ABSTRACT
Patients with systemic rheumatic diseases (SRD) are vulnerable for coronavirus disease (COVID-19). The Korean College of Rheumatology recognized the urgent need to develop recommendations for rheumatologists and other physicians to manage patients with SRD during the COVID-19 pandemic. The working group was organized and was responsible for selecting key health questions, searching and reviewing the available literature, and formulating statements. The appropriateness of the statements was evaluated by voting panels using the modified Delphi method. Four general principles and thirteen individual recommendations were finalized through expert consensus based on the available evidence. The recommendations included preventive measures against COVID-19, medicinal treatment for stable or active SRD patients without COVID-19, medicinal treatment for SRD patients with COVID-19, and patient evaluation and monitoring. Medicinal treatments were categorized according to the status with respect to both COVID-19 and SRD. These recommendations should serve as a reference for individualized treatment for patients with SRD. As new evidence is emerging, an immediate update will be required.
ABSTRACT
Wound healing is composed of a complex process that requires harmonies of various cell populations where fibroblasts play the main role. Oligomeric procyanidins (OPC) are main components of grape (Vitis vinifera) seed extracts, and recent studies showed OPC's effects on inflammation, cell migration, and proliferation. We investigated the effect of OPC on fibroblasts to regulate wound healing process. Human dermal fibroblast known as Hs27 cells were treated with various concentrations of OPC (0, 2.5, 5, 10, and 20 µg/µl). Cell cytotoxicity was evaluated by the Cell Counting Kit assay, and the expression levels of secreted procollagen were analyzed. Procollagen levels in OPC treated cells exposed to transforming growth factor beta 1 (TGF-β1) or ascorbic acid were evaluated using Western blot and immunocytochemistry. Relative mRNA expressions of procollagen, molecular chaperone such as HSP47, P4H were determined by real-time PCR in OPC treated cells. OPC showed no cytotoxicity on Hs27 cells at every concentration but inhibited procollagen secretion in a dose-dependent manner. The inhibitory effect also appeared under TGF-β1 induced collagen overproduction. Immunocytochemistry showed that higher levels of intracytoplasmic procollagen were accumulated in TGF-β1 treatment group, whereas ascorbic acid induced a release of accumulated procollagen under OPC treatment. The mRNA expressions of procollagen, molecular chaperone were not affected by OPC, but procollagen level was increased when exposed to TGF-β1. OPC inhibits procollagen secretion from fibroblasts with no effects on cell proliferations even under the environment of TGF-b1-induced collagen overproduction. OPC could regulate the diseases and symptoms of abnormal overabundant collagen production.
Subject(s)
Humans , Ascorbic Acid , Blotting, Western , Cell Count , Cell Movement , Collagen , Collagen Type I , Fibroblasts , Immunohistochemistry , Inflammation , Molecular Chaperones , Proanthocyanidins , Procollagen , Real-Time Polymerase Chain Reaction , RNA, Messenger , Transforming Growth Factor beta , Vitis , Wound HealingABSTRACT
BACKGROUND: Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass density and destruction of microstructure, which can lead to an increased risk of fracture. Although many studies have been published about the relationship between end-stage renal disease and osteoporosis, research on the relationship between proteinuria and the prevalence of osteoporosis is still lacking. METHODS: We assessed 91 postmenopausal women with type 2 diabetes who visited our hospital from January 2009 to January 2012. RESULTS: Among 91 patients, the prevalence of osteoporosis and osteopenia was 35.2% (32 cases) and 32.9% (30 cases) according to bone mineral density. The patients with microalbuminuria and macroalbuminuria (urine albumin-to-creatinine ratio [UACR] > or = 30) had a significantly higher incidence of osteoporosis compared to subjects with normoalbuminuria (P<0.05). CONCLUSIONS: This study indicates that UACR may be a useful biomarker for increased risk of osteoporosis in postmenopausal women with type 2 diabetes who have been linked to higher UACR levels.
