PMID- 18508226 OWN - NLM STAT- MEDLINE DCOM- 20080904 LR - 20230815 IS - 0732-8893 (Print) IS - 0732-8893 (Linking) VI - 61 IP - 3 DP - 2008 Jul TI - Integrated results of 2 phase 3 studies comparing tigecycline and levofloxacin in community-acquired pneumonia. PG - 329-38 LID - 10.1016/j.diagmicrobio.2008.04.009 [doi] AB - Tigecycline (TGC), a glycylcycline, has expanded activity against Gram-positive and Gram-negative, anaerobic, and atypical bacteria. Two phase 3 studies were conducted. Hospitalized patients with community-acquired pneumonia (CAP) were randomized to intravenous (IV) TGC (100 mg followed by 50 mg bid) or IV levofloxacin (LEV) (500 mg bid). In 1 study, patients could be switched to oral LEV after at least 3 days intravenously. The coprimary efficacy end points were as follows: clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (TOC). The secondary end points were as follows: microbiologic efficacy and susceptibility to TGC for CAP bacteria. Safety evaluations were included. Eight hundred ninety-one were patients screened: 846 mITT (TGC 424, LEV 422), 574 CE (TGC 282, LEV 292). Most patients had Fine Pneumonia Severity Index II to IV (80.7% TGC, 74.4% LEV, mITT). At TOC (CE), TGC cured 253/282 patients (89.7%) and LEV cured 252/292 patients (86.3%); the absolute difference of TGC-LEV was 3.4% (95% confidence interval [CI], -2.2 to 9.1, noninferior [P < 0.001]). In c-mITT, TGC cured 319/394 patients (81.0%) and LEV cured 321/403 patients (79.7%); the absolute difference of TGC-LEV was 1.3% (95% CI -4.5 to 7.1, noninferior [P < 0.001]). The drug-related adverse events (AEs) of nausea (20.8% TGC versus 6.6% LEV) and vomiting (13.2% TGC versus 3.3% LEV) were significantly higher in TGC; elevated alanine aminotransferase (2.8% TGC versus 7.3% LEV) and aspartate aminotransferase (2.6% TGC versus 6.9% LEV) were significantly higher in LEV. Discontinuations for AEs were low (TGC, 26 patients [6.1%]; LEV, 34 patients [8.1%]). TGC appeared safe and achieved cure rates similar to LEV in hospitalized patients with CAP. FAU - Tanaseanu, Cristina AU - Tanaseanu C AD - Department of Internal Medicine, St. Pantelimon Clinical Emergency Hospital, Bucharest OP 22, Romania. cristina.tanaseanu@gmail.com FAU - Bergallo, Carlos AU - Bergallo C FAU - Teglia, Osvaldo AU - Teglia O FAU - Jasovich, Abel AU - Jasovich A FAU - Oliva, Maria Eugenia AU - Oliva ME FAU - Dukart, Gary AU - Dukart G FAU - Dartois, Nathalie AU - Dartois N FAU - Cooper, C Angel AU - Cooper CA FAU - Gandjini, Hassan AU - Gandjini H FAU - Mallick, Rajiv AU - Mallick R CN - 308 Study Group CN - 313 Study Group LA - eng SI - ClinicalTrials.gov/NCT00079885 SI - ClinicalTrials.gov/NCT00081575 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20080527 PL - United States TA - Diagn Microbiol Infect Dis JT - Diagnostic microbiology and infectious disease JID - 8305899 RN - 0 (Anti-Bacterial Agents) RN - 6GNT3Y5LMF (Levofloxacin) RN - 70JE2N95KR (Tigecycline) RN - A4P49JAZ9H (Ofloxacin) RN - FYY3R43WGO (Minocycline) SB - IM MH - Adult MH - Aged MH - Anti-Bacterial Agents/administration & dosage/adverse effects/*therapeutic use MH - Community-Acquired Infections/*drug