Skip to main content
SpringerLink
Log in

Imipenem/Cilastatin

A Reappraisal of its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Efficacy

  • Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

An Erratum to this article was published on 01 December 1992

Abstract

Synopsis

Imipenem is an antibacterial agent of the carbapenem class of β-lactams, with a very broad spectrum of activity that includes most Gram-negative and Gram-positive pathogens, aerobes and anaerobes, and with marked activity against species producing β-lactamases. It is coadministered with cilastatin, a renal dehydropeptidase inhibitor that prevents renal metabolism of imipenem. As initial monotherapy, imipenem/cilastatin provides effective and well-tolerated treatment of moderate to severe infections in various body systems, including intr-abdominal, obstetric and gynaecological, lower respiratory tract, skin and soft tissue, and urinary tract infections, and also in bacteraemia and septicaemia, and in patients with malignancy-related febrile neutropenia. It is likely to be of particular benefit in cases where bacterial pathogens have not yet been identified, such as in the treatment of serious infections in immunocompromised patients, or in an intensive care setting. Thus, imipenem/cilastatin is effective as initial monotherapy of a variety of infections, including infections in neutropenic patients, with a clear role in empirical treatment of mixed infection.

Antibacterial Activity

Data published since the earlier review in the Journal confirm the in vitro activity of imipenem against a wide range of Enterobacteriaceae and other Gram-negative aerobic bacteria (except Xanthomonas maltophilia and Pseudomonas cepacia), Gram-positive aerobic bacteria and anaerobic microorganisms. Imipenem is generally more active than third-generation cephalosporins against Enterobacter cloacae and Citrobacter freundii and of similar activity to these antibacterial agents against other Enterobacteriaceae, but is generally less active than ciprofloxacin against Escherichia coli, Klebsieila pneumoniae, E. cloacae and Serratia marcescens. Recent studies confirm the excellent activity of imipenem against methicillin-susceptible strains of commonly isolated Gram-positive aerobic bacteria as well as less common strains such as Listeria monocytogenes and Rhodococcus equi. The activity of imipenem against the Bacteroides fragilis group, other Bacteroides species and Clostridium species is comparable with that of metronidazole and the investigational drug meropenem.

The minimum bactericidal concentration in vitro of imipenem against Enterobacteriaceae, Bacteroides species and most staphylococci and streptococci is equal to or within one dilution of the minimum inhibitory concentration (MIC). The drug has a postantibiotic effect lasting 3 hours (mean). The in vitro activity of imipenem is not significantly influenced by an increase in inoculum size to 106 colony forming units, but the drug is inactivated in thioglycolate broth. The activity of imipenem against coagulase negative staphylococci, like that of cefuroxime and ciprofloxacin, is reduced in used peritoneal dialysis fluid and when these bacteria adhere to silicone rubber.

Recent studies confirm the synergistic effect of the imipenem/amikacin combination against imipenem-susceptible Pseudomonas aeruginosa but show variable results when imipenem is combined with fluoroquinolones. Two studies have observed synergistic activity of imipenem and cefotiam, cefazolin or cefpiramide against a large proportion of tested strains of methicillin-re-sistant Staphylococcus aureus.

Although a strong inducer of class I β-lactamases, imipenem is not hydrolysed by these enzymes and has remained active against a wide range of β-lactamase- and non-β-lactamase-producing bacteria; studies conducted in many countries found that over 90% of large numbers of Gram-negative clinical isolates remained susceptible to imipenem 4 mg/L. A consistent finding was the general lack of cross-resistance between imipenem and other β-lactam antibiotics. Mutational loss of susceptibility of P. aeruginosa to imipenem is apparently due to loss of a specific outer membrane porin that facilitates entry of imipenem but not other agents.

The earlier reported efficacy of imipenem in eradicating experimental infection in animal models was confirmed in more recent studies. Fractional administration of imipenem to neutropenic mice, simulating treatment with 500mg 12-hourly intramuscularly or 6-hourly intravenously in humans, showed similar bactericidal efficacy with both routes, and indicated that in this model the duration that plasma antibiotic concentrations exceeded MIC was more important in determining efficacy than the magnitude of peak concentration above MIC. Imipenem and cefoxitin were generally more effective than cefotetan, ceftizoxime and ampicillin/sulbactam in reducing numbers of E. coli and B. fragilis group organisms in mice with subcutaneous abscesses. A murine peritonitis model, designed to detect and quantify resistance after short term antimicrobial therapy, suggested that resistance to third-generation cephalosporins, pefloxacin and ciprofloxacin developed more readily than to imipenem in tested Enterobacteriaceae and P. aeruginosa.

Pharmacokinetic Properties

In clinical practice, imipenem is administered with an equal amount of cilastatin to reduce the postexcretory metabolism of imipenem by dehydropeptidase-I, which is localised in the brush border microvilli of the proximal tubule. An additional reason for coadministration of cilastatin is to obviate nephrotoxicity observed in some animal species when imipenem is administered alone. A 1: 1 combination of imipenem/cilastatin is required to maintain inhibition of renal metabolism for more than 8 hours. Accumulation of cilastatin has been observed in patients with severe renal impairment and in neonates, but has not been associated with adverse sequelae.

Single dose intravenous infusion of imipenem/cilastatin 500 or 1000mg to healthy volunteers results in mean maximum plasma concentrations of 30 to 35 mg/L and 60 to 70 mg/L, respectively, which decline to 0.5 and 2 mg/L, respectively, 4 to 6 hours later. Following intramuscular administration of 500 or 750mg mean maximum imipenem plasma concentrations were 7.4 to 10.4 and 8.2 to 11.7 mg/L, respectively, and remained above 0.4 mg/L for 12 hours. Administration of imipenem 500mg intramuscularly provided mean plasma concentrations above 4 and 2 mg/L for a time period equivalent to that following intravenous injection of the same dose 8-hourly.

Steady-state volume of distribution following intravenous infusion was 14.4L and protein binding of imipenem was reported as < 10 to 20%. One to 2 hours after intravenous administration of imipenem/cilastatin 500mg, concentrations of imipenem in sputum, tonsillar tissue, prostatic tissue, female genital organs and synovial fluid exceed MICs for most susceptible Gram-negative and Gram-positive aerobic bacteria. Such concentrations are also achieved in surgical specimens of colon, peritoneum, intestinal mucosa, and abdominal muscle and in bile obtained by T-tube drainage. In patients with inflamed meninges, concentrations in cerebrospinal fluid ranged from 1.1 to 2.3 mg/L following intravenous administration of imipenem/cilastatin 1000mg.

The elimination half-life of both imipenem and cilastatin is about 1 hour after intravenous administration, but increases to 2.5 to 3.8 and 2.6 to 5.1 hours after intramuscular administration of 500 and 750mg, respectively. The proportion of a dose excreted in the urine is similar after either route; however, peak urinary concentrations are lower after intramuscular injection.

In patients with severely impaired renal function, the elimination half-life of cilastatin is prolonged (to between 7 and 16 hours), to a greater degree than that of imipenem (around 3 hours); in premature infants, half-lives are prolonged to 2.5 and 9.1 hours, respectively. As might be expected, the pharmacokinetic profile of imipenem/cilastatin in elderly volunteers is similar to that in young patients with mild renal impairment.