Subject(s)
Female , Humans , Albumins , Bone Density , Bone Diseases , Bone Diseases, Metabolic , Creatinine , Incidence , Kidney Failure, Chronic , Osteoporosis , Prevalence , ProteinuriaABSTRACT
Temporomandibular joint (TMJ) disorder is clinically important because of its prevalence, chronicity, and therapy-refractoriness of the pain. In this study, we investigated the effect of infliximab in a mouse model of TMJ pain using a specially-engineered transducer for evaluating the changes in bite force (BF). The mice were randomly divided into three groups (7 mice per group): the control group, the complete Freund's adjuvant (CFA) group, and the infliximab group. BF was measured at day 0 (baseline BF). After measuring the baseline BF, CFA or incomplete Freund's adjuvant was injected into both TMJs and then the changes in BF were measured at days 1, 3, 5, 7, 9, and 13 after the TMJ injection. For measuring the BF, we used a custom-built BF transducer. Control, CFA, and infliximab groups showed similar baseline BF at day 0. From day 1, a significant reduction in BF was observed in the CFA group, and this reduction in BF was statistically significant compared to that in the control group (P < 0.05). This reduction in BF was maintained until day 7, and BF started to recover gradually from day 9. In the infliximab group also, the reduction in BF was observed on day 1, and this reduction was maintained until day 7. However, the degree of reduction in BF was less remarkable compared to that in the CFA group. The reduction in BF caused by injection of CFA into the TMJ could be partially alleviated by the injection of anti-tumor necrosis factor alpha, infliximab.
Subject(s)
Animals , Male , Mice , Antirheumatic Agents/therapeutic use , Bite Force , Disease Models, Animal , Freund's Adjuvant/toxicity , Infliximab/therapeutic use , Mice, Inbred ICR , Temporomandibular Joint/pathology , Temporomandibular Joint Disorders/chemically induced , Time FactorsABSTRACT
BACKGROUND: Hemophagocytic syndrome (HS) is a distinct clinical entity characterized by high fever and hemophagocytosis with histiocytosis in tissue biopsy. We seldom encounter patients who suffer from unexplained, persistent fevers. Although there have been many studies about childhood HS, studies about adult HS are relatively rare. The causes and prognoses of HS in adults were evaluated in this study. We focused on infection-related HS. MATERIALS AND METHODS: We enrolled 41 adult patients with HS retrospectively from four hospitals in Kyungbuk province and Daegu city. The patients were diagnosed by bone marrow or liver biopsy, either of which showed hemophagocytosis with histiocytosis and had clinical findings consistent with HS. We explored the etiologies, clinical symptoms, laboratory findings, treatments, and outcomes of each case. RESULTS: The most common cause of HS was infection, such as the Epstein-Barr virus (EBV) or Mycobacterium tuberculosis. Old age and malignancy-associated HS had a poor prognosis. The overall mortality rate was 17.1%. Most patients survived after conservative therapy and the control of underlying diseases, in contrast to previous studies that showed a poor prognosis of infection-associated HS. CONCLUSIONS: A proper investigation is crucial to determine the cause of HS in patients who have unexplained persistent fever and hemophagocytosis with histiocytosis in their tissue. Cases of infection-related HS are common, but physicians should consider undiagnosed malignancy that may be related to a poor prognosis. Treatments appropriate to the causes are important for better outcomes in adult HS.
Subject(s)
Adult , Humans , Biopsy , Bone Marrow , Fever , Herpesvirus 4, Human , Histiocytosis , Liver , Lymphohistiocytosis, Hemophagocytic , Mycobacterium tuberculosis , Prognosis , Retrospective Studies , Risk FactorsABSTRACT
The purpose of this study was to establish a prediction rule for severe illness in adult patients hospitalized with pandemic influenza A (H1N1) 2009. At the time of initial presentation, the baseline characteristics of those with severe illness (i.e., admission to intensive care unit, mechanical ventilation, or death) were compared to those of patients with non-severe illnesses. A total of 709 adults hospitalized with pandemic influenza A (H1N1) 2009 were included: 75 severe and 634 non-severe cases. The multivariate analysis demonstrated that altered mental status, hypoxia (PaO2/FiO2 or = 65 yr) were independent risk factors for severe cases (all P or = 2 risk factors had a higher sensitivity, specificity, positive predictive value and negative predictive value than an APACHE II score of > or = 13. As a prediction rule, the presence of > or = 2 these risk factors is a powerful and easy-to-use predictor of the severity in adult patients hospitalized with pandemic influenza A (H1N1) 2009.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , APACHE , Antiviral Agents/therapeutic use , Hospitalization , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/drug therapy , Intensive Care Units , Pandemics , Predictive Value of Tests , ROC Curve , Respiration, Artificial , Risk Factors , Severity of Illness IndexABSTRACT
