Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ertapenem (MK-0826) is a novel, long-acting parenteral carbapenem. The purpose of this in vitro study was to test ertapenem's activity against a collection of multiply-resistant strains of gram-positive and -negative bacteria isolated from locations worldwide, and to examine its bactericidal activity and ability to act in a synergistic manner in combination with other antimicrobial agents. Ertapenem was active against a variety of gram-negative pathogens, with particular potency noted for Escherichia coli and Klebsiella pneumoniae (MIC90s < or =0.015-0.5 microg/mL) including extended spectrum beta-lactamase producing strains. Less ertapenem activity was seen against Pseudomonas aeruginosa, especially ceftazidime-resistant strains (MIC50 16 microg/mL). Except for enterococci, ertapenem was active against most gram-positive species, including beta-haemolytic streptococci (MIC90 0.03 microg/mL; 100% susceptible), viridans group streptococci (MIC90 2 microg/mL; 98.1% susceptible), and penicillin-susceptible Streptococcus pneumoniae (MIC90 < or =0.015 microg/mL; 100% susceptible). Ertapenem was also very potent against Haemophilus influenzae (MIC90 0.25 microg/mL; 100% susceptible). Bactericidal action was observed versus staphylococci, E. coli, and K. pneumoniae, and at least an additive effect was detected against the majority of the strains tested when ertapenem was combined with ciprofloxacin or gentamicin. These results from testing 902 organisms indicate that ertapenem appears to be a promising broad-spectrum carbapenem with a possible role against some emerging resistant species.
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PMID:In vitro evaluation of ertapenem (MK-0826), a long-acting carbapenem, tested against selected resistant strains. 1158 78

Ertapenem is a new 1-beta-methyl carbapenem, stable to dehydropeptidase, which binds preferable to penicillin-binding proteins (PBP) 2 and 3. Ertapenem has a broad antibacterial spectrum with MIC90 values < 0.5 mg/l for penicillin-susceptible Streptococcus pneumoniae, Streptococcus pyogenes, methicillin-sensitive Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Citrobacter spp., Klebsiella spp., Serratia spp., Proteus spp., Clostridium perfringens, Fusobacterium spp. Peptostreptococcus spp. and anaerobic Streptococcus spp. Ertapenem exhibits a bactericidal mode of action as shown by time-killing curves and exhibits a short PAE of 1.4 - 2.6 h against the Gram-positive strains but no PAE against Gram-negative strains. In an infection model in mice, it has been shown that ertapenem and imipenem were highly efficacious at a level of 2 mg/kg in bacterial clearance in comparison to ceftriaxone, cefepime, ceftazidime, cefazolin, cefonicid, cefotaxime and meropenem. In comparison to other available carbapenems, ertapenem has a long half-life of 4.5 h and is developed as a single daily dose carbapenem. The protein binding is dose-dependent and is estimated to 94% at concentrations under 100 mg/l and approximately 85% at 300 mg/l. Cmax after a dose of 1 g in healthy volunteers has been estimated to 190 mg/l. Given the pharmacokinetic/pharmacodynamic data, it may be predicted that ertapenem will have an effect on most Gram-positive and Gram-negative bacteria with the exception of Pseudomonas aeruginosa, Enterococcus spp. and Acinetobacter spp. For pathogens with a MIC of 0.5 mg/l, the estimated T > MIC will be 50% (of 24 h) and for pathogens with a MIC of 1 mg/l 31%. For anaerobic bacteria with MIC values between 1-2 mg/l, the T > MIC may not be sufficient for bacterial eradication. However, clinical trials have to confirm this hypothesis.
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PMID:Ertapenem: a new carbapenem. 1177 42