Therapeutic Use

Imipenem/cilastatin has been shown to be efficacious in controlled trials in patients with infections of various body systems. In randomised nonblind trials in intra-abdominal infections, intravenous imipenem/cilastatin was as efficacious as either triple therapy (an aminoglycoside plus a penicillin plus metronidazole or clindamycin), or a ‘third-generation’ cephalosporin plus metronidazole, whether clinical or bacteriological efficacy was considered. In one large comparison in which patients were stratified for severity of infection, imipenem/cilastatin was significantly superior to tobramycin plus clindamycin. Intravenous imipenem/cilastatin has produced clinical efficacy rates of between 81 and 100% in the treatment of obstetric and gynaecological infections, and a rate of clinical success of 89.7% has now been reported in one trial of intramuscular imipenem/cilastatin in such patients. In severe lower respiratory tract infection, addition of an aminoglycoside has been recommended to reduce the likelihood of development of resistance to imipenem associated with P. aeruginosa infection. Using such a strategy, clinical cure and/or improvement was apparent in 72 to 100% of patients with community-acquired infection treated intravenously and in 95% of those treated intramuscularly. In patients with hospital-acquired lower respiratory tract infections, imipenem/cilastatin was of comparable clinical efficacy to cefotaxime plus amikacin plus pefloxacin. Clinical efficacy rates for imipenem/cilastatin in skin and soft tissue infection approximate 95%, with bacteriological cure in 86%, these findings for intravenous administration being sustained in one trial of intramuscular use. Intramuscular imipenem/cilastatin also has demonstrated efficacy in urinary tract infection (UTI), overall efficacy of 76% being obtained in one study in complicated UTI. Clinical cure was obtained in 82% of patients with septicaemia treated with imipenem/cilastatin in a further trial.

In recent clinical research, imipenem/cilastatin has been shown to provide effective treatment of infections in neutropenic patients with malignant disease. Controlled comparative trials indicate that imipenem/cilastatin is more effective as initial monotherapy in febrile neutropenic patients than ceftazidime, or indeed, cefoperazone or ceftazidime plus piperacillin. In treatment of severe infections in patients in intensive care, rates of clinical cure with intravenous imipenem/ cilastatin have been reported variously as 77 and 83%, the latter figure being the same as that obtained with triple therapy with amoxicillin plus clindamycin plus netilmicin or tobramycin. In a small number of patients, resistance of P. aeruginosa to imipenem developed despite use of an aminoglycoside. Intravenous imipenem/cilastatin has also been used successfully in paediatric patients with cancer, as well as in trials in paediatric patients with infections of various body systems, where clinical efficacy rates approach 100%.

Tolerability

Imipenem/cilastatin is in general well tolerated in clinical trials. The most frequent adverse clinical events reported, in common with other β-lactam antibacterials, are nausea, vomiting and diarrhoea, skin rashes, phlebitis at the injection site, transient elevation of liver function test results, and eosinophilia. Seizures have occurred in patients with CNS dysfunction and renal failure, in conjunction with unadjusted dosage regimens. The risk of seizure increases sharply with increasing dosages (> 2 g/day), emphasising the necessity for careful dosage adjustment in patients with impaired renal function. The intramuscular formulation provides the advantage of avoiding some adverse events, such as phlebitis and nausea, associated with intravenous administration.

Dosage and Administration

In adults, the usual intravenous dosage of imipenem/cilastatin is 500 to 750mg, administered 6-hourly, depending on the severity of infection; a daily dosage of 2g is most frequently employed. Intramuscular dosages of between 500 and 750mg 8- to 12-hourly have been effective in treatment of infections of various body systems, including intra-abdominal, obstetric/gynaecological, urinary tract, and skin and soft tissue infections.

Intravenous dosages of 60 mg/kg/day in patients weighing 40kg or less, and adult doses in patients heavier than this, appear to be effective and well tolerated in paediatric patients.

The dosage of imipenem/cilastatin should be reduced in patients with renal impairment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahonkhai VI, Cyhan GM, Wilson SE, Brown KR. Imipenem-cilastatin in pediatric patients: an overview of safety and efficacy in studies conducted in the United States. Paediatric Infectious Diseases Journal 8: 740–744, 1989

    CAS  Google Scholar 

  • Animén J, Brünnestam R, Eriksson C, Torgersen AK, Carlsson L. Imipenem in the treatment of peritonitis during CAPD. Dialysis and Transplantation 20: 498–515, 1991

    Google Scholar 

  • Alarabi AA, Cars O, Danielson BG, Salmonson T, Wikstrom B. Pharmacokinetics of intravenous imipenem/cilastatin during intermittent haemofiltration. Journal of Antimicrobial Chemotherapy 26: 91–98, 1990

    PubMed  CAS  Google Scholar 

  • Aldridge KE, Henderberg A, Schiro DD, Sanders CV. Susceptibility of Bacteroides fragilis group isolates to broad-spectrum β-lactams, clindamycin, and metronidazole: rates of resistance, cross-resistance, and importance of β-lactamase production. Advances in Therapy 5: 273–282, 1988

    Google Scholar 

  • Apellaniz G, Valdés M, Perez R, Martin F, Soria F, et al. Comparison of the effectiveness of various antibiotics in the treatment of methicillin-susceptible Staphylococcus aureus experimental infective endocarditis. Journal of Chemotherapy 3: 91–97, 1991

    PubMed  CAS  Google Scholar 

  • Appelbaum PC, Spangler SK, Jacobs MR. Susceptibilities of 394 Bacteroides fragilis, Non-B, fragilis group Bacteroides species, and Fusobacterium species to newer antimicrobial agents. Antimicrobial Agents and Chemotherapy 35: 1214–1218, 1991

    PubMed  CAS  Google Scholar 

  • Appleman MD, Cherubin CE, Heseltine PNR, Stratton CW. Susceptibility testing of Listeria monocytogenes. A reassessment of bactericidal activity as a predictor for clinical outcome. Diagnostic Microbiology and Infectious Diseases 14: 311–317, 1991

    CAS  Google Scholar 

  • Baron EJ, Hindier JA. Bioactivity of imipenem as a function of medium, time, and temperature. Antimicrobial Agents and Chemotherapy 25: 781–782, 1984

    PubMed  CAS  Google Scholar 

  • Berkey P, Moore D, Rolston K. In vitro susceptibilities of Nocardia species to newer antimicrobial agents. Antimicrobial Agents and Chemotherapy 32: 1078–1079, 1988

    PubMed  CAS  Google Scholar 

  • Birnbaum J, Kahan FM, Kropp H, MacDonald JS. Carbapenems, a new class of β-lactam antibiotics. Discovery and development of imipenem/cilastatin. American Journal of Medicine 78 (Suppl. 6A): 3–21, 1985

    PubMed  CAS  Google Scholar 

  • Blandino G, Caccamo F, Di Marco R, Speciale A, Nicoletti G. Epidemiology of antibiotic resistance in human isolates of enterobacteriaceae in Sicily. Journal of Chemotherapy 2: 40–44, 1990

    PubMed  CAS  Google Scholar 

  • Brook I. Bacterial synergy in intra-abdominal infections: implications and management. In Solomkin JS (Ed.) The role of monotherapy in serious surgical infections, pp. 7–9, Excerpta Medica, 1989