BACKGROUND: Pregnant women are at an increased risk for severe illness and complications associated with pandemic (H1N1) 2009. This study was conducted to identify the severity of pandemic (H1N1) 2009 in pregnant Korean women. MATERIALS AND METHODS: The demographic and clinical data from pregnant women with laboratory confirmed pandemic (H1N1) 2009 during September to December 2009 were retrospectively collected from 8 hospitals in Korea. RESULTS: A total of 150 pregnant women with pandemic (H1N1) 2009 were identified. The median age was 30 years (range: 22-39 years), and the median gestational age (n=114) was 20 weeks (range: 1-39 weeks). All but one patient with secondary bacterial pneumonia had influenza without complication. Although 12 pregnant women needed hospitalization, there were no patients who needed admission to the intensive care unit or who died. Only one hospitalized patient had elective cesarean section because of oligohydamnios. No maternal or fetal complications directly related to the pandemic (H1N1) 2009 were identified among the 67 pregnant women who were followed up for 1 to 185 days after their influenza illness, including 6 women who delivered during the study period. CONCLUSIONS: In contrast with the reports from Western countries, pandemic (H1N1) 2009 among pregnant Korean women was mild.
Subject(s)
Female , Humans , Pregnancy , Cesarean Section , Gestational Age , Hospitalization , Influenza, Human , Intensive Care Units , Pandemics , Pneumonia, Bacterial , Pregnant Women , Retrospective StudiesABSTRACT
Pregnant women is known to be at risk of high morbiding and mortality from H1N1 2009. Since the emergence of H1N1 2009 in Korean in April 2009, fatal case has not been reported in the Korean pregnant women yet. This is the first report of fatal case in pregnant women associated with H1N1 2009 infection in Korea. A 29-year-old woman at 32 weeks of gestation presented with pneumonia associated with H1N1 2009 infection, progressed into acute respiratory distress syndrome. On the fourth day of admission fetal distress development. The patient died from refractory critical hypoxemia and multiple organ failure on the 5th hospital day in spite of receiving extracorporeal membrane oxygenation therapy and intravenous peramivir.
Subject(s)
Adult , Female , Humans , Pregnancy , Hypoxia , Cyclopentanes , Extracorporeal Membrane Oxygenation , Fetal Distress , Guanidines , Influenza, Human , Korea , Multiple Organ Failure , Pandemics , Pneumonia , Pregnant Women , Respiratory Distress SyndromeABSTRACT
The pandemic influenza (H1N1 2009) virus, after being introduced in Korea in April, 2009, spread rapidly nationwide in mid-2009. This study was conducted to characterize trend in age distribution of visitors to Flu-clinics during the pandemic. Demographic, clinical and laboratory data of visitors to flu clinic from Week 36 to 52 (August 30 to December 26) of 2009 were retrieved and collected from electronic databases at 9 hospitals. Visitors 0-6, 7-12, 13-18, 19-29, 30-64, and 65 years or more of age were classified into group I to VI, respectively. A total of 107,467 visitors were seen at Flu-clinics for a 17-week study period. Of those, 32,485 were laboratory-confirmed. Antivirals were prescribed for 62,533 visitors. Numbers of visits, prescriptions of antivirals, and laboratory-confirmed cases of the pandemic influenza (H1N1 2009) peaked at Week 44. A large number of visits by group II and III were followed by those of group I and V, especially around the peak. Numbers of visits by group VI were lowest in all hospitals. In some hospitals, higher number of visits lasted longer in children than in adults while vice versa in other hospitals depending on the location. In summary, the pandemic influenza (H1N1 2009) was presumed to peak in late October and involved majorly children and students in Korea. Unique age distribution of visitors to flu clinic was observed in some hospitals.
