History of Carbapenem In the 1970s Beecham research Laboratoriesidentified a Carbapenem group, called olivanicacid, which were beta-lactamase inhibitors andbroad spectrum antibiotics.Imipenem has one of the widest spectrumof the beta-lactam antibiotics. It is activeagainst nearly all common bacterial species,including those resistant toaminoglycosides and newer Cephalosporin.
History of Carbapenem The Carbapenem are a group of bicyclicbeta-lactam compounds with a commonCarbapenem nucleus.Imipenem is one of them.Imipenem has high activity againstboth aerobic and anaerobic, atypicalbacteria
We Introduces a New UniqueFamily in antibiotic segmentCarbapenem1. Meropenem2. Imipenem + cilastatin3. Ertapenem
We Introduces a New concept inthis Family……..CarbapenemFeropenem® TabletWhich is approved by FDAVery recently
Distribution of nosocomial infections among adult patients in medical intensive care unitsUTI 31%PNEU 27%BSI 19%GI 5%CVS 4%ENT 4%LRTI 4% Other 5%Blood stream Infections
In 1970s Merck, Sharp and DohmeResearch Laboratories independentlyidentified thienamycin, derived fromstreptococcus catteleya.History of IMIPEN
What is IMIPEN® 500 ?IMIPEN for intravenous use is suppliedas a white sterile powder in 100 mLvials. Each 100 ml vial contains 500 mgof imipenem equivalent and 500 mgcilastatin equivalent.
Therapeutic ClassCilastatin is a competitive,reversible and specific inhibitorof dehydropeptidase-I enzyme.
Therapeutic Uses of IMIPEN® 500 Intra-abdominal infections Lower respiratory tract infections Febrile Neutropenia Gynaecological infections Septicaemia Genitourinary tract infections Bone and joint infections Skin and soft tissue infections Endocarditis
The importance of using the mostappropriate empiric antibiotic earlyto treat nosocomial infections Nosocomial infections inICU
Choosing an appropriateantibiotic for ICUPatients in the ICU displaying signs of sepsisbelong to one of the following categories: infected with a known organism from anidentified site infected with a known organism from anunidentified site infected, but no causal agent has beenidentified uninfected.
Choosing an appropriateantibiotic for ICU Occasionally the clinical signs of aninfection suggest the causal organismand the appropriate antibiotic. However, the choice of antibiotic is oftenguided by the results of microbiologicalinvestigation.
Correlation between organism andsite of infection
Spectrum of activity of some antibioticsFROM THIS DISCUSSIONS I LIKE TOSAYTHATIMIPEN® 500 IS THE MOSTADVANCE , APPROPRIATE,ALTERNATIVE,EMPIRICALANIBIOTIC THERAPY
81.9%58.9%0.0%20.0%40.0%60.0%80.0%100.0%Empiric AntibioticTherapy Appropriate(n=238)Empiric AntibioticTherapy Inappropriate(n=56)PatientswithClinicalSuccess,%p<0.05*Successful outcome was defined as resolution with no change in treatment.Davey P et al. Presented at the International Society of Pharmacoeconomics andOutcomes Research Sixth Annual International Meeting, 2001.In an observational study (n=348) in patients with acute peritonitis, IAIpatients with adequate empiric therapy were significantly more likely tohave successful clinical outcomes.*Appropriate Empiric Therapy for IAI:Successful Clinical Outcome
Abdominal sepsisSepsis originating from the large bowel such asperitonitis, abdominal abscesses, gangrenousappendicitis and diverticulitis.Infection Types: Mixed Aerobic & anaerobicInfectionsDoses & administrations: 500mgimipenem/cilastatin given 6 or 8 hourly isrecommended.Maximum dose should be increased to1000mg three or four times daily.
Intra-abdominal InfectionsInfections contained within the peritoneum orretroperitoneal space. Peritoneal cavity contains: Stomach Jejunum, Ileum Appendix Large intestine (colon) Liver, gallbladder and spleen Retroperitoneal space: Duodenum Pancreas Kidneys
AppendicitisOne of the most common causes of intra-abdominal infections.Treatment: Both Surgical and AntibioticsDepends on presentation of appendix:Normal, inflamed, gangrenous or perforatedBegin antibiotics before appendectomy isperformedAppropriate Therapy: ImipenemContinue antibiotics for 7 to 10 days if appendixis perforated or gangrenous (Switch to oralequivalents)
Deep Gynaecological &Obstetric Infections Septic abortions, postoperativeinfections after vaginal hysterectomy andinfections. Similar to the intra-abdominalinfections. These infections are causedby a aerobic & anaerobic floraDoses & administrations: 500mgimipenem/cilastatin given 6 or 8 hourly isrecommended.Maximum dose should be increased to 1000mgthree or four times daily.
