The Changes in Epidemiology of Imipenem-Resistant Acinetobacter baumannii Bacteremia in a Pediatric Intensive Care Unit for 17 Years

Background@#Acinetobacter baumannii infections cause high morbidity and mortality in intensive care unit (ICU) patients. However, there are limited data on the changes of longterm epidemiology of imipenem resistance in A. baumannii bacteremia among pediatric ICU (PICU) patients. @*Methods@#A retrospective review was performed on patients with A. baumannii bacteremia in PICU of a tertiary teaching hospital from 2000 to 2016. Antimicrobial susceptibility tests, multilocus sequence typing (MLST), and polymerase chain reaction for antimicrobial resistance genes were performed for available isolates. @*Results@#A. baumannii bacteremia occurred in 27 patients; imipenem-sensitive A. baumannii (ISAB, n = 10, 37%) and imipenem-resistant A. baumannii (IRAB, n = 17, 63%). There was a clear shift in the antibiogram of A. baumannii during the study period. From 2000 to 2003, all isolates were ISAB (n = 6). From 2005 to 2008, both IRAB (n = 5) and ISAB (n = 4) were isolated. However, from 2009, all isolates were IRAB (n = 12). Ten isolates were available for additional test and confirmed as IRAB. MLST analysis showed that among 10 isolates, sequence type 138 was predominant (n = 7). All 10 isolates were positive for OXA-23-like and OXA-51-like carbapenemase. Of 27 bacteremia patients, 11 were male (41%), the median age at bacteremia onset was 5.2 years (range, 0–18.6 years). In 33% (9/27) of patients, A. baumannii was isolated from tracheal aspirate prior to development of bacteremia (median, 8 days; range, 5–124 days). The overall case-fatality rate was 63% (17/27) within 28 days. There was no statistical difference in the case fatality rate between ISAB and IRAB groups (50% vs. 71%; P = 0.422). @*Conclusion@#IRAB bacteremia causes serious threat in patients in PICU. Proactive infection control measures and antimicrobial stewardship are crucial for managing IRAB infection in PICU.

Association Between Toxin-antitoxin Systems on Plasmids and Persister Formation in CTX-15-producing Klebsiella pneumoniae ST11 Isolates

We investigated the effect of toxin-antitoxin (TA) systems in bla(CTX-M-15)-bearing plasmids of Klebsiella pneumoniae on persister formation. The persister formation rate was notably high in transconjugants in plasmids bearing TA system than the transconjugants in plasmids bearing no TA systems. Activation of relA and spoT expression was higher in transconjugants with plasmids bearing TA systems. Thus, TA systems in plasmids may contribute to the maintenance of bla(CTX-M-15)-bearing plasmids and host survival via persister formation.

Bacteremia caused by Leuconostoc species : 6-case series / 고신대학교의과대학학술지

Leuconostoc species are Gram-positive coccobacilli and are used in dairy products and are intrinsically resistant to vancomycin. Leuconostoc infections are rare in humans, usually occurring in immune-compromised patients. We describe 6 patients with Leuconostoc bacteremia at Dong-A university hospital between 1990 and 2015. One isolate (L. lactis) was identified to species level using 16S rRNA gene sequencing analysis. All patients had underlying diseases and 5 patients underwent procedures that interrupted the normal integumentary defense. Four patients died within 30 days after being identified as carrying Leuconostoc species.

First Case of Necrotizing Fasciitis Caused by Skermanella aerolata Infection Mimicking Vibrio Sepsis

No abstract available.

Current Situation of Antimicrobial Resistance and Genetic Differences in Stenotrophomonas maltophilia Complex Isolates by Multilocus Variable Number of Tandem Repeat Analysis / 감염과화학요법

