Skip to main content

Ertapenem

A Review of its Use in the Treatment of Bacterial Infections

Summary

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.

This is a preview of subscription content, access via your institution.

Table I
Table II
Table III
Table IV
Table V
Fig. 1
Table VI
Table VII
Table VIII
Fig. 2
Fig. 3
Fig. 4

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Shah PM, Isaacs RD. Ertapenem, the first of a new group of carbapenems. J Antimicrob Chemother 2003 Oct; 52(4): 538–42

    PubMed  CAS  Google Scholar 

  2. Curran M, Simpson D, Perry C. Ertapenem: a review of its use in the management of bacterial infections. Drugs 2003; 63(17): 1855–78

    PubMed  CAS  Google Scholar 

  3. Merck and Co., Inc. INVANZ® (ertapenem for injection): prescribing information [online]. Available from URL: http:// www.merck.com [Accessed 2005 Jun 20]

  4. European Medicines Agency (EMEA). Summary of product characterisitics: ertapenem [online]. Available from URL: http://www.emea.eu.int [Accessed 2005 Jun 20]

  5. Marchese A, Gualco L, Schito G. Time-kill evaluation of the invitro activity of ertapenem against S. pneumoniae [abstract no. P1748]. Clin Microbiol Infect 2004 May; 10 Suppl. 3: 496–7

    Google Scholar 

  6. Dorso KL, Woods GL, Motyl M, et al. In vitro killing of gram-negative enteric pathogens by ertapenem and other beta-lactams: effect of inoculum size and serum [abstract no. MO 139]. 23rd International Congress of Chemotherapy; 2003 Jun 7–9; Durban

  7. Hecht DW, Lolans K, Quinn JP. Ertapenem resistance in clinical isolates of Enterobacter cloacae associated with loss of a porin protein [abstract no. C1-1199]. 44th Interscience Conference of Antimicrobial Agents and Chemotherapy; 2004 Oct 30–Nov 2; Washington, DC

  8. Hernandez JR, Romero L, Velasco C, et al. Comparative in vitro activity of ertapenem against ESBL-producing E. coli and K. pneumoniae isolated in Spain [abstract no. R1971]. Clin Microbiol Infect 2005 Apr; 11 Suppl. 2: 655

    Google Scholar 

  9. Wexler HM, Molitoris D, Finegold SM. In vitro activities of MK-826 (L-749,345) against 363 strains of anaerobic bacteria. Antimicrob Agents Chemother 2000 Aug; 44(8): 2222–4

    PubMed  CAS  Google Scholar 

  10. Kohler J, Dorso KL, Young K, et al. In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum β-lactamase- and extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates. Antimicrob Agents Chemother 1999 May; 43(5): 1170–6

    PubMed  CAS  Google Scholar 

  11. Alhambra A, Cuadros JA, Cacho J, et al. In vitro susceptibility of recent antibiotic-resistant urinary pathogens to ertapenem and 12 other antibiotics. J Antimicrob Chemother 2004 Jun; 53(6): 1090–4

    PubMed  CAS  Google Scholar 

  12. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; fifteenth informational supplement. Wyane (PA): Clinical and Laboratory Standards Institute, 2005. Report no.: M100-S15

    Google Scholar 

  13. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing of anaerobic bacteria; informational supplement. Wayne (PA): National Committee for Clinical Laboratory Standards, 2003. Report no.: M100-S13 (M11)

    Google Scholar 

  14. Fuchs PC, Barry AL, Brown SD. In vitro activities of ertapenem (MK-0826) against clinical bacterial isolates from 11 North American medical centers. Antimicrob Agents Chemother 2001 Jun; 45(6): 1915–8

    PubMed  CAS  Google Scholar 

  15. Jones RN, Huynh HK, Biedenbach DJ, et al. Doripenem (S-4661), a novel carbapenem: comparative activity against contemporary pathogens including bactericidal action and preliminary in vitro methods evaluations. J Antimicrob Chemother 2004 Jul; 54(1): 144–54

    PubMed  CAS  Google Scholar 

  16. Livermore DM, Carter MW, Bagel S, et al. In vitro activities of ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia. Antimicrob Agents Chemother 2001 Jun; 45(6): 1860–7

    PubMed  CAS  Google Scholar 

  17. Marchese A, Gualco L, Schito AM, et al. In vitro activity of ertapenem against selected respiratory pathogens. J Antimicrob Chemother 2004 Nov; 54(5): 944–51

