Comparison The Effect of Single Daily Dose With 48 Hours Interval of Amikacin With Meropenem in Treatment With Urinary Tract Infection With E. Coli: A Clinical Trial Study

Objective: Urinary tract infection is among the most prevalent infections in humans, and E. coli is the most frequent pathogen causing this disease. The production of Beta lactamase enzymes (ESBL) in this bacterium makes it resistant to many antibiotics. The aim of this study was to evaluate a novel method single daily dose of Amikacin at 48 h intervals in a clinical trial This was a double-blind clinical trial study. Material and Methods: The patients were divided into two groups of Intervention (Administration of single daily dose of Amikacin at 48 h intervals Intervals for 1 week 3 doses) and control (Prescription of Meropenem for 1 Week). Results: The mean age of the Intervention group was (46.64±3.89) and control group (46.03±2.38). The frequency of E. coli infection was 61(54%), and that of other infections was 52(46%). Conclusion: The results of our study show the therapeutic effect of single daily dose administration of Amikacin every 48 hours


Introduction
Urinary tract infection is among the most prevalent infections in humans, and E. coli is the most frequent pathogen causing this disease (1,2). E.coli is a Gram-negative bacillus of the Enterobacteriaceae family.
Today, the treatment of E. coli infections is di cult because of antibiotic-resistant strains. The production of Beta lactamase enzymes(ESBL) in this bacterium makes it resistant to many antibiotics (3,4). Beta lactamases are produced by Gram-negative bacteria and are widely found in the members of the Enterobacteriaceae family. ESBL-producing bacteria are resistant not only to penicillin, cephalosporins, and aztreonam, but also to other antibiotics, including Co-trimoxazole, tetracycline, and uoroquinolones.
Moreover, the easy transfer of the ESBL-coding plasmid in its species is a major threat to hospitalized patients (5,6) .In recent years, numerous studies have been conducted in different parts of the world on the antibiotic resistance of this bacterium, indicating the resistance of several drugs as well as broadspectrum ESBL (7)(8)(9). In the USA, the level of multidrug resistance was 7.1%, while this value was 10.9% in Iran (10,11) . There are ongoing attempts to nd alternative drugs; drugs such as Fosfomycin, carbapenems, Tazocin, and aminoglycosides are currently under study. Carbapenems serve as the treatment of choice for these organisms; recently, Enterobacteriaceae resistant to carbapenems have been produced (12). Since the standard recommended treatment is the use of carbapenems, patients must be hospitalized, and this leads to the consequences of hospitalization and loss of working days, while also increasing the costs and the risk of nosocomial infections. The use of aminoglycoside has been reduced over the past decades. The main obstacles to their use is their side-effects which are higher than those of other antibiotics. However, the side-effects are lower in patients treated with aminoglycosides compared to those receiving beta lactams. The prevalence of microbial resistance to aminoglycosides has been low in recent years. Treatment with aminoglycosides has the same effectiveness as beta lactames or quinolones in reaching clinical improvement in the case of urinary tract infection (1,(13)(14)(15). Therefore, nding an effective alternative method is a therapeutic priority.
Accordingly, the present study, the aim of this study was to evaluate a novel method single dose of Amikacin at 48 h intervals in a clinical trial.

Materials And Methods
This was a double-blind clinical trial study. The inclusion criteria were having the following symptoms: burning sensation when urinating, frequent urination and fever; the exclusion criteria were recently taking antibiotics, taking immunosuppressive drugs, septic shock, having a GFR of less than 60 and creatinine level >3. The vital signs of those visiting the hospital with the mentioned symptoms were checked and after doctor visiting, a smear test and urine analysis and culture were performed. If the results of urine analysis indicated the chance of urinary tract infection, all the patients would be included in the study until a positive culture result would be obtained. Subsequently, those with a negative culture were excluded. Patients signed informed consent forms before inclusion. The patients were divided into two groups of intervention and control. The number of patients included in the study in both groups shown as owchart 1. The study was double-blind since the evaluating doctor, the laboratory, and the patients were blind to the group allocation.
Intervention group received Amikacin 3mg/kg every 48 hours for 7 days then treatment with oxacin 300 mg twice daily for 7 days at the end of the initial injectable treatment. Clinical signs were recorded and urine analysis and culture were performed.
Control group received Meropenem at a dose of 1 gr three times daily for one week, then treatment with oxacin 300 mg twice daily for 7 days at the end of the initial injectable treatment. Clinical signs were recorded and urine analysis and culture were performed.
Data Analysis: After inputting the data into SPSS 18, quantitative data were described as mean and SD, and qualitative data as frequency and percentage. Independent t test was used for comparing two quantitative variables.
Then, using the Fisher exact test, success of treatment was compared between the two groups.

Discussion
The results revealed that a treatment regimen with monotrapy and single daily dose Amikacin with twoday intervals act as the standard treatment of urinary tract infection in 48 hours since the onset of treatment, and one week after the onset of treatment, signi cantly reducing clinical symptoms; after two weeks of treatment, the clinical symptoms of urinary tract infection is resolved in both groups. These ndings were the same in terms of a reduced E. coli urinary tract infection. Although this reduction was more prominent in the control group after a week, after two weeks of treatment, E. coli infections was zero in both groups. As mentioned in the Introduction, the side-effects in patients treated with aminoglycosides are less compared to those receiving beta lactams. The standard recommended treatment is the use of Carbapenems, and patients must be hospitalized; this leads to consequences of hospitalization, increases the costs, ends in loss of working days, and increases the risk of nosocomial infections (1,(13)(14)(15). Based on our results, it seems that monotrapy and single daily dose Amikacin can be a good alternative for treatment of E. coli urine. Results showed that E. coli, followed by Klebsiella pneumoniae, were the most prevalent strains. E. coli had the highest antibiotic resistance to ampicillin, followed by Co-Trimoxazole, Nor oxacin, cipro oxacin, gentamicin, tetracycline, and Ceftazidime, and the least antibiotic resistance to amikacin and nitrofurantoin (17). The results of our study show the therapeutic effect of single dose administration of Amikacin every 48 hours. The main concern with regard to the use of aminoglycosides is their toxicity; the nephrotoxicity of these drugs is 8-14%, which is increased by increasing drug dosage, having a treatment period of 10 days or longer, or simultaneous prescription of nephrotoxic agents (1). Nevertheless, in our study, the renal function of the patients was examined by serum creatinine measurement repeatedly before, during, and after treatment. Moreover, to examine the ototoxicity of patients before and after treatment with Amikacin, they were followed-up in terms of clinical symptoms, e.g. Hearing loss, balance disorder, and vertigo, during and at the end of treatment, and the results showed no nephrotoxicity or ototoxicity in any patient.