptible to ceftriaxone. Serotypes 11A, 11E and 19A pneumococci showed high ceftriaxone non-susceptible rate (80%, 100% and 81.8% respectively), and they were related to sequence type (ST) 166 and ST320. In comparison, most serotype 3 isolates were ceftriaxone susceptible and related to ST180. CONCLUSIONS: PCV serotypes, especially 3 and 19A, are still prevalent in adult IPDs, suggesting that individual PCV13 immunization would be necessary for the elderly people and chronically ill patients. Ceftriaxone non-susceptible rate was remarkably high in invasive pneumococcal isolates.

In vitro activity of ceftazidime-avibactam and comparators against bacterial isolates collected in South Korea as part of the ATLAS global surveillance program (2016-2018).

Overall, 1,277 Enterobacterales and 296 P. aeruginosa isolates were collected in South Korea between 2016 and 2018. Rates of susceptibility were >95% to ceftazidime-avibactam, tigecycline, meropenem and amikacin among the Enterobacterales and of the P. aeruginosa collected, 92.9% were susceptibility to amikacin and 92.6% to ceftazidime-avibactam.

Clinical Features of Adult COVID-19 Patients without Risk Factors before and after the Nationwide SARS-CoV-2 B.1.617.2 (Delta)-variant Outbreak in Korea: Experience from Gyeongsangnam-do.

BACKGROUND: Data on severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) delta variant virulence are insufficient. We retrospectively compared the clinical features of adult coronavirus disease 2019 (COVID-19) patients without risk factors for severe COVID-19 who entered residential treatment centers (RTCs) before and after the delta variant outbreak. METHODS: We collected medical information from two RTCs in South Korea. On the basis of nationwide delta variant surveillance, we divided the patients into two groups: 1) the delta-minor group (diagnosed from December 2020-June 2021, detection rate < 10%) and 2) the delta-dominant group (diagnosed during August 2021, detection rate > 90%). After propensity-score matching, the incidences of pneumonia, hospital transfer and need for supplemental oxygen were compared between the groups. In addition, risk factors for hospital transfer were analysed. RESULTS: A total of 1,915 patients were included. The incidence of pneumonia (14.6% vs. 9.2%, P = 0.009), all-cause hospital transfer (10.4% vs. 6.3%, P = 0.020) and COVID-19-related hospital transfer (7.5% vs. 4.8%, P = 0.081) were higher in the delta-dominant group than those in the delta-minor group. In the multivariate analysis, the delta-dominant group was an independent risk factor for all-cause (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.16-3.13; P = 0.011) and COVID-19-related hospital transfer (aOR, 1.86; 95% CI, 1.04-3.32; P = 0.036). CONCLUSION: Hospitalization rates were increased in the adult COVID-19 patients during the delta variant nationwide outbreak. Our results showed that the delta variant may be more virulent than previous lineages.

Treatment effect of nafamostat mesylate in patients with COVID-19 pneumonia: study protocol for a randomized controlled trial.

BACKGROUND: This study is designed to evaluate the main hypothesis that nafamostat mesilate with standard therapy improves the severity and mortality rate in patients with COVID-19 pneumonia. METHODS: We conduct a randomized, open type, multi-institute/center, 2-group clinical trial with COVID-19 pneumonia patients in Korea. Eighty four patients with COVID-19 pneumonia are randomly assigned to intervention group or control group. Patients in intervention group receive the standard therapy with a dose of 0.1 to 0.2 mg/kg/h (2.4 to 4.8 mg/kg/day) of nafamostat mesilate. Patients in control group receive the standard therapy such as lopinavir/ritonavir, hydroxychloroquine, oxygen therapy, non-invasive and invasive ventilator, antibiotic therapy, renal-replacement therapy, and extracorporeal membrane oxygenation (ECMO). The primary outcome is proportion of patients with clinical improvement as defined by live discharge from hospital or a decline of 2 categories on the seven-category ordinal scale of clinical status, as well as secondary outcome comprised change in National Early Warning Score, duration of hospitalization, incidence of new-non-invasive ventilation or high flow oxygen use or ventilator, mortality at day 28, viral load change, and adverse events. DISCUSSION: Our study contributes to the establishment of therapeutic strategy in COVID-19 pneumonia by evaluating the therapeutic effect and safety of nafamostat mesilate. TRIAL REGISTRATION: ClinicalTrials.gov NCT04418128. Registered on 5 June 2020.

