Urinary Tract Infections PDF

URINARY TRACT INFECTIONS AND PROSTATITIS Stephanie Zampino, PharmD, BCPS  Objectives 1. Name organisms responsible for urinary tract infections (UTIs)and prostatitis 2. Identify patients who require treatment for UTI based on symptoms and laboratory asse...

URINARY TRACT INFECTIONS AND PROSTATITIS Stephanie Zampino, PharmD, BCPS  Objectives 1. Name organisms responsible for urinary tract infections (UTIs)and prostatitis 2. Identify patients who require treatment for UTI based on symptoms and laboratory assessment 3. Differentiate between complicated and uncomplicated UTIs, asymptomatic bacteriuria and pyelonephritis 4. List the antibiotics that achieve good tissue penetration to the prostate 5. Select appropriate empiric and targeted antibiotic therapy for UTI or prostatitis Readings and Resources ◦ Textbook: ◦ S. Durham, Pharmacotherapy Principles and Practice. 6e; Ch 82. ◦ J. DiPiro, Pharmacotherapy: A Pathophysiologic Approach. 12e; Ch 139. ◦ Infectious Diseases Society of America (IDSA) Guidelines: ◦ Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults (2019) ◦ Uncomplicated Cystitis and Pyelonephritis (2011) ◦ Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection In Adults (2010) Definitions infection ◦ Bacteriuria: presence of bacteria in the urine > - not sunonomous with bacteriuria - infection ◦ Cystitis: Inflammation of the bladder (lower urinary tract) ◦ Pyelonephritis: Inflammation of the kidney usually due to infection (upper urinary tract) ◦ UTI: Microorganisms in urinary tract that cannot be accounted for by contamination ◦ Prostatitis: inflammation of the prostate gland and surrounding tissue due to infection Definitions o Relapse: repeated infections with same organism (persistent infectious source) o Occurs within 1-2 weeks of initial infection ◦ Reinfection: new infection often with different organism than initially isolated ◦ Occurs 4-6 weeks after initial infection ◦ Recurrent: 2 or more infections in 6 months OR 3 or more infections in 1 year ◦ Recurrences can be either relapses OR reinfections URINARY TRACT INFECTIONS Epidemiology o Varies by age and gender o More common in young women o Approximately 1 in 5 women will experience a UTI in their lifetime o Lifetime risk may be as high as 60% o UTIs in children are more commonly the result of urinary tract abnormalities o Higher presence of bacteriuria in elderly Classification of UTI ◦ Uncomplicated UTI ◦ Absence of functional or structural abnormalities ◦ Young females (childbearing age) with no risk factors for failing therapy ◦ Involves only the bladder (lower urinary tract) ▪ Cystitis ◦ Complicated UTI ◦ Structural or functional abnormality of the urinary tract ◦ Risk factors for failing therapy ◦ May involve bladder or kidney (lower or upper urinary tract) ▪ Cystitis or pyelonephritis Risk Factors for Failing Therapy Recurrent Hospital or Male Pregnancy Infections Healthcare (resistance) Acquired Presence of Functional or Urinary Tract Indwelling Recent Urinary Anatomic Obstruction Catheter, Stent, Instrumentation Abnormality Tube > Immune system # cant mount Hx of UTIs in Immuno- a response Renal Transplant childhood suppression Probably have structural abnormality Etiology ◦ Bacterial organisms causing UTI usually originate from bowel flora Uncomplicated Infections: E. coli – 80 to 90% of infections ◦ Usually one single causative organism Complicated Infections: E.coli < 50% and resistance more common ◦ Enterococcus second most frequently isolated in hospitalized patients ◦ Vancomycin-Resistant Enterococci (VRE): E. faecium and E. faecalis ◦ May be polymicrobial Other Isolated Organisms * more common more common in ◦ Gram Positives: ◦ Gram Negatives e younger sexually , ◦ Staphylococcus saprophyticus active females ◦ Klebsiella pneumoniae, ◦ Enterococcus spp. - > hospital acquired ◦ Proteus spp. ◦ Staphylococcus aureus - > very rare De, ◦ Pseudomonas aeruginosa cautious of an infection from ◦ Enterobacter spp. another primary site ◦ Staphylococcus epidermidis – usually a contaminant (normal floral Pathophysiology ◦ Bacteria enter urinary tract through 3 Pathways: 1. Ascending Pathway 2. Hematogenous Pathway 3. Lymphatic Pathway Pathophysiology ◦ 1. Ascending Pathway > most - common ◦ Bacteria in urethra travel upward to the bladder ◦ Use of spermicides/diaphragms as contraception and intercourse can promote colonization and mobilization up the tract ◦ May explain higher incidence of UTIs in women ◦ Women have shorter urethra ◦ Bacteria in urethra due to proximity to perirectal area Pathophysiology ◦ 2. Hematogenous Pathway ◦ Seeding of the urinary tract