Study Comparing the Safety and Efficacy of Tigecycline With Ampicillin-Sulbactam or Amoxicillin-Clavulanate to Treat Skin Infections

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00368537
• Collaborator: (none)
• Enrollment: 550
• Locations: 58
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the safety and efficacy of the antibiotic tigecycline with other antibiotics, ampicillin-sulbactam, and amoxicillin-clavulanate in the treatment of a complicated skin and/or skin structure infection (cSSSI).

Condition or Disease	Intervention/Treatment	Phase
Skin Diseases, Bacterial	Drug: Tigecycline; Drug: ampicillin-sulbactam	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 550 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Open-Label Comparison of the Safety And Efficacy of Tigecycline With That of Ampicillin-Sulbactam or Amoxicillin-Clavulanate to Treat Complicated Skin And Skin Structure Infections
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Arm 1: Tigecycline	Drug: Tigecycline; Treatment A: Tigecycline every 12 hours intravenous (IV) (an initial dose of 100 mg followed by 50 mg every 12 hours)
Active Comparator: 2 Arm 2: Ampicillin-Sulbactam or Amoxicillin-Clavulanate plus or minus a glycopeptide	Drug: ampicillin-sulbactam; Ampicillin-sulbactam: 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (3 g ampicillin plus 1 g sulbactam) intravenous (IV) every 6 hrs or Amoxicillin-clavulanate: 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hrs. A glycopeptide antibiotic (either vancomycin 1 g IV every 12 hrs or teicoplanin IV loading dose of 400 mg the first day followed by a maintenance dose of 200 mg daily) may be added to the aminopenicillin/betalactamase inhibitor regimen if infection with methicillin-resistant staphylococcus aureus (MRSA) is suspected or confirmed within the first 72 hrs of enrollment. If culture results fail to show a resistant organism, use of the glycopeptide may be discontinued.

Outcome Measures

Primary Outcome Measures

1. Number of Clinically Evaluable (CE) Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit [up to 6 weeks]

   Investigator assigned clinical response of cure of the cSSSI defined as: resolution of all clinical signs and symptoms of infection (healing of chronic underlying skin ulcer not required) or improvement of signs or symptoms of the infection to such an extent that no further antibacterial therapy was necessary. CE population were those who completed TOC assessment of cure or failure (but not indeterminate) or, in case of premature discontinuation due to lack of efficacy, had completed end of treatment assessment such that assessment of clinical response could be made.

Secondary Outcome Measures

1. Number of Microbiologically Evaluable Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit [up to 6 weeks]

   Investigator assigned clinical response of cure of the cSSSI defined as: resolution of all clinical signs and symptoms of infection (healing of chronic underlying skin ulcer not required) or improvement of signs or symptoms of the infection to such an extent that no further antibacterial therapy was necessary. ME population were subjects who were CE and had baseline culture with at least 1 identified isolate that was susceptible to study drug and comparator. TOC performed 8-50 days after last dose of study drug.

2. Number of Microbiologically Evaluable Patients by Microbiologic Response at Test-of-Cure (TOC) Visit [up to 6 weeks]

   Microbiological response assessed at patient level. Eradication=baseline isolate not present in repeat culture from the original infection site; Presumed Eradication=clinical response of cure precluded the availability of a specimen for culture; Persistence=baseline isolate present in repeat culture from the original infection site; Presumed Persistence=culture data not available for patients with a clinical response of failure; Superinfection=culture from the primary infection site had new pathogen not identified as a baseline isolate and clinical response was failure.

3. Minimum Inhibitory Concentration (MIC) 50 and 90 by Baseline Isolate [up to 6 weeks]

   In vitro activity of the study drugs against a range of pathogenic bacteria that cause complicated skin and skin structure infection (cSSSI) were analyzed using MIC. MIC 50 and MIC 90 are the lowest concentrations of a drug that inhibit the growth of 50% and 90% of a microorganism, respectively. TOC performed 8-50 days after last dose of study drug.

