Clinical Implication of Candida Score in Multidrug-Resistant Pneumonia with Airway Candida Colonization

Background@#The growth of Candida in respiratory secretions is usually considered colonization, and antifungal therapy is rarely required. The role of Candida colonization in the progression of bacterial pneumonia remains controversial. The aim of this study was to identify the clinical implication of Candida score by analyzinge the relationship with multidrug-resistant (MDR) pneumonia and prognosis in patients with airway Candida colonization. @*Materials and Methods@#This study was a retrospective review of patients with airway Candida colonization by bronchial washing or bronchoalveolar lavage. The Candidascore was calculated according to the four factors (severe sepsis, surgery at baseline, total parenteral nutrition, and multifocal Candida colonization). Pneumonia related mortality or hopeless discharge expecting death was defined as a poor outcome. @*Results@#A total of 148 patients were enrolled in the study. In a multivariate analysis model, Candida score was identified as an independent predictor of poor outcomes (odds ratio 2.23;95% confidential interval 1.57 – 3.17; P<0.001) in pneumonia patients with airway Candida colonization. With a Candida score of three or higher compared with low score group, it was associated with bacterial pneumonia, especially methicillin-resistant Staphylococcus aureus (MRSA) infection (0.0% vs. 15.2%, P = 0.004). In addition, patients with a high Candida score had a longer hospital stay (13 vs. 38 days, P <0.001), longer duration of intensive care (7 vs.18 days, P <0.001), and higher pneumonia-related mortality (0.0% vs. 45.5%,P <0.001) as compared to the low Candida score group. The Candida score showed a positive correlation with other pneumonia severity scales such as CURB-65 (Confusion, Urea, Respiratory rate, Blood pressure, and age ≥65 years) (r = 0.461, P <0.001), Pneumonia Severity Index (r = 0.397, P <0.001), and predisposition, insult, response, and organ dysfunction (PIRO) score (r = 0.425, P <0.001). @*Conclusion@#This study revealed that Candida is no longer a bystander of airway colonization, and that it affects the progression of bacterial pneumonia, including multidrug-resistant pathogens, particularly MRSA infection. Also Candida score can be used to predict the prognosis of patients with pneumonia.

The clinical and economic burden of community-onset complicated skin and skin structure infections in Korea

Background/Aims@#To investigate epidemiologic characteristics, clinical and economic burdens, and factors associated with mortality in complicated skin and skin structure infection (cSSSI) patients in Korea. @*Methods@#A retrospective, observational, nationwide study was conducted between April to July 2012 at 14 tertiary-hospitals in Korea. Eligible patients were hospitalized adults with community acquired cSSSI, who underwent surgical intervention and completed treatment between November 2009 and October 2011. Data on demography, clinical characteristics, outcomes and medical resource utilization were collected through medical record review. Direct medical costs were calculated by multiplying quantities of resources utilized by each unit price in Korea. @*Results@#Of 473 patients enrolled, 449 patients (except 24 patients with no record on surgical intervention) were eligible for analysis. Microbiological testing was performed on 66.1% of patients and 8.2% had multiple pathogens. Among culture confirmed pathogens (n = 297 patients, 340 episodes), 76.2% were gram-positive (Staphylococcus aureus; 41.2%) and 23.8% were gram-negative. The median duration of hospital stay was 16 days. Among treated patients, 3.3% experienced recurrence and 4.2% died in-hospital. The mean direct medical costs amounted to $4,195/ person, with the greatest expenses for hospitalization and antibiotics. The in-hospital mortality and total medical costs were higher in combined antibiotics therapy than monotherapy (p < 0.05). Charlson’s comorbidity index ≥ 3, standardized early warning scoring ≥ 4, sub-fascia infections and combined initial therapy, were all found to be associated with higher mortality. @*Conclusions@#Korean patients with community-onset cSSSI suffer from considerable clinical and economic burden. Efforts should be made to reduce this burden through appropriate initial treatment.