    PubMed  CAS  Google Scholar 

  18. Paterson DL, Rossi F, Baquero F, et al. In vitro susceptibilities of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: the 2003 Study for Monitoring Antimicrobial Resistance Trends (SMART). J Antimicrob Chemother 2005 Jun; 55(6): 965–73

    PubMed  CAS  Google Scholar 

  19. Pelak BA, Bartizal K, Woods GL, et al. Comparative in vitro activities of ertapenem against aerobic and facultative bacterial pathogens from patients with complicated skin and skin structure infections. Diagn Microbiol Infect Dis 2002; 43: 129–33

    PubMed  CAS  Google Scholar 

  20. Pelak BA, Woods GL, Teppler H, et al. Comparative in-vitro activities of ertapenem against aerobic bacterial pathogens isolated from patients with complicated intra-abdominal infections. J Chemother 2002; 14(3): 227–33

    PubMed  CAS  Google Scholar 

  21. Pelak BA, Citron DM, Motyl M, et al. Comparative in vitro activities of ertapenem against bacterial pathogens from patients with acute pelvic infection. J Antimicrob Chemother 2002; 50: 735–41

    PubMed  CAS  Google Scholar 

  22. Reynolds R, Potz N, Colman M, et al. Antimicrobial susceptibility of the pathogens of bacteraemia in the UK and Ireland 2001–2002: the BSAC Bacteraemia Resistance Surveillance Programme. J Antimicrob Chemother 2004 Jun; 53(6): 1018–32

    PubMed  CAS  Google Scholar 

  23. Samaha-Kfoury JN, Kanj SS, Araj GF. In vitro activity of antimicrobial agents against extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae at a tertiary care center in Lebanon. Am J Infect Control 2005 Apr; 33(3): 134–6

    PubMed  Google Scholar 

  24. Bishara J, Livne G, Ashkenazi S, et al. Antibacterial susceptibility of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli. Isr Med Assoc J 2005 May; 7(5): 298–301

    PubMed  CAS  Google Scholar 

  25. Friedland I, Stinson L, Ikaiddi M, et al. Resistance in Enterobacteriaceae: results of a multicenter surveillance study, 1995–2000. Infect Control Hosp Epidemiol 2003 Aug; 24(8): 607–12

    PubMed  Google Scholar 

  26. Ge Y, Wilder MA, Sahm DF, et al. In vitro antimicrobial activity of doripenem, a new carbapenem. Antimicrob Agents Chemother 2004 Apr; 48(4): 1384–96

    PubMed  CAS  Google Scholar 

  27. Jones RN, Sader HS, Fritsche TR. Comparative activity of doripenem and three other carbapenems tested against Gram-negative bacilli with various β-lactamase resistance mechanisms. Diagn Microbiol Infect Dis 2005 May; 52(1): 71–4

    PubMed  CAS  Google Scholar 

  28. Jones RN, Huynh HK, Biedenbach DJ. Activities of doripenem (S-4661) against drug-resistant clinical pathogens. Antimicrob Agents Chemother 2004 Aug; 48(8): 3136–40

    PubMed  CAS  Google Scholar 

  29. Jones RN. Invitroevaluation of ertapenem (MK-0826), a long-acting carbapenem, tested against selected resistant strains. J Chemother 2001; 13(4): 363–76

    PubMed  CAS  Google Scholar 

  30. Livermore DM, Oakton KJ, Carter MW, et al. Activity of ertapenem (MK-0826) versus Enterobacteriaceae with potent β-lactamases. Antimicrob Agents Chemother 2001 Oct; 45(10): 2831–7

    PubMed  CAS  Google Scholar 

  31. Jacoby G, Han P, Tran J. Comparative in vitro activities of carbapenem L-749,345 and other antimicrobials against multiresistant Gram-negative clinical pathogens. Antimicrob Agents Chemother 1997 Aug; 41(8): 1830–1

    PubMed  CAS  Google Scholar 

  32. Hicks PS, Pelak B, Woods GL, et al. Comparative in vitro activity of ertapenem against bacterial pathogens isolated from patients with lower respiratory tract infections. Clin Microbiol Infect 2002 Nov; 8(11): 753–7

    PubMed  CAS  Google Scholar 

  33. Hilliard NJ, Johnson CN, Armstrong SH, et al. In vitro activity of ertapenem (MK-0826) against multi-drug resistant Streptococcus pneumoniaecompared with 13 other antimicrobials. Int J Antimicrob Agents 2002; 20: 136–40

