Moon Won Kang

Prevalence of metallo-β-lactamase among Pseudomonas aeruginosa and Acinetobacter baumannii in a Korean University hospital and comparison of screening methods for detecting metallo-β-lactamase

To identify the metallo-β-lactamases (MBLs) prevalent in Korea, a total of 130 clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii (99 P. aeruginosa and 31 A. baumannii) with a reduced susceptibility to imipenem (IPM) and/or ceftazidime (CAZ) was subjected to PCR analyses with primers specific to blaIMP-1, blaVIM-1, and blaVIM-2. In addition, inhibitor-potentiated disk diffusion methods (IPD) using two kinds of substrate–inhibitor combinations (ceftazidime–2-mercaptopropionic acid (2MPA) and imipenem–EDTA) were investigated. Thirty-three isolates (29 P. aeruginosa and 4 A. baumannii) carried blaVIM-2 and two P. aeruginosa isolates harbored blaIMP-1. The enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) pattern revealed that many of the VIM-2-producing P. aeruginosa isolates were clonally related, whereas the A. baumannii isolates were diverse. The inhibitor-potentiated disk diffusion test using imipenem–EDTA was highly sensitive and specific for detecting the VIM-2 producer. These results suggest that VIM-2 is an important MBL in P. aeruginosa and A. baumannii in the Korean hospital of this study and that the IMP-1-producing P. aeruginosa has also emerged. Screening for MBLs and strict infection control for these isolates will contribute to prevent further spread of resistance.

Infectious complications in living-donor liver transplant recipients: a 9-year single-center experience

Background. Infectious complications following living‐donor liver transplantation (LDLT) remain a major cause of morbidity and mortality. We analyzed the frequency and type of infectious complications according to the post‐transplantation period, and their risk factors with regard to morbidity and mortality.

Epidemiology and risk factors for bacteremia in 144 consecutive living-donor liver transplant recipients.

Purpose Bacteremia is a major infectious complication associated with mortality in liver transplant recipients. The causative organisms and clinical courses differ between medical centers due to variations in regional bacterial epidemiology and posttransplant care. Further, living donors in Korea contribute to 83% of liver transplants, and individualized data are required to improve survival rates. Patients and Methods We retrospectively analyzed 104 subjects who had undergone living-donor liver transplant from 2005 to 2007. Results Among the 144 consecutive living-donor liver transplant recipients, 24% (34/144) developed bacteremia, 32% (46/144) developed non-bacteremic infections, and 44% (64/144) did not develop any infectious complications. Forty episodes of bacteremia occurred in 34 recipients. The major sources of bacteremia were intravascular catheter (30%; 12/40), biliary tract (30%; 12/40), and abdomen (22.5%; 9/40). Gram-positive cocci were more common (57.5%; 23/40) than Gram-negative rods (32.5 %; 13/40) and fungi (10%; 4/40). The data revealed that the following factors were significantly different between the bacteremia, non-bacteremic infection, and no infection groups: age (p = 0.024), posttransplant hemodialysis (p = 0.002), ICU stay (p = 0.012), posttransplant hospitalization (p < 0.0001), and duration of catheterization (p < 0.0001). The risk factors for bacteremia were older than 55 years (odds ratio, 6.1; p = 0.003), catheterization for more than 22 days (odds ratio, 4.0; p = 0.009), UNOS class IIA (odds ratio, 6.6; p = 0.039), and posttransplant hemodialysis (odds ratio, 23.1; p = 0.001). One-year survival rates in the bacteremic, non-bacteremic infection, and no infection groups were 73.2%, 91.3%, and 93.5%, respectively. Conclusion Early catheter removal and preservation of renal function should focus for improving survival after transplant.

Carbapenem-resistant Acinetobacter baumannii: diversity of resistant mechanisms and risk factors for infection.

