Surveillance
Antibiotic susceptibility survey of blood-borne MRSA isolates in Japan from 2008 through 2011

https://doi.org/10.1016/j.jiac.2014.06.012Get rights and content

Abstract

We conducted an antibiotic susceptibility survey of 830 blood-borne methicillin resistant Staphylococcus aureus collected from nationwide hospitals in Japan over a three-year period from January 2008 through May 2011. Antibiotic susceptibility was judged according to the criteria recommended by the Clinical Laboratory Standard Institute. Over 99% of the MRSA showed to be susceptible to teicoplanin, linezolid, sulfamethoxazole/trimethoprim and vancomycin, and over 97% of them were susceptible to daptomycin, arbekacin and rifampin. The majority of the MRSA strains showed resistant to minocycline, meropenem, imipenem, clindamycin, ciprofloxacin, cefoxitin, and oxacillin in the rates of 56.6, 72.9, 73.7, 78.7, 89.0, 99.5, and 99.9%, respectively. Among the MRSA strains, 72 showed reduced susceptibility to vancomycin, including 8 strains (0.96%) of vancomycin-intermediate S. aureus (VISA), 54 (6.51%) of heterogeneous vancomycin-intermediate S. aureus (hVISA), and 55 (5.63%) of β-lactam antibiotics-induced vancomycin resistant S. aureus (BIVR). Unexpectedly, among the 54 hVISA and 55 BIVR, 45 isolates (83.3% and 81.8%, respectively) showed both hVISA and BIVR phenotypes. A new trend of vancomycin resistance found in this study was that VISA strains were still prevalent among the bacteremic specimens. The high rates of the hVISA/BIVR two-phenotypic vancomycin resistance, and the prevalence of VISA in the bloodborne MRSA call attention in the MRSA epidemiology in Japan.

Introduction

Staphylococcus aureus (S. aureus) is a leading cause of hospital- and community-associated infections. In the hospital, methicillin-resistant S. aureus (MRSA) is the highest risk of infection at surgical wounds, the lower respiratory tract and the cardiovascular system, and the second most common cause of health care-associated pneumonia and septicemia [1], [2], [3]. Infections caused by MRSA are worse than those caused by other pathogens due to the limited choices of available antibiotics and thus it is difficult to eradicate these strains. Moreover, the worst situation is that blood stream MRSA infection has a higher rate of mortality and must endure longer hospital stays [4].

Vancomycin has been the agent of choice for methicillin-resistant S. aureus (MRSA) infections as it provided efficacious and promising therapy [5]. Nevertheless, with the emergence of S. aureus strains having intermediate resistance towards vancomycin (vancomycin-intermediate S. aureus [VISA]), treatment options for patients infected with these strains have become limited [6]. Heterogeneous vancomycin-intermediate S. aureus (Hetero-VISA or hVISA) strains are also being reported more frequently worldwide [7]. These strains are interpreted as ‘susceptible’ to vancomycin using conventional MIC determination tests, but contain a sub-population of cells which can grow in the presence of >2 mg/L vancomycin [8], [9]. Another category of MRSA with reduced vancomycin-susceptibility, designated as BIVR, which is resistant to vancomycin only in the presence of β-lactam antibiotics was reported to be prevalent in Japan [10], and the combined phenotype of hVISA and BIVR was associated with a higher probability of mortality in patients with MRSA bacteremia [11]. Therefore, it is important to understand the current state of the prevalence of MRSA with reduced vancomycin-susceptibility from blood stream infections.

Here, we describe a current surveillance study of antibiotic susceptibility on the blood-borne MRSA strains collected from 11 university hospitals and 3 general hospitals covering from Tokyo-Nagoya-Osaka and Kyushyu regions of Japan isolated during a period from 2008 through 2010. The data were compared with the previous surveillance studies with non-bacteremic MRSA isolates studied in 2007 through 2009 by the same laboratory [12], [13], [14]. Our study also focused on determining the strains with reduced vancomycin susceptibility. Though information on MRSA epidemiology in Japan is growing [12], [13], [14], [15], significant gaps exist on the locality of sampling, availability of central laboratories to serve for characterizing MRSA, and availability of surveillance data. Our data presented here will provide information on the most recent trends in the emergence and dissemination of antibiotic resistant strains among the blood stream MRSA infections in Japan.

