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Abstract
Ertapenem is a new, structurally unique, parenteral beta-lactam antimicrobial agent that can be administered once daily.
This study compared the local tolerability of ertapenem 1 g once a day administered intramuscularly (IM) versus IM ceftriaxone, with both drugs reconstituted in lidocaine.
In this prospective, double-blind, multicenter study, adult patients with lower respiratory tract infection, skin infection, or urinary tract infection requiring initial parenteral therapy were randomly assigned in a 3:1 ratio to treatment with IM ertapenem 1 g once daily or IM ceftriaxone 1 g once daily. Although study drugs were administered by unmasked personnel, the patients, investigators, and the sponsor medical reviewer were blinded. Patients who improved clinically could be switched to oral amoxicillin-clavulanate after at least 2 days of IM therapy. Tolerability and safety analyses were carried out for the treated population, and efficacy analyses were performed for the modified intent-to-treat population.
A total of 117 patients were randomized. The 87 patients in the ertapenem group and 30 in the ceftriaxone group received IM therapy for a mean duration of 4.1 and 3.8 days, respectively. During treatment, 35.6% (31/87) of patients treated with ertapenem and 43.3% (13/30) of those treated with ceftriaxone experienced > or =1 symptom at the local injection site; the most common symptom was tenderness, followed by pain. Symptoms were moderate to severe in only 1 patient (1.1%) in the ertapenem group and 3 patients (10.0%) in the ceftriaxone group. Clinical drug-related adverse events were reported during IM therapy in 14 patients (16.1%) in the ertapenem group and 5 patients (16.7%) in the ceftriaxone group. Mean +/- SD creatine kinase concentrations, measured in all patients, were 204.8+/-234.8 U/L at the end of IM ertapenem therapy and 382.9+/-721.1 U/L at the end of IM ceftriaxone therapy; at follow-up, values had returned to normal or had decreased in all cases.
Ertapenem 1 g (reconstituted in lidocaine) administered once daily IM was generally well tolerated. The tolerability and safety profiles of IM ertapenem therapy in this study were comparable to those of IM ceftriaxone therapy.
... The anti-bacterial activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through the binding of ertapenem to penicillin binding proteins (PBPs). It is administered either via intravenous [3] or intramuscular [4] route and is almost completely absorbed following intramuscular administration [4]. The adult dose is 1 g parenterally once a day. ...
... The anti-bacterial activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through the binding of ertapenem to penicillin binding proteins (PBPs). It is administered either via intravenous [3] or intramuscular [4] route and is almost completely absorbed following intramuscular administration [4]. The adult dose is 1 g parenterally once a day. ...
In the era of multidrug resistance keen interest needs to be taken in developing newer antiinfective drugs and patents. We all are aware that not many such drugs are readily available and still less are in the pipeline, and thus, such patents are limited in number. This is an attempt to review some of the newer antiinfectives used as antibacterial, antifungal and antiparasitic agents. An attempt has been made here to review the lately added newer antiinfectives. However, there has not been much change in the antiparasitic drug development arena. But it is interesting to note that even much older antiparasitic formulations are still of much use and the reason for this is reviewed here. Among the antibacterial drugs ertapenem, gemifloxacin, tigecycline and daptamycin are discussed. Doripenem has not been included here, due to the paucity of randomized trials of the molecule; however, it appears to be a promising penem that is to get added to the list of available antibiotics. The antiparasitic and antifungal drugs have attracted major attention of the research scientists and clinicians because of the increasing incidence of parasitic and fungal infections in the immunocompromised patients, leading to added morbidity and mortality. In the present review, besides newer antibiotics, newer anti parasitic and antifungal drugs have also been discussed.
... Among carbapenems, ertapenem is a good alternative with its pharmacokinetic features and bactericidal activity. Additionally, it can be administered daily as a single intramuscular, subcutaneous, or intravenous injection and, therefore, it is suitable for OPAT [5][6][7]. Various studies in different countries have shown that OPAT was efficient, reliable and costeffective [8][9][10][11]. However, ertapenem has not yet been approved for OPAT programme in Turkey. ...
Introduction: The primary aim of this study was to evaluate whether there was a difference between outpatient parenteral antibiotic therapy (OPAT) and inpatient parenteral antibiotic therapy (IPAT) costs of ertapenem for urinary tract infections (UTI"s) due to extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacilli, and to discuss suitability of ertapenem for OPAT programme of Turkey for the near future.
Materials and Methods: A total of 53 patients hospitalized with the diagnosis of UTI and treated with ertapenem were retrospectively evaluated. The cost of ertapenem treatment as IPAT was actual costs retrieved from the hospital records. The estimated cost of the same antibiotic for the same patients as an OPAT programme was then calculated and the costs were compared.
Results: The cost difference between IPAT and OPAT was 12.305 (€ 5783). Outpatient parenteral antibiotic therapy programme would provide an estimated 20% reduction in treatment costs. The estimated number of bed days saved, if the patients had received the treatment as OPAT, was calculated to be 583 days, which constitutes about 5% of the total number of hospitalization days.
Conclusion: Applying ertapenem therapy through OPAT programme for UTIs caused by ESBL-producing Gram-negative bacilli will decrease the financial burden of health expenditures and the number of inpatient bed days in Turkey.
... Fourteen were randomized controlled trials with active comparator arms including cefepime, piperacillintazobactam, and ceftriaxone with or without metronidazole. [91][92][93][94][95][96][97][98][99][100][101][102][103][104] Two studies included openlabel experience in treating early ventilatorassociated pneumonia. 105,106 Overall, 2927 patients received a single 1-g dose or greater of ertapenem in the 16 studies. ...
