Beyond One-Size-Fits-All: Tailoring Teicoplanin Regimens for Normal Renal Function Patients Using Population Pharmacokinetics and Monte Carlo Simulation.

In patients with normal renal function, significant teicoplanin dose adjustments are often necessary. This study aimed to develop a population pharmacokinetic (PK) model for teicoplanin in healthy adults and use it to recommend optimal dosage regimens for patients with normal renal function. PK samples were obtained from 12 subjects and analyzed using a population approach. The derived parameters informed Monte Carlo simulations for dosing recommendations. The PK profile was best described using a three-compartment model, in which the estimated glomerular filtration rate calculated via the CKD-EPI equation and adjusted for body surface area was identified as a significant covariate affecting total clearance. For pathogens with a minimum inhibitory concentration of 1 mg/L, a loading dose (LD) of 14 mg/kg administered every 12 h for four doses, followed by a maintenance dose (MD) of 16 mg/kg administered every 24 h, is recommended. These findings indicate the need for dosage adjustments, such as increasing the LD and MD or decreasing the dosing interval of MD in patients with normal renal function. Because of the long half-life of teicoplanin and the requirement for long-term administration, therapeutic drug monitoring at strategic intervals is important to avoid nephrotoxicity associated with elevated trough concentrations.

Varicella-Zoster Virus Reactivation During the Incubation Period for Scrub Typhus: A Case Report.

BACKGROUND Herpes zoster caused by the reactivation of latent varicella-zoster virus is thought to result from the waning of specific cell-mediated immunity. Scrub typhus, an acute infectious disease caused by Orientia tsutsugamushi, affects multiple organs and is characterized by microangiopathies that result in significant vascular leakage and subsequent end-organ injury. Very few cases of reactivation of the varicella-zoster virus following scrub typhus occurrence have been reported. Furthermore, no previous studies have directly investigated whether Orientia tsutsugamushi infection is a potential risk factor for herpes zoster. CASE REPORT We present the case of a 64-year-old woman without a previous illness who simultaneously developed herpes zoster of the thoracic dermatome and scrub typhus. Clinical symptoms of scrub typhus appeared during the treatment course for herpes zoster symptoms. Based on positive virus antibody test results, the patient was diagnosed with scrub typhus. This is a unique case of reactivation of the varicella-zoster virus that occurred during a silent incubation period for scrub typhus. CONCLUSIONS This report indicates the possibility of reactivation of latent varicella-zoster virus following Orientia tsutsugamushi infection, although the relationship between the 2 remains undetermined. Physicians should be aware that scrub typhus might be a potential determinant of varicella-zoster virus reactivation.

Pharmacokinetics and Monte Carlo Simulation of Meropenem in Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation.

Objectives: There have been few clinical studies of ECMO-related alterations of the PK of meropenem and conflicting results were reported. This study investigated the pharmacokinetics (PK) of meropenem in critically ill adult patients receiving extracorporeal membrane oxygenation (ECMO) and used Monte Carlo simulations to determine appropriate dosage regimens. Methods: After a single 0.5 or 1 g dose of meropenem, 7 blood samples were drawn. A population PK model was developed using nonlinear mixed-effects modeling. The probability of target attainment was evaluated using Monte Carlo simulation. The following treatment targets were evaluated: the cumulative percentage of time during which the free drug concentration exceeds the minimum inhibitory concentration of at least 40% (40% fT>MIC), 100% fT>MIC, and 100% fT>4xMIC. Results: Meropenem PK were adequately described by a two-compartment model, in which creatinine clearance and ECMO flow rate were significant covariates of total clearance and central volume of distribution, respectively. The Monte Carlo simulation predicted appropriate meropenem dosage regimens. For a patient with a creatinine clearance of 50-130 ml/min, standard regimen of 1 g q8h by i. v. infusion over 0.5 h was optimal when a MIC was 4 mg/L and a target was 40% fT>MIC. However, the standard regimen did not attain more aggressive target of 100% fT>MIC or 100% fT>4xMIC. Conclusion: The population PK model of meropenem for patients on ECMO was successfully developed with a two-compartment model. ECMO patients exhibit similar PK with patients without ECMO. If more aggressive targets than 40% fT>MIC are adopted, dose increase may be needed.