Subject(s)
Adult , Child , Humans , Age Distribution , Antiviral Agents , Electronics , Electrons , Influenza, Human , Korea , Pandemics , Prescriptions , VirusesABSTRACT
Adult-onset Still's disease (AOSD) is an inflammatory disorder that's characterized by daily, spiking high fever, arthritis and an evanescent, salmon-pink rash. AOSD is diagnosed purely on the basis of the typical clinical features of the illness. The symptoms commonly include swelling of the lymph nodes, enlargement of the spleen and liver, and a sore throat. AOSD is difficult to differentiate from systemic lupus erythematosus (SLE) due to the similar clinical manifestations. We report here on a case of a 16-year-old female patient with autism and epilepsy and who complained of daily spiking fever for 20 days. The patient had maculopapular skin rashes on the face and whole body and lymphadenopathy. The liver function tests were elevated mildly. The initial rheumatoid factor (RF) and antinuclear antibody (ANA) tests were negative. We diagnosed her as having adult-onset Still's disease according to the criteria of Yamaguchi. We successfully treated her with oral prednisolone. But her antinuclear antibody test was changed to positive after discharge. So we finally diagnosed her as having SLE.
Subject(s)
Adolescent , Female , Humans , Antibodies, Antinuclear , Arthritis , Autistic Disorder , Epilepsy , Exanthema , Fever , Liver , Liver Function Tests , Lupus Erythematosus, Systemic , Lymph Nodes , Lymphatic Diseases , Pharyngitis , Prednisolone , Rheumatoid Factor , Spleen , Still's Disease, Adult-OnsetABSTRACT
Corynebacterium macginleyi is usually isolated from the eye surfaces and causes ocular infections such as conjunctivitis, keratitis, and endophthalmitis. However, cases that describe C. macginleyi as the causative agent for significant and life-threatening infections in immunocompromised patients are increasingly reported. Herein we report the first documented case of C. macginleyi pneumonia in a human immunodeficiency virus (HIV) patient. A 42-year-old homosexual man with HIV infection was hospitalized with a 1-month history of fever and dry cough. Chest radiograph revealed ill defined ground glass opacities in both lung fields. Methenamine silver stain of bronchoalveolar lavage fluid was negative. He showed clinical improvement after treatment with trimethoprim/sulfamethoxazole and prednisolone for three weeks, and was discharged. One month later, he presented with dyspnea and more progressive pulmonary infiltrations. Bronchial washing fluid culture yielded >100,000 colonies/mL of C. macginleyi, and he was given a 14-day course of antibiotic therapy with vancomycin, after which the patient fully recovered. This case suggest the importance of not overlooking the significance of positive cultures for C. macginleyi obtained from representative clinical samples in patients with signs and symptoms of bacterial infection.
Subject(s)
Adult , Humans , Bacterial Infections , Bronchoalveolar Lavage Fluid , Conjunctivitis , Corynebacterium , Cough , Dyspnea , Endophthalmitis , Eye , Eye Infections , Fever , Glass , HIV , HIV Infections , Homosexuality , Immunocompromised Host , Keratitis , Lung , Methenamine , Pneumonia , Prednisolone , Thorax , VancomycinABSTRACT
Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) with Panton-Valentine leukocidin (PVL) genes have recently emerged worldwide, but infections due to PVL carrying CA-MRSA strains have never been reported in Korea. We report a case of extensive perianal abscess due to PVL+ CA-MRSA in a 76-year-old Korean female patient, of which genetic background was very close to USA300. It belonged to staphylococcal cassette chromosome mec element (SCCmec) type IV, ST8 of multilocus sequence typing (MLST), type 1 spa type, and accessory gene regulator locus (agr) group I. Comprehensive literature reviews from the Far East showed molecular characteristics were diverse and PVL genes were infrequently found than in western countries.
Subject(s)
Aged , Female , Humans , Abscess , Bacterial Toxins , Exotoxins , Asia, Eastern , Korea , Leukocidins , Lifting , Methicillin Resistance , Methicillin-Resistant Staphylococcus aureus , Multilocus Sequence Typing , Staphylococcus aureusABSTRACT
Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) with Panton-Valentine leukocidin (PVL) genes have recently emerged worldwide, but infections due to PVL carrying CA-MRSA strains have never been reported in Korea. We report a case of extensive perianal abscess due to PVL+ CA-MRSA in a 76-year-old Korean female patient, of which genetic background was very close to USA300. It belonged to staphylococcal cassette chromosome mec element (SCCmec) type IV, ST8 of multilocus sequence typing (MLST), type 1 spa type, and accessory gene regulator locus (agr) group I. Comprehensive literature reviews from the Far East showed molecular characteristics were diverse and PVL genes were infrequently found than in western countries.