Antimicrobials are the most frequently implicated class of drugs in drug-induced seizure, with β-lactams being the class of antimicrobials most often implicated. The seizure-inducing potential of the carbapenem subclass may be directly related to their β-lactam ring structure. Data on individual carbapenems and seizure activity are scarce. To evaluate the available evidence on the association between carbapenem agents and seizure activity, we conducted a literature search of the MEDLINE (1966-May 2010), EMBASE (1974-May 2010), and International Pharmaceutical Abstracts (1970-May 2010) databases. Reference citations from the retrieved articles were also reviewed. Mechanistically, seizure propensity of the β-lactams is related to their binding to γ-aminobutyric acid (GABA) receptors. There are numerous reports of seizure activity associated with imipenem-cilastatin, with seizure rates ranging from 3-33%. For meropenem, doripenem, and ertapenem, the seizure rate for each agent is reported as less than 1%. However, as their use increases and expands into new patient populations, the rate of seizures with these agents may increase. High-dose therapy, especially in patients with renal dysfunction, preexisting central nervous system abnormalities, or a seizure history increases the likelihood of seizure activity. Although specific studies have not been conducted, data indicate that carbapenem-associated seizure is best managed with benzodiazepines, followed by other agents that enhance GABA transmission. Due to the drug interaction between carbapenems and valproic acid, resulting in clinically significant declines in valproic acid serum concentrations, the combination should be avoided whenever possible. Clinicians should be vigilant regarding the possibility of carbapenem-induced seizures when selecting and dosing antimicrobial therapy.
... Given its excellent in vitro activity against Streptococcus pneumoniae and Haemophilus influenzae, the pyogenic bacteria most commonly responsible for acute community-acquired lower respiratory tract infections [5,6], clinical trials were conducted to evaluate the efficacy of ertapenem for the treatment of community-acquired pneumonia and acute exacerbation of chronic bronchitis [7,8]. The present study was designed to assess the in vitro activity of ertapenem compared with ceftriaxone, cefepime, ciprofloxacin and amoxicillin-clavulanate against respiratory bacterial pathogens isolated from patients enrolled in those trials. ...
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.
... The intravenous (iv) formulation requires infusion over ∼30 min, whereas an intramuscular formulation, licensed in the USA but not in Europe, can be administered with 1% lidocaine in saline, achieving a bioavailability of 90%. 42 In either case, the standard daily dosage is 1 g. Key parameters are summarized in Table 2. ...
Ertapenem is a carbapenem that shares the activity of imipenem and meropenem against most species, but is less active against non-fermenters. Activity is retained against most strains with AmpC and extended-spectrum beta-lactamases, although resistance can arise if these enzymes are combined with extreme impermeability. Resistance can also be caused by IMP, VIM, KPC and NMC carbapenemases, but again, co-requires impermeability. Although the spread of carbapenemases in the future is a concern, they are currently very rare. Given as a 1 g intravenous (iv) infusion once daily, ertapenem has a plasma half-life of approximately 4 h in healthy volunteers, and a Cmax of 155 mg/L and 13 mg/L for total and free drug, respectively. Excretion is largely renal, divided equally between native drug and an open-ring derivative. Trials show equivalence to piperacillin/tazobactam or ceftriaxone in (a) intra-abdominal infections, (b) community-acquired pneumonia, (c) acute pelvic infections, (d) skin and skin structure infections and (e) complicated urinary tract infections. The USA licence grants all these five indications; the EU licence grants the first three. Further potential uses include home iv therapy, directed therapy against Enterobacteriaceae with AmpC or extended-spectrum cephalosporinases, and tentatively, surgical prophylaxis. Widening the usage of carbapenems raises public health concerns, somewhat allayed by the continued rarity of carbapenemases after 17 years of imipenem use, and by the fact that carbapenemases occur mostly in non-fermenters outside the spectrum of ertapenem, and co-require impermeability to confer resistance in Enterobacteriaceae. Nevertheless, if ertapenem is to be used widely, its effects on the resistance ecology need to be monitored carefully.
... With regard to tolerability of intramuscular administration, 28% of patients receiving ertapenem intramuscularly and 33% of patients receiving ceftriaxone intramuscularly experienced у1 symptom at the injection site. In a separate study comparing the tolerability of 1-g doses of ertapenem and ceftriaxone administered intramuscularly once daily (both drugs were reconstituted in lidocaine), 36% (31/ 87) and 43% (13/30) of patients, respectively, experienced symptoms at the injection site [22]. The most common symptom was tenderness, followed by pain. ...
Several parenteral antimicrobials have been introduced into clinical practice over the course of the last decade. Some of
these agents (e.g., linezolid, daptomycin, and tigecycline) are prototypes of new classes of compounds. In comparative clinical
trials, these newer anti-infectives have been shown to be safe and to have low rates of discontinuation by patients. However,
long-term use has revealed unique toxicities associated with the use of some of these drugs. The adverse events and potential
drug interactions associated with the use of these antibiotics are variable and require familiarity with the safety profile
of each drug. It is especially important that clinicians be able to recognize serious adverse events associated with the use
of specific drugs, because most of the adverse events can be readily reversed by cessation of therapy.
... Ertapenem is a once-a-day parenteral 1--methyl car- 2 bapenem administered as a single agent via either the intra- 3 venous or intramuscular route [1] [2] [3] [4]. It exhibits a long plasma 4 half-life (t 1/2 ) of ca. 4 h owing to its high plasma pro- 5 tein binding [5] and stability against human renal ...
Ertapenem activity in vitro was compared with that of nine reference antibiotics against 337 anaerobes by determining minimal inhibition concentrations (MICs). Amongst 246 Gram-negative anaerobes, 4, 8, 3, 4, 7, 2 and 52 strains showed resistance to ertapenem, amoxicillin/clavulanic acid, ticarcillin/clavulanic acid, piperacillin/tazobactam, cefoxitin, imipenem and clindamycin, respectively, and all strains were inhibited by metronidazole. Ertapenem MIC(50) values were 0.5, 0.25, 0.06 and <or=0.03mg/L for the Bacteroides fragilis group, Prevotella spp., fusobacteria and Gram-positive cocci, respectively. Overall resistance rates were 2.1%, 51.3%, 2.4%, 1.2%, 1.5%, 7.1%, 0.6%, 22% and 1.5% for ertapenem, amoxicillin, amoxicillin/clavulanic acid, ticarcillin/clavulanic acid, piperacillin/tazobactam, cefoxitin, imipenem, clindamycin and metronidazole, respectively. Ertapenem showed a broad spectrum and good activity against anaerobes.