therapy MH - Female MH - Gram-Negative Bacterial Infections MH - Haemophilus Infections/drug therapy MH - Humans MH - *Levofloxacin MH - Liver Function Tests MH - Male MH - Middle Aged MH - Minocycline/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use MH - Ofloxacin/administration & dosage/adverse effects/*therapeutic use MH - Pneumococcal Infections/drug therapy MH - Pneumonia, Bacterial/*drug therapy MH - Tigecycline MH - Treatment Outcome FIR - Abernethy, John IR - Abernethy J FIR - Adhikari, Prabha IR - Adhikari P FIR - Lynn, C IR - Lynn C FIR - Anderson, V IR - Anderson V FIR - Andrews, Charles P IR - Andrews CP FIR - Antolik, Jan IR - Antolik J FIR - Areyuna, Rebeca Georgina Northland IR - Areyuna RG FIR - Babjoniseva, Aurika IR - Babjoniseva A FIR - Bauer, Torsten IR - Bauer T FIR - Beechler, Cash Ralph IR - Beechler CR FIR - Bibi, Salah IR - Bibi S FIR - Bisits, Marta IR - Bisits M FIR - Bochan, Markian R IR - Bochan MR FIR - Bokarev, Igor IR - Bokarev I FIR - Calistru, Petre Iacob IR - Calistru PI FIR - Campos, Maria Isabel IR - Campos MI FIR - Chan, Kevin M IR - Chan KM FIR - Chavez, Eduardo Romulo Ticona IR - Chavez ER FIR - Chernyak, Valeriy IR - Chernyak V FIR - Chuang, Yin-Ching IR - Chuang YC FIR - Clark, Roderick V IR - Clark RV FIR - Counselman, Francis L IR - Counselman FL FIR - Cowan, Larry I IR - Cowan LI FIR - Danielsson, Per Erik IR - Danielsson PE FIR - Valery, Maria Ines Bueno de Andre IR - Valery MI FIR - de Barros, Joao Adriano IR - de Barros JA FIR - Freire, Antonio Tarcisio de Faria IR - Freire AT FIR - de Mattos, Waldo Luis Leite Dias IR - de Mattos WL FIR - Driver, Albert G IR - Driver AG FIR - Embil, John IR - Embil J FIR - Engelbrecht, Johannes M IR - Engelbrecht JM FIR - Ewig, Santiago IR - Ewig S FIR - Faulk, L Christine IR - Faulk LC FIR - Ferrer, Vicenc Falco I IR - Ferrer VF FIR - Feschenko, Yurii IR - Feschenko Y FIR - File, Thomas M Jr IR - File TM Jr FIR - French, Amalia Rodriguez IR - French AR FIR - Friedman, Bruce IR - Friedman B FIR - Fritscher, Carlos Cezar IR - Fritscher CC FIR - Georgiev, Ognyan IR - Georgiev O FIR - Gerrish, Catherine C IR - Gerrish CC FIR - Gezon, John A IR - Gezon JA FIR - Giordano, Philip A IR - Giordano PA FIR - Graham, Donald R IR - Graham DR FIR - Green, Jon Allen IR - Green JA FIR - Griffith, David IR - Griffith D FIR - Grimard, Doria IR - Grimard D FIR - Grossman, Colby H IR - Grossman CH FIR - Gudiol, Francesc IR - Gudiol F FIR - Guillermo, Luis IR - Guillermo L FIR - Gupta, Arvind K IR - Gupta AK FIR - Harnicarova, Adriana IR - Harnicarova A FIR - Hayes, Lloyd E IR - Hayes LE FIR - Heard, Kennon IR - Heard K FIR - Ionescu, Valentina IR - Ionescu V FIR - Iraqui, Ghali IR - Iraqui G FIR - Jacobs, Frederique IR - Jacobs F FIR - Jakob, Ernesto Julio IR - Jakob EJ FIR - Janaskova, Terezie IR - Janaskova T FIR - Jurgens, Jaco IR - Jurgens J FIR - Kamenik, Libor IR - Kamenik L FIR - Kazlauskas, Henrikas IR - Kazlauskas H FIR - Kearl, Robert A IR - Kearl RA FIR - Kelly, John J IR - Kelly JJ FIR - Klenha, Kamil IR - Klenha K FIR - Kozlov, Roman IR - Kozlov R FIR - Kumar, Preetam IR - Kumar P FIR - Kus, Jan IR - Kus J FIR - Lampron, Noel IR - Lampron N