BACKGROUND: Stenotrophomonas maltophilia is one of several opportunistic pathogens of growing significance. Several studies on the molecular epidemiology of S. maltophilia have shown clinical isolates to be genetically diverse. MATERIALS AND METHODS: A total of 121 clinical isolates tentatively identified as S. malophilia from seven tertiary-care hospitals in Korea from 2007 to 2011 were included. Species and groups were identified using partial gyrB gene sequences and antimicrobial susceptibility testing was performed using a broth microdilution method. Multi locus variable number of tandem repeat analysis (MLVA) surveys are used for subtyping. RESULTS: Based on partial gyrB gene sequences, 118 isolates were identified as belonging to the S. maltophilia complex. For all S. maltophilia isolates, the resistance rates to trimethoprime-sulfamethoxazole (TMP/SMX) and levofloxacin were the highest (both, 30.5%). Resistance rate to ceftazidime was 28.0%. 11.0% and 11.9% of 118 S. maltophilia isolates displayed resistance to piperacillin/tazobactam and tigecycline, respectively. Clade 1 and Clade 2 were definitely distinguished from the data of MLVA with amplification of loci. All 118 isolates were classified into several clusters as its identification. CONCLUSION: Because of high resistance rates to TMP/SMX and levofloxacin, the clinical laboratory department should consider providing the data about other antimicrobial agents and treatment of S. maltophilia infections with a combination of antimicrobials can be considered in the current practice. The MLVA evaluated in this study provides a fast, portable, relatively low cost genotyping method that can be employed in genotypic linkage or transmission networks comparing to analysis of the gyrB gene.

Efflux Pump Inhibitor Carbonyl Cyanide-m-chlorophenylhydrazone (CCCP) Enhances Bacteriostatic Activity of Trimethoprim-sulfamethoxazole Against Clinical Stenotrophomonas maltophilia Isolates from Korea

Although trimethoprim-sulfamethoxazole (TMP-SXT) is considered the first-line therapy for Stenotrophomonas maltophilia infections, there is debate on the use of the bacteriostatic drug in serious infections, and recently, there has been an increasing occurrence of acquired resistance to TMP-SXT. In the present study, the effect of efflux pump inhibitors on the susceptibility of TMP-SXT and other antibiotics were investigated in S. maltophilia complex. The sul and/or dfrA genes were identified in only up to 27.8% of all 36 TMP-SXT-resistant S. maltophilia complex isolates. Thus, TMP-SXT resistance in S. maltophilia was not explained completely by the presence of sul and dfrA genes. Carbonyl cyanide-m-chlorophenylhydrazone (CCCP) decreased the minimum inhibitory concentration (MIC) of TMP-SXT by eight to 128 folds in all 14 isolates. In contrast, 2,4-dinitrophenol (DNP), phenyl-arginine-β-naphthylamide (PAβN), and reserpine did not reduce the MIC of TMP-SXT. In addition to TMP-SXT, slight decrease in MICs was observed for tigecycline and piperacillin/tazobactam by CCCP (by two folds) in one isolate. Although efflux pump may play a role in TMP-SXT resistance in S. maltophilia, inhibition of the efflux pump could be done by active proton pore.

ISAba15 Inserted into Outer Membrane Protein Gene carO in Acinetobacter baumannii

We identified ISAba15 inserted into the carO gene in an Acinetobacter baumannii isolate. The insert disrupted the lpxD gene, resulting in colistin resistance in A. baumannii. Persistence in carbapenem resistance in A. baumannii isolates with an intact carO gene indicates that loss of the encoded CarO may play a minor role in carbapenem resistance.

The First Case of Non-retrospective Clinical Identification of Severe Fever with Thrombocytopenia Syndrome Patient in 2013 in South Korea

In this study, we report the first clinically identified case of severe fever with thrombocytopenia syndrome (SFTS) in a 73-year old man from Jeju Island, South Korea. Although his initial manifestation suggested tsutsugamushi disease with cutaneous lesion, later the patient presented with symptoms characteristic of SFTS. Despite intensive medical therapies upon the clinical diagnosis of SFTS, patient's condition rapidly deteriorated. SFTS is a fatal disease that requires early diagnosis and appropriate supportive treatment.

A Case of Paenibacillus pasadenensis Bacteremia in a Patient with Acute Respiratory Distress Syndrome after Microsurgical Clipping / 감염과화학요법

We report the first case of bacteremia by a novel Paenibacillus species, Paenibacillus pasadenensis, from a 55-year-old male patient with acute respiratory distress syndrome, following a microsurgical clipping procedure of a ruptured intracranial aneurysm. The bacterium was identified using 16S rRNA gene sequencing analysis, which was applied because current conventional methods employed in the clinical microbiology laboratory proved unsuccessful. Since this bacterium was first identified in 2006 and has never been reported elsewhere, we believe this report can provide practitioners with useful insight on the pathogenicity of this species.

