Gyu Yel Hwang

Macrolide Resistance Trends in beta-Hemolytic Streptococci in a Tertiary Korean Hospital

Purpose Erythromycin-resistant β-hemolytic streptococci (BHS) has recently emerged and quickly spread between and within countries throughout the world. In this study, we evaluate the antimicrobial susceptibility patterns and erythromycin resistance mechanisms of BHS during 2003-2004. Materials and Methods The MICs of seven antimicrobials were determined for 204 clinical isolates of BHS from 2003 to 2004. Resistance mechanisms of erythromycin-resistant BHS were studied by the double disk test as well as by polymerase chain reaction (PCR). Results Compared with our previous study, resistance among Streptococcus pyogenes isolates to a variety of drugs decreased strikingly: from 25.7% to 4.8% in erythromycin; 15.8% to 0% in clindamycin; and 47.1% to 19.0% in tetracycline. The prevalent phenotypes and genotypes of macrolide-lincosamide-streptograminB (MLSB) resistance in Streptococcus pyogenes isolates have been changed from the constitutive MLSB phenotype carrying erm(B) to the M phenotype with mef(A) gene. In contrast with Streptococcus pyogenes, resistance rates to erythromycin (36.7%), clindamycin (43.1%), and tetracycline (95.4%) in Streptococcus agalactiae isolates did not show decreasing trends. Among the Streptococcus dysgalactiae subsp. equisimilis isolates (Lancefield group C, G), resistance rates to erythromycin, clindamycin, tetracycline and chloramphenicol were observed to be 9.4%, 3.1%, 68.8%, and 9.4%, respectively. Conclusion Continual monitoring of antimicrobial resistance among large-colony-forming BHS is needed to provide the medical community with current data regarding the resistance mechanisms that are most common to their local or regional environments.

Antimicrobial Susceptibility Patterns and Macrolide Resistance Genes of β-Hemolytic Streptococci in Korea

ABSTRACT In 540 beta-hemolytic streptococci, the rates of resistance to tetracycline, chloramphenicol, erythromycin, and clindamycin were 80.0, 22.8, 20.2, and 19.1%, respectively. Of the erythromycin-resistant isolates, 63.3% had the constitutive macrolide-lincosamide-streptogramin B (MLSB) resistance phenotype, 23.9% had the M phenotype, and 12.8% had the inducible MLSB resistance phenotype. The constitutive MLSB resistance phenotype with the erm(B) gene was dominant in Korea.

Correlation of Serotypes and Genotypes of Macrolide-Resistant Streptococcus agalactiae

Despite the necessity for studies of group B streptococci (GBS), due to the increase in serious adult infections, the emergence of new serotypes, and the increased resistance to macrolide antibiotics, such studies have been limited in Korea. The primary purpose of the present study was to determine the frequency trends of GBS serotypes, including serotypes VI, VII, and VIII. The final objective was to elucidate the relationship between the genotypes and serotypes of macrolide-resistant GBS isolates from a Korean population. Among 446 isolates of Streptococcus agalactiae, isolated between January 1990 and December 2002 in Korea, the frequency of serotypes were III (36.5%), Ib (22.0%), V (21.1%), Ia (9.6%), VI (4.3%), II (1.8%), VIII (1.3%), IV (1.1%), and VII (0.9%). The resistance rates to erythromycin, by serotype, were 85% (V), 23% (III), 21% (VI), 3% (Ib), and 2% (Ia). Of 135 erythromycin-resistant S. agalactiae, ermB was detected in 105 isolates, mefA in 20 isolates, and ermTR in seven isolates; most type V isolates harbored the ermB gene, Ib type isolates had an equal distribution of resistance genes, type III isolates accounted for 70% of all isolates carrying mefA genes, and one fourth of type VI isolates had mefA genes.

Serotypes and Genotypes of Erythromycin-Resistant Group B Streptococci in Korea

ABSTRACT Among 78 erythromycin-resistant group B streptococcus (GBS) isolates from Korea, ermB was detected in 58 (74.4%), mefA was detected in 14 (17.9%), and ermTR was detected in 6 (7.7%). The most prevalent serotypes of erythromycin-resistant GBS were V (detected in 34 isolates [43.6%]) and III (detected in 33 isolates [42.3%]). All serotype V erythromycin-resistant GBS harbored the ermB gene.

