Transcript Slide 1

Inhibitory and bactericidal concentrations
of current and new antibiotics for
Methicillin-resistant Staphylococcal
ocular infections
Yousuf Qureshi, M.D.
Darlene Miller, DHSc
Neither author has any financial disclosures.
Bascom Palmer Eye Institute, Department of Microbiology, Miami, Florida.
Abrams Ocular Microbiology Laboratory
Email: [email protected]
Phone: 305-326-6000 X6034
McKnight Building, 1st floor
Background and Purpose
• Staphylococcus aureus remains the most common
ocular pathogen recovered from ocular infections.
• Increasing recovery of multidrug resistant isolates
compromises the selection of appropriate antibiotics for
prophylaxis and treatment of these infections.
• This study evaluates the percentage susceptible and in
vitro minimum inhibitory and bactericidal (MIC and
MBC) concentrations of standard and new antibiotics
for methicillin-resistant staphylococcus aureus (MRSA)
derived from cases of clinical ophthalmic infection.
Increasing MRSA prevalence
43.7
34
30
36.8
34.6
29
20
04
(N
=1
39
20
)
05
(N
=9
20
3)
06
(N
=1
83
20
)
07
(N
=1
44
20
)
08
(N
=1
59
)
Data
collected
from the
Bascom
Palmer Eye
Institute
(BPEI)
microbiology
laboratory in
Miami,
Florida
(N
=1
61
)
20
03
20
02
20
01
28
(N
=1
43
)
27
(N
=1
42
)
24
(N
=1
27
)
50
45
40
35
30
25
20
15
10
5
0
20
00
% MRSA Isolates
MRSA
All S. aureus ocular isolates
Methods
• One hundred and one random MRSA isolates (collected at the BPEI
microbiology laboratory from January 2005 and February 2009) were
selected
•
•
•
40 Conjunctival
30 Corneal or Contact lens
31 Periocular soft tissue sources
• Mean inhibitory concentrations (MIC50 & 90) were determined using the
Sensititre® microtiter assay
•
Trek Diagnostic Systems; Cleveland, OH; http://www.trekds.com.
• Mean bactericidal concentrations (MBC50 & 90) were also determined for
commonly used ophthalmic antibiotics by plating the “no-grow” wells on
blood agar
• Sensitivity data of the MRSA isolates were determined
•
Standard MIC90 data derived from Clinical and Laboratory Standards
Institute (formerly NCCLS), Wayne, PA and data supplied by the British
Society for Antimicrobial Chemotherapy, February 2008
Antibiotics Evaluated in Study
Methods
Fluoroquinolones
•
•
•
Ciprofloxacin
Moxifloxacin
Gemifloxacin*
Aminoglycosides
•
•
Gentamicin
Streptomycin
Macrolides
•
•
•
Azithromycin
Erythromycin
Clarithromycin
Miscellaneous Peptide
antibiotics
•
•
•
Daptomycin*

Chloramphenicol (UK)
•
Lipopeptide
Glycylcycline
Tigecycline*
Clindamycin
Ketolide
•
•
Nitrofurantoin
Sulfonamide
•
Sulfamethoxazole
Telithromycin*
Tetracycline
•
Rifamycin
Rifampin
Oxazolidinone
Linezolid*
* emerging antibiotic
Tetracycline
Penicillins
•
•
•
Nitrofuran
Trimethoprim
Non-macrolide 50s
ribosome inhibitor
•
•
Quinpristin*
Dalfopristin*
Tricyclic Glycopeptides
Lincosamide
•
•
Vancomycin

Dihydrofolate reductase
inhibitor
Streptogramins
•
•
Penicillin
Ampicillin
Oxacillin
Data Sheet Utilized
Methods
Results for Common Antibiotics against MRSA
(All sources)
Drug
%
Susceptible
MIC50
(ug/mL)
MIC90
(ug/mL)
MBC50
(ug/mL)
MBC90
(ug/mL)
Vancomycin
97.0
1
2
2
32
24.8
>4
>4
>4
>4
77.2
2
>16
8
>16
40.6
16
16
>16
>16
18.8
>2
>2
>2
>2
(MIC90 ≤ 2)
Moxifloxacin
(MIC90 ≤ 0.5)
Gentamicin
(MIC90 ≤ 4)
Chloramphenicol
(MIC90 ≤ 8)
Ciprofloxacin
(MIC90 ≤ 1)
(Percent susceptible data determined using MIC90 values from the Interpretation by Clinical and Laboratory Standards Institute, Wayne, PA)
Results for New Antibiotics against MRSA
(All sources)
Drug
Quinpristin /
dalfopristin
%
Susceptible
MIC50
(ug/mL)
MIC90
(ug/mL)
97.0
0.5
1
56.4
0.25
>2
92.1
0.5
0.5
96.0
4
4
94.1
0.25
0.5
24.8
>0.25
>0.25
(MIC90 ≤ 1)
Telithromycin
(MIC90 ≤ 1)
Daptomycin
(MIC90 ≤ 1)
Linezolid
(MIC90 ≤ 4)
Tigecycline
(MIC90 ≤ 0.5)
Gemifloxacin
(MIC90 ≤ 0.25)
(Percent susceptible data determined using MIC90 values from the Interpretation by Clinical and Laboratory Standards Institute, Wayne, PA and
data supplied by the British Society for Antimicrobial Chemotherapy, February 2008)
MRSA sensitivity to commonly used antibiotics
compared across different sources
100
96.8
93.3
97.5
Conjunctiva
Cornea
Soft Tissue
86.7
100
% Sensitive
80
60
55
58.1
40
Vancomycin
20
6.67
0
12.5
Gentamicin
Moxifloxacin
Does source affect antibiotic efficacy in
ophthalmic MRSA infections?
Moxifloxacin
Cornea
Soft Skin
Conjunctiva
# Sensitive
2
18
5
# Resistant
28
13
35
Total #
30
31
40
Chi square comparison of MRSA sources and moxifloxacin
using the Pearson coefficient of significance (95% CI)
Source
Cornea and
Conjunctiva
Cornea and
Soft Skin
Conjunctiva
and Soft Skin
p value
p = 0.4207
p = 0.0000
p = 0.0000
Conclusion
• There is an increasing prevalence of MRSA ophthalmic
infections
• Ocular MRSA isolates are rarely resistant to vancomycin
•
In our series, 97% were susceptible
• Four of the newer antibiotics proved potent against MRSA
ocular isolates
•
•
Isolate susceptibility was at least 92% when testing Daptomycin,
Tigecycline, Linezolid, and Quinpristin / dalfopristin
Adaptation of these for ocular use may prove vitally important
• Sensitivity of ocular MRSA isolates to varying antibiotics
depends on the source
•
Moxifloxacin has statistically greater efficacy against soft skin
infections (presumed community acquired variants) versus
conjunctival and corneal infections