Uh Jin Kim

Update on the Epidemiology, Treatment, and Outcomes of Carbapenem-resistant Acinetobacter infections

Carbapenem-resistant Acinetobacter species are increasingly recognized as major nosocomial pathogens, especially in patients with critical illnesses or in intensive care. The ability of these organisms to accumulate diverse mechanisms of resistance limits the available therapeutic agents, makes the infection difficult to treat, and is associated with a greater risk of death. In this review, we provide an update on the epidemiology, resistance mechanisms, infection control measures, treatment, and outcomes of carbapenem-resistant Acinetobacter infections.

First Imported Case of Zika Virus Infection into Korea

Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil.

Inappropriateness of Quinolone in Scrub Typhus Treatment Due to gyrA Mutation in Orientia tsutsugamushi Boryong Strain

The use of quinolone for treatment of rickettsial diseases remains controversial. Recent clinical studies suggest that quinolone is not as effective as others in patients with rickettsial diseases including scrub typhus, although the mechanism is not well understood. In this study, we evaluated the mutation in gyrA associated with quinolone resistance. We prospectively enrolled scrub typhus patients, collected blood samples and clinical data from October, 2010 to November, 2011. Among the 21 patients enrolled, one initially received ciprofloxacin for 3 days but was switched to doxycycline due to clinical deterioration. We obtained the gyrA gene of Orientia tsutsugamushi from 21 samples (20 Boryong strain, 1 Kato strain) and sequenced the quinolone resistance-determining region. All of 21 samples had the Ser83Leu mutation in the gyrA gene, which is known to be associated with quinolone resistance. This suggests that quinolones may be avoided for the treatment of serious scrub typhus.

Outcome of Intravenous Azithromycin Therapy in Patients with Complicated Scrub Typhus Compared with That of Doxycycline Therapy Using Propensity-Matched Analysis

ABSTRACT There are no well-matched, controlled studies comparing azithromycin with doxycycline for the treatment of complicated scrub typhus. A retrospective propensity score-matched case-control study was performed for patients who presented with complicated scrub typhus and were treated with doxycycline or azithromycin between 2001 and 2011. Data on comorbidities, clinical manifestations, laboratory studies, treatments, and outcomes were extracted for analysis. The clinical characteristics and outcomes of the azithromycin-treated group (n = 73) were compared to those of the doxycycline-treated group (n = 108). Of 181 patients, 73 from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment success and survival rates were not significantly different (89% [65/73 patients] versus 96% [70/73 patients] and 96% [70/73 patients] versus 96% [70/73 patients], respectively [P > 0.05]). No difference was observed in the time to defervescence or length of hospital stay between the two groups (P > 0.05). In complicated scrub typhus patients (n = 181), multivariate analysis showed that only APACHE II score was an independent risk factor for mortality (95% confidence interval, 1.11 to 1.56; P < 0.001). Our data suggest that outcomes of azithromycin therapy are comparable to those of doxycycline therapy in patients with complicated scrub typhus.

Successful treatment of rapidly progressing severe fever with thrombocytopenia syndrome with neurological complications using intravenous immunoglobulin and corticosteroid.

Since the first report of severe fever with thrombocytopenia syndrome (SFTS) in China, diagnostic methods have evolved. Despite definitive diagnoses, SFTS management has focused on prevention and supportive care. Although conservative treatment is effective for mild cases, there is an urgent need for an effective therapeutic modality to treat severe cases because of the high mortality associated with these. In this study, we report two cases of SFTS with neurological manifestations that fully recovered after a combination treatment consisting of intravenous immunoglobulin and corticosteroid.

Combination therapy with lopinavir/ritonavir, ribavirin and interferon-α for Middle East respiratory syndrome.

Since the first report of Middle East respiratory syndrome (MERS) in 2012 in Saudi Arabia, no standard treatment guideline has been set despite the virulence of MERS-coronavirus (CoV) and the high case-fatality rate. The outbreak in South Korea in 2015 demonstrates that MERS outbreaks can occur outside of the Middle East. The combination of ribavirin and interferon-α has been the most widely used therapy for this infection. However, due to the varying results of treatment with these drugs, a new antiviral combination regimen is urgently needed. This is a case report of use of lopinavir/ritonavir-based combination antiviral therapy for a patient with MERS-CoV infection.

Differences in the clinical presentation and the frequency of complications between elderly and non-elderly scrub typhus patients.

Age can affect the clinical features and severity of infectious disorders, such as scrub typhus. We performed this study to examine differences between elderly and non-elderly scrub typhus patients, and to identify risk factors predictive of disease outcomes. This retrospective study included patients admitted to a tertiary hospital with scrub typhus between 2001 and 2011. A total of 615 patients were enrolled in this study, 328 of which were >65 years of age. Of the elderly patients, 46.0% (151/328) experienced at least one complication compared to only 23.0% (66/287) in younger patients. A linear trend was observed between age and complication rates (p=0.002). The most common complication in elderly patients was acute kidney injury (75, 22.9%). Treatment failure was reported in 10 elderly patients (3.0%) compared to one non-elderly patient (0.3%). Mental confusion and dyspnea of clinical manifestations at admission were common in elderly patients. Frequency of fever, rash, and eschar were similar in both groups. The following four factors were significantly associated with severe scrub typhus in elderly patients: (1) white blood cell (WBC) counts>10,000/mm(3) (OR=2.569, CI=1.298-5.086), (2) MDRD GFR<60mL/min (OR=3.525, CI=1.864-6.667), (3) albumin≤3.0g/dL (OR=4.976, CI=2.664-9.294), and (4) acute physiology and chronic health evaluation II (APACHE II) score>10 points (OR=3.304, CI=1.793-60.87). Complications and mortality were more common in elderly patients, often associated with delays in diagnosis and treatment.