with pathogens carried by the blood ◦ Represents infection at another primary site of the body ◦ Less than 5% of documented urinary tract infections result from hematogenous spread Pathophysiology ◦ 3. Lymphatic Pathway ◦ Lymphatic system provides communication to the kidney: ◦ Bowl to kidney ◦ Bladder to kidney ◦ Little evidence supporting infections arising this way ◦ Not likely to have significant impact on development of UTIs Pathophysiology ◦ Host Defense Mechanisms: ◦ Low vaginal pH - > prevent other bacteria ◦ Lactobacillus spp. Secrete lactic acid > -prevent grow of of lactobacillus ◦ Estrogen > - help promote growth ◦ Urinary characteristics: ◦ Low pH, high urea and organic acid concentration, osmolality extremes ◦ Prostatic fluid secretions (males ( adhesion of bacteria to the endothelial lining ◦ Immunoglobulins > - prevent adhere for bladder to ◦ Initiation of micturition and bladder voiding -less time Other Risk Factors Women: Both: ◦ Sexual intercourse o Urological instrumentation o Renal Transplantation ◦ Use of diaphragm/spermicides o Neurogenic bladder - > newes can't Control bladder ◦ Diabetes > - uncontrolled , bacterear o Congenital Abnormalities movement o Urinary Tract Obstruction ◦ Pregnancy o Calculi o Tumors I compress ureters Men: o Bladder diverticuli ◦ Lack of circumcision o Urethral strictures and o Drugs - > anticholinergic ◦ Prostatic hyperplasia > - obstruction of prevention urinary goodoutflow Clinical Presentation #A localized (only confined willcause > - palpating ! pain if pyelonephritis to bladder) Cystitis: ◦ Pyelonephritis: (CUA) ◦Dysuria - > burning during ◦ Costovertebral urination ◦Urgency ↓ Tenderness/Flank Pain ◦Frequency 4 ◦ Fever Systemic Signs Nocturia ◦ Nausea/Vomiting ◦ stenderness of Infection Suprapubic heaviness palpitation ◦ Malaise upon ◦ ◦ Gross hematuria ◦ Gross hematuria ◦ May also have urinary urgency/frequency/dysuria Clinical Presentation ◦ Elderly patients: may present with additional atypical symptoms ◦ Altered mental status (should NOT be the only symptom) D has lead to overtreatment > - ◦ Change in eating habits ◦ Gastrointestinal symptoms ◦ Patients with indwelling catheters or neurologic disorders: ◦ May present only with flank pain or fever UTI Diagnosis ◦ Urine Collection: ◦ Midstream clean-catch – preferred and least invasive ↳ Will not start collecting untl Midstream to prevent contamination With skin cells or bacteria on outside the Skin ◦ Catheterization external us internal · straint catheter typically used ◦ Suprapubic bladder aspiration (most invasive UTI Diagnosis ◦ Dipstick – allows for rapid screening for uncomplicated infection ◦ Used in outpatient setting for quick analysis with instant results > - not as accurate and does not give quantitative result ◦ Urinalysis – qualitative (macroscopic) and quantitative (microscopic) ◦ Takes a few hours to return ◦ Urine Culture is Gold Standard for diagnosis D * ◦ Takes at least 24 hours for bacteria to grow in culture ◦ Radiographic images Urinary Dipstick ◦ Treated strip dipped into urine sample ◦ Color changes correlate to WBCs, nitrites, and specific gravity ◦ Nitrites produced by bacteria Inormally not precent ( ◦ Leukocyte esterase detects presence of pyuria (greater than 10 wbc/mm3) ◦ Treatment can be started based on results in patients who are symptomatic  Urinalysis - Macroscopic Normal Possible Infection Color yellow Normal or abnormal Clarity or Appearance Clear Cloudy D Nitrites Negative Positive Leukocyte esterase Negative Positive pH 5-8 Normal or elevated Specific Gravity ≤ 1.035 - *Some reference ranges may vary by institution *Nitrites may be negative if infection caused by a non-nitrite producing organism  Urinalysis - Microscopic Normal* Possible Infection Hyaline Casts/Crystals Negative Negative or Positive D WBC most important 0-5/mm3 > 10/mm3 component RBC 0-2/mm3 0-2/mm3 or greater Squamous Epithelial cells 3-5/mm3 < 5 mm3 Bacteria Negative Present *Some reference ranges may vary slightly by institution Elevated squamous epithelial cells often indicate a contaminated sample Not obtained by clean catch method Unreliable sample Will need re-collected UTI Diagnosis 1. Presence of symptoms 2. Presence of pyuria, nitrites and/or leukocyte esterase in urinalysis ◦ Pyuria correlates with significant bacteriuria in symptomatic patients ◦ Pyuria is defined as white blood cell (wbc) > 10 wbc/mm3 3. Isolation of significant quantity of bacteria from a urine sample ◦ More than 100,000 CFU/mL (105 CFU/mL) via gram stain/culture ◦ Symptoms may be present with lower colony counts in some patients CFU = colony forming units  Asymptomatic Bacteriuria (ASB) ◦ Presence of 1 or more species of bacteria growing in the urine in the absence of signs or symptoms attributable to urinary tract infection ◦ Bacteria in urine must be present in specified quantitative counts ◦ ≥105 colony forming units [CFU]/mL ◦ Does NOT need to be routinely treated D D ◦ Only recommended to treat in two patient populations: ◦ Pregnancy ◦ Patients undergoing endourological procedures that disrupt the mucosa > - opportunistic Infection Practice Question AP is a 24-year-old female presents to her doctor with dysuria, increased urinary frequency and urgency. She denies flank pain, nausea and vomiting and states she has never experienced these symptoms before. She has no other past medical history and her vital signs are all within normal range. What type of urinary tract infection are AP’s symptoms most consistent with? uncomplicated custits Practice Question AP is a 24-year-old female presents to her doctor with dysuria, increased urinary frequency and urgency. She denies flank pain, nausea and vomiting and states she has never experienced these symptoms before. She has no other past medical history and her vital signs are all within normal range. What type of urinary tract infection are AP’s symptoms most consistent with? Uncomplicated UTI/Cystitis - Patient experiencing symptoms (dysuria, increased frequency/urgency) - No systemic signs of infection or flank pain which rules out pyelonephritis - Young female with no other past medical history - No risk factors that would make this a complicated infection Treatment Goals for UTI 1 2 3 4 Eradicate the Prevent or Prevent Prevent invading treat systemic recurrence of antimicrobial organism consequences infection resistance of infection  Therapeutic Management Determine the presence of true infection Determine infection type is therapy indicated ? Initial Evaluation Empiric therapy selection (chosen prior to culture data available) Cystitis versus Pyelonephritis Antimicrobial Selection Complicated or Uncomplicated infection De-escalation and targeting of pathogen with susceptibilities Depends on site, severity of infection, and antibiotic Target Therapy and Duration Shorter courses appropriate for uncomplicated acute cystitis OTC: Urinary Products ◦ Phenazopyridine (Pyridium®, Azo® products) 100 - 200mg TID up to 2 days ◦ MOA: not fully understood; azo dye provides topical urinary analgesia ◦ Take with food to minimize GI irritation (most common side effect) ◦ Body fluid discoloration (urine, sweat, sclera, etc) – appears orange/reddish ◦ Can mask signs/symptoms of UTI ◦ Methenamine +/- sodium salicylate (Cystex®) ◦ Antibacterial (methenamine) and NSAID analgesic (sodium salicylate) ◦ Methenamine hydrolyzed in acidic urine to formaldehyde ◦ Methenamine can be used as prophylaxis for recurrent infection ◦ Evidence limited  Know first- Uncomplicated UTI Treatment line options, doses and duration Drug Usual Dose Duration Place in Therapy Trimethoprim- 1 DS tab twice daily 3 days First-line sulfamethoxazole (TMP- SMZ) Nitrofurantoin 100mg twice daily 5 days First-line Fosfomycin 3 grams as a single dose 1 day First-line Ciprofloxacin 250mg twice daily 3 days NOT first-line second line : fluoroquinolones Levofloxacin 250mg once daily 3 days NOT first-line augmentin. Amoxicillin-clavulanate 500mg every 8 hours 3-7 days NOT first-line Cephalosporin Cephalosporins Varies by agent 3-7 days NOT first-line Pivmecillinam (NEW) 185 mg three times daily 3-7 days Unknown (not likely DS = double first-line) strength  Nitrofurantoin ◦ Available as Macrodantin® or Macrobid® ◦ Nitrofurantoin macrocrystals (Macrodantin®): 50 to 100mg PO every 6 hours ◦ Nitrofurantoin monohydrate/macrocrystals (Macrobid®): 100mg PO twice daily ◦ Per Manufacturer/Package Insert: contraindicated with CrCl < 60 mL/min D ◦ Per Beers Criteria – avoid when CrCl < 30 mL/min (followed in clinical practice) S◦ Duration of Therapy = 5 days for uncomplicated infection in females okay to ◦ Extend to 7 days when treating males use until falls under 30 ◦ First-line therapy for uncomplicated lower UTIs D◦ Do NOT use in Pyelonephritis (upper UTIs) or systemic infection * - only concentrates well in bladder ! Nitrofurantoin ◦ First line due to minimal resistance, effectiveness, and well tolerated ◦ Minimal collateral damage with short-term use for uncomplicated UTIs ◦ May cause urine discoloration (brown) ◦ Safety Monitoring: rare but serious adverse effects (greater risk with long-term use) ◦ Pulmonary toxicity (dyspnea, cough, evidence of fibrosis or pneumonitis on X-ray) ◦ Hepatotoxicity – monitor LFTs ◦ Peripheral neuropathy ◦ Hemolytic Anemia – monitor CBC with long-term use ◦ Periodic renal function testing * * with long-term use Trimethoprim (TMP)/Sulfamethoxazole (SMZ) – Bactrim® ◦ Dose: 1 double strength (DS) tablet (160 mg TMP/ 800 mg SMZ) twice daily ◦ Duration: 3 days for uncomplicated infection in females ◦ If local resistance rates of likely pathogen do not exceed 20% ◦ Renal Dose adjustments: ◦ CrCl 15 – 30 mL/min: reduce to 50% of usual dose (i.e. use single strength tablets) ◦ CrCl < 15 mL/min: avoid or use with caution (may reduce to ~25 to 50% of usual dose) ◦ Contraindicated with marked hepatic damage, megaloblastic anemia due to folate deficiency, administration with dofetilide ◦ Adverse Effects: GI upset (Nausea/vomiting), rash (SJS/TEN), hyperkalemia, hyponatremia, hypoglycemia, blood dyscrasias, increased SCr, photosensitivity ↓ transient SJS = Stevens-Johnson Syndrome TEN = Toxic Epidermal Necrolysis  TMP/SMZ – Bactrim® ◦ First line therapy for uncomplicated UTIs ◦ Short 3-day duration ONLY for uncomplicated infection ◦ Longer duration needed for complicated UTI ◦ Avoid if resistance to E. coli within community is > 20% or used for UTI in past 3 months * ◦ Minimal collateral damage ◦ Sulfonamide → avoid with sulfa allergy ◦ Safety Monitoring: CBC, electrolytes, renal and hepatic function Fosfomycin – Monurol® ◦ Single dose regimen for uncomplicated UTI: ◦ 3 grams powder dissolved in 3-4 ounces cool water given as a single dose ◦ Multi-dose regimen may be used in patients with multidrug resistant infections (ESBL E. coli and Enterococcus) ◦ 3 grams once every 2-3 days for 3 doses ◦ Unknown if this has greater efficacy ◦ Side effects: nausea, diarrhea, headache Fosfomycin ◦ First-line therapy for uncomplicated UTI ◦ Very low rates of resistance → appropriate for ESBL E. coli and VRE ◦ Compared to TMP/SMX and Nitrofurantoin: ◦ Similar clinical efficacy but lower bacterial efficacy - gets rid of symptoms but may not eradicate ◦ Cost: $72 – 100.4 per dose $$$ ◦ Lower costs available via drug coupon websites ESBL = Extended Spectrum Beta-Lactamase VRE = Vancomycin Resistant Enterococci  Beta-lactams ◦ Avoid aminopenicillin empirically for uncomplicated UTI (amoxicillin, ampicillin) ◦ PO options: cefdinir, cefpodoxime, cefaclor, cephalexin, amoxicillin/clavulanic acid, pivmecillinam ◦ Cefdinir 300mg PO BID ◦ Amoxicillin/clavulanic acid 500mg PO every 8 hours ◦ Pivmecillinam 185 mg TID ◦ May start with broader empirical coverage then narrow based on susceptibilities from culture (i.e. 3rd gen → 1st gen cephalosporin) ◦ IV options: ceftriaxone, cefazolin, ampicillin-sulbactam ◦ Typical options for hospitalized patients without risk factors for MDR organisms ◦ Typically start with ceftriaxone empirically then narrow coverage based on susceptibilities ◦ Rising resistance for ampicillin-sulbactam (Ceftriaxone > amp/sulbactam for E. coli coverage) ◦ Not preferred MDR = Multi-Drug Resistant  Pivmecillinam (Pivya®) – NEW Approved April 2024 ◦ Approved for uncomplicated UTIs caused by susceptible isolates of E. coli, Proteus mirabilis, and S. saprophyticus in females > 18 years of age ◦ Early data shows clinical efficacy versus placebo and comparable efficacy to cephalexin ◦ Role in practice unclear (unknown cost) but adds another option for uncomplicated UTI ◦ MOA: Prodrug of mecillinam (beta-lactam) that carries high specificity against penicillin- binding protein 2 (PBP-2) in gram negative cell wall ◦ Dosing: 185 mg TID for 3 to 7 days, higher dose of 370 mg TID may be needed for ESBL producers ◦ Contraindications: hypersensitivity to beta-lactams, primary or secondary carnitine deficiency and other inborn errors of metabolism, porphyria ◦ Common Side Effects: GI upset, vaginal candidiasis/genital pruritus, headache, rash ESBL = extended spectrum beta-lactamase  Beta-lactams ◦ NOT first-line for uncomplicated UTI ◦ Decreased efficacy and increased collateral damage (disruption in GI flora) ◦ Compared to first-line agents ↓ ulauer risk for c dif. ◦ Cephalosporins do NOT cover Enterococcus * ◦ Duration of therapy: 3-7 days for uncomplicated infection ◦ Safety Monitoring: anaphylaxis after first dose, renal function and hepatic function (LFTs) if using prolonged course  Fluoroquinolones ◦ NOT first-line therapy for uncomplicated UTI (reserve as last-line option) ◦ Dosing in uncomplicated UTI: ◦ Ciprofloxacin 250mg PO BID for 3 days ◦ Levofloxacin 250mg PO daily for 3 days ◦ Renal Dose adjustments for CrCl < 50 mL/min ◦ Collateral damage → disruption of GI flora and increased risk for C. difficile infection ◦ Moxifloxacin NOT appropriate for UTIs due to poor concentration in bladder  Fluoroquinolones ◦ Black