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George Sakoulas - One of the best experts on this subject based on the ideXlab platform.
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cefazolin and Ertapenem salvage therapy rapidly clears persistent methicillin susceptible staphylococcus aureus bacteremia
Clinical Infectious Diseases, 2020Co-Authors: George Sakoulas, Victor Nizet, Erlinda R Ulloa, Kavindra V Singh, Matthew Geriak, Fadi Haddad, Barbara E MurrayAbstract:Cefazolin and Ertapenem combination therapy was used successfully to salvage 11 cases (6 endocarditis) of persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including immediate clearance (≤24 hours) in 8 cases. While in vitro synergy was modest, cefazolin plus Ertapenem exhibited synergistic action in a rat model of MSSA endocarditis. The combination of cefazolin and Ertapenem provides potent in vivo activity against MSSA beyond what is predicted in vitro and warrants further clinical study in the treatment of refractory MSSA bacteremia and endocarditis.
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cefazolin and Ertapenem a synergistic combination used to clear persistent staphylococcus aureus bacteremia
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: George Sakoulas, Joshua Olson, Juwon Yim, Niedita B Singh, Monika Kumaraswamy, Diana T Quach, Michael J Rybak, Joe Pogliano, Victor NizetAbstract:Ertapenem and cefazolin were used in combination to successfully clear refractory methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. In addition, recent work has demonstrated activity of combination therapy with beta-lactams from different classes against methicillin-resistant S. aureus (MRSA). The Ertapenem-plus-cefazolin combination was evaluated for synergy in vitro and in vivo in a murine skin infection model using an index MSSA bloodstream isolate from a patient in whom persistent bacteremia was cleared with this combination and against a cadre of well-described research strains and clinical strains of MSSA and MRSA. Against the index MSSA bloodstream isolate, Ertapenem and cefazolin showed synergy using both checkerboard (fractional inhibitory concentration [FIC] index = 0.375) and time-kill assays. Using a disk diffusion Ertapenem potentiation assay, the MSSA isolate showed a cefazolin disk zone increased from 34 to 40 mm. In vitro pharmacokinetic/pharmacodynamic modeling at clinically relevant drug concentrations demonstrated bactericidal activity (>3 log10-CFU/ml reduction) of the combination but bacteriostatic activity of ether drug alone at 48 h. A disk diffusion potentiation assay showed that Ertapenem increased the cefazolin zone of inhibition by >3 mm for 34/35 (97%) MSSA and 10/15 (67%) MRSA strains. A murine skin infection model of MSSA showed enhanced activity of cefazolin plus Ertapenem compared to monotherapy with these agents. After successful use in clearance of MSSA bacteremia, the combination of Ertapenem and cefazolin showed synergy against MSSA in vitro and in vivo This combination may warrant consideration for future clinical study in MSSA bacteremia.
Robin Isaacs - One of the best experts on this subject based on the ideXlab platform.
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Safety and tolerability of Ertapenem
Journal of Antimicrobial Chemotherapy, 2004Co-Authors: Hedy Teppler, Richard M. Gesser, Ian R. Friedland, Gail L. Woods, Anne R. Meibohm, Gary Herman, G. Mistry, Robin IsaacsAbstract: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.
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Ertapenem Therapy for Community‐Acquired Pneumonia in the Elderly
Journal of the American Geriatrics Society, 2003Co-Authors: Gail L. Woods, Robin Isaacs, Kathleen A Mccarroll, Ian R. FriedlandAbstract:Objectives: To compare the efficacy and safety of Ertapenem, 1 g once a day, with ceftriaxone, 1 g once a day, for treatment of the subgroup of patients aged 65 and older with community-acquired pneumonia (CAP) requiring parenteral therapy. Design: Combined data from patients aged 65 and older in two randomized, double-blind clinical trials. Setting: Eighty international centers. Participants: Eight hundred fifty-seven treated patients, of whom 351 were aged 65 and older. Interventions: Intravenous or intramuscular Ertapenem or ceftriaxone with the option to switch to oral amoxicillin-clavulanate after at least 3 days of parenteral therapy. Measurements: Clinical efficacy was assessed at completion of parenteral therapy and 7 to 14 days after all therapy had been completed (test of cure (TOC) assessment). Bacterial eradication was assessed at the TOC visit. Safety was assessed daily during study therapy and for 14 days thereafter. Results: One hundred forty-eight clinically evaluable patients aged 65 and older were treated with Ertapenem and 125 with ceftriaxone. Pathogens were identified in 157 (57.5%) patients (the most common being Streptococcus pneumoniae), most of which were penicillin-susceptible. Clinical cure rates were 95.9% for patients in the Ertapenem group and 92.7% for patients in the ceftriaxone group at completion of parenteral therapy and 93.9% and 90.4%, respectively, at the TOC assessment. Overall bacterial eradication rates were 92.8% (77 of 83) for patients treated with Ertapenem and 93.2% (69 of 74) for those treated with ceftriaxone. The most common drug-related adverse experiences in both treatment groups were diarrhea and mild to moderate elevation of serum aminotransferase levels. Conclusion: Ertapenem 1 g once a day was highly effective for treatment of elderly patients with CAP requiring parenteral therapy and was as effective as ceftriaxone. Ertapenem was generally well tolerated, with an overall safety profile similar to ceftriaxone.
