ABSTRACT
With the widespread use of broad-spectrum antibiotics in clinical practice, the emergence of multidrug-resistant (MDR) gram-negative bacteria has become a global problem. The MDR Pseudomonas aeruginosa infection is especially difficult to treat and increases mortality in critically ill patients. Ceftolozane-tazobactam (Zerbaxa™) is a fifth-generation cephalosporin and beta-lactamase inhibitor that has proved to be effective for treating complicated urinary tract infections and complicated intra-abdominal infections caused by MDR P. aeruginosa. Herein, we report the first case of pediatric hematologic cancer in Korea that was successfully treated for MDR P. aeruginosa bacteremia with Ceftolozane-tazobactam.
ABSTRACT
As nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 is immunogenic but not targeted in vaccines, it could be useful in distinguishing natural infection from vaccination. We aimed to investigate the clinical utility of sero-immunological responses against the nucleocapsid protein. Nucleocapsid antibody immunoassay study with 302 coronavirus disease 2019 (COVID-19) patients showed lower titers in immunocompromised patients (P < 0.001), higher titers in higher severity (P = 0.031), and different seroconversion rates and titers according to variants of concern. Longitudinal evaluation of nucleocapsid antibodies using 513 samples from 291 COVID-19 patients revealed that it could persist up to 556 days from symptom onset. Interferon gamma release assay against the nucleocapsid protein showed poor response, precluding the deduction of a cut-off for the nucleocapsid protein. In conclusion, nucleocapsid antibody provides instructive clues about the immunogenicity of nucleocapsid proteins by different seroconversion rates and titers according to the severity of infection, host immune status, and different variants of concern.
ABSTRACT
Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/ cilgavimab administration and the average PRNT ND 50 of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND 50 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND 50 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.
ABSTRACT
Increase in antimicrobial-resistant bacteria continues to be challenge to physicians. Particularly, multidrug-resistant (MDR) gram-negative bacilli (GNB), such as extended-spectrum beta-lactamase (ESBL)-producers and carbapenem-resistant pathogens, are becoming a major human health problem globally.Current Concepts: Gram-negative bacteria have developed resistance via mechanisms encoding AmpC beta-lactamases, ESBLs, and carbapenemases. The therapeutic options available for these pathogens are extremely limited. Infection by MDR bacteria is associated with ineffective antimicrobial therapy, which poses a major threat to the survival of patients with serious infections. Physicians should be familiar with the local epidemiology of MDR bacterial infections and the available therapeutic options. Carbapenems are considered as the drugs of choice for treating ESBL or AmpC-producers. However, increased use of carbapenems in response to an increased prevalence of MDR pathogens could be associated with the rapid emergence of carbapenem resistance. Therefore, there is an ongoing quest for carbapenem-sparing regimens for the treatment of MDR-GNB. Treatment of MDR-GNB infections need not be limited to carbapenems as novel antimicrobial agents are now available.Discussion and Conclusion: This comprehensive review aims to describe therapeutic options available for MDR-GNB infections in Korea, a country with a high prevalence of MDR pathogens. Recently developed antimicrobial agents that should be urgently introduced in Korea include ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and cefiderocol. These drugs have been shown to be effective against carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and Acinetobacter baumannii.