  • Broze De Mees J, Droissart R, Nolens VP, Staudt JP, et al. Randomized comparison of imipenem/cilastatin and ceftazidime in the empiric therapy of severe abdominal infections. A multicenter study. Acta Clinica Belgica 42: 431–436, 1987

    Google Scholar 

  • Buirma RJA, Horrevorts AM, Wagenaath JHT. Incidence of multiresistant Gram-negative isolates in eight Dutch hospitals. In Norrby SR (Ed.) Patterns of multi-resistance and their clinical significance. Scandinavian Journal of Infectious Diseases (Suppl. 78): 35–44, 1991

  • Burkitt DS, Donovan IA, Wise R, Lowe P. A comparison between imipenem and metronidazole prophylaxis against sepsis following appendicectomy. Journal of Hospital Infection 15: 283–286, 1990

    PubMed  CAS  Google Scholar 

  • Bush K. Characterisation of β-lactamases. Antimicrobial Agents and Chemotherapy 33: 259–276, 1989

    PubMed  CAS  Google Scholar 

  • Bustamante CI, Drusano GL, Wharton RC, Wade JC. Synergism of the combinations of imipenem plus ciprofloxacin and imipenem plus amikacin against Pseudomonas aeruginosa and other bacterial pathogens. Antimicrobial Agents and Chemotherapy 31: 632–634, 1987

    PubMed  CAS  Google Scholar 

  • Cáceres M, Palmgren A-C, Nord CE. Antimicrobial resistance in human anaerobic microflora in Nicaragua and Sweden. Revista Espanola de Quimioterapia 4: 151–155, 1991

    Google Scholar 

  • Calandra GB, Brown KR, Grad LC, Ahonkhai VI, Wang C, et al. Review of adverse experiences and tolerability in the first 2516 patients treated with imipenem/cilastatin. American Journal of Medicine 78 (Suppl. 6A): 73–78, 1985

    PubMed  CAS  Google Scholar 

  • Calandra GB, Raupp W, Brown KR. Imipenem/cilastatin treatment of lower extremity skin and soft tissue infections in diabetics. Scandinavian Journal of Infectious Diseases 52 (Suppl.): 15–19, 1987

    PubMed  CAS  Google Scholar 

  • Calandra GB, Ricci FM, Wang C, Brown KR. The efficacy results and safety profile of imipenem/cilastatin from the clinical research trials. Journal of Clinical Pharmacology 28: 120–127, 1988

    PubMed  CAS  Google Scholar 

  • Calandra GB, Wang C, Aziz M, Brown KR. The safety profile of imipenem/cilastatin: worldwide clinical experience based on 3470 patients. Journal of Antimicrobial Chemotherapy 18 (Suppl. E): 193–202, 1986

    PubMed  Google Scholar 

  • Chimura T, Banzai M, Yamazaki K, Miyata R, Yokoyama Y, et al. Clinical study of intramuscular imipenem/cilastatin sodium in the field of obstetrics and gynecology. Japanese Journal of Antibiotics 44: 1351–1358, 1991

    PubMed  CAS  Google Scholar 

  • Chin MJ, Bagshaw PF, Bremner JM. Imipenem/cilastatin (Primaxin): evaluation in general surgical practice. New Zealand Medical Journal 104: 22–23, 1991

    PubMed  CAS  Google Scholar 

  • Chow JW, Shlaes DM. Imipenem resistance associated with the loss of a 40 kDa outer membrane protein in Enterobacter aerogenes. Journal of Antimicrobial Chemotherapy 28: 499–504, 1991

    PubMed  CAS  Google Scholar 

  • Chow JW, Fine MJ, Shlaes DM, Quinn JP, Hooper DC, et al. Enterobacter Bacteremia: clinical features and emergence of antibiotic resistance during therapy. Annals of Internal Medicine 115: 585–590, 1991

    PubMed  CAS  Google Scholar 

  • Clarke AM, Zemcov SJV. In vitro activity of the novel cephalosporin GR69153. European Journal of Clinical Microbiology and Infectious Diseases 10: 683–687, 1991

    CAS  Google Scholar 

  • Clavé D, Archambaud M, Rouquet RM, Massip P, Moatti M. Activité in vitro de vingt antibiotiques sur Rhodococcus equi. Pathologie Biologie 39: 424–428, 1991

    PubMed  Google Scholar 

  • Clissold SP, Todd PA, Campoli-Richards DM. Imipenem/cilastatin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 33: 183–241, 1987

    PubMed  CAS  Google Scholar 

  • Cohen MA, Huband MD, Mailloux GB, Yoder SL, Roland GE, et al. In vitro antibacterial activities of the fluoroquinolones PD 117596, PD 124816, and PD 127391. Diagnostic Microbiology and Infectious Diseases 14: 245–258, 1991

    CAS  Google Scholar 

  • Cohn DL, Reimer LG, Relier B. Comparative in vitro activity of MK0787 (N-formimidoyl thienamycin) against 540 blood culture isolates. Journal of Antimicrobial Chemotherapy 9: 183–194, 1982

    PubMed  CAS  Google Scholar 

  • Cornelissen JJ, de Graeff A, Verdonck LF, Branger T, Rozenberg-Arska M, et al. Imipenem versus gentamicin combined with either cefuroxime or cephalothin as initial therapy for febrile neutropenic patients. Antimicrobial Agents and Chemotherapy 36: 801–807, 1992

    PubMed  CAS  Google Scholar 

  • Cristiano P, Iovene MR, Simioli F, Pezza M, Raucci G, et al. Clinical evaluation of the imipenem/cilastatin combination in the therapy of severe infections in patients with malignant diseases. Drugs in Experimental and Clinical Research 16: 293–297, 1990

    CAS  Google Scholar 

  • Cullmann W, Opferkuch W, Stieglitz M, Werkmeister U. A comparison of the antibacterial activities of N-formimidoyl thienamycin (MK0787) with those of other recently developed β-lactam derivatives. Antimicrobial Agents and Chemotherapy 22: 302–307, 1982

    PubMed  CAS  Google Scholar 

  • del Valle J, Noriega AR, Sanz F, Revilla AP, Otero JR. Efficacy and safety of imipenem/cilastatin in the empirical treatment of septicemia. Scandinavian Journal of Infectious Diseases 52: 20–25, 1987

    PubMed  Google Scholar 

  • Dornbusch K, Bengtsson S, Brorson JE, Fritz H, Henning C, et al. Susceptibility to beta-lactam antibiotics and gentamicin of gram-negative bacilli isolated from hospitalized patients: a Swedish multicenter study. Scandinavian Journal of Infectious Diseases 20: 641–647, 1988

    PubMed  CAS  Google Scholar 

  • Drusano GL, Standiford HC, Bustamante C, Forrest A, Rivera G, et al. Multiple-dose pharmacokinetics of imipenem-cilastatin. Antimicrobial Agents and Chemotherapy 26: 715–721, 1984

    PubMed  CAS  Google Scholar 

  • Duque A, Altimiras J, García-Cases C, Vidal P. Vertigo caused by intravenous imipenem/cilastatin. DICP: Annals of Pharmacotherapy 25: 1009, 1991

    PubMed  CAS  Google Scholar 

  • Eng RHK, Munsif AN, Yangco BG, Smith SM, Chmel H. Seizure propensity with imipenem. Archives of Internal Medicine 149: 1881–1883, 1989

