Kayoko Hayakawa

Autochthonous dengue fever, Tokyo, Japan, 2014.

After 70 years with no confirmed autochthonous cases of dengue fever in Japan, 19 cases were reported during August–September 2014. Dengue virus serotype 1 was detected in 18 patients. Phylogenetic analysis of the envelope protein genome sequence from 3 patients revealed 100% identity with the strain from the first patient (2014) in Japan.

Recent Exposure to Antimicrobials and Carbapenem-Resistant Enterobacteriaceae: The Role of Antimicrobial Stewardship

BACKGROUND Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly emerging worldwide. Control group selection is critically important when analyzing predictors of antimicrobial resistance. Focusing on modifiable risk factors can optimize prevention and resource expenditures. To identify specific predictors of CRE, patients with CRE were compared with 3 control groups: (1) patients with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, (2) patients with non-ESBL-containing Enterobacteriaceae, and (3) uninfected controls. DESIGN Matched multivariable analyses. PATIENTS AND SETTING Patients possessing CRE that were isolated at Detroit Medical Center from September 1, 2008, to August 31, 2009. METHODS Patients were matched (1∶1 ratio) to the 3 sets of controls. Matching parameters included (1) bacteria type, (2) hospital/facility, (3) unit/clinic, (4) calendar year, and (5) time at risk (ie, from admission to culture). Matched multivariable analyses were conducted between uninfected controls and patients with CRE, ESBL, and non-ESBL Enterobacteriaceae. Models were also designed comparing patients with CRE to patients with ESBL, patients with non-ESBL Enterobacteriaceae, and all 3 non-CRE groups combined. RESULTS Ninety-one unique patients with CRE were identified, and 6 matched models were constructed. Recent (less than 3 months) exposure to antibiotics was the only parameter that was consistently associated with CRE, regardless of the group to which CRE was compared, and was not independently associated with isolation of ESBL or non-ESBL Enterobacteriaceae. CONCLUSIONS Exposure to antibiotics within 3 months was an independent predictor that characterized patients with CRE isolation. As a result, antimicrobial stewardship efforts need to become a major focus of preventive interventions. Regulatory focus regarding appropriate antimicrobial use might decrease the detrimental effects of antibiotic misuse and spread of CRE.

Multilocus Sequence Typing (MLST) for Characterization of Enterobacter cloacae

Enterobacter cloacae is an important emerging pathogen, which sometime causes respiratory infection, surgical site infection, urinary infection, sepsis, and outbreaks at neonatal units. We have developed a multilocus sequence typing (MLST) scheme utilizing seven housekeeping genes and evaluated the performance in 101 clinical isolates. The MLST scheme yielded 83 sequence types (ST) including 78 novel STs found in the clinical isolates. These findings supported the robustness of the MLST scheme developed in this study.

Zika fever imported from Thailand to Japan, and diagnosed by PCR in the urines.

In July 2014, a Japanese traveller returning from Thailand was investigated for fever, headache, rash and conjunctivitis. Zika virus RNA was detected in his urine sample by real-time reverse transcription polymerase chain reaction. Serological tests showed cross reactivity of IgM against the dengue virus. Zika fever could be misdiagnosed or missed and should be considered in febrile patients with a rash, especially those returning from Thailand.

Outcomes and genetic relatedness of carbapenem-resistant enterobacteriaceae at Detroit medical center.

