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Microsoft powerpoint - yee sp 5 yr trend icaac 2007 poster v4.ppt

5-Year Surveillance (2003-2007) of Anti-pneumococcal Activity of Oral Agents Recommended for the Empirical Treatment of
Community Acquired Pneumonia (CAP) in Adults
T Evangelista1, M. Obot-Tucker2, N. P. Brown2, C. M. Pillar2, C. Th T ornsberry 2, D. F. Sahm 2, and S. Graff2 Daniel Sahm, Ph.DEurofins Medinet, Inc., Anti- Presentation No. C2-204
Infective ServicesHerndon, VA, USA dan.sahm@eurofinsmedinet.com ABSTRACT
Table 1. Susceptibility of S. pneumoniae (TRUST 7-11 [2003-2007])
BACKGROUND: Based on various criteria, recent guidelines for the empirical treatment
TRUST 7 (2003)
TRUST 8 (2004)
TRUST 9 (2005)
TRUST 10 (2006)
TRUST 11 (2007)
During 2003-2007, a total of 21,400 respiratory isolates of S. pneumoniae were collected from laboratories across the 9 US Bureau of of CAP encompass the use of one or more of the following; macrolides, doxycycline, β- Census regions for the TRUST surveillance initiative. These isolates were identified and tested by a central lab, Eurofins Medinet, Inc., lactams, and respiratory fluoroquinolones. This study analyzed 5 years of data from an Antimicrobial agent
using standard reference methodologies. Antimicrobial agents of clinical interest in the treatment of respiratory infections were tested ongoing surveillance initiative to identify trends in activity between Streptococcus including: amoxicillin/clavulanate, azithromycin, cefuroxime/axetil, levofloxacin, moxifloxacin, penicillin, pneumoniae (SP) and recommended oral agents. trimethoprim/sulfamethoxazole, and tetracycline. These agents were tested against S. pneumoniae isolates by broth microdilution according to CLSI methodology, M7-A6. MIC results were interpreted as resistant, intermediate, or susceptible according to CLSI METHODS: SP (n = 21,400) respiratory isolates from TRUST surveillance 2003-2007
were centrally tested by broth microdilution (CLSI M7-A6; M100-S16). Results for amoxicillin-clavulanate (AMX), azithromycin (AZM), cefuroxime-axetil (CXM), levofloxacin (LVX), moxifloxacin (MXF), tetracycline (TET), and penicillin (PEN) were •Resistance (R) rates to 4 common oral agents increased during the 5-year study period. From 2003 to 2007, azithromycin-R increased from 27.5% to 32.3% and amoxicillin/clavulanate-R increased from 4.1% to 9.1% (Table 1, Figure 1). In addition, tetracycline-R
increased from 13.5% to 18.8% (2004-2007) and cefuroxime-R increased from 17.5% to 18.5% (2005-2007) (Table 1, Figure 1).
RESULTS: From 2003-2007, susceptibility of SP to PEN was relatively stable (64.0-
of azithromycin from 2004 (16 µg/ml) to 2005 (>128 µg/ml) (Table 2), and higher MIC s
of 2 µg/ml. CXM resistance fluctuated between 20.7% for azithromycin were then detected in 2006 and 2007 (>128 µg/ml) (Table 2). From 2006 to 2007, the MIC
(2003) and 18.5% (2007) with MIC s > 4 µg/ml. AMX resistance increased from 4.1% amoxicillin/clavulanate increased from 2 to 4 g/mL and for cefuroxime from 4 to 8 g/mL (Table 2).
increased from 2 to 4 µg/ml. AZM resistance Table 2. Activity of oral agents against S. pneumoniae (TRUST 7-11 [2003-2007])
increased from 27.5% (2003) to 32.3 % (2007); from 2004 to 2005 the MIC •There was a slight decrease in the amount of penicillin resistant isolates (MIC  2 g/mL) over time (17.3% in 2003 to 13.3% in TRUST 7 (2003)
TRUST 8(2004)
TRUST 9(2005)
TRUST 10(2006)
TRUST 11(2007)
from 16 to >128 µg/ml and remained high into 2007. TET resistance increased from 2007) (Table 1, Figure 1).