Box Warnings and Serious Adverse Effects: ◦ Tendon rupture ◦ QT prolongation ◦ Peripheral neuropathy ◦ CNS and psychiatric effects (agitation, delirium, memory impairment) > - elderly pop ◦ Aortic dissection ◦ Glycemic disturbances ◦ Myasthenia Gravis exacerbations D◦ Ciprofloxacin contraindicated with concurrent tizanidine administration ◦ Safety Monitoring: ECG, CBC, renal and hepatic function, signs and symptoms of side effects Uncomplicated UTI - Summary Woman with acute uncomplicated Consider alternate cystitis: diagnosis (i.e. No fever, flank pain or other suspicion no pyelonephritis or for pyelonephritis complicated UTI) Able to take PO meds Use Beta-Lactams yes (avoid aminopenicillins alone) DCan one of the following be recommended based on availability, allergies and tolerance, and no OR resistance patterns? Nitrofurantoin 100 mg twice daily x 5 days Fluoroquinolones OR (last line) Trimethoprim-sulfamethoxazole 160/800 mg twice daily x 3 days Prescribe a OR yes recommended Fosfomycin 3 grams in a single dose antimicrobial **Choice of therapy should be individualized based on allergies, compliance, resistance, availability, cost, patient/provider preference, and threshold for failure Recap! ◦ What are Risk Factors for Failing UTI Therapy? (AKA Complicated UTI) ◦ Male gender ◦ Pregnancy ◦ Functional/Structural Abnormalities ◦ Presence of indwelling catheter/stent/tube ◦ Renal transplant ◦ Immunosuppression ◦ Hospital or Healthcare acquired infection ◦ History of UTIs in childhood ◦ Multidrug resistant infection ◦ Recent Urinary instrumentation This will change our treatment choice and duration of therapy  D Review: treat for Treatment Strategy: complicated UTI when patient has risk factors Complicated UTI for failing therapy ◦ Additional organisms may be present: Pseudomonas, Serratia, Providencia, Enterococci, Staphylococci ◦ AVOID empiric therapy with nitrofurantoin, TMP/SMZ, fosfomycin D D Nitro and fostoe only work in bladder ◦ Antibiotic choices: Dactrim - more resistance ◦ Oral: beta-lactams, fluoroquinolones ◦ IV: ceftriaxone (low Pseudomonas risk, no resistance), carbapenem, piperacillin- tazobactam, aminoglycosides, cephalosporin/beta-lactamase combinations ◦ If gram positive organism – ampicillin or amoxicillin if susceptible (Enterococcus infections) ◦ Duration of treatment 5 to 14 days ◦ Typically see 7 to 10 days in clinical practice ◦ Shorter durations for patients with prompt resolution of symptoms  Treatment Strategy: Review: Pyelonephritis Symptoms Flank Pain Pyelonephritis Systemic signs of infection * * ◦ Not synonymous with Complicated UTI, but also requires longer treatment duration ◦ May be treated in outpatient setting unless infection causes vomiting, decreased food intake, and dehydration ◦ May start with IV antibiotic therapy first and transition to oral therapy ◦ Gram stain and culture with susceptibilities are important to drive appropriate antimicrobial therapy decisions ◦ Empiric therapy may start out broad initially, then narrow to target specific organism Outpatient Pyelonephritis Treatment ◦ Mild Cases – low grade fever, flank pain, no nausea or vomiting, and normal or slightly elevated white blood cell count ◦ Beta-lactams ◦ Fluoroquinolones ◦ TMP/SMZ ◦ Duration of therapy: 5 to 14 days ◦ Often individualized based on response to therapy and choice of antimicrobial ◦ 5 days for high dose levofloxacin 750mg daily ◦ 7 days for ciprofloxacin 500mg BID and levofloxacin 500mg daily ◦ Up to 14 days for TMP/SMZ 1 DS tablet BID ◦ Up to 14 days for amoxicillin/clavulanate 500mg every 8 hours Inpatient Pyelonephritis Treatment ◦ Patients with more severe signs/symptoms and/or risk for dehydration ◦ Antimicrobial selection: ◦ Ceftriaxone, ceftazidime ◦ Piperacillin-tazobactam ◦ Carbapenems ◦ IV fluoroquinolone ◦ Newer cephalosporins or carbapenems with beta-lactamase inhibitors for patients with MDR ◦ Duration 5 to 14 days – adjust based on clinical response and antimicrobial choice ◦ Typically see 7 to 10-day duration in practice ◦ 5 days ONLY with high * * dose levofloxacin MDR = multi-drug resistance Newer Therapy for MDR UTIs ESBL CRE MDR Pseudomonas Ceftolozane/tazobactam (Zerbaxa®) + - + Ceftazidime/avibactam (Avycaz®) + + + Cefiderocol (Fetroja®) + + + Meropenem/vaborbactam + + - (Vabomere®) Imipenem-cilastatin/relebactam (Recarbrio®) + + + All indicated for Complicated UTIs including Pyelonephritis ESBL = Extended Spectrum Beta-Lactamase; CRE = Carbapenem-Resistant Enterobacterales; MDR = Multi-Drug Resistant Pipeline Antibiotics ◦ Cefepime and enmetazobactam (Exblifep®) – Newly approved in Feb 2024 ◦ IV option for complicated UTI or