    PubMed  CAS  Google Scholar 

  • Erttmann M, Krausse R, Ullmann U. Pharmacokinetics of imipenem in patients undergoing major colon surgery. Infection 18: 367–371, 1990

    PubMed  CAS  Google Scholar 

  • Fantin B, Leggett J, Ebert S, Craig WA. Correlation between in vitro and in vivo activity of antimicrobial agents against gram-negative bacilli in a murine infection model. Antimicrobial Agents and Chemotherapy 35: 1413–1422, 1991

    PubMed  CAS  Google Scholar 

  • Flückiger U, Segessenmann C, Gerber AU. Integration of pharmacokinetics and pharmacodynamics of imipenem in a human-adapted mouse model. Antimicrobial Agents and Chemotherapy 35: 1905–1910, 1991

    PubMed  Google Scholar 

  • Freij BJ, Kusmiesz H, Shelton S, Nelson JD. Imipenem and cilastatin in acute osteomyelitis and suppurative arthritis. Therapy in infants and children. American Journal of Diseases in Children 141: 335–342, 1987

    CAS  Google Scholar 

  • Fukuhara H, Kusano N, Nakamura H, Kaneshima H, Irabu Y, et al. Clinical evaluation of imipenem/cilastatin sodium in the internal medicine. Japanese Journal of Antibiotics 44: 877–885, 1991

    PubMed  CAS  Google Scholar 

  • Garau J, Calandra GB. Intramuscular imipenem/cilastatin in multiple-dose treatment regimens: review of the worldwide clinical experience. Chemotherapy 37 (Suppl. 2): 44–52, 1991

    PubMed  Google Scholar 

  • Garau J, Castané J, Martin A, Lite J, Linares J, et al. Treatment of bacterial infections with intravenous or intramuscular imipenem/cilastatin. Current Opinion in Infectious Diseases 4 (Suppl. 1): S13–S15, 1991

    Google Scholar 

  • Garau J, Martin R, Bouza E, Romero J, García Rodríguez JA, et al. Imipenem in the treatment of severe bacterial infections in seriously ill patients. Journal of Antimicrobial Chemotherapy 18 (Suppl. E): 131–140, 1986

    PubMed  Google Scholar 

  • García-Rodríguez JA, Sánchez JE, Bellido JL, Sánchez E, García MI. In-vitro activity of meropenem, a new carbapenem, against imipenem-resistant Pseudomonas aeruginosa and Xanthomonas maltophilia. Journal of Chemotherapy 3: 143–146, 1991

    PubMed  Google Scholar 

  • García-Rodríguez JE, García-Sánchez. Evolution of antimicrobial susceptibility in isolates of the Bacteroides fragilis group in Spain. Reviews of Infectious Diseases 12 (Suppl. 2): S142–S151, 1990

    PubMed  Google Scholar 

  • Gehrlein M, Leying H, Cullmann W, Wendt S, Opferkuch W. Imipenem resistance in Acinetobacter baumanii is due to altered penicillin-binding proteins. Chemotherapy 37: 405–412, 1991

    PubMed  CAS  Google Scholar 

  • Georgopapadakou NH, Smith SA, Sykes RB. Penecillin-binding proteins in Bacteroides fragilis. Journal of Antibiotics 36: 907–910, 1983

    PubMed  CAS  Google Scholar 

  • Geroulanos SJ, Stern A, Christen D, Buchmann P. Comparative study of imipenem/cilastatin vs. combination therapy in treating serious postoperative infections. Complications in Surgery 10: 37–39, 1991

    Google Scholar 

  • Geroulanos SJ, Stern A, Christen D, Buchmann P. Management of postoperative abdominal infections: Single versus combination therapy. Infections in Surgery 9 (Suppl. 1): 65–67, 1990a

    Google Scholar 

  • Geroulanos S, Stern A, Christen D, Buchmann P. Antimicrobial management of postoperative infections in abdominal surgery: single or combination regimen? Clinical Therapeutics 12 (Suppl. B): 34–36, 1990b

    PubMed  Google Scholar 

  • Giamarellou H, Mandragos K, Bechrakis P, Pigas K, Bilalis D, et al. Pefloxacin versus imipenem in the therapy of nosocomial lung infections of intensive care unit patients. Journal of Antimicrobial Chemotherapy 26 (Suppl. B): 117–127, 1990

    PubMed  Google Scholar 

  • Gibson TP, Demetriades JL, Bland JA. Imipenem/cilastatin: pharmacokinetic profile in renal insufficiency. American Journal of Medicine 78 (Suppl. 6A): 54–61, 1985

    PubMed  CAS  Google Scholar 

  • Gombert ME, áulico TM, duBouchet L, Berkowitz LR. Susceptibility of Nocardia asteroides to new quinolones and β-lactams. Antimicrobial Agents and Chemotherapy 31: 2013–2014, 1987

    PubMed  CAS  Google Scholar 

  • Gómez J, Ros J, Ruiz J, Canteras M, Valdés M, et al. Comparison of the efficacy of three different treatments with imipenem versus the classical clindamycin plus tobramycin in experimental peritonitis. Journal of Chemotherapy 3: 367–371, 1991

    PubMed  Google Scholar 

  • Gonzenbach HR, Simmen HP, Amgwerd R. Imipenem (N-F-Thienamycin) versus netilmicin plus clindamycin. Annals of Surgery 205: 271–275, 1987

    PubMed  CAS  Google Scholar 

  • Goto S, Katsuta M, Miyazaki S, Tsuji A, Kaneko Y, et al. Antibacterial activity of panipenem/betamiprom, a new carbapenem. Chemotherapy 39 (Suppl. 3): 24–45, 1991

    CAS  Google Scholar 

  • Gould IM, Hudson M, Morris J, Page G, Douglas JG, et al. Imipenem versus standard therapy in the treatment of serious soft tissue infection. Drugs Under Experimental and Clinical Research 14: 555–558, 1988

    PubMed  CAS  Google Scholar 

  • Gould IM, Wilson D, Milne K, Paterson A, Golder D, et al. Interaction of imipenem with erythromycin and tetracycline assessed by microdilution checkerboard techniques. Antimicrobial Agents and Chemotherapy 35: 2407–2409, 1991

    PubMed  CAS  Google Scholar 

  • Grassi C, Bariffi F, Bianchi L, Bisetti A, Ciaccia A, et al. Intramuscular imipenem/cilastatin in the treatment of lower respiratory tract infections. Current Opinion in Infectious Diseases 4 (Suppl. 1): S20–S23, 1991

    Google Scholar 

  • Gu J-W, Chin N-X, Neu In vitro activity of an oxycephem OCP 9–176 compared with its sulfur analog and other β-lactams. Diagnostic Microbiology and Infectious Diseases 14: 135–140, 1991

    CAS  Google Scholar 

  • Hackford AW, Tally FP, Reinhold RB, Barza M, Gorbach SL. Prospective study comparing imipenem/cilastatin with clindamycin and gentamicin for the treatment of serious surgical infections. Archives of Surgery 123: 322–326, 1988

    PubMed  CAS  Google Scholar 

  • Hanberger H, Nilsson LE, Maller R, Nilsson M. Pharmacodynamics of β-lactam antibiotics on gram-negative bacteria: initial killing, morphology and postantibiotic effect. Scandinavian Journal of Infectious Diseases (Suppl. 74): 118–123, 1991

