Doripreks – bactericidal, antibacterial
Doripenem – synthetic carbapenem broad-spectrum antibiotic, structurally related to other beta-lactam antibiotics. Doripenem has potent in vitro activity against aerobic and anaerobic Gram-positive and Gram-negative bacteria. As compared to imipenem and meropenem it is 2-4 times more active against Pseudomonas aeruginosa.
The mechanism of action. Doripenem has a bactericidal effect by disrupting bacterial cell wall biosynthesis. It inactivates many essential penicillin binding proteins (PBP), and this leads to disruption of bacterial cell wall synthesis and subsequent death of bacterial cells. Doripenem has the highest affinity against PSBStaphylococcus aureus. The cells of Escherichia coli and Pseudomonas aeruginosa doripenem binds strongly to the DPM, which is involved in maintaining the shape of the bacterial cell.
Experiments in vitro have shown that doripenem weakly inhibits the action of other antibiotics, and its action is not inhibited by other antibiotics. Described additive activity or weak synergy with amikacin and levofloxacin against Pseudomonas aeruginosa, as well as daptomycin, linezolid, vancomycin, and levofloxacin against Gram-positive bacteria.
The mechanisms of resistance. Mechanisms of bacterial resistance to doripenem include its inactivation by enzymes hydrolyzing carbapenems, mutant or acquired DPM, reduced permeability of the outer membrane and the active output of doripenem from bacterial cells. Doripenem is stable to hydrolysis by most beta-lactamases, including penicillinase and cephalosporinase that are produced by gram-positive and gram-negative bacteria, with the exception of relatively rare beta-lactamases that can hydrolyze doripenem.
The prevalence of acquired resistance of individual species may vary in different geographical areas and at different times, and therefore very useful information on the structure of local resistance, particularly when treating severe infections. Should seek advice from microbiologists, if the structure of the local resistance is such that the use of a particular drug, at least for some types of infections is questionable.
For doripenem sensitive:
Normally, sensitive species: Gram-positive aerobes – Enterococcus avium, Enterococcus faecalis, Staphylococcus aureus (strains sensitive to methicillin), Staphylococcus epidermidis (strains sensitive to methicillin), Staphylococcus haemolyticus (strains sensitive to methicillin), Streptococcus agalactiae (including strains resistant to macrolides), Staphylococcus saprophyticus, Streptococcus intermedius, Streptococcus constellatus, Streptococcus pneumoniae (including strains resistant to penicillin or ceftriaxone), Streptococcus pyogenes, Streptococcus viridans (including strains moderately sensitive and penicillin resistant); Gram-negative aerobes – Acinetobacter baumannii, Acinetobacter calcoaceticus, Aeromonas hydrophila, Citrobacter diversus, Citrobacter freundii (including strains resistant to ceftazidime), Enterobacter aerogenes, Enterobacter cloacae (including strains resistant to ceftazidime), Haemophilus influenzae (including strains that produce beta-lactamase or ampicillin resistant strains that do not produce beta-lactamase), Escherichia coli (including strains resistant to levofloxacin and strains producing beta-lactamase spread spectrum), Klebsiella pneumonia * (including strains producing ESBL), Klebsiella oxytoca, Morganella morganii, Proteus mirabilis (Including strains producing ESBL), Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa * (including strains resistant to ceftazidime), species of the genus Salmonella, Serratia marcescens (including strains resistant to ceftazidime), species of the genus Shigella; anaerobes – Bacteroides fragilis, Bacteroides caccae, Bacteroides ovatus, Bacteroides uniformis, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bilophora wadsworthia, species of the genus Clostridium, Peptostreptococcus magnus, Peptostreptococcus micros, rodaPorphyromonas species, species of the genus Prevotella, Suterella wadsworthia
resistant organisms: Gram-positive aerobes – Staphylococci resistant to methicillin Enterococcus faecium; Gram-negative aerobic – Stenotrophomonas maltophila
* Species for which doripenem was active in clinical studies.
acquired resistance may be Burkholderia cepacia.
Janssen Pharmaceutica NV, Belgium
Active substance: doripenem monohydrate (based on doripenem) 500 mg
- nosocomial (nosocomial) pneumonia, including pneumonia associated with mechanical ventilation (MV);
- complicated intra-abdominal infections;
- complicated urinary tract infections, including complicated and uncomplicated pyelonephritis and cases with concurrent bacteremia.
hypersensitivity to doripenem or other carbapenems and beta-lactam antibiotics; Children up to age 18 years.