pyelonephritis ◦ Anticipated availability/pricing to be determined ◦ Found to be non-inferior to piperacillin/tazobactam in clinical trials ◦ Cefepime and taniborbactam - Phase 3 trial completed ◦ Demonstrated superiority over meropenem in a Phase 3 trial for complicated UTI/pyelonephritis ◦ Not FDA approved yet (FDA requesting more data on manufacturing process) ◦ Mevcillinam - IV formulation in Phase 1 trial stages Special Populations -Most common cause of hospital acquired Catheter- Associated Pregnancy UTI Elderly UTIs in Men  Catheter-Associated UTI (CA-UTI) ◦ The most common cause of hospital-acquired infection ◦ Incidence of infection related to: ◦ Method and duration of catheterization ◦ Catheter system (open or closed) and care of the system ◦ Susceptibility of the patient ◦ Technique of healthcare personnel ◦ Closed systems capable of preventing bacteriuria for up to 10 days D ◦ Incidence of bacteriuria is 78% to 95% for indwelling catheters in place for > 30 days ◦ Symptomatic patients at risk for developing pyelonephritis and bacteremia CA-UTI (continued) ◦ UTI symptoms in this population are not clearly defined ◦ Asymptomatic patients with short-term catheter use (< 30 days): ◦ Hold off on systemic antibiotics, remove catheter as soon as possible ◦ Bacteriuria often represents colonization of catheter ◦ Unnecessary treatment increases risk for further colonization with resistant organisms ◦ Symptomatic patients: ◦ Remove and/or replace catheter BEFORE obtaining urinalysis and culture ◦ Start empiric therapy for complicated UTI  CA-UTI (continued) ◦ Optimal duration of therapy unknown ◦ Treat as complicated infection ◦ Typical duration 7 to 10 days in practice ◦ Antibiotics NOT recommended for prophylaxis for CA-UTI infections D * ◦ Delays bacterial colonization and selects for resistant pathogens  Pregnancy ◦ Pregnant patients with bacteriuria are at increased risk of: ◦ Pyelonephritis ◦ Low-birth weight ◦ Pre-term labor ◦ Anatomical and physiologic changes predisposing to infection ◦ Compression of ureters may predispose upward reflux of urine ◦ Decreased concentration of the urine ◦ Glucosuria ↑ With destational diabetes ◦ Progesterone effects promoting ureteric dilatation ◦ All pregnant patients should be screened and treated for Asymptomatic Bacteriuria  Pregnancy (continued) ◦ Guideline-preferred treatment options: ◦ Beta-lactam antibiotics ◦ Preferred over nitrofurantoin and TMP/SMZ during first trimester and at term ◦ Nitrofurantoin ◦ Contraindicated at term (38-42 weeks gestation), avoid in first trimester ◦ May be considered first-line during second and third trimesters (NOT at term) ◦ AVOID fluoroquinolones and tetracyclines in pregnancy ◦ AVOID TMP/SMZ in first trimester and at term ◦ Treatment Duration: 4 to 7 days require follow up cultures ! ◦ Fosfomycin ◦ Effective as a single-dose regimen ◦ Lacking outcome data on pyelonephritis and effects on pre-term labor  Elderly ◦ Multifactorial risk factors ◦ Anatomic abnormalities ◦ Hormonal and metabolic changes ◦ Neurologic disorders ◦ Poor peri-anal hygiene ◦ Smaller bladder capacity → increased frequency of urination ◦ Reduced fluid intake → more concentrated and malodorous urine Idehudration ( D◦ ASB in elderly is NOT associated with increased morbidity or mortalityD  Treatment in Patients with Dementia ◦ Patients with Dementia are often overtreated for UTI ◦ Inability to communicate symptoms ◦ Commonly have mental status changes ◦ In a study with 196 ‘suspected’ UTIs in dementia: ◦ 75% received antimicrobial agents ◦ Only 16% met the minimal criteria for antimicrobial initiation ◦ Treatment of bacteriuria did NOT improve survival J Am Geriatr Soc. 2015;63(12):2472-2477. Treatment in Patients with Delirium ◦ Prospective cohort study on 343 delirious inpatients ◦ 92 patients (27%) were treated for ASB ◦ Treatment associated with poor functional recovery (RR 1.3, 95% CI 1.14 – 1.48) ◦ Presence of altered mental status alone should NOT trigger therapy for UTI ◦ Signs/Symptoms helpful for determining infection presence in setting of alerted mentation: ◦ Costovertebral tenderness upon exam ◦ Suprapubic tenderness upon exam ◦ Systemic signs of infection (fever, leukocytosis, etc.) Archives of Gerontology and Geriatrics. 