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Diagnostic Microbiology and Infectious Disease 66 (2010) 407 – 418

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In vitro activity of tigecycline against patient isolates collected during

phase 3 clinical trials for diabetic foot infections
Peter J. Petersen, Alexey Ruzin, Margareta Tuckman, C. Hal Jones⁎
Infectious Diseases, Biosynthetic Chemistry, Wyeth Research, Pearl River, NY 10965, USA
Received 17 September 2009; accepted 22 November 2009

Abstract

The in vitro activity of tigecycline and comparative antimicrobial agents was evaluated against 1828 primary baseline pathogens isolated
from 844 patients enrolled in the phase 3 clinical trials investigating the efficacy of tigecycline in diabetic foot infection (DFI). The trials were
global, enrolling patients in 30 countries. Tigecycline was active against the most prevalent pathogens in DFI, including Gram-positive and
Gram-negative isolates of both aerobic and anaerobic bacteria with 95% of MICs ≤2 μg/mL for the entire collection. The spectrum of activity
of tigecycline included important pathogens for DFI, such as Staphylococcus aureus, Enterococcus faecalis, Streptococcus agalactiae,
Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis. As reported previously, Pseudomonas aeruginosa
and several pathogens in the Proteeae group were generally less susceptible to tigecycline by comparison to other Gram-negative pathogens.
The excellent in vitro expanded broad-spectrum activity of tigecycline in the clinical isolates confirmed the potential utility of tigecycline for
pathogens associated with DFIs.
© 2010 Elsevier Inc. All rights reserved.

Keywords: Tigecycline; Clinical isolates; In vitro susceptibility; Diabetic foot infection; MIC

1. Introduction tigecycline is not affected by the known tetracycline

Tigecycline is the first in class “glycylcycline” antibiotic
that was developed by Wyeth Pharmaceuticals (2005)
(Collegeville, PA) in response to the worldwide threat of
emerging resistance to antibiotics (Jones and Petersen, 2005;
Sum and Petersen, 1999). Tigecycline is currently approved
for treatment of complicated skin and skin structure
infections (cSSSIs), complicated intra-abdominal infections
(cIAIs), and community-acquired bacterial pneumonia
(CABP) (Babinchak et al., 2005; Bradford et al., 2005,
2008; Dukart et al., 2006; Ellis-Grosse et al., 2005). The
mode of action of tigecycline, the 9-t-butylglycylamido
derivative of minocycline, is through inhibition of protein
translation in bacteria. Similar to the classic tetracyclines,
tigecycline binds to the 30S ribosomal subunit and blocks
access of aminoacyl tRNA molecules to the A site (Olson
et al., 2006). In contrast to the classic tetracyclines,
⁎ Corresponding author. Tel.: +1-845-602-4612; fax: +1-845-602-5671.
E-mail address: jonesh3@wyeth.com (C.H. Jones).
0732-8893/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.diagmicrobio.2009.11.009
resistance determinants encoding monospecific tetracycline
efflux pumps (e.g., Tet(A), Tet(K)) or ribosomal protection
proteins (e.g., Tet(M), Tet(O)) (Jones et al., 2006, 2008;
Petersen et al., 1999; Tuckman et al., 2007). Tigecycline
demonstrates activity against a broad range of antibiotic-
susceptible and antibiotic-resistant Gram-positive and Gram-
negative aerobes, anaerobes, and “atypical” bacteria (Brad-
ford et al., 2005; Kenny and Cartwright, 2001; Petersen and
Bradford, 2005; Roblin and Hammerschlag, 2000).
Diabetic foot ulcers are the most common cause of lower
extremity amputation and are the primary cause of prolonged
hospitalization for diabetic patients (Lipsky et al., 2004;
Tentolouris et al., 2006). Of those diabetic patients who have
a foot ulcer (15% lifetime risk), between 40% and 80%
become infected (Lipsky et al., 2004). The predominant
pathogens in diabetic foot infection (DFI) are aerobic Gram-
positive cocci (e.g., Staphylococcus aureus); however, in
those patients who have chronic wounds or have received
antibiotic therapy, Gram-negative rods are also frequent
pathogens (Lipsky et al., 2004; Tentolouris et al., 2006).
408 P.J. Petersen et al. / Diagnostic Microbiology and Infectious Disease 66 (2010) 407–418

To evaluate the safety and efficacy of tigecycline in
treatment of DFIs a randomized, double-blind trial was
conducted with ertapenem as the active comparator (MB
Sabol et al. Phase 3 study comparing tigecycline (TGC) and
ertapenem (ERT) in patients (pts) with DFIs with and without
osteomyelitis. 47th annual meeting of the Infectious Disease
Society of America. 2009). Microbiologic cultures from the
patients enrolled in the clinical trials yielded 1828 baseline
bacterial isolates from 844 patients and were provided by 110
investigational sites in 30 countries worldwide. This analysis
was conducted to evaluate the susceptibility of the clinical
isolates to tigecycline and selected comparator agents.
25285, Bacteroides thetaiotaomicron ATCC 29741, and Eu-
bacterium lentum ATCC 43055.
2.3. Confirmation of extended-spectrum β-lactamase
E-test extended-spectrum β-lactamase (ESBL) strips
containing either ceftazidime or cefotaxime with and without
clavulanic acid were used according to the manufacturer's
instructions (AB Biodisk, Solna, Sweden) to confirm the
presence of an ESBL. An isolate was judged to be positive
by the E-test confirmatory test if the MIC ratio of either
β-lactam (ceftazidime or cefotaxime) alone versus the
β-lactam plus clavulanic acid was ≥8.

2. Materials and methods 2.4. Polymerase chain reaction analysis of

2.1. Clinical isolates
Baseline isolates from all patients enrolled (2007–2009) in
either the tigecycline or comparator treatment group were used
in this analysis. Each site laboratory processed patient speci-
mens and cultured bacterial pathogens according to local
practices. All bacterial pathogens were sent to a central labo-
ratory for identification and susceptibility testing, which were
performed in real time for the duration of the clinical trials.
resistance determinants
Methicillin (S. aureus) and tetracycline resistance deter-
minants (S. aureus, E. coli) were identified using diagnostic
polymerase chain reaction (PCR) assays as previously
described (Jones et al., 2006; Tuckman et al., 2007). In
addition, confirmed ESBL-containing isolates were further
examined by PCR to determine the class(es) of β-lactamase
(e.g., TEM, SHV, CTX, OXA) encoded using protocols
previously described (Jones et al., 2009).