Can Aminoglycosides Be Used as a New Treatment for Helicobacter pylori? In vitro Activity of Recently Isolated Helicobacter pylori

BACKGROUND@#Smectite can serve as a drug delivery system and gentamicin-intercalated smectite hybrids are expected to supersede the standard therapy for Helicobacter pylori eradication. The aim of this study was to confirm whether the minimum inhibitory concentration (MIC) of aminoglycosides applied as smectite hybrids remained low against recently isolated H. pylori strains.@*MATERIALS AND METHODS@#A total of 140 strains were collected for a minimum period of 3 years. Antimicrobial susceptibility tests were performed, and the MICs of eight antibiotics (amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, gentamicin, netilmicin, and tobramycin) were determined by using the Epsilometer test and following the European Committee on Antimicrobial Susceptibility Testing recommendations.@*RESULTS@#The resistance rate of clarithromycin was high, up to 30.7%, although it is a major antimicrobial agent used in standard therapy. The MIC50 and MIC90 of gentamicin (0.25 mg/L and 0.75 mg/L) and netilmicin (0.19 mg/L and 0.75 mg/L) were lower than other alternative therapies for H. pylori eradication. In clarithromycin-resistant strains, the MIC50 was 0.25 mg/L and the MIC90 was 1 mg/L for gentamicin; for netilmicin, the values were 0.25 mg/L and 0.75 mg/L, respectively.@*CONCLUSION@#Through the use of gentamicin and netilmicin, which have low MICs for H. pylori, aminoglycoside-intercalated smectite hybrids are expected to emerge as a new standard therapy for H. pylori eradication.

Peptide Nucleic Acid Probe-Based Analysis as a New Detection Method for Clarithromycin Resistance in Helicobacter pylori

BACKGROUND/AIMS: Helicobacter pylori eradication rates are decreasing because of increases in clarithromycin resistance. Thus, finding an easy and accurate method of detecting clarithromycin resistance is important. METHODS: We evaluated 70 H. pylori isolates from Korean patients. Dual-labeled peptide nucleic acid (PNA) probes were designed to detect resistance associated with point mutations in 23S ribosomal ribonucleic acid gene domain V (A2142G, A2143G, and T2182C). Data were analyzed by probe-based fluorescence melting curve analysis based on probe-target dissociation temperatures and compared with Sanger sequencing. RESULTS: Among 70 H. pylori isolates, 0, 16, and 58 isolates contained A2142G, A2143G, and T2182C mutations, respectively. PNA probe-based analysis exhibited 100.0% positive predictive values for A2142G and A2143G and a 98.3% positive predictive value for T2182C. PNA probe-based analysis results correlated with 98.6% of Sanger sequencing results (κ-value=0.990; standard error, 0.010). CONCLUSIONS: H. pylori clarithromycin resistance can be easily and accurately assessed by dual-labeled PNA probe-based melting curve analysis if probes are used based on the appropriate resistance-related mutations. This method is fast, simple, accurate, and adaptable for clinical samples. It may help clinicians choose a precise eradication regimen.

Effect of Central Line Bundle Compliance on Central Line-Associated Bloodstream Infections

PURPOSE: The present study aimed to evaluate the effect of central line (CL) bundle compliance on central line-associated bloodstream infections (CLABSIs) in different departments of the same hospital, including the intensive care unit (ICU) and other departments. MATERIALS AND METHODS: The four components of the CL bundle were hand hygiene, use of maximal sterile barrier precautions, chlorhexidine use, and selection of an appropriate site for venous access. Compliance of the CL bundle and CLABSIs were measured for every department [emergency room (ER), ICU, general ward (GW), and operating room (OR)]. A total of 1672 patients were included over 3 years (August 2013 through July 2016). RESULTS: A total of 29 CLABSI episodes (1.73%) were identified, and only 53.7% of the patients completed CL bundles. The performance rates of all components of the CL bundle were 22.3%, 28.5%, 36.5%, and 84.6% for the ER, ICU, GW, and OR, respectively. The highest CLABSI rate was observed in patients of the ICU, for whom all components were not performed perfectly. Conversely, the lowest CLABSI rate was observed for patients of GWs, for whom all components were performed. Among individual components, femoral insertion site [relative risk (RR), 2.26; 95% confidence interval (CI), 1.09–4.68], not using a full body drape (RR, 3.55; 95% CI, 1.44–8.71), and not performing all CL bundle components (RR, 2.79; 95% CI, 1.19–6.54) were significant variables associated with CLABSIs. CONCLUSION: This study provides direct evidence that completing all CL bundle components perfectly is essential for preventing CLABSIs. Customized education should be provided, according to specific weaknesses of bundle performance.

