Carbapenems ertapenem

Gentamicin (Garamycin, G Mycidn, others) CARBAPENEMS Ertapenem (Invanz)... 

Treatment for septic patients with hospital-acquired, ventilator-acquired, and health care-associated pneumonia is dependent on risk factors for multi-drug resistant (MDR) organisms (Fig. 79-2). Recommended treatment for patients with no MDR risk factors are third-generation cephalosporins, fluoroquinolones, ampicillin-sulbactam, or ertapenem (see Table 79-3).35 Recommended treatment for patients with MDR risk factors are P-lactam/p-lactamase inhibitors (piperacillin-tazobactam), antipseudomonal cephalosporin, or carbapenem, plus an aminoglycoside, plus vancomycin or linezolid (see Table 79-3).35 If an aminoglycoside is undesirable, a antipseudomonal fluoroquinolone may be utilized with a P-lactam/p-lactamase inhibitor. 

Hammond ML. (2004) Ertapenem A Group 1 carbapenem with distinct antibacterial and pharmacological properties. J Antimicrob. Chemother 53 ii7-9. 

Livermore DM, Mushtaq S, Warner M. (2005) Selectivity of ertapenem for Pseudomonas Aeruginosa mutants cross-resistant to other carbapenems. J Antimicrob Chemother 55 306-311. 

Ertapenem (Invanz) [Anti infective/Carbapenem] Uses Complicated intra-abd, acute pelvic, skin Infxns, pyelonepluitis, community-acquired pneumonia Action A carbapenem p-lactam antibiotic, cell wall synth Dose Adults. 1 g IM/IV daily 500 mg/d in CrCl <30 mL/min Peds. 3 mo-12 y ... 

The most common adverse effects of carbapenems—which tend to be more common with imipenem—are nausea, vomiting, diarrhea, skin rashes, and reactions at the infusion sites. Excessive levels of imipenem in patients with renal failure may lead to seizures. Meropenem, doripenem, and ertapenem are much less likely to cause seizures than imipenem. Patients allergic to penicillins may be allergic to carbapenems as well. 

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. 

Fig. 10.5 A, clavulanic acid B, latamoxef C, 1-carbapenems D,olivanicacid (general structure) E, thienamycin F, meropenem G, ertapenem H, 1-carbacephems I, loracarbef.

Ertapenem Sodium INVANZ 2002 antibacterial Zeneca Carbapenem 6 derivative (fungus)... 

The carbapenems (i.e., imipenem, meropenem, and ertapenem) and the 8-lactamase inhibitor combination antibiotics (ampicillin-sulbactam, ticarcihin-lavnlanic acid, and piperacillin-tazobactam) also appear to be eqnivalent to standard therapies in adults. " The greater cost of these newer agents without increased efficacy compared with other reliable regimens, however, makes them less desirable. 

Musson D.G. et al., Assay methodology for the quantitation of unbound ertapenem, a new carbapenem antibiotic, in human plasma, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 1, 783, 2003. 

Ertapenem is a carbapenem that inhibits cell wall synthesis. It is indicated in the treatment of moderate to severe complicated intra-abdominal infections, complicated skin and skin structure infections, community-acquired pneumonia, complicated urinary tract infections (UTIs) (including pyelonephritis), and acute pelvic infections (including postpartum endomyometritis, septic abortion. 

Williams, J.M., Brands, K.M.J., Skerlj, R.T. et al. (2005) Practical synthesis of the new carbapenem antibiotics ertapenem sodium. The Journal of Organic Chemistry, 70,7479-7487. Evindar, G. and Batey, R.A. (2003) Copper- and palladium-catalysed intramolecular aryl guanidinylation an efficient method for the s3mthesis of 2-aminobenzimidazoles. Organic Letters, 5, 133-136. 

Carbapenems Biapenem, Ertapenem, Faropenem, Imipenem, Meropenem, Panipenem... 

Although there is only an isolated report of an interaction between valproate and imipenem, there are now several reports of the interaction between valproate and meropenem or panipenem. Seizures or increased seizure frequeney have been reported. It would therefore seem prudent to monitor the valproate levels in any patient also given carbapenems, being alert for the need to increase the valproate dosage, or to use another antibacterial, or an alternative to valproate. Carbamazepine and phenytoin did not interact in the above reports. The manufacturers of ertapenem have no reports of an interaction on their files, but prudently warn about a possible interaction with valproate because of the interactions seen with other carbapenems. 

Carbapenems An old Chinese man with epilepsy had seizures when meropenem was added to treatment with valproate [407 ]. In a retrospective study of six critically ill patients taking valproate who concurrently received meropenem (n = 4), imipenem (n = 1), or ertapenem (n = 1) mean plasma valproate trough concentrations fell by 58% and estimated mean valproate clearance increased by 191% compared with values obtained while they were not receiving a carbapenem five patients had generalized seizures during concurrent valproate -b carbapenem treatment, including two with no prior history of seizures [408 ]. Meropenem is an enzyme inducer. Because of this pharmacokinetic interaction, concurrent use of these medications should be avoided. 

Like other beta-lactam antibiotics, the carbapenems can cause seizures, which have been reported in association with imipenem + cilastatin 2, 3", 4, 5", 6, ], dori-penem /8, P 7, ertapenem [10, ll ], and panipenem [12 ]. 

Drug-Drug Interactions Simultaneous use of carbapenem antibiotics and VPA is known to result in decreased serum levels of VPA. A retrospective report of interactions with various antibiotics in this class foxmd a mean reduction in serum VPA levels of 88.7% in three patients taking meropenem, a mean reduction of 74% in two patients taking ertapenem, and a reduction of 73.3% in one patient taking imipenem [Wl ]. 

Carbapenems have been associated with decreased valproic acid levels when administered concomitantly. A retrospective series of six cases of drug monitoring reports evaluated tiie combination with various carbapenems and found that this effect was most pronounced with meropenem. Clinicians should be aware of this interaction and choose alternative therapy when possible [76 ]. A conflicting case was reported of a 68-year-old patient whose valproic acid levels were affected by ertapenem, but not meropenem [77 ]. 

A 47-year-old man with a history of rash to cephalexin was treated for erysipelas with clindamycin. His condition did not improve on clindamycin, so it was discontinued and he was initiated on ertapenem. After 2 days of ertapenem treatment, he developed fever, a generalised rash and neufrophilia of 28 x fi cells/L (7.1 x 10 cells/L the day before). All other laboratory values, cultures and chest X-rays were normal. He was diagnosed with acute generalised exanthematous pustulosis (AGEP). Patch tests were posihve for penicillin, cephalothin, meropenem and ertapenem at 48 h. Per the autiiors, this was the first reported cause of carbapenem-induced AGEP confirmed by patch testing [79 ]. 

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