ABSTRACT
Purpose@#Real-world experience with tocilizumab in combination with dexamethasone in patients with severe coronavirus disease (COVID-19) needs to be investigated. @*Materials and Methods@#A retrospective cohort study was conducted to evaluate the effect of severity-adjusted dosing of dexamethasone in combination with tocilizumab for severe COVID-19 from August 2020 to August 2021. The primary endpoint was 30-day clinical recovery, which was defined as no oxygen requirement or referral after recovery. @*Results@#A total of 66 patients were evaluated, including 33 patients in the dexamethasone (Dexa) group and 33 patients in the dexamethasone plus tocilizumab (DexaToci) group. The DexaToci group showed a statistically significant benefit in 30-day clinical recovery, compared to the Dexa group (p=0.024). In multivariable analyses, peak FiO2 within 3 days and tocilizumab combination were consistently significant for 30-day recovery (all p<0.05). The DexaToci group showed a significantly steeper decrease in FiO2 (-4.2±2.6) than the Dexa group (−2.7±2.6; p=0.021) by hospital day 15. The duration of oxygen requirement was significantly shorter in the DexaToci group than the Dexa group (median, 10.0 days vs. 17.0 days; p=0.006). Infectious complications and cellular and humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the convalescence stage were not different between the two groups. @*Conclusion@#A combination of severity-adjusted dexamethasone and tocilizumab for the treatment of severe COVID-19 improved clinical recovery without increasing infectious complications or hindering the immune response against SARS-CoV-2.
ABSTRACT
Cushing's syndrome is characterized by excessive cortisol and immuno-suppression.We experienced a case of Cushing's syndrome caused by adrenocortical carcinoma that was complicated by multiple opportunistic infections. A 37-year-old woman with adrenocortical carcinoma (ACC) presented with decreased mental ability and high fever one week after undergoing chemotherapy. Her initial blood culture revealed methicillinresistant Staphylococcus aureus (MRSA) bacteremia accompanied by septic pneumonia. We admitted her to the intensive care unit and treated her for invasive pulmonary aspergillosis (IPA), Pneumocystis jirovecii pneumonia (PJP), candidemia, and Stenotrophomonas maltophilia pneumonia with broad-spectrum antibiotics and antifungal agents. Nevertheless, her clinical course worsened and she died. Herein, we report a case of Cushing's syndrome associated with cortisol-secreting ACC that presented with multiple opportunistic infections, including MRSA bacteremia, septic pneumonia, candidemia, PJP, and IPA, illuminating a relationship between hypercortisolemia and opportunistic infections.
ABSTRACT
Vancomycin and teicoplanin are representative glycopeptide antibiotics with activities against gram-positive cocci. The area under the drug concentration–time curve (AUC)/minimal inhibitory concentration (MIC) has been extensively used as an indicator of the bacteriological response to glycopeptide antibiotics, and the trough concentration has been used as a surrogate marker for the AUC/MIC. However, the guidelines for therapeutic drug monitoring (TDM) are being revised in accordance with increasing pharmacokinetic understanding of glycopeptide antibiotics. This review describes the pharmacokinetic/pharmacodynamic characteristics of glycopeptide antibiotics and discusses their optimal use with appropriate TDM.
ABSTRACT
As 16S ribosomal RNA (rRNA)-targeted sequencing can detect DNA from non-viable bacteria, it can be used to identify pathogens from clinical samples even in patients pretreated with antibiotics. We compared the results of 16S rRNA-targeted sequencing and culture for identifying bacterial species in normally sterile body fluid (NSBF): cerebrospinal, pericardial, peritoneal and pleural fluids. Over a 10-year period, a total of 312 NSBF samples were evaluated simultaneously using 16S rRNA-targeted sequencing and culture. Results were concordant in 287/312 (92.0%) samples, including 277 (88.8%) negative and 10 (3.2%) positive samples. Of the 16 sequencing-positive, culture-negative samples, eight showed clinically relevant isolates that included Fusobacterium nucleatum subsp. nucleatum, Streptococcus pneumoniae, and Staphylococcus spp. All these samples were obtained from the patients pretreated with antibiotics. The diagnostic yield of 16S rRNA-targeted sequencing combined with culture was 11.2%, while that of culture alone was 6.1%. 16S rRNA-targeted sequencing in conjunction with culture could be useful for identifying bacteria in NSBF samples, especially when patients have been pretreated with antibiotics and when anaerobic infection is suspected.
