Hyeri Seok

Serologic Evaluation of MERS Screening Strategy for Healthcare Personnel During a Hospital-Associated Outbreak

To evaluate the appropriateness of the screening strategy for healthcare personnel (HCP) during a hospital-associated Middle East Respiratory Syndrome (MERS) outbreak, we performed a serologic investigation in 189 rRT-PCR-negative HCP exposed and assigned to MERS patients. Although 20%-25% of HCP experienced MERS-like symptoms, none of them showed seroconversion by plaque reduction neutralization test (PRNT). Infect Control Hosp Epidemiol 2017;38:234-238.

Serologic responses of 42 MERS-coronavirus-infected patients according to the disease severity

Abstract We evaluated serologic response of 42 Middle East respiratory syndrome coronavirus (MERS-CoV)-infected patients according to 4 severity groups: asymptomatic infection (Group 0), symptomatic infection without pneumonia (Group 1), pneumonia without respiratory failure (Group 2), and pneumonia progressing to respiratory failure (Group 3). None of the Group 0 patients showed seroconversion, while the seroconversion rate gradually increased with increasing disease severity (0.0%, 60.0%, 93.8%, and 100% in Group 0, 1, 2, 3, respectively; P = 0.001). Group 3 patients showed delayed increment of antibody titers during the fourth week, while Group 2 patients showed robust increment of antibody titer during the third week. Among patients having pneumonia, 75% of deceased patients did not show seroconversion by the third week, while 100% of the survived patients were seroconverted (P = 0.003).

Wernicke's encephalopathy after total parenteral nutrition in patients with Crohn's disease

Micronutrient deficiencies in Crohns disease (CD) patients are not uncommon and usually result in a combination of reduced dietary intake, disease-related malabsorption, and a catabolic state. Decreased serum thiamine levels are often reported in patients with CD. Wernickes encephalopathy (WE) is a severe form of thiamine deficiency that can cause serious neurologic complications. Although WE is known to occur frequently in alcoholics, a number of non-alcoholic causes have also been reported. Here, we report two cases of non-alcoholic WE that developed in two severely malnourished CD patients who were supported by prolonged total parenteral nutrition without thiamine supplementation. These patients complained of sudden-onset ophthalmopathy, cerebellar dysfunction, and confusion. Magnetic resonance imaging allowed definitive diagnosis for WE despite poor sensitivity. The intravenous administration of thiamine alleviated the symptoms of WE dramatically. We emphasize the importance of thiamine supplementation for malnourished patients even if they are not alcoholics, especially in those with CD.

Disseminated Talaromyces marneffei and Mycobacterium intracellulare coinfection in an HIV-infected patient

A 25-year-old man with human immunodeficiency virus (HIV) infection presented with fever that had lasted 1 month. The CD4+ T lymphocyte count was 7 cells/μL and computed tomography showed several small lung nodules, splenomegaly, and multiple lymphadenopathy. Talaromyces marneffei was isolated in the initial blood cultures. As the fever persisted despite clearance of fungemia and 10 days of liposomal amphotericin B treatment, cervical lymph node fine-needle aspiration was performed. Mycobacterium intracellulare was isolated from sputum and neck node aspiration cultures. The patient was successfully treated with liposomal amphotericin B, clarithromycin, and ethambutol in addition to antiretroviral therapy. This case suggests that we should consider coinfection of opportunistic pathogens in febrile immunosuppressed patients if the patient does not respond properly to the initial treatment.

Bloodstream infections caused by Acinetobacter species with reduced susceptibility to tigecycline: clinical features and risk factors

