Meropenem Versus Imipenem/Cilastatin in the Treatment of Hospitalized Patients With Skin and Soft Tissue Infections

Nichols, Ronald; Smith, Jeffrey A.; Geckler, Ronald W.; Wilson, Samuel

doi:10.1097/00007611-199504000-00003

Cited by 49 publications

(17 citation statements)

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“…Although certain differences were noted, our data support that meropenem penetrates well into inflammatory exudate, with concentrations exceeding those in plasma after 2 h when given at a dose of 500 mg every 8 h. These data also support the efficacy seen with this regimen as monotherapy in the treatment of skin and soft tissue infections (6). Blister fluid models aim to simulate an infected tissue compartment with similarities that include leukocyte and protein content.…”

supporting

confidence: 71%

Pharmacokinetic Profile of Meropenem, Administered at 500 Milligrams Every 8 Hours, in Plasma and Cantharidin-Induced Skin Blister Fluid

Maglio¹,

Teng

Thyrum

et al. 2003

Antimicrob Agents Chemother

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The pharmacokinetic disposition of meropenem, administered at 500 mg every 8 h, in plasma and cantharidin-induced blister fluid is described. Peak meropenem concentrations in blister fluid lagged behind peak meropenem concentrations in plasma, while a lower elimination rate from blister fluid was also noted. The mean penetration of meropenem into blister fluid was 67%. The pharmacokinetic profile of meropenem in blister fluid supports the utility of this dose in the management of skin and soft tissue infections.In the United States, meropenem is Food and Drug Administration approved for intra-abdominal infections and bacterial meningitis (Merrem package insert; AstraZeneca Pharmaceuticals, Wilmington, Del., 2001). However, this agent has also been found effective for lower respiratory tract, skin and soft tissue, gynecologic, and complicated urinary tract infections as well as empirical therapy in the febrile neutropenic patient (2-4, 6, 9, 11). While these clinical findings may be anticipated from its plasma profile, it is the drug concentration at the site of infection that best supports clinical efficacy. In the context of skin and soft tissue infections, evaluation of drug concentrations in blister fluid may best approximate drug exposure at the infection site, since this fluid has been noted to resemble the situation within an infected tissue (1). In this study, we evaluated the steady-state pharmacokinetic profile of meropenem, administered at 500 mg every 8 h, in both blister fluid and plasma.Study design and population. Ten volunteers were enrolled in this multiple-dose, open-label study after approval was granted from the Hartford Hospital Institutional Review Board, and written informed consent was obtained. Volunteers were 21 to 42 years of age (mean age, 26.8 years), weighed between 68 and 118 kg (mean weight, 86.2 kg), and had a mean height of 1.8 m (range, 1.68 to 1.88 m). Volunteers underwent two complete physical exams within 21 days and 48 h before the study and were considered normal. Laboratory evaluations, including blood chemistries, hematology, and urinalysis, revealed no abnormalities.Blister induction and drug administration. Volunteers received intravenous doses of 500 mg of meropenem (lot no. 6199C; AstraZeneca Pharmaceuticals) in 250 ml of normal saline over 30 min every 8 h for a total of three doses. After the first dose, and approximately 14 h before pharmacokinetic sampling, 0.2-ml drops of an ointment containing 0.25% cantharidin made from cantharidin powder (Sigma Laboratories, St. Louis, Mo.) and standard ointment base were applied to the anterior forearms of the volunteers to produce a total of six blisters per volunteer. The integrity of the blisters was maintained by spraying them with a fast-drying plastic dressing (New-Skin Liquid Bandage Spray; Medtech Laboratories, Inc., Jackson, Wyo.). Volunteers were allowed to take food and drink ad libitum. Caffeine intake was not permitted.Pharmacokinetic sampling. Blood samples were collected into heparinized Vacutainers from an ind...

