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Meropenem. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy
L R Wiseman1, A J Wagstaff, R N Brogden
1Adis International Limited, Auckland, New Zealand.
Abstract:
The parenteral carbapenem meropenem is relatively stable to inactivation by human renal dehydropeptidase (DHP-1) and does not require concomitant administration of a DHP-1 inhibitor such as cilastatin. It has a broad spectrum of antibacterial activity in vitro, the majority of Gram-negative, Gram-positive and anaerobic pathogens being highly susceptible to the drug. Meropenem has shown clinical and bacteriological efficacy in the treatment of a wide range of serious infections in adults and children which is at least comparable with that of currently available treatment options. Its clinical and bacteriological efficacy is similar to that of imipenem/cilastatin, clindamycin plus tobramycin and cefotaxime plus metronidazole in the treatment of intraabdominal infections; cefotaxime or ceftriaxone in the treatment of meningitis; imipenem/cilastatin, and ceftazidime with or without an aminoglycoside, in lower respiratory tract infections; and imipenem/cilastatin or ceftazidime in the treatment of urinary tract infections. Satisfactory clinical and bacteriological response rates have also been achieved in patients with skin and skin structure infections, obstetric and gynaecological infections or septicaemia, and in immunocompromised patients with febrile episodes. Preliminary findings also indicate efficacy in the treatment of respiratory tract infections in patients with cystic fibrosis. The tolerability profile of meropenem is generally similar to that of comparator agents, although it is associated with a lower incidence of adverse gastrointestinal effects (nausea and vomiting) than imipenem/cilastatin. Importantly, the incidence of seizures in patients with meningitis is not increased following administration of meropenem. Thus, meropenem is an effective broad spectrum antibacterial drug for the treatment of a wide range of infections including polymicrobial infections in both adults and children, with comparable efficacy to imipenem/cilastatin and various other treatment regimens. Meropenem is likely to be of greatest value as empiric monotherapy in the treatment of serious infections for those caused by multiply-resistant pathogens. Further clinical experience is necessary, however, to ultimately define its place in therapy.
Insights
Meropenem, a parenteral carbapenem, demonstrates broad-spectrum antibacterial activity and clinical efficacy comparable to other treatments for serious infections in adults and children. It offers a favorable tolerability profile, especially with fewer gastrointestinal side effects than imipenem/cilastatin.
Area of Science:
- Infectious Diseases
- Pharmacology
- Microbiology
Background:
- Meropenem is a parenteral carbapenem antibiotic.
- It exhibits stability against human renal dehydropeptidase-1 (DHP-1).
- Unlike some carbapenems, it does not require a DHP-1 inhibitor.
Purpose of the Study:
- To evaluate the clinical and bacteriological efficacy of meropenem.
- To compare meropenem's effectiveness against various infections with existing treatment options.
- To assess meropenem's tolerability profile.
Main Methods:
- Clinical trials and bacteriological assessments were conducted.
- Efficacy was compared against established treatments for intra-abdominal, respiratory, urinary tract, and central nervous system infections.
- Tolerability was evaluated, focusing on adverse effects and specific patient populations.
Main Results:
- Meropenem showed broad-spectrum activity against Gram-negative, Gram-positive, and anaerobic pathogens.
- Clinical efficacy was comparable to imipenem/cilastatin, clindamycin/tobramycin, cefotaxime/metronidazole, cefotaxime, ceftriaxone, and ceftazidime in various infections.
- Favorable outcomes were observed in skin, obstetric, gynecological, and febrile episodes in immunocompromised patients.
- Lower incidence of nausea and vomiting compared to imipenem/cilastatin was noted.
- No increased incidence of seizures in meningitis patients.
Conclusions:
- Meropenem is an effective broad-spectrum antibacterial agent for treating diverse serious infections in adults and children.
- Its efficacy is comparable to other regimens, positioning it as a valuable option, particularly for multiply-resistant pathogens.
- Further clinical experience is needed to fully establish its therapeutic role.