INTRODUCTION During recent decades, the rates of multidrug resistance, including resistance to carbapenems, have increased dramatically among Acinetobacter species. Tigecycline has activity against multidrug-resistant Acinetobacter spp, including carbapenem-resistant isolates. However, reports of tigecycline-resistant Acinetobacter spp are emerging from different parts of the world. The purpose of this study was to evaluate potential risk factors associated with tigecycline non-susceptible Acinetobacter bacteremia. METHODS The medical records of 152 patients with Acinetobacter bacteremia attending Samsung Medical Center between January 2010 and December 2014 were reviewed. Non-susceptibility to tigecycline was defined as a minimum inhibitory concentration (MIC) of tigecycline ≥4μg/ml. Cases were patients with tigecycline non-susceptible Acinetobacter bacteremia and controls were those with tigecycline-susceptible Acinetobacter bacteremia. RESULTS Of the 152 patients included in the study, 61 (40.1%) had tigecycline non-susceptible Acinetobacter bacteremia (case group). These patients were compared to 91 patients with tigecycline-susceptible Acinetobacter bacteremia (control group). The case group showed high resistance to other antibiotics (>90%) except colistin (6.6%) and minocycline (9.8%) when compared to the control group, which exhibited relatively low resistance to other antibiotics (<50%). Multivariate analysis showed that recent exposure to corticosteroids (minimum 20mg per day for more than 5 days within 2 weeks) (adjusted odds ratio (OR) 2.887, 95% confidence interval (CI) 1.170-7.126) and carbapenems (within 2 weeks) (adjusted OR 4.437, 95% CI 1.970-9.991) were significantly associated with tigecycline non-susceptible Acinetobacter bacteremia. Although prior exposure to tigecycline was more common in the case group than in the control group (9.8%, 6/61 vs. 2.2%, 2/91; p=0.046), this variable was found not to be a significant factor associated with tigecycline non-susceptibility after adjustment for other variables (adjusted OR 1.884, 95% CI 0.298-11.920; p=0.501). CONCLUSIONS These data suggest that tigecycline non-susceptible Acinetobacter spp have emerged and disseminated in the hospital in association with a recent exposure to carbapenems and an immunosuppressed state. This indicates that the rational use of antibiotics through a comprehensive antimicrobial stewardship program, especially in immunosuppressed patients, may be essential in limiting the emergence and spread of multidrug-resistant organisms such as tigecycline-resistant Acinetobacter spp, which are difficult to treat.

Clinical features and risk factors for development of breakthrough Gram-negative bacteremia during carbapenem therapy

ABSTRACT With the increasing use of carbapenems, carbapenem-resistant Gram-negative bacteria have become a major concern in health care-associated infections. The present study was performed to evaluate the clinical and microbiological features of breakthrough Gram-negative bacteremia (GNB) during carbapenem therapy and to assess risk factors for development of breakthrough GNB. A case-control study was performed at a tertiary hospital from 2005 to 2014. Case patients were defined as individuals whose blood cultures grew Gram-negative bacteria while the patients were receiving carbapenems for at least 48 h before breakthrough GNB. Age-, sex-, and date-matched controls were selected from patients who received carbapenem for at least 48 h and did not develop breakthrough GNB during carbapenem treatment. A total of 101 cases of breakthrough GNB were identified and compared to 100 controls. The causative microorganisms for breakthrough GNB were Stenotrophomonas maltophilia (n = 33), Acinetobacter baumannii (n = 32), Pseudomonas aeruginosa (n = 21), and others (n = 15). Approximately 90% of S. maltophilia isolates were susceptible to levofloxacin and trimethoprim-sulfamethoxazole. The most common infection types were primary bacteremia (38.6%) and respiratory infections (35.6%). More than half of the patients died within a week after bacteremia, and the 30-day mortality rate was 70.3%. In a multivariate analysis, a longer hospital stay, hematologic malignancy, persistent neutropenia, immunosuppressant use, and previous colonization by causative microorganisms were significantly associated with breakthrough GNB. Our data suggest that S. maltophilia, A. baumannii, and P. aeruginosa are the major pathogens of breakthrough GNB during carbapenem therapy, in association with a longer hospital stay, hematologic malignancy, persistent neutropenia, immunosuppressant use, and previous colonization.

Suggested new breakpoints of anti-MERS-CoV antibody ELISA titers: performance analysis of serologic tests.