2.2. Susceptibility testing

3. Results
For aerobic organisms, MICs were determined in
Mueller–Hinton II broth (MHB). For streptococcal MIC The most prevalent pathogens isolated from patients
determinations, MHB containing 5% lysed horse blood was during the clinical trail (2007–2009) for DFI are listed in
used. MICs were determined using custom-prepared dehy- Table 1. The distribution of pathogens was representative for
drated microdilution panels (Trek Diagnostics, Westlake,
OH) according to the manufacturer's instructions and Table 1
following reference methodology as described by the Clini- Predominant pathogens collected during phase 3 clinical trials for DFI
cal and Laboratory Standards Institute (CLSI, 2009a, 2009b).
Organism n (%) MDR strains (%)a
Interpretations were made using CLSI (2009a) M100-S19
Gram-positive aerobes 1107 (60.5%) 145 (13%)
breakpoint criteria for all comparator agents tested. Tigecy-
S. aureus 447 (24.5%) 99 (22%)
cline breakpoints were those approved by the US Food and E. faecalis 196 (11%)
Drug Administration (US FDA) (Enterobacteriaceae ≤2, 4, S. agalactiae 135 (7.4%)
≥8 μg/mL [S, I, R]; anaerobes ≤4, 8, ≥16 μg/mL [S, I, R]; S. epidermidis 79 (4.3%) 46 (58%)
staphylococci spp. ≤0.5 μg/mL [S only breakpoint]; Strep- Gram-negative aerobes 607 (33.2%) 79 (13%)
E. coli 88 (4.8%) 14 (16%)
tococcus spp. other than Streptococcus pneumoniae, Enter-
P. mirabilis 74 (4.0%) 4 (5.4%)
ococcus faecalis, and Haemophilus influenzae ≤0.25 μg/mL E. cloacae 68 (3.7%)
[S only breakpoint]; S. pneumoniae ≤0.06 μg/mL [S only P. aeruginosa 58 (3.1%) 19 (32%)
breakpoint]) (Wyeth Pharmaceuticals, 2005). For anaerobes, K. pneumoniae 57 (3.1%) 7 (12%)
MICs were determined by standard agar dilution methodol- A. baumannii/calcoaceticus complex 45 (2.5%) 24 (53%)
K. oxytoca 43 (2.4%)
ogy following CLSI (2007) instructions, M11-A7.
P. vulgaris group 30 (1.6%)
Disk diffusion susceptibility testing for tetracycline was M. morganii 26 (1.4%)
carried out by standard methodology as instructed by the C. freundii 19 (1.0%)
CLSI (2006), M02-A9. Methicillin resistance of staphylo- Anaerobes 114 (6.2%)
cocci was determined by MIC tests for oxacillin supplemen- F. magna 30 (1.6%)
P. bivia 11 (0.6%)
ted with 2% NaCl and interpreted according to CLSI
Prevotella spp. 10 (0.5%)
interpretive criteria (CLSI, 2009a, 2009b). Quality control P. asaccharolyticus 10 (0.5%)
was performed using, S. aureus ATCC 29213, E. faecalis a
MDR strains are MRSA and methicillin-resistant S. epidermis
ATCC 29212, S. pneumoniae ATCC 49619, Escherichia (MRSE) isolates by default and pathogens having resistance to 3 classes
coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, of antibacterial agent. No entry in a row indicates that no MDR strains were
H. influenzae ATCC 49247, Bacteroides fragilis ATCC identified for the given organism.
 P.J. Petersen et al. / Diagnostic Microbiology and Infectious Disease 66 (2010) 407–418
the infection type and similar to reports from recent studies
(Lipsky et al., 2004; Sotto et al., 2007; Tentolouris et al.,
2006). A summary of the tigecycline susceptibility of the
baseline isolates obtained from 844 patients in the clinical
trial for DFI is presented in Table 2. The most prevalent
pathogens isolated were Staphylococci spp. (621 isolates);
there were 99 methicillin-resistant S. aureus (MRSA) and 348
methicillin-susceptible S. aureus (MSSA) isolates. In addi-
tion, among Gram-positive pathogens, E. faecalis (196
isolates) and Streptococcus agalactiae (135 isolates) were
predominant. E. coli was the most prevalent Gram-negative
pathogen isolated (88 baseline isolates), followed by Proteus
mirabilis, Enterobacter cloacae, and K. pneumonia (Table 1).
As shown in Table 2, 100% of the MRSA and MSSA
isolates were susceptible to tigecycline, with MIC90s of
0.25 μg/mL, and all isolates were susceptible at the FDA
assigned susceptible breakpoint of ≤0.5 μg/mL. Most of the
MRSA isolates were susceptible to minocycline, and the
4 isolates that were minocycline resistant (MIC, ≥8 μg/mL)
were susceptible to tigecycline (MICs, 0.12–0.25 μg/mL)
(Table 3). Three of the minocycline-resistant isolates
encoded both tet(M) and tet(K), and a single isolate encoded
only the tet(M) gene. Fifty-eight of the minocycline-
susceptible isolates were resistant to tetracycline; of these,
50 isolates encoded tet(K), 2 isolates encoded tet(L), a single
isolate encoded both tet(K) and tet(M), and 5 isolates were
negative for all tested determinants. As expected, a high
percentage of the MRSA isolates were resistant to cipro-
floxacin (MIC90, ≥4 μg/mL) (Table 3). All of the isolates of
Staphylococcus epidermidis were susceptible to 0.5 μg/mL
of tigecycline (MIC90, 0.25 μg/mL) irrespective of the
susceptibility of the organisms to oxacillin. When consider-
ing all isolates of Staphylococcus spp., N99% of isolates
were tigecycline susceptible, with a single isolate of Sta-
phylococcus haemolyticus having a tigecycline MIC of
1 μg/mL (susceptible breakpoint ≤0.5 μg/mL).
Tigecycline had good activity against all 213 isolates of
Enterococcus spp. collected (Table 2). The predominant
species obtained was E. faecalis (196 isolates), and all of the
isolates were susceptible to ≤0.25 μg/mL, which is the FDA-
assigned breakpoint for E. faecalis. By contrast, the MIC90s
for both ciprofloxacin (N4 μg/mL) and minocycline (16 μg/
mL) were at the resistant breakpoints for the E. faecalis
isolates (Table 3). All of the E. faecalis isolates were
susceptible to vancomycin (MIC90, 4 μg/mL), as were the
6 isolates of Enterococcus faecium that were collected.
Among the 11 isolates of Enterococcus spp. obtained, there
were 3 isolates (2 Enterococcus gallinarum and 1 Entero-
coccus casseliflavus) that were vancomycin intermediate
(MIC, 8 μg/mL). All 3 isolates were susceptible to
tigecycline with MICs of 0.12 μg/mL.
Tigecycline activity was determined against 135 isolates
of S. agalactiae and 27 isolates of Streptococcus dysgalac-
tiae; all of the isolates were inhibited by 0.25 μg/mL (MIC90,
0.06 μg/mL) and 0.5 μg/mL (MIC 90, 0.25 μg/mL)
tigecycline, respectively. In the case of both β-hemolytic
409
Streptococcus spp., the minocycline MIC90 of N32 μg/mL
was above the resistant breakpoint. Similar activity was seen
against a small sample (13 isolates) of Streptococcus
pyogenes isolates (MIC90, 0.12 μg/mL). Lastly, tigecycline
had potent activity against isolates of the Streptococcus
anginosus group with an MIC range of ≤0.03 to 0.06 μg/mL
and an MIC90 of 0.06 μg/mL.
Tigecycline showed good activity against Gram-negative
organisms of which E. coli was the predominant pathogen
isolated. For the 88 baseline patient isolates tested, all were
susceptible to 1 μg/mL tigecycline (MIC range, 0.06–1 μg/
mL), with an MIC90 of 0.5 μg/mL. Fourteen (16%) of these
isolates were multidrug-resistant (MDR) pathogens showing
resistance to ceftriaxone, ciprofloxacin, and tetracycline. The
MIC90s for ceftriaxone and ciprofloxacin were N64 and
N4 μg/mL, respectively. The E. coli isolates included 58
tetracycline-resistant isolates, determined by disk diffusion
(zone ≤19 mm); 29 of which were also resistant to
minocycline (MIC, ≥16 μg/mL). The tetracycline resistance
determinants in these isolates were identified by PCR as
previously described (Tuckman et al., 2007). Twenty-three
minocycline-resistant isolates were found to encode tet(B), 4
isolates encoded both tet(A) and tet(B), and a single isolate
encoded tet(A). Twenty-nine isolates were found to be
susceptible to minocycline and resistant to tetracycline.
Eighteen isolates were found to encode tet(A), and a single
isolate each encoded tet(B), tet(C), and both the tet(A) and
tet(C) determinants. In the case of 8 tetracycline-resistant
isolates and 1 minocycline-resistant isolate, a gene(s)
responsible for the resistance phenotype was not identified.
As previously shown, the presence of tetracycline resistance
determinants, specifically monospecific tetracycline efflux
pumps, had no effect on tigecycline susceptibility of the
isolates (Tuckman et al., 2007).
Fifteen E. coli isolates were identified as encoding ESBLs
due to a ceftriaxone MIC ≥2 μg/mL and confirmed using
ESBL E-test strips. As previously described (Jones et al.,
2009), the class of β-lactamase responsible for the ESBL
phenotype was determined by PCR. Thirteen of the isolates
were found to encode a blaCTX family enzyme with various
combinations of blaTEM, blaSHV, and blaOXA genes. One
isolate was found to carry both a blaTEM and blaSHV gene,
whereas another isolate was negative in all of the PCR
assays. Further analysis will be required to correlate the
phenotype and genotype in these isolates. As previously
described, E. coli isolates expressing ESBLs are as suscep-
tible as non-ESBL isolates to tigecycline (Jones et al., 2009).
When tested against Klebsiella pneumoniae, tigecy-
cline performed well with an MIC range and MIC90 of
0.25 to 4 and 2 μg/mL, respectively, for the 57 isolates
tested. Whereas in earlier studies, K. pneumoniae had shown
a tendency for elevated tigecycline MICs (Ruzin et al.,
2005), only a single isolate in the present study had an MIC
of 4 μg/mL, which is above the susceptible breakpoint set
by the FDA (Wyeth Pharmaceuticals, 2005). Seven (12%)
of the baseline isolates were MDR pathogens, resistant to
410 P.J. Petersen et al. / Diagnostic Microbiology and Infectious Disease 66 (2010) 407–418