Face à l’émergence des entérobactéries sécrétrices de bêta-lactamase à spectre étendu (EBLSE) en milieu communautaire, la Société de Pathologie Infectieuse de Langue Française produisait en 2014 et réactualisait en 2015 des recommandations sur la prise en charge des infections urinaires (IU) bactériennes communautaires de l’adulte. L’objectif de cette étude était de colliger un état des lieux des connaissances des médecins généralistes de la région dieppoise vis à vis de ces nouvelles recommandations et d'établir dans quelle mesure ils sont confrontés aux problèmes d'antibiorésistance afin de définir par la suite des outils d’aide à la prise en charge. Nous avons réalisé, grâce à l’envoi postal de 116 questionnaires, une enquête de pratique auprès de 116 médecins généralistes exerçant sur le territoire de santé de Dieppe. Il en ressort une faible connaissance des recommandations ainsi qu’une probable surprescription d’antibiothérapies due à des outils diagnostiques mal utilisés notamment chez les personnes âgées. Le principe de différer chaque fois que possible l’antibiothérapie dans le cadre des cystites à risque de complication reste minoritaire chez nos confrères. Une consommation trop grande d’antibiotiques dits « critiques » est constatée. Malgré une difficulté pour certains à l’interprétation de l’antibiogramme lors d’une IU à EBLSE, l’appel au référent était rarement envisagé. La création en 2016 du réseau NormAntibio et sa ligne téléphonique de conseil en antibiothérapie bénéficie d’un accueil plutôt favorable favorisant, espérons-le, la prise de conscience du problème de l’antibiorésistance. D’autres mesures pourraient être prises comme l’utilisation des antibiogrammes ciblés. En attendant, la soirée de formation proposée aux omnipraticiens à l’issu de ce travail ne reste plus qu’à se concrétiser puisque très attendue par une grande majorité d’entre eux.
It has been eight decades since the penicillin discovery. Despite efforts to improve antimicrobial regimens and availability of newer drugs of extended spectrum, the number of multirresistant microorganisms has increased in the last two decades. In the actual context and looking at the rates of antimicrobial resistance all around the world, the evaluation of new antimicrobials is an emerging issue. In this article, some of the new available antimicrobials are reviewed, including beta-lactams, macrolides, quinolones and newer options for resistant Gram-positive bacteri.
Ertapenem belongs to carbapenem antibiotics. Nevertheless it differs from other carbapenems registered in the Czech Republic (imipenem, meropenem, doripenem) in two important features: (a) low efficacy against Pseudomonas aeruginosa a Acinetobacter spp.; thus ertapenem is predestined for treatment community-acquired infections rather than nosocomial infections; (b) relatively long half-time that enables once daily dosing. Thus, ertapenem is a good choice for treatment of mixed community-acquired infections and/or for treatment of infections caused by E. coli, Klebsiella spp., or other bacteria producing extended-spectrum beta-lactamases (ESBL, AmpC). The long half-time make ertapenem very useful for out-patient therapy and home care.
Abstract The Group 1, 1β-methyl carbapenem ertapenem (Invanz®) is approved for parenteral use in patients with complicated intra-abdominal infection (cIAI), community-acquired pneumonia (CAP) and acute pelvic infection caused by susceptible strains of certain designated organisms in both the US and the EU. Additional approved indications in the US include complicated skin and skin structure infection (cSSSI) and complicated urinary tract infection (cUTI). Ertapenem is approved for use in adults in both the US and the EU and in paediatric patients aged ≥3 months in the US. Ertapenem has a broad spectrum of in vitro activity against Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae, Gram-positive pathogens and anaerobic pathogens. It has similar efficacy to comparator antibacterials such as piperacillin/tazobactam in cSSSI (including diabetic foot infection), cIAI and acute pelvic infection and ceftriaxone with or without metronidazole in cIAI, cUTI and CAP. The drug has also shown efficacy in the treatment of paediatric patients with complicated community-acquired bacterial infections. Ertapenem has a convenient once-daily administration schedule and is generally well tolerated. Thus, ertapenem is an important option for the empirical treatment of complicated community-acquired bacterial infections in hospitalised patients. Pharmacological Properties Ertapenem demonstrated good in vitro activity against clinically relevant Enterobacteriaceae (e.g. Escherichia coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., Morganella morganii, Proteus spp. and Serratia marcescens); the minimum concentration inhibiting 90% of strains (MIC90) was generally ≤1 mg/L and susceptibility rates, where reported, were 100%. Ertapenem was active against ESBL- and AmpC-producing Enterobacteriaceae, although MIC90 values for these strains were raised. Ertapenem was also active against Haemophilus influenzae and Moraxella catarrhalis, although it had poor activity against Pseudomonas aeruginosa and Acinetobacter spp. Ertapenem had good in vitro activity against the Gram-positive pathogens Staphylococcus aureus (methicillin/oxacillin-susceptible isolates), coagulase-negative staphylococci (oxacillin-susceptible isolates), Streptococcus pneumoniae (penicillin-susceptible and -intermediate isolates), S. agalactiae and S. pyogenes, with MIC90 values of ≤0.5 mg/L and susceptibility rates, where reported, of 100%. Ertapenem lacked activity against methicillin/oxacillin-resistant staphylococci, Enterococcus faecalis and E. faecium. Ertapenem had good in vitro activity against a wide range of anaerobes, including the Bacteroides fragilis group of pathogens, Clostridium clostridioforme, C. perfringens, Eubacterium lentum, Fusobacterium spp., Peptostreptococcus spp., Porphyromonas spp. and Prevotella spp., with MIC90 values of ≤4 mg/L and, where reported, susceptibility rates of 97–100%. The ertapenem MIC90 for various pathogens remained below the mean total ertapenem plasma concentration for 24 hours and below the mean unbound ertapenem plasma concentration for ≥8 hours after a single intravenous 1g dose. Ertapenem had rapid, time-dependent bactericidal activity and a minimal inoculum effect. Ertapenem is generally stable against hydrolysis by various β-lactamases, such as penicillinases, cephalosporinases and ESBLs, although it may be affected by carbapenemases. However, it is thought that additional factors besides the presence of carbapenemases, such as impermeability, are needed for substantive carbapenem resistance to develop. It is thought unlikely that ertapenem will select for P. aeruginosa isolates with cross resistance to other carbapenems in the clinical setting. The frequency of bowel colonisation with ertapenem-resistant Enterobacteriaceae was not increased with ertapenem therapy in three clinical studies in patients with cIAI. No accumulation of ertapenem was seen at steady state following intravenous or intramuscular administration; the mean bioavailability of the drug following intramuscular administration is ≈90%. Ertapenem is highly plasma protein bound in a nonlinear concentration-dependent manner, and achieves good penetration into