IHMA, Inc.

Tigecycline and Comparator Activity Against S. agalactiae Collected from the TEST Program (2010-2012) 2122 Palmer Dr.
Schaumburg, IL 60173
818 B. Johnson1, S. Bouchillon1, D. Hoban1, M. Hackel1, M. Renteria1 R. Badal1, J. Johnson1, S. Hawser2, H. Leister-Tebbe3
1International Health Management Associates, Inc., Schaumburg, IL, USA
Tel: +1.847.303.5003
2IHMA Europe Srl, Epalinges, Switzerland Fax: +1.847.303.5601
3Pfizer Inc., Collegeville, PA, USA www.ihmainc.com

Revised Abstract Introduction Results

Streptococcus agalactiae, or Group B streptococcus (GBS), is the leading infectious
Background: Streptococcus agalactiae or Group B cause of both early and late onset neonatal morbidity and mortality in developed
Streptococcus (GBS) is a major cause of neonatal countries worldwide. Clinical trials conducted in the 1980s demonstrated that Figure 1. Group B streptococcus infection site distribution, N=4,164 Table 1. In vitro activity of tigecycline and comparators against 4,164 isolates
administration of antibiotics prior to childbirth to women colonized with GBS or at risk of of Group B streptococcus.
and perinatal disease as well as a causative colonization by this pathogen could prevent invasive disease [1]. Penicillin or other
beta-lactam antibiotics remain the antibiotic agents of choice for prophylaxis.
pathogen of bacteremia and occasional skin and Frequently macrolides or lincosamides may be prescribed to women who are penicillin MIC (g/ml)
skin structure infections and urinary tract infections. or beta-lactam allergic. To date there have been no reported cases of isolates resistant
to either penicillin or ampicillin, although reduced susceptibility to penicillin has been
Drug Range MIC-50 MIC90 %Susa %Int %Res
The Tigecycline Evaluation Surveillance Trial reported. However in the United States between 5-25% of isolates have demonstrated Ampicillin 0.06 - 0.25 0.06 0.12 100 0.0 0.0
in vitro resistance to erythromycin and between 3-17% resistance to clindamycin [2-5].
(TEST) examines the susceptibility of tigecycline Resistance to cefoxitin has been reported but still remains rare. Vancomycin is used as Ceftriaxone 0.03 - 0.5 0.06 0.12 100 0.0 0.0
and comparators against pathogens isolated from an alternative to ampicillin and penicillin in patients with documented beta-lactam
allergies where anaphylaxis is of concern and where resistance to erythromycin or
Levofloxacin 0.06 - >32 0.5 1 98.3 0.4 1.3
patients in countries worldwide. Methods: Clinically clindamycin is documented. Meropenem 0.12 - 0.5 0.12 0.12 100 0.0 0.0
significant GBS were obtained from the following Alternatives to standard treatment regimens have not been examined but surveillance Penicillin 0.06 - 0.12 0.06 0.12 100 0.0 0.0
infection sites: blood, urine, respiratory, skin and studies examining the in vitro activities of carbapenems, glycylcyclines and
cephalosporins to GBS will help define the role of these agents in the future. GBS,
Tigecycline 0.008 - 0.25 0.03 0.12 100 0.0 0.0
skin structure, intra-abdominal and gastrointestinal. furthermore, can also cause infections of the bloodstream, central nervous system, Vancomycin 0.12 - 1 0.5 0.5 100 0.0 0.0
respiratory tract, urinary tract and skin/skin structures.
MIC values were determined for 1,769, 1,189 and a Susceptibility defined by CLSI document M100-S23 (2013) where available; tigecycline interpretive criteria defined by FDA (Tygacil, 2010)him