13.5% (2004) to 18.8% (2007) with a constant MIC MIC (µg/ml)
MIC (µg/ml)
MIC (µg/ml)
MIC (µg/ml)
MIC (µg/ml)
susceptibility of MXF and LVX was >99%; MXF and LVX MIC s remained constant at Antimicrobial agent
of the tested respiratory fluoroquinolones (levofloxacin and moxifloxacin) remained constant (1 µg/ml for levofloxacin 0.25 µg/ml and 1 µg/ml, respectively.
and 0.25 µg/ml for moxifloxacin) from 2003 to 2007 (Table 2). Greater than 99% of isolates were susceptible to both levofloxacin
and moxifloxacin for all years tested with the exception of 2004 (levofloxacin %S = 98.7%, moxifloxacin %S = 98.9%) (Table 1).
CONCLUSION: Trends indicate that SP penicillin resistance has slightly decreased,
Ciprofloxacin, for the purpose of comparison, differed from the respiratory fluoroquinolones with decreasing susceptibility rates of while resistance rates for AMX increased from 4.1% in 2003 to 9.1% in 2007. Increased 86.7% in 2005 to 82.0% in 2007 (Data on file). Since ciprofloxacin does not have CLSI breakpoints for S. pneumoniae, FDA
resistance to AZM and TET along with high MIC s indicate that continued use of breakpoints were used for the surveillance study.
macrolides and tetracyclines could be problematic. The activities of respiratory ratios for the respiratory fluoroquinolones (levofloxacin and moxifloxacin) exceeded 30 (the target PD ratio that fluoroquinolones remained high, and no trends that would indicate changes in activity correlates with clinical cure, microbiological eradication, and prevention of the emergence of resistance [Zhanel et al, JAC 2001;47:435]) (Table 3). Nearly identical AUC
were obtained for levofloxacin 750mg qd (71) and moxifloxacin 400mg qd BACKGROUND
(72) (Table 3). The ratio (7) of ciprofloxacin (500mg q12h) was < ¼ of the target PD (Table 3).
In 2007, the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) issued consensus guidelines for the management and treatment of Figure 1. Changes in percent resistant isolates over time
Table 3. Pharmacodynamic Activity of Fluoroquinolones
CONCLUSION
community-acquired pneumonia (CAP). Empiric treatment is directed by patient location of oral CAP agents against S. pneumoniae 2003-2007 (outpatient vs inpatient), and likelihood of the involvement of drug resistant S. pneumoniae •Resistance rates to 4 common oral agents increased during the 5-year study period: azithromycin (32.3%), amoxicillin/clavulanate based on risk factors and local resistance data. The use of respiratory fluoroquinolones (9.1%), cefuroxime (18.5%), and tetracycline (18.8%). These increasing resistance trends for these agents suggest that caution should be Antimic robial
(FQs), levofloxacin (LVX) and moxifloxacin (MXF), has been recommended for CAP AUC0-24h free/
used when treating respiratory infections caused by S. pneumoniae.
(single dose, PO)
total/ fre e ( mg•h/mL) b
patients with comorbidities, with recent antibiotic exposure, or in regions where high level •The respiratory fluoroquinolones (levofloxacin and moxifloxacin) were the most active agents in vitro against S. pneumoniae from resistance to macrolides (MIC  16 µg/ml) among S. pneumoniae is documented to occur at 2003-2007, as reflected by low MIC s and high percent susceptibilities.
high frequency (>25%). Previous studies of respiratory FQs have shown high activity against S. pneumoniae, and this study reviews data from the last 5 years (2003-2007) •Of the fluoroquinolones, levofloxacin and moxifloxacin provided pharmacodynamic activity above the target PD ratio of 30 (AUC comparing these agents with other recommended oral agents. In addition, the TRUST 11 (2006-2007), Data on file, Ortho-M cNeil, Inc. free/MIC ) for S. pneumoniae. Ciprofloxacin is not recommended for the treatment of CAP by ATS/IDSA, and the PD ratio of 7 (higher Zhanel et al. Drugs. 2002;62:13-59. Area under the serum concentration-time curve following single PO dose pharmacodynamic (PD) activity of the respiratory FQs is examined, since AUC/ MIC in normal volunteers. Free AUC based on 31% protein binding for levofloxacin, 30% for ciprofloxacin, and potential for emergence of resistance, and lower potential for successful clinical outcome and microbiologic eradication) supports this ratios above 30 for S. pneumoniae are considered to be good predictors of successful clinical outcomes, microbiologic eradication, and reduced potential for the emergence of resistance (Zhanel et al. JAC 2001;47:435). For the purpose of comparison, ciprofloxacin, ACKNOWLEDGEMENTS
an agent which is not recommended for treatment of CAP by the ATS/IDSA, was added to This study was supported by Ortho-McNeil, Inc., Raritan, NJ 7th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
Chicago, IL
September 17-20, 2006

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