Subject(s)
Aged , Female , Humans , Abscess , Bacterial Toxins , Exotoxins , Asia, Eastern , Korea , Leukocidins , Lifting , Methicillin Resistance , Methicillin-Resistant Staphylococcus aureus , Multilocus Sequence Typing , Staphylococcus aureusABSTRACT
OBJECTIVE: To investigate the clinical manifestation and prognostic factors of interstitial lung disease (ILD) in Korean patients with idiopathic inflammatory myopathies include with polymyositis (PM) and dermatomyositis (DM). METHODS: Clinical and laboratory data of 110 patients with PM/DM in our rheumatology clinic were investigated. Clinical data including history, medication, pulmonary function tests (PFT) findings, radiologic findings, and labaratory findings were obtained from medical records at the first diagnosis of ILD with PM/DM. ILD was diagnosed on the basis of the imaging abnormalities defined above on definite findings of chest X-rays and high resolution computed tomography (HRCT), restrictive changes on PFT with respiratory symptoms. During the course of treatment, we assessed chest radiograph and HRCT findings. RESULTS: Forty-two PM/DM patients (38.2%) developed ILD. Anti-extracellular nuclear antigen (ENA) antibody, anti-Jo-1 antibody and ground glass opacity in HRCT were significantly high in PM-ILD. However honeycoomb appearance (53% : 22%) and fibrosis (41% : 6%) in HRCT were significantly high in DM-ILD. Interest in aspects of prognosis including initial steroid treatment response in HRCT were favorable in PM-ILD. There were statistically significant association between normal level of CPK and usual interstitial pneumonia (UIP) pattern in HRCT in DM-ILD. Such cases had resistance to steroid therapy. Overall interval between steroid and immunosuppressant therapy was significantly shorter in those with DM-ILD. CONCLUSION: The clinical manifestations between PM-ILD and DM-ILD in Korean patients were not significant different from those of other populations. DM-ILD is more refractory to steroid treatment, expecting in poor prognosis compared with PM-ILD. So immediate intensive immunosuppressive therapy should be considered in DM-ILD.
Subject(s)
Humans , Dermatomyositis , Diagnosis , Fibrosis , Glass , Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Lung , Medical Records , Myositis , Polymyositis , Prognosis , Radiography, Thoracic , Respiratory Function Tests , Rheumatology , ThoraxABSTRACT
Kikuchi-Fujimoto's disease (KFD) is a rare self-limiting necrotizing lymphadenitis found mainly in young women. Patients typically present with lymphadenopathy and often with a high fever. The etiology of the disease remains unknown, but various infection and autoimmune processes have been postulated to be the cause. We report here on a 22-year-old female with 7-year history of systemic lupus erythematosus presented with high fever and many enlarged cervical lymph nodes. Neck computed tomography scan showed multiple lymphadenopathies and KFD was proven by under sonographic guidance percutaneous needle biopsy.
Subject(s)
Female , Humans , Young Adult , Biopsy, Needle , Fever , Histiocytic Necrotizing Lymphadenitis , Lupus Erythematosus, Systemic , Lymph Nodes , Lymphadenitis , Lymphatic Diseases , Neck , UltrasonographyABSTRACT
BACKGROUND: During the era of increasing penicillin resistant Streptococcus pneumoniae, it is important to have knowledge about adequate dosage and dosing interval of ceftriaxone (CTR). We examined efficacies of once-daily CTR and compared results in an in vitro pharmacodynamic infection model (IVPDIM) supplemented with albumin and those without albumin. METHODS: Using three clinically isolated S. pneumoniae that were susceptible (SM24), intermediate (SM47) and resistant (SM60) against CTR, we utilized a two-compartment IVPDIM. CTR 2 g was administered intravenously every 24 h. Human albumin was added with concentration of 4 g/dL. Samples were removed at multiple time points over a 48-h period to determine the colony counts. RESULTS: In SM24 and SM60, bactericidal effects were observed within 6 hours in groups without albumin. The number of colonies during 1st 6 hours were more decreased in albumin-free groups than in albumin-supplemented groups (P<0.05). In SM47, similar results were found during 1st 6 hours (P=0.03). But, regrowth was observed in albumin supplemented group at 30 h. Irrespective of results of minimal inhibitory concentrations and albumin supplementation, bactericidal effects were shown at 24 h in all 3 strains. All groups were decreased below the detection limit at 48 h. Development of resistance was not detected throughout the entire study period in either strain. CONCLUSIONS: Although extents of killing in albumin supplemented broth of once-daily CTR dosing were delayed in all 3 strains compared with those of albumin free broth, final efficacies were not different between the two groups.