BACKGROUND Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly emerging in hospitals in the United States and are posing a significant threat. To better understand the transmission dynamics and the acquisition of resistant strains, a thorough analysis of epidemiologic and molecular characteristics was performed. METHODS CRE isolated at Detroit Medical Center were analyzed from September 2008 to September 2009. bla(KPC) genes were investigated by polymerase chain reaction (PCR), and repetitive extragenic palindromic PCR (rep-PCR) was used to determine genetic similarity among strains. Epidemiologic and outcomes analyses were performed. RESULTS Ninety-two unique patient CRE isolates were recovered. Sixty-eight strains (74%) were Klebsiella pneumoniae, 7 were Klebsiella oxytoca, 15 were Enterobacter species, and 2 were Escherichia coli. Fifteen isolates (16%) were resistant to colistin, 14 (16%) were resistant to tigecycline, and 2 were resistant to all antimicrobials tested. The mean ± standard deviation age of patients was 63 ± 2 years. Sixty patients (68%) were admitted to the hospital from long-term care facilities. Only 70% of patients received effective antimicrobial therapy when infection was suspected, with a mean time to appropriate therapy of 120 ± 23 hours following sample culturing. The mean length of hospitalization after sample culturing was 18.6 ± 2.5 days. Of 57 inpatients, 18 (32%) died in the hospital. Independent predictors for mortality were intensive care unit stay (odds ratio [OR], 15.8; P = .003) and co-colonization with CRE and either Acinetobacter baumannii or Pseudomonas aeruginosa (OR, 17.2; P = .006). Among K. pneumoniae CRE, rep-PCR revealed 2 genetically related strains that comprised 70% and 20% of isolates, respectively. CONCLUSIONS In this large U.S. cohort of patients with CRE infection, which reflects the modern continuum of medical care, co-colonization with CRE and A. baumannii or P. aeruginosa was associated with increased mortality. Two predominant clones of K. pneumoniae accounted for the majority of cases of CRE infection.

Fever of Unknown Origin: An Evidence-Based Review

Abstract:Fever is a common problem for which patients seek medical advice. Fortunately, in most cases, fever is self-limiting or the etiology of fever is promptly established. Sustained, unexplained fever despite a comprehensive work up is recognized as fever of unknown origin (FUO), which frequently poses a clinical challenge. For a methodical approach, FUO is recently categorized into classic FUO, nosocomial FUO, neutropenic FUO and HIV-associated FUO based on the clinical setting and patients underlying immune status. This review focuses on the key factors of classic FUO. The etiologic clues obtainable from the history, bedside physical examination findings and pertinent laboratory tests are discussed. Also, FUO in older patients and tuberculosis as a cause of FUO are briefly discussed.

Risk factors for colonization due to carbapenem-resistant Enterobacteriaceae among patients exposed to long-term acute care and acute care facilities.

BACKGROUND This study aimed to identify risk factors associated with carbapenem-resistant Enterobacteriaceae (CRE) colonization among patients screened with rectal cultures upon admission to a hospital or long-term acute care (LTAC) center and to compare risk factors among patients who were screen positive for CRE at the time of hospital admission with those screen positive prior to LTAC admission. METHODS A retrospective nested matched case-control study was conducted from June 2009 to December 2011. Patients with recent LTAC exposure were screened for CRE carriage at the time of hospital admission, and patients admitted to a regional LTAC facility were screened prior to LTAC admission. Cases were patients with a positive CRE screening culture, and controls (matched in a 3∶1 ratio to cases) were patients with negative screening cultures. RESULTS Nine hundred five cultures were performed on 679 patients. Forty-eight (7.1%) cases were matched to 144 controls. One hundred fifty-eight patients were screened upon hospital admission and 521 prior to LTAC admission. Independent predictors for CRE colonization included Charlsons score greater than 3 (odds ratio [OR], 4.85 [95% confidence interval (CI), 1.64-14.41]), immunosuppression (OR, 3.92 [95% CI, 1.08-1.28]), presence of indwelling devices (OR, 5.21 [95% CI, 1.09-2.96]), and prior antimicrobial exposures (OR, 3.89 [95% CI, 0.71-21.47]). Risk factors among patients screened upon hospital admission were similar to the entire cohort. Among patients screened prior to LTAC admission, the characteristics of the CRE-colonized and noncolonized patients were similar. CONCLUSIONS These results can be used to identify patients at increased risk for CRE colonization and to help target active surveillance programs in healthcare settings.

Evaluation of an Automated Rapid Diagnostic Assay for Detection of Gram-Negative Bacteria and Their Drug-Resistance Genes in Positive Blood Cultures