  • Hashizume T, Ishino F, Nakagawa J-I, Tamaki S, Matsuhashi M. Studies on the mechanism of action of imipenem (N-formi-doylthienamycin) in vitro. Journal of Antibiotics 37: 394–400, 1984a

    PubMed  CAS  Google Scholar 

  • Hashizume T, Park W, Matsuhashi M. The affinity of imipenem (N-formidoylthienamycin) for the penecillin-binding proteins of Staphylococcus aureus — binding and release. Journal of Antibiotics 37: 1049–1053, 1984b

    PubMed  CAS  Google Scholar 

  • Hauer Urban Slavc I, Gamillscheg A, Lackner H. Imipe-nem-antibiotic monotherapy in juvenile cancer patients with neutropenia. Pediatric Hematology and Oncology 7: 229–241, 1990

    Google Scholar 

  • Heseltine PNR, Yellin AE, Berne TV, Appleman MD, Gill MA. Imipenem/cilastatin as adjunctive monotherapy to surgical treatment of intraabdominal infections. Infections in Surgery 9 (Suppl. 1): 75–80, 1990

    Google Scholar 

  • Huijgens PC, Ossenkoppele GJ, Weijers TF, van Loenen AC, Simoons-Smit AM, et al. Imipenem-cilastatin for empirical therapy in neutropenic patients with fever: an open study in patients with hematologic malignancies. European Journal of Haematology 46: 42–46, 1991

    PubMed  CAS  Google Scholar 

  • Igari J. Susceptibilities of clinical bacterial isolates to antimicrobial agents, 1989. A study mainly focused on imipenem. Japanese Journal of Antibiotics 44: 1329–1340, 1991

    PubMed  CAS  Google Scholar 

  • Inoue K, Hamana Y, Mitsuhashi S. Antibacterial activity of panipenem, a new carbapenem antibiotic. Chemotherapy 39 (Suppl. 3): 1–13, 1991

    CAS  Google Scholar 

  • Ito, Y, Yamada S, Komeda H, Saito A, Kanematsu M, et al. Antibacterial activity and clinical efficacy of intramuscular imipenem/cilastatin sodium in complicated urinary tract infections. Chemotherapy 39: 1071–1085, 1991

    Google Scholar 

  • Jacoby GA, Archer GL. New mechanisms of bacterial resistance to antimicrobial agents. New England Journal of Medicine 324: 601–612, 1991

    PubMed  CAS  Google Scholar 

  • Jorgensen JH, Maher LA, Howell AW. Activity of a new carbapenem antibiotic, meropenem, against Haemophilus influenzae strains with β-lactamase- and non-enzyme-mediated resistance to ampicillin. Antimicrobial Agents and Chemotherapy 35: 600–602, 1991

    PubMed  CAS  Google Scholar 

  • Kager L, Brismar B, Malmborg AS, Nord CE. Imipenem concentrations in colorectal surgery and impact on the colonic microflora. Antimicrobial Agents and Chemotherapy 33: 204–208, 1989

    PubMed  CAS  Google Scholar 

  • Kahan FM. Rogers JD. Imipenem/cilastatin: evolution of the sustained-release intramuscular formulation. Chemotherapy 37 (Suppl. 2): 21–25, 1991

    PubMed  CAS  Google Scholar 

  • Kapotas NM. Acclimatization resistance of a Pseudomonas aeruginosa prototype strain to imipenem. Journal of Antibiotics 44: 985–994, 1991

    PubMed  CAS  Google Scholar 

  • Kawada Y. Treatment of complicated urinary tract infections with imipenem/cilastatin. Abstract. 14th International Congress of Chemotherapy, Kyoto, 23–28, Jun, 1985

  • Kesado T, Hashizume T, Asahi Y. Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics. Antimicrobial Agents and Chemotherapy 17: 912–917, 1980

    PubMed  CAS  Google Scholar 

  • Klietmann W, Focht J, Nösner K. Retrospective resistance pattern of clinical isolates in vitro against imipenem and other antimicrobial agents between 1986 and 1989. Drug Investigation 3: 270–277, 1991

    Google Scholar 

  • Konaga E, Takeuchi H, Orita K, Fuchimoto S, Ogawa K, et al. Clinical evaluation of intramuscular imipenem/cilastatin sodium in surgical infections. Japanese Journal of Antibiotics 44: 1341–1350, 1991

    PubMed  CAS  Google Scholar 

  • Konishi K, Suzuki H, Saruta T, Hayashi M, Deguchi N, et al. Removal of imipenem and cilastatin by hemodialysis in patients with end-stage renal failure. Antimicrobial Agents and Chemotherapy 35: 1616–1620, 1991

    PubMed  CAS  Google Scholar 

  • Kono K, Onuki K, Tohara S, Takeda S. Imipenem/cilastatin as secondary therapy for bacterial infections. Clinical Therapeutics 13: 448–456, 1991

    PubMed  CAS  Google Scholar 

  • Krone A, Schaal KP, Brawanski A, Schuknecht B. Nocardial cerebral abscess cured with imipenem/amikacin and enucleation. Neurosurgical Review 12: 333–340, 1989

    PubMed  CAS  Google Scholar 

  • Kumar A, Wofford-McQueen R, Gordon RC. Ciprofloxacin, imipenem and rifampicin: in-vitro synergy of two and three drug combinations against Pseudomonas cepacia. Journal of Antimicrobial Chemotherapy 23: 831–835, 1989

    PubMed  CAS  Google Scholar 

  • Lackner R, Uranus S. Treatment of severe intraabdominal infections: imipenem/cilastatin vs combination antibiotics. Infections in Surgery 9 (Suppl. 1): 72–74, 1990

    Google Scholar 

  • Leaper DJ, Kennedy RH, Sutton A, Johnson E, Roberts N. Treatment of acute bacterial peritonitis: a trial of imipenem/cilastatin against ampicillin-metronidazole-gentamicin. Scandinavian Journal of Infectious Diseases 52: 7–10, 1987

    PubMed  CAS  Google Scholar 

  • Lee EH, Nicolas MH, Kitzis MD, Pialoux G, Collatz E, et al. Association of two resistance mechanisms in a clinical isolate of Enterobacter cloacae with high-level resistance to imipenem. Antimicrobial Agents and Chemotherapy 35: 1093–1098, 1991

    PubMed  CAS  Google Scholar 

  • Leo RJ, Ballow CH. Seizure activity associated with imipenem use. DICP Annals of Pharmacotherapy 25: 351–352, 1991

    CAS  Google Scholar 

  • Liang R, Yung R, Chau PY, Chan TK, Lam WK, et al. Imipenem/cilastatin as initial therapy for febrile neutropenic patients. Journal of Antimicrobial Chemotherapy 22: 765–770, 1988

    PubMed  CAS  Google Scholar 

  • Liang R, Yung R, Chiu E, Chau P-Y, Chan T-K, et al. Ceftazidime versus imipenem-cilastatin as initial monotherapy for febrile neutropenic patients. Antimicrobial Agents and Chemotherapy 34: 1336–1341, 1990

    PubMed  CAS  Google Scholar 

  • Lieschke GJ, Bell D, Rawlinson W, Green M, Sheridan W, et al. Imipenem/cilastatin versus tobramycin and piperacillin as initial empiric therapy for febrile episodes in neutropenic patients: interim analysis of a prospective randomized comparison. Australian and New Zealand Journal of Medicine 20: 424, 1990