Table 2
In vitro activity of tigecycline against bacterial isolates from phase 3 clinical trials for DFI
Organism (no. of strains) (μg/mL) %Sa No. of isolates with MIC (μg/mL) of
MIC50 MIC90 ≤0.03 0.06 0.12 0.25 0.5 1 2 4 8 N8
Gram-negative aerobes
C. freundii complex (19) 0.25 0.5 100 2 10 7
C. koseri (8) 0.25 NAb 100 7 1
E. aerogenes (8) 0.25 NA 100 4 3 1
E. cloacae (68) 0.5 0.5 100 13 51 4
E. coli (88) 0.25 0.5 100 2 37 37 11 1
K. oxytoca (43) 0.25 0.5 100 3 34 4 2
K. pneumoniae (57) 0.5 2 98 10 32 4 10 1
M. morganii (26) 1 2 96 3 12 10 1
P. mirabilis (74) 2 4 65 1 6 41 20 6
P. vulgaris (30) 2 2 97 1 1 7 20 1
Providencia spp.c (10) 2 2 100 1 2 7
Serratia spp.d (14) 0.5 1 100 2 5 6 1
A. calcoaceticus/baumannii complex (45) 0.5 2 NA 5 7 7 8 13 4 1
Acinetobacter lwoffii (5) 0.06 NA NA 2 3
P. aeruginosa (58) 8 32 NA 1 31 26
Stenotrophomonas maltophilia (6) 0.5 NA NA 3 3
Gram-positive aerobes
S. aureus (MRSA) (99) 0.12 0.25 100 2 13 41 38 5
S. aureus (MSSA) (348) 0.12 0.25 100 7 228 109 4
S. epidermidis (MRSE) (46) 0.25 0.5 100 2 12 18 14
S. epidermidis (methicillin susceptible) (33) 0.12 0.25 100 4 14 10 5
S. haemolyticus (16) 0.25 0.5 94 1 4 5 5 1
Staphylococcus hominis (12) 0.12 0.12 100 4 7 1
Staphylococcus lugdunensis (12) 0.06 0.25 100 1 5 3 3
Staphylococcus simulans (14) 0.12 0.12 100 4 10
Coagulase-negative Staphylococcuse (41) 0.12 0.25 100 1 4 20 15 1
E. faecalis (196) 0.12 0.25 100 1 23 101 71
Enterococcus spp.f (17) 0.06 0.12 100 9 6 2
S. agalactiae (135) 0.06 0.06 100 44 85 5 1
S. anginosus (13) ≤0.03 0.06 100 9 4
S. anginosus groupg (20) ≤0.03 0.06 100 15 5
S. dysgalactiae (27) 0.06 0.25 96 7 10 6 3 1
Streptococcus mitis group (7) 0.06 NA 86 4 1 1 1
Streptococcus oralis (14) ≤0.03 0.25 93 8 1 2 2 1
S. pyogenes (13) ≤0.03 0.25 100 7 4 2
Corynebacterium spp.h (31) 0.06 0.25 NA 12 8 6 4 1
Anaerobes
B. fragilis (8) 1 NA 100 2 1 3 1 1
P. bivia (11) 1 1 100 1 4 5 1
Prevotella spp.i (10) 0.12 0.25 100 1 5 3 1
Clostridium perfringens (4) 2 NA 100 1 3
F. magna (30) 0.12 0.25 100 20 10
P. asaccharolyticus (10) 0.12 0.25 100 1 3 3 3
Peptostreptococcus spp.j (7) 0.06 NA 100 5 1 1
Anaerococcus spp.k (6) 0.12 NA 100 5 1
%S is the percentage of strains susceptible at FDA susceptibility breakpoints for tigecycline: ≤2 μg/mL for Enterobacteriaceae, ≤0.5 μg/mL for
a