4. Inpatient Healthcare Resource Utilization on or Before Test-of-Cure - Number of Patients [up to 6 weeks]

   Healthcare resource utilization assessment included intensive care unit (ICU) and non-ICU inpatient hospitalization. TOC performed 8-50 days after last dose of study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical diagnosis of complicated skin or skin structure infection

• Male or female, 18 years or older

• Need for intravenous treatment for 4 to 14 days

Exclusion Criteria:

• Skin infection that can be treated by surgery & wound care alone

• Diabetic foot ulcers or bedsores where the infection is present longer than 1 week

• Poor circulation such that amputation of the infected site is likely within a month Other exclusions apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Scottsdale	Arizona	United States	85251
2		Jonesboro	Arkansas	United States	72401
3		Chula Vista	California	United States	91911
4		Mission Viejo	California	United States	92691
5		National City	California	United States	91950
6		Denver	Colorado	United States	80218
7		Washington	District of Columbia	United States	20017
8		Washington	District of Columbia	United States	20037
9		Orlando	Florida	United States	32803
10		Vero Beach	Florida	United States	32960
11		Ft. Gordon	Georgia	United States	30905
12		Idaho Falls	Idaho	United States	83404
13		Decatur	Illinois	United States	62526
14		Naperville	Illinois	United States	60540
15		Springfield	Illinois	United States	62702
16		Topeka	Kansas	United States	66606
17		Cambridge	Massachusetts	United States	02139
18		Worcester	Massachusetts	United States	01655
19		Detroit	Michigan	United States	48202
20		Lincoln	Nebraska	United States	68510
21		Hackensack	New Jersey	United States	07601
22		Neptune	New Jersey	United States	07754
23		Buffalo	New York	United States	14215
24		Elmira	New York	United States	14905
25		New Hyde Park	New York	United States	11040
26		Columbus	Ohio	United States	43214
27		Lima	Ohio	United States	45801
28		Lansdale	Pennsylvania	United States	19446
29		Philadelphia	Pennsylvania	United States	19140
30		Fort Worth	Texas	United States	76104
31		Ft. Worth	Texas	United States	76104
32		Houston	Texas	United States	77026
33		Winnipeg	Manitoba	Canada	R3A 1R9
34		Chicoutimi	Quebec	Canada	G7H 5H6
35		Montreal	Quebec	Canada	H1T 2M4
36		Sherbrooke	Quebec	Canada	J1H 5N4
37		Trois-Rivieres	Quebec	Canada	G8Z 3R9
38		Saskatoon	Saskatchewan	Canada	S7N 0W8
39		Quebec		Canada	G1V 4G5
40		Hong Kong		Hong Kong
41		Ramat Gan		Israel	52621
42		Daejeon		Korea, Republic of	301-721
43		Incheon		Korea, Republic of	405-760
44		Seoul		Korea, Republic of	120-752
45		Seoul		Korea, Republic of	133-791
46		Beirut		Lebanon	110 32090
47		Pulau Pinang		Malaysia	10990
48		Manila		Philippines	1000
49		Manila		Philippines	1014
50		Singapore		Singapore	169608
51		Cape Town		South Africa	7531
52		Gauteng		South Africa	0181
53		KZ-Natal		South Africa	3610
54		Mpumalanga		South Africa	1050
55		Taipei		Taiwan	220
56		Bangkok		Thailand	10330
57		Bangkok		Thailand	10400
58		Bangkok		Thailand	10700

Sponsors and Collaborators

• Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Medical Monitor, Wyeth is now a wholly owned subsidiary of Pfizer
• Principal Investigator: Trial Manager, For Hong Kong: [e-mail]
• Principal Investigator: Trial Manager, For South Africa: [e-mail]
• Principal Investigator: Trial Manager, For Taiwan: [e-mail]

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wyeth is now a wholly owned subsidiary of Pfizer
• ClinicalTrials.gov Identifier: NCT00368537
• Other Study ID Numbers: 3074A1-900
• First Posted: Aug 24, 2006
• Last Update Posted: Aug 9, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by Wyeth is now a wholly owned subsidiary of Pfizer: skin infection; antibiotics
• Additional relevant MeSH terms: Infections; Skin Diseases, Bacterial; Skin Diseases; Ampicillin; Tigecycline; Sulbactam; Sultamicillin

Study Results

Participant Flow

Recruitment Details	Patients were recruited worldwide from September 2006 to August 2008.
Pre-assignment Detail	Patients were screened according to the inclusion/exclusion criteria. Once informed consent was obtained, the patient was enrolled into the study and assigned a randomization number and a treatment regimen.

