Imipenem seizures with

These are structurally related to penicillins and are excreted predominantly by renal tubular secretion. The risk of seizures with imipenem is 0.2%. They are toxic to the proximal renal tubule cells. 

Seizures associated with imipenem + cilastatin have repeatedly been reported (5-7). As with other beta-lac-tam antibiotics, it is difficult to assess clearly the cause of a seizure in patients with a cluster of other predisposing factors for neurotoxicity (8) and hence to reach clear estimates of frequency. In a review of 1754 patients there was a similar incidence of seizures with imipenem -I- cilastatin as with other antibiotic regimens usually containing another beta-lactam (9). In rabbits imipenem -I- cilastatin and another carbapenems were more neurotoxic than benzylpenicillin (10). In mice, ataxia and seizures were seen, with much lower blood concentrations of imipenem than cefotaxime or benzylpenicillin (1900 pg/ml versus 3400 qg/ml and 5800 qg/ml) (11). In mice imipenem also lowered the convulsive threshold of pentetrazol (pentylenetetrazole) more than cefazolin or two other carbapenems (12). Cilastatin alone was not proconvulsant, but it increased the effects of co-adminis-tered imipenem. 

Most common side effects include diarrhea, nausea, vomiting, headache, rash, and infusion-related reactions. Frequency and potential risk of seizures with imipenem appear to be greater in comparison with the other carbapenems and beta-lactam antibiotics. Seizures have occurred most commonly in patients with CNS disorders or bacterial meningitis and/or compromised renal function. May be prevented by dose adjusting for renal insufficency. Pseudomembranous colitis. 

GI distress, drug fever (partial cross-allergenicity with penicillins), CNS effects, including seizures with imipenem in OD or renal dysfunction. 

In a review of 1754 patients there was a similar incidence of seizures with imipenem + cilastatin as with other antibiotic regimens usually containing another beta-lactam [3(f]. In another study, seven of 21 children developed seizure activity while receiving imipenem + cilastatin for bacterial meningitis [3T]. However, computer-assisted monitoring of imipenem + cilastatin dosages in relation to renal function resulted in a reduced incidence of seizures [32 ]. 

Isolated seizures that are not epilepsy can be caused by stroke, central nervous system trauma, central nervous system infections, metabolic disturbances (e.g., hyponatremia and hypoglycemia), and hypoxia. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures I or epilepsy. Medications can also cause seizures. Some drugs that are commonly associated with seizures include tramadol, bupropion, theophylline, some antidepressants, some antipsy-chotics, amphetamines, cocaine, imipenem, lithium, excessive doses of penicillins or cephalosporins, and sympathomimetics or stimulants. 

Imipenem-cilastatin IV is not recommended in pediatric patients with CNS infections because of the risk of seizures and in pediatric patients less than 30 kg with impaired renal function, as no data are available. 

Renal function impairment Do not give imipenem-cilastatin IV to patients with Ccr less than or equal to 5 mL/min/1.73 m, unless hemodialysis is instituted within 48 hours. For patients on hemodialysis, imipenem-cilastatin IV is recommended only when the benefit outweighs the potential risk of seizures. 

A patient is being treated with the compound imipenem for penicillin-resistant pneumococcal infection and is responding well. After several days of treatment, the patient begins vomiting and has diarrhea. You observe a slight seizure at the same time. The infection is very severe, and you do not wish to terminate the imipenem but you fear that the adverse effects will make this a necessity. What do you do ... 

Imipenem-cilastatin is one of the drugs of first choice for the empirical therapy of many polymicrobial pulmonary, intraabdominal, and soft tissue infections. The notable adverse effect of imipenem-cilastatin is seizures affecting 1% of patients. Risk factors for seizures are old age, head trauma, previous seizure disorder, cerebrovascular accident, and renal failure. Among patients with a history of penicillin allergy, 10% are cross-sensitive to imipenem-cilastatin. 

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. 

IMIPENEM WITH CILASTATIN ANTIVIRALS - GANCICLOVIR/ VALGANCICLOVIR t adverse effects (e.g. seizures) Additive side-effects these drugs can cause seizure activity Avoid combination if possible use only if benefit outweighs risk... 

GANCICLOVIR/ VALGANCICLOVIR ANTIBIOTICS- 1. IMIPENEM WITH CILASTATIN 2. TRIMETHOPRIM 1. T adverse effects (e.g. seizures) 2. Possibly t adverse effects (e.g. myelosuppression) when trimethoprim is co administered with ganciclovir or valgancidovir 1. Additive side-effects these drugs can cause seizure activity 2. Small t bioavailability possible additive toxicity 1. Avoid combination if possible use only if benefit outweighs risk 2. Well tolerated in one study. For patients at risk of additive toxicities, use only if benefits outweigh risks and monitor FBC closely... 

