Aprokam Mechanism of Action



Lab Thea


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ATC classification: Pharmacotherapeutic group: Sensory Organs - Ophthalmologicals - Antiinfectives - Antibiotics. ATC code: S01AA27.
Pharmacology: Pharmacodynamics: Mechanisms of action: Cefuroxime inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.
PD/PK (pharmacodynamics/pharmacokinetics) relationship: For cephalosporins, the most important pharmacokinetic-pharmacodynamic index correlating with in vivo efficacy has been shown to be the percentage of the dosing interval (%T) that the unbound concentration remains above the minimum inhibitory concentration (MIC) of cefuroxime for individual target species (i.e. %T>MIC).
After intracameral injection of 1 mg cefuroxime, cefuroxime levels in the aqueous humour were over MIC for several relevant species for up to 4-5 hours after surgery.
Mechanism of resistance: Bacterial resistance to cefuroxime may be due to one or more of the following mechanisms: hydrolysis by beta-lactamases. Cefuroxime may be efficiently hydrolysed by certain of the extended-spectrum beta-lactamases (ESBLs) and by the chromosomally-encoded (AmpC) enzyme that may be induced or stably derepressed in certain aerobic gram-negative bacterial species; reduced affinity of penicillin-binding proteins for cefuroxime; outer membrane impermeability, which restricts access of cefuroxime to penicillin binding proteins in gram-negative bacteria; bacterial drug efflux pumps.
Methicillin-resistant staphylococci (MRS) are resistant to all currently available β-lactam antibiotics including cefuroxime.
Penicillin-resistant Streptococcus pneumoniae are cross-resistant to cephalosporins such as cefuroxime through alteration of penicillin binding proteins.
Beta-lactamase negative, ampicillin resistant (BLNAR) strains of H. influenzae should be considered resistant to cefuroxime despite apparent in vitro susceptibility.
Breakpoints: The list of micro-organisms presented hereafter has been targeted to the indication (see Indications/Uses).
APROKAM should be used for intracameral application only and should not be used to treat systemic infections (see Pharmacokinetics as follows); clinical breakpoints are not relevant for this route of administration. Epidemiological cut-off values (ECOFF), distinguishing the wild-type population from isolates with acquired resistance traits are as follows: See table.

Click on icon to see table/diagram/image

Susceptibility of staphylococci to cefuroxime is inferred from the methicillin susceptibility.
The susceptibility of streptococcus groups A, B, C and G can be inferred from their susceptibility to benzylpenicillin.
Information from clinical trials: An academic prospective randomized partially masked multicentre cataract surgery study was performed on 16,603 patients. Twenty-nine patients (24 in "without cefuroxime" groups and 5 in "intracameral cefuroxime" groups) presented with endophthalmitis, of whom 20 (17 in "without cefuroxime" groups and 3 in "intracameral cefuroxime" groups) were classified as having proven infective endophthalmitis. Among these 20 proven endophthalmitis: 10 patients are in group "placebo eye drops and without cefuroxime", 7 patients in group "levofloxacin eye drops and without cefuroxime", 2 patients in group "placebo eye drops and intracameral cefuroxime" and 1 patient in group "levofloxacin eye drops and intracameral cefuroxime". The administration of intracameral cefuroxime prophylactic regimen at 1 mg in 0.1 ml sodium chloride 9 mg/ml (0.9%) solution for injection was associated with a 4.92-fold decrease in the risk for total postoperative endophthalmitis.
Two prospective studies (Wedje 2005 and Lundström 2007) and 5 retrospective studies were supportive to the pivotal ESCRS study further substantiating the efficacy of intracameral cefuroxime in postoperative endophthalmitis.
Pharmacokinetics: The systemic exposure following intracameral injection has not been studied but is expected to be negligible.
After intracameral injection at the recommended single dose of 0.1 ml of a 10 mg/ml solution of cefuroxime in cataract patients, the mean intracameral level of cefuroxime was 2614 ± 209 mg/l (10 patients) 30 seconds and 1027 ± 43 mg/l (9 patients) 60 minutes after drug administration.
Toxicology: Preclinical safety data: Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
Intravitreal injection of 1 mg cefuroxime in albino rabbits resulted in levels of 19-35 mg/l and 600-780 mg/l after 30 min following injection in the aqueous and in the vitreous, respectively. Levels after 6 h decreased to 1.9-7.3 and 190-260 mg/l respectively in these two structures. There was no increase in the intraocular pressure during the first 3 days. Histopathology showed no degenerative changes compared to saline.
ERG: a-, b- and c-waves diminished up until 14 days both in the control and antibiotic-injected eyes.
Recovery occurred and may be slower than in control. ERG showed no definite changes suggestive of retinal toxicity up to 55 days after intravitreal administration.
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