Multidrug-Resistant Corynebacterium striatum Bacteremia: First Case in Korea

Dear Editor Corynebacteria are aerobic, non-spore forming, and gram-positive bacilli that are commensal organisms of skin and mucosal membranes. C. striatum, like other Corynebacterium species, is a part of the normal human skin flora; therefore, it has been frequently dismissed as a blood and airway sample contaminant in the past. However, C. striatum is emerging as a cause of bloodstream infections and endocarditis [1]. Moreover, C. striatum infection outbreaks have been reported in long-stay patients with underlying disease [2]. We report a case of C. striatum bacteremia in a patient who had undergone gastrostomy. To our knowledge, there has been no report of C. striatum bacteremia in Korea so far. A 64-yr-old quadriplegic man visited the outpatient rehabilitation clinic for gastrostomy tube change. Before visiting our hospital, he was admitted to a secondary hospital and had hypertension and diabetes mellitus. Nine months before this visit, quadriplegia developed because of hypoxic ischemic encephalopathy; he underwent tracheostomy and gastrostomy tube placement. He was admitted to our hospital owing to persistent low-grade fever with blood pressure of 156/89 mmHg. The white blood cell count was 6.02×109/L (86% segmented neutrophils), and C-reactive protein level was 3.34 mg/dL (reference range: 128 µg/mL), and erythromycin (>128 µg/mL). At first, the physician assumed that C. striatum was a contaminant and the fever was caused by a urinary tract infection on the basis of the past history. Thus, only intravenous piperacillin/tazobactam was administered for the possible urinary tract infection. Culture for medical devices such as the gastrostomy or tracheostomy tubes was not performed. However, fever did not subside and C-reactive protein level was elevated; follow-up blood cultures performed on the 6th day of admission revealed C. striatum growth. The patient was continuously given intravenous piperacillin/tazobactam. As the fever subsided, he was transferred to a provincial medical center. The patient was readmitted for check-up a month after discharge and showed no sign of infection. It is difficult to distinguish simple colonization from real infection when Corynebacterium spp. are recovered from specimens [4]. C. striatum are commonly isolated in patients with significant underlying illnesses [2] and has close association with various medical devices such as prosthetic valve/joint and central venous catheter [5] and long hospitalization. In this case, the patient suffered from diabetes, hypertension, tracheostomy, and gastrostomy. Additionally, he had stayed at a secondary health care center before being admitted to our hospital. These factors probably increased the patients risk of C. striatum infection. Additionally, each of the blood culture sets was collected at regularly spaced intervals with adequate blood volumes, and turned positive within 24 hr. One of the recent issues related to C. striatum is the emergence and spread of multidrug resistance. Generally, most of the reported C. striatum isolates were susceptible to a wide range of antibiotics [6]; however, recent studies showed the emergence of multi-drug resistant strains with increasing use of broad-spectrum antibiotics (Table 1) [1, 4, 6, 7]. When invasive C. striatum infection is suspected, most initial therapies should include vancomycin, because in vitro resistance to vancomycin has not been reported in any of the Corynebacterium species [5]. If the patient is allergic to vancomycin, daptomycin may be an alternative. Fernandez et al. [1] reported successful treatment of a case of multidrug-resistant C. striatum endocarditis with daptomycin. Table 1 Multidrug resistant Corynebacterium striatum in the literature In conclusion, with increasing numbers of immunosuppressed patients and indwelling medical devices, C. striatum infections will be more commonly found and should never be overlooked as a contaminant. This report suggests the need to increase awareness of C. striatum as a pathogen causing bloodstream infections.

Antimicrobial Susceptibility Patterns and Macrolide Resistance Genes of β-Hemolytic Viridans Group Streptococci in a Tertiary Korean Hospital

The aim of this study was to investigate antimicrobial susceptibilities and macrolide resistance mechanisms of β-hemolytic viridans group streptococci (VGS) in a tertiary Korean hospital. Minimum inhibitory concentrations (MICs) of seven antimicrobials were determined for 103 β-hemolytic VGS isolated from various specimens. The macrolide resistance mechanisms of erythromycin-resistant isolates were studied by the double disk test and polymerase chain reaction (PCR). The overall resistance rates of β-hemolytic VGS were found to be 47.5% to tetracycline, 3.9% to chloramphenicol, 9.7% to erythromycin, and 6.8% to clindamycin, whereas all isolates were susceptible to penicillin G, ceftriaxone, and vancomycin. Among ten erythromycin-resistant isolates, six isolates expressed a constitutive MLSB (cMLSB) phenotype, and each of the two isolates expressed the M phenotype, and the inducible MLSB (iMLSB) phenotype. The resistance rates to erythromycin and clindamycin of β-hemolytic VGS seemed to be lower than those of non-β-hemolytic VGS in our hospital, although cMLSB phenotype carrying erm(B) was dominant in β-hemolytic VGS.