    PubMed  CAS  Google Scholar 

  34. Aldridge KE. Ertapenem (MK-0826), a new carbapenem: comparative in vitro activity against clinically significantly anaerobes. Diagn Microbiol Infect Dis 2002; 44: 181–6

    PubMed  CAS  Google Scholar 

  35. Betriu C, Sánchez A, Palau ML. In vitro activities of MK-0826 and 16 other antimicrobials against Bacteroidesfragilisgroup strains. Antimicrob Agents Chemother 2001 Aug; 45(8): 2372–4

    PubMed  CAS  Google Scholar 

  36. Goldstein EJC, Citron DM, Merriam CV, et al. General microbiology and in vitro susceptibility of anaerobes isolated from complicated skin and skin-structure infections in paitents enrolled in a comparative trial of ertapenem versus piperacillin tazabactam. Clin Infect Dis 2002; 35 Suppl. 1: S119–25

    PubMed  CAS  Google Scholar 

  37. Goldstein EJC, Citron DM, Merriam CV, et al. Comparative in vitro activities of ertapenem (MK-0826) against 469 less frequently identified anaerobes isolated from human infections. Antimicrob Agents Chemother 2002 Apr; 46(4): 1136–40

    PubMed  CAS  Google Scholar 

  38. Goldstein EJC, Citron DM, Merriam CV, et al. Comparative in vitro activities of ertapenem (MK-0826) against 1,001 anaerobes isolated form human intra-abdominal infections. Antimicrob Agents Chemother 2000 Sep; 44(9): 2389–94

    PubMed  CAS  Google Scholar 

  39. Hoellman DB, Kelly LM, Credito K, et al. In vitro antianaerobic activity of ertapenem (MK-0826) compared to seven other compounds. Antimicrob Agents Chemother 2002 Jan; 46(1): 220–4

    PubMed  CAS  Google Scholar 

  40. Odenholt I, Löwdin E, Cars O. In vitro pharmacodynamic studies of L-749,345 in comparison with imipenem and ceftriaxone against Gram-positive and Gram-negative bacteria. Antimicrob Agents Chemother 1998 Sep; 42(9): 2365–70

    PubMed  CAS  Google Scholar 

  41. Pankuch GA, Davies TA, Jacobs MR, et al. Antipenumococcal activity of ertapenem (MK-0826) compared to those of other agents. Antimicrob Agents Chemother 2002 Jan; 46(1): 42–6

    PubMed  CAS  Google Scholar 

  42. Cottagnoud P, Pfister M, Cottagnoud M, et al. Activities of ertapenem, a new long-acting carbapenem, against penicillin-sensitive or -resistant pneumococci in experiemental meningitis. Antimicrob Agents Chemother 2003 Jun; 47(6): 1943–7

    PubMed  CAS  Google Scholar 

  43. Nix DE, Matthias KR, Ferguson EC. Effect of ertapenem protein binding on killing of bacteria. Antimicrob Agents Chemother 2004 Sep; 48(9): 3419–24

    PubMed  CAS  Google Scholar 

  44. Mouton JW, Touw DJ, Horrevorts AM, et al. Comparative pharmacokinetics of the carbapenems: clinical implications. Clin Pharmacokinet 2000 Sep; 39(3): 185–201

    PubMed  CAS  Google Scholar 

  45. Friedland I, Mixson LA, Majumdar A, et al. Invitroactivity of ertapenem against common clinical isolates in relation to human pharmacokinetics. J Chemother 2002; 14(5): 483–91

    PubMed  CAS  Google Scholar 

  46. Xuan D, Banevicius M, Capitano B, et al. Pharmacodynamic assessment of ertapenem (MK-0826) against Streptococcus pneumoniaein a murine neutropenic thigh infection model. Antimicrob Agents Chemother 2002 Sep; 46(9): 2990–5

    PubMed  CAS  Google Scholar 

  47. Maglio D, Banevicius MA, Sutherland C, et al. Pharmacodynamic profile of ertapenem against Klebsiellapneumoniaeand Escherichiacoliin a murine thigh model. Antimicrob Agents Chemother 2005 Jan; 49(1): 276–80

    PubMed  CAS  Google Scholar 

  48. Bradford PA, Bratu S, Urban C, et al. Emergence of carbapenem-resistant Klebsiellaspecies possessing the class A carbapenem-hydrolyzing KPC-2 and inhibitor-resistant TEM-30 β-lactamases in New York City. Clin Infect Dis 2004 Jul 1; 39: 55–60

