A randomized trial of tigecycline versus ampicillin-sulbactam or amoxicillin-clavulanate for the treatment of complicated skin and skin structure infections

Peter Matthews, Marc Alpert, Galia Rahav, Denise Rill, Edward Zito, David Gardiner, Ron Pedersen, Timothy Babinchak, Paul C McGovern, Tigecycline 900 cSSSI Study Group, Marc Alpert, Peter Armstrong, Charles Bailey, German Berbel, Jack Bernstein, Jose Bordon, Lou Ann Bruno-Murtha, Russell Caprioli, Kathleen Casey, Tom Chiang, Allan Churukian, William Flynn, Donald Graham, Zijun Hao, Kenneth Kalassian, Richard Kohler, Juliet Lee, William Leeds, Christopher Lucasti, Gregory Malanoski, Tien Ko, Venkat Minnaganti, Miguel Mogyoros, Bill Morgan, Charles Moss, Satish Muluk, Rekha Murthy, William O'Riordan, Francis Pien, Hiram Polk, James B Augustinsky, Michelle Salvaggio, Leon Smith, Raymond Smith, R Scott Stienecker, Byungse Suh, Jose Vazquez, Dennis E Weiland, Mireya Wessolossky, Jonathan Zenilman, Carl Abraham, Richard Nathan, Phillip Sanchez, Ian Baird, Charles Callahan, Christian G Schrock, William Lau, Markian R Bochan, Michael Somero, Stanley R Klein, Charles Bellows 3rd, Annick D'Hooghe, Françoise Ceulemans, Jacques Gaillat, Bernard Garo, Christian Eckmann, Joerg Haier, Fredy Suter, Aldo Bertani, Francisco Acin, Manuel E Jiménez-Mejías, Ignacio Blanes, Dolores Sousa Regueiro, Nedim Cakir, Rabin Saba, Michael Giladi, Galia Rahav, Souha Kanj-Sharara, Abdulhakeem Okab Ahmed al Thaqafi, Wai-Man Ng, Andrew Burd, Utkrant Kurlekar, N Raghupathi Rao, Andhra Pradesh, T Devarajan, Junyong Choi, Yeonsook Kim, Hyunjoo Pai, Yoon-Soo Park, Suresh Kumar, Ting Soo Chow, Armando Crisostomo, Alex Erasmo, Alex Erasmo, Jose R Reyes, Jenny Low, M M Basson, Johannes Breedt, Eugene Marais, P A Matthews, D P Ross, His-Hsun Lin, Chun-Hsing Liao, Hsiang-Chi Kung, Vitoon Chinswangwatanakul, Kumthorn Malathum, Terapong Tantawichien, Sergio Ricardo Filho Penteado, Fernando Cardoso, Roosevelt Fajardo Gomez, David Fernandez Velazquez, Juan Carlos Tinoco-Favila, Andre Poirier, Louis Valiquette, Karl Weiss, Doria Grimard, John M A Embil, Steven E Sanche, Ken Smith, Sylvain Chouinard, Patrick Dolcé, Peter Matthews, Marc Alpert, Galia Rahav, Denise Rill, Edward Zito, David Gardiner, Ron Pedersen, Timothy Babinchak, Paul C McGovern, Tigecycline 900 cSSSI Study Group, Marc Alpert, Peter Armstrong, Charles Bailey, German Berbel, Jack Bernstein, Jose Bordon, Lou Ann Bruno-Murtha, Russell Caprioli, Kathleen Casey, Tom Chiang, Allan Churukian, William Flynn, Donald Graham, Zijun Hao, Kenneth Kalassian, Richard Kohler, Juliet Lee, William Leeds, Christopher Lucasti, Gregory Malanoski, Tien Ko, Venkat Minnaganti, Miguel Mogyoros, Bill Morgan, Charles Moss, Satish Muluk, Rekha Murthy, William O'Riordan, Francis Pien, Hiram Polk, James B Augustinsky, Michelle Salvaggio, Leon Smith, Raymond Smith, R Scott Stienecker, Byungse Suh, Jose Vazquez, Dennis E Weiland, Mireya Wessolossky, Jonathan Zenilman, Carl Abraham, Richard Nathan, Phillip Sanchez, Ian Baird, Charles Callahan, Christian G Schrock, William Lau, Markian R Bochan, Michael Somero, Stanley R Klein, Charles Bellows 3rd, Annick D'Hooghe, Françoise Ceulemans, Jacques Gaillat, Bernard Garo, Christian Eckmann, Joerg Haier, Fredy Suter, Aldo Bertani, Francisco Acin, Manuel E Jiménez-Mejías, Ignacio Blanes, Dolores Sousa Regueiro, Nedim Cakir, Rabin Saba, Michael Giladi, Galia Rahav, Souha Kanj-Sharara, Abdulhakeem Okab Ahmed al Thaqafi, Wai-Man Ng, Andrew Burd, Utkrant Kurlekar, N Raghupathi Rao, Andhra Pradesh, T Devarajan, Junyong Choi, Yeonsook Kim, Hyunjoo Pai, Yoon-Soo Park, Suresh Kumar, Ting Soo Chow, Armando Crisostomo, Alex Erasmo, Alex Erasmo, Jose R Reyes, Jenny Low, M M Basson, Johannes Breedt, Eugene Marais, P A Matthews, D P Ross, His-Hsun Lin, Chun-Hsing Liao, Hsiang-Chi Kung, Vitoon Chinswangwatanakul, Kumthorn Malathum, Terapong Tantawichien, Sergio Ricardo Filho Penteado, Fernando Cardoso, Roosevelt Fajardo Gomez, David Fernandez Velazquez, Juan Carlos Tinoco-Favila, Andre Poirier, Louis Valiquette, Karl Weiss, Doria Grimard, John M A Embil, Steven E Sanche, Ken Smith, Sylvain Chouinard, Patrick Dolcé