Comparisons of CTX-M-Producing Escherichia coli Isolates from Humans and Animals in South Korea

To investigate the possibility of transmission of CTX-M-producing Escherichia coli isolates among humans and animals, we compared CTX-M-producing E. coli isolates showing the same genotype from humans and dogs in Korea. Sixteen CTX-M-producing E. coli isolates from animals were selected and their genotypes were identified using MLST. Among clinical CTX-M-producing E. coli isolates from humans, which have been identified in previous studies, 12 isolates showing the same STs with those of E. coli isolates from animals were selected. For these 28 CTX-M-producing E. coli isolates, identification of bla CTX-M genes and their genetic environments, antimicrobial susceptibility testing, extended MLST, and PFGE were performed. Some CTX-M-producing E. coli isolates from humans showed the same genotypes, such as ST10, ST38, ST58, and ST95, but different CTX-M enzymes and PFGE patterns. Thus, it can be concluded that dissemination of ESBL-producing E. coli isolates between humans and animals is rare so far.

Persister Cells: Survival Strategies under Antimicrobiotic Stress

Persistence is dormant phenotypic variants of regular cells that are tolerant to antibiotics. The persistent cells did not acquire antibiotic resistance genetically, being produced in response to antibiotic stress. Because of dormant phenotypic variants due to little or no cell-wall synthesis, translation, or topoisomerase activity, persistent cells show antibiotic tolerance. Recently, such persistent cells have been reported in many bacterial pathogens and are known to play significant roles in clinical settings, particularly in chronic diseases such as cystic fibrosis. Therefore, development of anti-persister drug and appropriate antibiotic treatment are required to eliminate the persisters and to prevent the development of antibiotic resistance. Screening of genes related to persister formation would lead to new drugs to combat persisters during infection. By reviewing recent publications, we summarize phenomenon of survival and tolerance in persistent cells.

Clinical and Molecular Epidemiology of Community-Onset Bacteremia Caused by Extended-Spectrum beta-Lactamase-Producing Escherichia coli over a 6-Year Period

Although extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) has emerged as a significant community-acquired pathogen, there is little epidemiological information regarding community-onset bacteremia due to ESBL-EC. A retrospective observational study from 2006 through 2011 was performed to evaluate the epidemiology of community-onset bacteremia caused by ESBL-EC. In a six-year period, the proportion of ESBL-EC responsible for causing community-onset bacteremia had increased significantly, from 3.6% in 2006 to 14.3%, in 2011. Of the 97 clinically evaluable cases with ESBL-EC bacteremia, 32 (33.0%) were further classified as healthcare-associated infections. The most common site of infection was urinary tract infection (n=35, 36.1%), followed by biliary tract infections (n=29, 29.9%). Of the 103 ESBL-EC isolates, 43 (41.7%) produced CTX-M-14 and 36 (35.0%) produced CTX-M-15. In the multilocus sequence typing (MLST) analysis of 76 isolates with CTX-M-14 or -15 type ESBLs, the most prevalent sequence type (ST) was ST131 (n=15, 19.7%), followed by ST405 (n=12, 15.8%) and ST648 (n=8, 10.5%). No significant differences in clinical features were found in the ST131 group versus the other group. These findings suggest that epidemic ESBL-EC clones such as CTX-M-14 or -15 type ESBLs and ST131 have disseminated in community-onset infections, even in bloodstream infections, which are the most serious type of infection.

