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Antimicrobial Resistance Trends Among Sinus Isolates of Streptococcus pneumoniae from the
United States: 2000 – 2005
Daniel Sahm, Ph.D.
Focus Bio-Inova Inc.
Deborah Draghi1, Alan T. Evangelista2, Y. Cheung Yee2, Robert K. Flamm1, Mark E. Jones1, Clyde Thornsberry1, Daniel F. Sahm1
Herndon, VA, USA
1Focus Bio-Inova, Inc., Herndon, VA;2Janssen Ortho-McNeil Pharmaceutical, Raritan, NJ
Table 1. Susceptibility of S. pneumoniae from sinus specimen sources
Background: Streptococcus pneumoniae
(SP) is the leading cause of acute bacterial sinusitis and isolates from
these infections tend to exhibit more extensive antimicrobial resistance than is encountered among strains from
• Percent susceptibility among the antimicrobial agents tested, based on 2000-2005 cumulative data, ranged
other infection sites. Because sinus SP isolates tend to be more resistant, and sinusitis therapy is often empiric,
from 51.9% for penicillin to 99.4 % for levofloxacin, and was less than 60% for penicillin, trimethoprim-
current knowledge of the antimicrobial profiles prominent among these organisms is important. TRUST
Surveil ance data obtained with sinus SP isolates were analyzed to establish the antimicrobial resistance trends
specific to strains from this clinical entity.
• The MIC s for amoxicillin-clavulanate, azithromycin, cefuroxime, penicillin, and trimethoprim-
SP sinus isolates (n = 846) collected from across the United States from 2000 to 2005 (YTD) were tested
sulfamethoxazole were at or above their CSLI resistant breakpoints. Levofloxacin MIC (1 µg/ml) remained
against penicillin (PEN), cefuroxime (CFX), azithromycin (AZI), amoxicillin-clavulanate (AMC), trimethoprim-
one doubling dilution below the susceptible breakpoint of 2 µg/ml.
sulfamethoxazole (SXT), and levofloxacin (LVX) by broth microdilution according to CLSI guidelines. Activity was
evaluated based on % susceptibility (S), and multi-drug resistance (MDR) was defined as resistance to ≥ 2 of these agents.
• 48% of the sinus strains were susceptible to all of the antimicrobial agents analyzed and 40% were resistant
In ascending order of relative activity the %S (2000-2005) were: PEN (51.9%), SXT (57.6%), AZI
Table 2. Resistance phenotypes from
Table 3. Susceptibility of S. pneumoniae from sinus specimen
to two or more agents; of those 338 strains resistant to two or more agents three (0.9%) were resistant to
(59.7%), CFX (61.9%), AMC (85.5%), and LVX (99.4%). As with single drug resistance, the rates of MDR
S. pneumoniae from sinus specimen sources
sources trended by year
fluctuated year to year as fol ows: 37.9% (2001), 42.3% (2002), 41.0% (2003), 38.4% (2004) and 38.7% (2005).
• The three most prevalent resistant phenotypes were:
The most common MDR phenotype was resistance to PEN, CFX, AZI, and SXT. Three (0.9%) of the 338 of the
MDRSP strains exhibited LVX resistance.
¾ Resistance to four agents (penicillin, cefuroxime, azithromycin, trimethoprim-sulfamethoxazole) – 11.0%
Susceptibility trends among sinus SP strains appear to have remained relatively stable over the past
¾ Resistance to five agents (penicillin, cefuroxime, azithromycin, clindamycin, and trimethoprim-
five years, with consistently elevated rates of MDRSP. The high level of fluoroquinolone (LVX) activity (99% S)
against sinus strains is consistent with the level of activity that has been maintained against SP and MDRSP from
¾ Resistance to azithromycin alone – 6.7%
• The rates of resistance (%) varied from 2000 to 2005 for the fol owing agents: 0 to 0.3 for levofloxacin, 6.5
to 12.0 for amoxicillin-clavulanate, 12.1 to 15.1 for clindamycin, and 27.4 to 30.1 for penicillin.
is the leading cause of acute bacterial sinusitis and isolates from these infections tend to
exhibit more extensive antimicrobial resistance than is encountered among strains from other infection sites.
• From 2000-2005, the MIC remained at 1 µg/ml for levofloxacin and 8 µg/ml for cefuroxime. During this
same time period, the MIC shifted from 4 to 8 µg/ml for amoxicillin-clavulanate and from 2 to 4 µg/ml for
Because sinus isolates tend to be more resistant, and sinusitis therapy is often empiric, current knowledge
penicillin. The azithromycin MIC was consistently elevated (>32 to >256) during the study period.
of the antimicrobial profiles prominent among strains from this infection site is important. TRUST
Surveillance data obtained with sinus S. pneumoniae
isolates were analyzed to establish the antimicrobial
resistance trends specific to strains from this clinical entity.
Resistance to a variety of antimicrobial classes is highly prevalent among sinus isolates of S. pneumoniae
multi-drug resistance to four and five agents were the most common phenotypes encountered. An exception
to this pattern was the continued high level of fluoroquinolone (levofloxacin) activity (>99% susceptible; MIC90
sinus isolates (n = 846) col ected from across the United States from 2000 to 2005 were
of 1 µg/ml) against sinus strains. Based on these trends it appears that the antimicrobial choices for empiric
tested against penicillin, cefuroxime, azithromycin, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole,
therapy will become notably limited.
and levofloxacin by broth microdilution according to CLSI guidelines. Activity was evaluated based on
percent susceptibility, distribution of resistance phenotypes, multi-drug resistance (MDR; defined as
concurrent resistance to ≥ 2 of the agents tested), and MIC distributions.
Analysis included the following agents: cefuroxime-axetil (Cefur), clindamycin (Clinda), azithromycin
Two respiratory seasons are included in the 2002-2003 and 2004-2005 date ranges.
This study was supported by Ortho-McNeil Pharmaceutical Inc., Raritan, NJ.
(Azith), levofloxacin (Levo), penicillin (Pen), and trimethoprim-sulfamethoxazole (SXT)
Panel range may have varied by year studied.
43rd Infectious Diseases Society of America (IDSA), San Francisco, CA
October 6-9, 2005
Exhibit 99.5 Modification of the Presentation of LossesThis report is for informational purposes only. It should be read in conjunction with documents filed by The Chubb Corporation with the Securities and Exchange Commission, including the most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. THE CHUBB CORPORATION Beginning in the third quarter of 2008, the “net
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