Arm/Group Title	Tigecycline	Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Arm/Group Description	Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)	Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Period Title: Randomization
STARTED	281	269
COMPLETED	268	263
NOT COMPLETED	13	6
Period Title: Randomization
STARTED	268	263
COMPLETED	244	239
NOT COMPLETED	24	24

Baseline Characteristics

Arm/Group Title	Tigecycline	Ampicillin-Sulbactam or Amoxicillin-Clavulanate	Total
Arm/Group Description	Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)	Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.	Total of all reporting groups
Overall Participants	268	263	531
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.10 (16.11)	51.54 (16.90)	51.32 (16.49)
Sex: Female, Male (Count of Participants)
Female	105 39.2%	94 35.7%	199 37.5%
Male	163 60.8%	169 64.3%	332 62.5%

Outcome Measures

1. Primary Outcome

Title	Number of Clinically Evaluable (CE) Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit
Description	Investigator assigned clinical response of cure of the cSSSI defined as: resolution of all clinical signs and symptoms of infection (healing of chronic underlying skin ulcer not required) or improvement of signs or symptoms of the infection to such an extent that no further antibacterial therapy was necessary. CE population were those who completed TOC assessment of cure or failure (but not indeterminate) or, in case of premature discontinuation due to lack of efficacy, had completed end of treatment assessment such that assessment of clinical response could be made.
Time Frame	up to 6 weeks

Outcome Measure Data

Analysis Population Description

Clinically Evaluable (CE): Patients with cSSSI, no Pseudomonas aeruginosa as sole baseline isolate, met major inclusion/exclusion criteria, ≤24 hrs antibiotics pre-baseline, had ≥4 days of study drug, compliant with therapy. Excludes indeterminates.

Arm/Group Title	Tigecycline	Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Arm/Group Description	Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)	Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Measure Participants	209	196
Number [participants]	162 60.4%	152 57.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tigecycline, Ampicillin-Sulbactam or Amoxicillin-Clavulanate
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A 2-sided 95% CI (corrected for continuity) was calculated for the true difference between the cure rates. Non-inferiority will be concluded if the lower limit of the 2-sided CI is greater than -15%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.0
	Confidence Interval	() 95%; -8.7 to 8.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence interval calculated using asymptotic method corrected for continuity. Difference= Tigecycline minus Ampicillin-Sulbactam or Amoxicillin-Clavulanate.

2. Secondary Outcome

Title	Number of Microbiologically Evaluable Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit
Description	Investigator assigned clinical response of cure of the cSSSI defined as: resolution of all clinical signs and symptoms of infection (healing of chronic underlying skin ulcer not required) or improvement of signs or symptoms of the infection to such an extent that no further antibacterial therapy was necessary. ME population were subjects who were CE and had baseline culture with at least 1 identified isolate that was susceptible to study drug and comparator. TOC performed 8-50 days after last dose of study drug.
Time Frame	up to 6 weeks

Outcome Measure Data

Analysis Population Description

Microbiologically Evaluable patients:Clinically Evaluable (CE) patients who had baseline culture with ≥1 identified pathogen susceptible to both study drugs (ie, the pathogen is susceptible to tigecycline and comparator). Excludes indeterminates.

Arm/Group Title	Tigecycline	Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Arm/Group Description	Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)	Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Measure Participants	120	99
Number [participants]	96 35.8%	77 29.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tigecycline, Ampicillin-Sulbactam or Amoxicillin-Clavulanate
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A 2-sided 95% CI (corrected for continuity) was calculated for the true difference between the cure rates. Non-inferiority will be concluded if the lower limit of the 2-sided CI is greater than -15%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.2
	Confidence Interval	() 95%; -9.6 to 14.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence interval calculated using asymptotic method corrected for continuity. Difference= Tigecycline minus Ampicillin-Sulbactam or Amoxicillin-Clavulanate.

3. Secondary Outcome

Title	Number of Microbiologically Evaluable Patients by Microbiologic Response at Test-of-Cure (TOC) Visit
Description	Microbiological response assessed at patient level. Eradication=baseline isolate not present in repeat culture from the original infection site; Presumed Eradication=clinical response of cure precluded the availability of a specimen for culture; Persistence=baseline isolate present in repeat culture from the original infection site; Presumed Persistence=culture data not available for patients with a clinical response of failure; Superinfection=culture from the primary infection site had new pathogen not identified as a baseline isolate and clinical response was failure.
Time Frame	up to 6 weeks

Outcome Measure Data

Analysis Population Description

Microbiologically Evaluable patients:CE patients who had baseline culture with ≥1 identified pathogen susceptible to both study drugs (ie, the pathogen is susceptible to tigecycline and comparator). TOC performed 8-50 days after last dose of study drug.