Effects of steroid therapy in patients with severe fever with Thrombocytopenia syndrome: A multicenter clinical cohort study.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS. METHODS: A retrospective study was performed in a multicenter SFTS clinical cohort from 13 Korean university hospitals between 2013 and 2017. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests. RESULTS: Overall fatality rate was 23.2%, with 39.7% among 58 patients who underwent steroid therapy. Complications were observed in 37/58 (63.8%) and 25/83 (30.1%) patients in the steroid and non-steroid groups, respectively (P < .001). Survival analysis after propensity score matching showed a significant difference in mean 30-day survival time between the non-steroid and steroid groups in patients with a mild condition [Acute Physiology and Chronic Health Evaluation II (APACHE II) score <14; 29.2 (95% CI 27.70-30.73] vs. 24.9 (95% CI 21.21-28.53], P = .022]. Survival times for the early steroid (≤5 days from the start of therapy after symptom onset), late steroid (>5 days), and non-steroid groups, were 18.4, 22.4, and 27.3 days, respectively (P = .005). CONCLUSIONS: After steroid therapy, an increase in complications was observed among patients with SFTS. Steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score <14).

Differences in Clinical Characteristics and Chest Images between Coronavirus Disease 2019 and Influenza-Associated Pneumonia.

BACKGROUND: Concerns are arising about the simultaneous occurrence of the coronavirus disease 2019 (COVID-19) pandemic and the influenza epidemic, the so-called "twindemic". In this study, we compared clinical characteristics and chest images from patients with COVID-19 and influenza. METHODS: We conducted a case-control study of COVID-19 and age- and sex-matched influenza patients. Clinical characteristics and chest imaging findings between patients with COVID-19 and matched influenza patient controls were compared. RESULTS: A total of 47 patients were enrolled in each group. Anosmia (14.9%) and ageusia (21.3%) were only observed in COVID-19 patients. There were 31 (66%) and 23 (48.9%) patients with COVID-19 and influenza who had pulmonary lesions confirmed by chest computed tomography (CT), respectively. The interval between symptom onset and pneumonia was significantly longer in patients with COVID-19. Round opacities were more common in images from COVID-19 patients (41.9% vs. 8.7%, p = 0.007), whereas pure consolidation (0% vs. 34.9%, p < 0.001) and pleural effusion (0% vs. 17.4%, p = 0.028) were more common in images from influenza patients. Notably, the difference in the number of involved pulmonary lobes observed on CT and pulmonary fields observed on radiographic images was significantly higher in COVID-19-associated pneumonia than that in influenza-associated pneumonia (2.32 ± 1.14 vs. 1.48 ± 0.99, p = 0.010). CONCLUSIONS: Chest images and thorough review of clinical findings could provide value for proper differential diagnoses of COVID-19 patients, but they are not sufficiently sensitive for initial diagnoses. In addition, chest radiography could underestimate COVID-19 lung involvement because of the lesion characteristics of COVID-19-associated pneumonia.

Clinical impact of early reinsertion of a central venous catheter after catheter removal in patients with catheter-related bloodstream infections.