    PubMed  CAS  Google Scholar 

  49. Jacoby GA, Munoz-Price LS. The new β-lactamases. N Engl J Med 2005 Jan 27; 352(4): 380–91

    PubMed  CAS  Google Scholar 

  50. Jones RN, Biedenbach DJ, Sader HS, et al. Emerging epidemic of metallo-β-lactamase-mediated resistance. Diagn Microbiol Infect Dis 2005; 51: 77–84

    PubMed  CAS  Google Scholar 

  51. Mushtaq S, Ge Y, Livermore DM. Comparative activities of doripenem versus isolates, mutants, and transconjugants of Enterobacteriaceaeand Acinetobacterspp. with characterized β-lactamases. Antimicrob Agents Chemother 2004 Apr; 48(4): 1313–9

    PubMed  CAS  Google Scholar 

  52. Jacoby GA, Mills DM, Chow N. Role of β-lactamases and porins in resistance to ertapenem and other β-lactams in Klebsiella pneumoniae. Antimicrob Agents Chemother 2004 Aug; 48(8): 3203–6

    PubMed  CAS  Google Scholar 

  53. Bonfigilo G, Russo G, Nicoletti G. Recent developments in carbapenems. Expert Opin Investig Drugs 2002 Apr; 11(4): 529–44

    Google Scholar 

  54. Wexler HM. Invitroactivity of ertapenem: review of recent studies. J Antimicrob Chemother 2004 Jun; 53 Suppl. 2: ii11–21

    PubMed  CAS  Google Scholar 

  55. Livermore DM, Mushtaq S, Warner M. Selectivity of ertapenem for Pseudomonasaeruginosamutants cross-resistant to other carbapenems. J Antimicrob Chemother 2005 Mar; 55(3): 306–11

    PubMed  CAS  Google Scholar 

  56. DiNubile MJ, Friedland I, Chan CY, et al. Bowel colonization with resistant gram-negative bacilli after antimicrobial therapy of intra-abdominal infections: observations from two randomized comparative clinical trials of ertapenem therapy. Eur J Clin Microbiol Infect Dis 2005 Jul; 24(7): 443–9

    PubMed  CAS  Google Scholar 

  57. DiNubile MJ, Chow JW, Satishchandran V, et al. Acquisition of resistant bowel flora during a double-blind randomized clinical trial of ertapenem versus piperacillin-tazobactam therapy for intraabdominal infections. Antimicrob Agents Chemother 2005 Aug; 49(8): 3217–21

    PubMed  CAS  Google Scholar 

  58. Dela Pena A, Asperger W, Köckerling F, et al. Ertapenem vs. piperacillin/tazobactam for the treatment of intra-abdominal infections requiring surgical intervention (OASIS-1): results of a prospective, randomized, open-label study [abstract no. P1686 plus poster]. 14th European Congress of Clinical Microbiology and Infectious Diseases; 2004 May 1–4; Prague

  59. Namias N, Jensen EH, King TR, et al. Efficacy, safety, and tolerability of intravenous (IV) ertapenem (E) vs. piperacillin/ tazobactam (P/T) in the treatment of complicated intra-abdominal infections in hospitalized adults [abstract]. 25th Annual Meeting of the Surgical Infection Society; 2005 May 5–7; Miami (FL)

  60. Holland SD, Majumdar A, Musson D, et al. Pharmacokinetics of ertapenem in renal insufficiency [abstract no. PI-61]. Clin Pharmacol Ther 2001 Feb; 69(2): P16

    Google Scholar 

  61. Bertino JS, Michalak C, Victory J, et al. Comparative pharmacokinetics of ertapenem in normal weight, obese and morbidly obese adults [abstract no. A13 plus poster]. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2004 Oct 30–Nov 2; Washington, DC

  62. Chen M, Nafziger AN, Bertino JS. Pharmacodynamic target attainment in normal size, obese and morbidly obese healthy volunteers receiving one gram doses of ertapenem [abstract no. PI-44]. Clin Pharmacol Ther 2005 Feb; 77(2): P20

    Google Scholar 

  63. Pletz MWR, Rau M, Bulitta J, et al. Ertapenem pharmacokinetics and impact on intestinal microflora, in comparison to those of ceftriaxone, after multiple dosing in male and female volunteers. Antimicrob Agents Chemother 2004 Oct; 48(10): 3765–72

