Eun-Ha Koh

Platelet Inhibition by Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel in Patients With Acute Myocardial Infarction According to Cytochrome P450 2C19 Genotype

OBJECTIVES The aim of this study was to assess the degree of platelet inhibition by adjunctive cilostazol in patients with acute myocardial infarction (AMI) according to hepatic cytochrome P450 2C19 (CYP2C19) genotype. BACKGROUND Although adjunctive cilostazol intensifies platelet inhibition in AMI patients, it is not established whether this regimen can be free from the effect of CYP2C19 loss-of-function variants (*2/*3). METHODS We randomly assigned 126 AMI patients with available CYP2C19 genotyping to receive adjunctive cilostazol (triple group; n = 64) or high maintenance-dose (MD) clopidogrel of 150 mg/day (high-MD group; n = 62). Using conventional aggregometry and VerifyNow (Accumetrics Inc., San Diego, California), platelet reactivity was measured at pre-discharge and 30-day follow-up. Primary endpoint was change in maximal platelet aggregation (ΔAgg(max)) between pre-discharge and 30-day follow-up. High on-treatment platelet reactivity (HPR) was defined as 20 μmol/l adenosine diphosphate-induced maximal platelet aggregation (Agg(max)) >59%. RESULTS In noncarriers, despite numerically greater inhibition by adjunctive cilostazol, changes in platelet measures and the rate of HPR did not significantly differ between the 2 groups. In carriers, ΔAgg(max) after 5 and 20 μmol/l adenosine diphosphate stimuli was significantly higher in the triple (n = 39) versus high-MD group (n = 38) (21.8 ± 13.9% vs. 9.0 ± 13.3%, p < 0.001, and 24.2 ± 17.2% vs. 7.7 ± 15.5%, p < 0.001, respectively). Likewise, changes in late platelet aggregation and P2Y12 reaction unit were consistently greater in the triple versus high-MD group. Fewer patients in the triple group met the criteria of HPR at 30-day follow-up than in the high-MD group (15.4% vs. 44.7%, p = 0.005). CONCLUSIONS Compared with high-MD clopidogrel, adjunctive cilostazol significantly enhances platelet inhibition and reduces the rate of HPR, especially in AMI patients with CYP2C19 loss-of-function variants. (Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel in Acute Myocardial Infarction (AMI) Patients According to CYP2C19 Polymorphism [ACCELAMI2C19]; NCT00915733).

Decline in erythromycin resistance in group A streptococci from acute pharyngitis due to changes in the emm genotypes rather than restriction of antibiotic use.

BACKGROUND Group A streptococcus (GAS) is the most common cause of bacterial pharyngitis in children. Antibiotic resistance rates and emm genotypes of GAS isolated from patients with acute pharyngitis were studied in 2009. METHODS Throat cultures were taken from 499 children with acute pharyngitis in Jinju, Korea, in 2008-2009. A total of 174 strains (34.9%) of GAS were isolated, and antimicrobial susceptibility testing was performed using the disk diffusion method. The phenotypes of macrolide resistance and macrolide resistance genes were determined. The emm genotypes were identified using PCR and sequencing. The data were compared with those acquired in 2002 in the same region. Data on the annual macrolide production were collected between 1999 and 2008. RESULTS The resistance rates of GAS to erythromycin, clindamycin, and tetracycline were 4.6%, 2.9%, and 2.3%, respectively. The constitutive resistance rate was 62.5% for the erm(B) gene and 37.5% for the M phenotype of the mef(A) gene. emm4 was most frequently detected (28.2%), followed by emm89 (20.1%). Most of the erythromycin resistant strains had the emm28 genotype. We noted a gradual increase in macrolide production during the study period. CONCLUSIONS The erythromycin resistance rate of GAS isolated from children with acute pharyngitis was significantly lower in 2009 (4.6%) than in 2002 (44.8%). We observed a remarkable change in the distribution of emm genotypes during the 7-yr period. The significant decline in erythromycin resistance in 2009 might be associated with a prominent decrease in the resistant genotype emm12 (3.4% in 2009 vs. 28.0% in 2002) rather than restriction of macrolide use.

Clinical Evaluation of BacT/Alert FA Plus and FN Plus Bottles Compared with Standard Bottles