Staphylococcus spp., ≤0.25 μg/mL for Streptococcus spp., ≤0.25 μg/mL for Enterococcus spp., and ≤4 μg/mL for anaerobes.
b
NA = not applicable due to number of strains or no approved interpretive criteria are available.
c
Providencia rettgeri (9), Providencia stuartii (1).
d
Serratia marcescens (9), Serratia liquefaciens (4), Serratia plymuthica (1).
e
Staphylococcus capitis (8), Staphylococcus caprae (4), Staphylococcus carnosus (1), Staphylococcus cohnii (7), Staphylococcus hyicus (1), Staphylococcus
intermedius (1), Staphylococcus kloosii (2), Staphylococcus pasteuri (1), Staphylococcus sciuri (6), Staphylococcus warneri (8), Staphylococcus xylosus (2).
f
Enterococcus avium (5), E. casseliflavus (3), E. faecium (6), E. gallinarum (2), Enterococcus harae (1).
g
S. anginosus (13), Streptococcus constellatus (5), S. intermedius (2).
h
Corynebacterium glucuronolyticum (1), Corynebacterium accolens (1), Corynebacterium amycolatum (6), Corynebacterium diphtheriae (1),
Corynebacterium macginleyi (1), Corynebacterium minutissimum (4), Corynebacterium striatum (11), Corynebacterium spp. (6).
i
Prevotella buccae (2), Prevotella denticola (1), Prevotella disiens (1), Prevotella intermedia (1), Prevotella melaninogenica (1), Prevotella oralis (1),
Prevotella spp. (3).
j
Peptostreptococcus anaerobius (4), Peptostreptococcus micros (1), Peptostreptococcus tetradius (2).
k
Anaerococcus hydrogenalis (1), Anaerococcus prevotii (5).
 P.J. Petersen et al. / Diagnostic Microbiology and Infectious Disease 66 (2010) 407–418
β-lactam and at least 2 other classes of agents, in this case,
ciprofloxacin and minocycline (Table 4). The ESBL status
of 16 isolates was confirmed (ceftriaxone MIC, ≥2 μg/mL,
and E-test positive) and the class of genetic determinant
responsible for the ESBL status identified by PCR. Fifteen
of 16 isolates encoded a blaSHV gene with 13 of the 15
encoding additional determinants in various combinations
of the blaTEM, blaCTX, and blaOXA classes. A single isolate
encoded only a blaCTX family β-lactamase. All 43 of
the Klebsiella oxytoca isolates collected were inhibited by
1 μg/mL tigecycline with MIC90 of 0.5 μg/mL.
As demonstrated in prior studies (Bradford et al., 2005;
Ruzin et al., 2005; Visalli et al., 2003) tigecycline MICs for
the Proteeae are generally higher than for other Enterobac-
teriaceae. Mechanistic studies revealed that a multidrug
efflux system, AcrAB, is responsible for reduced tigecycline
susceptibility in P. mirabilis and the other Proteeae (Visalli
et al., 2003). Against the collection of P. mirabilis from DFI,
tigecycline showed results in agreement with what has been
seen in prior studies: MIC range, 0.5 to 8 μg/mL, and MIC90,
4 μg/mL. All of the P. mirabilis isolates were resistant to
minocycline (MIC range, 8 to N32 μg/mL) (Table 4). In
addition, 3 baseline isolates were found to express the ESBL
phenotype (ceftriaxone MIC, ≥2 μg/mL, and E-test
positive), and PCR analysis revealed that 2 of the isolates
encoded blaCTX family enzymes and the third encoded a
blaCMY family enzyme. Tigecycline performed well against
the 30 Proteus vulgaris group isolates in the study, with an
MIC range and MIC90 of 0.25 to 4 and 2 μg/mL,
respectively. Similar activity for tigecycline was seen with
the 26 isolates of Morganella morganii: MIC range, 0.5 to 4
μg/mL, MIC90, 2 μg/mL. The minocycline MIC90 for
P. vulgaris was 16 μg/mL, and for M. morganii, it was
N32 μg/mL.
The activity of tigecycline was evaluated against 68
E. cloacae isolates, with the result that all isolates were
susceptible to 1 μg/mL with an MIC90 of 0.5 μg/mL. The
findings were similar for the small collection (8) of Entero-
bacter aerogenes isolates: all isolates were susceptible to
1 μg/mL tigecycline. When tested against 19 isolates of
Citrobacter freundii complex and 8 isolates of Citrobacter
koseri, tigecycline performed well with all isolates suscep-
tible to 0.5 μg/mL. The MIC90 for the C. freundii complex
isolates was 0.5 μg/mL.
Tigecycline demonstrated good activity against 45
baseline isolates of Acinetobacter baumannii/calcoaceticus
complex; tigecycline and minocycline were the only agents
on the panel that showed MIC90s (2 μg/mL for both
agents) in the susceptible range against this important
pathogen. The MIC90s for cefoxitin, ceftriaxone, cipro-
floxacin, ertapenem, and piperacillin/tazobactam were all
above the resistance breakpoint (CLSI, 2009a) (Table 4).
Equivalent or better activity for minocycline versus
tigecycline against A. baumannii/calcoaceticus complex
has been noted before and is not fully understood (Bradford
et al., 2005).
411
The 58 P. aeruginosa isolates collected during the
clinical trial had MIC90s in the resistant range for all of the
test agents. The tigecycline MIC90 was 32 μg/mL,
which is reflective of earlier studies demonstrating reduced
susceptibility of this organism to tigecycline (Dean et al.,
2003). Like the Proteeae, P. aeruginosa expresses a family
of multidrug efflux pumps that efficiently remove
tigecycline from the cytoplasm, reducing its effectiveness
(Poole, 2005).
Against the anaerobic organisms collected, tigecycline
performed well with all of the isolates susceptible to
tigecycline at 4 μg/mL (Table 5). The MIC90s for the most
prevalent anaerobes tested were 0.25 μg/mL for Finegoldia
magna, Peptoniphilus asaccharolyticus, and Prevotella spp.
and 1 μg/mL for Prevotella bivia.
4. Discussion
Tigecycline is an antibacterial agent that has an
expanded broad spectrum of activity against many
important bacterial pathogens and has demonstrated
clinical utility for cSSSI, cIAI, and CABP indications
(Babinchak et al., 2005; Bradford et al., 2005, 2008;
Dukart et al., 2006; Ellis-Grosse et al., 2005). This agent
was specifically designed to overcome the 2 classic tetra-
cycline resistance mechanisms: ribosomal protection and
monospecific tetracycline efflux pumps (Petersen et al.,
1999; Sum and Petersen, 1999). During preclinical
development, tigecycline was shown to have activity
against a broad range of clinically important pathogens
(Edlund and Nord, 2000; Jacobus et al., 2004; Kenny and
Cartwright, 2001; Roblin and Hammerschlag, 2000). The
potent antibacterial activity of tigecycline demonstrated in
the present study echoed that seen in earlier clinical studies
for the approved indications, cIAI, cSSSI, and CABP, as
well as during preclinical development (Babinchak et al.,
2005; Bradford et al., 2005, 2008; Dukart et al., 2006;
Ellis-Grosse et al., 2005). For example, the tigecycline
MIC90s for MRSA and E. coli were 0.25 and 0.5 μg/mL,
respectively, for isolates from earlier clinical trials for
cSSSI and cIAI and the present DFI study. In addition,
tigecycline activity in the present study was not impacted
by the presence of the classic tetracycline resistance
mechanisms in E. coli and S. aureus or ESBLs in E. coli
and K. pneumoniae.
The isolates from the clinical trials were obtained from
patients enrolled in 30 countries in North America, Latin
America, Eastern Europe, Western Europe, Asia, South
Africa, and Australia. Regional variation supporting a trend
for differences in the MICs of tigecycline in certain regions
was not noted for isolates from the various regions
conducting trials. These results are in agreement with results
obtained previously from a number of large in vitro
susceptibility studies that included isolates from North
America, Latin America, Europe, the Middle East, and
412 P.J. Petersen et al. / Diagnostic Microbiology and Infectious Disease 66 (2010) 407–418