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a prospective randomized double blind multicenter comparison of parenteral Ertapenem and ceftriaxone for the treatment of hospitalized adults with community acquired pneumonia
Clinical Therapeutics, 2002Co-Authors: Norbert Vetter, Eduardo Cambronerohernandez, Jane Rohlf, Stuart Simon, Alexandra D Carides, B Teresa S Oliveria, Robin IsaacsAbstract:Abstract Background: Ertapenem is a once-daily parenteral beta-lactam licensed in the United States in November 2001 and in Europe in May 2002. Objective: This study compared the efficacy and safety profiles of Ertapenem with those of ceftriaxone for the treatment of hospitalized adult patients with serious community-acquired pneumonia (CAP) requiring parenteral therapy. Methods: In this prospective, double-blind (with sponsor blinding), multicenter study, adult patients with CAP were stratified by Pneumonia Severity Index (≤3 or >3) and age (≤65 or >65 years ) and randomized (2:1) to receive IV or intramuscular (IM) Ertapenem 1 g once daily or IV or IM ceftriaxone 1 g once daily. Investigators could switch patients to an oral antimicrobial agent if clinical improvement was shown after at least 3 days of parenteral therapy. Results: A total of 364 patients were randomized to treatment: 239 to the Ertapenem group and 125 to the ceftriaxone group. Three patients in the Ertapenem group and 2 in the ceftriaxone group did not receive study therapy. Of the treated patients, 77.1% (182/236) of patients in the Ertapenem group and 75.6% (93/123) in the ceftriaxone group were clinically evaluable. Among clinically evaluable patients, the mean (SD) durations of parenteral and total (parenteral plus optional oral) therapy were 5.5 (2.6) and 11.5 (2.7) days for Ertapenem and 5.6 (2.8) and 11.7 (3.0) days for ceftriaxone, respectively. Streptoccocus pneumoniae was the most frequently isolated pathogen in both treatment groups. Cure rates were 92.2% for clinically evaluable patients in the Ertapenem group and 93.6% for those in the ceftriaxone group (95% CI for the difference, adjusted for stratum, −8.6 to 5.7), fulfilling the criteria for statistical equivalence. At completion of parenteral therapy, 94.7% of patients in the Ertapenem group and 95.8% in the ceftriaxone group showed clinical improvement. Infused vein complications (Ertapenem, 3.4% [8/236]; ceftriaxone, 7.3% [9/123]) and elevated transaminase levels (Ertapenem, 6.3% [13/207]; ceftriaxone, 7.1% [8/113]) were the most common adverse events in both groups. Conclusions: In this study of hospitalized adult patients, Ertapenem therapy, with an oral switch option, was as effective as ceftriaxone with the same oral switch option for treatment of CAP requiring initial parenteral therapy. The overall safety profiles of the 2 drugs were comparable.
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Use of surrogate antimicrobial agents to predict susceptibility to Ertapenem
Diagnostic microbiology and infectious disease, 2002Co-Authors: Ian R. Friedland, Robin Isaacs, Lori Mixson, Mary Motyl, Gail L. WoodsAbstract: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.
G. Mistry - One of the best experts on this subject based on the ideXlab platform.
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Safety and tolerability of Ertapenem
Journal of Antimicrobial Chemotherapy, 2004Co-Authors: Hedy Teppler, Richard M. Gesser, Ian R. Friedland, Gail L. Woods, Anne R. Meibohm, Gary Herman, G. Mistry, Robin IsaacsAbstract: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.