Carbapenem-resistant Acinetobacter baumannii (CRAB) are an increasing infectious threat in hospitals. We investigated the clinical epidemiology of CRAB infections vs. colonization in patients, and examined the mechanisms of resistance associated with elevated minimum inhibitory concentrations (MICs) for carbapenems. From January to June 2009, 75 CRAB strains were collected. CRAB infection was significantly associated with malignancy and a high APACHE II score. The most dominant resistance mechanism was ISAba1 preceding OXA-51, producing strains with overexpression of efflux pump. Strains carrying blaOXA-23-like enzymes had higher carbapenem MICs than those carrying blaOXA-51-like enzymes; however, the presence of multiple mechanisms did not result in increased resistance to carbapenems. There was no difference in the resistance mechanisms in strains from infected and colonized patients. The majority of strains were genetically diverse by DNA macrorestriction although there was evidence of clonal spread of four clusters of strains in patients.

Diagnostic value of 18F‐FDG PET/CT in patients with fever of unknown origin

This study investigates the diagnostic value of 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) in patients with 109 classical fever of unknown origin (FUO). Of the 48 18F‐FDG PET/CT scans, 41 (85.4%) were interpreted as abnormal, and 25 (52.1% of all scans) were considered clinically helpful. The final cause of fever was determined in 41 patients (85.4%); infection (25%), malignancy (12.5%), non‐infectious inflammatory disease (16.7%) and miscellaneous causes (31.3%). 18F‐FDG PET/CT contributed to the final diagnosis of FUO in 65.8%.

Risk factors for vancomycin-resistant enterococci infection and mortality in colonized patients on intensive care unit admission

This study examined the incidence of and risk factors for development of vancomycin-resistant enterococci (VRE) infection and death in VRE-colonized patients in a medical intensive care unit. VRE colonization was identified in 184 patients (17.6%) in whom VRE perianal swab cultures were obtained. Of these, 28 (11.9%) developed VRE infection. Control of infectious sources is crucial to decrease development of VRE infections and optimize the survival of VRE-colonized patients.

Acute cytomegalovirus pneumonia and hepatitis presenting during acute HIV retroviral syndrome

Cytomegalovirus (CMV) disease is a frequent opportunistic infection that usually occurs in the late stages of HIV infection as a result of reactivation of a latent infection. We report a case of a 23-year-old man with acute retroviral syndrome complicated by coexisting CMV pneumonia and CMV hepatitis, which were documented by histopathological examination. His CMV pneumonia and hepatitis were assumed to be primary CMV diseases owing to the absence of CMV IgG antibody. To the best of our knowledge, this is the first case of simultaneous CMV pneumonia and hepatitis occurring as primary CMV diseases during primary HIV infection. This case indicates that invasive CMV diseases such as pneumonia and hepatitis should be considered even in patients with primary HIV infection.

Anxiety and depressive symptoms among patients infected with human immunodeficiency virus in South Korea

Patients infected with human immunodeficiency virus (HIV) may develop mental health problems such as anxiety and depression, which negatively impact of disease progression. We investigated factors associated with the prevalence of anxiety and depression symptoms among HIV-infected patients in Korea. A total of 840 HIV-infected patients who participated in the Korea HIV/AIDS Cohort Study from 2006 to 2012 were evaluated. Socio-demographic, epidemiologic, and clinical variables were obtained through standardized questionnaires. The State-Trait Anxiety Inventory and Beck Depression Inventory were used to assess the symptoms of anxiety and depression. Multiple logistic regression analyses were performed to identify factors associated with symptoms of anxiety and depression. The prevalence of anxiety and depressive symptoms among HIV-infected patients was 32% and 36%, respectively. Ex-smoker and persistent symptoms for more than one week within the past six months and diagnosis of HIV infection within one year were associated with increased anxiety symptoms (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.09–2.69; OR 1.52, 95% CI 1.09–2.11; OR 1.49, 95% CI 1.02–2.20) and current smoking and persistent symptoms were also associated with increased depressive symptoms (OR 2.10, 95% CI 1.31–3.30; OR 1.87, 95% CI 1.25–2.79). Marital status, current smoking, current drinking, and persistent symptoms were associated with both increased anxiety and depressive symptoms (OR 1.75, 95% CI 1.07–2.88; OR 1.66, 95% CI 1.06–2.61; OR 1.88, 95% CI 1.18–2.99). The prevalence of anxiety and depressive symptoms among HIV-infected patients is higher than those estimated for the general population. This study shows the necessity to evaluate symptoms of anxiety and depression and suggest psychological support for HIV-infected patients who smoke or have persistent symptoms or have sexual partner or drink.