Table 3
In vitro activities of tigecycline and comparative antibacterial agents against Gram-negative clinical isolates from DFI
Organism (no. of isolates tested) Antibiotic MIC (μg/mL) %Sa
Range 50% 90%
C. freundii complex (19) Tigecycline 0.12 to 0.5 0.25 0.5 100
Cefoxitin 16 to N32 N32 N32 0
Ceftriaxone 0.12 to N64 0.25 0.5 95
Ciprofloxacin ≤0.12 to N4 ≤0.12 0.5 89
Ertapenem ≤0.03 to 2 ≤0.03 ≤0.03 100
Minocycline 1 to 8 2 4 89
Piperacillin–tazobactam 1 to 128 2 8 95
C. koseri (8) Tigecycline 0.25 to 0.5 0.25 NAb 100
Cefoxitin 2 to 16 2 NA 88
Ceftriaxone ≤0.03 to 0.25 0.06 NA 100
Ciprofloxacin ≤0.12 ≤0.12 NA 100
Ertapenem ≤0.03 ≤0.03 NA 100
Minocycline 1 to 4 2 NA 100
Piperacillin–tazobactam 2 to 8 2 NA 100
E. aerogenes (8) Tigecycline 0.25 to 1 0.25 NA 100
Cefoxitin N32 N32 NA 0
Ceftriaxone 0.06 to 4 0.12 NA 100
Ciprofloxacin ≤0.12 to 2 ≤0.12 NA 100
Ertapenem ≤0.03 to 0.25 0.06 NA 100
Minocycline 1 to 8 2 NA 88
Piperacillin–tazobactam 2 to 8 4 NA 100
E. cloacae (68) Tigecycline 0.25 to 1 0.5 0.5 100
Cefoxitin 16 to N32 N32 N32 0
Ceftriaxone 0.06 to N64 0.25 2 93
Ciprofloxacin ≤0.12 to N4 ≤0.12 0.5 96
Ertapenem ≤0.03 to 0.5 ≤0.03 0.12 100
Minocycline 2 to 32 4 8 82
Piperacillin–tazobactam 1 to 128 2 4 94
E. coli (88) Tigecycline 0.06 to 1 0.25 0.5 100
Cefoxitin 2 to N32 4 16 88
Ceftriaxone ≤0.03 to N64 0.06 N64 84
Ciprofloxacin ≤0.12 to N4 ≤0.12 N4 65
Ertapenem ≤0.03 to 1 ≤0.03 0.12 100
Minocycline 0.5 to N32 2 32 67
Piperacillin–tazobactam 0.5 to N128 2 16 90
K. oxytoca (43) Tigecycline 0.12 to 1 0.25 0.5 100
Cefoxitin 2 to 16 2 8 98
Ceftriaxone ≤0.03 to 2 0.06 0.12 100
Ciprofloxacin ≤0.12 to 0.25 ≤0.12 ≤0.12 100
Ertapenem ≤0.03 to 0.06 ≤0.03 ≤0.03 100
Minocycline 1 to 32 2 2 95
Piperacillin–tazobactam 1 to 16 2 4 100
K. pneumoniae (57) Tigecycline 0.25 to 4 0.5 2 98
Cefoxitin 1 to N32 4 32 84
Ceftriaxone ≤0.03 to N64 0.06 N64 77
Ciprofloxacin ≤0.12 to N4 ≤0.12 N4 77
Ertapenem ≤0.03 to 4 ≤0.03 0.25 96
Minocycline 1 to N32 4 16 63
Piperacillin–tazobactam 0.5 to N128 4 64 84
M. morganii (26) Tigecycline 0.5 to 4 1 2 96
Cefoxitin 8 to N32 16 16 35
Ceftriaxone ≤0.03 to N64 ≤0.03 4 92
Ciprofloxacin ≤0.12 to N4 ≤0.12 N4 77
Ertapenem ≤0.03 to 0.06 ≤0.03 ≤0.03 100
Minocycline 4 to N32 8 N32 23
Piperacillin–tazobactam ≤0.12 to 32 0.25 2 96
P. mirabilis (74) Tigecycline 0.5 to 8 2 4 65
Cefoxitin 1 to N32 4 4 99
Ceftriaxone ≤0.03 to N64 ≤0.03 0.06 97
Ciprofloxacin ≤0.12 to N4 ≤0.12 2 82
Ertapenem ≤0.03 to 0.25 ≤0.03 ≤0.03 100
Minocycline 8 to N32 32 N32 0
 P.J. Petersen et al. / Diagnostic Microbiology and Infectious Disease 66 (2010) 407–418 413