Subject(s)
Humans , Ceftriaxone , Homicide , Limit of Detection , Penicillins , Pneumonia , Streptococcus pneumoniae , StreptococcusABSTRACT
OBJECTIVE: To evaluate concordance rate between tuberculin skin test (TST) and T-SPOT.TB (T-SPOT) for detecting latent tuberculosis in patients with rheumatoid arthritis (RA) received disease modifying antirheumatic drugs (DMARDs) and/or immunosuppressant. METHODS: Fifty four patients with RA refractory to conventional DMARDs and planned ahead to be received tumor necrosis factor-alpha (TNF-alpha) blockade were enrolled in this study. The TST was performed by Mantoux method. Over 10 mm induration size was considered to be positive in the TST. The peripheral blood were collected from all patients and used for the T-SPOT. RESULTS: Only six patients (11.11%) had a positive TST, and 48 patients (88.89%) had a negative TST. The mean TST values were 13.51+/-3.51 mm (range: 10~19 mm) in TST (+) group and 2.50+/-3.12 mm (range: 0~9 mm) in TST (-) group, respectively. T-SPOT was indeterminate in 7 patients (12.96%). Twenty-five patients (53.19%) had a positive result, and 22 patients (46.81%) had a negative result in 47 patients determinated with T-SPOT. There was poor overall agreement between results of TST and T-SPOT (p=0.194). CONCLUSION: There was no concordance between TST and T-SPOT in patients with RA received DMARDs and/or immunosuppressant. Therefore, the results of TST should be interpreted with caution, taking into consideration of the result of T-SPOT in patients with RA who are prone to having false negative of TST.
Subject(s)
Humans , Antirheumatic Agents , Arthritis, Rheumatoid , Latent Tuberculosis , Mycobacterium tuberculosis , Mycobacterium , Skin Tests , Skin , Tuberculin , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND: Small colony variants (SCVs) of Staphylococcus aureus have emerged to be commonly associated with persistent and relapsing infections. Arbekacin (ABK) is one of a few alternatives to vancomycin in intractable case of methicillin resistant S. aureus (MRSA) infection. However, it has not yet been defined whethter ABK tends to be efficacious to the MRSA SCVs. In this study, we employed an in vitro pharmacodynamic infection model (IVPDIM) to define efficacies of ABK against MRSA SCVs. MATERIALS AND METHODS: Using four strains of clinically isolated MRSA (MRSA122, MRSA160, MRSA18, MRSA123), we adopted IVPDIM comprised of two-compartment in which effective surface-to-volume ratio of 5.34 cm(-1). Human pharmacokinetic regimen simulations of ABK were as follows: 100 mg every 12 h (q12h), 200 mg q24h, 200 mg q12h, and 400 mg q24h. Samples were taken from each model at 0, 1, 2, 4, 6, 12, 24, and 30 h, and the bacterial colony counts were determined. The experiments were repeated twice with ABK-administered groups and control group. RESULTS: MICs of ABK for MRSA122, MRSA160, MRSA18, and MRSA123 were 2, 2, 2, and 1 microgram/mL, respectively. In case of MRSA122, MRSA160, MRSA18, C(max)/MIC were less than 9.0 except for ABK 400 mg q24h regimen. In MRSA123, C(max)/MIC were 8.9 on average at ABK 100 mg q12h regimen. But, other regimen showed C(max)/MIC >9. Four regimens for 4 strains showed statistically different colony counts at 30 h (P=0.000). The more dosage or less frequent dosing interval, the more colonies tended to reduce in all strains. In 100 mg q12h groups, SCVs were observed in all strains within 24 h. With increment of dosage or changing dosing interval from q12h to 24h, SCVs were reduced (P=0.000). Regimen of 400 mg q24h did not let SCVs appear in all strains of MIC 2 microgram/mL during the experiments. CONCLUSION: SCVs were observed when MIC of ABK against MRSA were 1-2 microgram/mL, especially in most cases of C(max)/MIC <9. Those findings were also associated with re-growth of colony during the experiments. Once-daily dosing of ABK could reduce or eliminate the appearance of SCV.
