Antibiotic resistance pattern of bacteria in urinary tract infection Done by : Hasan Abu Awwad Yazan AL-Soud Mustfa AL-Rawi Mohammad Najdat Mahmoud AL-saify Mouaoia AL-Shafie

Contents Simple introduction UTI introduction ( Diagnosis , Etiology , 2 ..etc ) Treatment Guidelines Mechanisms of resistance of major UTI pathogens UTI resistance pattern in Jordan Antimicrobial Susceptibility testing Management and recommendations

Time And Region 2002 A B C 2015

. Urinary tract infection (UTI) is an acute or chronic infection, usually bacterial in origin, that may affect any part of the upper or lower urinary system. . Infections of the urinary tract represent a wide variety of syndromes

UTI classification anatomic site of involvement Lower : urethritis, cystitis, prostatitis Upper : Pyelonephritis Uncomplicated/Complicated Complicated UTIs are defined by the FDA as a clinical syndrome characterized by pyuria and a documented microbial pathogen on culture of urine or blood complicated UTI are those associated with risks of treatment failure

Complicated UTIs may be subdivided into the following 4 categories: Structural abnormalities - Calculi, catheters Metabolic/hormonal abnormalities - Diabetes, pregnancy Impaired host responses - Transplant recipients, patients with AIDS Unusual pathogens - Yeast

Epidemiology Approximately 1 in 3 females will have had a urinary tract infection by age 24 years. 40%-50%of female population will experience a UTI in their life Geriatrics is age group with the highest risk of UTI

Clinical Presentation of Urinary Tract Infections (UTIs) in Adults Signs and symptoms Lower UTI: dysuria(pain on urination), urgency, frequency, nocturia, suprapubic heaviness ,gross hematuria Upper UTI: flank pain, fever, nausea, vomiting, malaise , presence of costovertebral tenderness

for men Risk factors homosexuality intercourse with an infected woman, lack of circumcision. prostate hyperplasia

Risk factors common risk factors for both men and women include: for women: sexual intercourse lack of voiding after intercourse use of a diaphragm use of spermicidal jellies pregnancy. common risk factors for both men and women include: DM Urologic instrumentation Renal transplantation Neurogenic bladder Urinary tract obstructio

Treatment Guidelines

First line treatment Nitrofurantoin monohydrate macrocrystals, 100 mg twice daily for 5 days TMP-SMX, 160/800 mg twice daily for 3 days Fosfomycin trometamol, 3g sachet in a single dose

Second-line Treatment Ciprofloxacin, 250 mg twice daily for 3 days Levofloxacin, 250 mg or 500 mg once daily for 3 days Amoxicillin-clavulanate, 500 mg/125 mg twice daily for 7 days Cefpodoxime, 100-mg twice daily for 3 to 7 days

Treat the symptom of dysuria with Phenazopyridine.

In Case Of Pregnancy UTI Urinary tract infections are common during pregnancy, and the most common causative organism is Escherichia coli Pregnant women should be treated when bacteriuria is identified. The choice of antibiotic should address the most common infecting organisms (i.e., gram-negative gastrointestinal organisms). Pregnant women are at increased risk for UTIs. Beginning in week 6 and peaking during weeks 22 to 24, approximately 90 percent of pregnant women develop ureteral dilatation

The antibiotic should also be safe for the mother and fetus. Historically, ampicillin has been the drug of choice, but in recent years E. coli has become increasingly resistant to ampicillin. Ampicillin resistance is found in 20 to 30 percent of E. coli cultured from urine in the out-patient setting.

Nitrofurantoin (Macrodantin) is a good choice because of its high urinary concentration. Alternatively, cephalosporins are well tolerated and adequately treat the important organisms. Fosfomycin (Monurol) is a new antibiotic that is taken as a single dose.

Sulfonamides can be taken during the first and second trimesters but, during the third trimester, the use of sulfonamides carries a risk that the infant will develop kernicterus, especially preterm infants. Other common antibiotics (e.g., Fluoroquinolones and Tetracyclines) should not be prescribed during pregnancy because of possible toxic effects on the fetus.

In Case Of Men UTI As a general rule, all urinary tract infections (UTIs) in men are considered complicated. because the urethra is much longer and the distance between the anus and urethral meatus is greater than in women. Same As adullt Guidline. The EAU guidelines state that nitrofurantoin should not be used in men as it does not reach reliably sufficient tissue concentrations.

In Case Of Pyelonephritis Most episodes of uncomplicated pyelonephritis can be treated in the outpatient setting with an empirical regimen of ciprofloxacin (500 mg twice daily for 7 days) or levofloxacin (750 mg once daily for 5 days). If quinolone resistance is a concern, TMP-SMX (160/800 mg twice daily for 14 days) can be used once the antibiogram shows susceptibility to this medication.

Treatment Of UTI In Children Acute urinary tract infections are relatively common in children, with 8 percent of girls and 2 percent of boys having at least one episode by seven years of age. The most common pathogen is Escherichia coli, accounting for approximately 85 percent of urinary tract infections in children.