lung tissue and skin blister fluid following intravenous administration. The main route of elimination for ertapenem is renal and the pharmacokinetics of the drug are altered to a clinically significant extent in patients with advanced or end-stage renal impairment. The plasma elimination half-life of ertapenem (≈4 hours) allows for once-daily dosing. Clinical Efficacy The efficacy of ertapenem in adults with complicated bacterial infections has been examined in large well designed trials. The efficacy of ertapenem was equivalent to that of piperacillin/tazobactam in the treatment of cSSSI with clinical cure rates of 82% and 84% in the respective treatment groups at the test-of-cure (TOC) visit. In addition, ertapenem had similar efficacy to piperacillin/tazobactam in diabetic foot infection, with favourable clinical response rates of 94% and 92% in the respective treatment groups at the discontinuation of intravenous therapy. Ertapenem had similar efficacy to piperacillin/tazobactam in three trials in patients with cIAI with clinical cure rates of 82–94% and 82–93% and combined clinical and microbiological cure rates of 87% and 81% in the corresponding treatment groups at the TOC visit. Combined clinical and microbiological cure rates of 84% and 85% were reported in ertapenem and ceftriaxone plus metronidazole recipients in a fourth trial. The efficacy of ertapenem was equivalent to that of ceftriaxone in two trials in patients with cUTI with microbiological eradication rates of ≥85% at the TOC visit, and in two trials in patients with CAP with clinical cure rates of >90% at the TOC visit. Ertapenem had equivalent efficacy to piperacillin/tazobactam in women with acute pelvic infection with cure rates of 94% and 92% in the respective treatment groups at the TOC visit. Subgroup analyses demonstrated the efficacy of ertapenem in patients with Enterobacteriaceae infections, polymicrobial infections and mixed anaerobic infections. In addition, results of a retrospective chart review showed the efficacy of ertapenem in patients with infections caused by ESBL-producing organisms. Ertapenem was effective in paediatric patients aged 3 months to 17 years with complicated bacterial infections, according to the results of two randomised, multicentre studies. In patients with cUTI, microbiological success rates were 87% with ertapenem and 90% with ceftriaxone. Clinical success rates with ertapenem and ceftriaxone were 96% and 100% in patients with cSSSI and 96% and 96% in patients with CAP. Moreover, clinical success rates with ertapenem and ticarcillin/clavulanic acid were 84% and 64% in patients with cIAI and 100% and 100% in patients with acute pelvic infection. Tolerability Intravenous ertapenem was generally well tolerated in patients with complicated bacterial infections, with most adverse events being of mild-to-moderate severity. In adults with complicated bacterial infections who received ertapenem, the most commonly reported drug-related adverse effects included diarrhoea, infused vein complications, nausea, headache, vaginitis, phlebitis/thrombophlebitis and vomiting. Seizures were reported in 0.5% of ertapenem recipients. The most commonly reported drug-related laboratory abnormalities included increased levels of ALT, AST, serum alkaline phosphatase, platelets and eosinophils. Intramuscular ertapenem was also generally well tolerated in adults with bacterial infections; the most commonly reported local symptoms at the injection site included tenderness, pain, induration and ecchymosis. The adverse event profile of ertapenem in paediatric patients with complicated bacterial infections was similar to that seen in adults. The most commonly reported drug-related adverse effects included diarrhoea, infusion site pain, infusion site erythema and vomiting, and the most commonly reported drug-related laboratory abnormalities included decreased neutrophil counts and increased ALT and AST levels.
Ertapenem has been demonstrated to be highly effective for the treatment of complicated infections. The aim of this study was to compare the efficacy and safety of ertapenem with ceftriaxone.
We searched the PubMed, EMBASE, and the Cochrane Library for published randomized controlled trials (RCTs) that compared the efficacy and safety of ertapenem with ceftriaxone for the treatment of complicated infections including community-acquired pneumonia (CAP), complicated urinary tract infections (cUTIs), and complicated intra-abdominal infections (cIAIs). Meta-analysis was performed by RevMan 5.0.
Eight RCTs, involving 2 883 patients, were included in our meta-analysis. Ertapenem was associated with similar clinical treatment success with ceftriaxone for complicated infections (1 326 patients, fixed-effect model, OR: 1.13, 95% CI: 0.75-1.71). There was no difference between the compared treatment groups with regard to the microbiological treatment success, and no difference was found with regard to the incidence of clinical and laboratory drug-related adverse events between ertapenem and ceftriaxone groups. As to local tolerability, overall, there was no difference between the compared groups; however, in the subgroup analysis, local reaction was significantly less in the ertapenem subgroup than the ceftriaxone plus ceftriaxone subgroup.
Ertapenem can be used as effectively and safely as ceftriaxone for the treatment of complicated infections. It is an appealing option for the treatment of these complicated infections.
Background
Use of carbapenems is expected to increase with rising prevalence of multidrug-resistant bacteria. Available literature indicates that the incidence of seizure with ertapenem use ranges from 0.2% to 0.5% in adults. However, anecdotal clinical experience suggests that the frequency of seizures in frail geriatric patients could be higher.AimWe sought to estimate the rate of seizures with the use of ertapenem in older hospitalized patients and to identify possible predisposing factors for their occurrence.Methods
We performed a retrospective chart review for hospital episodes of patients who were admitted to the department of geriatric medicine of an acute care hospital and received at least one dose of ertapenem between October 2009 and September 2010.ResultsChart reviews for 116 patients were conducted. The mean age of the study population was 82.9 years [standard deviation (SD) = 8.1] and 69% of the patients were female. The mean number of comorbidities was 8.6 (SD = 3.7) and the mean number of assisted or dependent activities of daily living out of 5 was 3.5 (SD = 2.0). Seizures occurred in six (5.17%) hospitalized patients. The Naranjo Adverse Drug Reaction Probability Scale revealed a causality relationship graded as “possible” in two episodes and “probable” in the remaining four episodes. Patients who experienced seizures were significantly younger (mean age: 75.7 vs. 83.3 years, p = 0.023) and had fewer comorbidities (5.5 vs. 8.8, p = 0.033). Seizure occurrence had statistically nonsignificant associations with a history of central nervous system disorders and previous seizures.Conclusion
We found a higher rate of seizures amongst older hospitalized patients who were using ertapenem than reported in existing literature. Further studies should include a wider population of older hospitalized patients and compare seizure incidence with the use of carbapenem alternatives.