From the nervous system: very often – headache
Since the cardiovascular system: often – phlebitis
On the part of the digestive tract: often – nausea, diarrhea; rarely – colitis caused by Clostridium Difficile
Skin and subcutaneous tissue: often – itching, rash
Allergic reactions: rarely – hypersensitivity reactions (anaphylactic shock)
Liver: often – increased levels of liver enzymes
Other: often – oral candidiasis, a fungal infection of the vulva
During the post-marketing use of doripenem observed adverse effects.
From the blood and lymphatic system: very rarely – neutropenia
How to accept, acceptance rate and dosage
Doripreks introduced into / in. The following table shows the recommended method for application Doripreks drug (doripenem) at a dose of 500 mg every 8 hours for adults.
The infusion time, h
The duration of therapy, days **
In-hospital (nosocomial) pneumonia, including ventilator-related
1 or 4 *
Complicated intra-abdominal infections
Complicated urinary tract infections, including pyelonephritis
* For treatment of patients with nosocomial pneumonia recommended infusion over 1 hour. In the presence of the risk of infection less sensitive organisms recommended infusion for 4 hours.
** Duration of therapy involves the possible transition on the proper oral therapy after 3-day (at least) parenteral therapy, caused clinical improvement (in transition to oral therapy may be administered fluoroquinolones, broad-spectrum penicillins in combination with clavulanic acid, and antibiotics any pharmacotherapeutic group).
1 In patients with concurrent bacteremia duration of treatment can reach 14 days.
In the dark place at a temperature of 15-30 ° C, in the original package.
Probenetsid competes with doripenem for renal tubular secretion and reduces renal clearance doripenema.Probenetsid doripenem AUC increases by 75%, and T1 / 2 from the plasma by 53%. Therefore, it is not recommended to use both probenetsid and doripenem.
Doripenem does not inhibit the major isozymes of cytochrome P450, and therefore, not likely to interact with drugs that are metabolized by these enzymes. Doripenem, judging by the results of in vitro studies, has no ability to induce enzyme activity.
In healthy volunteers doripenem reduces the concentration of valproic acid in the plasma to subtherapeutic levels (AUC valproic acid was reduced to 63%), which is also consistent with the results obtained for other carbapenems. The pharmacokinetics of doripenem are not changed. At simultaneous reception of doripenem and valproic acid concentrations should be monitored and the latter to consider the possibility of appointing another treatment.
In patients receiving beta-lactam antibiotics, there may be serious and sometimes fatal hypersensitivity reactions (anaphylaxis). Before treatment, the patient should be carefully doripenem ask about whether he had prior hypersensitivity reaction to other carbapenems and beta-lactam antibiotics.
In the event of hypersensitivity reactions to doripenem it is necessary immediately to cancel and carry out the appropriate treatment. Severe hypersensitivity reactions (anaphylactic shock) require emergency treatment involving administration of corticosteroids and pressor amines (adrenaline) and holding other measures including oxygen therapy, on / in the introduction of liquids, and also if necessary antihistamines and maintaining airway patency.
pseudomembranous colitis caused by Clostridium difficile, can occur in the treatment of nearly all antibacterial agents, and range from mild to life-threatening. That is why you need to be aware of this complication, if the patient is receiving doripenem, there is diarrhea.
Avoid prolonged treatment doripenem to prevent excessive propagation of microorganisms resistant to it.
The drug should not be mixed with other drugs except for those specified in section “Storage».
recommended to bacteriological examination Before using the product: it is necessary to take adequate samples for bacteriological tests to isolate pathogens, their identification and their susceptibility to doripenem. In the absence of such data, empirical selection of drugs should be performed on the basis of the local epidemiological data structure and local susceptibility of microorganisms.
Symptoms in case of overdose, discontinue administration of doripenem and perform support activities to its complete elimination by the kidneys
Treatment: general symptomatic supportive therapy, including monitoring of vital signs and observation of the clinical status of the patient. Doripenem is removed from the body by hemodialysis, but currently not described no cases of overdose hemodialysis doripenem.