FIR - Leal, Iris Lorena Cazali IR - Leal IL FIR - Levine, Donald IR - Levine D FIR - Liebhart, Jerzy IR - Liebhart J FIR - Lode, Hartmut IR - Lode H FIR - Lorch, Daniel G Jr IR - Lorch DG Jr FIR - Lukacs, Judith IR - Lukacs J FIR - Many, Wickliffe J IR - Many WJ FIR - Marinov, Rosen IR - Marinov R FIR - Mazal, Juraj IR - Mazal J FIR - McIvor, Andrew IR - McIvor A FIR - Meriste, Sulev IR - Meriste S FIR - Metev, Hristo IR - Metev H FIR - Molnar, Sandor IR - Molnar S FIR - Montalvan, Nestor Rodolfo Sosa IR - Montalvan NR FIR - Moran, Gregory J IR - Moran GJ FIR - Moreira, Maria Auxiliadora Carmo IR - Moreira MA FIR - Milutinovic, Slobodan IR - Milutinovic S FIR - Murthy, Bangalore R S IR - Murthy BR FIR - Nonikov, Vladimir IR - Nonikov V FIR - O'Riordan, William D IR - O'Riordan WD FIR - Otero, Maria del Rayo Morfin IR - Otero Mdel R FIR - Paris, Carlos Alberto Morales IR - Paris CA FIR - Paulovic, Daniel IR - Paulovic D FIR - Pedersen, Court IR - Pedersen C FIR - Penn, Robert L IR - Penn RL FIR - Perez, Nora Patricia Quintero IR - Perez NP FIR - Popov, Dimitar IR - Popov D FIR - Pyttsep, Enn IR - Pyttsep E FIR - Rabie, Willem J IR - Rabie WJ FIR - Ramage, Anthony S IR - Ramage AS FIR - Ramirez, Julio IR - Ramirez J FIR - Ramos, Carlos Rafael Seas IR - Ramos CR FIR - Rapa, Vanda IR - Rapa V FIR - Rebedea, Ileana IR - Rebedea I FIR - Regulski, Marcin IR - Regulski M FIR - Reinhardt, John F IR - Reinhardt JF FIR - Reiterer, Pavel IR - Reiterer P FIR - Reyes, Milagros P IR - Reyes MP FIR - Rohlf, Jane IR - Rohlf J FIR - Roubec, Jaromir IR - Roubec J FIR - Rugina, Sorin IR - Rugina S FIR - Sanina, Natalia IR - Sanina N FIR - Ruiz-Palacios y Santos, Guillermo M IR - Ruiz-Palacios y Santos GM FIR - Schrock, Christian Gerald IR - Schrock CG FIR - Simon, Stuart J IR - Simon SJ FIR - Sioson, Priscilla B IR - Sioson PB FIR - Skerk, Visnja IR - Skerk V FIR - Snyman, Hans IR - Snyman H FIR - Standiford, Harold C IR - Standiford HC FIR - Starling, Carlos Ernesto Ferreira IR - Starling CE FIR - Stirbulov, Roberto IR - Stirbulov R FIR - Strausz, Janos IR - Strausz J FIR - Souza, George D IR - Souza GD FIR - Tanasescu, Coman IR - Tanasescu C FIR - Tello, Anthony M IR - Tello AM FIR - Thompson, Austin B 3rd IR - Thompson AB 3rd FIR - Tokmalaev, Anatoly IR - Tokmalaev A FIR - Tsoi, Alla IR - Tsoi A FIR - Urbina, Fernando Cruz Mendo IR - Urbina FC FIR - Van Dyk, Christo IR - Van Dyk C FIR - Vasquez, Patricia Elena Fernandez IR - Vasquez PE FIR - Villatoro, Carlos Rodolfo Mejia IR - Villatoro CR FIR - Vrooman, Peter S Jr IR - Vrooman PS Jr FIR - Weiss, Karl IR - Weiss K FIR - Yashyna, Lyudmyla IR - Yashyna L FIR - Zaidi, Syed W A IR - Zaidi SW FIR - Zolubas, Marius IR - Zolubas M EDAT- 2008/05/30 09:00 MHDA- 2008/09/05 09:00 CRDT- 2008/05/30 09:00 PHST- 2008/03/13 00:00 [received] PHST- 2008/04/15 00:00 [revised] PHST- 2008/04/17 00:00 [accepted] PHST- 2008/05/30 09:00 [pubmed] PHST- 2008/09/05 09:00 [medline] PHST- 2008/05/30 09:00 [entrez] AID - S0732-8893(08)00228-9 [pii] AID - 10.1016/j.diagmicrobio.2008.04.009 [doi] PST - ppublish SO - Diagn Microbiol Infect Dis. 2008 Jul;61(3):329-38. doi: 10.1016/j.diagmicrobio.2008.04.009. Epub 2008 May 27.