The safety profile of the carbapenems is comparable to that of other beta-lactam antibiotics, in particular with regard to laboratory abnormalities, the most common ones being those related to liver function (3,4). In patients with pre-existing nervous system disease or who take dosages above the recommended limits (for example in renal impairment) seizures appear to be more common with imipenem + cilastatin. 

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). 

Carbapenems (imipenem more than meropenem) are believed to increase central nervons system excitation by inhibition of GABA binding to receptors. Combinations with other GABA inhibiting drngs snch as theophylline or qninolones have been reported to provoke seizures (45,46). 

In contrast to what has previously been stated, there was no significant increase in the frequency of seizures among 77 patients with bone marrow transplants who were taking ciclosporin alone (three seizures), 45 patients taking ciclosporin plus imipenem/cilastatin (two seizures), and 44 patients taking imipenem/cilastatin alone (no seizures) (272). 

F Meropenem is the best choice. Ertapenem and ampicillin/sul-bactam do not adequately cover Acinetobacter baumannii. Also, with her history of renal insufficiency and seizures, imipenem would not be appropriate because the patient would be at increased risk for seizures. 

Primaxin cilastatin imipenem. primidolol [ban, inn, usan] is a -adrenoceptor antagonist with antihypertensive, antiarrhythmic and antianginal properties, primidone [ban, inn, usan] (Mysoline ) is a pyrimidinedione closely related to the barbiturates, and its actions are similar to phenobarbitone. It is an anticonvulsant that can be used in oral antiepileptic treatment of all forms of epilepsy (except absence seizures) and of essential tremor. 

Meropenem (Merrem IV) is a dimethylcarbamoyl pyro-lidinyl derivative of thienamycin. It does not require coadministration with cilastatin because it is not sensitive to renal dipeptidase. Its toxicity is similar to that of imipenem except that it may be less likely to cause seizures (0.5% of meropenem- and 1.5% of imipenem-treated patients seized). Its in vitro activity is similar to that of imipenem, with activity against some imipenem-resistant P. aeruginosa but less activity against Gram-positive cocci. Chnical experience with meropenem demonstrates therapeutic equivalence with imipenem. 

Nausea and vomiting are the most common side effects. Seizures have been noted in up to 1.5% of patients, especially when high doses are given to patients with CNS lesions or with renal insufficiency. Patients who are allergic to other jS-lactam antibiotics may have hypersensitivity reactions to imipenem. 

MEROPENEM Meropenem (merrem iv) is a derivative of thienamycin that does not require coadministration with cilastatin because it is not sensitive to renal dipeptidase. Its toxicity and clinical efficacy are similar to imipenem, except that it may be less likely to cause seizures. 

Adverse effects of imipenem-cilastatin include gastrointestinal distress, skin rash, and, at very high plasma levels, CNS toxicity (confusion, encephalopathy, seizures). There is partial cross-allergenicity with the penicillins. Meropenem is similar to imipenem except that it is not metabolized by renal dehydropeptidases and is less likely to cause seizures. 

Some resistant strains lack thymidine kinase. Cannot activate drug. Granuiocytopenia, thrombocytopenia. IV. Excreted unchanged in urine, decrease dose with renal dysfunction. Do not coadminister zidovudine (granulocytopenia) or imipenem-cilastatin (seizures). 

Contraindications Use with caution witb clients with allergy to imipenem, cUastin or otber beta-lactams. Kidney problems require a reduced dosage. More than 2 g daily increase the risk for seizures... 

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. 

Based on an early possible report, the manufacturer notes that generalised seizures have been reported in patients who received ganciclovir with imipenem-cilastatin. They recommend that ganciclovir and its prodrug valganciclovir should not be used with imipenem unless the benefits outweigh the risks.No further reports of this interaction appear to have been published, or reported to the manufacturer. Note that both ganciclovir and imipenem alone may cause seizures. 

Four transplant patients who were taking eiclosporin developed seizures when they were given imipenem/cilastatin 1 g daily, and a fifth patient developed myoclonia. These patients all had chronic renal impairment. In contrast, imipenem/cilastatin 2 g daily for 4 weeks, given with ciprofloxacin, was effectively and successfully used in another patient taking ciclosporin after a heart transplant. This patient was switched to imipenem/cilastatin and ciprofloxacin after developing acute renal failure while receiving amikacin. Reduced serum ciclosporin levels following the use of imipenem/cilastatin have been seen in rats ... 

Calandra G, Lydick E, Carrigan J, Weiss L, Guess H. FactoiB redisposing to seizures in seriously iU infected patients receivii antibiotics experience with imipenem/cilastatin. Am JMed (1988) 84, 911-18. 

Nervous system The carbapenems can cause seizures [SEDA-33, 491]. A 69-year-old man with diabetes and hypertension developed a glioblastoma, which was removed [4 j. About 1 month later, he developed skin and respiratory infections and was given imipenem. During the next 2 days his consciousness became impaired... 

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. 

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