2017;72:127-134 UTIs in Men ◦ Not always “complicated” if only risk factor is gender ◦ Abnormality in structure or functionality should be suspected and historically has required treatment as complicated infection ◦ Can utilize first-line antibiotics seen in uncomplicated UTI but with longer durations ◦ NOT appropriate for shortest durations of therapy used in women (3-5 days) ◦ Duration: 7 to 14 days ◦ May use shorter 7-10 day duration for most males with prompt symptom resolution Efficacy Monitoring ◦ Symptoms should resolve within 48-72 hours after start of antibiotics ◦ “prompt” resolution ◦ Can use the shorter end of duration range for patients with good response ◦ Treat with longer duration for those without prompt resolution ◦ Follow-up on susceptibilities from urine culture to ensure proper antibiotic choice ◦ Use the most narrow-spectrum option that will cover the organism found D D ◦ Repeat culture if symptoms do not resolve or concern for recurrent infection ◦ Other monitoring for safety contingent on specific antibiotic selected Relapse vs. Reinfection Relapse Reinfection Occurs in 1 to 2 Occurs in 4 to 6 weeks with same weeks with different organism organism May require longer Primarily in women duration of treatment Methods to reduce recurrent UTI Preventative Measures Frequent Proper wiping Hydration Voiding/Postcoital technique Voiding Lactobacillus Estrogen Cranberry Juice Probiotics replacement topical proanthocianidines Recurrent UTI Prevention - after sexual intercourse ◦ Postcoital dose of antimicrobial ◦ TMP/SMZ single strength (SS) in a single dose ◦ Intermittent self-treatment ◦ Self-diagnosis and treatment with a short course ◦ Continuous low-dose prophylaxis ◦ TMP/SMZ 40/200mg once daily ◦ TMP/SMZ 40/200mg three times weekly ◦ Trimethoprim 100mg once daily ◦ Nitrofurantoin 50 to 100mg once daily ◦ Cephalexin 125 to 250mg once daily ◦ Ciprofloxacin 125mg once daily UTI Summary ◦ Bowel flora organisms are the most likely organisms to cause UTIs ◦ Patients with symptoms and significant pyuria require treatment for UTI ◦ Uncomplicated UTIs are those in young women without structural abnormalities or risk factors for failing therapy ◦ Complicated UTI may involve upper OR lower urinary tract ◦ Complicated UTIs and Pyelonephritis require longer durations of treatment ◦ Asymptomatic bacteriuria should ONLY be treated in cases of pregnancy and urological surgery involving the mucosa PROSTATITIS Prostatitis ◦ Inflammation of the prostate gland as a result of infection ◦ Bacteria and inflammatory cells must be present in prostatic secretions and urine ◦ Can be acute or chronic ◦ Associated with recurrent infection in men > 30 years old ◦ As many as 50% of males may experience during lifetime Pathophysiology ◦ Exact mechanism of bacterial infection not well understood ◦ Gram negative pathogens more common – E. coli in 75% of cases ◦ Possible routes of infection similar to UTIs but also include: ◦ > secretions reflux back onto prostate Intraprostatic reflux - ◦ Sexual intercourse ◦ Indwelling urethral and condom catheterization ◦ Urethral instrumentation ◦ Transurethral prostatectomy in patients with infected urine Pathophysiology (continued) ◦ Normally functioning prostate gland produces secretions with an antibacterial factor ◦ Heat-stable cation complexed with zinc ◦ Zinc content related directly to antibacterial activity ◦ Patients with prostatitis appear to have lower zinc levels in prostatic fluid ◦ pH of prostatic secretions is altered in those with prostatitis ◦ Shift from more acidic (pH 6.6 to 7.6) to a more alkaline (pH 7 to 9) environment ◦ Affects pathogenesis AND therapy options Clinical Presentation ◦ Acute Bacterial Prostatitis ◦ Sudden onset fever, chills, tenderness, and urinary symptoms (frequency, urgency, retention) ◦ Localized pain (perineal, rectal, sacrococcygeal) ◦ Chronic Bacterial Prostatitis ◦ Recurring infection from incomplete organism eradication ◦ Few symptoms related to prostate ◦ Urinary difficulty, low back pain, perineal pressure, or combination Diagnosis ◦ Made from clinical presentation and presence of significant bacteriuria ◦ Bacteria will also readily grow from prostatic secretions ◦ Prostatic massage contraindicated * * in acute bacterial prostatitis ◦ Midstream urine culture utilized in most cases ◦ Chronic prostatitis more difficult to diagnose and treat ◦ Characterized by recurrent UTIs with the same pathogen ◦ Diagnosis can be made if bacteria in prostatic secretions is 10-fold higher than midstream and urethral urine samples Antimicrobials in Prostatitis ◦ Not all antibiotics penetrate prostatic tissue to therapeutic concentrations ◦ Trimethoprim and Fluoroquinolones (ciprofloxacin and levofloxacin) preferred ◦ Utilize local antibiograms and urine cultures to tailor therapy towards pathogen ◦ Alternative antibiotics include cephalosporins and beta-lactam with beta-lactamase inhibitor (not as good prostatic tissue penetration) ◦ Factors that determine antibiotic diffusion into prostatic secretions ◦ Lipid solubility ◦ Degree of ionization → only unionized molecules can cross the lipid barrier ◦ pH gradient ◦ Low protein binding ◦ Small molecular size Acute Bacterial Prostatitis o Acute inflammation allows for antimicrobials to cross prostatic membrane o Appropriate to empirically start IV therapy and transition to oral therapy o PO transition once patient afebrile for 48 hours or after 3 to 5 days of IV therapy o Total Duration = 4 weeks o May be able to stop at 2 weeks in some patients with good clinical resolution and no growth on repeat urine culture o Goal is to prevent progression to chronic bacterial prostatitis Chronic Bacterial Prostatitis ◦ Choice of antibiotics limited to those that can achieve good tissue penetration ◦ Trimethoprim (can prescribe Bactrim but SMX has no beneat) ◦ Fluoroquinolones o Sulfamethoxazole commonly used in combination with trimethoprim due to drug availability but NOT likely to contribute towards efficacy for prostatitis o Treatment duration = 6 weeks (longer courses up to 12 weeks may be considered) o Some patients may require chronic suppressive therapy Summary ◦ Prostatitis is associated with recurrent UTIs in men ◦ Acute prostatitis usually presents with systemic signs of infection ◦ Fluoroquinolones and Trimethoprim antibiotics achieve good tissue penetration ◦ Treatment duration for acute disease is between 2 to 4 weeks ◦ Chronic bacterial prostatitis requires longer treatment courses of at least 6 weeks Assessment Question AJ is a 32-year-old female presents to the emergency department with nausea, vomiting, dysuria and flank pain. She endorses subjective fever and chills and has labs significant for a wbc 14,000, heart rate of 105 bpm, temperature 100.4 F. pueconepurins Which antibiotic regimen is most appropriate for empiric therapy to treat this UTI? Juncomplicated A. Nitrofurantoin 100 mg BID B. Trimethoprim/sulfamethoxazole 1 DS tab BID C. Ceftriaxone IV 1 gram daily D. Levofloxacin IV 500 mg daily J avoid IQ's if possible Assessment Question AJ is a 32-year-old female presents to the emergency department with nausea, vomiting, dysuria and flank pain. She endorses subjective fever and chills and has labs significant for a wbc 14,000, heart rate of 105 bpm, temperature 100.4 F. Which antibiotic regimen is most appropriate for empiric therapy to treat this UTI? A. Nitrofurantoin 100 mg BID B. Trimethoprim/sulfamethoxazole 1 DS tab BID C. Ceftriaxone IV 1 gram daily D. Levofloxacin IV 500 mg daily  Assessment Question AJ was started on Ceftriaxone 1 gram IV once daily for her pyelonephritis infection and has completed 2 days of therapy. Her urinary symptoms have resolved, wbc count decreased to 9,000 and vital signs are normal. Her urine culture returned positive for E. coli (>100,000 CFUs) that is pan-sensitive to all antibiotics during susceptibility testing (see table for results). The team asks for your recommendation for an oral antibiotic for discharge today. Which antibiotic therapy plan is most appropriate to recommend for de-escalation? A. Nitrofurantoin 100 mg BID for 7 more days x neveru fons Amoxicillin Escherichia coli ( > 100,000 colony forming units/mL) Sensitive B. Trimethoprim-sulfamethoxazole 1 DS BID for 3 more days ↓ Ampicillin-sulbactam Sensitive C. Cefdinir 300 mg BID for 5 more days Cefazolin Sensitive D. Fosfomycin 3 grams PO as a single dose 5 Move Ceftriaxone Sensitive days ↓ Cefepime Sensitive not used Piperacillin-tazobactam Sensitive for puelonepurts Trimethoprim-sulfamethoxazole Sensitive Meropenem Sensitive Ciprofloxacin Sensitive Nitrofurantoin Sensitive  Assessment Question AJ was started on Ceftriaxone 1 gram IV once daily for her pyelonephritis infection and has completed 2 days of therapy. Her urinary symptoms have resolved, wbc count decreased to 9,000 and vital signs are normal. Her urine culture returned positive for E. coli (>100,000 CFUs) that is pan-sensitive to all antibiotics during susceptibility testing (see table for results). The team asks for your recommendation for an oral antibiotic for discharge today. Which antibiotic therapy plan is most appropriate to recommend for de-escalation? A. Nitrofurantoin 100 mg BID for 7 more days Escherichia coli ( > 100,000 colony forming units/mL) Amoxicillin Sensitive B. Trimethoprim-sulfamethoxazole 1 DS BID for 3 more days Ampicillin-sulbactam Sensitive C. Cefdinir 300 mg BID for 5 more days Cefazolin Sensitive D. Fosfomycin 3 grams PO as a single dose Ceftriaxone Sensitive Cefepime Sensitive Piperacillin-tazobactam Sensitive Trimethoprim-sulfamethoxazole Sensitive Meropenem Sensitive Ciprofloxacin Sensitive Nitrofurantoin Sensitive