Subject(s)
Humans , Linear Energy Transfer , Methicillin Resistance , Methicillin , Methicillin-Resistant Staphylococcus aureus , Staphylococcus aureus , Staphylococcus , VancomycinABSTRACT
BACKGROUND: During the era of increasing penicillin resistant Streptococcus pneumoniae, it is important to have knowledge about adequate dosage and dosing interval of ceftriaxone (CTR). We examined efficacies of once-daily CTR and compared results in an in vitro pharmacodynamic infection model (IVPDIM) supplemented with albumin and those without albumin. METHODS: Using three clinically isolated S. pneumoniae that were susceptible (SM24), intermediate (SM47) and resistant (SM60) against CTR, we utilized a two-compartment IVPDIM. CTR 2 g was administered intravenously every 24 h. Human albumin was added with concentration of 4 g/dL. Samples were removed at multiple time points over a 48-h period to determine the colony counts. RESULTS: In SM24 and SM60, bactericidal effects were observed within 6 hours in groups without albumin. The number of colonies during 1st 6 hours were more decreased in albumin-free groups than in albumin-supplemented groups (P<0.05). In SM47, similar results were found during 1st 6 hours (P=0.03). But, regrowth was observed in albumin supplemented group at 30 h. Irrespective of results of minimal inhibitory concentrations and albumin supplementation, bactericidal effects were shown at 24 h in all 3 strains. All groups were decreased below the detection limit at 48 h. Development of resistance was not detected throughout the entire study period in either strain. CONCLUSIONS: Although extents of killing in albumin supplemented broth of once-daily CTR dosing were delayed in all 3 strains compared with those of albumin free broth, final efficacies were not different between the two groups.
Subject(s)
Humans , Ceftriaxone , Homicide , Limit of Detection , Penicillins , Pneumonia , Streptococcus pneumoniae , StreptococcusABSTRACT
BACKGROUND: Small colony variants (SCVs) of Staphylococcus aureus have emerged to be commonly associated with persistent and relapsing infections. Arbekacin (ABK) is one of a few alternatives to vancomycin in intractable case of methicillin resistant S. aureus (MRSA) infection. However, it has not yet been defined whethter ABK tends to be efficacious to the MRSA SCVs. In this study, we employed an in vitro pharmacodynamic infection model (IVPDIM) to define efficacies of ABK against MRSA SCVs. MATERIALS AND METHODS: Using four strains of clinically isolated MRSA (MRSA122, MRSA160, MRSA18, MRSA123), we adopted IVPDIM comprised of two-compartment in which effective surface-to-volume ratio of 5.34 cm(-1). Human pharmacokinetic regimen simulations of ABK were as follows: 100 mg every 12 h (q12h), 200 mg q24h, 200 mg q12h, and 400 mg q24h. Samples were taken from each model at 0, 1, 2, 4, 6, 12, 24, and 30 h, and the bacterial colony counts were determined. The experiments were repeated twice with ABK-administered groups and control group. RESULTS: MICs of ABK for MRSA122, MRSA160, MRSA18, and MRSA123 were 2, 2, 2, and 1 microgram/mL, respectively. In case of MRSA122, MRSA160, MRSA18, C(max)/MIC were less than 9.0 except for ABK 400 mg q24h regimen. In MRSA123, C(max)/MIC were 8.9 on average at ABK 100 mg q12h regimen. But, other regimen showed C(max)/MIC >9. Four regimens for 4 strains showed statistically different colony counts at 30 h (P=0.000). The more dosage or less frequent dosing interval, the more colonies tended to reduce in all strains. In 100 mg q12h groups, SCVs were observed in all strains within 24 h. With increment of dosage or changing dosing interval from q12h to 24h, SCVs were reduced (P=0.000). Regimen of 400 mg q24h did not let SCVs appear in all strains of MIC 2 microgram/mL during the experiments. CONCLUSION: SCVs were observed when MIC of ABK against MRSA were 1-2 microgram/mL, especially in most cases of C(max)/MIC <9. Those findings were also associated with re-growth of colony during the experiments. Once-daily dosing of ABK could reduce or eliminate the appearance of SCV.