Subject(s)
Humans , Anti-Bacterial Agents , Bacteria , Body Fluids , DNA , Fusobacterium nucleatum , RNA, Ribosomal, 16S , Staphylococcus , Streptococcus pneumoniaeABSTRACT
Purpose@#Epstein-Barr virus (EBV) infection is related to infectious mononucleosis or nasopharyngeal cancer, and its epidemiology may change according to the socioeconomic development of communities. This study aimed to evaluate the recent epidemiology of EBV seropositive rate in Korea. @*Methods@#We retrospectively reviewed EBV serology test results obtained from a part of clinical care at Samsung Medical Center, Seoul, South Korea, from January 2000 to December 2017. @*Results@#The EBV seropositive rate in 26,527 subjects during the study period was 81.0% (21,485/26,527): 44.4% (2,716/6,122) in subjects aged 0–9 years, 75.8% (2,077/2,739) in those aged 10–19 years, and 94.5% (16,692/17,666) in those aged ≥20 years. The EBV seropositive rate decreased from 89.4% (8,592/9,616) in 2000–2008 to 76.2% (12,893/16,911) in 2009– 2017 (P<0.001). Especially, the EBV seropositive rate in subjects aged 0–19 years significantly decreased from 2000–2008 to 2009–2017 (0–9 years, 62.8% [1,172/1,866] in 2000–2008 and 36.3% [1,544/4,256] in 2009–2017; 10–19 years, 83.8% [745/858] in 2000–2008 and 70.8% (1,332/1,881) in 2009–2017) (P<0.001). @*Conclusions@#The EBV seropositive rate in children has decreased in the last 20 years. As the age of patients with primary EBV infection increased, there is a need for interest in clinical manifestation, such as infectious mononucleosis, in adolescents and young adults.
ABSTRACT
Coronavirus disease 2019 (COVID-19) outbreak is spreading rapidly all over the world, being a major threat to public health. Since clinical feature of COVID-19 has not been fully evaluated yet, empirical antibacterial agents are frequently combined for the treatment of COVID-19 in addition to antiviral agents, concerning co-existing bacterial pathogens. We experienced a case of severe thrombocytopenia with epistaxis and petechiae, while treating a COVID-19 patient with ceftriaxone, levofloxacin, and lopinavir/ritonavir. The platelet count decreased to 2,000/mm 3 and recovered after discontinuation of the three suspected drugs. In treating a potentially fatal emerging infectious disease, empirical and/or experimental approach would be unavoidable. However, the present case suggests that the possibility of adverse effects caused by polypharmacy should also be carefully considered.
ABSTRACT
Background@#Cancer patients can be at a higher risk of infection due to drug-resistant bacteria than the general population for various reasons. We performed a retrospective study to evaluate possible risk factors and outcomes of extended-spectrum beta-lactamaseproducing Klebsiella pneumoniae (ESBL-KP) bacteremia in cancer patients. @*Materials and Methods@#Cases were divided into two groups based on whether or not the isolated strain produced ESBL and multivariable regressions were done to identify possible risk factors of ESBL-KP bacteremia and mortality. For ESBL-producing strain, additional molecular analysis was done. @*Results@#278 cases with KP bacteremia were identified between 2010 and 2012, of which ESBLproducers were 50 (18%). The presence of percutaneous drainage catheter [odds ratio (OR) 4.99, P <0.001] and prior exposure to certain classes of antibiotics including third-generation cephalosporin (OR 2.14, P = 0.03) had significant associations with ESBL-KP bacteremia. Individuals who died within 14 days after the onset of KP bacteremia were more likely to have higher mean Pitt bacteremia score (1.56 in survival group vs. 3.43 in mortality group, P <0.001), hemodialysis (OR 17.03, P = 0.01) and chronic liver disease (OR 5.57, P = 0.01). Although 14-day mortality was higher with ESBL production (OR 2.76, P = 0.04), no significant differences in 30-day mortality (OR 1.67, P = 0.20) and other morbidity indices were observed. 49 ESBL-KP isolates, 65.4% of them produced CTX-M-14 and CTX-M-15 enzymes, and ST711 was the most common. @*Conclusion@#There were several differences in clinical characteristics between ESBL-KP and nonESBL-KP bacteremia in cancer patients, similar to previous reports including non-cancer patients.
