Tigecycline in combination with other antimicrobials: a review of in vitro, animal and case report studies

Entenza, José M.; Moreillon, Philippe

doi:10.1016/j.ijantimicag.2008.11.006

Cited by 92 publications

(78 citation statements)

References 65 publications

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“…Pournaras et al also showed that MERϩTIG is not synergic in vitro (21). Previous studies of nonlethal and nonsystemic infections were discordant about the antagonistic effects of TIGϩMER in vivo (20,22) and in vitro (23). Further investigation using this combination is required, but we believe that TIGϩMER should be used with caution for treatment of infections due to KPC-producing isolates.…”

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confidence: 62%

Activity of Antimicrobial Combinations against KPC-2-Producing Klebsiella pneumoniae in a Rat Model and Time-Kill Assay

Toledo

Aranha

Arend³

et al. 2015

Antimicrob Agents Chemother

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f This study evaluated the efficacy of tigecycline (TIG), polymyxin B (PMB), and meropenem (MER) in 80 rats challenged with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae infection. A time-kill assay was performed with the same strain. Triple therapy and PMB؉TIG were synergistic, promoted 100% survival, and produced negative peritoneal cultures, while MER؉TIG showed lower survival and higher culture positivity than other regimens (P ‫؍‬ 0.018) and was antagonistic. In vivo and in vitro studies showed that combined regimens, except MER؉TIG, were more effective than monotherapies for this KPC-producing strain. Infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are associated with therapeutic failure and increased mortality (1-5). It has been suggested that antibiotic combination might be a better alternative compared to monotherapy for treatment of KPC-producing isolates (4-9); however, further investigation on this therapeutic strategy is required (10, 11).In the present study, we evaluated the efficacy of regimes for a KPC-producing K. pneumoniae strain in an experimental model of systemic infection and in a time-kill assay (TKA).A KPC-producing K. pneumoniae strain, coded RM-1209, was isolated from a patient's blood and identified by Vitek 2 (bioMérieux, Craponne, France) in 2012. Antibiotic MICs were determined by agar dilution and interpreted according to CLSI and EUCAST for tigecycline (TIG) (12, 13). The strain presented MICs of Ͼ32 mg/liter, 1 mg/liter, and 0.5 mg/liter for meropenem (MER), tigecycline, and polymyxin B (PMB), respectively. Detection of the bla KPC gene was performed with BigDye v1.1 Sequencing kits (Applied Biosystems, Foster City, CA, USA), and KPC-2 was confirmed at databases queried by NCBI BLAST (6).The study was approved by the ethical committee, according to the Protocol for the Protection and Welfare of Animals (European Union). The animal model has been previously described (13). In brief, male and female immunocompetent Wistar rats weighing between 190 and 300 g were randomized into each treatment group. Absence of immunosuppression demanded administration of highly concentrated inoculums with 1.5 ϫ 10 10 CFU/ml. This solution, when diluted 1:20 presents an absorbance of 0.546 at 625 nm wavelength on spectrophotometry (corresponding to tube 50 of nephelometric scale). Seven groups of 10 rats were treated with the following regimens: MER, TIG, PMB, MERϩPMB, MERϩTIG, PMBϩTIG, or PMBϩMERϩTIG. Ten rats were untreated (control group). The sample size (80 rats) was calculated using the formula n ϭ z2PQ/d2 based on the expected proportion of deaths (50%) and 8% standard error with an 80% statistical power.Animals were injected with a 0.7-ml intraperitoneal aliquot of 1.5 ϫ 10 10 CFU/ml KPC-producing K. pneumoniae inoculum in the log growth state (14). After infection, rats received antimicrobials intraperitoneally, TIG (Tygacil) at 7 mg/kg of body weight every 12 h (15, 16), PMB (polymyxin B) at 2 mg/kg every 12 h (17, 18), or MER ...