Long Pentraxin 3 as a Predictive Marker of Mortality in Severe Septic Patients Who Received Successful Early Goal-Directed Therapy

PURPOSE: Pentraxin 3 (PTX3) has been suggested to be a prognostic marker of mortality in severe sepsis. Currently, there are limited data on biomarkers including PTX3 that can be used to predict mortality in severe sepsis patients who have undergone successful initial resuscitation through early goal-directed therapy (EGDT). MATERIALS AND METHODS: A prospective cohort study was conducted among 83 severe sepsis patients with fulfillment of all EGDT components and the achievement of final goal. Plasma PTX3 levels were measured by sandwich ELISA on hospital day (HD) 0, 3, and 7. The data for procalcitonin, C-reactive protein and delta neutrophil index were collected by electric medical record. The primary outcome was 28-day all-cause mortality. RESULTS: 28-day all-cause mortality was 19.3% and the median (interquartile range) APHCH II score of total patients was 16 (13–19). The non-survivors (n=16) had significantly higher PTX3 level at HD 0 [201.4 (56.9–268.6) ng/mL vs. 36.5 (13.7–145.3) ng/mL, p=0.008]. PTX3 had largest AUC(ROC) value for the prediction of mortality among PTX3, procalcitonin, delta neutrophil index, CRP and APACHE II/SOFA sore at HD 0 [0.819, 95% confidence interval (CI) 0.677–0.961, p=0.008]. The most valid cut-off level of PTX3 at HD 0 was 140.28 ng/mL (sensitivity 66.7%, specificity 73.8%). The PTX3 and procalcitonin at HD 0 showed strong correlation (r=0.675, p<0.001). However, PTX3 at HD 0 was the only independent predictive marker in Cox's proportional hazards model (≥140 ng/mL; hazard rate 7.16, 95% CI 2.46–15.85, p=0.001). CONCLUSION: PTX3 at HD 0 could be a powerful predictive biomarker of 28-day all-cause mortality in severe septic patients who have undergone successful EGDT.

Change in Renal Function among HIV-Infected Koreans Receiving Tenofovir Disoproxil Fumarate-Backbone Antiretroviral Therapy: A 3-Year Follow-Up Study

PURPOSE: Tenofovir disoproxil fumarate (TDF) is commonly prescribed as a fixed-dose, co-formulated antiretroviral drug for HIV-1 infection. The major concern of long-term TDF use is renal dysfunction. However, little is known about the long-term patterns of changes in renal function in HIV-infected Koreans receiving TDF. MATERIALS AND METHODS: We prospectively followed 50 HIV-infected Koreans, performing laboratory tests every 3 months during the first year and every 6 months for the next 2 years. Urine N-acetyl-β-D-glucosaminidase (NAG) and plasma cystatin-C were measured using samples collected in the first year. Data on renal function were retrospectively collected on HIV-infected patients receiving first-line TDF (n=40) and in antiretroviral therapy (ART)-naïve patients (n=24) for 3 years. Renal function was evaluated as estimated glomerular filtration rate (eGFR) from serum creatinine [Modification of Diet in Renal Disease (MDRD)] and cystatin-C. RESULTS: The eGFR (cystatin-C) showed significant changes from 0 to 48 wks (p=0.002), with the lowest levels at 24 wks (84.3±18.8 mL/min vs. 90.3±22.5 mL/min, p=0.021 by post hoc test). Urine NAG levels did not differ at 0, 12, 24, and 48 wks, although eGFR (MDRD) significantly decreased from 0 (98.7±18.9 mL/min/1.73 m²) to 144 wks (89.0±14.7 mL/min/1.73 m²) (p=0.010). The first-line TDF group had significantly lower eGFR (MDRD) than the ART-naïve group at 144 wks (89.7 mL/min/1.73 m² vs. 98.4 mL/min/1.73 m², p=0.036). Thirteen (26%) participants experienced a decrease in renal impairment of 10 mL/min/1.73 m² in eGFR (MDRD) at 144 wks. CONCLUSION: These data suggest that clinically meaningful renal injury can develop in HIV-infected Koreans receiving long-term TDF.