Empirical Treatment ofSepticaemia IMIPEN® 500 is effective in patientswith Bacterial septicemiaDoses & AdministrationsThe dose should be 500 to1000mg every 6 to 8 hr dependingon the severity of infections.
Lower Respiratory Tract Infection In patients with pneumoniae caused byGram – Negative pathogens IMIPEN® 500at a dose of 1000mg three times dailymay be used.
Cystic fibrosis In patients with cystic fibrosis IMIPEN®500 at a dose of 1000mg three timesdaily may be used.
Urinary Tract infections IMIPEN® 500 at a dose of 500mg threetimes daily can be used in cases ofhospital acquired lower or upper urinarytract infections.
Infections in NeutropenicPatients First Line Therapy: IMIPEN® 500 Conventional Antibiotic:Aminoglycosides + CephalosporinsDose: The dose documented in 1gm every6 hours.
Bone & Joint InfectionsIMIPEN® 500 has been used to treatosteomyelitis resulting from accidents orprosthesis implantation, involving gram– positive and gram negative organisms.Dose: The dose documented in 1gm every6 hours.
Skin & soft tissueinfectionsModerately severe to severe softtissue infections.Success rate: 95%
Where u will promote IMIPEN 500INTENSIVE CARE UNITIMIPEN (imipenem/cilastatin) asempirical monotherapy for seriousbacterial infections in the………ICU
Why IMIPEN® 500 is used in ICU ?IMIPEN 500 (imipenem/cilastatin) isused as empirical monotherapy inintensive care unit (ICU) patients withserious bacterial infections.
Serious bacterial infections arecommon in patients in the intensive careunit (ICU) and they result in considerablemorbidity and mortality.What is Serious BacterialInfections ?
Approximately 45% of the 10,038 ICUpatients included in the EuropeanPrevalence of Infection in Intensive Care(EPIC) Survey of 1992 had at least onebacterial infection .Serious Bacterial Infectionsenhances Morbidity rate in ICU?
Pneumonia and other lower respiratorytract infections (LRTIs) are the mostprevalent infections (64.7%), followed byurinary tract (17.6%) and bloodstreaminfections (12.0%).What are the Serious BacterialInfections occur in ICU ? Fifty-five percent of ICU-acquired infectionsare polymicrobial.
What is CAPD PERITONITIS ?CAPD means continuesambulatory peritoneal dialysis(CAPD PERITONITIS)
CAPD Primary response, relapse and overallcure rate were 93%, 4%, 89%respectively in imipenem/cilastatintreatment.
Success rate in IMIPEN® 500 It can be concluded thatImipenem/cilastatin first-linetreatment is highly efficient in CAPDperitonitis.
Why IMIPEN® 500 calledBroad Spectrum Antibiotic ? The activity of IMIPEN® 500 against anunusually broad spectrum of pathogensmakes it particularly useful in thetreatment of polymicrobic mixedaerobic/anaerobic infections as well asinitial therapy prior to the identification ofthe causative organisms.
Dosage and Administrationof IMIPEN® 500 The dosage recommendations forIMIPEN® 500 (for intravenous use only)represent the quantity of imipenem to beadministered. An equivalent amount ofcilastatin is also present.
Dosage and Administrationof IMIPEN® 500 The total daily dosage of IMIPEN® 500should be based on the type or severityof infection and given in equally divideddoses based on consideration of degreeof susceptibility of the pathogens, renalfunction and body-weight.
Adult Dosage Schedule forPatientsMost infections respond to a dailydose of 1-2 g administered in 3-4divided doses.
Adult Dosage Schedule forPatients For the treatment of moderate infection,a 1 g b.i.d. dosage regimen may also beused.
Adult Dosage Schedule forPatients In infections due to less susceptibleorganisms, the daily dosage of IMIPEN®500 may be increased to a maximum of4 g/day or 50 mg/kg/day, whichever islower.
Adult Dosage Schedule forPatients Each dose of 250 - 500 mg of IMIPEN®500 should be given by intravenousinfusion over 20 to 30 minutes.
Adult Dosage Schedule forPatients Each dose 1000 mg should be infusedover 40 to 60 minutes. In patients whodevelop nausea during the infusion,the rate of infusion may be slowed. In patients who develop nauseaduring the infusion, the rate ofinfusion may be slowed.