    PubMed  CAS  Google Scholar 

  64. Musson DG, Majumdar A, Birk K, et al. Pharmacokinetics of intramuscularly administered ertapenem. Antimicrob Agents Chemother 2003 May; 47(5): 1732–5

    PubMed  CAS  Google Scholar 

  65. Majumdar AK, Musson DG, Birk KL, et al. Pharmacokinetics of ertapenem in healthy young volunteers. Antimicrob Agents Chemother 2002 Nov; 46(11): 3506–11

    PubMed  CAS  Google Scholar 

  66. Nix DE, Majumdar AK, DiNubile MJ. Pharmacokinetics and pharmacodynamics of ertapenem: an overview for clinicians. J Antimicrob Chemother 2004 Jun; 53 Suppl. 2: ii23–8

    PubMed  CAS  Google Scholar 

  67. Burkhardt O, Majcher-Peszynska J, Borner K, et al. Penetration of ertapenem into different pulmonary compartments of patients undergoing lung surgery. J Clin Pharmacol 2005 Jun; 45(6): 659–65

    PubMed  CAS  Google Scholar 

  68. Laethem T, De Lepeleire I, McCrea J, et al. Tissue penetration by ertapenem, a parenteral carbapenem administered once daily, in suction-induced skin blister fluid in healthy young volunteers. Antimicrob Agents Chemother 2003 Apr; 47(4): 1439–42

    PubMed  CAS  Google Scholar 

  69. Wong BK, Xu X, Yu S, et al. Comparative disposition of [14C]ertapenem, a novel carbepenem antibiotic, in rat, monkey and man. Xenobiotica 2004 Apr; 34(4): 379–89

    PubMed  CAS  Google Scholar 

  70. Musson DG, Majumdar A, Holland S, et al. Pharmacokinetics of total and unbound ertapenem in healthy elderly subjects. Antimicrob Agents Chemother 2004 Feb; 48(2): 521–4

    PubMed  CAS  Google Scholar 

  71. Roy S, Higareda I, Angel-Muller E, et al. Ertapenem once a day versus piperacillin-tazobactam every 6 hours for treatment of acute pelvic infections: a prospective, multicenter, randomized, double-blind study. Infect Dis Obstet Gynecol 2003; 11(1): 27–37

    PubMed  CAS  Google Scholar 

  72. Graham DR, Lucasti C, Malafaia O, et al. Ertapenem once daily versus piperacillin-tazobactam 4 times per day for treatment of complicated skin and skin-structure infections in adults: results of a prospective, randomized, double-blind multicenter study. Clin Infect Dis 2002 Jun 1; 34(11): 1460–8

    PubMed  CAS  Google Scholar 

  73. Lipsky B, Armstrong D, Citron D, et al. Efficacy and safety of ertapenem compared with piperacillin/tazobactam for diabetic foot infections: the SIDESTEP Study [abstract no. O407]. Clin Microbiol Infect 2005 Apr; 11 Suppl. 2: 97. Plus poster presented at the 15th European Congress of Clinical Microbiology and Infectious Diseases; 2005 Apr 2–5; Copenhagen

    Google Scholar 

  74. Solomkin JS, Yellin AE, Rotstein OD, et al. Ertapenem versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections: results of a double-blind, randomized comparative phase III trial. Ann Surg 2003 Feb; 237(2): 235–45

    PubMed  Google Scholar 

  75. Yellin AE, Hassett JM, Fernandez A, et al. Ertapenem monotherapy versus combination therapy with ceftriaxone plus metronidazole for treatment of complicated intra-abdominal infections in adults. Int J Antimicrob Agents 2002 Sep; 20(3): 165–73

    PubMed  CAS  Google Scholar 

  76. Jimenez-Cruz F, Jasovich A, Cajigas J, et al. A prospective, multicenter, randomized, double-blind study comparing ertapenem and ceftriaxone followed by appropriate oral therapy for complicated urinary tract infections in adults. Urology 2002 Jul; 60(1): 16–22

    PubMed  Google Scholar 

  77. Tomera KM, Burdmann EA, Pamo Reyna OG, et al. Ertapenem versus ceftriaxone followed by appropriate oral therapy for treatment of complicated urinary tract infections in adults: results of a prospective, randomized, double-blind multicenter study. Antimicrob Agents Chemother 2002 Sep; 46(9): 2895–900