Acute respiratory distress syndrome caused by carbon monoxide poisoning and inhalation injury recovered after extracorporeal membrane oxygenation along with direct hemoperfusion with polymyxin B-immobilized fiber column: a case report.

BACKGROUND: Inhalation injury from smoke or chemical products and carbon monoxide poisoning are major causes of death in burn patients from fire accidents. Respiratory tract injuries from inhalation injury and carbon monoxide poisoning can lead to acute respiratory distress syndrome and cytokine storm syndrome. In the case of acute respiratory failure needing mechanical ventilation accompanied by cytokine storm, mortality is high and immediate adequate treatment at the emergency department is very important. CASE PRESENTATION: This report describes a case of acute respiratory distress syndrome and cytokine storm followed by carbon monoxide poisoning in a 34-year-old Korean male patient who was in a house fire, and was successfully treated by extracorporeal membrane oxygenation and direct hemoperfusion with polymyxin B-immobilized fiber column at emergency department. CONCLUSIONS: To prevent mortality in acute respiratory distress syndrome with cytokine storm from inhalation injury and to promote a better prognosis, we suggest that early implication of extracorporeal membranous oxygenation along with direct hemoperfusion with polymyxin B-immobilized fiber column even at the emergency department should be considered.

Risk factors for isolation of multi-drug resistant organisms in coronavirus disease 2019 pneumonia: A multicenter study.

OBJECTIVES: Superimposed multi-drug resistant organisms (MDROs) co-infection can be associated with worse outcomes in patients with severe coronavirus disease 2019 (COVID-19), even if these patients were managed with strict airborne and contact precautions. Identifying risk factors for isolation of MDROs is critical to COVID-19 treatment. METHODS: All eligible adult patients with confirmed COVID-19 pneumonia from 10 hospitals in the Republic of Korea between February 2020 and May 2020 were retrospectively enrolled. Using this cohort, epidemiology and risk factors for isolation of MDROs were evaluated. RESULTS: Of 152 patients, 47 with microbial culture results were included. Twenty isolates of MDROs from 13 (28%) patients were cultured. Stenotrophomonas maltophilia (5 isolates) was the most common MDRO, followed by methicillin-resistant staphylococcus aureus (4 isolates). MDROs were mostly isolated from sputum samples (80%, 16/20). The median time from hospitalization to MDRO isolation was 28 days (interquartile range, 18-38 days). In-hospital mortality was higher in patients with MDRO isolation (62% vs 15%; P = .001). Use of systemic corticosteroids after diagnosis of COVID-19 (adjusted odds ratio [aOR]: 15.07; 95% confidence interval [CI]: 2.34-97.01; P = .004) and long-term care facility (LTCF) stay before diagnosis of COVID-19 (aOR: 6.09; 95% CI: 1.02-36.49; P = .048) were associated with MDRO isolation. CONCLUSIONS: MDROs were isolated from 28% of COVID-19 pneumonia patients with culture data and 8.6% of the entire cohort. Previous LTCF stay and adjunctive corticosteroid use were risk factors for the isolation of MDROs. Strict infection prevention strategies may be needed in these COVID-19 patients with risk factors.

Coxsackievirus A6-induced Hand-Foot-and-Mouth Disease Mimicking Stevens-Johnson Syndrome in an Immunocompetent Adult.

Hand-foot-and-mouth disease, a highly contagious viral infection, occurs more common in children than in adults. However, there was a recent outbreak of Coxsackievirus A6-induced infection with an atypical presentation among the adult population. Stevens-Johnson syndrome is a severe mucocutaneous disease characterized by extensive necrosis and detachment of the epidermis, and this condition is commonly caused by medications. Herein, we describe a 30-year-old male patient taking allopurinol for the management of gout. The patient presented with numerous erythematous papules, vesicles, and patches with mucosal eruptions on the whole body, oral mucositis, and fever, and he was finally diagnosed with hand-foot-and-mouth disease.

Diagnostic usefulness of differential time to positivity in neutropenic cancer patients with suspected catheter-related candidemia.