OBJECTIVE: Early replacement of a new central venous catheter (CVC) may pose a risk of persistent or recurrent infection in patients with a catheter-related bloodstream infection (CRBSI). We evaluated the clinical impact of early CVC reinsertion after catheter removal in patients with CRBSIs. METHODS: We conducted a retrospective chart review of adult patients with confirmed CRBSIs in 2 tertiary-care hospitals over a 7-year period. RESULTS: To treat their infections, 316 patients with CRBSIs underwent CVC removal. Among them, 130 (41.1%) underwent early CVC reinsertion (≤3 days after CVC removal), 39 (12.4%) underwent delayed reinsertion (>3 days), and 147 (46.5%) did not undergo CVC reinsertion. There were no differences in baseline characteristics among the 3 groups, except for nontunneled CVC, presence of septic shock, and reason for CVC reinsertion. The rate of persistent CRBSI in the early CVC reinsertion group (22.3%) was higher than that in the no CVC reinsertion group (7.5%; P = .002) but was similar to that in the delayed CVC reinsertion group (17.9%; P > .99). The other clinical outcomes did not differ among the 3 groups, including rates of 30-day mortality, complicated infection, and recurrence. After controlling for several confounding factors, early CVC reinsertion was not significantly associated with persistent CRBSI (OR, 1.59; P = .35) or 30-day mortality compared with delayed CVC reinsertion (OR, 0.81; P = .68). CONCLUSIONS: Early CVC reinsertion in the setting of CRBSI may be safe. Replacement of a new CVC should not be delayed in patients who still require a CVC for ongoing management.

Response System for and Epidemiological Features of COVID-19 in Gyeongsangnam-do Province in South Korea.

BACKGROUND: The South Korean government has been combating the coronavirus disease 2019 (COVID-19) outbreak using public information and extensive viral screening. We describe the application of the Korean response system in Gyeongsangnam-do province and outline the epidemiological features of COVID-19 in the cohort. METHODS: A Rapid Response Team tracked the patients' activities and identified close contacts. A Patient Management Team made decisions regarding the severity of illness, hospital allocation depending on severity, and time of discharge. A national medical center with 155 beds and 4 university-affiliated hospitals with 48 negative-pressure isolation rooms were dedicated for patients with COVID-19. RESULTS: As of 15 April, 17 400 residents were tested, of whom 111 were confirmed positive cases. Of the 111 patients, 78 were cured and discharged, 2 recovered after mechanical ventilation, and none died. One healthcare worker at the national center tested positive for SARS-CoV-2. All 412 staff members at the center were tested, but there were no additional infections. Cough (30.0%) was the most common initial symptom, whereas anosmia and ageusia were the first symptoms in 14.7% and 15.7% of the patients, respectively. Overall, 25 patients (22.5%) reported having no symptoms at admission and 7 (6.3%) remained asymptomatic at discharge. CONCLUSIONS: A response system that enabled the early detection of COVID-19 cases, including asymptomatic and presymptomatic cases, and timely quarantine of these patients and their contacts, along with efficient allocation of medical resources, was the key to curbing the COVID-19 outbreak in Gyeongsangnam-do Province.

Comparison of the clinical characteristics and outcomes of bloodstream infections caused by Raoultella species and Klebsiella pneumoniae.

Background: There have been few clinical studies of Raoultella infections but Raoultella is potentially virulent and multidrug resistant. The aims of the study were to compare the clinical characteristics and outcomes of patients with Raoultella and Klebsiella pneumoniae bloodstream infections (BSIs).Methods: We retrospectively reviewed the records of patients with Raoultella and K. pneumoniae BSIs admitted to a tertiary hospital between 2008 and 2017.Results: A total of 37 cases of Raoultella BSIs were identified and matched to 160 cases of K. pneumoniae BSIs by age and sex using propensity score matching. Patients with Raoultella BSIs were more likely to have underlying biliary tract disease (54.1% versus 24.4%; p < .001) and have a community-acquired infection (62.2% versus 43.1%; p = .04) than those with K. pneumoniae BSIs. Intra-abdominal infection was the most common primary focus of infection. Biliary tract infection (64.9% versus 38.8%; p = .004) and pancreatitis (13.5% versus 3.8%; p = .03) were more common in patients with Raoultella BSIs. Raoultella isolates exhibited significantly higher susceptibility to aztreonam, cefepime, and cefotaxime. The 14-day and 30-day mortality rates were lower among the patients with Raoultella BSIs but did not differ significantly between groups (11% versus 22%; p = .16 and 11% versus 26%; p = .08 for Raoultella and K. pneumoniae BSIs, respectively).Conclusion:Raoultella spp. BSI more likely to occur in patients with underlying biliary tract disease and in community settings compared with K. pneumoniae BSIs. Biliary tract infection was the most common primary focus of Raoultella BSIs.