Broth or agar dilution susceptibility test results for Enterobacteriaceae (11,775 strains), anaerobes (2888 strains), staphylococci (2206 strains), Haemophilus spp. (840 strains), group A streptococci (280 strains), group B streptococci (269 strains), Streptococcus pneumoniae (709 strains), and 160 other streptococci were analyzed to identify surrogate antimicrobial agents to predict susceptibility to ertapenem. Ertapenem MIC interpretive categories approved by the United States FDA were compared to those of imipenem, oxacillin (staphylococci), or penicillin (streptococci). Ertapenem resistance was rare (1.2%) among 8187 consecutively collected clinical isolates of Enterobacteriaceae, including a large proportion of isolates from intensive care units. Absolute categorical agreement between ertapenem and imipenem, and very major (false susceptible) and major errors (false resistant) using imipenem to predict ertapenem results were 97.2%, 0.9%, and 0.4%, respectively, for Enterobacteriaceae (10,992 strains tested against both drugs) and 99.0%, 0.2%, and 0% for anaerobes. All Haemophilus spp., groups A and B streptococci, penicillin-susceptible and -intermediate S. pneumoniae, and other penicillin-susceptible streptococci were susceptible to ertapenem. All oxacillin-susceptible Staphylococcus aureus were ertapenem susceptible, except 1 that was intermediate. Surrogate antimicrobial agents that can be used to reliably predict ertapenem susceptibility by MIC tests are imipenem for Enterobacteriaceae and anaerobes, oxacillin for staphylococci, and penicillin for streptococci.
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PMID:Use of surrogate antimicrobial agents to predict susceptibility to ertapenem. 1205 30

This study compared the in vitro activity of ertapenem, ceftriaxone, cefepime, ciprofloxacin and amoxicillin-clavulanate against 381 aerobic and facultative bacterial pathogens isolated from 320 patients with acute bacterial exacerbation of chronic bronchitis or community-acquired pneumonia. Streptococcus pneumoniae and Haemophilus influenzae accounted for 54.6% of the isolates. The ertapenem MIC was < or =2 mg/L for 98.4% of isolates and > or =8 mg/L for 1.0% (all methicillin-resistant Staphylococcus aureus). Ertapenem had the most potent activity against Enterobacteriaceae, Moraxella catarrhalis, and methicillin-susceptible S. aureus, and its activity against H. influenzae and H. parainfluenzae, all strains of which were susceptible, was not altered by beta-lactamase production. Only one S. pneumoniae strain, a penicillin-resistant isolate, was resistant to ertapenem. Ertapenem was highly active in vitro against pyogenic bacteria recovered from patients with community-acquired lower respiratory tract infections.
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PMID:Comparative in vitro activity of ertapenem against bacterial pathogens isolated from patients with lower respiratory tract infections. 1244 16

The in vitro activity of ertapenem against bacterial pathogens isolated from patients with moderate to severe complicated intra-abdominal, complicated skin/skin structure, acute pelvic, or complicated urinary tract infection or community acquired pneumonia was compared to ceftriaxone and piperacillin-tazobactam and related to known plasma concentrations of the three agents. Ertapenem was more potent against methicillin-susceptible Staphylococcus aureus (MSSA) than ceftriaxone and piperacillin-tazobactam and was more potent and more active than both of these agents against Enterobacteriaceae and anaerobes. Piperacillin-tazobactam was the most active agent against enterococci and Pseudomonas aeruginosa. All isolates of Enterobacteriaceae (n=1088), Streptococcus pyogenes (n=37), Streptococcus agalactiae (n=48), MSSA (n=187), Haemophilus influenzae (n=59), and Moraxella catarrhalis (n=9) were susceptible to ertapenem; < 1% of 1284 anaerobes and only 1 of 113 Streptococcus pneumoniae (a penicillin-resistant isolate) were resistant to ertapenem. The MIC value at which 90% of all Enterobacteriaceae, streptococci, MSSA, H. influenzae, M. catarrhalis, and anaerobes were inhibited (MIC90) was < or = 1 microg/ml and below the mean plasma concentration of total ertapenem following a 1 g intravenous infusion for at least 24 hours, i.e., the entire recommended dosing interval, and below the free drug concentration for at least 8 h.
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PMID:In vitro activity of ertapenem against common clinical isolates in relation to human pharmacokinetics. 1246 28

