Kotaro Aoki

Epidemiology of extended-spectrum β-lactamase producing Escherichia coli in the stools of returning Japanese travelers, and the risk factors for colonization.

Objective Travel overseas has recently been considered a risk factor for colonization with drug-resistant bacteria. The purpose of this study was to establish the epidemiology and risk factors associated with the acquisition of drug-resistant bacteria by Japanese travelers. Methods Between October 2011 and September 2012, we screened the stools of 68 Japanese returning travelers for extended-spectrum β-lactamase (ESBL) producing Escherichia coli. All specimens were sampled for clinical reasons. Based on the results, the participants were divided into an ESBL-producing E. coli positive group (18 cases; 26%) and an ESBL-producing E. coli negative group (50 cases; 74%), and a case-control study was performed. Microbiological analyses of ESBL-producing strains, including susceptibility tests, screening tests for metallo-β-lactamase, polymerase chain reaction amplification and sequencing of bla CTX-M genes, multilocus sequence typing, and whole genome sequencing, were also conducted. Results In a univariate comparison, travel to India was a risk factor (Odds Ratio 13.6, 95% Confidence Interval 3.0–75.0, p<0.0001). There were no statistical differences in the characteristics of the travel, such as backpacking, purpose of travel, interval between travel return and sampling stool, and duration of travel. Although 10 of 13 analyzed strains (77%) produced CTX-M-15, no ST131 clone was detected. Conclusion We must be aware of the possibilities of acquiring ESBL-producing E. coli during travel in order to prevent the spread of these bacteria not only in Japan but globally.

In vitro susceptibility of characterized β-lactamase-producing Gram-negative bacteria isolated in Japan to ceftazidime-, ceftaroline-, and aztreonam-avibactam combinations

Avibactam displays potent inhibition of extended-spectrum, AmpC, KPC and some OXA β-lactamases. We examined the combinations of avibactam with ceftazidime, ceftaroline and aztreonam by the broth microdilution method against Gram-negative bacteria harboring molecularly-characterized β-lactamase genes collected in Toho University, Japan. Bacterial isolates included: Ambler class A β-lactamase-producing Enterobacteriaceae (n = 26); class C β-lactamase-producing Enterobacteriaceae (n = 9) and class D β-lactamase-producing Acinetobacter baumannii (n = 9) and Enterobacteriaceae (n = 3). Ceftazidime-avibactam, ceftaroline-avibactam ands aztreonam-avibactam were active against the strains with an extended-spectrum β-lactamase (ESBL) or AmpC enzymes, but combination with avibactam did not reduce β-lactam MICs against A. baumannii with OXA β-lactamases including carbapenemases, such as OXA-40 and -69.

Metagenomic analysis for detecting pathogens in culture-negative infective endocarditis

Pathogen identification is important for proper diagnosis and optimal treatment of infective endocarditis (IE). Blood and valve cultures are the gold standard for detecting pathogens responsible for IE. However, these tests only detect culturable pathogens, and have low sensitivity, especially in patients previously treated with antibiotics. Culture-negative IE is still a major clinical problem and a diagnostic challenge. Recently, metagenomic analysis using next generation sequencing has been used to detect pathogens directly from clinical samples. However, there are very few reports of the use of metagenomic analysis for pathogen identification in culture-negative IE cases and the usefulness of this new method is unknown. Here, we report a case of successful pathogen detection with metagenomic analysis in a patient of culture-negative IE. The patient underwent valve replacement surgery and received antibiotics for 5 weeks and survived. Using metagenomic analysis of resected vegetation, we detected Abiotrophia defectiva, which is often associated with culture-negative IE due to its fastidious growth. This method may be useful for pathogen identification in future cases of culture-negative IE.

Spread of CTX-M-15 Extended-Spectrum β-Lactamase-Producing Escherichia coli Isolates through Household Contact and Plasmid Transfer

ABSTRACT We document the household spread of extended-spectrum β-lactamase-producing Escherichia coli. One isolate belonged to sequence type 1193 and caused urinary tract infection in a 4-month-old female, and the other isolate belonged to sequence type 131 and colonized three family members, including the index patient. These isolates carried similar Inc-I1-Iγ plasmids, harboring bla CTX-M-15.