Table 3 (continued)
Organism (no. of isolates tested) Antibiotic MIC (μg/mL) %Sa
Range 50% 90%
Piperacillin–tazobactam ≤0.12 to 32 0.25 0.5 99
P. vulgaris (30) Tigecycline 0.25 to 4 2 2 97
Cefoxitin 2 to 16 4 8 97
Ceftriaxone ≤0.03 to N64 ≤0.03 4 97
Ciprofloxacin ≤0.12 to 4 ≤0.12 0.5 90
Ertapenem ≤0.03 to 0.06 ≤0.03 ≤0.03 100
Minocycline 4 to 32 8 16 17
Piperacillin–tazobactam 0.25 to 128 0.5 1 97
Providencia spp.c (10) Tigecycline 0.5 to 2 2 2 100
Cefoxitin 1 to 8 2 4 100
Ceftriaxone ≤0.03 to 64 0.06 0.25 90
Ciprofloxacin ≤0.12 to N4 ≤0.12 N4 70
Ertapenem ≤0.03 ≤0.03 ≤0.03 100
Minocycline 8 to N32 16 16 0
Piperacillin–tazobactam 0.25 to 128 0.5 128 80
Serratia spp.d (14) Tigecycline 0.25 to 2 0.5 1 100
Cefoxitin 8 to N32 16 N32 14
Ceftriaxone 0.06 to 2 0.25 1 100
Ciprofloxacin ≤0.12 to 0.5 ≤0.12 ≤0.12 100
Ertapenem ≤0.03 to 0.12 ≤0.03 ≤0.03 100
Minocycline 1 to 16 2 16 64
Piperacillin–tazobactam 1 to 8 2 8 100
A. calcoaceticus/baumannii complex (45) Tigecycline 0.06 to 4 0.5 2 NA
Cefoxitin 32 to N32 N32 N32 NA
Ceftriaxone 4 to N64 N64 N64 22
Ciprofloxacin ≤0.12 to N4 N4 N4 NA
Ertapenem 1 to N32 8 N32 NA
Minocycline ≤0.12 to 8 0.25 2 96
Piperacillin–tazobactam ≤0.12 to N128 128 N128 29
A. lwoffii (5) Tigecycline 0.06 to 0.25 0.06 NA NA
Cefoxitin 4 to N32 4 NA NA
Ceftriaxone 2 to 64 4 NA 60
Ciprofloxacin ≤0.12 to 0.5 ≤0.12 NA NA
Ertapenem 0.5 to 8 2 NA NA
Minocycline ≤0.12 to 0.5 ≤0.12 NA 100
Piperacillin–tazobactam ≤0.12 to N128 ≤0.12 NA 60
P. aeruginosa (58) Tigecycline 4 to N32 8 32 NA
Cefoxitin N32 N32 N32 NA
Ceftriaxone 8 to N64 N64 N64 5
Ciprofloxacin ≤0.12 to N4 0.5 N4 60
Ertapenem 1 to N32 8 N32 NA
Minocycline 8 to N32 16 N32 NA
Piperacillin–tazobactam 2 to N128 8 128 86
S. maltophilia (6) Tigecycline 0.5 to 1 0.5 NA NA
Cefoxitin N32 N32 NA NA
Ceftriaxone N64 N64 NA NA
Ciprofloxacin 2 to N4 4 NA NA
Ertapenem 32 to N32 N32 NA NA
Minocycline 0.25 to 1 0.25 NA 100
Piperacillin–tazobactam 16 to N128 N128 NA NA
a
FDA, Tygacil label accessed May 2009 (Wyeth Pharmaceuticals, 2005) or CLSI (2009a), M100-S19, assigned breakpoints were used to determine
percentage susceptible. NA = breakpoints not established.
b
NA = not applicable—less than 10 organisms analyzed.
c
P. rettgeri (9), P. stuartii (1).
d
S. marcescens (9), S. liquefaciens (4), S. plymuthica (1).

Asia (Fritsche et al., 2005; Reinert et al., 2007; Sader et al., Tigecycline has been shown to be safe and effective in
2005). All of these studies reported good activity against a double-blind, multicenter, global clinical trials for cSSSI,
wide variety of pathogens, most of which were inhibited cIAI, and, most recently, CABP (Babinchak et al., 2005;
by ≤2 μg/mL of tigecycline. Dukart et al., 2006; Ellis-Grosse et al., 2005; Wyeth
414 P.J. Petersen et al. / Diagnostic Microbiology and Infectious Disease 66 (2010) 407–418

Table 4
In vitro activities of tigecycline and comparative antibacterial agents against Gram-positive clinical isolates from DFI
Organism Antibiotic MIC (μg/mL) %Sa
(no. of isolates tested)
Range 50% 90%
MRSA (99) Tigecycline 0.06 to 0.5 0.12 0.25 100
Cefoxitin 4 to N32 32 N32 NA
Ceftriaxone 4 to N64 64 N64 NA
Ciprofloxacin ≤0.12 to N4 N4 N4 21
Ertapenem 0.25 to N32 2 N32 NA
Linezolid 1 to 4 2 2 100
Minocycline ≤0.12 to 16 0.25 8 89
Piperacillin–tazobactam 2 to N128 16 128 NA
Vancomycin 0.5 to 2 1 2 100
Oxacillin 8 to N32 N32 N32 0
MSSA (348) Tigecycline ≤0.03 to 0.5 0.12 0.25 100
Cefoxitin ≤0.5 to 32 4 4 NA
Ceftriaxone 1 to 64 4 4 99.7
Ciprofloxacin ≤0.12 to N4 0.5 0.5 92
Ertapenem 0.06 to 4 0.25 0.25 99.7
Linezolid 1 to 4 2 4 100
Minocycline ≤0.12 to 8 ≤0.12 0.25 99
Piperacillin–tazobactam ≤0.12 to 4 1 2 100
Vancomycin 0.5 to 2 1 2 100
Oxacillin ≤0.06 to 2 0.5 1 100
MRSE (46) Tigecycline 0.06 to 0.5 0.25 0.5 100
Cefoxitin 4 to N32 8 32 NA
Ceftriaxone 2 to N64 8 32 NA
Ciprofloxacin ≤0.12 to N4 4 N4 43
Ertapenem 0.25 to N32 2 16 NA
Linezolid 0.5 to 2 1 2 100
Minocycline ≤0.12 to 2 0.5 1 100
Piperacillin–tazobactam 0.25 to 64 1 4 NA
Vancomycin 1 to 4 2 2 100
Oxacillin 0.5 to N32 8 N32 0
Methicillin-susceptible Tigecycline 0.06 to 0.5 0.12 0.25 100
S. epidermidis (33) Cefoxitin 1 to 4 2 4 NA
Ceftriaxone 0.5 to 4 2 2 100
Ciprofloxacin ≤0.12 to N4 0.25 N4 85
Ertapenem 0.06 to 0.5 0.25 0.5 100
Linezolid 0.5 to 2 1 2 100
Minocycline ≤0.12 to 1 ≤0.12 0.5 100
Piperacillin–tazobactam ≤0.12 to 0.5 0.25 0.5 100
Vancomycin 1 to 4 2 2 100
Oxacillin ≤0.06 to 0.25 0.12 0.25 100
S. haemolyticus (16) Tigecycline 0.06 to 1 0.25 0.5 94
Cefoxitin 2 to N32 16 N32 NA
Ceftriaxone 4 to N64 32 N64 25
Ciprofloxacin ≤0.12 to N4 N4 N4 31
Ertapenem 0.5 to N32 4 N32 38
Linezolid 0.5 to 2 1 2 100
Minocycline ≤0.12 to 16 0.5 1 88
Piperacillin–tazobactam 0.5 to N128 8 N128 50
Vancomycin 0.5 to 2 1 2 100
Oxacillin 0.12 to N32 32 N32 19
S. hominis (12) Tigecycline 0.06 to 0.5 0.12 0.12 100
Cefoxitin 2 to 32 4 16 NA
Ceftriaxone 2 to 16 4 8 92
Ciprofloxacin ≤0.12 to 0.5 ≤0.12 0.5 100
Ertapenem 0.12 to 16 0.5 4 83
Linezolid 1 to 2 1 2 100
Minocycline ≤0.12 to 0.5 ≤0.12 0.25 100
Piperacillin–tazobactam 0.25 to 4 0.5 4 100
Vancomycin 0.5 to 2 1 2 100
Oxacillin ≤0.06 to N32 0.12 N32 67
 P.J. Petersen et al. / Diagnostic Microbiology and Infectious Disease 66 (2010) 407–418 415

