URINARY TRACT INFECTION TREATMENT IN COMMUNITY PRACTICE Jihan Sf Safwan, Pharm.D. Clinical Assistant Professor School of Pharmacy LIU
LEARNING OBJECTIVES Identify patients with uncomplicated cystitis (UC) presenting to the communitypharmacy Select optimal treatment based on in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) 2
GUIDELINE International Clinical PracticeGuidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women 3 Infectious Diseases Society of America European Society for Microbiology and Infectious Diseases
DEFINITION Urinary Tract Infection (UTI) Inflammatory response of the urothelium after a bacterial invasion accompanied with bacteriuriaand i pyuria Presence of at least 100,000 colony forming units (cfu)/ ml in a pure culture of voided clean catch urine 4
CLASSIFICATION Upper Lower Uncomplicated Pyelonephritis Intra renal abscess Perinephric abscess Cystitis Urethritis Prostatitis Infection in a structurally and neurologically normal urinary tract Uncomplicated Cystitis Complicated Infection in a urinary tract with functional or structural abnormalities (eg. Indwelling catheter or renal calculi) 5
EPIDEMIOLOGY One of the most common indications for prescribing antibiotics at the communitypharmacy Country Lebanon Extrapolated Population estimated Gender prevalence used Females : Males 105,000 4.43 million 30:1 (Anatomy and reproductive 2.37 % physiology) 40% of all females have at least one episode of a UTI at some time in their lives Major cause for the development of resistant bacteria 6 www.rightdiagnosis.com/c/cystitis/statscountry.htm#extrapwarning
EPIDEMIOLOGY Overview of UTI by age and sex 7
CLINICAL SCENARIO 1 Which of the following microorganisms is the main cause ofuncomplicated cystitis? a. Escherichia hi coli b. Pseudomonas aeroginosa c. Streptococcus pneumoniae d. Candida albicans 8
BACTERIOLOGY Bacteria Escherichia coli (E. coli) Klebsiella pneumoniae Percentage 60.64 % 8.27 % Pseudomonas aeroginosa 3.98% Enterococcus Candida albicans species 3.58% 2.37% Proteus species 6.27% Streptococcus agalactiae 1.91% Proteus species 6.27 % Pseudomonas aeroginosa 3.98 % Klebsiella pneumoniae 8.27% Enterococcus species 3.58 % E. coli 60.64% Candida albicans 2.37 % Streptococcus agalactiae 1.91 % 9 Ziad Daoud,Claude Afif Escherichia coli Isolated from Urinary tract infection of Labanese patients between 2000 and 2009: epidemiology and profiles of resistance Chemotherapy Research and Practice vol 2011 Article IO 218431, 6 page Doi 10 1155/2011/218431.
BACTERIOLOGY 10 Prevalence of ESBL E. coli and K. pneumoniae, and MRSA over the past years G.F. ARAJ et al. Antimicrobial bacterial resistance over a decade. Lebanese Medical Journal 2012 Volume 60 (3)
BACTERIOLOGY Antimicrobial susceptibility of E. coli vs years 11 G.F. ARAJ et al. Antimicrobial bacterial resistance over a decade. Lebanese Medical Journal 2012 Volume 60 (3)
PATHOPHYSIOLOGY Colonization of the vaginal introitus by uropathogens from the fecal flora Followed by ascension via the urethra into the bladder UNCOMPLICATED 12 UNCOMPLICATED CYSTITIS
RISK FACTORS Uncomplicated Immunocompetent No co morbidities No known urologic abnormalities Non pregnant Premenopausal Sexual intercourse Female gender Decrease in fluid intake Complicated History of childhood urinary tract infections Immunocompromised Preadolescent or postmenopausal Pregnant Underlying metabolic disorder (e.g., diabetes mellitus) Urologic abnormalities (e.g., stones, stents, indwelling catheters, neurogenic bladder, polycystic kidney disease) 13
SIGNS AND SYMPTOMS Frequency Dysuria Urgency Micturition Suprapubic pain +/ Hematuria 14
DIAGNOSIS Laboratory diagnostic tools (not necessary for UC) Urinalysis (microscopy or dipstick) Urine culture If atypical presentation Nitrites and leukocyte esterase If antimicrobial resistance suspected 15
TREATMENT Considerations in selecting the agent for acute UC: Active againstusualorganisms Achieve high urinary concentrations Tolerable / Low toxicity Resistance rates Propensity to cause Collateral Damage Cost Drug availability 16
TREATMENT Women with acute UC: No fever No Flank pain Nitrofurantoin Trimethoprim Sulfamethoxazole (TMP SMX) Fosfomycin Pivmecillinam Not tin Lebanon Alternatives 17 Fluoroquinolones (FQ) or Beta Lactams
NITROFURANTOIN Mechanism Inactivates or alters bacterial ribosomal proteins and other macromolecules that may interfere with metabolism and cell wall synthesis Dosing 100 mg PO bid for 5 days Clinical 90 95 % Minimal collateral damage Efficacy May be effective ect eagainst ESBL Nausea, vomiting, loss of appetite Take with food Urine may turn dark yellow or brown in color Disappears after discontinuation Contraindicated (CI) if Creatinine Clearance (Cr Cl) < 60 ml/min Pregnancy category B Side effects and 18 counseling ESBL: extended spectrum β lactamase producing gram negative rods; PO: Orally; bid: twice per day