The recommended initial antibiotic for most children with UTI is trimethoprim/sulfamethoxazole (Bactrim, Septra). Alternative antibiotics include amoxicillin/clavulanate (Augmentin) or cephalosporins, such as cefixime (Suprax), cefpodoxime, cefprozil (Cefzil), or cephalexin

Urinary tract infection (UTI) is one of the most common pediatric infections. It distresses the child, concerns the parents, and may cause permanent kidney damage.

Identification and molecular characterization of Escherichia coli blaSHV genes. This study identified and molecularly characterized E. coli blaSHV genes from 490 E. coli strains with multi-drug resistance in a hospital population. PCR and molecular cloning and southern blot were performed to assess functions and localizations of this resistant E. coli gene and the pulsed- field gel electrophoresis (PFGE) was utilized to demonstrate the clonal relatedness of the positive E. coli strains. The data showed that 4 of these 490 E. coli strains (4/499, 0.8%) carried blaSHV genes: EC D2485 (blaSHV-5) EC D2487 (blaSHV-5) EC D2684 (blaSHV-11) EC D2616 (blaSHV-195, a novel blaSHV)

blaSHV-5 had a high hydrolysis activity to the broad-spectrum penicillin (ampicillin or piperacillin), ceftazidime, ceftriaxone, cefotaxime and aztreonam. blaSHV-195 and blaSHV-11 had similar resistant characteristics with high hydrolysis activities to ampicillin and piperacillin, but low activities to cephalosporins. The two blaSHV-5 genes were located on a transferable plasmid (23kb), whereas the other two blaSHV variants (blaSHV-11 and blaSHV-195) seemed to be located in the chromosomal material.

ciprofloxacin-resistant Escherichia coli and Klebsiella pneumoniae The aims of this study were to investigate the prevalence of qnrA, qnrB, and qnrS determinants and their molecular characteristics in ciprofloxacin-resistant isolates of Escherichia coli and Klebsiella pneumoniae from urinary tract infections (UTI). A total of 202 nonduplicated clinical isolates of ciprofloxacin-resistant E. coli (n = 143) and K. pneumoniae (n = 59) were collected between July 2005 and August 2006. The qnrB gene was detected in 41 of the 202 isolates. Among 33 of 59 (55.9%) K. pneumoniae isolates showing qnrB, 29 isolates contained the qnrB4 gene, 3 isolates had the qnrB2 gene, and 1 isolate had the qnrB6 gene and all 8 (5.6%) of E-coli strains possessed the qnrB4 gene.

The minimum inhibitory concentrations (MICs) of ciprofloxacin for the transconjugants were 0.03-2 mug/ml, representing an increase of 4- to 256-fold relative to the recipient, E. coli J53Az(r). Resistances to various other antimicrobial agents also were transferred with the plasmid.

UTI resistance pattern in Jordan In general the pattern is changing according to region and time Retrospective Study was conducted in 2014 in Zarqa city / Jordan 3756 urine samples were collected 392 (10.4%) show positive urine cultures ( female 81%) Bacterial isolation and identification

Pathogen isolates from patients with UTI Baceria Male patients Female patients % Male % Female Total Escherichia coli 54 263 13.77 67.09 80.86 Klebsiella spp 14 32 3.57 8.16 11.73 Proteus spp 1 15 .25 3.83 4.08 Psudomonas spp 2 8 .51 2.04 2.55 Staphylococcus aureus .76

Antimicrobial Susceptibility testing 14 antibiotics were tested eight antibiotics were tested for Gram negative , and six ABs were tested for Gram positive bacteria Antibiotics E.coli Klebsiella spp Proteus Spp Psedomonas spp Staphylococcus aureus Cefatoxime 41.46 50 31.25 30.0   Cephalothin 55.06 58.70 50.0 Gentamamicin 26.58 17.39 18.75 40.0 Ampicillin 84.18 89.13 62.5 Nitrofurantion 10.44 52.21 68.75 Norfloxacin 34.81 15.21 10.0 Cotrimoxazole 70.89 54.34 Naldixic acid 66.77 45.65 37.5 Pencillin Erythromycin Gentamicin Vancomycin Lincomycin Teicoplanin Cloxaciiln 66.67 100   33.33

A similar study was conducted in Jordan in 2008 and published in 2001 , showed Overall, high E-coli resistance rate was observed for ampicillin (84%), followed by amoxicillin-clavulanic acid (74.3%), cotrimoxazole (71%), nalidixic acid (47.3%), cephalothin (41%). Lower resistance rates were observed for amikacin (0%) followed by Cefotaxime (11%), Ceftriaxone (11.7%), ciprofloxacin (14.5%), Norfloxacin (16.5%), gentamicin (17.3%) cephalexin (20.9%), Ceftazidime (22.5%), cefixime (29.6%), and cefaclor (32.8%) FQs and indiscriminate use in empirical treatment , Risk Of E-Coli resistance !  

Management and recommendations We don’t prefer the use of agents that showed high levels of resistance like pencillins and cotrimoxazole . An agent with a resistance rate above 20% should not be prescribed empirically . This reinforce the use of nitrofurantoin for uncomplicated cystitis a warning about increasing of E-coli for FQs and sulfamethoxazole-trimethoprim ! . Regular monitoring is required to establish reliable information about susceptibility pattern of urinary pathogens .