Arm/Group Title	Tigecycline	Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Arm/Group Description	Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)	Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Measure Participants	120	99
Eradication + presumed eradication	95 35.4%	76 28.9%
Persistence + Presumed persistence	25 9.3%	23 8.7%
Superinfection	2 0.7%	1 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tigecycline, Ampicillin-Sulbactam or Amoxicillin-Clavulanate
	Comments	Group comparison of eradication + presumed eradication
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A 2-sided 95% CI (corrected for continuity) was calculated for the true difference between the cure rates. Non-inferiority will be concluded if the lower limit of the 2-sided CI is greater than -15%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.4
	Confidence Interval	() 95%; -9.6 to 14.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence interval calculated using asymptotic method corrected for continuity. Difference= Tigecycline minus Ampicillin-Sulbactam or Amoxicillin-Clavulanate.

4. Secondary Outcome

Title	Minimum Inhibitory Concentration (MIC) 50 and 90 by Baseline Isolate
Description	In vitro activity of the study drugs against a range of pathogenic bacteria that cause complicated skin and skin structure infection (cSSSI) were analyzed using MIC. MIC 50 and MIC 90 are the lowest concentrations of a drug that inhibit the growth of 50% and 90% of a microorganism, respectively. TOC performed 8-50 days after last dose of study drug.
Time Frame	up to 6 weeks

Outcome Measure Data

Analysis Population Description

m-mITT: Patients with ≥1 dose of study drug, had cSSSI and baseline isolate from infection site / blood. MIC reported for isolates present in ≥10 m-mITT patients. In the categories below "n" is the actual number of isolates used to caluculate the MIC 50 and MIC 90.

Arm/Group Title	Tigecycline	Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Arm/Group Description	Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)	Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Measure Participants	120	99
Enterococcus Faecalis MIC50 (n=20,20)	0.12	1.00
Enterococcus Faecalis MIC90 (n=20,20)	0.25	1.00
Escherichia Coli MIC50 (n=29,29)	0.25	8.00
Escherichia Coli MIC90 (n=29,29)	0.50	32.00
Klebsiella Pneumoniae MIC50 (n=13,13)	0.50	2.00
Klebsiella Pneumoniae MIC90 (n=13,13)	2.00	8.00
Staphylococcus Aureus MIC50 (n=176,176)	0.12	2.00
Staphylococcus Aureus MIC90 (n=176,176)	0.25	8.00
Streptococcus Agalactiae MIC50 (n=18,18)	0.03	0.12
Streptococcus Agalactiae MIC90 (n=18,18)	0.06	0.12
Streptococcus Pyogenes MIC50 (n=18,18)	0.03	0.06
Streptococcus Pyogenes MIC90 (n=18,18)	0.06	0.06

5. Secondary Outcome

Title	Inpatient Healthcare Resource Utilization on or Before Test-of-Cure - Number of Patients
Description	Healthcare resource utilization assessment included intensive care unit (ICU) and non-ICU inpatient hospitalization. TOC performed 8-50 days after last dose of study drug.
Time Frame	up to 6 weeks

Outcome Measure Data

Analysis Population Description

All patients who received at least 1 dose of study article.