Abstract

Background: Complicated skin and skin structure infections (cSSSIs) frequently result in hospitalization with significant morbidity and mortality.

Methods: In this phase 3b/4 parallel, randomized, open-label, comparative study, 531 subjects with cSSSI received tigecycline (100 mg initial dose, then 50 mg intravenously every 12 hrs) or ampicillin-sulbactam 1.5-3 g IV every 6 hrs or amoxicillin-clavulanate 1.2 g IV every 6-8 hrs. Vancomycin could be added at the discretion of the investigator to the comparator arm if methicillin-resistant Staphylococcus aureus (MRSA) was confirmed or suspected within 72 hrs of enrollment. The primary endpoint was clinical response in the clinically evaluable (CE) population at the test-of-cure (TOC) visit. Microbiologic response and safety were also assessed. The modified intent-to-treat (mITT) population comprised 531 subjects (tigecycline, n = 268; comparator, n = 263) and 405 were clinically evaluable (tigecycline, n = 209; comparator, n = 196).

Results: In the CE population, 162/209 (77.5%) tigecycline-treated subjects and 152/196 (77.6%) comparator-treated subjects were clinically cured (difference 0.0; 95% confidence interval [CI]: -8.7, 8.6). The eradication rates at the subject level for the microbiologically evaluable (ME) population were 79.2% in the tigecycline treatment group and 76.8% in the comparator treatment group (difference 2.4; 95% CI: -9.6, 14.4) at the TOC assessment. Nausea, vomiting, and diarrhea rates were higher in the tigecycline group.

Conclusions: Tigecycline was generally safe and effective in the treatment of cSSSIs.

Trial registration: ClinicalTrials.gov NCT00368537.

Figures

Figure 1
Figure 1
Analysis population. Footnote: *Subjects could be excluded for more than 1 reason. ITT, intent-to-treat; mITT, modified intent-to-treat; TGC, tigecycline; Comp, comparator. c-mITT, clinical modified intent-to-treat; TOC, test-of-cure; m-mITT, microbiologic-modified intent-to-treat; CE, clinically evaluable; ME, microbiologically evaluable.

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