Activity of Tigecycline (GAR936) against Acinetobacter baumannii Strains, Including Those Resistant to Imipenem (original) (raw)
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Tigecycline: A New Treatment Choice Against Acinetobacter baumannii
Recent Patents on Anti-Infective Drug Discovery, 2008
Acinetobacter baumannii (AB) is a gram-negative organism that has emerged recently as a major cause of nosocomial infections, because of the extent of its antimicrobial resistance and its persistence in the hospital environment, where intensive care units are the place of greatest risk for acquiring AB. There is no treatment of choice for AB and it's treatment is based on clinical experience and in vitro susceptibility testing. Also, nowadays Acinetobacter resistance to carbapenems is common and isolates resistant to colistin and polymyxin B have been reported. Tigecycline, the 9-tert-butyl-glycylamido derivative of minocycline, exhibits a broad-spectrum of activity against numerous pathogens, including AB and several reports place it among the antimicrobials with lower MIC for AB. Tigecycline overcomes the two major mechanisms of resistance to tetracyclines (ribosomal protection and efflux), but tigecycline resistance emerging during therapy has been reported. Tigecycline efficacy has been demonstrated in clinical studies in skin and skin structure infections and in complicated intra-abdominal infections but, although it seems a good alternative for the treatment of AB infections, there is few evidence about its use in these cases and more clinical experience and adequate trials are needed. The present review shows the recent patents related to treatment by tigecycline in different AB infections.
Annals of Clinical Microbiology and Antimicrobials, 2009
Infections sustained by multidrug-resistant (MDR) and pan-resistant Acinetobacter baumannii have become a challenging problem in Intensive Care Units. Tigecycline provided new hope for the treatment of MDR A. baumannii infections, but isolates showing reduced susceptibility have emerged in many countries, further limiting the therapeutic options. Empirical combination therapy has become a common practice to treat patients infected with MDR A. baumannii, in spite of the limited microbiological and clinical evidence supporting its efficacy. Here, the in vitro interaction of tigecycline with seven commonly used anti-Acinetobacter drugs has been assessed.
Jundishapur Journal of Microbiology, 2013
Background: Acinetobacter species, specially, Acinetobacter baumannii, is known, as an important opportunistic pathogen, with a variety of infections such as pneumonia, bacteraemia, meningitis, urinary tract, skin and soft tissue infections, associated with high mortality. High prevalence of multidrug resistance in A. baumannii, limits our therapeutic choices in the treatment of infections caused by this bacterium. Objectives: The current study aimed to determine in vitro activity of tigecycline and colistin against clinical isolates of MDR A. baumannii, from patients admitted in ICUs Tehran hospitals. Material and Methods: This study was conducted from March 2009 to November 2010, on a total of 91 Acinetobacter species isolated from clinical specimens in ICUs. All isolates were subjected to PCR to detect blaOXA-51-like gene that is unique to A. baumannii. The antimicrobial susceptibility for 13 different antibiotics was tested. Results: A. baumannii (blaOXA-51-like gene) was detected in 84 (92.30%) isolates.Resistance rates in A. baumannii, were found to be for Imipenem 50 (59.52%), Gentamicin 65 (77.38%), Ciprofloxacin 81 (96.42%), Amikacin 44 (52.38%), Cefotaxime 81 (96.42%), Cefepime 69 (82.14%), Ceftazidim 81 (96.42%), Meropenem 74 (88.09%), Trimethoprim-sulfamethoxazole 78 (92.85%), Aztreonam 82 (97.61%), Colistin and Polymyxin-B 0%. No interpretive criteria have been approved for tigecycline against Acinetobacter spp. so; the results were interpreted by the criteria recommended by Jones, and US FDA for Enterobacteriaceae. Resistance rates for tigecycline were 3 (3.57%) (Jones criteria) and 19 (22.61%) (FDA criteria). Conclusions: It is clear that new antimicrobials are needed to treat MDR A. baumannii. Polymyxins and tigecycline are among the few antibiotics available to treat infections with these bacteria but little was known about the antimicrobial activity of these agents. The Present study provided valuable information about the effects of the above mentioned drugs that can be used for health policy. It should be noted that there is a need for regular surveillance of bacterial resistance to these antimicrobial agents.
Journal of Antimicrobial Chemotherapy, 2009
Multidrug-resistant Acinetobacter baumannii (MRAB) is an increasing problem in UK hospitals, with many strains now resistant to all available antibiotics except polymyxins. Tigecycline has been used for the treatment of MRAB as it demonstrates activity in vitro, but there are limited data on its clinical efficacy in Gram-negative infections, especially those involving the lower respiratory tract or bacteraemia. A retrospective study of the clinical and microbiological outcomes of all patients treated with tigecycline for MRAB over an 18 month period was undertaken. Thirty-four patients received tigecycline for MRAB or polymicrobial infection involving MRAB. Twenty-three (68%) had a positive clinical outcome: microbiological clearance was demonstrated in 10 of these. The overall mortality was 41% (n = 14), with nine deaths directly attributable to sepsis. Three patients had episodes of Gram-negative bacteraemia while receiving treatment with tigecycline, with documented resistance occurring in one patient. Overall, the correlation between microbiological and clinical outcomes was poor. While tigecycline retains excellent in vitro activity against MRAB, its clinical efficacy remains uncertain. A prospective study, including the use of tigecycline in combination with other antimicrobial agents, should be undertaken to define its role in the treatment of MRAB.