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Pharmacokinetics of Total and Unbound Ertapenem in Healthy Elderly Subjects
Antimicrobial agents and chemotherapy, 2004Co-Authors: Donald G Musson, G. Mistry, Anup Majumdar, Kimberly L Birk, S Holland, D. Sciberras, J. Muckow, Paul Deutsch, J.d. RogersAbstract:Ertapenem is a new once-a-day parenteral carbapenem antimicrobial agent. The pharmacokinetics of unbound and total concentrations of Ertapenem in plasma were investigated in elderly subjects and compared with historical data from young adults. In a single- and multiple-dose study, healthy elderly males and females (n = 14) 65 years old or older were given a 1-g intravenous (i.v.) dose once daily for 7 days. Plasma and urine samples collected for 24 h on days 1 and 7 following administration of the 1-g doses were analyzed by reversed-phase high-performance liquid chromatography. Areas under the concentration-time curve from 0 h to infinity (AUC(0- infinity )) for elderly females and males were similar following administration of 1-g single i.v. doses, and thus, the genders were pooled in subsequent analyses. Concentrations in plasma and the half-life of Ertapenem were generally higher and longer, respectively, in elderly subjects than in young adults. The mean AUC(0- infinity ) of total Ertapenem in the elderly was 39% higher than that in young subjects following administration of a 1-g dose. The differences were slightly greater for the mean AUC(0- infinity ) of unbound Ertapenem (71%). The unbound fraction of Ertapenem in elderly subjects ( approximately 5 to 11%) was generally greater than that in young adults ( approximately 5 to 8%). As in young adults, Ertapenem did not accumulate upon multiple dosing in the elderly. The pharmacokinetics of Ertapenem in elderly subjects, while slightly different from those in young adults, do not require a dosage adjustment for elderly patients.
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pharmacokinetics of Ertapenem in healthy young volunteers
Antimicrobial Agents and Chemotherapy, 2002Co-Authors: Anup Majumdar, G. Mistry, Donald G Musson, Kimberly L Birk, Chester J Kitchen, S Holland, Jacqueline B Mccrea, Michael Hesney, R Haesen, Robert A BlumAbstract:Ertapenem (INVANZ) is a new once-a-day parenteral beta-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 approximately 95% bound at concentrations of <50 micro g/ml to approximately 92% bound at concentrations of 150 micro g/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 (AUC(0- infinity )) of total Ertapenem. The single-dose AUC(0- infinity ) 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 approximately 145 to 175 micro g/ml at the end of a 30-min infusion, from approximately 30 to 34 micro g/ml at 6 h, and from approximately 9 to 11 micro g/ml at 12 h. The mean plasma t(1/2) ranged from 3.8 to 4.4 h. About 45% of the plasma clearance (CL(P)) was via renal clearance. The remainder of the CL(P) was primarily via the formation of the beta-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.
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Pharmacokinetics of Ertapenem in Healthy Young Volunteers
Antimicrobial agents and chemotherapy, 2002Co-Authors: Anup Majumdar, G. Mistry, Donald G Musson, Kimberly L Birk, Chester J Kitchen, S Holland, Jacqueline B Mccrea, Michael HesneyAbstract:Ertapenem (INVANZ) is a new once-a-day parenteral beta-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 approximately 95% bound at concentrations of
Gail L. Woods - One of the best experts on this subject based on the ideXlab platform.
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Safety and tolerability of Ertapenem
Journal of Antimicrobial Chemotherapy, 2004Co-Authors: Hedy Teppler, Richard M. Gesser, Ian R. Friedland, Gail L. Woods, Anne R. Meibohm, Gary Herman, G. Mistry, Robin IsaacsAbstract: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.
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Ertapenem Therapy for Community‐Acquired Pneumonia in the Elderly
Journal of the American Geriatrics Society, 2003Co-Authors: Gail L. Woods, Robin Isaacs, Kathleen A Mccarroll, Ian R. FriedlandAbstract:Objectives: To compare the efficacy and safety of Ertapenem, 1 g once a day, with ceftriaxone, 1 g once a day, for treatment of the subgroup of patients aged 65 and older with community-acquired pneumonia (CAP) requiring parenteral therapy. Design: Combined data from patients aged 65 and older in two randomized, double-blind clinical trials. Setting: Eighty international centers. Participants: Eight hundred fifty-seven treated patients, of whom 351 were aged 65 and older. Interventions: Intravenous or intramuscular Ertapenem or ceftriaxone with the option to switch to oral amoxicillin-clavulanate after at least 3 days of parenteral therapy. Measurements: Clinical efficacy was assessed at completion of parenteral therapy and 7 to 14 days after all therapy had been completed (test of cure (TOC) assessment). Bacterial eradication was assessed at the TOC visit. Safety was assessed daily during study therapy and for 14 days thereafter. Results: One hundred forty-eight clinically evaluable patients aged 65 and older were treated with Ertapenem and 125 with ceftriaxone. Pathogens were identified in 157 (57.5%) patients (the most common being Streptococcus pneumoniae), most of which were penicillin-susceptible. Clinical cure rates were 95.9% for patients in the Ertapenem group and 92.7% for patients in the ceftriaxone group at completion of parenteral therapy and 93.9% and 90.4%, respectively, at the TOC assessment. Overall bacterial eradication rates were 92.8% (77 of 83) for patients treated with Ertapenem and 93.2% (69 of 74) for those treated with ceftriaxone. The most common drug-related adverse experiences in both treatment groups were diarrhea and mild to moderate elevation of serum aminotransferase levels. Conclusion: Ertapenem 1 g once a day was highly effective for treatment of elderly patients with CAP requiring parenteral therapy and was as effective as ceftriaxone. Ertapenem was generally well tolerated, with an overall safety profile similar to ceftriaxone.