IV dosage schedule for adults with normalrenal function and body weightSeverity ofInfectionDose of IMIPEN Dosage Interval Total DailyModerate 500mg1000mg8 hrs 1.5gmSevere –Full susceptible500mg 6 hrs 2gmSevere and/orLife threatening– due to lesssusceptibleorganisms1000mg1000mg8 hrs6 hrs3gm4gm
Due to high antimicrobial activity ofIMIPEN® 500 , it is recommended thatthe maximum total daily dosage notexceed 50 mg/kg/day or 4 g/day. However cystic fibrosis patients withnormal renal function have been treatedwith IMIPEN® 500 at doses up to 90mg/kg/day in divided doses notexceeding 4 g/day.Maximum Dose for Patientswith Normal Renal Function
IMIPEN® 500 has been usedsuccessfully as monotherapy inimmunocompromised cancer patients forconfirmed or suspected infections suchas sepsis.Maximum Dose for Patientswith Normal Renal Function
Paediatric Dosing Schedule(3 months or older) For children and infants the followingdosage schedule is recommended: CHILDREN >40 kg body weightshould receive adult doses.
Paediatric Dosing Schedule(3 months or older) CHILDREN AND INFANTS <40 kgbody weight should receive 15 mg/kgat six-hour intervals. The total dailydose should not exceed 2 g.
TREATMENT OF SERIOUS INFECTIOUSCOMPLICATIONS IN BURNED PATIENTS WITH-IMIPENEM/CILASTATIN The use of Imipenem/Cilastatin in thetreatment of severe infections in patientswith extensive deep Burns. The results of the treatment were evaluated asvery good (80.0%) . The symptoms of infectioninitially resolved before the 36th hour.
TREATMENT OF SERIOUS INFECTIOUSCOMPLICATIONS IN BURNED PATIENTS WITH-IMIPENEM/CILASTATIN Imipenem/Cilastatin is a correct choice inempirical treatment and improved seriouscases, including mixed infections, withmultiresistant bacterial pathogens.
Treatment of uncomplicated gonorrheawith single-dose imipenem-cilastatin. Single 500-mg intramuscular doses ofimipenem-cilastatin cured 116 (95%) of122 men and 9 of 9 women withuncomplicated gonorrhea due to beta-lactamase-negative Neisseriagonorrhoeae. Most co-existingChlamydia trachomatis infectionspersisted. Imipenem-cilastatin iseffective for uncomplicated gonorrhea .
Mode of Action of IMIPEN Imipenem prevents the bacteria from makingthe cell wall, so the cells die. Cilastatin sodiumis added to prevent an enzyme made by thekidneys from breaking down the antibioticimipenem. The drug is used to treat grampositive and negative bacteria. It is used to treatinfections of the lower respiratory tract, urinarytract, abdomen, pelvis, skin, bones and joints.
Pharmacokinetics IV admin only half life of both drugs approx 1 hour when given together 2/3 of dose of Imipenem isexcreted unchanged in urine; remaining 1/3 inhyrolysed form < 1% excreted in bile - too little to disturbcolonic flora plasma protein binding of Imipenem only20% Cilastatin excreted almost entirely by kidney
Reconstitution, IntravenousSolution IMIPEN® 500 for intravenous infusion issupplied as a white sterile powder invials containing 500 mg imipenemequivalent and 500 mg cilastatinequivalent.
Reconstitution, IntravenousSolution IMIPEN® 500 is buffered with sodiumbicarbonate to provide solutions in thepH range of 6.5 to 8.5. There is nosignificant change in pH when solutionsare prepared and used as directed.
Reconstitution of IMIPEN® IVDose of IMIPEN® IV(mg of Imipenem)Volume of Diluentto be Added (ml)Approximateaverageconcentration ofImipen IV(mg/ml ofImipenem)500 100 5A suggested procedure is to add approximately 10 mL fromthe appropriate infusion solution to the vial. Shake well andtransfer the resulting suspension to the infusion solutioncontainer.
Where can you keep mymedicine? Imipenem-cilastatin is usually given in ahospital. You may be given imipenem-cilastatin to take home to complete yourtreatment. If you are given this medicineto take at home, store at roomtemperature or as directed until it is timeto mix the medicine.
Compatibility IMIPEN® 500 is compatible with the following infusion fluids: 0.9% sodium chloride intravenous infusion 5% or 10% glucose intravenous infusion 5% glucose intravenous infusion with 0.02% sodium bicarbonate 5% glucose and 0.9% sodium chloride intravenous infusion 5% glucose with 0.225% sodium chloride intravenous infusion 5% glucose with 0.15% potassium chloride intravenous infusion 2.5% and 10% mannitol intravenous infusion normosol-M in 5% glucose intravenous infusion.