Arm/Group Title	Tigecycline	Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Arm/Group Description	Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)	Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Measure Participants	268	263
Intensive care unit	6 2.2%	9 3.4%
Non-ICU inpatient hospitalization	268 100%	263 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tigecycline, Ampicillin-Sulbactam or Amoxicillin-Clavulanate
	Comments	Intensive care unit
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.444
	Comments
	Method	Fisher Exact
	Comments	2-sided
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-1.2
	Confidence Interval	() 95%; -4.4 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	This data represents the number of times a given adverse event was reported. The given participant may have experienced more than one adverse event. We are looking at the frequency of adverse events based on event and not by participant.
Arm/Group Title	Tigecycline		Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Arm/Group Description	Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)		Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
All Cause Mortality
	Tigecycline		Ampicillin-Sulbactam or Amoxicillin-Clavulanate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tigecycline		Ampicillin-Sulbactam or Amoxicillin-Clavulanate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/268 (14.2%)		29/263 (11%)
Blood and lymphatic system disorders
International normalized ratio increased	0/268 (0%)		1/263 (0.4%)
Cardiac disorders
Heart arrest	3/268 (1.1%)		2/263 (0.8%)
Myocardial infarct	1/268 (0.4%)		0/263 (0%)
Ventricular tachycardia	1/268 (0.4%)		0/263 (0%)
Gastrointestinal disorders
Cholecystitis	1/268 (0.4%)		0/263 (0%)
Diarrhea	1/268 (0.4%)		0/263 (0%)
Esophageal hemorrhage	0/268 (0%)		1/263 (0.4%)
Gastrointestinal hemorrhage	1/268 (0.4%)		0/263 (0%)
Hepatic failure	0/268 (0%)		1/263 (0.4%)
Liver function tests abnormal	0/268 (0%)		1/263 (0.4%)
Nausea	1/268 (0.4%)		0/263 (0%)
Peptic ulcer	1/268 (0.4%)		0/263 (0%)
Stomach ulcer	0/268 (0%)		1/263 (0.4%)
Vomiting	1/268 (0.4%)		0/263 (0%)
General disorders
Cellulitis	7/268 (2.6%)		6/263 (2.3%)
Infection	6/268 (2.2%)		1/263 (0.4%)
Abscess	1/268 (0.4%)		2/263 (0.8%)
Chest pain	2/268 (0.7%)		0/263 (0%)
General physical health deterioration	1/268 (0.4%)		1/263 (0.4%)
Asthenia	1/268 (0.4%)		0/263 (0%)
Carcinoma	0/268 (0%)		1/263 (0.4%)
Fever	0/268 (0%)		1/263 (0.4%)
Generalized edema	0/268 (0%)		1/263 (0.4%)
Overdose	1/268 (0.4%)		0/263 (0%)
Retroperitoneal hemorrhage	1/268 (0.4%)		0/263 (0%)
Sepsis	1/268 (0.4%)		0/263 (0%)
Septic shock	1/268 (0.4%)		0/263 (0%)
Traumatic hematoma	1/268 (0.4%)		0/263 (0%)
Metabolism and nutrition disorders
Dehydration	1/268 (0.4%)		1/263 (0.4%)
Hypoglycemia	1/268 (0.4%)		1/263 (0.4%)
Healing abnormal	0/268 (0%)		1/263 (0.4%)
Musculoskeletal and connective tissue disorders
Necrotising fasciitis	0/268 (0%)		2/263 (0.8%)
Osteomyelitis	0/268 (0%)		1/263 (0.4%)
Nervous system disorders
Convulsion	1/268 (0.4%)		0/263 (0%)
Encephalopathy	0/268 (0%)		1/263 (0.4%)
Renal and urinary disorders
Acute kidney failure	3/268 (1.1%)		1/263 (0.4%)
Kidney failure	0/268 (0%)		1/263 (0.4%)
Kidney function abnormal	1/268 (0.4%)		0/263 (0%)
Urinary tract infection	0/268 (0%)		1/263 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	3/268 (1.1%)		0/263 (0%)
Lung edema	1/268 (0.4%)		1/263 (0.4%)
Respiratory failure	1/268 (0.4%)		1/263 (0.4%)
Carcinoma of lung	1/268 (0.4%)		0/263 (0%)
Chronic obstructive airways disease	0/268 (0%)		1/263 (0.4%)
Skin and subcutaneous tissue disorders
Skin necrosis	2/268 (0.7%)		1/263 (0.4%)
Herpes simplex	1/268 (0.4%)		0/263 (0%)
Vascular disorders
Pulmonary embolus	1/268 (0.4%)		1/263 (0.4%)
Deep vein thrombosis	1/268 (0.4%)		0/263 (0%)
Occlusion	1/268 (0.4%)		0/263 (0%)
Other (Not Including Serious) Adverse Events
	Tigecycline		Ampicillin-Sulbactam or Amoxicillin-Clavulanate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	396/268 (147.8%)		241/263 (91.6%)
Blood and lymphatic system disorders
Anemia	8/268 (3%)		7/263 (2.7%)
Gastrointestinal disorders
Nausea	117/268 (43.7%)		44/263 (16.7%)
Vomiting	64/268 (23.9%)		14/263 (5.3%)
Diarrhea	38/268 (14.2%)		14/263 (5.3%)
Constipation	17/268 (6.3%)		22/263 (8.4%)
Dyspepsia	17/268 (6.3%)		7/263 (2.7%)
General disorders
Headache	20/268 (7.5%)		22/263 (8.4%)
Pain	15/268 (5.6%)		18/263 (6.8%)
Abdominal pain	17/268 (6.3%)		7/263 (2.7%)
Fever	9/268 (3.4%)		6/263 (2.3%)
Chest pain	5/268 (1.9%)		8/263 (3%)
Metabolism and nutrition disorders
Hypokalemia	6/268 (2.2%)		17/263 (6.5%)
Nervous system disorders
Insomnia	22/268 (8.2%)		17/263 (6.5%)
Anxiety	9/268 (3.4%)		7/263 (2.7%)
Dizziness	9/268 (3.4%)		6/263 (2.3%)
Skin and subcutaneous tissue disorders
Pruritus	15/268 (5.6%)		16/263 (6.1%)
Vascular disorders
Hypertension	8/268 (3%)		9/263 (3.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.