Meropenem dosing

Use in pediatric patients For pediatric patients 3 months of age and older, the meropenem dose is 20 or 40 mg/kg every 8 hours (maximum dose, 2 g every 8 hours), depending on the type of infection (intra-abdominal or meningitis). Administer pediatric patients weighing more than 50 kg 1 g every 8 hours for intra-abdominal infections and 2 g every 8 hours for meningitis. Give over approximately 15 to 30 minutes or as an IV bolus injection (5 to 20 ml) over approximately 3 to 5 minutes. 

Streptococcus gentamicin (5 mg/kg per day, dosing based on serum levels) Alternative Therapies Trimethoprim-sulfamethoxazole (TMP-SMX) 10-20 mg/kgTMP IV per day in divided doses every 6-8 hours or meropenem Standard Therapy TMP-SMX Rash, Stevens-Johnson syndrome, bone marrow suppression, nausea/vomiting, hepatotoxicity 14-21... 

Empirical therapy for postoperative infections in neurosurgical patients (including patients with CSF shunts) should include vancomycin in combination with either cefepime, ceftazidime, or meropenem. Linezolid has been reported to reach adequate CSF concentrations and resolve cases of meningitis refractory to vancomycin.35 However, data with linezolid are limited. The addition of rifampin should be considered for treatment of shunt infections. When culture and sensitivity data are available, pathogen-directed antibiotic therapy should be administered. Removal of infected devices is desirable aggressive antibiotic therapy (including high-dose intravenous antibiotic therapy plus intraventricular vancomycin and/or tobramycin) may be effective for patients in whom hardware removal is not possible.36... 

Dual therapy with Cefepime, ceftazidime, imipenem, meropenem, Gentamicin or tobramycin 2 mg/kg loading dose... 

Monotherapy with imipenem 0.5 g IV every 6-8 hours, meropenem 1 g IV every 8 hours, ertapenem 1 g IV every 24 hours, extended-spectrum penicillins with a /3-lactamase inhibitor (piperacillin/tazobactam 4.5 g IV every 6 hours), or tigecycline 100 mg IV as loading dose, then 50 mg IV every 12 hours... 

In subjects with normal renal function, the elimination half-life of meropenem is approximately 1 hour. Meropenem is excreted by the kidney with a half-life of 0.8 to 1.24 hours 65% to 83% of the dose is recovered in the urine as meropenem and 20% to 28% as the inactive open -lactam metabolite. 

The pharmacokinetics of meropenem in pediatric patients 2 years of age and oider are essentiaiiy simiiar to those in aduits. In infants and chiidren 2 months to 12 years of age, no age- or dose-dependent effects on pharmacokinetic parameters were observed. Mean haif-iife was 1.13 hours, mean voiume of distribution at steady state was 0.43 L/kg, mean residence time was 1.57 hours, ciearance was 5.63 mL/min/kg and renai ciearance was 2.53 mL/min/kg. The eiimination haif-iife is siightiy proionged (1.5 hours) in pediatric patients 3 months to 2 years of age. 

Mercaptopurine [6-MP] (Purinethol) [Antineoplastic/ Antimeta lite] Uses Acute leukemias, 2nd-line Rx of CML NHL, maint ALL in children, immunosuppressant w/ autoimmune Dzs (Crohn Dz) Action Antimetabolite, mimics hypoxanthine Dose Adults. 80-100 mg/mVd or 2.5-5 mg/kg/d maint 1.5-2.5 mg/kg/d Peds. Per protocol X w/ renal/hepatic insuff on empty stomach Caution [D, ] Contra Severe hepatic Dz, BM suppression, PRG Disp Tabs SE Mild hematotox, mucositis, stomatitis, D rash, fever, eosinophilia, jaundice. Hep Interactions T Effects W/ allopurinol T risk of BM suppression W/ trimethoprim-sulfamethoxazole X effects OF warfarin EMS May falsely T glucose OD May cause NA and liver necrosis symptomatic and supportive Meropenem (Merrem) [Antibiotic/Carbapenem] Uses lntra-abd Infxns, bacterial meningitis Action Carbapenem X cell wall synth, a [3-lactam Dose Adults. 1 to 2 g IV q8h Peds. >3 mo, <50 kg 10-40 mg/kg IV q 8h in renal insuff Caution [B, ] Contra [3-Lactam sensitivity Disp Inj 500 mg, 1 g SE Less Sz potential than imipenem D, thrombocytopenia Interactions T Effects W/ probenecid EMS Monitor for signs of electrolyte disturbances and... 

Daily dosing is advantage over imipenem or meropenem Individualize treatment based on local susceptibility patterns. 

Carbapenems penetrate body tissues and fluids well, including the cerebrospinal fluid. All are cleared renally, and the dose must be reduced in patients with renal insufficiency. The usual dose of imipenem is 0.25-0.5 g given intravenously every 6-8 hours (half-life 1 hour). The usual adult dose of meropenem is 1 g intravenously every 8 hours. Ertapenem has the longest half-life (4 hours) and is administered as a once-daily dose of 1 g intravenously or intramuscularly. Intramuscular ertapenem is irritating, and for that reason the drug is formulated with 1% lidocaine for administration by this route. 