Ocular syphilis characterised by severe scleritis in a patient infected with HIV.

A 71-year-old man presented with decreased vision and red eye in his left eye that had lasted for 1 month. He was diagnosed as HIV-positive 2 years previously and had received highly active antiretroviral therapy (HAART). Visual acuity was hand motion only, and conjunctival injection and chemosis were noted (fi gure, A). A fundus examination showed prominent vitritis, and sectorial haemorrhagic retinitis in the superonasal periphery, which was much the same as viral retinitis (fi gure, B). After 5 days, the visual acuity had decreased to light perception, and the retinal lesion had enlarged and was protruding (fi gure, C). A viral PCR of the aqueous humour was negative. The patient’s CD4 cell count was 377 cells per μL. Rapid plasma reagin and fl uorescent treponemal antibody absorbed tests of the serum were positive. 5 days after intravenous penicillin G was given, the infl ammatory reaction substantially improved (fi gure, D, E). At 6 months, the eye had no infl ammation, and the patient’s vision was 20/50 (fi gure, F). His CD4 cell count was 517 cells per μL, and the patient’s condition was stable without any complications. Ocular syphilis is known as a great imitator and does not have a pathognomonic ocular feature. It can involve the entire ocular section, and its clinical manifestations can include scleritis, iritis, chorioretinitis, and optic neuritis. Retinitis in patients infected with HIV can be associated with various ocular infections such as viral retinitis, toxoplasmosis, and syphilis. Delayed diagnosis and treatment of retinitis can lead to permanent visual impairment. Clinical manifestations and the immune status of the patient can provide clues to help with the diff erential diagnosis. Cytomegalovirus retinitis, which is the most common opportunistic infection in the HIV population despite HAART, usually develops in quiet eyes (those with a clear cornea without redness or irritation of the conjunctiva or sclera) with lower CD4 cell counts. In our patient, severe scleritis was a characteristic presenting sign distinguishable from cytomegalovirus retinitis. The possibility of ocular syphilis should be considered in a diff erential diagnosis of retinitis in an infl amed red eye in HIV-positive patients receiving HAART, to ensure early diagnosis and treatment.

Two cases of scrub typhus presenting with Guillain-Barre syndrome with respiratory failure.

