Meropenem clinical studies

# Clinical Studies

## Skin and Skin Structure
Adult patients with complicated skin and skin structure infections including complicated cellulitis, complex abscesses, perirectal abscesses, and skin infections requiring intravenous antimicrobials, hospitalization, and surgical intervention were enrolled in a randomized, multi-center, international, double-blind trial.  The study evaluated meropenem at doses of 500 mg administered intravenously every 8 hours and Imipenem/cilastatinat doses of 500 mg administered intravenously every 8 hours.  The study compared the clinical response between treatment groups in the clinically evaluable population at the follow-up visit (test-of-cure). The trial was conducted in  the United States, South Africa, Canada, and Brazil. At enrollment, approximately 37% of the patients had underlying diabetes, 12% had underlying peripheral vascular disease and 67% had a surgical intervention.  The study included 510 patients randomized to  meropenem and 527 patients randomized to  Imipenem/cilastatin.  Two hundred and sixty-one (261) patients randomized to meropenem and 287 patients randomized to Imipenem/cilastatin were clinically evaluable.  The success rates in the clinically evaluable patients at the follow-up visit were 86% (225/261) in the Meropenem arm and 83% (238/287) inImipenem/cilastatin arm.
The following table provides the results for the overall as well as subgroup comparisons in clinically evaluable population.
- Percent of satisfactory clinical response at follow-up evaluation.
 n=number of patients with satisfactory response.
 N=number of patients in the clinically evaluable population or respective subgroup within treatment groups.
The following clinical efficacy rates were obtained, per organism.  The values represent the number of patients clinically cured/number of clinically evaluable patients at the post-treatment follow-up visit, with the percent cure in parentheses (Fully Evaluable analysis set).
- Patients may have more than one pretreatment pathogen.
 n=number of patients with satisfactory response.
 N=number of patients in the clinically evaluable population or subgroup within treatment groups.
 %= Percent of satisfactory clinical response at follow-up evaluation.
The proportion of patients who discontinued study treatment due to an adverse event was similar for both treatment groups.  (meropenem, 2.5% and Imipenem/cilastatin, 2.7%).

## Intra-abdominal
One controlled clinical study of complicated intra-abdominal infection was performed in the United States where meropenem was compared with  clindamycin/tobramycin.  Three controlled clinical studies of complicated intra-abdominal infections were performed in Europe; meropenem was compared with imipenem (two trials) and cefotaxime/metronidazole (one trial).
Using strict evaluability criteria and microbiologic eradication and clinical cures at follow-up which occurred 7 or more days after completion of  therapy, the following presumptive microbiologic eradication/clinical cure rates and statistical findings were obtained:
The finding that meropenem was not statistically  equivalent to cefotaxime/metronidazole may have been due to uneven assignment of more seriously ill patients to the meropenem arm.  Currently there is no additional information available to further interpret this observation.

## Bacterial Meningitis
Four hundred forty-six patients (397 pediatric patients > 3 months to < 17 years of age) were enrolled in 4 separate clinical trials  and randomized to treatment with  meropenem
(n=225) at a dose of 40 mg/kg q 8 hours or a comparator drug, i.e., cefotaxime (n=187) or ceftriaxone (n=34), at the approved dosing regimens.  A comparable number of  patients were found to be clinically evaluable (ranging from 61-68%) and with a similar distribution of pathogens isolated on initial CSF culture.
Patients were defined as clinically not cured if any one of the following three criteria were met:
1.  At the 5-7 week post-completion of therapy visit, the patient had any one of the following: moderate to severe motor, behavior or development deficits,hearing loss of >60
decibels in one or both ears, or blindness.
2.  During therapy the patients clinical status necessitated the addition of other antibiotics.
3.  Either during or post-therapy, the patient developed a large subdural effusion needing surgical drainage, or a cerebral abscess, or a bacteriologic relapse.
Using the definition, the following efficacy rates were obtained, per organism.  The values represent the number of patients clinically cured/number of clinically evaluable patients, with the percent cure in parentheses.
Sequelae were the most common reason patients were assessed as clinically not cured.
Five patients were found to be bacteriologically not cured, 3 in the comparator group (1 relapse and 2 patients with cerebral abscesses) and 2 in the meropenem group (1 relapse and 1 with continued growth of Pseudomonas aeruginosa).
The adverse events seen were comparable between the two treatment groups both in type and frequency.  The meropenem group did  have a statistically higher number of patients with transient elevation of liver enzymes. (See ADVERSE REACTIONS).  Rates of seizure activity during therapy were comparable between patients with no CNS abnormalities who received meropenem and those who received comparator agents. In the Meropenem treated group, 12/15 patients with seizures had late onset seizures (defined as occurring on day 3 or later) versus 7/20 in the comparator arm.
With respect tohearing loss, 263 of the 271 evaluable patients had at least one hearing test performed post-therapy.  The following table shows the degree ofhearing loss between the meropenem-treated patients and the comparator-treated patients.