    Google Scholar 

  • Linton DM, Aitchison JM, Potgieter PD. Evaluation of the efficacy and tolerance of intravenously administered imipenem/ cilastatin in the treatment of septicaemia. South African Medical Journal 75: 529–531, 1989

    PubMed  CAS  Google Scholar 

  • Liu C-Y, Wang F-D. A comparative study of ceftriaxone plus amikacin, ceftazidime plus amikacin and imipenem/cilastatin in the empiric therapy of febrile granulocytopenic cancer patients. Chemotherapy 35 (Suppl. 2): 16–22, 1989

    PubMed  Google Scholar 

  • Livermore DM. Mechanisms of resistance to β-lactam antibiotics. Scandinavian Journal of Infectious Diseases (Suppl. 78): 5–16, 1991

  • Livermore DM. Resistance to β-lactams, and β-lactamase induction. In Livermore DM (Ed.) The clinical importance of β-lactam resistance. Current Topics in Infectious Diseases and Clinical Microbiology 3: 3–10, 1990

    Google Scholar 

  • Lode H, Wiley R, Höffken G, Wagner J, Borner K. Prospective randomised controlled study of ciprofloxacin versus imipe-nem-cilastatin in severe clinical infections. Antimicrobial Agents and Chemotherapy 31: 1491–1496, 1987

    PubMed  CAS  Google Scholar 

  • Machka K. Bactericidal activity of imipenem in serum. European Journal of Clinical Microbiology 3: 495–497, 1984

    PubMed  CAS  Google Scholar 

  • Marier RL. Role of imipenem/cilastatin in the treatment of soft tissue infections. American Journal of Medicine 79 (Suppl. 6A): 140–144, 1985

    Google Scholar 

  • Matsuda S, Oh K, Tateno M, Kojima Y, Hirabayashi K, Okada E, et al. Clinical study of intramuscular imipenem/cilastatin sodium in the field of obstetrics and gynecology. Japanese Journal of Antibiotics 44: 1359–1367, 1991

    PubMed  CAS  Google Scholar 

  • Matsui K, Masuda N, Takada M, Kusunoki Y, Fukuoka M. A randomized trial comparing imipenem/cilastatine alone with latamoxef plus tobramycin in febrile neutropenic patients with lung cancer. Japanese Journal of Clinical Oncology 21: 428–434, 1991

    PubMed  CAS  Google Scholar 

  • Mayer M, Tophof Ch, Opferkuch W. Bile levels of imipenem in patients with T-drain following the administration of imipenem/cilastatin. Infection 16: 225–228, 1988

    PubMed  CAS  Google Scholar 

  • McGregor JA, Christensen FB, French JI. Use of intramuscular imipenem/cilastatin in the treatment of upper reproductive tract infections in women. Current Opinion in Infectious Diseases 4 (Suppl. 1): S24–S27, 1991a

    Google Scholar 

  • McGregor JA, Christensen FB, French JI. Intramuscular imipenem/cilastatin treatment of upper reproductive tract infection in women: efficacy and use characteristics. Chemotherapy 37 (Suppl. 2): 31–36, 1991b

    PubMed  Google Scholar 

  • Mehtar S, Tsakris A, Pitt TL. Imipenem resistance in Proteus mirabilis. Journal of Antimicrobial Chemotherapy 28: 612–615, 1991

    PubMed  CAS  Google Scholar 

  • Miano L, Vicentini C, Carlucci G, Biordi L, Goldoni S, et al. Imipenem concentrations in human prostatic tissue: clinical implications. Current Therapeutic Research 46: 614–618, 1989

    Google Scholar 

  • Mortimer J, Miller S, Black D, Kwok K, Kirby WM. Comparison of cefoperazone and mezlocillin with imipenem as empiric therapy in febrile neutropenic cancer patients. American Journal of Medicine 85 (Suppl. 1A): 17–20, 1988

    PubMed  CAS  Google Scholar 

  • Mounier M, Denis F, Adenis JP. An experimental model to assess imipenem diffusion into the infected eye. Current Therapeutic Research 51: 129–136, 1992

    Google Scholar 

  • Mouton Y, Deboscker Y, Bazin C, Fourrier F, Moulront S, et al. Prospective, randomized, controlled trial of imipenem-cilastatin versus cefotaxime-amikacin in the treatment of lower respiratory tract infections and septicaemia in intensive care units. Presse Medicale 19: 607–612, 1990

    CAS  Google Scholar 

  • Nakagawa K, Koyama T, Hayase Kesado T. Imipenem, cilastatin sodium, imipenem/cilastatin sodium clinical phase I study. Chemotherapy (Tokyo) 33 (Suppl. 4): 357–378, 1985

    CAS  Google Scholar 

  • National Committee for Clinical Laboratory Standards 8 (No. 8), 1988

  • Neu Labthavikul P. Comparative in vitro activity of N-for-mimidoyl thienamycin against Gram-positive and Gram-negative aerobic and anaerobic species and its β-lactamase stability. Antimicrobial Agents and Chemotherapy 21: 180–187, 1982

    Google Scholar 

  • Nilsson-Ehle I, Hutchison M, Haworth SJ, Norrby SR. Pharmacokinetics of meropenem compared to imipenem-cilastatin in young, healthy males. European Journal of Clinical Microbiology and Infectious Diseases 10: 85–88, 1991

    CAS  Google Scholar 

  • Nishino T, Fukuoka T, Honmura T, Nishiguchi Y, Otsuki M. In vitro and in vivo antibacterial activity of panipenem/betamipron, a new carbapenem antibiotic. Chemotherapy 39 (Suppl. 3): 55–74, 1991

    CAS  Google Scholar 

  • Norrby SR, Alestig K, Ferber F, Huber JL, Jones KH, et al. Phar-macokinetics and tolerance of N-formimidoyl thienamycin (MK0787) in humans. Antimicrobial Agents and Chemotherapy 23: 293–299, 1983

    PubMed  CAS  Google Scholar 

  • Ohishi A, Takita M, Suzuki E, Nakamura H, Ishii M, et al. Basic and clinical studies on panipenem/betamipron. Chemotherapy 39 (Suppl. 3): 339–349, 1991

    Google Scholar 

  • Okada K, Nakajima N, Miyabita H, Kawashima T, Tanigawa K, et al. Fundamental and clinical studies of imipenem/cilastatin sodium in the field of urology. Chemotherapy (Tokyo) 33 (Suppl. 4): 778–792, 1985

    CAS  Google Scholar 

  • Onishi A, Otawa M, Hara K. A clinical phase 1 study on intramuscular imipenem/cilastatin sodium. Japanese Journal of Antibiotics 44: 860–875, 1991

    PubMed  CAS  Google Scholar 

  • Pacelli F, Brisinda G, Bellantone R, Doglietto GB, Crucitti F. Single dose imipenem-cilastatin compared with three doses of cefuroxime and metronidazole as prophylaxis in elective colorectal surgery: a prospective randomised study. Journal of Chemotherapy 3: 372–375, 1991

    PubMed  CAS  Google Scholar 

  • Panichi G, Di Rosa R, Enrico P, Babudieri S. Anaerobic bacteria and bacterial infections: perspectives on treatment and resistance in Italy. Reviews of Infectious Diseases 12 (Suppl. 2): S152–S156, 1990