ABSTRACT The performance of the BacT/Alert FA Plus and FN Plus resin bottles was evaluated in comparison with that of standard aerobic (SA) and standard anaerobic (SN) bottles. Twenty milliliters of blood from adult patients was equally distributed into four types of bottles: FA Plus, FN Plus, SA, and SN. The detection of clinically significant organisms and the time to detection (TTD) were monitored for each bottle. Among the 3,103 blood culture sets that were requested, the blood volume of each bottle was over 4 ml in 1,481 sets (47.7%). Among these 1,481 sets, 158 cultures grew in the FA Plus and SA bottles, and 136 grew in the FN Plus and SN bottles. Growth in only one type of bottle was more commonly observed for the FA Plus (n = 38) than for the SA (n = 14) (P = 0.001) bottles and for the FN Plus (n = 27) than for the SN (n = 10) (P = 0.008) bottles. Gram-negative bacilli were more frequently isolated in the resin bottles (P < 0.05). The skin contamination rate was 1.2% in the resin bottles and the standard bottles. The mean TTD was 11.1 h in the FA Plus bottles versus 13.1 h in the SA bottles (P < 0.001) and 12.0 h in the FN Plus bottles versus 12.8 h in the SN bottles (P = 0.083). Clinically significant bacteria, including Gram-negative bacilli, were isolated more frequently from the resin bottles than from the standard bottles. Clinically significant bacteria were detected faster using the aerobic resin bottles than using the standard aerobic bottles. This finding might not be applicable to the standard-practice 10-ml protocol for each bottle because the results from using a smaller volume (5 ml) might be less pronounced.

Antimicrobial Susceptibilities of Ureaplasma urealyticum and Mycoplasma hominis in Pregnant Women

Background: Ureaplasma urealyticum and Mycoplasma hominis are associated with an increased risk of pregnancy complications, such as preterm birth and premature membrane rupture. The purpose of this study was to determine the isolation rates and antimicrobial susceptibilities of genital mycoplasma in a sample of pregnant women from Jinju, Korea. Methods: Vaginal swabs were obtained from 258 pregnant women between 2004 and 2008 and tested for the presence of U. urealyticum and M. hominis at Gyeongsang National University Hospital. The identification and antimicrobial susceptibilities of U. urealyticum and M. hominis were determined with a commercially available kit, the Mycoplasma IST2 Kit (bioMe rieux, Marcy-l’Etoile, France), and evaluated according to standards set by the Clinical and Laboratory Standards Institute (CLSI). Results: U. urealyticum only was detected in 105 specimens (38.6%), while M. hominis only was detected only in 2 specimens (1.8%). Seven specimens (6.7%) were positive both for U. urealyticum and M. hominis. Susceptibilities of U. urealyticum to azithromycin, erythromycin, clarithromycin, and doxycycline were 75.2%, 82.9%, 88.6%, and 88.6%, respectively, while almost all of the isolates were susceptible to josamycin (99.0%) and pristinamycin (100%). The susceptibility of U. urealyticum to ofloxacin and ciprofloxacin was 56.2% and 15.2%, respectively. Conclusion: The rate of isolation of genital mycoplasma in pregnant women was 44.2% in Jinju; most of the mycoplasma were U. urealyticum. U. urealyticum and M. hominis were highly resistant to quinolones, but susceptible to josamycin. Therefore, empirical treatment without prior identification and determination of the antimicrobial susceptibility of genital mycoplasma will fail in many cases. (Korean J Clin Microbiol 2009;12:159-162)

Growth dynamics of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa as a function of time to detection in BacT/alert 3D blood culture bottles with various preincubation conditions.

Background Delayed entry of blood culture bottles is inevitable when microbiological laboratories do not operate for 24 hr. There are few studies reported for prestorage of these bottles. The growth dynamics of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were investigated with respect to various preincubation conditions. Methods Fifteen or 150 colony-forming units (CFU) of bacteria were inoculated into standard aerobic or anaerobic blood culture bottles. Bottles were preincubated at 25℃ or 37℃ for 0, 2, 4, 8, 12, 24, or 48 hr. The time to detection (TTD) then was monitored using the BacT/Alert 3D system (bioMerieux Inc., USA). Results Significant difference in TTD was observed following preincubation for 8 hr at 25℃ vs. 4 hr at 37℃ for S. aureus, 4 hr at 25℃ vs. 4 hr at 37℃ for E. coli, 12 hr at 25℃ vs. 4 hr at 37℃ for P. aeruginosa, compared to no preincubation (P<0.005). TTD values did not vary significantly with bacterial CFU or with aerobic or anaerobic bottle type. The BacT/Alert 3D system returned false negatives following preincubation of P. aeruginosa for 48 hr at 25℃ or 24 hr at 37℃. Conclusions TTD was mainly affected by preincubation temperature and duration rather than by input CFU quantity or bottle type for the 3 experimental bacteria.