We evaluated the performance of the Verigene Gram-Negative Blood Culture Nucleic Acid Test (BC-GN; Nanosphere, Northbrook, IL, USA), an automated multiplex assay for rapid identification of positive blood cultures caused by 9 Gram-negative bacteria (GNB) and for detection of 9 genes associated with β-lactam resistance. The BC-GN assay can be performed directly from positive blood cultures with 5 minutes of hands-on and 2 hours of run time per sample. A total of 397 GNB positive blood cultures were analyzed using the BC-GN assay. Of the 397 samples, 295 were simulated samples prepared by inoculating GNB into blood culture bottles, and the remaining were clinical samples from 102 patients with positive blood cultures. Aliquots of the positive blood cultures were tested by the BC-GN assay. The results of bacterial identification between the BC-GN assay and standard laboratory methods were as follows: Acinetobacter spp. (39 isolates for the BC-GN assay/39 for the standard methods), Citrobacter spp. (7/7), Escherichia coli (87/87), Klebsiella oxytoca (13/13), and Proteus spp. (11/11); Enterobacter spp. (29/30); Klebsiella pneumoniae (62/72); Pseudomonas aeruginosa (124/125); and Serratia marcescens (18/21); respectively. From the 102 clinical samples, 104 bacterial species were identified with the BC-GN assay, whereas 110 were identified with the standard methods. The BC-GN assay also detected all β-lactam resistance genes tested (233 genes), including 54 bla CTX-M, 119 bla IMP, 8 bla KPC, 16 bla NDM, 24 bla OXA-23, 1 bla OXA-24/40, 1 bla OXA-48, 4 bla OXA-58, and 6 bla VIM. The data shows that the BC-GN assay provides rapid detection of GNB and β-lactam resistance genes in positive blood cultures and has the potential to contributing to optimal patient management by earlier detection of major antimicrobial resistance genes.

Epidemiology and Risk Factors for Isolation of Escherichia coli Producing CTX-M-Type Extended-Spectrum β-Lactamase in a Large U.S. Medical Center

ABSTRACT A case-case-control study was conducted to identify independent risk factors for recovery of Escherichia coli strains producing CTX-M-type extended-spectrum β-lactamases (CTX-M E. coli) within a large Southeastern Michigan medical center. Unique cases with isolation of ESBL-producing E. coli from February 2010 through July 2011 were analyzed by PCR for blaCTX-M, blaTEM, and blaSHV genes. Patients with CTX-M E. coli were compared to patients with E. coli strains not producing CTX-M-type ESBLs (non-CTX-M E. coli) and uninfected controls. Of 575 patients with ESBL-producing E. coli, 491 (85.4%) isolates contained a CTX-M ESBL gene. A total of 319 (84.6%) patients with CTX-M E. coli (282 [74.8%] CTX-M-15 type) were compared to 58 (15.4%) non-CTX-M E. coli patients and to uninfected controls. Independent risk factors for CTX-M E. coli isolation compared to non-CTX-M E. coli included male gender, impaired consciousness, H2 blocker use, immunosuppression, and exposure to penicillins and/or trimethoprim-sulfamethoxazole. Compared to uninfected controls, independent risk factors for isolation of CTX-M E. coli included presence of a urinary catheter, previous urinary tract infection, exposure to oxyimino-cephalosporins, dependent functional status, non-home residence, and multiple comorbid conditions. Within 48 h of admission, community-acquired CTX-M E. coli (n = 51 [16%]) and non-CTX-M E coli (n = 11 [19%]) strains were isolated from patients with no recent health care contacts. CTX-M E. coli strains were more resistant to multiple antibiotics than non-CTX-M E. coli strains. CTX-M-encoding genes, especially blaCTX-M-15 type, represented the most common ESBL determinants from ESBL-producing E. coli, the majority of which were present upon admission. Septic patients with risk factors for isolation of CTX-M E. coli should be empirically treated with appropriate agents. Regional infection control efforts and judicious antibiotic use are needed to control the spread of these organisms.

Efficacy of Ertapenem for Treatment of Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae

ABSTRACT Ertapenem is active against extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae organisms but inactive against Pseudomonas aeruginosa and Acinetobacter baumannii. Due to a lack of therapeutic data for ertapenem in the treatment of ESBL bloodstream infections (BSIs), group 2 carbapenems (e.g., imipenem or meropenem) are often preferred for treatment of ESBL-producing Enterobacteriaceae, although their antipseudomonal activity is unnecessary. From 2005 to 2010, 261 patients with ESBL BSIs were analyzed. Outcomes were equivalent between patients treated with ertapenem and those treated with group 2 carbapenems (mortality rates of 6% and 18%, respectively; P = 0.18).