The clinical and economic burden of community-onset complicated skin and skin structure infections in Korea.

BACKGROUND/AIMS: To investigate epidemiologic characteristics, clinical and economic burdens, and factors associated with mortality in complicated skin and skin structure infection (cSSSI) patients in Korea. METHODS: A retrospective, observational, nationwide study was conducted between April to July 2012 at 14 tertiary-hospitals in Korea. Eligible patients were hospitalized adults with community acquired cSSSI, who underwent surgical intervention and completed treatment between November 2009 and October 2011. Data on demography, clinical characteristics, outcomes and medical resource utilization were collected through medical record review. Direct medical costs were calculated by multiplying quantities of resources utilized by each unit price in Korea. RESULTS: Of 473 patients enrolled, 449 patients (except 24 patients with no record on surgical intervention) were eligible for analysis. Microbiological testing was performed on 66.1% of patients and 8.2% had multiple pathogens. Among culture confirmed pathogens (n = 297 patients, 340 episodes), 76.2% were gram-positive (Staphylococcus aureus; 41.2%) and 23.8% were gram-negative. The median duration of hospital stay was 16 days. Among treated patients, 3.3% experienced recurrence and 4.2% died in-hospital. The mean direct medical costs amounted to $4,195/ person, with the greatest expenses for hospitalization and antibiotics. The in-hospital mortality and total medical costs were higher in combined antibiotics therapy than monotherapy (p < 0.05). Charlson's comorbidity index ≥ 3, standardized early warning scoring ≥ 4, sub-fascia infections and combined initial therapy, were all found to be associated with higher mortality. CONCLUSION: Korean patients with community-onset cSSSI suffer from considerable clinical and economic burden. Efforts should be made to reduce this burden through appropriate initial treatment.

Activity of ceftaroline against pathogens associated with community-acquired pneumonia collected as part of the AWARE surveillance program, 2015-2016.

We report Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) program data for ceftaroline and comparators against isolates collected from identified lower respiratory tract sources in 2015 and 2016. MICs and susceptibility were determined using CLSI broth microdilution methodology and EUCAST breakpoints. Ceftaroline susceptibility among penicillin-resistant Streptococcus pneumoniae (MIC≥4 mg/L [nonmeningitis breakpoint]) ranged from 77.4% (Asia, 72/93) to 100% (Oceania, 16/16; Latin America, 15/15). Among MRSA, ceftaroline susceptibility ranged from 72.3% (Asia, 553/765) to 100% (Oceania, 39/39). Among ß-lactamase-positive Haemophilus influenzae, ceftaroline susceptibility ranged from 69.2% (Asia, 36/52) to 100% (Oceania, 19/19). Susceptibility to ceftaroline against non-ESBL-producing Klebsiella pneumoniae was between 91.4% (Europe, 659/721) and 100% (Oceania, 55/55) and for Escherichia coli between 85.7% (Africa/Middle East, 42/49) and 92.1% (Oceania, 35/38). Ceftaroline is not active against ESBL producers. In this study, susceptibility to ceftaroline was high among the S. pneumoniae, Staphylococcus aureus, ß-lactamase-negative H. influenzae, and ESBL-negative K. pneumoniae and E. coli collected.

Direct effectiveness of pneumococcal polysaccharide vaccine against invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia in elderly population in the era of pneumococcal conjugate vaccine: A case-control study.