Table 4 (continued)
Organism Antibiotic MIC (μg/mL) %Sa
(no. of isolates tested)
Range 50% 90%
S. lugdunensis (12) Tigecycline ≤0.03 to 0.25 0.06 0.25 100
Cefoxitin 2 to 8 4 4 NA
Ceftriaxone 1 to 4 4 4 100
Ciprofloxacin ≤0.12 to 0.25 0.25 0.25 100
Ertapenem 0.5 to 1 0.5 0.5 100
Linezolid 1 to 2 1 1 100
Minocycline ≤0.12 to 0.25 ≤0.12 0.25 100
Piperacillin–tazobactam 0.25 to 2 1 1 100
Vancomycin 0.5 to 1 1 1 100
Oxacillin 0.25 to 4 0.5 1 92
S. simulans (14) Tigecycline 0.06 to 0.12 0.12 0.12 100
Cefoxitin 2 to 16 2 4 NA
Ceftriaxone 2 to 32 4 8 93
Ciprofloxacin ≤0.12 to N4 ≤0.12 N4 86
Ertapenem 0.12 to 1 0.25 1 100
Linezolid 1 to 2 2 2 100
Minocycline ≤0.12 to 0.25 ≤0.12 ≤0.12 100
Piperacillin–tazobactam 0.25 to 2 0.5 1 100
Vancomycin 0.5 to 1 1 1 100
Oxacillin 0.12 to 16 0.25 4 57
Coagulase-negative Tigecycline ≤0.03 to 0.5 0.12 0.25 100
Staphylococcus spp.b (41) Cefoxitin ≤0.5 to N32 4 32 NA
Ceftriaxone 0.12 to N64 4 N64 68
Ciprofloxacin ≤0.12 to N4 0.25 N4 83
Ertapenem 0.06 to N32 0.5 8 78
Linezolid ≤0.25 to 2 2 2 100
Minocycline ≤0.12 to 8 0.25 0.5 95
Piperacillin–tazobactam ≤0.12 to N128 1 64 80
Vancomycin ≤0.25 to 4 1 2 100
Oxacillin 0.12 to N32 1 N32 29
E. faecalis (196) Tigecycline ≤0.03 to 0.25 0.12 0.25 100
Cefoxitin N32 N32 N32 NA
Ceftriaxone 2 to N64 N64 N64 NA
Ciprofloxacin 0.5 to N4 0.5 N4 64
Ertapenem 4 to 32 8 16 NA
Linezolid 1 to 8 2 2 98
Minocycline ≤0.12 to 32 16 16 25
Piperacillin–tazobactam 0.5 to 32 4 8 NA
Vancomycin 0.5 to 4 2 4 100
Enterococcus spp.c (17) Tigecycline 0.06 to 0.25 0.06 0.12 100
Cefoxitin 16 to N32 32 N32 NA
Ceftriaxone 0.5 to N64 16 N64 NA
Ciprofloxacin 0.5 to N4 2 N4 41
Ertapenem 0.12 to N32 8 N32 NA
Linezolid 1 to 4 2 4 82
Minocycline ≤0.12 to 32 ≤0.12 32 47
Piperacillin–tazobactam 2 to N128 16 N128 NA
Vancomycin 0.5 to 8 1 8 82
S. agalactiae (135) Tigecycline ≤0.03 to 0.25 0.06 0.06 100
Cefoxitin 2 to 32 8 8 NA
Ceftriaxone ≤0.03 to 0.25 0.12 0.12 100
Ciprofloxacin 0.5 to N4 0.5 0.5 NA
Ertapenem ≤0.03 to 0.25 0.06 0.12 100
Linezolid 1 to 2 1 2 100
Minocycline ≤0.12 to N32 16 N32 NA
Piperacillin–tazobactam ≤0.12 to 1 0.5 0.5 NA
Vancomycin 0.5 to 1 0.5 1 100
S. anginosus (13) Tigecycline ≤0.03 to 0.06 ≤0.03 0.06 100
Cefoxitin ≤0.5 to 16 8 8 NA
Ceftriaxone ≤0.03 to 0.5 0.25 0.5 100
Ciprofloxacin 0.25 to 0.5 0.5 0.5 NA
Ertapenem 0.06 to 0.5 0.25 0.5 100
(continued on next page)
416 P.J. Petersen et al. / Diagnostic Microbiology and Infectious Disease 66 (2010) 407–418

Table 4 (continued)
Organism Antibiotic MIC (μg/mL) %Sa
(no. of isolates tested)
Range 50% 90%
Linezolid 1 to 2 1 2 100
Minocycline ≤0.12 to 16 ≤0.12 16 NA
Piperacillin–tazobactam ≤0.12 to 0.5 ≤0.12 0.5 NA
Vancomycin 0.5 to 1 1 1 100
S. anginosus groupd (20) Tigecycline ≤0.03 to 0.06 ≤0.03 0.06 100
Cefoxitin ≤0.5 to 16 8 8 NA
Ceftriaxone ≤0.03 to 0.5 0.25 0.5 100
Ciprofloxacin 0.25 to 0.5 0.5 0.5 NA
Ertapenem ≤0.03 to 1 0.25 0.5 100
Linezolid ≤0.25 to 2 1 2 100
Minocycline ≤0.12 to 16 ≤0.12 8 NA
Piperacillin–tazobactam ≤0.12 to 1 ≤0.12 0.5 NA
Vancomycin 0.5 to 1 1 1 100
S. dysgalactiae (27) Tigecycline ≤0.03 to 0.5 0.06 0.25 96
Cefoxitin ≤0.5 to 2 1 2 NA
Ceftriaxone ≤0.03 to 0.06 ≤0.03 0.06 100
Ciprofloxacin 0.25 to N4 0.5 0.5 NA
Ertapenem ≤0.03 ≤0.03 ≤0.03 100
Linezolid 0.5 to 2 1 2 100
Minocycline ≤0.12 to N32 16 N32 NA
Piperacillin–tazobactam ≤0.12 ≤0.12 ≤0.12 NA
Vancomycin ≤0.25 to 1 0.5 0.5 100
S. mitis group (7) Tigecycline 0.06 to 0.5 0.06 NAe 86
Cefoxitin 1 to 16 2 NA NA
Ceftriaxone ≤0.03 to 0.25 0.06 NA 100
Ciprofloxacin 4 to N4 4 NA NA
Ertapenem ≤0.03 to 0.5 0.06 NA 100
Linezolid 0.5 to 1 1 NA 100
Minocycline 0.25 to 32 1 NA NA
Piperacillin–tazobactam ≤0.12 to 1 ≤0.12 NA NA
Vancomycin 0.5 to 1 0.5 NA 100
Streptococcus oralis (14) Tigecycline ≤0.03 to 0.5 ≤0.03 0.25 93
Cefoxitin 1 to 16 2 4 NA
Ceftriaxone 0.06 to 0.5 0.12 0.5 100
Ciprofloxacin 0.5 to N4 4 N4 NA
Ertapenem ≤0.03 to 0.25 0.06 0.12 100
Linezolid 1 to 2 1 2 100
Minocycline ≤0.12 to 16 ≤0.12 8 NA
Piperacillin–tazobactam ≤0.12 to 2 ≤0.12 0.5 NA
Vancomycin 0.5 to 1 1 1 100
S. pyogenes (13) Tigecycline ≤0.03 to 0.25 ≤0.03 0.25 100
Cefoxitin 1 to 2 2 2 NA
Ceftriaxone ≤0.03 to 0.06 ≤0.03 ≤0.03 100
Ciprofloxacin 0.25 to 0.5 0.5 0.5 NA
Ertapenem ≤0.03 ≤0.03 ≤0.03 100
Linezolid 1 to 2 1 2 100
Minocycline ≤0.12 to 16 ≤0.12 8 NA
Piperacillin–tazobactam ≤0.12 ≤0.12 ≤0.12 NA
Vancomycin ≤0.25 to 1 0.5 0.5 100
Corynebacterium spp.f (31) Tigecycline ≤0.03 to 0.5 0.06 0.25 NA
Cefoxitin ≤0.5 to N32 4 N32 NA
Ceftriaxone 0.12 to N64 4 32 NA
Ciprofloxacin ≤0.12 to N4 2 N4 NA
Ertapenem 0.06 to N32 0.5 2 NA
Linezolid ≤0.25 to 1 0.5 0.5 NA
Minocycline ≤0.12 to 16 0.25 16 NA
Piperacillin–tazobactam ≤0.12 to N128 16 64 NA
Vancomycin ≤0.25 to 1 0.5 1 NA
 P.J. Petersen et al. / Diagnostic Microbiology and Infectious Disease 66 (2010) 407–418 417