NDM-5 and OXA-48 Co-producing Uropathogenic Escherichia coli Isolate: First Case in Korea

Dear Editor, The increasing incidence of carbapenem-resistant Enterobacteriaceae (CRE) is a major concern for global health [1]. Among CRE, the prevalence of carbapenemase-producing Enterobacteriaceae (CPE) ranges from 11% to 20.1% in Korea [2, 3]. The most clinically significant CPE are of the KPC-, IMP-, VIM-, NDM-, and OXA-48 types, mostly identified from Klebsiella pneumoniae isolates as sources of nosocomial outbreaks [4]. The microorganisms carrying these genes are a grave threat to global health, not only because of their resistance capacity but also because the genes are carried on plasmids. OXA-48-producing Enterobacteriaceae have been found worldwide since the first isolation of this gene from a K. pneumoniae isolate in Turkey in 2003 [4]. Although only one isolate of OXA-48-producing Escherichia coli has been previously detected in Korea in a urine specimen from a foreign patient [2], such bacteria are likely to emerge and spread owing to travel or patient exchanges from other countries [4]. NDM-1and NDM-5-producing E. coli have been reported in Korea, although they are uncommon [5, 6]. While NDM and OXA co-producing Enterobacteriaceae are emerging [4, 7], NDM-5 and OXA-48 co-producing E. coli have not been reported worldwide to date. Here, we describe the first identification of NDM-5 and OXA-48 co-producing E. coli in Korea. This case has got an exemption (2017-11-0222) from the approval of the Institutional Review Board for Human Research in Yonsei University Wonju Severance Christian Hospital. Informed consent from the patient was not required for this report because the patient was de-identified. A 76-year-old female patient was admitted to the Wonju Severance Christian Hospital for aortic valve replacement surgery due to severe aortic stenosis. The patient had a medical history of recent cerebral infarction, coronary artery occlusion disease, paroxysmal atrial fibrillation, and hypertension. She had no known recent history of travel. Following the surgery, she was treated for pneumonia with cefepime. A few days later, the patient newly developed a fever of 38.2°C. Two aerobic and anaerobic blood culture sets drawn from both arms were incubated in the BacT/Alert 3D system (bioMérieux, Marcy l’Etoile, France), and no organisms were detected from the blood cultures after five days of incubation. The laboratory findings showed an elevated white blood cell count of 11.22×10/L (segmented neutrophils, 67.2%) and serum C-reactive protein level of 224.76 nmol/L (reference range: <28.57 nmol/L). The platelet count decreased to 86×10/L. Urinalysis showed bacteriuria, and urine culture revealed the presence of Enterococcus faecium (>10 CFU/mL). Levofloxacin was administered to the patient, and the

First Case of Pasteurella multocida Pneumonic Bacteremia in Korea

Dear Editor, There are rising concerns related to the high incidence of zoonotic diseases in humans, caused by close encounters with pets and other wild or domestic animals [1]. Pasteurella species are one of the most prevalent commensal and opportunistic infection-causing pathogens found in domestic and wild animals worldwide, and are part of the normal flora of the oral, nasal, and respiratory cavities in many animals such as dogs and cats [2]. Although Pasteurella mostly causes local wound infections in humans following animal bites or scratches, cases of infections including those of the bloodstream or respiratory system have also been reported for this opportunistic pathogen [3, 4]. However, to our knowledge, there is no report of pneumonic bacteremia caused by Pasteurella in Korea. We describe a case of a systemic infection of Pasteurella multocida in the bloodstream and respiratory system of a Korean patient. This study was exempted from review by the Institutional Review Board for Human Research, Yonsei University, Wonju Severance Christian Hospital (2017-12-0145). Informed consent from the patient was not required for this report because de-identified patient data was used. A 70-year-old man was admitted to Wonju Severance Christian Hospital because of abdominal pain and low blood pressure for one day. The patient also complained of coughing, a brownish blood-tinged sputum, rhinorrhea, heating sensation, chills, and chest discomfort. The patient had a medical history of hypertension, stable angina, pulmonary tuberculosis, chronic obstructive pulmonary disease, allergic rhinitis, and asthma. The patient does not breed any animals and did not report any contact with animals in the previous year. He was a chronic alcoholic with a more than 50-year history of heavy drinking, but had quit drinking one year prior to hospital admission and had no history of liver dysfunction. Physical examination revealed a low blood pressure of 76/52 mmHg and crackles on the right lower lung field. Laboratory findings showed an elevated white blood cell count of 21.3×10/L (94% segmented neutrophils) and serum C-reactive protein level (170.0 mg/L, reference: <3.0 mg/L). Chest computerized tomography showed consolidation in the right lower lobe. The patient was diagnosed as having community-acquired pneumonia and was empirically treated with cefoperazone-sulbatam and moxifloxacin. A blood specimen was incubated using two aerobic and anaerobic culture sets in the BacT/Alert 3D system (bioMérieux, Durham, NC, USA). After a 14-hour incubation period, gramnegative coccobacilli grew in the aerobic bottle and were identified as P. multocida by VITEK 2 systems (bioMérieux) using the gram-negative identification card (Bionumber 0001410100040001, bioMérieux). A sputum specimen was also inoculated on 5%