    PubMed  Google Scholar 

  • Pechère J-C. Newer strategies for control of resistant bacteria. Presented at a symposium on antibiotic-resistant infections held in West Hollywood, California on 22 October 1988. HP Publishing Company, New York, 1989

    Google Scholar 

  • Pignatari A, Jones RN, Barrett MR, Sesso R, Lerne I, et al. Use of antimicrobial susceptibility testing for epidemiology and the selection of oral, parenteral and topical regimens for control of CAPD — associated Staphylococcus aureus infection. Journal of Chemotherapy 3: 108–116, 1991

    PubMed  CAS  Google Scholar 

  • Poenaru D, De Santis M, Christou NV. Imipenem versus tobramycin — antianaerobe antibiotic therapy in intra-abdominal infections. Canadian Journal of Surgery 33: 415–422, 1990

    CAS  Google Scholar 

  • Potel G, Baron S. Imipenem/cilastatin for treatment of acute bacterial peritonitis: a French multicenter study. Complications in Surgery 10: 18–21, 1991

    Google Scholar 

  • Potgieter PD, Linton DM, Forder AA, Plumb H. Imipenem/cilastatin in the treatment of severe nosocomial pneumonia. South African Medical Journal 74: 390–392, 1988

    PubMed  CAS  Google Scholar 

  • Powell M, Williams JD. In vitro activities of aztreonam, imipenem, and amoxycillin-clavulanate against ampicillin-resistant Haemophilus influenzae. Antimicrobial Agents and Chemotherapy 31: 1871–1873, 1987

    PubMed  CAS  Google Scholar 

  • Quinn JP, Dudek EJ, DiVicenzo CA, Lucks DA, Lerner SA. Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections. Journal of Infectious Diseases 154: 289–294, 1986

    PubMed  CAS  Google Scholar 

  • Quinn JP, Miyashiro D, Darzins A, Miller R. Imipenem resistance in Pseudomonas aeruginosa. In Homma et al. (Eds) Pseudomonas aeruginosa in Human Diseases p. 240–244, Karger, Basel, 1991

    Google Scholar 

  • Raimondi A, Traverso A, Nikaido H. Imipenen- and merope-nem-resistant mutants of Enterobacter cloacae and Proteus rettgeri lack porins. Antimicrobial Agents and Chemotherapy 35: 1174–1180, 1991

    PubMed  CAS  Google Scholar 

  • Reed MD, Kliegman RM, Yamashita T, Myers CM, Blumer JL. Clinical pharmacology of imipenem in premature infants during the first week of life. Antimicrobial Agents and Chemotherapy 34: 1172–1177, 1990

    PubMed  CAS  Google Scholar 

  • Riikonen P. Imipenem compared with ceftazidime plus vancomycin as initial therapy for fever in neutropenic children with cancer. Pediatric Infectious Diseases Journal 10: 981–923, 1991

    Google Scholar 

  • Rolston KVI, Berkey P, Body GP, Anaissie EJ, Khardori NM, et al. A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients. Archives of Internal Medicine 152: 283–291, 1992

    PubMed  CAS  Google Scholar 

  • Rouveix E, Bure AM, Regnier Wolff M, Pangon et al. Experience with imipenem/cilastatin in the intensive care unit. Journal of Antimicrobial Chemotherapy 18 (Suppl. E): 153–160, 1986

    PubMed  Google Scholar 

  • Salata RA, Gebhart RL, Palmer DL, Wade BH, Scheid WM, et al. Pneumonia treated with imipenem/cilastatin. American Journal of Medicine 78 (Suppl. 6A): 104–109, 1985

    PubMed  CAS  Google Scholar 

  • Schreiner A. Imipenem/cilastatin as monotherapy in severe infections: comparison with cefotaxime in combination with metronidazole and cloxacillin. Report from a Norwegian Study Group. Scandinavian Journal of Infectious Diseases 19: 667–675, 1987

    Google Scholar 

  • Semel JD, Allen N. Seizures in patients simultaneously receiving theophylline and imipenem or ciprofloxacin or metronidazole. Southern Medical Journal 84: 465–468, 1991

    PubMed  CAS  Google Scholar 

  • Sexton DJ, Wlodaver CG, Tobey LE, Yangco BG, Graziani AL, et al. Twice daily intramuscular imipenem/cilastatin in the treatment of skin and soft tissue infections. Chemotherapy 37 (Suppl. 2): 26–30, 1991

    PubMed  Google Scholar 

  • Shah PM. Activity of imipenem in an in vitro model simulating pharmacokinetic parameters in human blood. Journal of Antimicrobial Chemotherapy 15 (Suppl. A): 153–157, 1985

    PubMed  CAS  Google Scholar 

  • Shah PM, Asanger R, Kahan FM. Incidence of multi-resistance in gram-negative aerobes from intensive care units of 10 German hospitals. In Norrby SR (Ed.) Patterns of multiresistance and their clinical significance. Scandinavian Journal of Infectious Diseases (Suppl. 78): 22–34, 1991

  • Shungu DL, Weinberg E, Cerami AT. Evaluation of three broth disk methods for testing the susceptibility of anaerobic bacteria to imipenem. Journal of Clinical Microbiology 21: 875–879, 1985

    PubMed  CAS  Google Scholar 

  • Snydman DR. Clinical implications of multi-drug resistance in the intensive care unit. Scandinavian Journal of Infectious Diseases (Suppl. 78): 54–63, 1991

  • Solomkin JS, Dellinger EP, Christou NV, Busuttil RW. Results of a multicenter trial comparing imipenem/cilastatin to tobramycin/clindamycin for intra-abdominal infections. Annals of Surgery 212: 581–591, 1990

    PubMed  CAS  Google Scholar 

  • Somani P, Freimer EH, Gross ML, Higgins JT. Pharmacokinetics of imipenem-cilastatin in patients with renal insufficiency undergoing continuous ambulatory peritoneal dialysis. Antimicrobial Agents and Chemotherapy 32: 530–534, 1988

    PubMed  CAS  Google Scholar 

  • Sugiura A, Jono K, Kono T, Higashide E. The effect of combinations of cefotiam and other antibiotics on methicillin-resistant Staphylococcus aureus in vitro. Journal of Antimicrobial Chemotherapy 28: 707–717, 1991

    PubMed  CAS  Google Scholar 

  • Sumita Y, Mitsuhashi S. In vitro synergistic activity between meropenem and other beta-lactams against methicillin-resistant Staphylococcus aureus. New Antimicrobial Agents 10: 77–81, 1991

    CAS  Google Scholar 

  • Swedish Study Group. Immune response in patients with intraabdominal infections treated with imipenem. Infection 17: 369–373, 1989

    Google Scholar 

  • Tierno PM. β-lactamase update. Presented at a symposium on antibiotic-resistant infections held in West Hollywood, California on 22 October 1988. HP Publishing Company, New York, 1989

    Google Scholar 

  • Toon S, Hopkins KJ, Garstang FM, Aarons L, Rowland M. Pharmacokinetics of imipenem and cilastatin after their simultaneous administration to the elderly. British Journal of Clinical Pharmacology 23: 143–149, 1987

