292. The Prevalence of an Inoculum Effect (InE) with Cefazolin (CFZ) and the Association with Certain blaZ Gene Types among Methicillin-Susceptible Staphylococcus aureus (MSSA) Isolates from Four Major Chicago Medical Centers
Session: Poster Abstract Session: HAI: MSSA, MRSA, and other Gram-Positives
Thursday, October 27, 2016
Room: Poster Hall
Posters
  • Bla Study_IDWeekposter_10 2016FINAL.pdf (927.0 kB)
  • Background: CFZ offers a convenient dosing scheme, a favorable adverse event profile and is cost effective for MSSA infections. Recent clinical findings suggest treatment failure is no different between CFZ and oxacillin for deep-seated MSSA BSI. However, clinician preference for a semisynthetic penicillin over CFZ continues for high burden infections due to in vitro findings of certain blaZ genes (e.g. type A) known to hydrolyze CFZ inactive. This study aims to determine the local prevalence of an InE with CFZ and associated blaZ gene types among MSSA isolates collected from surrounding Chicagoland medical centers.

    Methods: Four Chicago hospitals contributed MSSA isolates from any source (except urine/CSF) between 10/2014 and 2/2015. CFZ MICs were determined at 24 hours by broth microdilution method using standard inocula (SI) (5 x 105 CFU/ml) and high inocula (HI) (5 x 107 CFU/ml). The InE was defined as isolates with a ≥ 4-fold increase in CFZ MIC between SI and HI. A pronounced InE was represented by a ≥ 4-fold increase in MIC from SI to HI with a nonsusceptible CFZ MIC of ³16 mg/L at HI. PCR was used to amplify the blaZ gene. Followed by agarose gel electrophoresis and sequencing to determine the gene type.

    Results:

    InE, n (%)

    blaZ Gene Types in Positive Samples, n (%)

    MSSA Isolates

    > 4-fold increase in CFZ MIC

    (SI to HI)

    > 4-fold increase in CFZ MIC

    (SI to HI) and

    MIC ≥ 16 at HI*

    MSSA Isolates

    type A

    type B

    type C

    type D

    All Sites

    (n=306)

    50 (16.3)

    5 (1.6)

    All Sites

    (n=198)**

    61 (31)

    25 (13)

    110 (55)

    2 (1)

    Site 1

    (n=80)

    11 (13.8)

    2 (2.5)

    Site 1

     (n=47)

    Pronounced InE (n=2)

    16 (34)

    1

    2 (4)

    27 (58)

    2 (4)

    1

    Site 2

    (n=68)

    11 (16.2)

    0 (0)

    Site 2

     (n=54)

    15 (28)

    9 (17)

    30 (55)

    0 (0)

    Site 3

    (n=81)

    18 (22.2)

    3 (3.8)

    Site 3

     (n=55)

    Pronounced InE

    (n=2)

    14 (25)

    1

    11 (20)

    30 (55)

    1

    0 (0)

    Site 4

    (n=77)

    10 (13)

    0 (0)

    Site 4

    (n=42)

    16 (38)

    3 (7)

    23 (55)

    0 (0)

    *Pronounced InE

    **Preliminary data. 198/310 MSSA isolates (64%) were blaZ positive.

    Conclusion: In contrast to related studies, our MSSA isolates from varying infectious sites, present with a significantly lower prevalence of a pronounced InE with CFZ overall and with expression of the type A gene strain. The InE is an in vitro phenomenon. Other factors such as expression or dosage of the blaZ gene, geographical and seasonal influences, as well as site of infection may also influence this prevalence. Further research is needed.

    Sheila Wang, PharmD, BCPS AQ-ID1, Ira Sigar, Ph.D.2, Annette Gilchrist, Ph.D.3, Balbina Plotkin, Ph.D.2, Tristan O'driscoll, Pharm.D.4, John O'donnell, BS Biochemistry3, Nathaniel Rhodes, PharmD, MSc5, Marc Scheetz, PharmD, MSc, BCPS AQ-ID6, Alan Gross, Pharm.D.7, Natasha Pettit, PharmD8, Cindy Bethel, BS9, Angella Charnot-Katsikas, MD10, John Segreti, MD, FIDSA, FSHEA11 and Kamaljit Singh, MD12, (1)Chicago College of Pharmacy, Midwestern University, Rush University Medical Center, Downers Grove, IL, (2)Midwestern University, Downers Grove, IL, (3)Midwestern University Chicago College of Pharmacy, Downers Grove, IL, (4)RUSH University Medical Center, Chicago, IL, (5)Pharmacy Practice, Midwestern University, Chicago College of Pharmacy, Downers Grove, IL, (6)Department of Pharmacy, Northwestern Medicine, Chicago, IL, (7)University of Illinois Medical Center, Chicago, IL, (8)Pharmacy Services, The University of Chicago Medicine, Chicago, IL, (9)UCH, Chicago, IL, (10)Department of Pathology, The University of Chicago Medicine, Chicago, IL, (11)Infectious Disease, Rush University Medical Center, Chicago, IL, (12)Department of Pathology, NorthShore University Health System, Evanston, IL

    Disclosures:

    S. Wang, None

    I. Sigar, None

    A. Gilchrist, None

    B. Plotkin, None

    T. O'driscoll, None

    J. O'donnell, None

    N. Rhodes, None

    M. Scheetz, None

    A. Gross, None

    N. Pettit, None

    C. Bethel, None

    A. Charnot-Katsikas, None

    J. Segreti, None

    K. Singh, None

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.