Table 5
In vitro activities of tigecycline and comparative antibacterial agents against Gram-negative and Gram-positive anaerobic clinical isolates from DFI
Organism Antibiotic MIC (μg/mL) %Sa
(no. of isolates tested)
Range 50% 90%
B. fragilis (8) Tigecycline 0.25 to 4 1 NAb 100
Ceftriaxone 2 to N128 32 NA 13
Clindamycin 1 to N64 2 NA 63
Imipenem 0.12 to 0.25 0.25 NA 100
Metronidazole 1 to 4 1 NA 100
P. bivia (11) Tigecycline 0.25 to 2 1 1 100
Ceftriaxone 0.25 to N128 8 32 64
Clindamycin ≤0.03 to N64 ≤0.03 N64 64
Imipenem ≤0.015 to 0.06 0.03 0.06 100
Metronidazole 0.5 to 16 2 8 91
Prevotella spp.c (10) Tigecycline 0.06 to 2 0.12 0.25 100
Ceftriaxone 0.12 to N128 2 64 70
Clindamycin ≤0.03 to N64 ≤0.03 N64 80
Imipenem 0.03 to 0.12 0.03 0.06 100
Metronidazole 0.5 to 8 1 4 100
C. perfringens (4) Tigecycline 0.12 to 2 2 NA 100
Ceftriaxone 0.06 to 4 0.5 NA 100
Clindamycin 0.06 to 2 0.06 NA 100
Imipenem 0.06 to 0.25 0.06 NA 100
Metronidazole 0.5 to 4 2 NA 100
F. magna (30) Tigecycline 0.12 to 0.25 0.12 0.25 100
Ceftriaxone 1 to 16 8 16 100
Clindamycin 0.06 to N64 2 N64 53
Imipenem ≤0.015 to 0.12 0.06 0.06 100
Metronidazole 0.12 to 2 0.5 1 100
P. asaccharolyticus (10) Tigecycline ≤0.03 to 0.25 0.12 0.25 100
Ceftriaxone 0.12 to 1 0.25 1 100
Clindamycin ≤0.03 to N64 0.5 N64 60
Imipenem ≤0.015 to 0.06 ≤0.015 0.06 100
Metronidazole 0.25 to 2 1 2 100
Peptostreptococcus spp.d (7) Tigecycline 0.06 to 0.5 0.06 NA 100
Ceftriaxone 0.25 to 64 0.5 NA 86
Clindamycin ≤0.03 to N64 0.25 NA 71
Imipenem ≤0.015 to 0.12 0.06 NA 100
Metronidazole ≤0.06 to 2 1 NA 100
Anaerococcus spp.e (6) Tigecycline 0.12 to 0.25 0.12 NA 100
Ceftriaxone 0.12 to 1 0.25 NA 100
Clindamycin ≤0.03 to N64 0.25 NA 83
Imipenem ≤0.015 to 0.25 ≤0.015 NA 100
Metronidazole 1 to 128 2 NA 67
a
FDA, Tygacil label accessed May 2009 (Wyeth Pharmaceuticals, 2005) or CLSI (2007), M11-A7, assigned breakpoints were used to determine percentage
susceptible.
b
NA = not applicable—less than 10 isolates analyzed.
c
P. buccae (2), P. denticola (1), P. disiens (1), P. intermedia (1), P. melaninogenica (1), P. oralis (1), Prevotella spp. (3).
d
P. anaerobius (4), P. micros (1), P. tetradius (2).
e
A. hydrogenalis (1), A. prevotii (5).

Notes to Table 4:
a
FDA, Tygacil label accessed May 2009 (Wyeth Pharmaceuticals, 2005) or CLSI (2009a), M100-S19, assigned breakpoints were used to determine
percentage susceptible. NA = breakpoints not established.
b
S. capitis (8), S. caprae (4), S. carnosus (1), S. cohnii (7), S. hyicus (1), S. intermedius (1), S. kloosii (2), S. pasteuri (1), S. sciuri (6), S. warneri (8),
S. xylosus (2).
c
E. avium (5), E. casseliflavus (3), E. faecium (6), E. gallinarum (2), E. harae (1).
d
S. anginosus (13), S. constellatus (5), S. intermedius (2).
e
NA = not applicable—less than 10 isolates analyzed.
f
C. glucuronolyticum (1), C. accolens (1), C. amycolatum (6), C. diphtheriae (1), C. macginleyi (1), C. minutissimum (4), C. striatum (11), Coryne-
bacterium spp. (6).
418 P.J. Petersen et al. / Diagnostic Microbiology and Infectious Disease 66 (2010) 407–418
Pharmaceuticals, 2005). In summary, the in vitro activity
of tigecycline against a broad spectrum of Gram-positive
and Gram-negative pathogens isolated from patients
enrolled in phase 3 clinical trials conducted worldwide for
DFI showed an excellent susceptibility profile and suggests
utility in the treatment of patients with this disease.
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