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supporting

confidence: 71%

Pharmacokinetic Profile of Meropenem, Administered at 500 Milligrams Every 8 Hours, in Plasma and Cantharidin-Induced Skin Blister Fluid

Maglio¹,

Teng

Thyrum

et al. 2003

Antimicrob Agents Chemother

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“…Meropenem has been shown to be effective in several animal models [13]. In clinical trials, it has been used successfully to treat pneumonia [26,29], meningitis [11,21,37], intra-abdominal infections [16,17,20], soft tissue infections [22,30], bacteremia [29], and urinary tract infections [8,29].…”

Section: Discussionmentioning

confidence: 99%

Meropenem monotherapy versus combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients

Behre

Link

Maschmeyer³

et al. 1998

Annals of Hematology

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Infections remain the major cause of morbidity and mortality among neutropenic cancer patients. The current study addresses the question whether monotherapy with the new broad-spectrum carbapenem meropenem exhibits efficacy comparable to that of the standard combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. Seventy-one patients with hematological malignancies (55%) or solid tumors (45%), neutropenia < 500/microliter, and fever > 38.5 degrees C were randomly assigned to either meropenem (1 g every 8 h) or ceftazidime (2 g every 8 h) and amikacin (15 mg/kg/day) intravenously. Meropenem (n = 34) and ceftazidime/amikacin (n = 37) were equivalent with respect to the clinical response at 72 h (62% versus 68%) (p > 0.05) and at the end of unmodified therapy (59% versus 62%). Gram-positive bacteremia responded poorly in the meropenem and ceftazidime/amikacin group (29% versus 25%), whereas all gram-negative bacteremias responded except for one in the meropenem group caused by Pseudomonas aeruginosa. All patients survived to 72 h. One patient in each group died of gram-positive sepsis resistant to study medication. No significant side effects occurred in any regimen. This study suggests that meropenem monotherapy might be as effective as combination therapy with ceftazidime and amikacin for the empirical treatment of febrile neutropenic patients.

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“…For instance, newer clinical trials comparing imipenemcilastatin with meropenem almost uniformly ensure dosage adjustments for both carbapenems based on renal function as a part of study protocols. 53,70,71 Meropenem Meropenem is the second carbapenem approved by the FDA for use against multidrugresistant infections. Currently, it is approved for complicated skin and skin structure infections, intraabdominal infections, and, unlike imipenemcilastatin, pediatric bacterial meningitis (patients aged ≥ 3 mo).…”

Section: Imipenem-cilastatinmentioning

confidence: 99%

Epileptogenic Potential of Carbapenem Agents: Mechanism of Action, Seizure Rates, and Clinical Considerations

et al. 2011

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Antimicrobials are the most frequently implicated class of drugs in drug-induced seizure, with β-lactams being the class of antimicrobials most often implicated. The seizure-inducing potential of the carbapenem subclass may be directly related to their β-lactam ring structure. Data on individual carbapenems and seizure activity are scarce. To evaluate the available evidence on the association between carbapenem agents and seizure activity, we conducted a literature search of the MEDLINE (1966-May 2010), EMBASE (1974-May 2010), and International Pharmaceutical Abstracts (1970-May 2010) databases. Reference citations from the retrieved articles were also reviewed. Mechanistically, seizure propensity of the β-lactams is related to their binding to γ-aminobutyric acid (GABA) receptors. There are numerous reports of seizure activity associated with imipenem-cilastatin, with seizure rates ranging from 3-33%. For meropenem, doripenem, and ertapenem, the seizure rate for each agent is reported as less than 1%. However, as their use increases and expands into new patient populations, the rate of seizures with these agents may increase. High-dose therapy, especially in patients with renal dysfunction, preexisting central nervous system abnormalities, or a seizure history increases the likelihood of seizure activity. Although specific studies have not been conducted, data indicate that carbapenem-associated seizure is best managed with benzodiazepines, followed by other agents that enhance GABA transmission. Due to the drug interaction between carbapenems and valproic acid, resulting in clinically significant declines in valproic acid serum concentrations, the combination should be avoided whenever possible. Clinicians should be vigilant regarding the possibility of carbapenem-induced seizures when selecting and dosing antimicrobial therapy.

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Meropenem Versus Imipenem/Cilastatin in the Treatment of Hospitalized Patients With Skin and Soft Tissue Infections

Cited by 49 publications

References 0 publications

Pharmacokinetic Profile of Meropenem, Administered at 500 Milligrams Every 8 Hours, in Plasma and Cantharidin-Induced Skin Blister Fluid

Pharmacokinetic Profile of Meropenem, Administered at 500 Milligrams Every 8 Hours, in Plasma and Cantharidin-Induced Skin Blister Fluid

Meropenem monotherapy versus combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients

Epileptogenic Potential of Carbapenem Agents: Mechanism of Action, Seizure Rates, and Clinical Considerations

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