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confidence: 62%

Activity of Antimicrobial Combinations against KPC-2-Producing Klebsiella pneumoniae in a Rat Model and Time-Kill Assay

Toledo

Aranha

Arend³

et al. 2015

Antimicrob Agents Chemother

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“…New treatment strategies have included the use of select antibiotics in synergy. Using the checkerboard method, some synergism has been observed between tigecycline and TMP-SMX, and between tigecycline and amikacin, against S. maltophilia (100,349). In vitro pharmacodynamic model results revealed that TMP-SMX in combination with either ciprofloxacin, ceftazidime, or tobramycin demonstrated higher bactericidal efficacy (P Ͻ 0.0001) against S. maltophilia clinical isolates than TMP-SMX alone (379).…”

Section: New Treatment Strategiesmentioning

confidence: 99%

Stenotrophomonas maltophilia: an Emerging Global Opportunistic Pathogen

2012

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SUMMARY Stenotrophomonas maltophilia is an emerging multidrug-resistant global opportunistic pathogen. The increasing incidence of nosocomial and community-acquired S. maltophilia infections is of particular concern for immunocompromised individuals, as this bacterial pathogen is associated with a significant fatality/case ratio. S. maltophilia is an environmental bacterium found in aqueous habitats, including plant rhizospheres, animals, foods, and water sources. Infections of S. maltophilia can occur in a range of organs and tissues; the organism is commonly found in respiratory tract infections. This review summarizes the current literature and presents S. maltophilia as an organism with various molecular mechanisms used for colonization and infection. S. maltophilia can be recovered from polymicrobial infections, most notably from the respiratory tract of cystic fibrosis patients, as a cocolonizer with Pseudomonas aeruginosa . Recent evidence of cell-cell communication between these pathogens has implications for the development of novel pharmacological therapies. Animal models of S. maltophilia infection have provided useful information about the type of host immune response induced by this opportunistic pathogen. Current and emerging treatments for patients infected with S. maltophilia are discussed.

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“…For treatment of endocarditis, fosfomycin showed synergistic activity with high-dose daptomycin against Staphylococcus aureus (22). Tigecycline, the first glycylcycline in clinical use, has an expanded broadspectrum activity, including activity against resistant Gram-negative bacilli, when combined with other antimicrobials (23). Colistin has been increasingly used in the last decade because of the emergence of multidrug-resistant Gram-negative bacilli in the past years, especially in combination with other drugs (17,24).…”

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confidence: 99%

Activities of Fosfomycin, Tigecycline, Colistin, and Gentamicin against Extended-Spectrum-β-Lactamase-Producing Escherichia coli in a Foreign-Body Infection Model

Corvec

Tafin

Bétrisey

et al. 2013

Antimicrob Agents Chemother

105

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Limited antimicrobial agents are available for the treatment of implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli. We compared the activities of fosfomycin, tigecycline, colistin, and gentamicin (alone and in combination) against a CTX-M15-producing strain of Escherichia coli (Bj HDE-1) in vitro and in a foreign-body infection model. The MIC and the minimal bactericidal concentration in logarithmic phase (MBC log ) and stationary phase (MBC stat ) were 0.12, 0.12, and 8 g/ml for fosfomycin, 0.25, 32, and 32 g/ml for tigecycline, 0.25, 0.5, and 2 g/ml for colistin, and 2, 8, and 16 g/ml for gentamicin, respectively. In time-kill studies, colistin showed concentration-dependent activity, but regrowth occurred after 24 h. Fosfomycin demonstrated rapid bactericidal activity at the MIC, and no regrowth occurred. Synergistic activity between fosfomycin and colistin in vitro was observed, with no detectable bacterial counts after 6 h. In animal studies, fosfomycin reduced planktonic counts by 4 log 10 CFU/ml, whereas in combination with colistin, tigecycline, or gentamicin, it reduced counts by >6 log 10 CFU/ml. Fosfomycin was the only single agent which was able to eradicate E. coli biofilms (cure rate, 17% of implanted, infected cages). In combination, colistin plus tigecycline (50%) and fosfomycin plus gentamicin (42%) cured significantly more infected cages than colistin plus gentamicin (33%) or fosfomycin plus tigecycline (25%) (P < 0.05). The combination of fosfomycin plus colistin showed the highest cure rate (67%), which was significantly better than that of fosfomycin alone (P < 0.05). In conclusion, the combination of fosfomycin plus colistin is a promising treatment option for implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli.

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Tigecycline in combination with other antimicrobials: a review of in vitro, animal and case report studies

Cited by 92 publications

References 65 publications

Activity of Antimicrobial Combinations against KPC-2-Producing Klebsiella pneumoniae in a Rat Model and Time-Kill Assay

Activity of Antimicrobial Combinations against KPC-2-Producing Klebsiella pneumoniae in a Rat Model and Time-Kill Assay

Stenotrophomonas maltophilia: an Emerging Global Opportunistic Pathogen

Activities of Fosfomycin, Tigecycline, Colistin, and Gentamicin against Extended-Spectrum-β-Lactamase-Producing Escherichia coli in a Foreign-Body Infection Model

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