To provide optimal cut-off values of anti-Middle East respiratory syndrome coronavirus (MERS-CoV) serologic tests, we evaluated performance of ELISA IgG, ELISA IgA, IFA IgM, and IFA IgG using 138 serum samples of 49 MERS-CoV-infected patients and 219 serum samples of 219 rRT-PCR-negative MERS-CoV-exposed healthcare personnel and patients. The performance analysis was conducted for two different purposes: (1) prediction of neutralization activity in MERS-CoV-infected patients, and (2) epidemiologic surveillance of MERS-CoV infections among MERS-CoV-exposed individuals. To evaluate performance according to serum collection time, we used ‘days post onset of illness (dpoi)’ and ‘days post exposure (dpex)’ assessing neutralization activity and infection diagnosis, respectively. Performance of serologic tests improved with delayed sampling time, being maximized after a seroconversion period. In predicting neutralization activity, ELISA IgG tests showed optimal performance using sera collected after 21 dpoi at cut-off values of OD ratio 0.4 (sensitivity 100% and specificity 100%), and ELISA IgA showed optimal performance using sera collected after 14 dpoi at cut-off value of OD ratio 0.2 (sensitivity 85.2% and specificity 100%). In diagnosis of MERS-CoV infection, ELISA IgG exhibited optimal performance using sera collected after 28 dpex, at a cut-off value of OD ratio 0.2 (sensitivity 97.3% and specificity 92.9%). These new breakpoints are markedly lower than previously suggested values (ELISA IgG OD ratio 1.1, sensitivity 34.8% and specificity 100% in the present data set), and the performance data help serologic tests to be practically used in the field of MERS management.

Clinical predictors of Stenotrophomonas maltophilia bacteremia in adult patients with hematologic malignancy

Stenotrophomonas maltophilia (SM) has emerged as an important nosocomial pathogen with high morbidity and mortality. Because of its unique antimicrobial susceptibility pattern, appropriate antimicrobial therapy for SM bacteremia is still challenging, especially in immunocompromised patients. The present study was performed to assess clinical predictors of SM bacteremia in adult patients with hematologic malignancy. From 2006 through 2016, a case-control study was performed at a tertiary-care hospital. Case patients were defined as SM bacteremia in patients with hematologic malignancy. Date- and location-matched controls were selected from among patients with gram-negative bacteremia (GNB) other than SM. A total of 118 cases of SM bacteremia were identified and compared to 118 controls. While pneumonia was the most common source of SM bacteremia, centralline-associated infection was most common in the controls. The overall 30-day mortality rate of cases with SM bacteremia was significantly higher than that of the controls (61.0 and 32.2%, respectively; P < 0.001). A multivariable analysis showed that polymicrobial infection, previous SM isolation, the number of antibiotics previously used ≥ 3, and breakthrough bacteremia during carbapenem therapy were significantly associated with SM bacteremia (all P < 0.01). Previous use of trimethoprim/sulfamethoxazole (TMP/SMX) was negatively association with SM bacteremia (P = 0.002). Our data suggest that SM is becoming a significant pathogen in patients with hematologic malignancy. Several clinical predictors of SM bacteremia can be used for appropriate antimicrobial therapy in hematologic patients with suspected GNB.

Relapsing polychondritis presenting with inflammatory pseudotumor.