Post-influenza Pneumonia Caused by the USA300 Community-Associated Methicillin-Resistant Staphylococcus aureus in Korea

Panton-Valentine leukocidin (PVL)-positive USA300 clone has been the most successful community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone spreading in North America. In contrast, PVL-negative ST72-CA-MRSA has been predominant in Korea, and there has been no report of infections by the USA300 strain except only one case report of perianal infection. Here, we describe the first case of pneumonia caused by the USA300 strain following pandemic influenza A (H1N1) in Korea. A 50-year-old man was admitted with fever and cough and chest radiograph showed pneumonic consolidation at the right lower lung zone. He received a ventilator support because of respiratory failure. PCR for pandemic influenza A (H1N1) in nasopharyngeal swab was positive, and culture of sputum and endotracheal aspirate grew MRSA. Typing of the isolate revealed that it was PVL-positive, ST 8-MRSA-SCCmec type IV. The analysis of the PFGE patterns showed that this isolate was the same pulsotype as the USA300 strain.

Antimicrobial Resistance and Clones of Acinetobacter Species and Pseudomonas aeruginosa

Antimicrobial resistance in bacteria is problematic in clinical settings and is a growing threat to public health. Multidrug-resistant and pandrug-resistant non-fermenters such as Acinetobacter spp. and Pseudomonas aeruginosa have recently emerged as a great concern worldwide. Particularly, the prevalence of carbapenem resistance in Acinetobacter spp. and P. aeruginosa is problematic, and emergence of polymyxin resistance is ominous. In this review, we discuss carbapenem and polymyxin resistance in Acinetobacter spp. and P. aeruginosa isolates and their major clones.

A Case of a Submandibular Abscess caused by Panton-Valentine leukocidin Positive USA 300 Community-associated Methicillin Resistant Staphylococcus aureus in a Foreign Resident of South Korea / 감염과화학요법

The incidence of community-associated, methicillin-resistant, Staphylococcus aureus (CA-MRSA) has increased in North America and Europe. One of most important reasons is the spread of Panton-Valentine leukocidin (PVL) positive CA-MRSA strains. On the other hand, CA-MRSA is not associated with the PVL positive strain in South Korea. Few cases of PVL positive CA-MRSA infections were reported in South Korea. We encountered a case of a submandibular abscess caused by MRSA in an otherwise healthy 29-year-old foreign female resident in a military camp. The CA-MRSA infection was confirmed by culture after abscess aspiration. Staphylococcal cassette chromosome mec (SCCmec) typing, multilocus sequence typing and spa typing revealed type IV, ST8 and t008, respectively. The PVL gene was also identified.

Bacteremia Caused by Laribacter hongkongensis Misidentified as Acinetobacter lwoffii: Report of the First Case in Korea

Laribacter hongkongensis is an emerging pathogen in patients with community-acquired gastroenteritis and traveler's diarrhea. We herein report a case of L. hongkongensis infection in a 24-yr-old male with liver cirrhosis complicated by Wilson's disease. He was admitted to a hospital with only abdominal distension. On day 6 following admission, he complained of abdominal pain and his body temperature reached 38.6degrees C. The results of peritoneal fluid evaluation revealed a leukocyte count of 1,180/microL (polymorphonuclear leukocyte 74%). Growth on blood culture was identified as a gram-negative bacillus. The isolate was initially identified as Acinetobacter lwoffii by conventional identification methods in the clinical microbiology laboratory, but was later identified as L. hongkongensis on the basis of molecular identification. The patient was successfully treated with cefotaxime. To the best of our knowledge, this case is the first report of hospital-acquired L. hongkongensis bacteremia with neutrophilic ascites.

Catheter-related Candidemia Caused by Candida haemulonii in a Patient in Long-term Hospital Care

Candida haemulonii, one of the non-albicans Candida species, is an emerging yeast pathogen that is known to be resistant to amphotericin B and other antifungal agents such as azoles. These anti-fungal agents have often been associated with clinical treatment failure, so no treatment regimen has been clearly established for invasive C. haemulonii infections. We investigated a catheter-related infection of C. haemulonii candidemia in an adult patient in long-term hospital care. In the early stages, the candidemia remained persistent despite treatment with fluconazole. However, after changing the antifungal agent to caspofungin, the candidemia was resolved. Fluconazole and amphotericin B are not reliable empirical antifungal agents for invasive C. haemulonii infections, as shown in previous case reports. An echinocandin such as caspofungin may be an appropriate empirical choice of antifungal agent for an invasive C. haemulonii infection.