The in vitro activity of ertapenem (MK-0826), a new carbapenem, was studied against 389 aerobic microorganisms (187 Enterobacteriaceae, 15 Aeromonas spp., 42 Staphylococcus spp., 43 Streptococcus spp., 15 Enterococcus spp., 30 Haemophilus spp., 15 Moraxella catarrhalis, 12 Neisseria gonorrhoeae, 15 Pseudomonas aeruginosa and 15 Acinetobacter spp.) and 54 anaerobic isolates (15 Clostridium spp., 12 Peptostreptococcus spp. and 27 fragilis group Bacteroides recovered from four Spanish hospitals. Ertapenem activity was compared with that of imipenem, piperacillin-tazobactam, cefoxitin, ceftriaxone, ceftazidime, cefepime, and norfloxacin. Ertapenem was the most active antibiotic against Enterobacteriaceae (MIC(90) < or =0.5 mg/l) particularly in the case of broad-spectrum, extended-spectrum and chromosomally encoded AmpC betalactamase-producing strains. Ertapenem exhibited less activity, even lower than that of imipenem, against P. aeruginosa, Acinetobacter spp. and enterococci (MIC(90) > or =16 mg/l). Ertapenem was active against methicillin-susceptible S. aureus and coagulase-negative staphylococci, beta-haemolytic streptococci, and Streptococcus pneumoniae (MIC(90) < or =1 mg/l). In the case of Haemophilus spp., M. catarrhalis and N. gonorrhoeae, ertapenem, with a MIC(90) < or =0.06 mg/l resulted the most active antibiotic tested. When considering the anaerobes, ertapenem displayed a broad spectrum of activity, similar to that of imipenem, against Clostridium spp. (MIC(90) 2 mg/l) and was slightly less active against Bacteroides fragilis (MIC(90) 0.5 mg/l). Both carbapenems were the most active among the tested compounds. Due to its activity against almost all pathogens studied, ertapenem appears to be an option for the treatment of mixed bacterial infections.
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PMID:[Comparative in vitro activity of ertapenem against aerobic and anaerobic bacteria]. 1297 59

In vitro activities of ertapenem and 11 other comparator agents were tested against 1025 isolates of respiratory pathogens collected from 12 Asian countries. Resistance rate to ertapenem was 1.2% in 602 isolates of Streptococcus pneumoniae (MIC(50), 0.06/MIC(90), 1 microg/mL). Ertapenem was also very active against penicillin-, ciprofloxacin-, erythromycin-, and multidrug-resistant pneumococcal isolates (resistance rate: 3.5%, 2.7%, 1.9%, and 2.7%, respectively). Ertapenem-resistant pneumococcal isolates were found only in Vietnam and Korea. Ertapenem resistance was not found in methicillin-susceptible Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, and Klebsiella pneumoniae, including extended-spectrum beta-lactamase producers. In vitro data suggest that ertapenem could be a useful treatment option for community-acquired pneumonia.
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PMID:In vitro activities of ertapenem against drug-resistant Streptococcus pneumoniae and other respiratory pathogens from 12 Asian countries. 1694 83

This study was conducted to assess the in vitro activity of ertapenem against clinical bacterial isolates from patients with community-acquired intra-abdominal and lower tract respiratory infections in Spain in 2003. As the study was conducted before the marketing of ertapenem, it was also useful to define a baseline susceptibility pattern for ertapenem in each of the participating hospitals for later surveillance studies. Each partipating site identified a variable number of aerobic and facultative bacteria isolated from patients with community-acquired intra-abdominal infection or pneumonia using standard procedures. E-test strips were used for determining the minimum inhibitory concentration (MIC) of ertapenem, while for other antimicrobials either quantitative dilution techniques or qualitative diffusion procedures were used according to each microbiology laboratory's routine practice. MIC breakpoints for categorization of susceptibility provided by the CLSI were used for interpreting MIC values. A total of 2,901 recent clinical isolates from patients with community-acquired intra-abdominal infection or pneumonia hospitalized in 69 Spanish medical centers were tested. These isolates included 2,039 Gram-negative bacteria (1,646 Enterobacteriaceae, 216 Haemophilus, 123 non-fermenting Gram-negative bacteria [NFGNB] and 54 others) and 862 Gram-positive bacteria (556 pneumococci, 159 staphylococci, 96 streptococci other than S. pneumoniae, 44 enterococci and 7 others). Ertapenem was very active in vitro against Enterobacteriaceae (99.8% susceptible), Haemophilus (96.3% susceptible), pneumococci (99.6% susceptible, of which 31% were penicillin non-susceptible strains), streptococci other than S. pneumoniae (99.0% susceptible) and methicillin-susceptible staphylococci (94.8% susceptible). For other Gram-positive and Gram-negative pathogens for which ertapenem susceptible breakpoints have not been defined, MIC(90) values were 0.38 and 0.064 mg/l, respectively. As expected, ertapenem had minimal activity in vitro against NFGNB, enterococci and methicillin-resistant staphylococci (MIC(90) of >32 mg/l for all three). Ertapenem was highly active in vitro against most bacteria isolated from patients with community-acquired intra-abdominal and lower respiratory tract infections.
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PMID:[In vitro activity of ertapenem against clinical bacterial isolates in 69 Spanish medical centers (E-test study)]. 1856 13