A New Bacterial Growth Graph Pattern Analysis to Improve Positive Predictive Value of Continuous Monitoring Blood Culture System

False positive signals (FPSs) of continuous monitoring blood culture system (CMBCS) cause delayed reporting time and increased laboratory cost. This study aimed to analyze growth graphs digitally in order to identify specific patterns of FPSs and true positive signals (TPSs) and to find the method for improving positive predictive value (PPV) of FPS and TPS. 606 positive signal samples from the BACTEC FX (BD, USA) CMBCS with more than one hour of monitoring data after positive signal were selected, and were classified into FPS and TPS groups using the subculture results. The pattern of bacterial growth graph was analyzed in two steps: the signal stage recorded using the monitoring data until positive signal and the post-signal stage recorded using one additional hour of monitoring data gained after the positive signal. The growth graph before the positive signal consists of three periods; initial decline period, stable period, and steeping period. Signal stage analyzed initial decline period and stable period, and classified the graphs as standard, increasing, decreasing, irregular, or defective pattern, respectively. Then, all patterns were re-assigned as confirmed or suspicious pattern in the post-signal stage. Standard, increasing, and decreasing patterns with both initial decline period and stable period are typical patterns; irregular patterns lacking a smooth stable period and defective patterns without an initial decline period are false positive patterns. The false positive patterns have 77.2% of PPV for FPS. The confirmed patterns, showing a gradually increasing fluorescence level even after positive signal, have 97.0% of PPV for TPS.

Vancomycin Resistance due to vanA Gene Expression in an Aerococcus viridans Isolate: First Case in Korea

Dear Editor, Aerococcus viridans is a catalase-negative gram-positive coccus that appears in clusters, tetrads, or irregular arrangements [1]. This organism is generally considered as a contaminant in clinical cultures, but is also infrequently reported as a clinically significant isolate that causes endocarditis, bacteremia, spondylodiscitis, and urinary tract infections [2-5]. Although most A. viridans strains were susceptible to penicillin and other commonly used antibiotics, Uh et al [6] described a case of bacteremia caused by an A. viridans strain showing high resistance to penicillin, erythromycin, clindamycin, and ceftriaxone. In 2014, Zhou et al [7] reported a peritoneal dialysis-related infection caused by vancomycin-resistant A. viridans harboring the vanA gene. We report a case of a vancomycin-resistant A. viridans isolate obtained from an excisional biopsy wound. As far as we know, no study regarding vancomycin-resistant A. viridans has yet been published in Korea. A 77-yr-old farmer visited the emergency room complaining of severe chills. Swelling in an external wound was observed on the inguinal areas where previous excisional biopsy was performed. He had recently been diagnosed as having colon adenocarcinoma and angioimmunoblastic T-cell lymphoma. On admission, his body temperature was 39.0°C. Hematological investigation revealed a hemoglobin level of 9.2 g/dL, white blood cell (WBC) count of 18.96×10/L (segmented neutrophils; 92.2%), and platelet count of 262×10/L. Serum C-reactive protein (CRP) level (14.36 mg/dL, reference range: <0.30 mg/dL) was elevated. Two aerobic and anaerobic blood culture sets were incubated in the BacT/Alert 3D system (bioMérieux, Durham, NC, USA). The mucus-like whitish aspirate from the wound was plated onto 5% sheep blood agar (BD Diagnostic Systems, Sparks, MD, USA), MacConkey agar (BD Diagnostic Systems), and fluid thioglycollate medium (BD Diagnostic Systems). Some colonies grew on the 5% sheep blood agar after 24 hr aerobic incubation at 35°C; these colonies were identified as oxacillin-resistant Staphylococcus hemolyticus by VITEK 2 (bioMérieux, Marcy l’Etoile, France). No growth was detected in the blood cultures after five days of incubation. Thirteen days after hospital admission, chemotherapy for lymphoma was initiated. Although WBC count and CRP level were within reference ranges at that time, mucus-like discharge from the wound remained, and CRP started to rise steadily. A. viridans and S. hemolyticus were repeatedly simultaneously isolated from wound cultures. The identification probability of A. viridans by VITEK 2 was 98%. Antimicrobial susceptibility test by a MicroScan MICroSTREP plus panel (Beckman Coulter, Brea, CA, USA) showed that A. viridans was susceptible to tetracycline, but resistant to vancomycin, penicillin, cefotaxime, ceftriaxone, sulfamethoxazole/tri-