Annals of Clinical Microbiology and Antimicrobials, 2008
Background In a recent multi-centre Italian survey (2003–2004), conducted in 45 laboratories throughout Italy with the aim of monitoring microorganisms responsible for severe infections and their antibiotic resistance, Acinetobacter baumannii was isolated from various wards of 9 hospitals as one of the most frequent pathogens. One hundred and seven clinically significant strains of A. baumannii isolates were included in this study to determine the in vitro activity of tigecycline and comparator agents. Methods Tests for the susceptibility to antibiotics were performed by the broth microdilution method as recommended by CLSI guidelines. The following antibiotics were tested: aztreonam, piperacillin/tazobactam, ampicillin/sulbactam, ceftazidime, cefepime, imipenem, meropenem tetracycline, doxycycline, tigecycline, gentamicin, amikacin, ciprofloxacin, colistin, and trimethoprim/sulphametoxazole. The PCR assay was used to determine the presence of OXA, VIM, or IMP genes in the carbapenem resistant strains. Results A. baumannii showed widespread resistance to ceftazidime, ciprofloxacin and aztreonam in more than 90% of the strains; resistance to imipenem and meropenem was 50 and 59% respectively, amikacin and gentamicin were both active against about 30% of the strains and colistin about 99%, with only one strain resistant. By comparison with tetracyclines, tigecycline and doxycycline showed a higher activity. In particular, tigecycline showed a MIC90 value of 2 mg/L and our strains displayed a unimodal distribution of susceptibility being indistinctly active against carbapenem-susceptible and resistant strains, these latter possessed OXA-type variant enzymes. Conclusion In conclusion, tigecycline had a good activity against the MDR A. baumannii strains while maintaining the same MIC90 of 2 mg/L against the carbapenem-resistant strains.
Journal of Chemotherapy, 2012
The in vitro susceptibility of clinical and environmental isolates of Acinetobacter baumannii to tigecycline and other antibiotics was determined by disk diffusion method. The E-test was used to determine the minimum inhibitory concentration (MIC). The growth curves of tigecycline treated environmental and clinical strains were established. Fifty-seven percent and 75% of the clinical and environmental isolates were MDR strains, respectively. Ninety-five percent of the clinical isolates were susceptible to tigecycline and 5% showed intermediate resistance with MIC ranging between 0.032 and 3 mg/l. Tigecycline susceptible and intermediate resistance among the environmental isolates were 40% and 60%, respectively, with a significantly lower MIC range of 0.5-4 mg/l. The bacterial growth curves demonstrated the higher ability of the environmental strains to tolerate the antibiotic effects than the clinical strains. The relatively high resistance profile among the environmental isolate suggests an insidious emergence of tigecycline resistance amongst A. baumannii. Strict infection control procedures are imperative to prevent the dissemination of tigecycline-resistant A. baumannii strains in the hospital environment.
Electronic physician
The Acinetobacter species, particularly A. baumannii, has emerged as one of the main causes of nosocomial infections in recent years. The high prevalence of drug resistance in A. baumannii limits the therapeutic options for treating infections caused by these bacteria. The objective of this study was to determine the in vitro activity of Tigecycline and Colistin against clinical isolates of A. baumannii in Tehran and Bandar Abbas, Iran. This study was conducted from March 2009 to November 2010 at three hospitals in Tehran and Bandar Abbas, Iran, using 165 Acinetobacter species isolated from clinical specimens. All isolates were subjected to PCR to detect bla OXA-51-like genes that are unique to Acinetobacter baumannii. Isolates that gave a band for the bla OXA-51-like genes were identified as A. baumannii. Anti-microbial susceptibility tests were performed for Tigecycline, Colistin, and other antibiotics. Sensitivity rates to Colistin and Polymyxin-B were 100%. Resistance rates for ...