Native Valve Infective Endocarditis due to Staphylococcus lugdunensis Confirmed by 16S Ribosomal RNA Sequencing / 감염과화학요법

Staphylococcus lugdunensis is a Gram-positive, coagulase-negative Staphylococcus (CNS) species that is found as a skin commensal and has been implicated in fulminant invasive diseases such as infective endocarditis. S. lugudunensis infections resemble Staphylococcus aureus infections in terms of virulence, tissue destruction and clinical course. Although correct identification and determination of the susceptibility profile are important, some commercial systems may misidentify S. lugdunensis. We report a case of native valve infective endocarditis caused by S. lugdunensis, which was misidentified by the Vitek 2 system but identified correctly by 16S ribosomal RNA (rRNA) gene sequencing in a 72-year-old male patient. The patient had multiple vegetations on his mitral valve, and the largest one was found on the posterior mitral valve leaflet. It was 2.5 cm in size and hypermobile. Diffuse valvular abscess was also observed. He had persistent bacteremia for appoximately 8 days, which was resolved after immediate surgery and antibiotic therapy. When a patient with severe sepsis syndrome grows S. aureus or CNS other than S. lugdunensis on a commercial automatic culture system, the possibility of S. lugdunensis should be considered and further confirmatory testing such as 16S rRNA sequencing may be very useful.

Bloodstream Infections and Clinical Significance of Healthcare-associated Bacteremia: A Multicenter Surveillance Study in Korean Hospitals

Recent changes in healthcare systems have changed the epidemiologic paradigms in many infectious fields including bloodstream infection (BSI). We compared clinical characteristics of community-acquired (CA), hospital-acquired (HA), and healthcare-associated (HCA) BSI. We performed a prospective nationwide multicenter surveillance study from 9 university hospitals in Korea. Total 1,605 blood isolates were collected from 2006 to 2007, and 1,144 isolates were considered true pathogens. HA-BSI accounted for 48.8%, CA-BSI for 33.2%, and HCA-BSI for 18.0%. HA-BSI and HCA-BSI were more likely to have severe comorbidities. Escherichia coli was the most common isolate in CA-BSI (47.1%) and HCA-BSI (27.2%). In contrast, Staphylococcus aureus (15.2%), coagulase-negative Staphylococcus (15.1%) were the common isolates in HA-BSI. The rate of appropriate empiric antimicrobial therapy was the highest in CA-BSI (89.0%) followed by HCA-BSI (76.4%), and HA-BSI (75.0%). The 30-day mortality rate was the highest in HA-BSI (23.0%) followed by HCA-BSI (18.4%), and CA-BSI (10.2%). High Pitt score and inappropriate empirical antibiotic therapy were the independent risk factors for mortality by multivariate analysis. In conclusion, the present data suggest that clinical features, outcome, and microbiologic features of causative pathogens vary by origin of BSI. Especially, HCA-BSI shows unique clinical characteristics, which should be considered a distinct category for more appropriate antibiotic treatment.

In vitro Evaluation of Antibiotic Lock Technique for the Treatment of Candida albicans, C. glabrata, and C. tropicalis Biofilms

Candidaemia associated with intravascular catheter-associated infections is of great concern due to the resulting high morbidity and mortality. The antibiotic lock technique (ALT) was previously introduced to treat catheter-associated bacterial infections without removal of catheter. So far, the efficacy of ALT against Candida infections has not been rigorously evaluated. We investigated in vitro activity of ALT against Candida biofilms formed by C. albicans, C. glabrata, and C. tropicalis using five antifungal agents (caspofungin, amphotericin B, itraconazole, fluconazole, and voriconazole). The effectiveness of antifungal treatment was assayed by monitoring viable cell counts after exposure to 1 mg/mL solutions of each antibiotic. Fluconazole, itraconazole, and voriconazole eliminated detectable viability in the biofilms of all Candida species within 7, 10, and 14 days, respectively, while caspofungin and amphotericin B did not completely kill fungi in C. albicans and C. glabrata biofilms within 14 days. For C. tropicalis biofilm, caspofungin lock achieved eradication more rapidly than amphotericin B and three azoles. Our study suggests that azoles may be useful ALT agents in the treatment of catheter-related candidemia.