    PubMed  CAS  Google Scholar 

  78. Ortiz-Ruiz G, Caballero-Lopez J, Friedland IR, et al. A study evaluating the efficacy, safety, and tolerability of ertapenem versus ceftriaxone for the treatment of community-acquired pneumonia in adults. Clin Infect Dis 2002 Apr 15; 34(8): 1076–83

    PubMed  CAS  Google Scholar 

  79. Vetter N, Cambronero-Hernandez E, Rohlf J, et al. A prospective, randomized, double-blind multicenter comparison of parenteral ertapenem and ceftriaxone for the treatment of hospitalized adults with community-acquired pneumonia. Clin Ther 2002 Nov; 24(11): 1770–85

    PubMed  CAS  Google Scholar 

  80. Gesser R, McCarroll K, Woods G. Ertapenem (ETP) vs piperacillin-tazobactam (PT) for the treatment of serious complicated cellulitis [abstract no. 316]. 41st Annual Meeting of the Infectious Diseases Society of America; 2003 Oct 9–12; San Diego (CA)

  81. Gesser R, McCarroll K, Chan C, et al. Abscesses of skin and skin structures: insights from a randomised study of ertapenem vs. piperacillin-tazobactam [abstract no. P1668 and poster]. 14th European Congress of Clinical Microbiology and Infectious Diseases; 2004 May 1–4; Prague

  82. Dela Pena A, Asperger W, Warren B, et al. Microbiological results from a randomised, open-label study of ertapenem vs. piperacillin/tazobactam for the treatment of community-acquired intra-abdominal infections requiring surgery [abstract no. P1685]. 14th European Congress of Clinical Microbiology and Infectious Diseases; 2004 May 1–4; Prague

  83. Friedland I, Teppler H, Meibohm A, et al. Efficacy of ertapenem versus piperacillin/tazobactam for treatment of postoperative complicated intra-abdominal infection [abstract no. MO 142]. 23rd International Congress of Chemotherapy; 2003 Jun 7–9; Durban

  84. Woods G, Isaacs R, McCarroll K, et al. Ertapenem for treatment of CAP caused by Gram-negative enteric pathogens [abstract no. P782]. 13th European Congress of Clinical Microbiology and Infectious Diseases; 2003 May 10–13; Glasgow

  85. Munoz LS, Hovsepian M, Snydman DR, et al. Ertapenem for the treatment of extended spectrum beta-lactamase (ESBL) producing organisms [abstract no. K-1591]. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2004 Oct 30–Nov 2; Washington, DC

  86. Gesser RM, McCarroll KA, Woods GL. Efficacy of ertapenem against methicillin-susceptible Staphylococcusaureusin complicated skin/skin structure infections: results of a double-blind clinical trial versus piperacillin-tazobactam. Int J Antimicrob Agents 2004 Mar; 23(3): 235–9

    PubMed  CAS  Google Scholar 

  87. Gesser RM, McCarroll KA, Woods GL. Evaluation of outpatient treatment with ertapenem in a double blind controlled clinical trial of complicated skin/skin structure infections. J Infect 2004 Jan; 48(1): 32–8

    PubMed  Google Scholar 

  88. Teppler H, Meibohm AR, Woods GL. Management of complicated appendicitis and comparison of outcome with other primary sites of intra-abdominal infection: results of a trial comparing ertapenem and piperacillin-tazobactam. J Chemother 2004 Feb; 16(1): 62–9

    PubMed  CAS  Google Scholar 

  89. Wells WG, Woods GL, Jiang Q, et al. Treatment of complicated urinary tract infection in adults: combined analysis of two randomized, double-blind, multicentre trials comparing ertapenem and ceftriaxone followed by appropriate oral therapy. J Antimicrob Chemother 2004 Jun; 53 Suppl. S2: ii67–74

    PubMed  CAS  Google Scholar 

  90. Ortiz-Ruiz G, Vetter N, Isaacs R, et al. Ertapenem versus ceftriaxone for the treatment of community-acquired pneumonia in adults: combined analysis of two multicentre randomized, double-blind studies. J Antimicrob Chemother 2004 Jun; 53 Suppl. S2: ii59–66

    PubMed  CAS  Google Scholar 

  91. Friedland IR, McCarroll KA, DiNubile MJ, et al. Ertapenem as initial antimicrobial monotherapy for patients with chronic obstructive pulmonary disease hospitalized with typical com pneumonia. Pulm Pharmacol Ther 2004; 17(4): 199–203