ABSTRACT
Background/Aims@#Healthcare-associated (HCA) infection is a recently suggested new category of community-onset infections. The implications of HCA infections in terms of diagnosis, treatment, and outcomes of spontaneous bacterial peritonitis (SBP) are not well understood. We sought to delineate the differences between community-acquired (CA) SBP and HCA SBP with specific interest in the antimicrobial resistance of causative microorganisms and outcomes. @*Methods@#We conducted a retrospective cohort study of all SBP episodes with positive ascitic culture and/or blood culture from June 2000 to August 2011. Community-onset SBP episodes were included when they occurred within 48 hours after admission and were classified as CA SBP and HCA SBP based on the predefined criteria. @*Results@#A total of 188 episodes of community-onset SBP were analyzed (65.4% HCA SBP and 34.6% CA SBP). HCA SBP had a higher resistance rate to third-generation cephalosporin (6.8% vs. 1.6%, p = 0.168). The overall 30-day mortality was similar between both groups (37.4% vs. 41.5%, p = 0.638). The independent risk factors for 30-day all-cause mortality in community-onset SBP included high Child-Pugh score, acute kidney injury, and resistance to third-generation cephalosporins; HCA infection was not associated. @*Conclusions@#Hepatic functional status, renal dysfunction, and third-generation cephalosporin resistant pathogens more adversely affected the outcome of cirrhotic patients with community-onset SBP rather than HCA infection. The higher rate of third-generation cephalosporin resistance was notable in HCA SBP, which will require a novel approach to empirical antibiotic treatment selection in this population.
ABSTRACT
Background@#Teicoplanin is used to treat serious gram-positive infections. Optimal teicoplanin trough levels are considered to be ≥ 10 μg/mL. Despite its wide use in various clinical settings, data on teicoplanin trough level in pediatric patients are limited. Therefore, the aim of this study was to investigate the therapeutic drug level monitoring of teicoplanin in Korean pediatric patients, including those with impaired renal function. @*Methods@#A retrospective study was performed in pediatric patients (age ≤ 18 years old) who received teicoplanin from September 2014 to April 2018. The regimen included a loading dose of 10 mg/kg/dose at 12 hours' interval three times in a row, and a maintenance dose of 10 mg/kg/dose commenced at 24 hours of interval after the loading dose, with a maximum of 400 mg/dose, respectively. The first therapeutic drug levels were measured. Distribution and characteristics of trough levels in patients with decreased renal function and those with bacteremia were also assessed. @*Results@#A total of 187 trough levels were collected from 143 patients. Hematologic and oncologic diseases were the most common underlying diseases (83.2%, n = 119). One hundred eighty trough levels were first measured, and their median value was 16.2 μg/mL (range, 2.3–100 μg/mL) and the median interval between initial teicoplanin injection and 1st trough level was 96.5 hours (range 47.6–179.3 hours). Lower steady-state levels were observed in younger age group (median, 13.5 vs. 18.0 μg/mL, P = 0.038). Median trough levels were higher in patients with decreased renal functions (P < 0.001). In addition, among eight with gram-positive bacteremia, seven of them had a favorable outcome. @*Conclusion@#This study provides additive information on trough level monitoring of teicoplanin in children with impaired renal function and treatment effect in patients with gram-positive bacteremia. Careful monitoring for steady state trough levels of teicoplanin is warranted.
ABSTRACT
The original version of the article contained error.
ABSTRACT
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.