Antimicrobial Agents and Chemotherapy, 2007
The activities of tigecycline alone and in combination with other antimicrobials are not well defined for carbapenem-intermediate or -resistant Acinetobacter baumannii (CIRA). Pharmacodynamic activity is even less well defined when clinically achievable serum concentrations are considered. Antimicrobial susceptibility testing of clinical CIRA isolates from 2001 to 2005 was performed by broth or agar dilution, as appropriate. Tigecycline concentrations were serially increased in time-kill studies with a representative of the most prevalent carbapenem-resistant clone (strain AA557; imipenem MIC, 64 mg/liter). The in vitro susceptibility of the strain was tested by time-kill studies in duplicate against the average free serum steady-state concentrations of tigecycline alone and in combination with various antimicrobials. Ninetythree CIRA isolates were tested and were found to have the following antimicrobial susceptibility profiles: tigecycline, MIC 50 of 1 mg/liter and MIC 90 of 2 mg/liter; minocycline, MIC 50 of 0.5 mg/liter and MIC 90 of 8 mg/liter; doxycycline, MIC 50 of 2 mg/liter and MIC 90 of >32 mg/liter; ampicillin-sulbactam, MIC 50 of 48 mg/liter and MIC 90 of 96 mg/liter; ciprofloxacin, MIC 50 of >16 mg/liter and MIC 90 of >16 mg/liter; rifampin, MIC 50 of 4 mg/liter and MIC 90 of 8 mg/liter; polymyxin B, MIC 50 of 1 mg/liter and MIC 90 of 1 mg/liter; amikacin, MIC 50 of 32 mg/liter and MIC 90 of >32 mg/liter; meropenem, MIC 50 of 16 mg/liter and MIC 90 of >128 mg/liter; and imipenem, MIC 50 of 4 mg/liter and MIC 90 of 64 mg/liter. Among the tetracyclines, the isolates were more susceptible to tigecycline than minocycline and doxycycline, according to FDA breakpoints (95%, 88%, and 71% of the isolates were susceptible to tigecycline, minocycline, and doxycycline, respectively). Concentration escalation studies with tigecycline revealed a maximal killing effect near the MIC, with no additional extent or rate of killing at concentrations 2؋ to 4؋ the MIC for tigecycline. Time-kill studies demonstrated indifference for tigecycline in combination with the antimicrobials tested. Polymyxin B, minocycline, and tigecycline are the most active antimicrobials in vitro against CIRA. Concentration escalation studies demonstrate that tigecycline may need to approach concentrations higher than those currently achieved in the bloodstream to adequately treat CIRA bloodstream infections. Future studies should evaluate these findings in vivo.
Journal of Antimicrobial Chemotherapy, 2008
New antibacterial agents are required for the treatment of infections caused by multidrugresistant (MDR) Acinetobacter spp. Whether tigecycline constitutes an effective treatment option or not, is not well established. We sought to evaluate the available evidence regarding the microbiological activity and clinical effectiveness of tigecycline for MDR (including the subset of carbapenemresistant) Acinetobacter spp. Methods: We searched PubMed for relevant articles and extracted/evaluated the available evidence. Results: We identified 22 microbiological studies reporting data for 2384 Acinetobacter spp. (1906 Acinetobacter baumannii). Susceptibility of at least 90% of the Acinetobacter isolates to tigecycline (with an MIC breakpoint of susceptibility 2 mg/L) was noted in 9/18 studies reporting data on MDR Acinetobacter and in 7/15 studies reporting specific data on carbapenem-resistant Acinetobacter. In an additional study reporting data for both resistance categories, adequate susceptibility of Acinetobacter spp. was observed by one (broth microdilution) of the methods employed. The effectiveness of tigecycline for MDR Acinetobacter infections was evaluated in eight identified clinical studies, reporting retrospective data regarding 42 severely ill patients, among whom 31 had respiratory tract infection (in 4 cases with secondary bacteraemia) and 4 had bacteraemia. Tigecycline therapy (in combination with other antibiotics in 28 patients) was effective in 32/42 cases. In three cases, resistance to tigecycline developed during treatment. Conclusions: Tigecycline showed considerable, though not consistent, antimicrobial activity against MDR (including carbapenem-resistant) Acinetobacter spp. However, data to support its clinical use, particularly for ventilator-associated pneumonia or bacteraemia, caused by these pathogens, are still limited.
European Journal of Clinical Microbiology & Infectious Diseases, 2010
The in vivo activity of tigecycline was evaluated in an experimental pneumonia model (C57BL/6 mice) by Acinetobacter baumannii. Two clinical strains were used: minimum inhibitory concentrations (MICs) of imipenem and tigecycline 1 and 2 µg/mL (imipenem-susceptible, IPM-S), and 8 and 2 µg/mL (imipenem-intermediate, IPM-I), respectively. For imipenem (30 mg/Kg), ∆T/CMI (h) were 1.04 and 0.51 for IPM-S and IPM-I, respectively. For tigecycline (5 mg/Kg), the area under the concentrationtime curve (AUC)/MIC 0-24 h (serum and lung) were 9.24 and 4.37 (for the two strains), respectively. In the efficacy experiments with the IPM-S, imipenem (log CFU/g 3.59± 0.78, p = 0.006) and tigecycline (2.82 ± 1.2, p = 0.054) decreased the bacterial counts in lungs with respect to its controls; with the IPM-I, both imipenem (1.21±0.52, p= 0.002) and tigecycline (3.21±0.28, p=0.035) decreased the bacterial counts with respect to the controls. In the survival experiments, with the IPM-S, the mortality was the same in the control (67%) and in the tigecycline (77%) groups, and imipenem reduced it (21%, p=0.025); with the IPM-I, the mortality was the same in the control (87%) and in the tigecycline (85%) groups, and imipenem (0%) reduced it (p<0.001). In summary, the present study shows that tigecycline is less efficacious than imipenem in the treatment of experimental A. baumannii pneumonia caused by IPM-S and IPM-I strains.