To the Editor, Scrub typhus is an acute febrile disease caused by Rickettsia, and traditionally occurs in autumn. Orientia tsutsugamushi is an obligate intracellular Gram-negative bacterium that proliferates in vascular endothelial cells; this characteristic enables the involvement of multiple organs. The most common clinical features are conjunctival injection, high fever, and lymphadenopathy. Neurological complications, such as meningitis and hearing impairment with suspected cranial nerve (VIII) invasion, were reported in 12.5% cases [1,2]. However, involvement of brain parenchyma or peripheral nerves is rare. Only three cases of Guillain-Barre syndrome (GBS) related to scrub typhus have been reported [3-5]. We experienced two cases of scrub typhus-related GBS that presented with severe respiratory failure and were managed with mechanical ventilation, doxycycline, and immunoglobulin. A 60 year-old male visited the emergency department after suffering weakness of the lower extremities for two days. Ten days before the visit, he had visited a local private clinic for headache and chills. After being diagnosed with scrub typhus, he was treated with doxycycline. His symptoms marginally improved, but weakness in both lower extremities developed. He had no other medical history except pulmonary tuberculosis 10 years previously. Vital signs were stable (blood pressure 120/70 mmHg, pulse rate 68/min, body temperature 36.6℃). A physical examination revealed lymphadenopathy in the right inguinal area, a maculopapular rash on the chest wall, and eschar on the right knee. He showed an alert mental status, and a manual muscle test (MMT) revealed lower extremity weakness (upper extremity, grade V; lower extremity, grade IV). Laboratory results showed a WBC count of 9,020/mm3 (neutrophils 51.9%, lymphocytes 35.7%); hemoglobin (Hb), 12.2 g/dL; platelets, 269,000/mm3; alanine aminotransferase (AST), 100 IU/L; alanine aminotransferase (ALT), 110 IU/L; blood urea nitrogen (BUN), 10 mg/dL; creatinine, 0.52 mg/dL; total protein, 6.5 mg/dL; albumin, 3.3 mg/dL; and C-reactive protein, 2.10 mg/dL. Lumbar puncture revealed a glucose level of 74 mg/dL, a total protein level 210 mg/dL, and white blood cell (WBC) count of 20/mm3 (lymphocytes 90%). Serum O. tsutsugamushi antibody titer was positive (1:320). There was no serologic evidence of Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infection or reactivation (VCA-IgG/IgM +/-, EADR-IgG -/±, EBNA IgG +/-, CMV IgG/IgM +/-). A human immunodeficiency virus (HIV) test was negative. Two days after admission, weakness in both extremities progressed (upper, grade II; lower, grade II), and he developed a mild disturbance of consciousness. Serum anti-ganglioside antibodies, GD1b IgG and GM1 IgG, and anti-myelin-associated glycoprotein antibody were negative, but GM1 IgM and GD1b IgM antibodies were positive (Table 1). An electromyography showed diffuse demyelinated neuropathy, which was prominent in the lower extremities. The brain magnetic resonance diffusion image was normal. Intravenous immunoglobulins were administered for five days (22 g, 400 mg/kg/day), and doxycycline was maintained at 100 mg/12 hr (PO). On day 4 after admission, the patient complained of dysphagia and dyspnea. The patient required mechanical ventilation due to respiratory muscle weakness. Eleven days after admission, he recovered spontaneous breathing, and the ventilator was removed. At 48 days after admission, his MMT grade recovered to normal, and he was discharged without complications. Table 1 Comparison of clinical characteristics In the second case, a 46 year-old female without any prior medical history, presented at an emergency department having suffered decreased mental status for 12 hours. Before admission, she had visited the local clinic complaining of fever and myalgia for the previous seven days. After diagnosis with type II diabetes mellitus and ketoacidosis, intravenous fluid replacement and glycemic control were initiated. During management of ketoacidosis, an unexplained decrease in mental status and hypoxemia were noticed. After intubation, she was transferred to our hospital. Initial vital signs were unstable (blood pressure 70/50 mmHg, pulse rate 127/min, respiration 12 times/min, and body temperature 38.6℃). Chest examination revealed rale sounds in the lower right lung field. A maculopapular rash on the entire body and eschar on the posterior site of the left knee were also noticed. MMT revealed weakness in both extremities (upper, grade III; lower, grade III). Laboratory results showed a WBC count of 12,560/mm3 (neutrophils, 77%; lymphocytes, 