    PubMed  CAS  Google Scholar 

  92. Woods GL, Isaacs RD, McCarroll KA, et al. Ertapenem therapy for community-acquired pneumonia in the elderly. J Am Geriatr Soc 2003 Nov; 51(11): 1526–32

    PubMed  Google Scholar 

  93. Gesser RM, McCarroll K, Teppler H, et al. Efficacy of ertapenem in the treatment of serious infections caused by Enterobacteriaceae: analysis of pooled clinical trial data. J Antimicrob Chemother 2003 May; 51: 1253–60

    PubMed  CAS  Google Scholar 

  94. Solomkin J, Teppler H, Graham DR, et al. Treatment of polymicrobial infections: posthocanalysis of three trials comparing ertapenem and piperacillin-tazobactam. J Antimicrob Chemother 2004 Jun; 53 Suppl. S2: ii51–7

    PubMed  CAS  Google Scholar 

  95. Tellado J, Woods GL, Gesser R, et al. Ertapenem versus piperacillin-tazobactam for treatment of mixed anaerobic complicated intra-abdominal, complicated skin and skin structure, and acute pelvic infections. Surg Infect (Larchmt) 2002; 3(4): 303–14

    Google Scholar 

  96. Legua P, Lema J, Moll J, et al. Safety and local tolerability of intramuscularly administered ertapenem diluted in lidocaine: a prospective, randomized, double-blind study versus intramuscular ceftriaxone. Clin Ther 2002; 24(3): 434–44

    PubMed  CAS  Google Scholar 

  97. Sader HS, Gales AC. Emerging strategies in infectious diseases: new carbapenems and trinem antibacterial agents. Drugs 2001; 61(5): 553–64

    PubMed  CAS  Google Scholar 

  98. Thomson KS, Moland ES. CS-023 (R-115685), a novel carbapenem with enhanced in vitro activity against oxacillin-resistant staphylococci and Pseudomonas aeruginosa. J Antimicrob Chemother 2004 Aug; 54(2): 557–62

    PubMed  CAS  Google Scholar 

  99. DiNubile MJ, Lipsky BA. Complicated infections of skin and skin structures: when the infection is more than skin deep. J Antimicrob Chemother 2004 Jun; 53 Suppl. 2: ii37–50

    PubMed  CAS  Google Scholar 

  100. Armstrong DG, Lipsky BA. Advances in the treatment of diabetic foot infections. Diabetes Technol Ther 2004; 6(2): 167–77

    PubMed  CAS  Google Scholar 

  101. Goldstein EJC, Snydman DR. Intra-abdominal infections: review of the bacteriology, antimicrobial susceptibility and the role of ertapenem in their therapy. J Antimicrob Chemother 2004 Jun; 53 Suppl. 2: ii29–36

    PubMed  CAS  Google Scholar 

  102. Carson C, Naber KG. Role of fluoroquinolones in the treatment of serious bacterial urinary tract infections. Drugs 2004; 64(12): 1359–73

    PubMed  CAS  Google Scholar 

  103. Lipsky BA, Berendt AR, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2004 Oct 1; 39(7): 885–910

    PubMed  Google Scholar 

  104. Solomkin JS, Mazuski JE, Baron EJ, et al. Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections. Clin Infect Dis 2003 Oct 15; 37(8): 997–1005

    PubMed  Google Scholar 

  105. Mazuski JE, Sawyer RG, Nathens AB, et al. The Surgical Infection Society Guidelines on antimicrobial therapy for intra-abdominal infections: an executive summary. Surg Infect 2002; 3(3): 161–73

    Google Scholar 

  106. Mandell LA, Bartlett JG, Dowell SF, et al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 2003 Dec 1; 37(11): 1405–33

    PubMed  Google Scholar 

  107. Woodford N, Ward ME, Kaufmann ME, et al. Community and hospital spread of Escherichiacoliproducing CTX-M extended-spectrum β-lactamases in the UK. J Antimicrob Chemother 2004; 54: 735–43

    PubMed  CAS  Google Scholar 

  108. Munday CJ, Whitehead GM, Todd NJ, et al. Predominance and genetic diversity of community- and hospital-acquired CTX-M extended-spectrum β-lactamases in York, UK. J Antimicrob Chemother 2004; 54: 628–33

    PubMed  CAS  Google Scholar 

  109. Colodner R, Rock W, Chazan B, et al. Risk factors for the development of extended-spectrum beta-lactamase-producing bacteria in nonhospitalized patients. Eur J Clin Microbiol Infect Dis 2004; 23: 163–7