A Case of Community-Acquired Pneumonia Caused by Multidrug-Resistant Acinetobacter baumannii in Korea

Acinetobacter baumannii is an aerobic Gram-negative coccobacillus that causes nosocomial pneumonia in patients on mechanical ventilation or previously treated with broad-spectrum antibiotics. Nevertheless, community-acquired pneumonia (CAP) caused by A. baumannii, especially multi-drug resistant (MDR) strains, is rare. We experienced the first case of CAP caused by MDR A. baumannii in Korea in a 78-year-old man. This case shows that MDR A. baumannii can cause CAP in Korea.

A Case of Infective Endocarditis caused by Abiotrophia defectiva in Korea

Abiotrophia defectiva, a nutritionally variant streptococci can cause bacteremia, brain abscess, septic arthritis and in rare cases, infective endocarditis, which accounts for 5-6% of all cases. A. defectiva is characteristically difficult to diagnose and the mortality, morbidity and complication rates are high. Here, we discuss a case of infective endocarditis caused by A. defectiva. A 62-year-old female had previously undergone prosthetic valve replacement 6 years prior to admission. She developed infective endocarditis after tooth extraction. Her endocarditis was successfully treated with antimicrobial therapy and mitral valve replacement surgery. This is the first case of infective endocarditis caused by A. defectiva reported in Korea. This case shows that A. defectiva could be considered as a causative organism of infective endocarditis in Korea.

Risk Factors for Mortality in Patients with Serratia marcescens Bacteremia

PURPOSE: Over the last 30 years, Serratia marcescens (S. marcescens) has emerged as an important pathogen, and a common cause of nosocomial infections. The aim of this study was to identify risk factors associated with mortality in patients with S. marcescens bacteremia. MATERIALS AND METHODS: We performed a retrospective cohort study of 98 patients who had one or more blood cultures positive for S. marcescens between January 2006 and December 2012 in a tertiary care hospital in Seoul, South Korea. Multiple risk factors were compared with association with 28-day all-cause mortality. RESULTS: The 28-day mortality was 22.4% (22/98 episodes). In a univariate analysis, the onset of bacteremia during the intensive care unit stay (p=0.020), serum albumin level (p=0.011), serum C-reactive protein level (p=0.041), presence of indwelling urinary catheter (p=0.023), and Sequential Oran Failure Assessment (SOFA) score at the onset of bacteremia (p<0.001) were significantly different between patients in the fatal and non-fatal groups. In a multivariate analysis, lower serum albumin level and an elevated SOFA score were independently associated with 28-day mortality [adjusted odds ratio (OR) 0.206, 95% confidential interval (CI) 0.044-0.960, p=0.040, and adjusted OR 1.474, 95% CI 1.200-1.810, p<0.001, respectively]. CONCLUSION: Lower serum albumin level and an elevated SOFA score were significantly associated with adverse outcomes in patients with S. marcescens bacteremia.

A Case of Polymicrobial Fungal and Bacterial Spondylodiscitis / 대한내과학회지

A 66-year-old female who had undergone surgery for a herniated disc at the L5-S1 level at another hospital 3 months earlier was admitted with persistent back and leg pain. She was diagnosed with spondylodiscitis at the L5-S1 level by magnetic resonance imaging. A biopsy was performed, and Candida parapsilosis and Enterococcus faecium were isolated from the excised material. We report herein a case of successful treatment of polymicrobial spondylodiscitis in accordance with accurate microbiological diagnosis. Based on this case, we hope to encourage physicians to perform biopsies more aggressively or repeatedly to improve the diagnostic yield.

Middle East Respiratory Syndrome Infection Control and Prevention Guideline for Healthcare Facilities

Middle East Respiratory Syndrome (MERS) is an acute viral respiratory illness with high mortality caused by a new strain of betacoronavirus (MERS-CoV). Since the report of the first patient in Saudi Arabia in 2012, large-scale outbreaks through hospital-acquired infection and inter-hospital transmission have been reported. Most of the patients reported in South Korea were also infected in hospital settings. Therefore, to eliminate the spread of MERS-CoV, infection prevention and control measures should be implemented with rigor. The present guideline has been drafted on the basis of the experiences of infection control in the South Korean hospitals involved in the recent MERS outbreak and on domestic and international infection prevention and control guidelines. To ensure efficient MERS-CoV infection prevention and control, care should be taken to provide comprehensive infection control measures including contact control, hand hygiene, personal protective equipment, disinfection, and environmental cleaning.

Transfusion-free Management for the Severe Anemia Developed after Nephrectomy / 이화의대지

A 56-year-old woman with emphysematous pyelonephritis underwent an emergent left nephrectomy due to her religious creed. Postoperative hemoglobin level was decreased to 4.4 g/dL from preoperative value of 13.9 g/dL. The patient completely recovered without transfusion and was discharged on the 40th postoperative day without complication.

Clinical Factors Associated with Acquisition of Resistance to Levofloxacin in Stenotrophomonas maltophilia

PURPOSE: Fluoroquinolones, rapidly gaining prominence in treatment of Stenotrophomonas maltophilia (SMP), are noted for their potency and tolerability. However, SMP may rapidly acquire resistance to fluoroquinolones. We evaluated associations of clinical factors with acquisition of levofloxacin resistance (LFr) in SMP. MATERIALS AND METHODS: Our retrospective cohort study was based on patient data collected between January 2008 and June 2010. Through screening of 1275 patients, we identified 122 patients with data for SMP antibiotic susceptibility testing in > or =3 serial SMP isolates. RESULTS: We assigned the 122 patients to either the SS group (n=54) in which levofloxacin susceptibility was maintained or the SR group (n=31) in which susceptible SMP acquired resistance. In multivariate regression analysis, exposure to levofloxacin for more than 3 weeks [odds ratio (OR) 15.39, 95% confidential interval (CI) 3.08-76.93, p=0.001] and co-infection or co-colonization with Klebsiella pneumoniae resistant to levofloxacin (OR 4.85, 95% CI 1.16-20.24, p=0.030) were independently associated with LFr acquisition in SMP. CONCLUSION: Acquisition of LFr during serial sampling of SMP was related to the levofloxacin exposure.

Delta Neutrophil Index as a Prognostic Marker of Early Mortality in Gram Negative Bacteremia

BACKGROUND: Sepsis is a syndrome that results in high morbidity and mortality. We investigated the delta neutrophil index (DN) as a predictive marker of early mortality in patients with gram-negative bacteremia. MATERIALS AND METHODS: We conducted a retrospective study at a tertiary referral hospital in South Korea from November 2010 to March 2011. The DN was measured at onset of bacteremia and 24 hours and 72 hours later. The DN was calculated using an automatic hematology analyzer. Factors associated with 10-day mortality were assessed using logistic regression. RESULTS: A total of 172 patients with gram-negative bacteremia were included in the analysis; of these, 17 patients died within 10 days of bacteremia onset. In multivariate analysis, Sequental organ failure assessment scores (odds ratio [OR]: 2.24, 95% confidence interval [CI]: 1.31 to 3.84; P = 0.003), DN-day 1 > or = 7.6% (OR: 305.18, 95% CI: 1.73 to 53983.52; P = 0.030) and DN-day 3 > or = DN-day 1 (OR: 77.77, 95% CI: 1.90 to 3188.05; P = 0.022) were independent factors associated with early mortality in gram-negative bacteremia. Of four multivariate models developed and tested using various factors, the model using both DN-day 1 > or = 7.6% and DN-day 3 > or = DN-day 1 was most predictive early mortality. CONCLUSIONS: DN may be a useful marker of early mortality in patients with gram-negative bacteremia. We found both DN-day 1 and DN trend to be significantly associated with early mortality.