To compare ertapenem pharmacokinetics, pharmacodynamics, and tolerability when administered as a rapid 5-minute infusion to the standard 30-minute infusion.
Prospective, randomized, crossover pharmacokinetic study.
Clinical research center.
Twelve healthy adult volunteers.
Each subject received ertapenem 1 g intravenously, administered either as a rapid 5-minute infusion or the standard 30-minute infusion, every 24 hours for 3 days (first phase); after a 4-day washout period, each subject then received the other infusion every 24 hours for 3 days (second phase).
Plasma samples were collected after the first and third (steady-state) doses of each study phase, and protein binding was assessed by use of ultrafiltration. Pharmacokinetic analyses were conducted using noncompartmental and compartmental methods. A 5000-subject Monte Carlo simulation was used to assess the probability of target attainment for free drug concentration remaining above the minimum inhibitory concentration (MIC) for 40% or greater of the dosing interval (40% fT > MIC) over an MIC range. Ertapenem was well tolerated and adverse events were similar for both infusions. The ertapenem steady-state mean ± SD maximum concentrations were 193.3 ± 43.3 and 165.7 ± 20.4 mg/L for the 5- and 30-minute infusions, respectively; the mean ± SD areas under the concentration-time curves from 0-24 hours were 561.2 ± 77.0 and 531.3 ± 56.9 μg · hr/ml (geometric mean ratio 1.008, 90% confidence interval 0.999-1.017), respectively. Protein binding was concentration dependent (range 87.9-98.9%). A two-compartment model best described ertapenem pharmacokinetics with the following parameter estimates: clearance 1.89 ± 0.19 L/hr, volume of central compartment 5.04 ± 0.56 L, and transfer constants k 0.43 ± 0.08/hr and k 0.44 ± 0.07/hr. The probabilities of target attainment for 5- and 30-minute infusions were 97.0% and 97.9% at an MIC of 0.25 mg/L and 1.7% and 2.8% at an MIC of 0.5 mg/L, respectively.
Ertapenem administered as a rapid 5-minute infusion provides a well tolerated, bioequivalent, and pharmacodynamically equivalent regimen to the 30-minute infusion at clinically relevant MICs.
Given their broad-spectrum and safety, carbapenems are a widely used class of antibiotics, especially in the treatment of hospital-acquired infections including infections due to multidrug-resistant organisms. Ertapenem is a unique member of this class, with a narrower spectrum that lacks reliable activity against Pseudomonas and Enterococcus. Given its spectrum and half-life of 4 h it is better suited to use in community-acquired infections and it is particularly well positioned for use in the outpatient setting.
Chemistry, mechanism of action, pharmacokinetics/pharmacodynamics, safety and indications for use will be covered in this review. Similar to other beta-lactams, the carbapenems inhibit cell wall synthesis by binding to and inhibiting penicillin-binding proteins. Their resistance to beta-lactamases including AmpC and extended-spectrum beta-lactamases enhances their usefulness. Similar to other beta-lactams, ertapenem exhibits time-dependent killing. Given this profile, ertapenem has been found to be useful in intra-abdominal infections, acute pelvic infections, complicated skin and skin structure infections, community-acquired pneumonia and complicated urinary tract infections.
This review will enable the reader to understand differences between the different carbapenems, especially with regard to ertapenem. Once an understanding is gained with regard to pharmacology and microbiology, the reader will be positioned to understand better those circumstances in which use of ertapenem should be considered.
Substantial differences between the carbapenems exist. Ertapenem has unique characteristics that may make it useful in specific clinical circumstances that are detailed in this review.
Steady-state pharmacokinetics of ertapenem were compared in patients after 1-g intravenous and subcutaneous (s.c.) infusions.
Bioavailability was 99% ± 18% after s.c. administration, but peaks were reduced by about (43 ± 29 versus 115 ± 28 μg/ml) and
times to peak were delayed. Simulations based on unbound concentrations show that time over the MIC should always be longer
than 30% to 40% of the dosing interval, suggesting that s.c. infusion could be an alternative in patients with reduced vascular
access.
β-Lactam antimicrobials have been widely prescribed to treat serious infections for nearly 60 years owing to their excellent efficacy, safety and tolerability profiles. Among the many different structurally dis- tinct classes of β-lactams, the carbapenem class, while sharing these general β-lactam features, is regarded as the class that is most potent and that has the widest spectrum of antimicrobial activity. At the time that the carbapenems were last reviewed in this journal, 1 imipenem and meropenem were the only carbapenems that were available in the majority of the world. Since then ertapenem (formerly MK-0826), a new long-acting, parenteral carbapenem (Figure 1), has received regulatory approval in the United States (November 2001) and the European Union (April 2002). The introduction of ertapenem should make us reconsider how we think of the carbapenems. Ertapenem is sufficiently different in some key attributes from imipenem and meropenem that we can no longer consider all available carbapenems as if they were a homogeneous class. In order to consider the appropriate role of ertapenem in the current antimicrobial armamentarium, this article reviews the key attributes of ertapenem and the other carbapenems and proposes a classification scheme for the carbapenem class; imipenem and mero- penem will be discussed first. 1,2
Ertapenem is a parenteral carbapenem antimicrobial with pharmacological properties that allow it to be given once daily. This makes it a consideration for outpatient parenteral antimicrobial therapy (OPAT). In comparison with information from the OPAT Outcomes Registry, ertapenem seems well suited for the types of infections and bacteria that are commonly treated with OPAT, plus it has additional activity against anaerobic bacteria. This added spectrum makes it possible to treat complicated skin/skin-structure, complicated intra-abdominal and pelvic infections with a single antibiotic instead of the multiple agents that have usually been required. Ertapenem is also comparable to other OPAT antimicrobials in terms of adverse effects and clinical outcomes. This antimicrobial can be given with any delivery model, although its stability when mixed is such that daily preparation or self-mixing systems need to be considered. Ertapenem should be added to the growing list of once-daily parenteral antibiotics that can be given to outpatients.