    PubMed  CAS  Google Scholar 

  110. Paterson DL, Ko W-C, Von Gottberg A, et al. Antibiotic therapy forKlebsiellapneumoniaebacteremia: implications of production of extended-spectrum β-lactamases. Clin Infect Dis 2004 Jul 1; 39: 31–7

    PubMed  CAS  Google Scholar 

  111. Moczygemba LR, Frei CR, Burgess DS. Pharmacodynamic modeling of carbapenems and fluoroquinolones against bacteria that produce extended-spectrum beta-lactamases. Clin Ther 2004 Nov; 26(11): 1800–7

    PubMed  CAS  Google Scholar 

  112. Jones RN, Biedenbach DJ, Gales AC. Sustained activity and spectrum of selected extended-spectrum β-lactams (carbapenems and cefepime) against Enterobacter spp. and ESBL-producing Klebsiellaspp.: report from the SENTRY antimicrobial surveillance program (USA, 1997–2000). Int J Antimicrob Agents 2003 Jan; 21(1): 1–7

    PubMed  CAS  Google Scholar 

  113. Valverde A, Coque TM, Sánchez-Moreno MP, et al. Dramatic increase in prevalence of fecal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceaeduring nonout-break situations in Spain. J Clin Microbiol 2004 Oct; 42(10): 4769–75

    PubMed  CAS  Google Scholar 

  114. Rodríguez-Baño J, Navarro DM, Romero L, et al. Epidemiology and clinical features of infections caused by extended-spectrum beta-lactamase-producing Escherichiacoliin nonhospitalized patients. J Clin Microbiol 2004 Mar; 42(3): 1089–94

    PubMed  Google Scholar 

  115. Briggs S, Ussher J, Taylor S. Extended-spectrum beta-lactamase-producing Enterobacteriaceaeat Middlemore Hospital. N Z Med J 2005 Jul 15; 118(1218): U1563

    PubMed  Google Scholar 

  116. Villegas MV, Quinn JP. An update on antibiotic-resistant Gram-negative bacteria. Infect Med 2004; 21(12): 595–9

    Google Scholar 

  117. Livermore DM, Sefton AM, Scott GM. Properties and potential of ertapenem. J Antimicrob Chemother 2003 Sep; 52(3): 331–44

    PubMed  CAS  Google Scholar 

  118. Paramythiotou E, Lucet J-C, Timsit J-F, et al. Acquisition of multidrug-resistant Pseudomonasaeruginosain patients in intensive care units: role of antibiotics with antipseudomonal activity. Clin Infect Dis 2004 Mar 1; 38: 670–7

    PubMed  Google Scholar 

  119. Nordmann P, Poirel L. Emerging carbapenemases in Gram-negative aerobes. Clin Microbiol Infect 2002; 8: 321–31

    PubMed  CAS  Google Scholar 

  120. Tice AD. Ertapenem: a new opportunity for outpatient parenteral antimicrobial therapy. J Antimicrob Chemother 2004 Jun; 53 Suppl. 2: ii83–6

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

At the request of the journal, Merck & Co. provided a non-binding review of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gillian M. Keating.

Additional information

Various sections of the manuscript reviewed by: D.G. Armstrong, Dr William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA; J. Bishara, Infectious Disease Unit, Rabin Medical Center, Petah-Tikva, Israel; E.J.C. Goldstein, R. M. Alden Research Laboratory, Santa Monica, California, USA; D.R. Graham, Department of Infectious Diseases, Springfield Clinic, Springfield, Illinois, USA; R.N. Jones, The JONES Group/JMI Laboratories, North Liberty, Iowa, USA; S. Roy, Keck School of Medicine of the University of South California, Women’s and Children’s Hospital, Los Angeles, California, USA.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘ertapenem’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE search terms were ‘ertapenem’. EMBASE search terms were ‘ertapenem’. AdisBase search terms were ‘ertapenem’. Searches were last updated 26 September 2005.

Selection: Studies in patients with bacterial infections who received ertapenem. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Ertapenem, skin and skin structure infection, intra-abdominal infection, urinary tract infection, community-acquired pneumonia, pelvic infection, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Keating, G.M., Perry, C.M. Ertapenem. Drugs 65, 2151–2178 (2005). https://doi.org/10.2165/00003495-200565150-00013

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200565150-00013

Keywords

  • Ceftriaxone
  • Ertapenem
  • Clinical Cure Rate
  • Evaluable Population
  • Outpatient Parenteral Antimicrobial Therapy