17%); Hb, 14 g/dL; platelets, 144,000/mm3; AST, 40 IU/L; ALT, 29 IU/L; BUN, 45.1 mg/dL; creatinine, 1.06 mg/dL; total protein, 5.5 mg/dL; albumin, 2.3 mg/dL; and C-reactive protein, 3.17 mg/dL. Sodium, potassium, chloride, and glucose levels of 150 mEq/L, 3.8 mEq/L, 116 mEq/L, and 196 mg/dL, respectively, were also detected. HbA1C was 12.3%, and D-dimer, fibrin degradation product, and fibrinogen were 14 mg/mL, 52 mg/mL, and 137 g/L, respectively. An arterial blood gas test before intubation showed metabolic acidosis and hypoxemia (pH 7.122; PCO2, 58.0 mmHg; PaO2, 53.1 mmHg; HCO3-, 15.3 mmol/L; SpO2, 75.6%). Chest X-ray revealed ground glass opacity on both the lower lung fields. Serum O. tsutsugamushi antibody titer was positive at 1:320. There was no serologic evidence of EBV and CMV infection or reactivation, and an HIV test was negative. Bacterial growth was not detected on blood, urine, and sputum cultures. Serum Mycoplasma pneumoniae IgM and IgG, and Streptococcus pneumoniae and Legionella urinary antigens were also negative. Due to the diagnosis of diabetic ketoacidosis, nosocomial pneumonia, and septic shock with pulmonary edema, empirical antibiotics were administered (meropenem 1 g/8 hr, teicoplanin 400 mg/24 hr). Intravenous insulin injection and doxycycline 100 mg/12 hr (PO) were maintained for seven days. Five days after admission, her vital signs were stable, and her mental status was alert. Although her chest X-ray markedly improved after 13 days, muscle weakness in the extremities (upper, grade IV; lower, grade III) remained, and a low respiration rate (7-8/min) was detected. A brain computed tomography scan was normal, and electromyography showed acute sensoriomotor polyneuropathy, which may have been due to GBS. Spinal tapping revealed a WBC count of 1/m3; RBC, 0/mm3; protein, 118 mg/dL; and glucose, 64 mg/dL. Serum anti-ganglioside antibodies GD1b IgG/IgM and GM1 IgG/IgM and anti-myelin-associated glycoprotein antibody were all negative (Table 1). After recovery from intubation, rehabilitation maintenance was required. Two months after admission, MMT revealed normal muscle power, and she was discharged without complications. GBS is known to be associated with several infections, such as Campylobacter jejuni, CMV, EBV, and M. pneumoniae. Our first case was diagnosed as scrub typhus based on maculopapular rash, eschar, and an O. tsutsugamushi antibody test. Additionally, we could diagnose GBS based on neurological examination, electromyography, and the presence of anti-ganglioside antibodies. We excluded EBV, CMV, Mycoplasma, and other bacteria. Involvement of the respiratory system is observed in 10-30% GBS patients [3]; however, there is no evidence of respiratory failure requiring mechanical ventilation among the reported cases of scrub typhus-related GBS [3-5]. Typical electromyography findings of demyelinated neuropathy and lower extremity weakness were detected, and GD1b and GM1 IgM antibody results were also positive. A positive result for the anti-ganglioside antibody had not been observed in the reported cases [3-5]. GBS mortality rates are usually 3-7%, but mortality in patients requiring respiratory support can be as high as 20% [2]. Our cases required mechanical ventilation, but both recovered completely. The second case was combined with pneumonia, diabetic ketoacidosis, and scrub typhus, and was treated with a broad spectrum of empirical antibiotics and fluid replacement. After laboratory and radiologic findings improved, ongoing dyspnea, progressive respiratory failure, and extremity weakness were observed. We diagnosed GBS based on neurological examination and electromyography, and excluded other GBS-related infections, such as CMV, EBV, and other bacteria. Mimicry involves the sharing of antigens between the host and an infecting microorganism, and is a type of cross-reactivity similar to an autoimmune disease. It is enabled by the activation of receptors on B- or T-lymphocytes by both the host and microorganism [5]. Scrub typhusrelated GBS is suspected to undergo a similar phenomenon. Gangliosides are important glycolipids associated with cell growth and signal transduction, and more than 100 subtypes exist [1]. O. tsutsugamushi antibody or antigens presented on infected cells are suspected to activate mimicry on myelin cells or peripheral nerve axons, which elicits immune reactions similar to autoimmune diseases. A positive result for the anti-ganglioside antibodies GD1b and GM1 IgM supports the conclusion that mimicry between pathogenic antigens and the myelin of peripheral nerves caused the immune reaction and GBS.