Ertapenem is a Group 1 carbapenem that was licensed in the USA in November 2001 and in Europe in April 2002. Its safety profile has been assessed in 240 healthy volunteers participating in 12 clinical pharmacology studies and in 2046 patients enrolled in five Phase IIa and eight Phase IIb/III clinical trials. The most common drug-related adverse events (AEs) reported in trials comparing ertapenem and piperacillin-tazobactam and in trials comparing ertapenem and ceftriaxone were: diarrhoea (ertapenem versus piperacillin-tazobactam 5.0% versus 7.0%; ertapenem versus ceftriaxone 5.6% versus 5.9%); infused vein complications (ertapenem versus piperacillin-tazobactam 4.5% versus 7.9%; ertapenem versus ceftriaxone 3.2% versus 4.6%); nausea (ertapenem versus piperacillin-tazobactam 2.5% versus 3.4%; ertapenem versus ceftriaxone 3.4% versus 3.3%); and elevations in alanine aminotransferase levels (ertapenem versus piperacillin-tazobactam 8.8% versus 7.3%; ertapenem versus ceftriaxone 8.3% versus 6.9%). Most ertapenem-related AEs were reported as mild-to-moderate in intensity. Ertapenem was not associated with prolongation of the QTc interval. Local reactions of moderate-to-severe intensity at the infusion site were infrequent and occurred with similar frequency in the ertapenem and comparator treatment groups. No overall differences in safety were observed between elderly (aged > or = 65 years and > or = 75 years) and younger patients. Ertapenem, 1 g once a day given by intravenous infusion or intramuscular injection, was generally well tolerated and had overall safety and tolerability profiles similar to those of piperacillin-tazobactam and ceftriaxone.
beta-Lactam antibiotics share a common structure and mechanism of action, although they differ in their spectrum of antimicrobial activity and utility in treating different infections. The current classes include the penicillins, the penicillinase-resistant penicillins, the extended- spectrum penicillins, the cephalosporins, the carbapenems, and the monobactams. This article discusses some of the newest beta-lactams available for use in the United States: ertapenem, cefditoren, and cefepime. A new formulation of amoxicillin-clavulanate, which contains higher doses of amoxicillin, is also discussed.
The carbapenems are beta-lactam-type antibiotics with an exceptionally broad spectrum of activity. Ertapenem is a new carbapenem developed to address the pharmacokinetic shortcomings (short half-life) of imipenem and meropenem. Ertapenem shares similar structural features with meropenem, including its stability to dehydropeptidase-1, allowing it to be administered without a dehydropeptidase-1 inhibitor. Ertapenem, like imipenem and meropenem, demonstrates broad-spectrum antimicrobial activity against many Gram-positive and -negative aerobes and anaerobes and is resistant to nearly all beta-lactamases, including extended-spectrum beta-lactamases and AmpCs. However, it differs from both imipenem and meropenem in demonstrating limited activity against Enterococcusspp., Pseudomonasaeruginosa and other nonfermentative Gram-negative bacteria commonly associated with nosocomial infections. The extensive protein binding of ertapenem extends the half-life and allows for once-daily dosing. Prospective, multicenter, randomized, double-blind, comparative clinical studies demonstrate similar clinical efficacy of ertapenem compared with other agents. Clinical trials of complicated intra-abdominal infection, acute pelvic infection, complicated skin and soft-structure infection, community-acquired pneumonia and complicated urinary tract infections demonstrated that ertapenem has equivalent efficacy and safety compared with ceftriaxone and piperacillin/tazobactam. Ertapenem is a promising new carbapenem with excellent efficacy and safety for the treatment of a variety of community-acquired infections. It also appears to be of great value as an outpatient parenteral antimicrobial therapy.
Some drug formulations for intramuscular use may cause damage, which potentially can be associated with pain. In animals, spinal nociception can be assessed by stereological quantification of number of regional dorsal horn neurones containing intranuclear Fos-protein as a consequence of expression of the c-fos gene. The aim of the present study was to use c-fos gene expression as a measure of nociceptive input after intramuscular injection of different oxytetracycline formulations. Rats were given a 0.3 ml intramuscular injection in the thigh of one of two 100 mg/ml oxytetracycline preparations (Maxicyklin Vet., Boehringer-Ingelheim or Engemycin Vet., Intervet; n=6 for both), 0.9% saline (n=4) or 4% formalin (n=2). In addition, five pigs were given an intramuscular injection of Aquacykline Vet. (Rosco) in a dose of 1.0 ml/10 kg. After three hours the animals were anaesthetised and perfusion fixed and their spinal cords were taken out. Cryostate sections of the spinal cords were stained immunohistochemically for Fos-protein in dorsal horn neurones and then subjected to stereological quantification of Fos-positive neurones. Rats receiving a saline injection had 905+/-586 (mean+/-S.D.) Fos-positive neurones, whereas formalin injection increased this number to 11,091+/-4,825. Rats receiving an injection of Engemycin had 1,932+/-893 Fos-positive neurones, which was not significantly different from the saline group. In contrast, injection with Maxicyklin increased the number of Fos-positive neurones to 5,488+/-3,116, which was higher than after injection of saline (P<0.05). In pigs receiving an Aquacyklin injection, the number of Fos-positive neurones was 3,493+/-2,027, which was not significantly higher than the previously determined basal level. The increased neuronal activation after intramuscular injection of Maxicyklin Vet. may suggest that injection of this drug may be more painful than injection with saline. In contrast, no significant difference in neuronal activation caused by saline and Engemycin Vet. was found.
Ertapenem, a parenteral broad-spectrum 1-beta-methyl-carbapenem, was licensed 5 years ago for clinical practice in the US and Europe. The substance has a good in vitro activity against many common aerobic and anaerobic Gram-positive and -negative bacteria. Its in vitro activity against Enterobacteriaceae carrying plasmid- or chromosomal-mediated beta-lactamases, including AmpC- and extended-spectrum beta-lactamases, is especially clinically significant. Advantages concerning in vitro activity and low potential for so-called 'collateral damage', and development of own resistance during therapy, as shown in several randomized, controlled clinical trials, make ertapenem an excellent treatment choice for complicated aerobic and anaerobic mix infections caused by ertapenem-sensitive bacteria. On the other hand, due to its limited activity against Acinetobacter spp., enterococci and Pseudomonas aeruginosa, it is less suitable for late-onset nosocomial infections. International guidelines recommend the initial empirical use of ertapenem for intra-abdominal infections, skin and skin-structure infections, acute pelvic infections, complicated urinary tract infections and pneumonia (both community-acquired and 'early-onset' nosocomial) in a dose of 1.0 g administered once daily. However, recent results from pharmacokinetic/pharmacodynamic modelling studies in critically ill patients with ventilator-associated pneumonia and adipose volunteers with a body mass index of > or = 20 kg/m(2) showed that the standard dose of 1.0 g/day may not provide adequate free, protein-unbound drug concentrations in plasma and organ tissues. Therefore, a shortening of the dosage interval or continuous infusion of ertapenem should be considered to ensure optimal free concentrations in these particular populations.