Subject(s)
Humans , Amikacin , Febrile Neutropenia , MortalityABSTRACT
BACKGROUND/AIMS@#Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in hospitals, and has recently emerged in the community. The impact of methicillin-resistance on mortality and medical costs for patients with S. aureus bacteremia (SAB) requires reevaluation.@*METHODS@#We searched studies with SAB or endocarditis using electronic databases including Ovid-Medline, Embase-Medline, and Cochrane Library, as well as five local databases for published studies during the period January 2000 to September 2011.@*RESULTS@#A total of 2,841 studies were identified, 62 of which involved 17,563 adult subjects and were selected as eligible. A significant increase in overall mortality associated with MRSA, compared to that with methicillin-susceptible S. aureus (MSSA), was evidenced by an odds ratio (OR) of 1.95 (95% confidence interval [CI], 1.73 to 2.21; p < 0.01). In 13 endocarditis studies, MRSA increased the risk of mortality, with an OR of 2.65 (95% CI, 1.46 to 4.80). When three studies, which compared mortality rates between CA-MRSA and CA-MSSA, were combined, the risk of methicillin-resistance increased 3.23-fold compared to MSSA (95% CI, 1.25 to 8.34). The length of hospital stay in the MRSA group was 10 days longer than that in the MSSA group (95% CI, 3.36 to 16.70). Of six studies that reported medical costs, two were included in the analysis, which estimated medical costs to be $9,954.58 (95% CI, 8,951.99 to 10,957.17).@*CONCLUSIONS@#MRSA is still associated with increased mortality, longer hospital stays and medical costs, compared with MSSA in SAB in studies published since the year 2000.
ABSTRACT
The original version of the article contained error.
ABSTRACT
Carbapenem-resistance emerging in Gram-negative pathogens, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, has become a major human health problem globally. The therapeutic options available for carbapenem-resistant pathogens are very limited. Antibiotics such as colistin, tigecycline, fosfomycin, and aminoglycosides are often the only ones that can be used to treat carbapenem-resistant pathogens. Carbapenem may still be an option in certain circumstances. The administration of combination therapy for carbapenem-resistant pathogens is controversial. This review presents the current knowledge of available antimicrobial therapeutic options for infections due to carbapenem-resistant pathogens in Korea.
Subject(s)
Humans , Acinetobacter baumannii , Aminoglycosides , Anti-Bacterial Agents , Colistin , Drug Resistance , Fosfomycin , Gram-Negative Bacteria , Klebsiella pneumoniae , Korea , Pseudomonas aeruginosa , Treatment OutcomeABSTRACT
Urinary tract infections (UTIs) are infectious diseases that commonly occur in communities. Although several international guidelines for the management of UTIs have been available, clinical characteristics, etiology and antimicrobial susceptibility patterns may differ from country to country. This work represents an update of the 2011 Korean guideline for UTIs. The current guideline was developed by the update and adaptation method. This clinical practice guideline provides recommendations for the diagnosis and management of UTIs, including asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, complicated pyelonephritis related to urinary tract obstruction, and acute bacterial prostatitis. This guideline targets community-acquired UTIs occurring among adult patients. Healthcare-associated UTIs, catheter-associated UTIs, and infections in immunocompromised patients were not included in this guideline.
Subject(s)
Adult , Humans , Bacteriuria , Communicable Diseases , Cystitis , Diagnosis , Immunocompromised Host , Methods , Prostatitis , Pyelonephritis , Urinary Tract Infections , Urinary TractABSTRACT
Community-acquired pneumonia is common and important infectious disease in adults. This work represents an update to 2009 treatment guideline for community-acquired pneumonia in Korea. The present clinical practice guideline provides revised recommendations on the appropriate diagnosis, treatment, and prevention of community-acquired pneumonia in adults aged 19 years or older, taking into account the current situation regarding community-acquired pneumonia in Korea. This guideline may help reduce the difference in the level of treatment between medical institutions and medical staff, and enable efficient treatment. It may also reduce antibiotic resistance by preventing antibiotic misuse against acute lower respiratory tract infection in Korea.