BACKGROUND: While herd effects and serotype replacement by childhood pneumococcal protein conjugated vaccines (PCVs) continues to accumulate worldwide, direct effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases in the elderly has been challenged. We estimated the direct effectiveness of PPV23 in the elderly population. METHODS: For a hospital-based case-control study, cases of invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) (adults ≥ 65 years) were identified in 14 hospitals participated in the pneumococcal surveillance program from March 2013 to October 2015, following implementation of PPV23 national immunization program (NIP) for the elderly in the Republic of Korea. Controls matched by age, sex, and hospital were selected at ratios of 1:2 (IPD) or 1:1 (NBPP). Clinical data and vaccination records were collected. Vaccine effectiveness was calculated as (1-adjusted odds ratio) × 100. RESULTS: We enrolled 148 IPD and 557 NBPP cases, and 295 IPD and 557 NBPP controls for analyses. Overall effectiveness of PPV23 against IPD was 28.5% [95% confidence interval (CI) -5.8%-51.6%] and against NBPP was 10.2% (-15.1-30.6) in all patients ≥ 65 years. However, in subgroup analysis of patients aged 65-74 years, PPV23 was protective against IPD [effectiveness 57.4% (19.4-77.5)] and against NBPP [effectiveness 35.0% (2.3-56.7)]. Furthermore, serotype-specific effectiveness of PPV23 against IPD was 90.6% (27.6-98.8) for PPV23-unique serotypes and 81.3% (38.6-94.3) for PPV23 serotypes excluding serotype 3. CONCLUSIONS: This study indicates that PPV23 with broad serotype coverage might be beneficial in preventing IPD and NBPP due to non-PCV13 serotypes in the young-elderly, with potentially increasing effectiveness in the setting of childhood PCV NIP.

Selection of an appropriate empiric antibiotic regimen in hematogenous vertebral osteomyelitis.

BACKGROUND: Empiric antibiotic therapy for suspected hematogenous vertebral osteomyelitis (HVO) should be initiated immediately in seriously ill patients and may be required in those with negative microbiological results. The aim of this study was to inform the appropriate selection of empiric antibiotic regimens for the treatment of suspected HVO by analyzing antimicrobial susceptibility of isolated bacteria from microbiologically proven HVO. METHOD: We conducted a retrospective chart review of adult patients with microbiologically proven HVO in five tertiary-care hospitals over a 7-year period. The appropriateness of empiric antibiotic regimens was assessed based on the antibiotic susceptibility profiles of isolated bacteria. RESULTS: In total, 358 cases of microbiologically proven HVO were identified. The main causative pathogens identified were methicillin-susceptible Staphylococcus aureus (33.5%), followed by methicillin-resistant S. aureus (MRSA) (24.9%), Enterobacteriaceae (19.3%), and Streptococcus species (11.7%). Extended spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and anaerobes accounted for only 1.7% and 1.4%, respectively, of the causative pathogens. Overall, 73.5% of isolated pathogens were susceptible to levofloxacin plus rifampicin, 71.2% to levofloxacin plus clindamycin, and 64.5% to amoxicillin-clavulanate plus ciprofloxacin. The susceptibility to these oral combinations was lower in cases of healthcare-associated HVO (52.6%, 49.6%, and 37.6%, respectively) than in cases of community-acquired HVO (85.8%, 84.0%, and 80.4%, respectively). Vancomycin combined with ciprofloxacin, ceftriaxone, ceftazidime, or cefepime was similarly appropriate (susceptibility rates of 93.0%, 94.1%, 95.8%, and 95.8%, respectively). CONCLUSIONS: Based on our susceptibility data, vancomycin combined with a broad-spectrum cephalosporin or fluoroquinolone may be appropriate for empiric treatment of HVO. Fluoroquinolone-based oral combinations may be not appropriate due to frequent resistance to these agents, especially in cases of healthcare-associated HVO.