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a study evaluating the efficacy safety and tolerability of Ertapenem versus ceftriaxone for the treatment of community acquired pneumonia in adults
Clinical Infectious Diseases, 2002Co-Authors: Guillermo Ortizruiz, Ian R. Friedland, Gail L. Woods, Jose Caballerolopez, Alexandra D CaridesAbstract: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.
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Use of surrogate antimicrobial agents to predict susceptibility to Ertapenem
Diagnostic microbiology and infectious disease, 2002Co-Authors: Ian R. Friedland, Robin Isaacs, Lori Mixson, Mary Motyl, Gail L. WoodsAbstract: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.
Ian R. Friedland - One of the best experts on this subject based on the ideXlab platform.
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Safety and tolerability of Ertapenem
Journal of Antimicrobial Chemotherapy, 2004Co-Authors: Hedy Teppler, Richard M. Gesser, Ian R. Friedland, Gail L. Woods, Anne R. Meibohm, Gary Herman, G. Mistry, Robin IsaacsAbstract: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.
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Ertapenem Therapy for Community‐Acquired Pneumonia in the Elderly
Journal of the American Geriatrics Society, 2003Co-Authors: Gail L. Woods, Robin Isaacs, Kathleen A Mccarroll, Ian R. FriedlandAbstract:Objectives: To compare the efficacy and safety of Ertapenem, 1 g once a day, with ceftriaxone, 1 g once a day, for treatment of the subgroup of patients aged 65 and older with community-acquired pneumonia (CAP) requiring parenteral therapy. Design: Combined data from patients aged 65 and older in two randomized, double-blind clinical trials. Setting: Eighty international centers. Participants: Eight hundred fifty-seven treated patients, of whom 351 were aged 65 and older. Interventions: Intravenous or intramuscular Ertapenem or ceftriaxone with the option to switch to oral amoxicillin-clavulanate after at least 3 days of parenteral therapy. Measurements: Clinical efficacy was assessed at completion of parenteral therapy and 7 to 14 days after all therapy had been completed (test of cure (TOC) assessment). Bacterial eradication was assessed at the TOC visit. Safety was assessed daily during study therapy and for 14 days thereafter. Results: One hundred forty-eight clinically evaluable patients aged 65 and older were treated with Ertapenem and 125 with ceftriaxone. Pathogens were identified in 157 (57.5%) patients (the most common being Streptococcus pneumoniae), most of which were penicillin-susceptible. Clinical cure rates were 95.9% for patients in the Ertapenem group and 92.7% for patients in the ceftriaxone group at completion of parenteral therapy and 93.9% and 90.4%, respectively, at the TOC assessment. Overall bacterial eradication rates were 92.8% (77 of 83) for patients treated with Ertapenem and 93.2% (69 of 74) for those treated with ceftriaxone. The most common drug-related adverse experiences in both treatment groups were diarrhea and mild to moderate elevation of serum aminotransferase levels. Conclusion: Ertapenem 1 g once a day was highly effective for treatment of elderly patients with CAP requiring parenteral therapy and was as effective as ceftriaxone. Ertapenem was generally well tolerated, with an overall safety profile similar to ceftriaxone.
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a study evaluating the efficacy safety and tolerability of Ertapenem versus ceftriaxone for the treatment of community acquired pneumonia in adults
Clinical Infectious Diseases, 2002Co-Authors: Guillermo Ortizruiz, Ian R. Friedland, Gail L. Woods, Jose Caballerolopez, Alexandra D CaridesAbstract: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.
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Use of surrogate antimicrobial agents to predict susceptibility to Ertapenem
Diagnostic microbiology and infectious disease, 2002Co-Authors: Ian R. Friedland, Robin Isaacs, Lori Mixson, Mary Motyl, Gail L. WoodsAbstract: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.