To the Editor, Relapsing polychondritis (RP) is an uncommon, chronic multisystem disorder characterized by recurrent episodes of cartilaginous tissue inflammation. It can be life threatening, debilitating, and difficult to diagnose [1]. Cartilaginous tissues are the primary targets of destruction, but immune damage can spread to involve non-cartilaginous tissues such as the kidney and blood vessels [2]. Central nervous system (CNS) involvement is rare, and can manifest as cranial neuropathies, meningitis, or meningoencephalitis [3]. Only a few patients with RP and nervous system involvement have been reported in Korea. In this report, we describe a patient with multiple cranial nerve palsies due to RP related inflammatory pseudotumor. A 60-year-old man was diagnosed with RP when he presented with auricular chondritis, hearing loss, and saddle nose deformity. He had a history of recurrent inflammatory episodes involving auricular and nasal cartilage, as well as a history of conjunctivitis. Laboratory evaluation revealed elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Autoantibody tests for rheumatoid factor, anti-nuclear antibodies, and anti-neutrophil cytoplasmic antibodies were negative. The diagnosis of RP was established based on typical clinical manifestations, without pathological examination. The patient was treated with 1 mg/kg/day of oral prednisolone and experienced symptomatic improvement. With gradual prednisolone tapering, azathioprine was added. During a 3-month follow-up, he remained well while continuing to receive 5 mg prednisolone and 100 mg azathioprine per day orally. Four months after the diagnosis of RP, the patient began experiencing visual difficulties. He developed ptosis and diplopia in the left eye without any history of head trauma or ocular injury. When he was evaluated in the emergency room, his vital signs were within normal limits. Neurological examinations showed third, fourth, and sixth cranial nerve palsies of the left eye (Fig. 1). Pupils were equal in size and responded normally to light. The patient also complained of paresthesia in the territory of the first division of the left trigeminal nerve. Except for these neurologic abnormalities, his physical findings were non-specific. Figure 1. Extraocular left eye movements were disturbed in all directions. Blood tests showed normal CRP and ESR at 0.08 mg/dL and 10 mm/hr, respectively. Lumbar puncture revealed an opening pressure of 14 cm H2O. The cerebrospinal fluid (CSF) tests results were white blood cell count, 0/mm3; glucose, 70 mg/dL (plasma glucose level 100 mg/dL); protein, 23.7 mg/dL, adenosine deaminase 0.1 IU/L. No organisms were observed on Gram stain and acid-fast bacillus stain. Cryptococcus antigen test and mycobacterium tuberculosis polymerase chain reaction test were negative. The final CSF culture results revealed no organisms. CSF cytology was negative for malignant cells. Magnetic resonance imaging (MRI) of the cranial nerves showed diffuse thickening and enhancement of the bilateral cavernous sinuses, orbital apex, and pachymeninges along with Meckel’s cave (Fig. 2). These findings suggest inflammatory pseudotumor involvement of the cranial nerve pathways. Nerve conduction study, electromyography, and blink test were performed. The results indicated bilateral trigeminal nerve dysfunction. Biopsy of the lesion was not performed because it was difficult to reach and the procedure was considered high risk for complications such as nerve injury. Figure 2. Fat-saturated contrast-enhanced T1-weighted magnetic resonance imaging showing: (A, C) diffuse enhancing thickening involving left orbital apex (arrows); (B) enhancing pachymeningeal thickening, including in left Meckel’s (trigeminal) cave (arrowheads); ... The patient was started on intravenous (IV) methylprednisolone, 1 mg/kg/day. After 4 days, extraocular movements were slightly improved, but the left eye ptosis remained. He was started on IV methylprednisolone, 1 g/day over 5 days followed by oral prednisolone, 60 mg/day. High dose steroid therapy resulted in full neurologic recovery after 3 weeks. The prednisolone dosage was gradually reduced. Few previous cases of RP with CNS involvement have been reported. In most cases, the clinical manifestation was meningoencephalitis. Other associated neurological disorders include impaired cognitive dysfunction, seizure, ptosis, and diplopia. The etiology of CNS involvement in RP patients remains unknown but likely originates from autoimmunity. Wang et al. [3] speculated that vasculitis or non-specific inflammation might involve the leptomeninges and brain parenchyma. Ocular manifestations of RP are diverse. The most common manifestations are scleritis and episcleritis. Iritis may occur in as many as 30% of patients who present with scleritis or keratitis. Proptosis with chemosis simulating an orbital pseudotumor is the uncommon manifestation, but may be the initial presentation of RP [4]. Extraocular muscle palsies have been reported and are probably related to a vasculitis involving muscles or related to nerve insults. The current patient presented with multiple cranial nerve palsies and without any findings of meningoencephalitis or scleritis. MRI revealed diffuse thickening and enhancement of the cranial nerve pathways including bilateral cavernous sinuses, orbital apex, and Meckel’s cave. If an orbital mass is seen, biopsy may be necessary to reveal the type of inflammatory histology and exclude neoplastic causes. In this case, a biopsy was not performed for tissue confirmation because of the lesion location. Lichauco et al. [5] reported an orbital mass in a patient with RP that was confirmed by biopsy as mucosa-associated lymphoid tissue type B cell lymphoma. In the reported case by Lichauco et al. [5], biopsy was performed because the initial steroid treatment was only partially effective. Our patient completely recovered after steroid treatment, but biopsy would be necessary if his symptoms reappear or if any suspicion of malignancy arises. We report our experience with a patient diagnosed with RP and pseudotumor who presented with multiple cranial nerve palsies. In RP patients, CNS and ocular manifestations are diverse. If neurologic or ophthalmologic symptoms develop, careful neurologic examination, imaging, and biopsy should be considered to establish a diagnosis.

Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently

A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses.