Moo Suk Park

Risk factors for multi-drug resistant Acinetobacter baumannii bacteremia in patients with colonization in the intensive care unit

BackgroundEpidemic outbreaks of multi-drug resistant (MDR) Acinetobacter baumannii (AB) in intensive care units (ICUs) are increasing. The incidence of MDR AB bacteremia, which develops as a result of colonization, is increasing through widespread dissemination of the pathogen, and further colonization. We sought to determine risk factors for MDR AB bacteremia in patients colonized with MDR AB in the ICU.MethodsWe conducted a retrospective, observational study of 200 patients colonized with MDR AB in the ICU at Severance Hospital, South Korea during the outbreak period between January 2008 and December 2009.ResultsOf the 200 patients colonized with MDR AB, 108 developed MDR AB bacteremia, and 92 did not. APACHE II scores were higher in bacteremic than non-bacteremic patients at the time of ICU admission and colonization (24.0 vs. 21.6; P = 0.035, 22.9 vs. 16.8; P < 0.001, respectively). There was no difference between the two groups in the duration of time from ICU admission to colonization (7.1 vs. 7.2 days; P = 0.923), but the duration of time at risk was shorter in bacteremic patients (12.1 vs. 6.0 days; P = 0.016). A recent invasive procedure was a significant risk factor for development of bacteremia (odds ratio = 3.85; 95% CI 1.45-10.24; P = 0.007). Multivariate analysis indicated infection and respiratory failure at the time of ICU admission, maintenance of mechanical ventilation, maintenance of endotracheal tube instead of switching to a tracheostomy, recent central venous catheter insertion, bacteremia caused by other microorganism after colonization by MDR AB, and prior antimicrobial therapy, were significant risk factors for MDR AB bacteremia.ConclusionsPatients in the ICU, colonized with MDR AB, should be considered for minimizing invasive procedures and early removal of the invasive devices to prevent development of MDR AB bacteremia.

Delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis

BackgroundThe immature granulocyte count has been reported to be a marker of infection and sepsis. The difference in leukocyte subfractions (delta neutrophil index, DNI) in ADVIA 2120 reflects the fraction of circulating immature granulocytes in the blood. This study evaluated the clinical utility of DNI as a severity and prediction marker in critically ill patients with sepsis.MethodsOne hundred and three patients admitted to the medical intensive care unit with sepsis were studied. DNI (the difference in leukocyte subfractions identified by myeloperoxidase and nuclear lobularity channels) was determined using a specific blood cell analyzer.ResultsForty four patients (42.7%) were diagnosed with severe sepsis/septic shock. Overt disseminated intravascular coagulation (DIC) occurred in 40 (38.8%). DNI was significantly higher in patients with severe sepsis/septic shock and overt DIC than in patients without (p < 0.05). DNI correlated with DIC score (r = 0.54, p < 0.001). We observed a monotonic increase in the proportion of overt DIC and severe sepsis/septic shock associated with increasing quartiles of DNI (p < 0.001). A DNI value > 6.5% was a better indicator of severe sepsis/septic shock than C-reactive protein, lactate, white blood cell count, and absolute neutrophil count (sensitivity, 81.3%; specificity, 91.0%; positive predictive value, 88.6%; and negative predictive value, 84.7%). In 36 (82%) of the 44 patients with severe sepsis/septic shock, DNI values were already elevated up to 12 hours before the onset of organ/circulatory failure.ConclusionsDNI may be used as a marker of disease severity in critically ill patients with sepsis. High levels of DNI may help to identify patients with an impending risk of developing severe sepsis/septic shock.

Performance of the tuberculin skin test and interferon-γ release assay for detection of tuberculosis infection in immunocompromised patients in a BCG-vaccinated population

BackgroundInterferon-γ release assay (IGRA) may improve diagnostic accuracy for latent tuberculosis infection (LTBI). This study compared the performance of the tuberculin skin test (TST) with that of IGRA for the diagnosis of LTBI in immunocompromised patients in an intermediate TB burden country where BCG vaccination is mandatory.MethodsWe conducted a retrospective observational study of patients given the TST and an IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT), at Severance Hospital, a tertiary hospital in South Korea, from December 2006 to May 2009.ResultsOf 211 patients who underwent TST and QFT-IT testing, 117 (55%) were classified as immunocompromised. Significantly fewer immunocompromised than immunocompetent patients had positive TST results (10.3% vs. 27.7%, p 0.001), whereas the percentage of positive QFT-IT results was comparable for both groups (21.4% vs. 25.5%). However, indeterminate QFT-IT results were more frequent in immunocompromised than immunocompetent patients (21.4% vs. 9.6%, p 0.021). Agreement between the TST and QFT-IT was fair for the immunocompromised group (κ = 0.38), but moderate agreement was observed for the immunocompetent group (κ = 0.57). Indeterminate QFT-IT results were associated with anaemia, lymphocytopenia, hypoproteinemia, and hypoalbuminemia.ConclusionIn immunocompromised patients, the QFT-IT may be more sensitive than the TST for detection of LTBI, but it resulted in a considerable proportion of indeterminate results. Therefore, both tests may maximise the efficacy of screening for LTBI in immunocompromised patients.

Pulmonary inflammatory pseudotumor -A report of 28 cases-

Background Pulmonary inflammatory pseudotumor is an uncommon benign lesion of the lung. In Korea, most literature of the pulmonary inflammatory pseudotumor was case reports. Methods: We collected 28 cases of pulmonary inflammatory pseudotumor in Korea. This collective series included 4 cases from our hospital and 24 cases were reviewed from the literature since 1977. The analysis involved the age, sex, chief complaint, hematologic examination, size and location of the lesion, cavity formation, presence of calcification and treatment method. Results: Male was more prevalent (81.5%) than female and mean age was 37.9 years old (6–63 yrs). Chief complaints were cough (44.4%), chest pain (29.6%), fever (22.2%), hemoptysis (15%), sputum (15%) and dyspnea (11.1%). There were asymptomatic cases in 11.1%. Hematologic examination revealed normal finding (53.3%) and anemia (20%). The mean size of the lesion was 4.76 cm (1.5–14 cm) and the locations were parenchymal (85.7%), endobronchial (10.7%) and endotracheal (3.6%). Except the endotracheal case, the lesions were in the right (46.4%), the left (42.8%) and bilateral (7.1%). Calcifications (18.5%) and cavitations (11.1%) were present. Diagnostic methods were open thoracotomy (82.1%), bronchoscopy (3.6%), needle aspiration biopsy (7.1%) and core needle gun biopsy (7.1%). Treatments were surgery (85.2%), steroid therapy (7.4%), rigid bronchoscopic removal (3.7%) and observation (3.7%). Postoperative recurrence occurred in only 1 case (4.3%). Conclusion: Pulmonary inflammatory pseudotumor was more prevalent in the male, and patients presented with the respiratory symptoms were common. It was necessary to do surgery in most cases for diagnosis and/or treatment.

Healthcare-associated pneumonia among hospitalized patients in a Korean tertiary hospital

BackgroundHealthcare-associated pneumonia (HCAP) has more similarities to nosocomial pneumonia than to community-acquired pneumonia (CAP). However, there have only been a few epidemiological studies of HCAP in South Korea. We aimed to determine the differences between HCAP and CAP in terms of clinical features, pathogens, and outcomes, and to clarify approaches for initial antibiotic management.MethodsWe conducted a retrospective, observational study of 527 patients with HCAP or CAP who were hospitalized at Severance Hospital in South Korea between January and December 2008.ResultsOf these patients, 231 (43.8%) had HCAP, and 296 (56.2%) had CAP. Potentially drug-resistant (PDR) bacteria were more frequently isolated in HCAP than CAP (12.6% vs. 4.7%; P = 0.001), especially in the low-risk group of the PSI classes (41.2% vs. 13.9%; P = 0.027). In-hospital mortality was higher for HCAP than CAP patients (28.1% vs. 10.8%, P < 0.001), especially in the low-risk group of PSI classes (16.4% vs. 3.1%; P = 0.001). Moreover, tube feeding and prior hospitalization with antibiotic treatment within 90 days of pneumonia onset were significant risk factors for PDR pathogens, with odds ratios of 14.94 (95% CI 4.62-48.31; P < 0.001) and 2.68 (95% CI 1.32-5.46; P = 0.007), respectively.ConclusionsFor HCAP patients with different backgrounds, various pathogens and antibiotic resistance of should be considered, and careful selection of patients requiring broad-spectrum antibiotics is important when physicians start initial antibiotic treatments.

High EGFR Gene Copy Number and Skin Rash as Predictive Markers for EGFR Tyrosine Kinase Inhibitors in Patients with Advanced Squamous Cell Lung Carcinoma

Purpose: This study aimed to search for predictors of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) efficacy in previously treated patients with advanced squamous cell lung carcinoma in which EGFR mutations are very rare. Experimental Design: EGFR gene copy numbers were assessed by FISH and evaluated as predictors of EGFR-TKI efficacy in 71 patients with advanced squamous cell lung cancer who received gefitinib or erlotinib as a second-line or higher therapy. The tumors were classified into EGFR/FISH-positive (high polysomy/gene amplification) and EGFR/FISH-negative (other) groups. Results: EGFR/FISH was positive in 19 (26.7%) patients. Only EGFR/FISH positive status was correlated with the EGFR-TKIs response (EGFR/FISH+ vs. EGFR/FISH−, 26.3% vs. 2.0%; P = 0.005). In a multivariate analysis, the risk of progression was lower in EGFR/FISH-positive patients (HR of EGFR/FISH+ vs. EGFR/FISH−, 0.57; P = 0.057) or patients experiencing grade 2 or more rash (HR for rash grade 2 or more vs. less than 2, 0.54; P = 0.042), compared with EGFR/FISH-negative patients or those experiencing grade of less than 2 rash, respectively. When the combined criteria of EGFR/FISH and skin rash severity were analyzed, EGFR/FISH-negative patients with grade less than 2 rash had poorer clinical outcomes than patients with positive EGFR/FISH or grade 2 or more rash, apparent as a lower response rate (0.0% vs. 21.4%; P = 0.003) and a shorter median progression-free survival (1.13 months vs. 3.90 months; P = 0.0002). Conclusions: EGFR/FISH and skin rash severity may be used to identify which patients are likely to gain a benefit from EGFR-TKIs in this population. Clin Cancer Res; 18(6); 1760–8. ©2012 AACR.

Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided platinum-based 2-drug chemotherapy for unresectable nonsmall-cell lung cancer†

The study investigated correlations between adenosine triphosphate / chemotherapy response assay (ATP‐CRA) and clinical outcomes after ATP‐CRA‐guided platinum‐based chemotherapy for unresectable nonsmall‐cell lung cancer (NSCLC).

A phase I study of nimotuzumab in combination with radiotherapy in stages IIB–IV non-small cell lung cancer unsuitable for radical therapy: Korean results

PURPOSE This study was undertaken to determine safety and tolerability of nimotuzumab, a humanized anti-epidermal growth factor receptor monoclonal antibody, in combination with radiotherapy in stages IIB-IV non-small cell lung cancer (NSCLC) patients who are unsuitable for radical therapy or chemotherapy. METHODS Nimotuzumab (100mg, 200mg and 400mg) was administered weekly from week 1 to week 8 with palliative radiotherapy (30-36 Gy, 3 Gy/day). If tumor control was achieved, nimotuzumab was continued every 2 weeks until unacceptable toxicity or disease progression. Serial skin biopsies were collected for pharmacodynamic assessment. RESULTS Fifteen patients were enrolled in the study, with cohorts of five patients assigned in each dose level of nimotuzumab. Patients and disease characteristics included median age 73 years; Eastern Cooperative Oncology Group performance status (PS) 0-1/2 (n=3/12); female sex (n=2); adenocarcinoma (n=5); never-smoker status (n=2); and stages IIB/IIIB/IV (n=1/8/6). All patients were unable to tolerate radical therapy because of old age or multiple comorbidities. The most commonly reported adverse events were lymphopenia and asthenia (grades 1-2 in most patients). No skin rash or allergic toxicities appeared. Dose-limiting toxicity occurred with pneumonia with grade 4 neutropenia at the 200mg dose of nimotuzumab. Objective response rate and disease control rate inside the radiation field were 46.7% and 100.0%, respectively. CONCLUSIONS Nimotuzumab in combination with radiotherapy is well-tolerated and feasible. Further clinical investigation of nimotuzumab in NSCLC patients is warranted.

The drug susceptibility profile and inducible resistance to macrolides of Mycobacterium abscessus and Mycobacterium massiliense in Korea

We conducted drug susceptibility testing (DST) against various antimicrobial agents, including new candidate drugs, and investigated the relationship between inducible resistance (IR) to macrolides and erm(41) gene in Mycobacterium abscessus complex. Sixty-two isolates of M. abscessus complex from 2 tertiary care hospitals in South Korea were tested against 10 antimicrobial agents. Thirty-five isolates were M. abscessus, and 27 were Mycobacterium massiliense. Amikacin, moxifloxacin, linezolid, clofazimine, and tigecycline were active against most isolates and cefoxitin and ciprofloxacin against moderate number of isolates. M. massiliense remained susceptible to macrolides; in contrast, M. abscessus became highly resistant on day 14 after incubation. DST pattern did not differ between clarithromycin and azithromycin. IR to clarithromycin was correlated with erm(41) genotype in M. abscessus. Variations in susceptibility to antimicrobial agents within species and the difference in DST patterns between M. abscessus and M. massiliense suggest that DST and identification of M. abscessus complex are significant before treatment.

Poor prediction of potentially drug-resistant pathogens using current criteria of health care-associated pneumonia

BACKGROUND Health care-associated pneumonia (HCAP) includes a broad range of patients having frequent or chronic contact with health care systems. However, the relationship between current defining criteria for HCAP and the risk of potentially drug-resistant (PDR) pathogens is controversial. METHODS We retrospectively evaluated patients admitted to Severance Hospital in South Korea with culture-positive pneumonia from January 2008 to December 2009. We analyzed the associations between risk factors for HCAP and infection with PDR pathogens, and developed a new scoring system to predict infection with PDR pathogens. RESULTS Among 339 patients, PDR pathogens were observed in 122 (36.0%). PDR pathogens were more common in HCAP than community-acquired pneumonia (CAP) (48.5% versus 23.8%, P<0.001). In a logistic regression, prior hospitalization within 90 days of pneumonia (OR=2.51, P=0.003), recent treatment with antimicrobials (OR=2.35, P=0.039), and nasogastric tube feeding (OR=15.28, P<0.001) were independently associated with PDR pathogens. For the prediction of PDR pathogens, the sensitivity and specificity of current HCAP criteria were 66.4% and 60.4%, respectively, and 68.0% and 67.3%, respectively, for the new scoring system. Moreover, the new scoring system showed better diagnostic accuracy than current HCAP criteria (area under curve=0.711 versus 0.634, P<0.001). CONCLUSIONS The current HCAP criteria are poor predictors of PDR pathogens and all patients with HCAP should not be empirically treated for these pathogens. To avoid excessive antibiotic use, individual risk stratification approaches should be considered.