Methods for distinguishing catheter-related candidemia (CRC) from non-CRC before catheter removal remain limited. We thus evaluated the diagnostic performance of differential time to positivity (DTP) to diagnose CRC in neutropenic cancer patients with suspected CRC. Of the 35 patients enrolled, 15 (43%) with CRC (six definite and nine probable) and 17 (49%) with non-CRC were finally analyzed. Based on the receiver operating characteristic curve, the optimal cutoff value of DTP for diagnosing CRC was ≥1.45 hours with the sensitivity 80% (95% confidence interval [CI], 51-95) and specificity 100% (95% CI, 80-100), respectively.

Serum Aminotransferase Level in Rhabdomyolysis according to Concurrent Liver Disease.

BACKGROUND/AIMS: The serum aminotransferase level is usually elevated in rhabdomyolysis, and these enzymes originate from the skeletal muscle. On the other hand, there is limited data showing whether the degree of elevation of these enzymes differs according to the concurrent liver disease. METHODS: Patients with rhabdomyolysis were selected when their serum creatinine kinase level was >1,000 U/L. They were categorized as the group with and without concurrent liver disease. The AST and ALT levels in both groups were compared. In addition, the aminotransferase level was compared between those with rhabdomyolysis and those with alcoholic liver disease. RESULTS: Among the 165 patients with rhabdomyolysis, 19 had concurrent liver disease. The median peak AST was higher in the group with concurrent liver disease (332 U/L [interquartile range (IQR), 127-1,604] vs. 219 U/L [IQR, 115-504]). In addition, the median peak ALT was higher in the group with concurrent liver disease (107 U/L [IQR, 74-418] vs. 101 U/L [IQR, 56-218]). On the other hand, there was no significant difference in both enzymes between the two groups. The median peak AST level was significantly higher in those with rhabdomyolysis than in those with alcoholic liver disease (221 U/L [IQR, 118-553] vs. 103 U/L [IQR, 59-206]), but the median peak ALT was not significantly different (102 U/L [IQR, 58-222] vs. 51 U/L [IQR, 26-117]). CONCLUSIONS: Rhabdomyolysis showed an elevated AST-dominant aminotransferase level, which is not different according to concurrent liver disease. Therefore, it is recommended that rhabdomyolysis be considered first in cases of elevated aminotransferase levels in patients with a suspicious skeletal muscle injury.

Diagnostic performance of immunohistochemistry for the aspergillosis and mucormycosis.

OBJECTIVE: To investigate the accuracy of immunohistochemistry (IHC) tests for distinguishing between mucormycosis and aspergillosis and compare the clinical characteristics of mucormycosis patients according to galactomannan (GM) results. METHODS: We evaluated diagnostic performance of IHC test with tissue sections of patients with culture-proven invasive fungal infection. In addition, we conducted PCR assay with tissue sections of mucormycosis patients with positive GM results to evaluate the possibility of co-infection. RESULTS: In culture-proven mucormycosis (n = 13) and aspergillosis (n = 20), the sensitivity and specificity of IHC test were both 100% for mucormycosis and 85% and 100%, respectively, for aspergillosis. Among the 53 patients who met the modified criteria for proven mucormycosis and had GM assay results, 24 (45%) were positive. Compared with those with negative GM results (n = 29), mucormycosis patients with positive GM results had significantly higher incidence of gastrointestinal tract infections (6/24 [25%] vs 0/29 [0%], P = .006) and were more likely to be histomorphologically diagnosed as aspergillosis (7/24 [29%] vs 2/29 [7%], P = .06). PCR assay amplified both Aspergillus- and Mucorales-specific DNA in 6 of these 24 cases. CONCLUSIONS: Immunohistochemistry tests seem useful for compensating for the limitations of histomorphologic diagnosis in distinguishing between mucormycosis and aspergillosis. Some proven mucormycosis patients with positive GM results had histopathology consistent with aspergillosis and gastrointestinal mucormycosis. In addition, about one quarter of these patients revealed the evidence of co-infection with aspergillosis by PCR assay.

Rapidly Fatal Emphysematous Osteomyelitis with Multiple Septic Emboli and Liver Abscess Caused by Klebsiella pneumoniae.