Diagnostic Use of Serum Ferritin Levels to Differentiate Infectious and Noninfectious Diseases in Patients with Fever of Unknown Origin

INTRODUCTION: In this study, we determined whether serum ferritin levels could be used to differentiate between fever of unknown origin (FUO) caused by infectious and noninfectious diseases. METHODS: FUO patients were hospitalized at Chonnam National University Hospital between January, 2005 and December, 2011. According to the final diagnoses, five causes were identified, including infectious diseases, hematologic diseases, noninfectious inflammatory diseases, miscellaneous and undiagnosed. RESULTS: Of the 77 patients, 11 were caused by infectious diseases, 13 by hematologic diseases, 20 by noninfectious inflammatory diseases, 8 by miscellaneous diseases, and 25 were undiagnosed. The median serum ferritin levels in infectious diseases was lower than those in hematologic diseases and (median (interquartile range) of 282.4 (149.0–951.8) ng/mL for the infectious disease group, 1818.2 (485.4–4789.5) ng/mL for the hematologic disease group, and 563.7 (399.6–1927.2) ng/mL for the noninfectious inflammatory disease group, p = 0.048, Kruskal–Wallis test). By comparison using the Mann–Whitney test, statistically significant differences were found only between the infectious disease and hematologic disease groups (p = 0.049) and between the infectious disease and groups (p = 0.04). CONCLUSION: An optimal cutoff value of serum ferritin levels to predict FUO caused by a noninfectious disease (hematologic diseases, noninfectious inflammatory diseases) was established as 561 ng/mL.

Activation, Impaired Tumor Necrosis Factor-α Production, and Deficiency of Circulating Mucosal-Associated Invariant T Cells in Patients with Scrub Typhus.

Background Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. However, little is known about the role of MAIT cells in Orientia tsutsugamushi infection. Hence, the aims of this study were to examine the level and function of MAIT cells in patients with scrub typhus and to evaluate the clinical relevance of MAIT cell levels. Methodology/Principal Findings Thirty-eight patients with scrub typhus and 53 health control subjects were enrolled in the study. The patients were further divided into subgroups according to disease severity. MAIT cell level and function in the peripheral blood were measured by flow cytometry. Circulating MAIT cell levels were found to be significantly reduced in scrub typhus patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAT cell levels reflect disease severity. MAIT cells in scrub typhus patients displayed impaired tumor necrosis factor (TNF)-α production, which was restored during the remission phase. In addition, the impaired production of TNF-α by MAIT cells was associated with elevated CD69 expression. Conclusions This study shows that circulating MAIT cells are activated, numerically deficient, and functionally impaired in TNF-α production in patients with scrub typhus. These abnormalities possibly contribute to immune system dysregulation in scrub typhus infection.

Predictors of Viral Pneumonia in Patients with Community-Acquired Pneumonia

Background Viruses are increasingly recognized as major causes of community-acquired pneumonia (CAP). Few studies have investigated the clinical predictors of viral pneumonia, and the results have been inconsistent. In this study, the clinical predictors of viral pneumonia were investigated in terms of their utility as indicators for viral pneumonia in patients with CAP. Methods Adult patients (≥18 years old) with CAP, tested by polymerase chain reaction (PCR) for respiratory virus, at two teaching hospitals between October 2010 and May 2013, were identified retrospectively. Demographic and clinical data were collected by reviewing the hospital electronic medical records. Results During the study period, 456 patients with CAP were identified who met the definition, and 327 (72%) patients were tested using the respiratory virus PCR detection test. Viral pneumonia (n = 60) was associated with rhinorrhea, a higher lymphocyte fraction in the white blood cells, lower serum creatinine and ground-glass opacity (GGO) in radiology results, compared to non-viral pneumonia (n = 250) (p<0.05, each). In a multivariate analysis, rhinorrhea (Odd ratio (OR) 3.52; 95% Confidence interval (CI), 1.58–7.87) and GGO (OR 4.68; 95% CI, 2.48–8.89) were revealed as independent risk factors for viral pneumonia in patients with CAP. The sensitivity, specificity, positive- and negative-predictive values (PPV and NPV) of rhinorrhea were 22, 91, 36 and 83%: the sensitivity, specificity, PPV and NPV of GGO were and 43, 84, 40 and 86%, respectively. Conclusion Symptom of rhinorrhea and GGO predicted viral pneumonia in patients with CAP. The high specificity of rhinorrhea and GGO suggested that these could be useful indicators for empirical antiviral therapy.