Establishing the heparin therapeutic range using aPTT and anti-Xa measurements for monitoring unfractionated heparin therapy

Background Unfractionated heparin (UFH) has unstable pharmacokinetics and requires close monitoring. The activated partial thromboplastin time (aPTT) test has been used to monitor UFH therapy for decades in Korea, but its results can be affected by numerous variables. We established an aPTT heparin therapeutic range (HTR) corresponding to therapeutic anti-Xa levels for continuous intravenous UFH administration, and used appropriate monitoring to determine if an adequate dose of UFH was applied. Methods A total of 134 ex vivo samples were obtained from 71 patients with a variety of thromboembolisms. All patients received intravenous UFH therapy and were enrolled from June to September 2015 at Gyeongsang National University Hospital. All laboratory protocols were in accordance with the Clinical and Laboratory Standards Institute guidelines and the College of American Pathologist requirements for aPTT HTR. Results An aPTT range of 87.1 sec to 128.7 sec corresponded to anti-Xa levels of 0.3 IU/mL to 0.7 IU/mL for HTR under our laboratory conditions. Based on their anti-Xa levels, blood specimen distribution were as follows: less than 0.3 IU/mL, 65.7%; 0.3–0.7 IU/mL (therapeutic range), 33.6%; and more than 0.7 IU/mL, 0.7%. No evidence of recurring thromboembolism was observed. Conclusion Using the conventional aPTT target range may lead to inappropriate dosing of UFH. Transitioning from the aPTT test to the anti-Xa assay is required to avoid the laborious validation of the aPTT HTR test, even though the anti-Xa assay is more expensive.

Upregulation of Human Mammaglobin Reduces Migration and Invasion of Breast Cancer Cells

Little is known about the biological role of human mammaglobin (hMAM) that is considered as a promising marker for breast cancer. Here, we investigated hMAMs role related to migration and invasion of human breast cancer cells (hBCC). Compared to normal cells, hBCC have high MAM mRNA expression levels. Of the hBCC tested, MAM mRNA expression levels were higher in noninvasive than in invasive cells. Overexpression of hMAM in breast cancer cells decreased migration and invasion, whereas knockdown of hMAM increased both. Taken together, these results suggest that metastasis of hBCC could be controlled by hMAM expression levels.

Effects of Preincubating Blood Culture Bottles at 37℃ during the Night Shift and of Collected Blood Volume on Time to Detection and Days to Final Report

Background: By varying the collected blood volume and storage temperature of the blood culture bottles prior to entry in an automated blood culture system, growth of organisms will be affected. Methods: Blood culture bottles with a 20 mL blood volume per set were stored at 37 o C (1 st period) and room temperature (RT, 2nd period) upon arrival at the laboratory after working hours compared to baseline period (10 mL, RT). The time to detection (TTD) for all strains and the number of days until the final report after bottle entry were compared among the three periods. Results: The median TTD for all strains was 13.5 h, 10.6 h, and 11.3 h in the baseline (N=268), 1st (N=454), and 2 nd period (N=370), respectively (P＜0.001). The final identification report was available within two days of bottle entry for 12.3%, 30.6% and 15.1% of bottles in the three different periods, respectively (P＜0.001). Conclusion: Collecting an adequate blood volume is critical to reduce TTD. The preincubation of blood culture bottles at 37 o C during the night shift might enable earlier final reports than storage at RT for samples with the same collected blood volume. (Ann Clin Microbiol 2014;17:14-19)

A Multicentre Study about Pattern and Organisms Isolated in Follow-up Blood Cultures

accounted for 2.3% of events, whereas immune clea- rance was confirmed in 8.5% of events. Previously undetected pathogens were isolated in 5.2% of the follow-up cultures, the majority of which grew after an interval of six days. Skin contaminants were de- tected in 7.6% of the repeated cultures, and 76.1% of the follow-ups displayed no growth of microorganisms. Conclusion: The most common numbers of repeat culture requests were two and three, and these were typically performed within three days of the initial culture. Among the follow-up cultures, new patho- gens were identified in 5.2%, and the majority of this group likely presented for follow-up during a new dis- ease episode. (Ann Clin Microbiol 2013;16:8-12)

Effect of Sodium Citrate on Growth of Bacteria in Blood Culture

Background: This study compared the growth of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Haemophilus influenzae in blood culture bottles containing anticoagulants, sodium polyanethol sulfonate (SPS) and sodium citrate. Methods: One hundred and fifty colony forming units of five different bacterial species were inoculated into standard aerobic (SA) and standard anaerobic (SN) bottles and were combined with 5 mL of human blood in solution with SPS or sodium citrate. Time to detection (TTD) was then monitored using the BacT/ Alert 3D system (bioMerieux Inc.). Results: Compared to the bacteria-only controls, cultures containing S. aureus, E. coli, P. aeruginosa, and S. pneumoniae plus SPS blood or citrated blood trended toward reduced TTD in both SA and SN bottles; however, there was no significant difference in TTD between SPS and sodium citrate anticoagulant. Although H. influenzae showed a remarkable difference in TTD between SPS (SA 14.8 h, SN 15.0 h) and sodium citrate (SA 23.5 h, SN 18.3 h), this difference was not statistically significant (P=0.10). Conclusion: Addition of blood enhanced growth of bacteria. All experimental bacteria except H. influenzae showed similar TTD in SPS blood and citrated blood. These results support the usefulness of sodium citrate anticoagulant for artificial inoculation in blood culture bottles. (Ann Clin Microbiol 2013;16: 168-173)