In animals, meropenem (17) and other carbapenems (18,19) were less epileptogenic than imipenem. In 403 children there was no meropenem-associated neurotoxicity (20) and meropenem was well tolerated in children with bacterial meningitis (21). In summary, a larger dose range of meropenem than imipenem appears to be tolerated, but when strictly observing known risk factors for seizure propensity the difference between the two compounds is very small (22,23). 

A 50-year-old woman, a renal transplant recipient, developed a brain abscess dne to Nocardia otitidisca-viarum after craniotomy and was given meropenem and rifampicin. The dose of tacrolimns had to be increased three-fold to maintain adequate trough concentrations. 

Thienamycin (Fig. 10.5E) is a broad-spectrum p-lactam antibiotic with high P-lactamase resistance. Unfortunately, it is chemically unstable, although the N-formimidoyl derivative, imipenem, overcomes this defect. Imipenem (Fig. 10.5E) is stable to most P-lactamases but is readily hydrolysed by kidney dehydropeptidase and is administered with a dehydropeptidase inhibitor, cilastatin. Meropen-em, marketed more recently, is more stable than imipenem to this enzyme and may thus be administered without cilastatin. Its chemical structure is depicted in Fig. 10.5F. Ertapenem (Fig. 10.5G) has properties similar to those of meropenem but affords the additional advantage of once-daily dosing. 

Response Surface Model A dose-response surface is an extension of dose-response lines (isobols) to three dimensions. In this representation there can be a dose-response surface representing additivity and surfaces above and below suggesting deviation from additivity. Tam et al. [90] studied the combined pharmacodynamic interactions of two antimicrobial agents, meropenem and tobramycin. Total bacterial density data, expressed as CFU (colony forming units), were modeled using a three-dimensional surface. Effect summation was used as the definition of additivity (null interaction hypothesis) and the pharmacodynamic model was assumedi to take the functional form... 

In 6 healthy subjects probenecid (1 g given orally 2 hours before meropenem and 500 mg given orally 1.5 hours after meropenem) increased the AUC of meropenem 500 mg by 43%. Another study in 6 healthy subjects found that probenecid (1.5 g in divided doses the day before and 500 mg one hour before meropenem) increased the AUC of meropenem 1 g by up to 55% and increased its half-life by 33% (from 0.98 to 1.3 hours). In both studies the serum levels of meropenem were modestly increased. This is possibly because meropenem and probenecid compete for active kidney tubular secretion. The manufacturers say that because the potency and duration of meropenem are adequate without probenecid, they do not recommend concurrent use. ... 

A report describes two patients whose valproate levels fell when meropenem and amikacin were given. The first patient had heen maintained on intravenous valproate 1.2 to 1.6 g daily with valproate levels of between 50 and 100 mg/L. Two days after the addition of the antihacterials the levels had halved, and after 3 days of subtherapeutic levels, phenytoin was substituted for valproate. The other patient experienced a drop in valproate levels from 44 mg/L to 5 mg/L within 24 hours of being given meropenem, despite being given greater doses of valproic acid. Other reports " describe reductions in valproate levels in several other patients when they were also given meropenem three of them developed seizures. . ... 

The antimicrobial activity of cinnamon bark, lavender, marjoram, tea tree, peppermint EOs combined with ampicillin, piperacillin, cefazolin, cefuroxime, carbenicillin, ceftazidime, and merope-nem was investigated against p-lactamase-producing E. coll Fractional inhibitory concentration (FIC) values were the results of the trial. It was found that peppermint EO improved the activity of piperacillin against multidrug-resistant E. coli strains (FIC 0.31) compared with piperacillin alone. Also the used dose of meropenem can be reduced when combined with peppermint oil (FIC 0.26) (Xi Yap et ah, 2013). 

In summary, a larger dose range of meropenem than imipenem appears to be tolerated, but when strictly observing known risk factors for seizure propensity the difference between the two compounds is very small [39, 40 ]. 

Krueger, W.A., Bulitta, J., Kinzig-Schippers, M., Landersdorfer,C., Holzgrabe, U., Naber, K.G., Drusano, G.R. and Sorgel, R, Evaluation by monte carlo simulation of the pharmacokinetics of two doses of meropenem administered intermittently or as a continuous infusion in healthy volunteers. Antimicrob. Agents Chemother., 49(5), 1881-1889 (2005). 

Change fo oral therapy as soon as possible if patient s condition improves. Amoxicillin 500 mg (adult dose) or 80 mgAg (child dose) p.o. t.d.s. if organism is found to be penicillin-sensitive. Additional antibiotics shown to have in vitro activity against anthrax may include rifampicin, vancomycin, gentamicin, chloramphenicol, clindamycin, penicillin, amoxicillin, meropenem or imipenem (depending upon sensitivities). ... 

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