Underestimation of the Calculated Area Under the Concentration-Time Curve Based on Serum Creatinine for Vancomycin Dosing

BACKGROUND: The ratio of the steady-state 24-hour area under the concentration-time curve (ssAUC24) to the MIC (AUC24/MIC) for vancomycin has been recommended as the preferred pharmacodynamic index. The aim of this study was to assess whether the calculated AUC24 (cAUC24) using the creatinine clearance (CLcr) differs from the ssAUC24 based on the individual pharmacokinetic data estimated by a commercial software. MATERIALS AND METHODS: The cAUC24 was compared with the ssAUC24 with respect to age, body mass index, and trough concentration of vancomycin and the results were expressed as median and interquartile ranges. A correlation between the cAUC24 and ssAUC24 and the trough concentration of vancomycin was evaluated. The probability of reaching an AUC24/MIC of 400 or higher was compared between the cAUC24 and ssAUC24 for different MICs of vancomycin and different daily doses by simulation in a subgroup with a trough concentration of 10 mg/L and higher. RESULTS: The cAUC24 was significantly lower than the ssAUC24 (392.38 vs. 418.32 mg.hr/L, P < 0.0001) and correlated weakly with the trough concentration (r = 0.649 vs. r = 0.964). Assuming a MIC of 1.0 mg/L, the probability of reaching the value of 400 or higher was 77.5% for the cAUC24/MIC and 100% for the ssAUC24/MIC in patients with a trough concentration of 10 mg/L and higher. If the MIC increased to 2.0 mg/L, the probability was 57.7% for the cAUC24/MIC and 71.8% for the ssAUC24/MIC at a daily vancomycin dose of 4,000 mg. CONCLUSIONS: The cAUC24 using the calculated CLcr is usually underestimated compared with the ssAUC24 based on individual pharmacokinetic data. Therefore, to obtain a more accurate AUC24, therapeutic monitoring of vancomycin rather than a simple calculation based on the CLcr should be performed, and a more accurate biomarker for renal function is needed.

Pandemic Influenza (H1N1) and Mycobacterium tuberculosis Co-infection / 결핵및호흡기질환

We hereby observe four co-infection cases of pandemic influenza H1N1 and Mycobacterium tuberculosis with various clinical presentations. It may be prudent to consider M. tuberculosis co-infections when patients with pandemic influenza reveal unusual clinical features that do not improve despite appropriate treatments against the influenza, especially in Korea, in the endemic areas of M. tuberculosis.

A Case of Systemic Capillary Leak Syndrome Presenting as Septic Shock / 대한내과학회지

Systemic capillary leak syndrome is a rare disease characterized by life-threatening attacks of reversible plasma extravasation and vascular collapse accompanied by hypotension, hemoconcentration, and hypoalbuminemia. A 36-year-old woman was admitted to this hospital with a fever, along with symptoms consistent with an upper respiratory tract infection and hypotension. Initial laboratory tests revealed several abnormal findings, including an elevated leukocyte count and hematocrit, hypoalbuminemia, and acute renal failure. Here, we report a case of successful treatment of systemic capillary leak syndrome, which can be difficult to distinguish from septic shock.

A Case of Giant Hemangioma of the Liver Presenting with Fever and Cough / 대한내과학회지

Hemangioma of the liver is usually asymptomatic and incidentally discovered. However, giant hemangioma of the liver may be symptomatic, which is an indication for treatment. A 31-year-old female was admitted with a fever and 1-month history of a nonproductive cough. Her blood test results revealed thrombocytopenia, anemia, and mild coagulopathy. A giant hemangioma of the liver was the cause of her symptoms and signs, and was too large for surgical treatment. Therefore, we performed two sessions of transcatheter hepatic arterial embolization (TAE). The patient has been doing well without fever for 1 year following the second TAE procedure. Surgical resection and enucleation are the traditional treatments of choice for symptomatic giant hemangioma of the liver. However, the signs and symptoms of giant hemangioma of the liver improved by TAE in the present case. We herein report a case of complicated giant hemangioma of the liver that was partially treated by TAE and conservative management.

A Case of Skin and Soft Tissue Infection by Mycobacterium massiliense / 대한내과학회지

Mycobacterium massiliense (M. massiliense) was identified recently as a species that separated from M. abscessus. Unlike M. abscessus, M. massiliense responds well to clarithromycin-based antibiotic treatment. Many cases of M. massiliense infections related to iatrogenic procedures have been reported. We report a case of skin and soft tissue infection by M. massiliense, which was not caused by medical appliances, that was treated successfully using clarithromycin monotherapy for -6 months after initial treatment with empirical antibiotics for 4 weeks.