TMP SMX Mechanism TMP Inhibits dihydrofolate reductase Blocks production of tetrahydrofolic acid from dihydrofolic acid SMX Inhibits bacterial synthesis of dihydrofolic acid by competing with para aminobenzoic acid Dosing One double strength tablet (160/800 mg) bid for 3 days Clinical Efficacy 86 100 % Minimal collateral damage Nausea, vomiting, diarrhea, and lossofappetiteof Do not use if you are allergic to sulfa medications High plasma protein binding Drug Interactions Pregnancy category: D Side effects and counseling 19
FOSFOMYCIN Mechanism Dosing Clinical Efficacy Blocks bacterial cell wall synthesis by inactivating enolpyruvyl transferase Reduces bacterial adherence to uroepithelialcells 3 g PO once Dissolve 1 packet (3 g) in a glass of water 91% Minimal collateral damage May be effective against ESBL Good oral absorption Excreted unchanged in urine High urine concentration lasting > 24 hrs Diarrhea, nausea, stomach upset, headache, or dizziness Minimal drug interactions Pregnancy Category: B Side effects and counseling 20
FLUOROQUINOLONES Ciprofloxacin Levofloxacin Ofloxacin Norfloxacin Available In Lebanon Prulifloxacin BUT Notin Guideline 21
FLUOROQUINOLONES Collateral Damage High BBW Increased risk of tendinitis and tendon rupture Contraindication Children Pregnancy Category C Side Effects Nausea / Diarrhea / Dizziness / Headache Lightheadedness / Trouble sleeping Duration 3 days in UC Ciprofloxacin Levofloxacin Ofloxacin Immediate release 250 mg PO bid Extended release 500 mg PO qd 250 mg PO qd 200 mg PO bid 22
BETA LACTAMS Less effective than FQ and TMP SMX Cfdii Cefdinir Duration of treatment 7 days Cefaclor Amoxicillin Clavulanate Cefpodoxime Proxetil Amoxicillin and Ampicillin Not for empiric treatment Poor efficacy High resistance 23
COLLATERAL DAMAGE Ecological adverse effect of antimicrobial therapy Selection of drug resistantresistant organisms Promote colonization or infection with MDR Associated with use of: Broad spectrum cephalosporins hl AND Fluoroquinolones l 24 MDR: Multi Drug Resistant
COLLATERAL DAMAGE Vancomycinresistant enterococci Extended spectrum β lactamase producing Klebsiella pneumoniae Broad spectrum cephalosporins β lactam resistant Acinetobacter Clostridium difficile 25
COLLATERAL DAMAGE Fluoroquinolones FQ resistant gram negative bacilli (pseudomonas) Methicillinresistant S. aureus ESBL 26
COLLATERAL DAMAGE Preserved in vitro susceptibility of E. coli over many years to: Nitrofurantoin Fosfomycin Cause minimal collateral damage (minimal i effects on normal fecal flora) Mecillinam 27
NON PHARMACOLOGICAL TREATMENT Drink plenty of water and other fluids every day (8 10 glasses) Drink cranberry juice Effective toilet hygiene (Wipe front to back) Regular and complete emptying of bladder Fragrance/feminine Shower rather deodorisers Voiding and than bathe Synthetic underwear hygiene post Carbonated, caffeinated, sexual alcoholic and acidic intercourse foods and fluids Avoid irritants 28
CONCLUSION Health care is a multidisciplinary service Pharmacists play a major role Patients seek direct medical advice from pharmacists Follow guideline in treating UTIs & encourage nonpharmacological treatment of UTIs 29
CLINICAL SCENARIO 2 Tamara is a 56 y.o. woman complaining of 1 day of increased urinary frequency, dysuria and sensation of incomplete voiding. She says she does not have fever, chills, vaginal discharge, or flank pain. She states that she is on Acenocoumarol (oral anticoagulant: VitaminK Antagonist) 4 mgpo for stroke prevention. Which of the following would you dispense to treat Tamara? Nitrofurantoin 100 mg PO bid for 5 days TMP SMX double strength tablet (160/800 mg) bid for 3 days Ciprofloxacin 500 mg PO qd for 3 days None of the above since she should perform a urinalysis 30
CLINICAL SCENARIO 3 Nina is a 28 year old woman who presents with a 2 day history of dysuria, frequency, and urgency. She has no significant medical history. She reports that she is very noncompliant and forgets taking any medications. Which one of the following is the best empiric therapy for Nina? Nitrofurantoin t i PO 100 mg twice daily dil for 3 days Ofloxacin PO 200 mg 2 times/day for 3 days TMP SMX PO double strength th2 times/day for 3 days Fosfomycin 3 g PO once 31
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