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THE INTERNATIONAL ARABIC JOURNALOF ANTIMICROBIAL AGENTS
was reported to be similar to imipenem/cilastatin, thoughsome data reported that it may be more efcient in certainclinical and bacteriological studies. (1, 3) Our aim is to demon-strate any possible dierence between the two carbapenemsin major septic clinical scenarios. Fever deervescence wasselected as a clinical primary “broad” outcome measure andmortality as a secondary outcome measure to assess theircomparative efcacy. For the treating physician and patients,ever deervescence is a major parameter that demonstratesan adequate response in septic ebrile patients to the pre-scribed antibacterial.
Patients and methods
Study and setup
A prospective multicenter observational comparative openlabel study evaluating the dierence in ever deervescencein adult ebrile septic patients, when being treated with imi-penem/cilastatin or meropenem, the study was approved bythe internal review board o each hospital, study teams hasno inuence on the treating team or the selection o eitherantimicrobial. Patients’ selection took place by reviewing andollowing up cases which were treated with the concernedantibacterials. Sampling was done by recruiting all cases thatwere started on either carbapenem, the treating physiciansstart their patients on either carbapenem at their discretion.The administered doses were; imipenem/cilastatin 500 mgintravenous every 6 hours, or meropenem 1000 mg intrave-nous every 8 hours. The study took place in three hospitals inAmman-Jordan with 610 beds, with 69 ICCU beds. The threehospitals host an array o patients including cancer patients,bone marrow transplant, solid organ transplants includingkidney in all three hospitals, and one host in addition, livertransplants.
Diagnosis and recruitment of febrile septicpatient
All patients with ever were selected defned as; Single rectaltemperature o 38.2 C
measured within twenty-our hoursor two 38C
spikes o ever at least two hours apart, and sys-temic inammatory response syndrome (SIRS) with suspicionor documentation o microbial cause. (4) SIRS criteria (38°C <Temperature < 36°C, Heart rate > 90 beats/min, Respiratoryrate > 20 breaths/min, PaCO2 < 32 mm Hg, 12,000/mm3 <WBC < 4000/mm3, OR > 10% immature (band) orms). Pa-tients’ temperature was measured rectally. When (rarely) tem-perature was measured orally, a 0.5 C
was added as a cor-rection actor to account or rectal temperature. Normalizedtemperature is defned as any twenty-our hours without theabove defnition or ever. The acute physiologic and chronichealth evaluation (APACHE II) score is used as a measure opatient clinical illness severity.
Eligible patients are all ebrile septic patients who are ≥ 18years old. Both genders, meet defnition o ebrile sepsis,including patients with SSTI, CAP, HCAP, VAP (early and late),UTI, IAI, took carbapenem at least or three days, 500 mg i.v.every 6 hours or imipenem/cilastatin, or 1000 mg i.v. every8 hours or meropenem. Patients on previous antimicrobi-als with continuous ever judged to have no response e.g.anti-MRSA agent, and a study antimicrobial was added ornon-resolving ever.Excluded patient are <18 years old, pregnant women or lac-tating women, took the observed study antimicrobials orless than 3 days, ambiguity and repeated interruption otreatment and CNS inection. Blood culture growing MRSA,VRE or any organism resistant to either carbapenem, unlessthe patient was not improving on anti-MRSA agent and astudy antimicrobial was added or non-resolving ever. Pa-tients whom were on one study drug and switched to theother with ever deervescence in less than 48 hours. Pendingmortality defned as death or anticipated death within 24hours o patients being on either antimicrobial, in additionto violation o the defnition o septic patients.
The aim o the study is to demonstrate whether there is adierence between imipenem/cilastatin and meropenem inhow many days it took either study antimicrobial to deer-vesce ever in treated patients. The comparison was done bytesting the proportion dierence between the deervescencedays o both antimicrobials. The assumption is that there wasno dierence, otherwise it would be rejected, and existenceo dierence is declared. Proportions’ dierence is assumednormality, its signifcance is tested by 95% confdence inter-val (C.I. 95%) and P ≤ 0.05 was accepted as signifcance level.The number o patients needed to be studied assuming nor-mal distribution ollowing z statistics is ≥ 30 per study arm.
The primary measure is the days’ dierence in that imipenem/ cilastatin versus meropenem takes to normalize temperatureor ≥ 48 continuous hours. The secondary outcome measureis mortality by discharge, including mortality ater startingeither study antimicrobial.