The pharmacokinetics and tolerability of 1-g doses of ceftriaxone diluted in sterile water, 1% lidocaine, or buffered lidocaine were investigated. No difference in bioequivalence was noted between the three treatments. No difference in peak creatine kinase values was seen. By use of a quantitative pain scale, injection of ceftriaxone with the water diluent was significantly more painful than that with either of the other two diluents. No difference in injection pain was noted for lidocaine or buffered lidocaine.
Ertapenem (MK-0826, L-749,345) is a 1-β-methyl carbapenem with a long serum half-life. Its in vitro activity was determined
by broth microdilution against 3,478 bacteria from 12 centers in Europe and Australia, with imipenem, cefepime, ceftriaxone,
and piperacillin-tazobactam used as comparators. Ertapenem was the most active agent tested against members of the familyEnterobacteriaceae, with MICs at which 90% of isolates are inhibited (MIC90s) of ≤1 μg/ml for all species. Ertapenem also was more active than imipenem against fastidious gram-negative bacteria and
Moraxella spp.; on the other hand, ertapenem was slightly less active than imipenem against streptococci, methicillin-susceptible staphylococci,
and anaerobes, but its MIC90s for these groups remained ≤0.5 μg/ml.Acinetobacter spp. and Pseudomonas aeruginosawere also much less susceptible to ertapenem than imipenem, and mostEnterococcus faecalis strains were resistant. Ertapenem resistance, based on a provisional NCCLS MIC breakpoint of ≥16 μg/ml, was seen in only
3 of 1,611 strains of the familyEnterobacteriaceae tested, all of them Enterobacter aerogenes. Resistance was also seen in 2 of 135 anaerobes, comprising 1 Bacteroides fragilis strain and 1Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of
≤2 μg/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were
as high as 2 μg/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 μg/ml and one required an MIC of 4 μg/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 μg/ml. These streptococci also had diminished susceptibilities
to other β-lactams, including imipenem as well as ertapenem. The Etest and disk diffusion gave susceptibility test results
in good agreement with those of the broth microdilution method for ertapenem.
In a double-blind, multicenter trial, 502 patients hospitalized with community-acquired pneumonia were randomized to receive
therapy with either ertapenem or ceftriaxone (for each, 1 g given intravenously once daily). After a minimum of 3 days, therapy
could be switched to oral amoxicillin-clavulanate. The median duration of intravenously administered therapy for the 383 clinically
evaluable patients was 4 days for both treatment groups; 345 patients (90.1%) had their treatment switched to orally administered
therapy. Of the clinically evaluable patients, 168 (92.3%) in the ertapenem group and 183 (91.0%) in the ceftriaxone group
had a favorable clinical response. Streptococcus pneumoniae was the most commonly isolated pathogen, and high cure rates were observed both for penicillin-susceptible and -nonsusceptible
infections in the ertapenem group (28 [87.5%] of 32 patients versus 17 [100%] of 17 patients, respectively). Both treatment
regimens were generally well tolerated; the most common drug-related adverse events reported were diarrhea (2.9% versus 2.7%)
and nausea (0.8% versus 2.0%) in the ertapenem and ceftriaxone groups, respectively. These results suggest that ertapenem
and ceftriaxone therapy have similar efficacy and safety in hospitalized patients with community-acquired pneumonia.
We conducted a prospective, randomized, double-blind trial comparing ertapenem (1 g once daily) with piperacillin-tazobactam
(3.375 g every 6 h) as parenteral treatment for 540 adults with complicated skin and skin-structure infections. The most common
diagnoses were skin or soft-tissue abscesses and lower-extremity infections associated with diabetes. The mean duration (±
standard deviation) of therapy was 9.1 ± 3.1 days for ertapenem and 9.8 ± 3.3 days for piperacillin-tazobactam. At the assessment
of primary efficacy end point, 10–21 days after treatment, 82.4% of those who received ertapenem and 84.4% of those who received
piperacillin-tazobactam were cured. The difference in response rates, adjusting for the patients' assigned strata, was -2.0%
(95% confidence interval, -10.2% to 6.2%), indicating that the response rates in the 2 treatment groups were equivalent. Cure
rates for the 2 treatment groups were similar when compared by stratum, diagnosis, and severity of infection. The frequency
and severity of drug-related adverse events were similar in the treatment groups.
Ertapenem (INVANZ) is a new once-a-day parenteral β-lactam antimicrobial shown to be effective as a single agent for treatment
of various community-acquired and mixed infections. The single- and multiple-dose pharmacokinetics of ertapenem at doses up
to 3 g were examined in healthy young men and women volunteers. Plasma and urine samples collected were analyzed using reversed-phase
high-performance liquid chromatography with UV detection. Ertapenem is highly bound to plasma protein. The protein binding
changes from ∼95% bound at concentrations of <50 μg/ml to ∼92% bound at concentrations of 150 μg/ml (concentration at the
end of a 30-min infusion following the 1-g dose). The nonlinear protein binding of ertapenem resulted in a slightly less than
dose proportional increase in the area under the curve from 0 h to infinity (AUC0-∞) of total ertapenem. The single-dose AUC0-∞ of unbound ertapenem was nearly dose proportional over the dose range of 0.5 to 2 g. The mean concentration of ertapenem
in plasma ranged from ∼145 to 175 μg/ml at the end of a 30-min infusion, from ∼30 to 34 μg/ml at 6 h, and from ∼9 to 11 μg/ml
at 12 h. The mean plasma t1/2 ranged from 3.8 to 4.4 h. About 45% of the plasma clearance (CLP) was via renal clearance. The remainder of the CLP was primarily via the formation of the β-lactam ring-opened metabolite that was excreted in urine. There were no clinically
significant differences between the pharmacokinetics of ertapenem in men and women. Ertapenem does not accumulate after multiple
once-daily dosing.
To determine if two ceftriaxone solutions of different concentrations are bioequivalent when administered intramuscularly.