    PubMed  CAS  Google Scholar 

  • Trias J, Nikaido H. Outer membrane protein D2 catalyzes facilitated diffusion of carbapenems and penems through the outer membrane ofPseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 34: 52–57, 1990

    PubMed  CAS  Google Scholar 

  • Tsuda S, Nakai H, Murakami T, Seryu S, Takashima T, Tanaka S, et al. Clinical evaluation of imipenem/cilastatin sodium as a second line regimen in severe infections associated with hematologic disorders. Japanese Journal of Antibiotics 44: 74–86, 1991

    Google Scholar 

  • Urabe A, Takaku F, Mizoguchi H. Imipenem-cilastatin monotherapy in severe infections accompanying hematological malignancies. Japanese Journal of Medicine 30: 420–423, 1991

    PubMed  CAS  Google Scholar 

  • Utsui Y, Ohya S, Domon H, Katsuta M, Takenouchi T, et al. Microbiological evaluation of panipenem/betamipron, a new parenterally active carbapenem I. In vitro antibacterial activities. Chemotherapy 39 (Suppl. 3): 83–101, 1991

    CAS  Google Scholar 

  • Venditti M, Santini C, Serra P, Micozzi A, Gentile G, et al. Comparative in vitro activities of new fluorinated quinolones and other antibiotics against coagulase-negative Staphylococcus blood isolates from neutropenic patients, and relationship between susceptibility and slime production. Antimicrobial Agents and Chemotherapy 33: 209–211, 1989

    PubMed  CAS  Google Scholar 

  • Verbist L. Incidence of multi-resistance in gram-negative bacterial isolates from intensive care units in Belgium: A surveillance study. In Norrby SR (Ed.) Patterns of multi-resistance and their clinical significance. Scandinavian Journal of Infectious Diseases (Suppl. 78): 45–53, 1991

  • Verpooten GA, Verbist L. Buntinx AP, Entwistle LA, Jones KH, et al. The pharmacokinetics of imipenem (thienamycin for-manidine) and the renal dehydropeptidase inhibitor cilastatin sodium in normal subjects and patients with renal failure. British Journal of Clinical Pharmacology 18: 183–193, 1984

    PubMed  CAS  Google Scholar 

  • Walther F, Fischer M, Shah PM. Therapie von Infektionen bei abwehrgeschwächten Patienten mit Imipenem/Cilastatin. Münchener Medizinische Wochenschrift 131: 366–368, 1989

    Google Scholar 

  • Wang Calandra GB, Aziz MA, Brown KR. Efficacy and safety of imipenem/cilastatin: a review of worldwide clinical experience. Reviews of Infectious Diseases 7 (Suppl. 3): S528–S536, 1985

    Google Scholar 

  • Watanakunakorn C. Imipenem/gentamicin and imipenem/rifampin against methicillin-resistant Staphylococcus aureus. Chemotherapy 37: 283–286, 1991

    PubMed  CAS  Google Scholar 

  • Watanakunakorn C. In vitro activity of imipenem against methicillin-resistant Staphylococcus aureus: discordance between results from broth dilution test and 10-mcg disk diffusion test. Current Therapeutic Research 45: 684–689, 1989

    CAS  Google Scholar 

  • Wathen CG, Carbarns NJ, Jones PA, Millar A, Croughan MJ, et al. Imipenem-cilastatin in the treatment of respiratory infections in patients with chronic airways obstruction. Journal of Antimicrobial Chemotherapy 21: 107–112, 1988

    PubMed  CAS  Google Scholar 

  • Wilcox MH, Geary I, Spencer RC. In-vitro activity of imipenem, in comparison with cefuroxime and ciprofloxacin, against coa-gulase-negative staphylococci in broth and peritoneal, dialysis fluid. Journal of Antimicrobial Chemotherapy 29: 49–55, 1992

    PubMed  CAS  Google Scholar 

  • Winston DJ, Ho WG, Bruckner DA, Champlin RE. Beta-lactam antibiotic therapy in febrile granulocytopenic patients. A randomized trial comparing cefoperazone plus piperacillin, ceftazidime plus piperacillin, and imipenem alone. Annals of Internal Medicine 115: 849–859, 1991

    PubMed  CAS  Google Scholar 

  • Yamamoto M, Ina Y, Takada Noda M, Morishita M, et al. Therapeutic efficacy of imipenem/cilastatin sodium on respiratory tract infections in lung cancer patients. Japanese Journal of Antibiotics 44: 388–396, 1991

    PubMed  CAS  Google Scholar 

  • Yellin AE, Heseltine PNR, Berne TV, Appleman MD, Gill MA, et al. Intramuscular imipenem as adjuvant therapy for acute cholecystitis and perforated or gangrenous appendicitis. Chemotherapy 37 (Suppl. 2): 37–43, 1991

    PubMed  Google Scholar 

  • Yokota T, Kanda K, Suzuki E. Panipenem, its in vitro antibacterial activity, binding affinity to bacterial PBPs, inactivation of β-lactamases, stability to DHP-I, and synergy in bactericidal effect with complement or mouse cultured macrophages. Chemotherapy 39 (Suppl. 3): 14–23, 1991

    CAS  Google Scholar 

  • Yonezu S, Yasunaga K, Ueda Y. Laboratory and clinical studies on panipenem/betamipron. Chemotherapy 39 (Suppl. 3): 385–393, 1991

    Google Scholar 

  • Yoshida M, Mitsuhashi S. In vitro antibacterial activity and betalactamase stability of the new carbapenem LJC10,627. European Journal of Clinical Microbiology and Infectious Diseases 9: 625–629, 1990

    CAS  Google Scholar 

  • Yoshimura F, Nikaido H. Diffusion of β-lactam antibiotics through the porin channels of Escherichia coli K-12. Antimicrobial Agents and Chemotherapy 27: 84–92, 1985

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centonan Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Micaela M. Buckley, Rex N. Brogden, Lee B. Barradell & Karen L. Goa

Authors
  1. Micaela M. Buckley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rex N. Brogden
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lee B. Barradell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karen L. Goa
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Various sections of the manuscript reviewed by: H. Giamarellou, 1st Department of Propedeutic Medicine, Athens University School of Medicine, Athens, Greece; C. Hauer, Department of Pediatrics, University of Graz, Graz, Austria; H. Lode, Department of Medicine, Krankenhaus Zehlendorf, Berlin, Federal Republic of Germany; R. Liang, Department of Medicine, University of Hong Kong, Hong Kong; C.E. Nord, Department of Microbiology, Karolinska Institutet, Huddinge, Sweden; K.V.I. Rolston, Section of Infectious Diseases, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA; C. Watanakunakorn, Infectious Disease Section, Department of Internal Medicine, St Elizabeth Hospital Medical Center, Youngstown, and the Northeastern Ohio Universities College of Medicine, Rootstown, Ohio, USA; D. J. Winston, UCLA School of Medicine, University of California, Los Angeles, California, USA; A.E. Yellin, Department of Surgery, University of Southern California, Los Angeles, California, USA.

An erratum to this article is available at http://dx.doi.org/10.1007/BF03259143.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Buckley, M.M., Brogden, R.N., Barradell, L.B. et al. Imipenem/Cilastatin. Drugs 44, 408–444 (1992). https://doi.org/10.2165/00003495-199244030-00008

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199244030-00008

Keywords

Search

Navigation