Emphysematous osteomyelitis, characterized by intraosseous gas, is a rare but potentially fatal condition that requires prompt diagnosis and aggressive therapy. Causative organisms are members of the bacterial family Enterobacteriaceae or anaerobes in most cases and significant comorbidities such as diabetes mellitus and malignancy, may predispose an individual to the development of emphysematous osteomyelitis. We report a case of extensive emphysematous osteomyelitis via hematogenous spread from Klebsiella pneumoniae liver abscess, complicated by gas-containing abscesses in adjacent soft tissues and epidural space, and multiple systemic septic emboli in a diabetic patient.

Giant Brunner's Gland Hamartoma of the Duodenal Bulb Presenting with Upper Gastrointestinal Bleeding and Obstruction.

Brunner's gland hamartomas are small benign lesions that are most commonly found in the bulb of the duodenum. They are very uncommon, and most are found incidentally during upper gastrointestinal series or esophagogastroduodenoscopy. The lesions tend to be asymptomatic, but patients may present with symptoms of duodenal obstruction or hemorrhage secondary to ulceration. Histologically, a Brunner's gland hamartoma consists of the components of Brunner's gland cells, as well as glandular, adipose and muscle cells. In this study, we report the case of a 30-year-old man who presented with upper gastrointestinal bleeding and obstructive symptoms due to a giant Brunner's gland hamartoma in the duodenal bulb. The hamartoma was successfully removed by endoscopic resection. No significant complications were observed. Microscopically, the lesion was found to be entirely composed of variable Brunner's glands and adipocytes.

[Concomitant Drug Reaction with Eosinophilia and Systemic Symptom Syndrome from Ethambutol and Autoimmune Hepatitis from Isoniazid].

Anti-tuberculosis drugs can produce levels of hepatotoxicity ranging from mild elevation of aminotransferase to severe acute hepatitis. A few cases of drug-induced autoimmune hepatitis or the drug reaction with eosinophilia and systemic symptom (DRESS) syndrome by anti-tuberculosis medications have been reported. However, concomitant occurrence of these two disorders has not been reported. Here, we present a case of severe acute hepatitis with DRESS syndrome and autoimmune hepatitis resulting from primary standard anti-tuberculosis drugs. Both conditions were successfully treated with a systemic steroid regimen.

Childhood colon cancer in a patient with ataxia telangiectasia.

BACKGROUND: Ataxia-telangiectasia (AT) is a rare autosomal recessive disease characterized by progressive neurologic impairment and cerebellar ataxia. In addition, patients with this disease are known to have an inherent increased susceptibility to the development of cancer, predominantly hematologic malignancies. METHODS: We report the case of a young boy with AT from Russia, who had abdominal pain. Laboratory tests and radiologic examinations were performed to him. RESULTS: After abdominal computed tomography (CT), colonoscopy and surgical interventions, the young boy was diagnosed with colon cancer that had signet ring cell features. CONCLUSIONS: It is known that the patient with AT appeared to be predisposed to various tumors, including leukemia or lymphoma, which are more common in childhood. Even if the patient with AT could have solid tumor such as stomach cancer or breast cancer, it is less likely to have colon cancer, especially signet ring cell type. Actually, no case of colon cancer has ever been reported, especially in young patient and hence, we have focused on this point and are hereby reporting this unique case.

Nephrotic syndrome complicated with portal, splenic, and superior mesenteric vein thrombosis.

Thromboembolism is a major complication of nephrotic syndrome. Renal vein thrombosis and deep vein thrombosis are relatively common, especially in membranous nephropathy. However, the incidence of portal vein and superior mesenteric vein (SMV) thrombosis in patients with nephrotic syndrome is very rare. To date, several cases of portal vein thrombosis treated by anticoagulation therapy, not by thrombolytic therapy, have been reported as a complication of nephrotic syndrome. Here, we report a case of portal, splenic, and SMV thrombosis in a patient with a relapsed steroid dependent minimal change disease who was treated successfully with anticoagulation and thrombolytic therapy using urokinase. Radiologic findings and his clinical conditions gradually improved. Six months later, a complete remission of the nephrotic syndrome was observed and the follow-up computed tomography scan showed the disappearance of all portal vein, splenic vein, and SMV thrombi.