1,206 isolates of GBS during the years of 2010, The Tigecycline Evaluation and Surveillance Trial (TEST) examined the activity of
tigecycline and comparative agents against over 278,000 pathogens collected Table 2. MIC50 values of tigecycline and comparators against 4,164 isolates of Table 3. MICI are90 values of tigecycline and comparators against 4,164
2011 and 2012, respectively. Isolates were collected worldwide since 2004. This report documents the in vitro activity of tigecycline and
comparators against 4,164 isolates of GBS isolated worldwide during 2010-2012. Group B streptococcus stratified by year. isolates of Group B streptococcus stratified by year.
from a cumulative total of 781 sites in 56 countries
using supplied broth microdilution panels. Results MIC50 Values (g/ml) by Year MIC90 Values (g/ml) by Year
were interpreted according to FDA/CLSI guidelines. Materials & Methods 2010 2011 2012 2010 2011 2012
Results: The MIC50 and MIC90 (mcg/mL) for 4,164 All isolates were derived from a variety of clinical specimens/infectious process
Drug n=1,769 n=1,189 n=1,206 Drug n=1,769 n=1,189 n=1,206
including blood, central nervous system, respiratory, urine, and skin/skin
GBS versus comparative antimicrobial agents is Ampicillin 0.06 0.12 0.06
structure, worldwide. Only one isolate per patient was accepted into the study. Ampicillin 0.12 0.12 0.12
shown in the following table: Clinical isolates were collected and tested between 2010 and 2012 from 781
cumulative study centers in 56 countries. Isolates were identified to the species Ceftriaxone 0.06 0.06 0.06 Ceftriaxone 0.12 0.12 0.12
level and tested at each site by the participating laboratory.
Levofloxacin 0.5 1 0.5 Levofloxacin 1 1 1
Minimum inhibitory concentrations were determined by the CLSI recommended
S. agalactiae - MIC50/90 mcg/mL broth microdilution testing method [6]. Panels were manufactured by MicroScan Meropenem 0.12 0.12 0.12 Meropenem 0.12 0.12 0.12
(Siemens Medical Solutions Diagnostics, West Sacramento, CA, USA) or Trek
2010 2011 2012 (TREK Diagnostic Systems, Cleveland, OH, USA). Penicillin 0.06 0.06 0.06 Penicillin 0.059 0.12 0.12
Antibiotic n=1,769 n=1,189 n=1,206 QC of broth microdilution panels followed manufacturers and CLSI guidelines
Tigecycline 0.06 0.03 0.03 Tigecycline 0.12 0.25 0.12
using Streptococcus pneumoniae ATCC 49619.
Ampicillin <0.06/0.12 0.12/0.12 <0.06/0.12 Quality controls were performed by each testing site on each day of testing and Vancomycin 0.5 0.5 0.5 Vancomycin 0.5 1 0.5
Ceftriaxone 0.06/0.12 0.06/0.12 0.06/0.12 results were included in the analysis only when corresponding QC isolates tested
were within the acceptable range according to CLSI (2011) guidelines [7].
Levofloxacin 0.5/1 1/1 0.5/1 Table 4. Percents susceptible (%) of tigecycline and comparators against 4,164
Meropenem <0.12/<0.12 <0.12/<0.12 <0.12/<0.12 References isolates of Group B streptococcus stratified by year.
Conclusions
Penicillin <0.06/<0.06 <0.06/0.12 <0.06/0.12 1. MMWR November 19, 2010. P.1-32.
No resistance or increase in either MIC50 or MIC90 was detected in GBS
2. Andrews JJ, Diekma DJ, Hunter SK, et al. 2000. Group B streptococci causing neonatal % Susceptible by Year against ampicillin, ceftriaxone, meropenem, penicillin, tigecycline,
Tigecycline 0.06/0.12 0.03/0.25 0.03/0.12 bloodstream infection: antimicrobial susceptibility and serotyping results from the SENTRY centers
in the Western Hemisphere. Am J Obstet Gynecol; 183:859-862. 2010 2011 2012 vancomycin over the 3 year study period between 2010 and 2012.
Vancomycin 0.5/0.5 0.5/1 0.5/0.5 3. Fernandez M, Hickman ME, Baker CJ. 1998. Antimicrobial susceptibilities of group B streptococci
isolated between 1992 and 1996 from patients with bacteremia and meningitis. AAC; 42: 1517-
1519.
Drug n=1,769 n=1,189 n=1,206 Only levofloxacin demonstrated any decrease in susceptibility against GBS
4. Lin FYC, Azimi PH, Weisman LE et al. 2000. Antibiotic susceptibility profiles for group B
streptococci isolated from neonates, 1995-1998. CID; 31: 76-79.
Ampicillin 100 100 100 with 1.7% of the isolates non-susceptible. The annual fluctuations seen in
5. Morales WJ, Dickey SS, Bornick P, Lim DV. 1999. Change in antibiotic resistance of group B
Conclusions: The MIC50/90 values did not increase streptococcus: impact on intrapartum management. Am J Obstet Gynecol; 181:310-314. Ceftriaxone 100 100 100 the percents susceptible for levofloxacin were not statistically significant
6. CLSI, 2012, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow
for any studied antimicrobial over the three year Aerobically; Approved Standards, Ninth edition. CLSI document M07-A9. CLSI, Wayne, Levofloxacin 98.9 96.9 98.8* over the study period (p=0.421).
Pennsylvania 19807 USA.
study period. Global GBS isolated from a variety of 7. CLSI. 2013. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Third Meropenem 100 100 100 Global GBS isolated from a variety of clinical specimens continue to
Informational Supplement. CLSI Document M100-S23. CLSI, Wayne, Pennsylvania 19087 USA.
clinical specimens continue to demonstrate low 8. Tygacil, 2012. FDA product information. Pfizer Inc., Collierville, PA, USA Penicillin 100 100 100 demonstrate low MIC50 and MIC90 values for all of the study antimicrobials.
MIC50 and MIC90 for all of the antimicrobials. Tigecycline 100 100 100 This surveillance of over 4,164 GBS between 2010-2012 documents the
Levofloxacin and vancomycin demonstrated the Acknowledgments Vancomycin 100 100 100 continued excellent in vitro activity of tigecycline and comparator
highest MIC50/90 at 0.5/1. We gratefully acknowledge the contributions of the investigators, laboratory personnel, and all members
of the Tigecycline Evaluation Study Trials program group. This study was sponsored by a grant from * P-value = 0.421 (Cochran-Armitage Trend Test) antimicrobials.
Pfizer, Inc.