Pediatric hypervirulent Klebsiella pneumoniae septic arthritis

Cases of infection with hypervirulent Klebsiella pneumoniae are gradually increasing in number, and cause life‐threatening community‐acquired infection even in immunocompetent patients. A 14‐year‐old boy developed septic hip arthritis due to hypervirulent K. pneumoniae (sequence type 23, serotype K1, magA positive). The patient initially seemed to have been successfully treated with antibiotics and surgical intervention, but septic arthritis developed into osteomyelitis of the femoral head and myositis, which required long‐term antibiotic therapy and additional surgical intervention. This is the first pediatric case of hypervirulent K. pneumoniae septic hip arthritis. Treatment plans should mainly consist of antibiotic therapy and surgical intervention. Clinicians, even pediatricians, in developed countries should be aware of the increasing incidence of hypervirulent Klebsiella pneumoniae infection.

Combination Therapy against Polymicrobial Infection, Including by NDM-1-Producing Enterobacteriaceae Resistant to Colistin

A 49-year-old male presented with continuous recurrent chronic gluteal pyoderma. A total surgical excision of a subcutaneous abscess, followed by skin graft surgery, was performed. Three days postsurgery, skin engraftment failure was observed with local infection signs, including pain and

Molecular epidemiology of Klebsiella pneumoniae K1 and K2 isolates in Japan

Although severe infections caused by hypervirulent Klebsiella pneumoniae isolates, such as K1 isolates belonging to sequence type (ST) 23, have been a significant problem in Asian countries, epidemiology of these isolates in Japan remains unclear. We performed a nationwide molecular epidemiological study of K. pneumoniae K1 and K2 isolates in Japan. Of the 259K. pneumoniae isolates collected, 14 and 16 isolates were identified as capsular genotypes K1 and K2, respectively. All K1 isolates were ST23 or its closely related clones and showed high genetic similarity by pulsed-field gel electrophoresis (PFGE) and the DiversiLab system (DL). K2 isolates, belonging to ST14, ST25, ST65, ST86, and ST110, were more genetically diverse than K1 isolates. Isolates belonging to a specific ST showed identical virulence gene profiles with a few exceptions. PFGE and DL results using K1 and K2 isolates were generally in agreement.

Nosocomial transmission of carbapenem-resistant Klebsiella pneumoniae elucidated by single-nucleotide variation analysis: a case investigation

Abstract Identifying transmission route of antimicrobial-resistant pathogen is essential for appropriate infection control strategy in healthcare facilities. We report the utility of single-nucleotide variation analysis in tracing nosocomial transmission of antimicrobial-resistant pathogens by describing a pseudo-outbreak case of carbapenem-resistant Klebsiella pneumoniae. The present case highlights that infection control strategy should encompass pathological dissection rooms, neglected but potentially highly contaminated places in hospitals.

Carbapenem-resistant Klebsiella pneumoniae in a Febrile Neutropenia Patient With Acute Myelogenous Leukemia After Hematopoietic Stem Cell Transplantation.

Ampicillin >16 (R) >16 (R) Piperacillin >64 (R) >64 (R) Cefazolin >16 (R) ≦4 (S) Cefotiam >16 (R) ≦8 (S) Cefotaxime >2 (R) ≦1 (S) Ceftazidime >8 (R) ≦4 (S) Cefepime 16 (R) ≦2 (S) Ceftriaxone >2 (R) ≦1 (S) Cefaclor >16 (R) ≦8 (S) Cefcapene >1 (R) >1 (R) Cefmetazole >32 (R) ≦8 (S) Flomoxef >32 (R) ≦8 (S) Ampicillin/Sulbactam >16/8 (R) 16/8 (I) Piperacillin/Tazobactam >64 (R) ≦16 (S) Cefoperazone/Sulbactam >32/16 (R) ≦16/8 (S) Aztreonam >8 (R) ≦4 (S) Doripenem 4 (R) ≦1 (S) Imipenem >8 (R) ≦1 (S) Meropenem >8 (R) ≦1 (S) Gentamicin >8 (R) >8 (R) Amikacin >32 (R) >32 (R) Minocycline >8 (R) >8 (R) Levofloxacin >4 (R) >4 (R) Ciprofloxacin >2 (R) >2 (R) Sulfamethoxazole-Trimethoprim >2/38 (R) >2/38 (R) Fosfomycin >16 (R) >16 (R) Tigecycline 0.25 (S) 0.25 (S) Colistin 1 (S) 1 (S)

Evidence of latent molecular diversity determining the virulence of community-associated MRSA USA300 clones in mice: Virulence diversity of USA300 clones

The USA300 clone of community‐associated MRSA is reported to be hypervirulent and epidemic in the United States. This clone causes a variety of diseases from lethal pneumonia to mild skin infections. We hypothesized that evolutionary diversity may exist among USA300 clones, which may link virulence traits with host responses and mortality rates.