Double-blind, single-dose, two-period, randomized crossover study.
A clinical research center.
Seventeen healthy volunteers.
Ceftriaxone 500 mg administered in either 2 or 1.4 mL of lidocaine 1% solution, with final ceftriaxone concentrations of 250 and 350 mg/mL, respectively.
Blood samples were assayed for ceftriaxone concentrations with HPLC and pharmacokinetic parameters were calculated from the resulting plasma-concentration time profiles: maximum plasma concentration (Cmax) of ceftriaxone and areas under the concentration-time curve (AUC) from 0 to 36 h and 0 to infinity were the primary parameters considered in the determination of bioequivalence.
The two solutions were generally well tolerated and had similar safety profiles. Administration of both solutions resulted in similar mean values for all pharmacokinetic parameters. Statistical analysis showed no significant differences between the two solutions in any pharmacokinetic parameter, indicating that the two solutions are statistically bioequivalent (p < or = 0.05). The 90% CI for the ratio of the means for AUC0-36 (0.86 to 1.11), AUC0.36 (0.89 to 1.14), and Cmax (0.84 to 1.12) are within the Food and Drug Administration range of bioequivalence (0.80 to 1.25).
These results demonstrate that the more concentrated solution of ceftriaxone (350 mg/mL) is bioequivalent to the currently marketed solution of 250 mg/mL.
L-749,345 is a carbapenem antibiotic, currently in phase II clinical trials, which possesses a broad antibacterial spectrum and extended half-life. The time courses of levels of the drugs in plasma and urinary recovery were evaluated for L-749,345, imipenem-cilastatin (IPM), and ceftriaxone (CTX) in male rhesus monkeys (Macaca mulatta) and a chimpanzee (Pan troglodytes). The chimpanzee pharmacokinetics was predictive of human results and indicated a compound that was superior to IPM and approached CTX in its ability to persist in the circulation. Levels of binding to protein, in the range of clinically relevant concentrations in serum, are virtually equivalent for L-749,345 and CTX in humans. Results of a crossover bioassay versus those of a high-pressure liquid chromatography assay of 1-g human samples showed that there were no bioactive metabolites of L-749,345. The extended half-life at elimination phase of L-749,345 allows consideration of single daily dosing. In contrast to results with IPM, the improved stability of L-749,345 with respect to hydrolysis by the renal dehydropeptidase I (0.25 times the rate of IPM) results in urinary recovery sufficient for the drug's use as a single agent.
MK-826 (formerly L-749,345), is a potent 1-beta-methyl carbapenem with a long half-life and broad spectrum of activity. This compound is presently in phase-II clinical trials. Its activity against a number of gram-positive and gram-negative organisms was compared to those of imipenem (IPM) and eight other beta-lactam agents in two in vivo murine infection models. The distribution in tissue and pharmacokinetic properties of MK-826 and ceftriaxone (CTRX) were also evaluated in CD-1 mice following a single intraperitoneal dose (10 mg/kg of body weight). In addition, concentrations in plasma as well as biliary and urinary recovery of MK-826 were compared to that of CTRX in a cannulated rat model. In a localized murine thigh infection model, MK-826 and IPM were superior to a variety of beta-lactam antibiotics in reduction of Staphylococcus aureus CFU compared with results from nontreated controls (eliminating >/=4 log10 CFU). Similar activities of IPM and MK-826 were observed in a gram-positive bacterial murine systemic infection model. While IPM demonstrated greater efficacy than MK-826 against Enterobacter cloacae (50% effective doses [ED50s] of 0.062 and 0.227 mg/kg, respectively) and Pseudomonas aeruginosa (ED50s of 0.142 and 3.0 mg/kg, respectively) systemic infections, MK-826 was 8- to 350-fold more efficacious than IPM against all other gram-negative organisms in this infection model. In mice, MK-826 demonstrated a higher peak concentration in serum (62.8 versus 42.6 microg/ml) and a larger area under the curve (AUC) (150.8 versus 90.0 microg . hr/ml) than CTRX. The concentrations of MK-826 and CTRX in serum declined slowly, with levels of 3.6 and 2.0 microg/ml remaining, respectively, at 6 h posttreatment. The rat pharmacokinetic model showed the average AUC of MK-826 to be greater than that of CTRX (284 versus 142 microg . hr/ml) following a single 10-mg/kg dose. Also, a half-life of MK-826 longer than that of CTRX (3.2 versus 2.3 h) was observed in this species. The total amount of drug excreted in the bile in 8 h was greater for CTRX (55 to 64% of the dose) than for MK-826 (6 to 12.5% of the dose). Urinary recovery was similar for both antibiotics, with 16 to 18% of the dose recovered over an 8-h period. This excellent broad-spectrum in vivo efficacy of MK-826, together with advantageous pharmacokinetics, supports the argument for its further clinical development.
This study compared the in vitro activities of the new long-half-life carbapenem ertapenem (also known as MK-0826 and L-749,345)
with those of imipenem, amoxicillin-clavulanate, and ciprofloxacin against 5,558 recent clinical isolates from 11 North American
medical centers. We confirmed the greater activity of ertapenem than of imipenem against the Enterobacteriaceae and the greater activity of imipenem against pseudomonads and gram-positive bacteria.
A prospective, multicenter, one in the treatment of community-double-blind, randomized, comparative acquired pneumonia in adults. Clin Infect study to evaluate the safety, tolerability, Dis. In press. Address correspondence to
- G Ortiz-Ruiz
- J Cabellero-Lopez
- I Fried
Ortiz-Ruiz G, Cabellero-Lopez J, Fried-and efficacy of ertapenem versus ceftriax-land I, et al. A prospective, multicenter, one in the treatment of community-double-blind, randomized, comparative acquired pneumonia in adults. Clin Infect study to evaluate the safety, tolerability, Dis. In press. Address correspondence to: Ian Friedland, MD, Merck Research Laboratories, BL 3-4, PO Box 4, West Point, PA 19486-0004. E-mail: ian_friedland@merck.com
A double-blind, multicenter, randomized, phase III study of ertapenem (ETP) vs ceftriaxone (CTX) for treatment of serious community-acquired pneumonia
- Vetter
A large, multicenter, double-blind study of ertapenem vs ceftriaxone in complicated urinary tract infections
- Tomera
Two binomial samples
- Mehta