Section snippets

Participating hospitals and collection of bacterial isolate

Blood-borne MRSA strains were isolated during Jan. 2008 through May 2011 at 11 university hospitals and 3 general hospitals in Japan located Kanto, Kinki, Tokai and Kyushyu regions. Only one MRSA sample was collected from the same patient. All the blood-borne MRSA strains were primarily identified at the local participating hospitals. The clinical isolates were suspended in Micro-bank tubes (Asuka Junyaku, Tokyo, Japan) at the local hospitals, and delivered under frozen states to the

Results

The overall susceptibility profile of MRSA isolates to 14 antibiotics was shown in Table 1 and Fig. 1. As shown in Table 1, the MIC50, MIC90 and MIC ranges of 11 antibiotics including TEIC, VCM, ABK, MINO, MPIPC, IMP, CLDM, CPFX, LZD, CFX and MEPM were comparable with those of in non-bacteremic MRSA isolates studied in 2007 through 2009 by this Central Laboratory [12], [13], [14]. Those of the antibiotics that showed high MIC90 and MIC50 (16–32 μg/ml) were MINO, MPIPC, IPM, CLDM, CPFX, CFX and

Discussion

The bacteremic infections caused by the methicillin-resistant S. aureus are problematic due to the high mortality and only limited antibiotics are available for the treatment [24]. In this paper, we carried out nationwide surveillance of antimicrobial susceptibility of bloodborne MRSA isolates to ascertain resistance patterns in order to assist in the enforcement of infection control measures. Our major findings were that over 97% of the isolates were susceptible to teicoplanin, linezolid,

References (50)

  • Y. Hososaka et al.

    Characterization of oxacillin-susceptible mecA-positive Staphylococcus aureus: a new type of MRSA

    J Infect Chemother

    (2007)
  • H. Hanaki et al.

    Occurrence of vancomycin-intermediate-resistant Staphylococcus aureus in Japan

    J Infect Chemother

    (2007)
  • J. Ariza et al.

    Vancomycin in surgical infections due to methicillin-resistant Staphylococcus aureus with heterogeneous resistance to vancomycin

    Lancet

    (1999)
  • M.E. Reverdy et al.

    Incidence of Staphylococcus aureus with reduced susceptibility to glycopeptides in two french hospitals

    Clin Microbiol Infect

    (2001)
  • S. Tsiodras et al.

    Linezolid resistance in a clinical isolate of Staphylococcus aureus

    Lancet

    (2001)
  • H. Hanaki et al.

    Method of detecting beta-lactam antibiotic induced vancomycin resistant MRSA (BIVR)

    Int J Antimicrob Agents

    (2004)
  • C.A. Loffler et al.

    Update on prevalence and treatment of methicillin-resistant Staphylococcus aureus infections

    Expert Rev Anti Infect Ther

    (2007)
  • M.J. Richards et al.

    Nosocomial infections in combined medical-surgical intensive care units in the United States

    Infect Control Hosp Epidemiol

    (2000)
  • M.J. Richards et al.

    Nosocomial infections in medical intensive care units in the United States. National nosocomial infections surveillance system

    Crit Care Med

    (1999)
  • C. Ruef

    Epidemiology and clinical impact of glycopeptide resistance in Staphylococcus aureus

    Infection

    (2004)
  • M. Shoji et al.

    walk and Clpp mutations confer reduced vancomycin susceptibility in Staphylococcus aureus

    Antimicrob Agents Chemother

    (2011)
  • B.P. Howden et al.

    Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications

    Clin Microbiol Rev

    (2010)
  • T. Takata et al.

    Presence of both heterogeneous vancomycin-intermediate resistance and beta-lactam antibiotic-induced vancomycin resistance phenotypes is associated with the outcome in methicillin-resistant Staphylococcus aureus bloodstream infection

    Scand J Infect Dis

    (2013)
  • Clinical and laboratory standards institute
    (2009)
  • T.R. Walsh et al.

    Evaluation of current methods for detection of staphylococci with reduced susceptibility to glycopeptides

    J Clin Microbiol

    (2001)
  • Cited by (39)

    • Prevalence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA among methicillin-resistant S. aureus with high vancomycin minimal inhibitory concentrations in Taiwan: A multicenter surveillance study, 2012–2013

      2016, Journal of Microbiology, Immunology and Infection
      Citation Excerpt :

      A wide range of prevalence of hVISA has been reported and the prevalence varied between different geographic area, source of isolates, and detection methods. hVISA isolates generally accounted for a substantial portion of MRSA among Asian countries (16.5% from 830 blood-borne MRSA isolates in Japan, 11.1% from 1175 various clinical isolates in 14 Chinese hospitals, and 22.1% from 184 sterile site isolates in China).10,27,28 One previously published epidemiological study in Taiwan reported an hVISA prevalence of only 0.7% in 2003.11

    View all citing articles on Scopus
    View full text